Jussi Kauhanen

Low-risk limits recommended for alcohol consumption vary substantially across different national guidelines. To define thresholds associated with lowest risk for all-cause mortality and cardiovascular disease, we studied individual-participant data from 599 912 current drinkers without previous cardiovascular disease.We did a combined analysis of individual-participant data from three large-scale data sources in 19 high-income countries (the Emerging Risk Factors Collaboration, EPIC-CVD, and the UK Biobank). We characterised dose-response associations and calculated hazard ratios (HRs) per 100 g per week of alcohol (12·5 units per week) across 83 prospective studies, adjusting at least for study or centre, age, sex, smoking, and diabetes. To be eligible for the analysis, participants had to have information recorded about their alcohol consumption amount and status (ie, non-drinker vs current drinker), plus age, sex, history of diabetes and smoking status, at least 1 year of follow-up after baseline, and no baseline history of cardiovascular disease. The main analyses focused on current drinkers, whose baseline alcohol consumption was categorised into eight predefined groups according to the amount in grams consumed per week. We assessed alcohol consumption in relation to all-cause mortality, total cardiovascular disease, and several cardiovascular disease subtypes. We corrected HRs for estimated long-term variability in alcohol consumption using 152 640 serial alcohol assessments obtained some years apart (median interval 5·6 years [5th-95th percentile 1·04-13·5]) from 71 011 participants from 37 studies.In the 599 912 current drinkers included in the analysis, we recorded 40 310 deaths and 39 018 incident cardiovascular disease events during 5·4 million person-years of follow-up. For all-cause mortality, we recorded a positive and curvilinear association with the level of alcohol consumption, with the minimum mortality risk around or below 100 g per week. Alcohol consumption was roughly linearly associated with a higher risk of stroke (HR per 100 g per week higher consumption 1·14, 95% CI, 1·10-1·17), coronary disease excluding myocardial infarction (1·06, 1·00-1·11), heart failure (1·09, 1·03-1·15), fatal hypertensive disease (1·24, 1·15-1·33); and fatal aortic aneurysm (1·15, 1·03-1·28). By contrast, increased alcohol consumption was log-linearly associated with a lower risk of myocardial infarction (HR 0·94, 0·91-0·97). In comparison to those who reported drinking >0-≤100 g per week, those who reported drinking >100-≤200 g per week, >200-≤350 g per week, or >350 g per week had lower life expectancy at age 40 years of approximately 6 months, 1-2 years, or 4-5 years, respectively.In current drinkers of alcohol in high-income countries, the threshold for lowest risk of all-cause mortality was about 100 g/week. For cardiovascular disease subtypes other than myocardial infarction, there were no clear risk thresholds below which lower alcohol consumption stopped being associated with lower disease risk. These data support limits for alcohol consumption that are lower than those recommended in most current guidelines.UK Medical Research Council, British Heart Foundation, National Institute for Health Research, European Union Framework 7, and European Research Council.

Persistent inflammation has been proposed to contribute to various stages in the pathogenesis of cardiovascular disease. Interleukin-6 receptor (IL6R) signalling propagates downstream inflammation cascades. To assess whether this pathway is causally relevant to coronary heart disease, we studied a functional genetic variant known to affect IL6R signalling.In a collaborative meta-analysis, we studied Asp358Ala (rs2228145) in IL6R in relation to a panel of conventional risk factors and inflammation biomarkers in 125,222 participants. We also compared the frequency of Asp358Ala in 51,441 patients with coronary heart disease and in 136,226 controls. To gain insight into possible mechanisms, we assessed Asp358Ala in relation to localised gene expression and to postlipopolysaccharide stimulation of interleukin 6.The minor allele frequency of Asp358Ala was 39%. Asp358Ala was not associated with lipid concentrations, blood pressure, adiposity, dysglycaemia, or smoking (p value for association per minor allele ≥0·04 for each). By contrast, for every copy of 358Ala inherited, mean concentration of IL6R increased by 34·3% (95% CI 30·4-38·2) and of interleukin 6 by 14·6% (10·7-18·4), and mean concentration of C-reactive protein was reduced by 7·5% (5·9-9·1) and of fibrinogen by 1·0% (0·7-1·3). For every copy of 358Ala inherited, risk of coronary heart disease was reduced by 3·4% (1·8-5·0). Asp358Ala was not related to IL6R mRNA levels or interleukin-6 production in monocytes.Large-scale human genetic and biomarker data are consistent with a causal association between IL6R-related pathways and coronary heart disease.British Heart Foundation; UK Medical Research Council; UK National Institute of Health Research, Cambridge Biomedical Research Centre; BUPA Foundation.

The prevalence of cardiometabolic multimorbidity is increasing.To estimate reductions in life expectancy associated with cardiometabolic multimorbidity.Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates.A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI).All-cause mortality and estimated reductions in life expectancy.In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy.Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

To help adapt cardiovascular disease risk prediction approaches to low-income and middle-income countries, WHO has convened an effort to develop, evaluate, and illustrate revised risk models. Here, we report the derivation, validation, and illustration of the revised WHO cardiovascular disease risk prediction charts that have been adapted to the circumstances of 21 global regions.In this model revision initiative, we derived 10-year risk prediction models for fatal and non-fatal cardiovascular disease (ie, myocardial infarction and stroke) using individual participant data from the Emerging Risk Factors Collaboration. Models included information on age, smoking status, systolic blood pressure, history of diabetes, and total cholesterol. For derivation, we included participants aged 40-80 years without a known baseline history of cardiovascular disease, who were followed up until the first myocardial infarction, fatal coronary heart disease, or stroke event. We recalibrated models using age-specific and sex-specific incidences and risk factor values available from 21 global regions. For external validation, we analysed individual participant data from studies distinct from those used in model derivation. We illustrated models by analysing data on a further 123 743 individuals from surveys in 79 countries collected with the WHO STEPwise Approach to Surveillance.Our risk model derivation involved 376 177 individuals from 85 cohorts, and 19 333 incident cardiovascular events recorded during 10 years of follow-up. The derived risk prediction models discriminated well in external validation cohorts (19 cohorts, 1 096 061 individuals, 25 950 cardiovascular disease events), with Harrell's C indices ranging from 0·685 (95% CI 0·629-0·741) to 0·833 (0·783-0·882). For a given risk factor profile, we found substantial variation across global regions in the estimated 10-year predicted risk. For example, estimated cardiovascular disease risk for a 60-year-old male smoker without diabetes and with systolic blood pressure of 140 mm Hg and total cholesterol of 5 mmol/L ranged from 11% in Andean Latin America to 30% in central Asia. When applied to data from 79 countries (mostly low-income and middle-income countries), the proportion of individuals aged 40-64 years estimated to be at greater than 20% risk ranged from less than 1% in Uganda to more than 16% in Egypt.We have derived, calibrated, and validated new WHO risk prediction models to estimate cardiovascular disease risk in 21 Global Burden of Disease regions. The widespread use of these models could enhance the accuracy, practicability, and sustainability of efforts to reduce the burden of cardiovascular disease worldwide.World Health Organization, British Heart Foundation (BHF), BHF Cambridge Centre for Research Excellence, UK Medical Research Council, and National Institute for Health Research.

Even though previous studies have suggested an association between high fish intake and reduced coronary heart disease (CHD) mortality, men in Eastern Finland, who have a high fish intake, have an exceptionally high CHD mortality. We hypothesized that this paradox could be in part explained by high mercury content in fish.We studied the relation of the dietary intake of fish and mercury, as well as hair content and urinary excretion of mercury, to the risk of acute myocardial infarction (AMI) and death from CHD, cardiovascular disease (CVD), and any cause in 1833 men aged 42 to 60 years who were free of clinical CHD, stroke, claudication, and cancer. Of these, 73 experienced an AMI in 2 to 7 years. Of the 78 decreased men, 18 died of CHD and 24 died of CVD. Men who had consumed local nonfatty fish species had elevated hair mercury contents. In Cox models with the major cardiovascular risk factors as covariates, dietary intakes of fish and mercury were associated with significantly increased risk of AMI and death from CHD, CVD, and any death. Men in the highest tertile (> or = 2.0 micrograms/g) of hair mercury content had a 2.0-fold (95% confidence interval, 1.2 to 3.1; P = .005) age- and CHD-adjusted risk of AMI and a 2.9-fold (95% CI, 1.2 to 6.6; P = .014) adjusted risk of cardiovascular death compared with those with a lower hair mercury content. In a nested case-control subsample, the 24-hour urinary mercury excretion had a significant (P = .042) independent association with the risk of AMI. Both the hair and urinary mercury associated significantly with titers of immune complexes containing oxidized LDL.These data suggest that a high intake of mercury from nonfatty freshwater fish and the consequent accumulation of mercury in the body are associated with an excess risk of AMI as well as death from CHD, CVD, and any cause in Eastern Finnish men and this increased risk may be due to the promotion of lipid peroxidation by mercury.

The prevalence of alexithymia and its association with sociodemographic variables were studied in a sample of 1285 subjects representing the general population of Finland. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20). Alexithymia was normally distributed in the population in both genders, confirming that it is a personality dimension. The prevalence of alexithymia was 13%. Men were alexithymic almost twice (17%) as often as women (10%). Multivariate analysis showed that alexithymia was associated with male gender, advanced age, low educational level, and low socioeconomic status. As to the three factors of the TAS-20, men scored higher in factors 2 (difficulty in describing feelings) and 3 (externally oriented thinking), but there was no gender difference in factor 1 (difficulty in identifying feelings). Comparative population studies in other countries are needed to find out whether there are any differences in the prevalence of alexithymia between cultures.

This study aims to demonstrate the prevalence of pain as a reason for seeing a physician in primary care. We also performed an analysis of the localization, duration and frequency of pains, as well as the diagnoses of patients having pain. A total of 28 physicians at 25 health centers in Finland collected the data, comprising 5646 patient visits. Pain was identified as the reason for 2237 (40%) of the visits. The most common localizations were in the lower back, abdomen and head. One-fifth of the pain patients had experienced pain for over six months. Analysis of the diagnoses revealed half of the pains to be musculoskeletal. Patients experienced considerable limitations in various activities of life due to pain. A quarter of the pain patients of active working age received sick leave. Our results confirm that pain is a major primary health care problem, which has an enormous impact on public health.

The extent to which adult height, a biomarker of the interplay of genetic endowment and early-life experiences, is related to risk of chronic diseases in adulthood is uncertain.We calculated hazard ratios (HRs) for height, assessed in increments of 6.5 cm, using individual-participant data on 174374 deaths or major non-fatal vascular outcomes recorded among 1085949 people in 121 prospective studies.For people born between 1900 and 1960, mean adult height increased 0.5-1 cm with each successive decade of birth. After adjustment for age, sex, smoking and year of birth, HRs per 6.5 cm greater height were 0.97 (95% confidence interval: 0.96-0.99) for death from any cause, 0.94 (0.93-0.96) for death from vascular causes, 1.04 (1.03-1.06) for death from cancer and 0.92 (0.90-0.94) for death from other causes. Height was negatively associated with death from coronary disease, stroke subtypes, heart failure, stomach and oral cancers, chronic obstructive pulmonary disease, mental disorders, liver disease and external causes. In contrast, height was positively associated with death from ruptured aortic aneurysm, pulmonary embolism, melanoma and cancers of the pancreas, endocrine and nervous systems, ovary, breast, prostate, colorectum, blood and lung. HRs per 6.5 cm greater height ranged from 1.26 (1.12-1.42) for risk of melanoma death to 0.84 (0.80-0.89) for risk of death from chronic obstructive pulmonary disease. HRs were not appreciably altered after further adjustment for adiposity, blood pressure, lipids, inflammation biomarkers, diabetes mellitus, alcohol consumption or socio-economic indicators.Adult height has directionally opposing relationships with risk of death from several different major causes of chronic diseases.

<h3>Importance</h3> It is uncertain to what extent established cardiovascular risk factors are associated with venous thromboembolism (VTE). <h3>Objective</h3> To estimate the associations of major cardiovascular risk factors with VTE, ie, deep vein thrombosis and pulmonary embolism. <h3>Design, Setting, and Participants</h3> This study included individual participant data mostly from essentially population-based cohort studies from the Emerging Risk Factors Collaboration (ERFC; 731 728 participants; 75 cohorts; years of baseline surveys, February 1960 to June 2008; latest date of follow-up, December 2015) and the UK Biobank (421 537 participants; years of baseline surveys, March 2006 to September 2010; latest date of follow-up, February 2016). Participants without cardiovascular disease at baseline were included. Data were analyzed from June 2017 to September 2018. <h3>Exposures</h3> A panel of several established cardiovascular risk factors. <h3>Main Outcomes and Measures</h3> Hazard ratios (HRs) per 1-SD higher usual risk factor levels (or presence/absence). Incident fatal outcomes in ERFC (VTE, 1041; coronary heart disease [CHD], 25 131) and incident fatal/nonfatal outcomes in UK Biobank (VTE, 2321; CHD, 3385). Hazard ratios were adjusted for age, sex, smoking status, diabetes, and body mass index (BMI). <h3>Results</h3> Of the 731 728 participants from the ERFC, 403 396 (55.1%) were female, and the mean (SD) age at the time of the survey was 51.9 (9.0) years; of the 421 537 participants from the UK Biobank, 233 699 (55.4%) were female, and the mean (SD) age at the time of the survey was 56.4 (8.1) years. Risk factors for VTE included older age (ERFC: HR per decade, 2.67; 95% CI, 2.45-2.91; UK Biobank: HR, 1.81; 95% CI, 1.71-1.92), current smoking (ERFC: HR, 1.38; 95% CI, 1.20-1.58; UK Biobank: HR, 1.23; 95% CI, 1.08-1.40), and BMI (ERFC: HR per 1-SD higher BMI, 1.43; 95% CI, 1.35-1.50; UK Biobank: HR, 1.37; 95% CI, 1.32-1.41). For these factors, there were similar HRs for pulmonary embolism and deep vein thrombosis in UK Biobank (except adiposity was more strongly associated with pulmonary embolism) and similar HRs for unprovoked vs provoked VTE. Apart from adiposity, these risk factors were less strongly associated with VTE than CHD. There were inconsistent associations of VTEs with diabetes and blood pressure across ERFC and UK Biobank, and there was limited ability to study lipid and inflammation markers. <h3>Conclusions and Relevance</h3> Older age, smoking, and adiposity were consistently associated with higher VTE risk.

The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain.To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk.Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment.Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk.During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels.In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

Background Low total testosterone (TT) and sex hormone-binding globulin (SHBG) concentrations have been associated with the metabolic syndrome (MetS) in men, but the reported strength of association varies considerably. Objectives We aimed to investigate whether associations differ across specific subgroups (according to age and body mass index (BMI)) and individual MetS components. Data sources Two previously published meta-analyses including an updated systematic search in PubMed and EMBASE. Study Eligibility Criteria Cross-sectional or prospective observational studies with data on TT and/or SHBG concentrations in combination with MetS in men. Methods We conducted an individual participant data meta-analysis of 20 observational studies. Mixed effects models were used to assess cross-sectional and prospective associations of TT, SHBG and free testosterone (FT) with MetS and its individual components. Multivariable adjusted odds ratios (ORs) and hazard ratios (HRs) were calculated and effect modification by age and BMI was studied. Results Men with low concentrations of TT, SHBG or FT were more likely to have prevalent MetS (ORs per quartile decrease were 1.69 (95% CI 1.60-1.77), 1.73 (95% CI 1.62-1.85) and 1.46 (95% CI 1.36-1.57) for TT, SHBG and FT, respectively) and incident MetS (HRs per quartile decrease were 1.25 (95% CI 1.16-1.36), 1.44 (95% 1.30-1.60) and 1.14 (95% 1.01-1.28) for TT, SHBG and FT, respectively). Overall, the magnitude of associations was largest in non-overweight men and varied across individual components: stronger associations were observed with hypertriglyceridemia, abdominal obesity and hyperglycaemia and associations were weakest for hypertension. Conclusions Associations of testosterone and SHBG with MetS vary according to BMI and individual MetS components. These findings provide further insights into the pathophysiological mechanisms linking low testosterone and SHBG concentrations to cardiometabolic risk.

<h3>Importance</h3> It is uncertain whether depressive symptoms are independently associated with subsequent risk of cardiovascular diseases (CVDs). <h3>Objective</h3> To characterize the association between depressive symptoms and CVD incidence across the spectrum of lower mood. <h3>Design, Setting, and Participants</h3> A pooled analysis of individual-participant data from the Emerging Risk Factors Collaboration (ERFC; 162 036 participants; 21 cohorts; baseline surveys, 1960-2008; latest follow-up, March 2020) and the UK Biobank (401 219 participants; baseline surveys, 2006-2010; latest follow-up, March 2020). Eligible participants had information about self-reported depressive symptoms and no CVD history at baseline. <h3>Exposures</h3> Depressive symptoms were recorded using validated instruments. ERFC scores were harmonized across studies to a scale representative of the Center for Epidemiological Studies Depression (CES-D) scale (range, 0-60; ≥16 indicates possible depressive disorder). The UK Biobank recorded the 2-item Patient Health Questionnaire 2 (PHQ-2; range, 0-6; ≥3 indicates possible depressive disorder). <h3>Main Outcomes and Measures</h3> Primary outcomes were incident fatal or nonfatal coronary heart disease (CHD), stroke, and CVD (composite of the 2). Hazard ratios (HRs) per 1-SD higher log CES-D or PHQ-2 adjusted for age, sex, smoking, and diabetes were reported. <h3>Results</h3> Among 162 036 participants from the ERFC (73%, women; mean age at baseline, 63 years [SD, 9 years]), 5078 CHD and 3932 stroke events were recorded (median follow-up, 9.5 years). Associations with CHD, stroke, and CVD were log linear. The HR per 1-SD higher depression score for CHD was 1.07 (95% CI, 1.03-1.11); stroke, 1.05 (95% CI, 1.01-1.10); and CVD, 1.06 (95% CI, 1.04-1.08). The corresponding incidence rates per 10 000 person-years of follow-up in the highest vs the lowest quintile of CES-D score (geometric mean CES-D score, 19 vs 1) were 36.3 vs 29.0 for CHD events, 28.0 vs 24.7 for stroke events, and 62.8 vs 53.5 for CVD events. Among 401 219 participants from the UK Biobank (55% were women, mean age at baseline, 56 years [SD, 8 years]), 4607 CHD and 3253 stroke events were recorded (median follow-up, 8.1 years). The HR per 1-SD higher depression score for CHD was 1.11 (95% CI, 1.08-1.14); stroke, 1.10 (95% CI, 1.06-1.14); and CVD, 1.10 (95% CI, 1.08-1.13). The corresponding incidence rates per 10 000 person-years of follow-up among individuals with PHQ-2 scores of 4 or higher vs 0 were 20.9 vs 14.2 for CHD events, 15.3 vs 10.2 for stroke events, and 36.2 vs 24.5 for CVD events. The magnitude and statistical significance of the HRs were not materially changed after adjustment for additional risk factors. <h3>Conclusions and Relevance</h3> In a pooled analysis of 563 255 participants in 22 cohorts, baseline depressive symptoms were associated with CVD incidence, including at symptom levels lower than the threshold indicative of a depressive disorder. However, the magnitude of associations was modest.

Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment.In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure.We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure.In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention.British Heart Foundation, Austrian Science Fund, UK Medical Research Council, National Institute for Health Research, European Research Council, and European Commission Framework Programme 7.

The prevalence of type 2 diabetes is increasing rapidly, particularly among younger age groups. Estimates suggest that people with diabetes die, on average, 6 years earlier than people without diabetes. We aimed to provide reliable estimates of the associations between age at diagnosis of diabetes and all-cause mortality, cause-specific mortality, and reductions in life expectancy.For this observational study, we conducted a combined analysis of individual-participant data from 19 high-income countries using two large-scale data sources: the Emerging Risk Factors Collaboration (96 cohorts, median baseline years 1961-2007, median latest follow-up years 1980-2013) and the UK Biobank (median baseline year 2006, median latest follow-up year 2020). We calculated age-adjusted and sex-adjusted hazard ratios (HRs) for all-cause mortality according to age at diagnosis of diabetes using data from 1 515 718 participants, in whom deaths were recorded during 23·1 million person-years of follow-up. We estimated cumulative survival by applying age-specific HRs to age-specific death rates from 2015 for the USA and the EU.For participants with diabetes, we observed a linear dose-response association between earlier age at diagnosis and higher risk of all-cause mortality compared with participants without diabetes. HRs were 2·69 (95% CI 2·43-2·97) when diagnosed at 30-39 years, 2·26 (2·08-2·45) at 40-49 years, 1·84 (1·72-1·97) at 50-59 years, 1·57 (1·47-1·67) at 60-69 years, and 1·39 (1·29-1·51) at 70 years and older. HRs per decade of earlier diagnosis were similar for men and women. Using death rates from the USA, a 50-year-old individual with diabetes died on average 14 years earlier when diagnosed aged 30 years, 10 years earlier when diagnosed aged 40 years, or 6 years earlier when diagnosed aged 50 years than an individual without diabetes. Using EU death rates, the corresponding estimates were 13, 9, or 5 years earlier.Every decade of earlier diagnosis of diabetes was associated with about 3-4 years of lower life expectancy, highlighting the need to develop and implement interventions that prevent or delay the onset of diabetes and to intensify the treatment of risk factors among young adults diagnosed with diabetes.British Heart Foundation, Medical Research Council, National Institute for Health and Care Research, and Health Data Research UK.

Research has suggested that social-class differences in adult health may be at least partly determined by conditions earlier in life. In 2636 Finnish men, we assessed impact of childhood and adult socioeconomic conditions on adult mortality risk by examining whether differing socioeconomic lifecourses from early childhood to adulthood were associated with different risks of all-cause and cardiovascular mortality. Compared with high-income adults, those with low income had increased relative risks of all-cause (2·54, 95% CI 1·83-3·53) and cardiovascular (2·37, 1·51-3·7) mortality, but these increased risks were not related in either adult group to childhood socioeconomic conditions. Men who went from low-income childhood to high-income adulthood had the same mortality risks as those whose socioeconomic circumstances were good in both childhood and adulthood (1·14, 0·56-2·31, all causes; 0·99, 0·39-2·51, cardiovascular). By contrast, men who experienced poor socioeconomic circumstances as both children and adults were about twice as likely to die as those whose position improved (2·39, 1·28-4·44, all causes; 2·02, 0·9-4·54, cardiovascular). Our findings suggest that socioeconomic conditions in childhood are not important determinants of adult health. We caution against this interpretation—a lifecourse approach to socioeconomic differences in adult health requires understanding of the social and economic context in which individual lifecourses are determined.

Cynical hostility has been associated with increased cardiovascular morbidity and mortality; yet few studies have investigated this relation in population-based samples, and little is known about underlying mechanisms. This study examined the association between hostility, measured by the eight-item Cynical Distrust Scale, and risk for all-cause and cardiovascular mortality and incident myocardial infarction. Subjects were 2,125 men, ages 42-60 years, from the Kuopio Ischemic Heart Disease Risk Factor Study, a longitudinal study of unestablished and traditional risk factors for ischemic heart disease, mortality, and other outcomes. There were 177 deaths (73 cardiovascular) in 9 years of follow-up. Men with hostility scores in the top quartile were at more than twice the risk of all-cause mortality (relative hazards (RH) 2.30, 95% confidence interval (CI) 1.47-3.59) and cardiovascular mortality (RH 2.70, 95% CI 1.27-5.76), relative to men with scores in the lowest quartile. Among 1,599 men without previous myocardial infarction or angina, high scorers also had an increased risk of myocardial infarction (RH 2.18, 95% CI 1.01-4.70). Biologic and socioeconomic risk factors, social support, and prevalent diseases had minimal impact on these associations, whereas adjustments for the behavioral risk factors of smoking, alcohol consumption, physical activity, and body mass index substantially weakened the relations. Simultaneous risk factor adjustment eliminated the observed associations. Results show that high levels of hostility are associated with increased risk of all-cause and cause-specific mortality and incident myocardial infarction and that these effects are mediated primarily through behavioral risk factors.

Objective: To examine the association between beer binging (regular sessions of heavy beer drinking) and mortality.Design: Prospective population based study with the baseline assessment of level of alcohol intake (dose), by type of drink and drinking pattern, previous and existing diseases, socioeconomic background, occupational status, involvement in organisations during leisure time, physical activity in leisure time, body mass index, blood pressure, serum lipids and plasma fibrinogen concentration, during an average of 7.7 years' follow up of mortality.Setting: Finland.Subjects: A population sample of 1641 men who consumed beer who were aged 42, 48, 54, or 60 years at baseline.Main outcome measures: All cause mortality, cardiovascular mortality, death due to external causes, fatal myocardial infarctions. Results:The risk of death was substantially increased in men whose usual dose of beer was 6 or more bottles per session compared with men who usually consumed less than 3 bottles, after adjustment for age and total alcohol consumption (relative risk 3.01 (95% confidence interval 1.54 to 5.90) for all deaths; 7.10 (2.01 to 25.12) for external deaths; and 6.50 (2.05 to 20.61) for fatal myocardial infarction).The association changed only slightly when smoking, occupational status, previous diseases, systolic blood pressure, low density lipoprotein and high density lipoprotein cholesterol concentration, plasma fibrinogen concentration, body mass index, marital status, leisure time physical activity, and involvement in organisations were controlled for. Conclusion:The pattern of beer binging is associated with increased risk of death, independently of the total average consumption of alcoholic drinks.The relation is not explained by known behavioural, psychosocial, or biological risk factors.Death due to injuries and other external causes is overrepresented Papers

Objectives: To examine the influence of childhood and adult socioeconomic position, socioeconomic mobility, and cumulative disadvantage across the lifecourse on cognitive function in late middle age. Methods: Cross-sectional population-based study of 486 men age 58 and 64 from eastern Finland. Respondent's socioeconomic position in childhood was measured using parent's education and occupation, and respondent's position in adulthood was indicated by attained education and personal income. Cognitive function was assessed using five neuropsychological tests: Trail Making, Selective Reminding, Verbal Fluency, Visual Reproduction, and the Mini-Mental State Exam. Results: Each indicator of socioeconomic position made statistically independent contributions to levels of cognitive function: Respondents from poor childhood backgrounds, and those who attained a limited education and earned a low income, performed worst on each test. Men who occupied a disadvantaged socioeconomic position in childhood and then experienced upward mobility over the lifecourse exhibited better cognitive performance than those with similar socioeconomic origins but limited or no upward mobility. Conversely, men from advantaged childhood backgrounds who later in life experienced downward mobility scored poorer on each cognitive test than their counterparts who remained in the most advantaged groups throughout the lifecourse. There was a strong, graded association between cumulative socioeconomic disadvantage and cognitive function: Men who occupied a low socioeconomic position during both childhood and adulthood scored worse on every test than those who occupied a high position at all points in their lives. Discussion: Socioeconomic conditions across all stages of the lifecourse appear to make unique contributions to cognitive function in late middle age. These results also suggest that in terms of cognitive function, origin is not necessarily destiny, as disadvantaged socioeconomic circumstances in childhood may be overcome to some extent by upward mobility later in life.

Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22-5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3-25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism.

The serpin plasminogen activator inhibitor-1 (PAI-1) is a specific inhibitor of plasminogen activators and a potential therapeutic target in cancer and cardiovascular diseases. Accordingly, formation of a basis for development of specific PAI-1-inactivating agents is of great interest. One possible inactivation mode for PAI-1 is conversion to the inactive, so-called latent state. We have now screened a phage-displayed peptide library with PAI-1 as bait and isolated a 31-residue cysteine-rich peptide that will be referred to as paionin-4. A recombinant protein consisting of paionin-4 fused to domains 1 and 2 of the phage coat protein g3p caused a 2- to 3-fold increase in the rate of spontaneous inactivation of PAI-1. Paionin-4-D1D2 bound PAI-1 with a <i>K</i>_D in the high nanomolar range. Using several biochemical and biophysical methods, we demonstrate that paionin-4-D1D2-stimulated inactivation consists of an acceleration of conversion to the latent state. As demonstrated by site-directed mutagenesis and competition with other PAI-1 ligands, the binding site for paionin-4 was localized in the loop between α-helix D and β-strand 2A. We also demonstrate that a latency-inducing monoclonal antibody has an overlapping, but not identical binding site, and accelerates latency transition by another mechanism. Our results show that paionin-4 inactivates PAI-1 by a mechanism clearly different from other peptides, small organochemical compounds, or antibodies, whether they cause inactivation by stimulating latency transition or by other mechanisms, and that the loop between α<b>-</b>helix D and β-strand 2A can be a target for PAI-1 inactivation by different types of compounds.

This study prospectively assessed the effects of occupational physical activity on atherosclerosis progression.This population-based prospective study of ultrasonographically assessed carotid intima media thickness (IMT) used repeated measures of occupational physical activity during baseline, 4-year, and 11-year examinations of 612 Finnish men 42-60 years of age at baseline. The association between five measures of energy expenditure and the 11-year change in maximum IMT was evaluated in regression models adjusting for 21 potential confounders, including biological factors, leisure-time physical activity, smoking, socioeconomic status, psychosocial job factors, and baseline health status.At baseline, 31% of all the men and 51% of those with ischemic heart disease (IHD) exceeded the recommended maximum levels of relative aerobic strain. All five measures of energy expenditure were significantly associated with adjusted 11-year IMT change. Significant interactions were found between IHD and several measures of energy expenditure. Maximum relative aerobic strain resulted in a 90% increase in IMT among the men with IHD compared with a 46% increase among those without IHD. The men with preexisting carotid stenosis also had higher rates of IMT progression than the men without this condition.This study shows that high energy expenditures at work are associated with an accelerated progression of atherosclerosis even after control for virtually all known cardiovascular risk factors, especially among older workers and workers with preexisting IHD or carotid artery stenosis. The findings support the hemodynamic theory of atherosclerosis and have important implications for workplace surveillance and disease prevention.

There is an ongoing debate concerning the temporal stability of alexithymia. Most previous studies have been conducted on clinical populations of psychiatric and somatic patients. However, psychiatric and somatic morbidity have been found to confound the findings so that in their presence, alexithymia appears to be less stable. Nevertheless, few general population studies have been published, and there have been no follow-ups longer than 5 years. In a population-based sample of middle-aged Finnish men, 755 participants completed the Toronto Alexithymia Scale (TAS)–26 at baseline and on 11-year follow-up. Absolute or mean stability refers to the extent to which scores change over time, and it was measured with group comparisons of paired samples. Relative stability refers to the consistency of relative differences in alexithymia levels among the study subjects, and it was measured with test-retest correlations. Changes in the total scores and the subscales of the TAS-26 were all statistically significant but had low effect sizes (0.09-0.20) for the change-suggested absolute stability. The correlations between baseline and follow-up scores were high (ρ = 0.51-0.63), indicating relative stability. The exclusion of depressive symptoms, a history of mental illnesses, and cancer or cardiovascular diseases at baseline and at the 4- and 11-year follow-ups did not essentially alter these findings. Of the background variables, a higher age independently associated with the increase in the TAS-26 scores. Those with alexithymia at baseline were more likely to have elevated depressive symptoms at the 4- and 11-year follow-ups. Both the absolute and relative stabilities of alexithymia in the general population are high, even for a long follow-up period. These results may support the assumption that alexithymia represents a stable personality trait in general. Alexithymia may increase vulnerability to depressive symptoms.

ABSTRACT Background Only few prospective population studies have been able so far to investigate depression and drinking patterns in detail. Therefore, little is known about what aspect of alcohol consumption best predicts symptoms of depression in the general population. Participants and design In this prospective population‐based two‐wave cohort study, a cohort of alcohol‐drinking men and women ( n = 15 926) were followed‐up after 5 years. A postal questionnaire was sent in 1998 (response proportion 40%) and again in 2003 (response proportion 80% of the baseline participants) to Finnish adults aged 20–54 years at baseline. Measurements Alcohol consumption was measured by average intake (g/week) and by measures of binge drinking (intoxications, hangovers and alcohol‐induced pass‐outs). Depressive symptoms were assessed with the 21‐item Beck Depression Inventory. In addition, information from hospital discharge register for depression and alcohol abuse were linked to the data. Findings This study found a positive association between baseline binge drinking and depressive symptoms 5 years later. Adjustment for several possible confounders attenuated the observed relationships only slightly, suggesting that binge drinking contributes independently to the occurrence of depressive symptoms. Binge drinking was related to symptoms of depression independently of average intake. Conclusions This study supports the hypothesis that heavy drinking, and in particular a binge pattern involving intoxications, hangovers or pass‐outs, produces depressive symptoms in the general population. The frequency of hangovers was the best predictor for depressive symptoms.

There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied.Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms.Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

there are no previous studies linking repeated heat exposure of sauna and the risk of memory diseases. We aimed to investigate whether frequency of sauna bathing is associated with risk of dementia and Alzheimer's disease.prospective population-based study.the frequency of sauna bathing was assessed at baseline in the Kuopio Ischaemic Heart Disease population-based prospective cohort study of 2,315 apparently healthy men aged 42-60 years at baseline, with baseline examinations conducted between 1984 and 1989. Hazard ratios (HRs) with 95% confidence intervals (CIs) for dementia and Alzheimer's disease were ascertained using Cox-regression modelling with adjustment for potential confounders.during a median follow-up of 20.7 (interquartile range 18.1-22.6) years, a total of 204 and 123 diagnosed cases of dementia and Alzheimer's disease were respectively recorded. In analysis adjusted for age, alcohol consumption, body mass index, systolic blood pressure, smoking status, Type 2 diabetes, previous myocardial infarction, resting heart rate and serum low-density lipoprotein cholesterol, compared with men with only 1 sauna bathing session per week, the HR for dementia was 0.78 (95% CI: 0.57-1.06) for 2-3 sauna bathing sessions per week and 0.34 (95% CI: 0.16-0.71) for 4-7 sauna bathing sessions per week. The corresponding HRs for Alzheimer's disease were 0.80 (95% CI: 0.53-1.20) and 0.35 (95% CI: 0.14-0.90).in this male population, moderate to high frequency of sauna bathing was associated with lowered risks of dementia and Alzheimer's disease. Further studies are warranted to establish the potential mechanisms linking sauna bathing and memory diseases.

Copper (Cu) is a component of enzymes catalyzing oxidation-reduction reactions. With the persisting burden of cardiovascular disease (CVD), there is evident need to identify biomarkers and potential risk factors for CVD. We therefore examined the association between serum Cu levels and the risk of CVD death in Finnish men and across different body mass index (BMI) categories.This Finnish prospective study is based on 1911 men aged 42-60 years who were free of coronary heart disease at baseline. Cu concentrations (mg/l) were determined using atomic absorption spectrometer and categorized into quartiles (<1.0; 1 to <1.1; 1.1 to <1.21; ≥1.21). Participants were categorized into normal weight <25 kg/m2, pre-obesity 25-29.9 kg/m2, and obesity >30 kg/m2. The association between Cu and CVD death was analyzed using multivariable Cox regression models. During a median follow-up of 25.8 years, 358 CVD deaths occurred. The risk of CVD death increased continuously with increasing Cu levels (for non-linearity, p = 0.64). Using the first quartile as reference after adjustment for covariates, the hazard ratios (HR) (95% confidence interval (CI)) for CVD death for Cu concentrations in second, third and fourth quartiles were 1.45(1.05-2.01), 1.69(1.25-2.27), and 1.68(1.23-2.29), respectively. Obese men in the third quartile of serum Cu concentrations had highest risk of CVD death (HR (95%CI) 2.71(1.27-5.78)).Elevated serum Cu level was associated with increased risk of CVD death across all BMI categories in middle-aged and older Finnish men. Serum Cu may have prognostic implication for CVD mortality risk; however, further studies are needed.

We prospectively examined the association between alexithymia and risk of death over an average follow-up time of nearly 5.5 years in 42- to 60-year-old men (N = 2297) participating in the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD). Alexithymia, impairment in identification, processing, and verbal expression of inner feelings, was assessed by the validated Toronto Alexithymia Scale (TAS) In age-adjusted survival analyses, men in the highest alexithymia quintile had a twofold greater risk of all-cause death (p<0.001) and a threefold greater risk of death from accidents, injury, or violence (p<0.02) relative to the men in the three lowest alexithymia quintiles. There was little evidence for confounding by behavioral factors (smoking, alcohol consumption, physical activity), physiological risk factors (LDL, HDL, body mass index, hypertension), socioeconomic status, marital status, perceived health, prior diseases and diagnoses, depressive symptoms or social connections. Consistent and even stronger associations between alexithymia and all-cause death were found in a healthy subgroup (N = 1650). Why difficulties in dealing with emotions associate with increased mortality remains unclear. Our findings suggest that the association is independent from the effect of well-known behavioral, biological, and psychosocial risk factors.

Early recognition of and intervention in risky alcohol consumption has been shown to be an effective way to reduce the harm. However, primary care physicians are still not screening for and intervening sufficiently in their patients' alcohol misuse.The purpose of this study was to explore factors having an effect on primary health care physicians inquiring about patients' alcohol consumption.A qualitative study of primary care physicians' experiences and views based on tape recorded semi-structured interviews was carried out on all physicians (n = 35) working at four health centres in Eastern Finland.Seven main categories were identified that either prevent or promote discussion about alcohol consumption: the sensitive nature of alcohol drinking; the reason for consultation; awareness of a patient's alcohol problem; patient factors; availability of intervention tools; expectations of effectiveness of interventions; and lack of time.There still exist many barriers to initiating discussions about alcohol in the consultation room. Changing the frame of reference of the concept of alcohol drinking from an addictive disease to a general lifestyle risk factor could overcome many of these barriers.

The authors conducted a population study to assess the relationship between heavy alcohol consumption and alexithymia, defined as difficulty in identifying and expressing feelings. The study sample consisted of 2,297 middle-aged men from eastern Finland. The proportion of men who reported either frequent intoxication or unpleasant aftereffects of heavy drinking increased linearly with alexithymia. Alexithymia and the heavy acute intake of different sorts of alcoholic drinks were also consistently associated. Long-term heavy use, taking into account both the dose and frequency, was also linearly related to the alexithymia measure. In multivariate models to assess whether high alcohol consumption in alexithymic individuals might relate to stress, the authors found nothing to support the stress-dampening hypothesis.

The aim of this study was to examine the factor structure and the validity of the Finnish version of the 20-item Toronto Alexithymia Scale (TAS-20). As part of the Northern Finland 1966 Birth Cohort Project, the TAS-20 was presented to a sample of 5034 31-year old persons. A confirmatory factor analysis showed that the three-factor model, earlier established with the original TAS-20, was in agreement with the Finnish version of the scale. Three criteria of goodness-of-fit met the standards for adequacy of fit. For the total scale, internal reliability (Cronbach's alpha) was 0.83 and for the three subscales (factors 1, 2, and 3) it was 0.81, 0.77, and 0.66, respectively. Two- and one-factor models for TAS-20 were also examined, but the other models did not perform as well as the three-factor model. The factor model also worked well with a sample of 516 students with a mean age of 24.8 years. In conclusion, the TAS-20 scale is useful in the Finnish version, too.

This study examined the association between perceived health and early retirement.A cohort of 1748 men aged 42 to 60 years from eastern Finland was followed from 1984 to 2000. At baseline, the participants had answered a questionnaire regarding their general (as measured by physician diagnoses) and perceived health status. Comprehensive pension records were obtained from the Social Insurance Institution of Finland and the Central Pension Security Institute. The risk of disability pensioning in various disease categories and nonillness-based early pensioning was analyzed using Cox regression modeling.Over 11 years, 855 (48.9%) men received a disability pension, and 331 (18.9%) received a nonillness-based early pension. Only 273 (15.6%) received an old age pension, without previous early pensioning. At the end of the follow-up, 289 (16.5%) were still working. After adjustment for potential confounders, men with poor perceived health at baseline had a relative risk of 2.37 [95% confidence interval (95% CI) 1.79-3.13] for disability pensioning and the highest risk of disability was due to mental illness (RR 3.84, 95% CI 1.86-7.92), followed by musculoskeletal disorders and cardiovascular diseases. The relative risk of receiving a nonillness-based pension was 2.94 (95% CI 1.92-4.50) for this group.Self-assessed poor health is a strong predictor of early retirement due to mental disorders, musculoskeletal disorders, and cardiovascular diseases. Moreover, the risk of retirement on a nonillness-based pension is increased among those with poor perceived health.

Social characteristics of alexithymic individuals were examined in a population-based study of 2,682 middleaged men from Eastern Finland. Alexithymia, referring to difficulties in identifying and verbally describing inner feelings, was assessed using the Toronto Alexithymia Scale (TAS). Men whose high TAS score suggested reduced ability in verbal emotional expression were more often unmarried and had low levels of social contacts and acquaintances. Education, income, and occupational status were inversely related to the TAS score. These associations remained statistically significant after adjustment for confounding factors. The results suggest that alexithymia could be viewed not only as a psychological phenomenon, but also partly as a socially determined one.

The association between five socioeconomic indices (lifetime occupation, education, income, ownership of material possessions, and childhood socioeconomic status) and plasma flbrinogen levels was investigated in middle-aged Finnish men who were part of the Kuopio Ischernic Heart Disease Risk Factor Study. The Kuopio Ischemic Heart Disease Risk Factor Study is based on a representative age-stratified sample of 2,682 men aged 42, 48, 54, and 60 years. The data were collected between 1984 and 1989. The present analysis is restricted to the 2,011 men for whom information on fibnnogen and all covariates was available. The covariates were alcohol consumption, body mass index, physical fitness, smoking, coffee consumption, high density lipoprotein cholesterol, low density lipoprotein cholesterol, blood leukocyte count, and prevalent disease (at least one sign of ischemic heart disease, hypertension, diabetes, or previous stroke). An age-adjusted inverse association was found between levels of plasma fibrinogen and four of the five socioeconomic indices: current income, education, lifetime occupation status, and current material possessions. After adjustment for the covariates, the association persisted for education, current income, and lifetime occupation. Analysis of the joint effect of childhood and adult socioeconomic status indicated that those who were economically disadvantaged at both times had the highest fibrinogen levels, but the fibrinogen levels of those who were not poor as adults had no variation by childhood socioeconomic status.

Objective: To explore the associations between alexithymia and increased somatic morbidity. The mechanisms underlying these associations, however, are still unclear. Furthermore, data on the association between alexithymia and mortality are scarce. Methods: A total of 2321 Finnish men, aged 46 to 61 years, were followed up for an average of 20 years. Mortality rates were obtained from the national register. The associations between baseline alexithymia and cardiovascular disease (CVD), all-cause, injury, and cancer deaths were examined with adjustments for age and several behavioral (smoking, alcohol consumption, physical activity), physiological (low- and high-density lipoprotein cholesterol, body mass index, systolic blood pressure, history of CVD), and psychosocial (marital status, education, depression) factors. Results: After all adjustments, the risk of CVD death was increased by 1.2% for each 1-point increase in Toronto Alexithymia Scale-26 scores. Conclusions: Alexithymia is associated with increased cardiovascular mortality. BDI = Beck Depression Inventory; BMI = body mass index; CI = confidence interval; CVD = cardiovascular disease; HDL-C = high-density lipoprotein cholesterol; HPL Depression Scale = Human Population Laboratory Depression Scale; LDL-C = low-density lipoprotein cholesterol; RR = risk ratio; TAS = Toronto Alexithymia Scale.

Large-scale epidemiological evidence on the role of inflammation in early atherosclerosis, assessed by carotid ultrasound, is lacking. We aimed to quantify cross-sectional and longitudinal associations of inflammatory markers with common-carotid-artery intima-media thickness (CCA-IMT) in the general population. Information on high-sensitivity C-reactive protein, fibrinogen, leucocyte count and CCA-IMT was available in 20 prospective cohort studies of the PROG-IMT collaboration involving 49,097 participants free of pre-existing cardiovascular disease. Estimates of associations were calculated within each study and then combined using random-effects meta-analyses. Mean baseline CCA-IMT amounted to 0.74 mm (SD = 0.18) and mean CCA-IMT progression over a mean of 3.9 years to 0.011 mm/year (SD = 0.039). Cross-sectional analyses showed positive linear associations between inflammatory markers and baseline CCA-IMT. After adjustment for traditional cardiovascular risk factors, mean differences in baseline CCA-IMT per one-SD higher inflammatory marker were: 0.0082 mm for high-sensitivity C-reactive protein (p < 0.001); 0.0072 mm for fibrinogen (p < 0.001); and 0.0025 mm for leucocyte count (p = 0.033). ‘Inflammatory load’, defined as the number of elevated inflammatory markers (i.e. in upper two quintiles), showed a positive linear association with baseline CCA-IMT (p < 0.001). Longitudinal associations of baseline inflammatory markers and changes therein with CCA-IMT progression were null or at most weak. Participants with the highest ‘inflammatory load’ had a greater CCA-IMT progression (p = 0.015). Inflammation was independently associated with CCA-IMT cross-sectionally. The lack of clear associations with CCA-IMT progression may be explained by imprecision in its assessment within a limited time period. Our findings for ‘inflammatory load’ suggest important combined effects of the three inflammatory markers on early atherosclerosis.

This study overcomes several methodological problems of an inconsistent literature and provides evidence for a detrimental role of occupational physical activity on cardiovascular health for men with and without baseline ischemic heart disease.The study also demonstrates that choice of exposure measure and analytic strategy can change direction and size of estimated effects, possibly explaining known inconsistencies in the literature.

Carotid intima-media thickness (CIMT) is a marker of subclinical organ damage and predicts cardiovascular disease (CVD) events in the general population. It has also been associated with vascular risk in people with diabetes. However, the association of CIMT change in repeated examinations with subsequent CVD events is uncertain, and its use as a surrogate end point in clinical trials is controversial. We aimed at determining the relation of CIMT change to CVD events in people with diabetes.In a comprehensive meta-analysis of individual participant data, we collated data from 3,902 adults (age 33-92 years) with type 2 diabetes from 21 population-based cohorts. We calculated the hazard ratio (HR) per standard deviation (SD) difference in mean common carotid artery intima-media thickness (CCA-IMT) or in CCA-IMT progression, both calculated from two examinations on average 3.6 years apart, for each cohort, and combined the estimates with random-effects meta-analysis.Average mean CCA-IMT ranged from 0.72 to 0.97 mm across cohorts in people with diabetes. The HR of CVD events was 1.22 (95% CI 1.12-1.33) per SD difference in mean CCA-IMT, after adjustment for age, sex, and cardiometabolic risk factors. Average mean CCA-IMT progression in people with diabetes ranged between -0.09 and 0.04 mm/year. The HR per SD difference in mean CCA-IMT progression was 0.99 (0.91-1.08).Despite reproducing the association between CIMT level and vascular risk in subjects with diabetes, we did not find an association between CIMT change and vascular risk. These results do not support the use of CIMT progression as a surrogate end point in clinical trials in people with diabetes.

The social health insurance coverage is relatively high in Mongolia; however, escalation of out-of-pocket payments for health care, which reached 41 % of the total health expenditure in 2011, is a policy concern. The aim of this study is to analyse the incidence of catastrophic health expenditures and to measure the rate of impoverishment from health care payments under the social health insurance scheme in Mongolia.We used the data from the Household Socio-Economic Survey 2012, conducted by the National Statistical Office of Mongolia. Catastrophic health expenditures are defined an excess of out-of-pocket payments for health care at the various thresholds for household total expenditure (capacity to pay). For an estimate of the impoverishment effect, the national and The Wold Bank poverty lines are used.About 5.5 % of total households suffered from catastrophic health expenditures, when the threshold is 10 % of the total household expenditure. At the threshold of 40 % of capacity to pay, 1.1 % of the total household incurred catastrophic health expenditures. About 20,000 people were forced into poverty due to paying for health care.Despite the high coverage of social health insurance, a significant proportion of the population incurred catastrophic health expenditures and was forced into poverty due to out-of-pocket payments for health care.

BACKGROUNDSauna bathing is associated with reduced cardiovascular risk, but the mechanisms underlying this beneficial effect are not entirely understood. We aimed to assess the relationship between sauna bathing and risk of incident hypertension.

Previous studies assessing the role of dietary factors in depression have mainly focused on nutrients, while the association between dietary patterns and depression is less studied. The aim was to assess the role of dietary patterns in depression in both cross-sectional and prospective analyses. The study population consisted of 1003 Finnish middle-aged or older men from the Kuopio Ischemic Heart Disease Risk Factor Study. Food consumption was assessed by food frequency questionnaire in 1991–1993 and dietary patterns from 25 predefined food groups were extracted by factor analysis. Depressive symptoms were assessed with the self-administered Human Population Laboratory Depression Scale, cut-off point of five or more indicating elevated depressive symptoms. Altogether 72 (7.2%) subjects had elevated depressive symptoms. Three dietary patterns were identified: “prudent”, “Western” and “mixed”. In cross-sectional analysis, after adjustments for age, examination year, BMI, smoking, alcohol consumption, education, marital status, leisure-time physical activity, history of mental illness and cardiovascular disease the prudent dietary pattern was associated with a 25% lower prevalence of elevated depressive symptoms (OR: 0.75; 95% CI: 0.57, 0.99; P=0.036), whereas the Western dietary pattern was associated with increased prevalence of elevated depressive symptoms (OR: 1.41; 95% CI: 1.08, 1.84; P=0.011). In the prospective analysis (16.5 follow-up years), the prudent dietary pattern was inversely associated with the risk of getting a hospital discharge diagnosis of depression (HR: 0.66; 95% CI 0.47, 0.93; P=0.018). Adherence to healthy dietary pattern is associated with lower risk of getting a hospital discharge diagnosis of depression.

Carotid intima media thickness (CIMT) predicts cardiovascular (CVD) events, but the predictive value of CIMT change is debated. We assessed the relation between CIMT change and events in individuals at high cardiovascular risk.From 31 cohorts with two CIMT scans (total n = 89070) on average 3.6 years apart and clinical follow-up, subcohorts were drawn: (A) individuals with at least 3 cardiovascular risk factors without previous CVD events, (B) individuals with carotid plaques without previous CVD events, and (C) individuals with previous CVD events. Cox regression models were fit to estimate the hazard ratio (HR) of the combined endpoint (myocardial infarction, stroke or vascular death) per standard deviation (SD) of CIMT change, adjusted for CVD risk factors. These HRs were pooled across studies. In groups A, B and C we observed 3483, 2845 and 1165 endpoint events, respectively. Average common CIMT was 0.79mm (SD 0.16mm), and annual common CIMT change was 0.01mm (SD 0.07mm), both in group A. The pooled HR per SD of annual common CIMT change (0.02 to 0.43mm) was 0.99 (95% confidence interval: 0.95-1.02) in group A, 0.98 (0.93-1.04) in group B, and 0.95 (0.89-1.04) in group C. The HR per SD of common CIMT (average of the first and the second CIMT scan, 0.09 to 0.75mm) was 1.15 (1.07-1.23) in group A, 1.13 (1.05-1.22) in group B, and 1.12 (1.05-1.20) in group C.We confirm that common CIMT is associated with future CVD events in individuals at high risk. CIMT change does not relate to future event risk in high-risk individuals.

There remains a dearth of life-course studies analyzing childhood environment and late-life chronic illness. In particular, few have addressed possible early-life predictors of dementia. This study examines relationships between childhood stress and later-age dementia, specifically Alzheimer's disease (AD).We used data from 2682 men in the population-based Kuopio Ischemic Heart Disease Risk Factor Study who participated in extensive baseline health examinations and interviews between 1984 and 1989, when they were between 42 and 61 years of age. Childhood events were documented in these structured interviews. We created a composite childhood stress variable that included living in custody or an orphanage, experience of crisis in childhood, having problems with teachers and emigrating because of war. Data on incident cases of dementia, including AD, were obtained through 2014 via national health register linkages. Risk of developing dementia was estimated using Cox regression adjusting for age, education, income and prior/existing diseases at baseline.Childhood stress was associated with increased risk of dementia (HR = 1.86, 95% CI: 1.12-3.10). Associations remained statistically significant after adjustment for age, education, income and other covariates (HR = 1.93, 95% CI: 1.14-3.25). Associations were marginally significant with AD, with HRs of similar magnitude.Childhood stress plays an important role in late-life dementia risk among men. Support systems should be developed for children suffering from stressful conditions. Further research examining childhood social and environmental effects on later morbidity, in diverse populations, is necessary to develop a holistic understanding of life-course disease burden.

The relationship between resting heart rate (RHR) and incident heart failure (HF) has been questioned.RHR was assessed at baseline in 7073 participants in 3 prospective cohorts (Cardiovascular Health Study, Health ABC study and Kuopio Ischemic Heart Disease Study) that recorded 1189 incident HF outcomes during 92 702 person-years of follow-up. Mean age of participants was 67 (9.9) years and mean RHR was 64.6 (11.1) bpm. Baseline RHR correlated (P<0.001) positively with body mass index (r=0.10), fasting glucose (r=0.18), and C-reactive protein (r=0.20); and inversely with serum creatinine (r=-0.05) and albumin (r=-0.05). Baseline RHR was non-linearly associated with HF risk. The age and sex-adjusted hazard ratio for HF comparing the top (>72 bpm) versus the bottom (<57 bpm) quartile of baseline RHR was 1.48 (95% confidence interval [CI] 1.26 to 1.74) and was modestly attenuated (1.30, 95% CI 1.10 to 1.53) with further adjustment for body mass index, history of diabetes, hypertension, smoking status, serum creatinine, and left ventricular hypertrophy. These findings remained consistent in analyses accounting for incident coronary heart disease, excluding individuals with prior cardiovascular events, or those taking beta-blockers; and in subgroups defined by several individual participant characteristics. In a pooled random effects meta-analysis of 7 population-based studies (43 051 participants and 3476 HF events), the overall hazard ratio comparing top versus bottom fourth of RHR was 1.40 (95% CI: 1.19 to 1.64).There is a non-linear association between RHR and incident HF. Further research is needed to understand the physiologic foundations of this association.

Abstract Background The Syrian conflict has endured for a decade, causing one of the most significant humanitarian crises since World War II. The conflict has inflicted massive damage to civil infrastructure, and not even the health care sector has been spared. On the contrary, health care has been targeted, and as a result, many health professionals have left the country. Despite the life-threatening condition, many health professionals continued to work inside Syria even in the middle of the acute crisis. This qualitative study aims to determine the factors that have motivated Syrian health professionals to work in a conflict-affected country. Methods The research is based on 20 semi-structured interviews of Syrian health care workers. Interviews were conducted in 2016–2017 in Gaziantep, Turkey. A thematic inductive content analysis examined the motivational factors Syrian health care workers expressed for their work in the conflict area. Results Motivating factors for health care workers were intrinsic and extrinsic. Intrinsic reasons included humanitarian principles and medical ethics. Also, different ideological reasons, patriotic, political and religious, were mentioned. Economic and professional reasons were named as extrinsic reasons for continuing work in the war-torn country. Conclusions The study adds information on the effects of the Syrian crisis on health care—from healthcare workers' perspective. It provides a unique insight on motivations why health care workers are continuing their work in Syria. This research underlines that the health care system would collapse totally without local professionals and leave the population without adequate health care.

Background: End-stage renal disease is associated with a high risk of cardiovascular events. It is unknown, however, whether mild-to-moderate kidney dysfunction is causally related to coronary heart disease (CHD) and stroke. Methods: Observational analyses were conducted using individual-level data from 4 population data sources (Emerging Risk Factors Collaboration, EPIC-CVD [European Prospective Investigation into Cancer and Nutrition–Cardiovascular Disease Study], Million Veteran Program, and UK Biobank), comprising 648 135 participants with no history of cardiovascular disease or diabetes at baseline, yielding 42 858 and 15 693 incident CHD and stroke events, respectively, during 6.8 million person-years of follow-up. Using a genetic risk score of 218 variants for estimated glomerular filtration rate (eGFR), we conducted Mendelian randomization analyses involving 413 718 participants (25 917 CHD and 8622 strokes) in EPIC-CVD, Million Veteran Program, and UK Biobank. Results: There were U-shaped observational associations of creatinine-based eGFR with CHD and stroke, with higher risk in participants with eGFR values &lt;60 or &gt;105 mL·min –1 ·1.73 m –2 , compared with those with eGFR between 60 and 105 mL·min –1 ·1.73 m –2 . Mendelian randomization analyses for CHD showed an association among participants with eGFR &lt;60 mL·min –1 ·1.73 m –2 , with a 14% (95% CI, 3%–27%) higher CHD risk per 5 mL·min –1 ·1.73 m –2 lower genetically predicted eGFR, but not for those with eGFR &gt;105 mL·min –1 ·1.73 m –2 . Results were not materially different after adjustment for factors associated with the eGFR genetic risk score, such as lipoprotein(a), triglycerides, hemoglobin A1c, and blood pressure. Mendelian randomization results for stroke were nonsignificant but broadly similar to those for CHD. Conclusions: In people without manifest cardiovascular disease or diabetes, mild-to-moderate kidney dysfunction is causally related to risk of CHD, highlighting the potential value of preventive approaches that preserve and modulate kidney function.

Our aim was to study whether an insertion/deletion (I/D) polymorphism in the alpha2B-adrenoceptor gene is associated with the risk for cardiovascular diseases.alpha2-adrenoceptors mediate contraction of vascular smooth muscle and induce coronary vasoconstriction in humans. The alpha2-adrenoceptor subtype B mediates vasoconstriction in mice. A variant of the human alpha2B-adrenoceptor gene that encodes a D of three residues in an intracellular acidic motif has been shown to confer decreased receptor desensitization. This receptor variant could, therefore, be involved in diseases associated with enhanced vasoconstriction.This study was part of a prospective population-based study investigating risk factors for cardiovascular diseases in a cohort of middle-aged men from eastern Finland. Nine hundred twelve men aged 46 to 64 years were followed for an average time of 4.5 years.In this study population, 192 men (21%) had the D/D genotype; 256 (28%) had the I/I genotype, and 464 (51%) had a heterozygous genotype. In a Cox model adjusting for other coronary risk factors, men with the D/D genotype had 2.2 times (95% confidence interval: 1.1 to 4.4, p = 0.02) the risk to experience an acute coronary event (n = 15 for D/D, 10 for I/I and 12 for I/D) compared with men carrying either of the other two genotypes. The alpha2B-adrenoceptor genotype was not associated with hypertension in this study population.The D/D genotype of the alpha2B-adrenoceptor is a novel genetic risk factor for acute coronary events, but not for hypertension.

Early retirement produces a heavy economic burden in many western societies. There is a need to identify single risk factors for early retirement and to find methods for preventing it. To estimate the effect of heavy physical work on early retiring, a cohort of 1755 men aged 42 to 65 years from eastern Finland was followed up from 1984 to 2000. Self-estimated physical workload was assessed at baseline. The inclusive pension records were obtained from national pension institutions. Logistic regression modeling was used to estimate the effect of physical workload and single physical risk factors on the risk of disability pension and nonillness-based pension. Risks were estimated for both disease-specific and all disability pensions. The interaction of physical fitness and physical workload and the resulting effects on risk were also estimated. During the follow-up, 861 (49.1%) men retired on a disability pension and 331 men (18.9%) retired on a nonillness-based early pension. Only 273 (15.6%) men reached the age for getting the normal old-age pension without having had any other early pension After adjustment for age, body mass index, alcohol consumption, smoking, maximal oxygen uptake, education and corresponding illness at baseline, heavy physical work was found to be associated with an increased risk of being retired on a disability pension due to musculoskeletal disorders (odds ratio (OR) 2.21, 95% confidence interval 1.36 to 3.61) but not due to cardiovascular or mental diseases. The association was stronger if cardiorespiratory fitness was poor. Lifting, static muscular loading and uncomfortable work positions increased the risk of early retirement especially due to musculoskeletal disorders. Loading of the upper extremity alone or with the neck and shoulder region seems to be an independent risk factor for early retirement. We concluded that physical workload increases the risk of retirement on a disability pension especially due to musculoskeletal disorders. In heavy physical work, the risk is increased especially among men with musculoskeletal or cardiovascular disease and poor cardiorespiratory fitness.

A rather common leucine7-to-proline7 (Leu7Pro) polymorphism in the preproneuropeptide Y (prepro-NPY) gene signal peptide may be important in blood pressure regulation, cholesterol metabolism and the pathogenesis of atherosclerosis in humans. We examined the associations of the Leu7Pro polymorphism with carotid atherosclerotic progression, blood pressure and serum lipids in a population-based sample of 966 men aged 42–60 years in Finland. The Pro7 substitution (carrier frequency 12.2%) was associated with accelerated four-year increase in the mean (P=0.01) and maximal (P=0.007) common carotid intima-media thickness (IMT) and with slightly increased systolic (P=0.03) and diastolic (P=0.02) blood pressures, adjusted for other major risk factors. Men with Pro7 substitution had 30.6% (95% CI 6.9–54.0%) greater increase in the mean IMT and 20.0% (95% CI 5.3–34.4%) greater increase in the maximal IMT than men with Leu7/Leu7 genotype. The Pro7 substitution was also related to increased serum total cholesterol (P=0.01) and LDL cholesterol (P=0.02) in obese (body mass index (BMI)>30 kg/m2) men. This study provides important evidence suggesting that the Pro7 substitution in the prepro-NPY is an important risk factor for accelerated atherosclerotic progression, increased blood pressure and increased serum cholesterol in humans.

Background: A common functional genetic polymorphism in the catechol‐ O ‐methyltransferase (COMT) gene (Val158 Met) results in 3‐ to 4‐fold differences in COMT enzyme activity and dopamine inactivation rate. Previous studies have shown that type I alcoholism is more common among subjects with low activity COMT genotype (LL), compared with high activity (HH) or heterozygotic (LH) genotypes. Methods: We studied alcohol consumption and the COMT genotype in middle‐aged Finnish men ( n = 896), who represented an unselected ethnically homogenous population sample and reported using alcohol during the past year. Average alcohol use in pure ethanol (grams per week) was compared between subjects with LL genotype and subjects with LH or HH genotypes. Results: Men with LL genotype (30% of all subjects) reported 27% higher weekly alcohol consumption compared with the two other genotype groups ( p &lt; 0.05). The difference remained statistically significant after a multivariate adjustment for sociodemographic factors and prior or existing diseases ( p = 0.031). Conclusions: The results indicate that COMT polymorphism may contribute significantly to alcohol intake not only in alcoholics but also in a general male population.

Childhood socioeconomic circumstances have been shown to contribute to adult mortality. The purpose of this study was to compare the association between objective historical records and recalled questionnaire-based information on childhood socioeconomic position (SEP) with regard to cardiovascular and all-cause mortality.We examined the association between a socially disadvantaged childhood and all-cause mortality, cardiovascular disease (CVD) mortality, coronary heart disease (CHD) mortality, and acute coronary events among male participants in the Kuopio Ischemic Heart Disease (KIHD) Risk Factor Study, a population-based cohort study in eastern Finland with follow-up until 2002. The historical data on childhood factors were collected from school health records (n = 698), mainly from the 1930s to the 1950s. Recall data on socioeconomic conditions in childhood were obtained from the baseline examinations of the KIHD cohort (n = 2,682) in 1984-89.According to original school health records the men who were socially disadvantaged in childhood had a 1.41-fold (95% confidence interval 1.01-1.97) age-adjusted and examination-year-adjusted risk of all-cause death, a 1.32-fold (0.83-2.11) risk of CVD death, a 1.48-fold (0.85-2.57) risk of CHD death, and a 1.50-fold (1.02-2.20) risk of acute coronary events. After adjustment for biological and behavioural risk factors and for the SEP in adulthood the association was attenuated in all-cause death but did not change in CVD death, CHD death, and acute coronary events. On the contrary, the questionnaire-based recalled childhood data on childhood SEP showed no associations with mortality or acute coronary events.With regard to adult mortality, the use of historical records concerning hygiene and living conditions collected in childhood may either provide more accurate measures of early-life socioeconomic conditions or capture more relevant aspects of childhood socioeconomic disadvantage than retrospective recall data.

Most studies that examine the role of alcohol consumption in atherosclerosis and cardiovascular disease have overlooked the possible effect of drinking pattern. We investigated the association between the habit of heavy acute intake of beer and spirits (binging) and the 4-year progression of carotid atherosclerosis in a population-based sample of middle-aged Finnish men. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD) were used to estimate changes in maximum and mean intima-media thickness (IMT) and the maximum plaque height in 764 KIHD participants who reported using beer and in 871 participants who used spirits. After adjustment for age, baseline carotid atherosclerosis, and average weekly alcohol consumption level, we observed the highest atherosclerosis progression in men who usually consumed a whole bottle of vodka or more in 1 session. For beer binging (>6 beers at a time), the magnitude of IMT progression was even higher, although this association was only marginally significant (P<0.1) because of smaller numbers. The associations were largely unaffected by adjustments for blood pressure, lipids, smoking, BMI, and medication. The magnitude of the difference was generally higher in a subgroup that was free of IHD at baseline. We conclude that the pattern of drinking associates with the progression of carotid atherosclerosis independently of the total level of alcohol consumption and risk factors.

Temporal stability is a basic assumption underlying any personality trait construct. Previous research on the stability of alexithymia has led to a controversy over whether alexithymia should be viewed as a state-dependent phenomenon or as a stable personality trait. The aim of this 5-year longitudinal study was to examine the temporal stability of alexithymia in the general population in Finland. Alexithymia was measured with the 20-Item Toronto Alexithymia Scale (TAS-20) at the baseline and 5 years later. The test–retest correlations of the TAS-20 total and factor-specific scores at the baseline and at the 5-year follow-up ranged from moderate to high in both genders, reflecting a rather high relative stability of the TAS-20 scores over a period of 5 years. The findings of our study suggest that alexithymia behaves like a stable personality trait in the general population.

Small size at birth has been associated with components of the metabolic syndrome, but little is known about the association with the metabolic syndrome itself or whether leisure-time physical activity (LTPA) and cardiorespiratory fitness modify that association. We studied the association of size at birth with the metabolic syndrome.Birth weight and length, the metabolic syndrome (World Health Organization criteria), LTPA over the previous 12 months, and VO(2max) were assessed in 462 nondiabetic middle-aged Finnish men who were part of a population-based cohort study.Men with a ponderal index (kg/m(3)) at birth in the lower third had higher fasting insulin and glucose levels than men in the upper third in age-adjusted analyses and were at least twofold more likely to have the metabolic syndrome, even in men without cardiovascular disease. Adjustment for childhood or adult socioeconomic status or adult BMI did not attenuate the association. Thinness at birth was even more clearly associated with hyperinsulinemia and the metabolic syndrome in men engaging in <25 min/wk of vigorous LTPA and in men with a VO(2max) <28.6 ml x kg(-1) x min(-1) or <2.44 l/min. In active and fit men, however, the association was absent.Small size at birth was associated with the metabolic syndrome in middle-aged men already before development of diabetes or cardiovascular disease. Thinness at birth may carry with it lifelong metabolic consequences, but regular strenuous physical activity and maintenance of cardiorespiratory fitness may alleviate or eliminate those consequences.

The aim of this population-based study was to investigate differences in dietary patterns in relation to the level of alcohol consumption among Finnish adults. This study was part of the FinDrink project, an epidemiologic study on alcohol use among Finnish population. It utilized data from the Kuopio Ischaemic Heart Disease Risk Factor Study. A total of 1720 subjects comprising of 816 men and 904 women aged 53-73 years were included in the study in 1998-2001. Food intake was collected via a 4-day food diary method. Self-reported alcohol consumption was assessed with quantity-frequency method based on the Nordic Alcohol Consumption Inventory. Weekly alcohol consumption was categorized into three groups: non-drinkers (<12 grams), moderate drinkers (12-167.9 grams for men, 12-83.9 grams for women) and heavy drinkers (≥ 168 grams for men, ≥ 84 grams for women). Data were analyzed for men and women separately using multiple linear regression models, adjusted for age, occupational status, marital status, smoking, body mass index and leisure time physical activity. In women, moderate/heavy drinkers had lower fibre intake and moderate drinkers had higher vitamin D intake than non-drinkers. Male heavy drinkers had lower fibre, retinol, calcium and iron intake, and moderate/heavy drinkers had higher vitamin D intake than non-drinkers. Fish intake was higher among women moderate drinkers and men moderate/heavy drinkers than non-drinkers. In men, moderate drinkers had lower fruit intake and heavy drinkers had lower milk intake than non-drinkers. Moderate drinkers had higher energy intake from total fats and monosaturated fatty acids than non-drinkers. In contrast, energy intake from carbohydrates was lower among moderate/heavy drinkers than non-drinkers. In conclusion, especially male heavy drinkers had less favorable nutritional intake than moderate and non-drinkers. Further studies on the relationship between alcohol consumption and dietary habits are needed to plan a comprehensive dietary intervention programs in future.

To assess the efficacy of methylphenidate as a substitution therapy for amphetamine/methamphetamine dependence in Finland and New Zealand.Parallel-group, double-blind, randomized placebo-controlled trial.Out-patient care.Amphetamine-/methamphetamine-dependent, aged 16-65 years.The primary outcome measure was presence/absence of amphetamine/methamphetamine in urine samples collected twice weekly. Secondary measures included treatment adherence, alterations in craving scores and self-reported use. Primary analysis was by intention-to-treat (ITT). The study drug, methylphenidate (as Concerta(®) ), was up-titrated over 2 weeks to a maximum dose of 54 mg daily and continued for a further 20 weeks. Doses were given under daily supervision at the clinics.Seventy-nine participants were randomized (40 methylphenidate; 39 placebo); 76 received allocated treatment and 27 completed the trial. ITT analysis (n = 78) showed no statistically significant difference in the percentage of positive urines between the methylphenidate and placebo arms (odds ratio: 0.95, 95% confidence interval: 0.83-1.08). However, there was a significant difference (P < 0.05) between the active and placebo arms in retention, the placebo arm displaying a significantly lower retention from 6 weeks that persisted until the end of the trial.The trial failed to replicate earlier findings suggesting that methylphenidate was superior to placebo. The low retention rate confounded the ability to draw firm conclusions about efficacy. The higher retention rate was observed in the methylphenidate arm. Any replication of this work would need to consider alternatives to the rigid clinic attendance criteria, and consider an increased dose.

Background: Exposure to methylmercury from fish has been associated with increased risk of myocardial infarction (MI) in some studies. At the same time, marine n−3 (omega-3) PUFAs are an inherent constituent of fish and are regarded as beneficial. To our knowledge, no risk-benefit model on the basis of data on methylmercury, PUFA, and MI risk has yet been presented. Objective: The objective of this study was to describe how exposure to both marine n−3 PUFAs and methylmercury relates to MI risk by using data from Finland and Sweden. Design: We used matched case-control sets from Sweden and Finland that were nested in population-based, prospective cohort studies. We included 361 men with MI from Sweden and 211 men with MI from Finland. MI risk was estimated in a logistic regression model with the amount of mercury in hair (hair-Hg) and concentrations of n−3 PUFAs (EPA and DHA) in serum (S-PUFA) as independent variables. Results: The median hair-Hg was 0.57 μg/g in Swedish and 1.32 μg/g in Finnish control subjects, whereas the percentage of S-PUFA was 4.21% and 3.83%, respectively. In combined analysis, hair-Hg was associated with higher (P = 0.005) and S-PUFA with lower (P = 0.011) MI risk. Our model indicated that even a small change in fish consumption (ie, by increasing S-PUFA by 1%) would prevent 7% of MIs, despite a small increase in mercury exposure. However, at a high hair-Hg, the modeled beneficial effect of PUFA on MI risk was counteracted by methylmercury. Conclusions: Exposure to methylmercury was associated with increased risk of MI, and higher S-PUFA concentrations were associated with decreased risk of MI. Thus, MI risk may be reduced by the consumption of fish high in PUFAs and low in methylmercury.

The aim of this harmonized meta-analysis was to examine the independent and combined effects of physical activity and BMI on the incidence of type 2 diabetes.Our systematic literature review in 2011 identified 127 potentially relevant prospective studies of which 9 fulfilled the inclusion criteria (total N = 117,878, 56.2 % female, mean age = 50.0 years, range = 25-65 years). Measures of baseline physical activity (low, intermediate, high), BMI-category [BMI < 18.4 (underweight), 18.5-24.9 (normal weight), 25.0-29.9 (overweight), 30+ (obese)] and incident type 2 diabetes were harmonized across studies. The associations between physical activity, BMI and incident type 2 diabetes were analyzed using Cox regression with a standardized analysis protocol including adjustments for age, gender, educational level, and smoking. Hazard ratios from individual studies were combined in a random-effects meta-analysis.Mean follow-up time was 9.1 years. A total of 11,237 incident type 2 diabetes cases were recorded. In mutually adjusted models, being overweight or obese (compared with normal weight) and having low physical activity (compared with high physical activity) were associated with an increased risk of incident type 2 diabetes (hazard ratios 2.33, 95 % CI 1.95-2.78; 6.10, 95 % CI: 4.63-8.04, and 1.23, 95 % CI: 1.09-1.39, respectively). Individuals who were both obese and had low physical activity had 7.4-fold (95 % CI 3.47-15.89) increased risk of type 2 diabetes compared with normal weight, high physically active participants.This harmonized meta-analysis shows the importance of maintaining a healthy weight and being physically active in diabetes prevention.

Previous studies have suggested an association between sleep duration and cancer. However, the information on sleep duration regard to risk of lung cancer is scanty. Analysed data comprised prospective population-based cohort of 2586 men (aged 42–60 years) from Eastern Finland. Baseline survey and clinical examinations took place 1984–1989, and diagnosed lung cancers were obtained until the end of 2011 through linkage with the Finnish Cancer Registry. Self-reported sleep was categorized as ≤6.5 h, 7–7.5 h, and ≥8 h. Subjects with prior history of cancer or psychotropic medication (hypnotics or sedatives) were excluded from the analyses. Cox proportional hazards models with adjustments for possible confounders were used to examine the association. Significant association between sleep duration and increased lung cancer risk was observed after adjustments for age, examination years, cumulative smoking history, family cancer history and Human Population Laboratory Depression scale scores (HR 2.12, 95% CI 1.17-3.85 for ≤6.5 h sleep, and HR 1.88, 95% CI 1.09-3.22 for ≥8 h sleep). Associations were even stronger among current smokers (HR 2.23, 95% CI 1.14-4.34 for ≤6.5 h sleep, and HR 2.09, 95% CI 1.14-3.81 for ≥8 h sleep). After further adjustments for alcohol consumption, physical activity, body mass index, marital status, education years, night work, employment status, asthma and chronic bronchitis, the association remained significant both in the whole study population and among smokers. When cumulative smoking history was replaced by current smoking in the adjustments, the increased risk was limited to those who slept <6.5 h. Sleep duration of less than 7–7.5 hours or more than 7–7.5 hours associates with increased lung cancer risk. The physiological factors underlying the association are complex, and they may relate to melatonin excretion patterns, low-grade inflammation in cancer development process or disruptions in circadian rhythmicity.

Individual participant time-to-event data from multiple prospective epidemiologic studies enable detailed investigation into the predictive ability of risk models. Here we address the challenges in appropriately combining such information across studies. Methods are exemplified by analyses of log C-reactive protein and conventional risk factors for coronary heart disease in the Emerging Risk Factors Collaboration, a collation of individual data from multiple prospective studies with an average follow-up duration of 9.8 years (dates varied). We derive risk prediction models using Cox proportional hazards regression analysis stratified by study and obtain estimates of risk discrimination, Harrell's concordance index, and Royston's discrimination measure within each study; we then combine the estimates across studies using a weighted meta-analysis. Various weighting approaches are compared and lead us to recommend using the number of events in each study. We also discuss the calculation of measures of reclassification for multiple studies. We further show that comparison of differences in predictive ability across subgroups should be based only on within-study information and that combining measures of risk discrimination from case-control studies and prospective studies is problematic. The concordance index and discrimination measure gave qualitatively similar results throughout. While the concordance index was very heterogeneous between studies, principally because of differing age ranges, the increments in the concordance index from adding log C-reactive protein to conventional risk factors were more homogeneous.

Depression is a major global public health concern. The aetiology of depression is partly unclear; however, intake of nutrients, such as magnesium, have been suggested to affect depressive symptoms and modify depression risk.This research is a part of the Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, conducted on a sample of 2320 Eastern Finnish men aged 42-61 years old at the baseline. Magnesium intake was assessed by a 4-day food record. Hospital discharge diagnosis of unipolar depressive disorder was used as an outcome variable.Participants in the middle tertile of dietary magnesium intake had a statistically significantly decreased risk of getting a hospital discharge diagnosis of depression compared to participants in the lowest tertile of magnesium intake (HR 0.49, CI 0.25-0.95, P=0.035) in the prospective setting after multivariable adjustments. In addition, an inverse association between magnesium intake and the risk of depression was found when the combined middle and highest tertiles of magnesium intake were compared with the lowest tertile (HR 0.53, CI 0.29-0.95, P=0.033).Our findings may not be generalizable to individuals below middle-age or women. Moreover, we were unable to consider cases with mild depression in the longitudinal setting.The results of this study suggest that magnesium intake may have an effect on the risk to develop depression. Further studies are needed to investigate whether sufficient magnesium intake could have implications for prevention or treatment of depression.

Background Fatty liver disease (FLD) has been identified as constituting cardiometabolic risk. However, evidence on the association of fatty liver index (FLI) with cardiovascular disease (CVD) is largely cross-sectional, with limited evidence on the predictability of incident CVD, and specifically, acute myocardial infarction (AMI). Therefore, we aimed to investigate the prospective associations between fatty liver as estimated by FLI and incident CVD, and specifically AMI, in the Kuopio Ischaemic Heart Disease Risk Factor Study cohort. Patients and methods Our patients were 1205 middle-aged men free of CVD at baseline. The associations of baseline FLI with incident CVD and incident AMI were analyzed using multivariable-adjusted Cox regression models. Results During a median follow-up of 17 years, a total of 690 incident cases of CVD and 269 cases of AMI were recorded through Finnish registries. For incident CVD, for the high (FLI≥60) versus the low (≤30) FLI category, the hazard ratio (HR) was 1.77 [95% confidence interval (CI): 1.46–2.14] in the minimally adjusted model. With increasing adjustment, the association was attenuated progressively. In the most adjusted model, the HR was 1.41 (95% CI: 1.10–1.79). For incident AMI, for the high FLI category, the HR was 1.65 (95% CI: 1.22–2.23) in the minimally adjusted model, but in most comprehensive models when we included metabolic factors, the HR was not significant (HR=1.136, 95% CI: 0.777–1.662). Conclusion FLI can predict incident CVD. However, the predictability of AMI using FLI is subject to interactions of metabolic factors. Individuals with FLI in the moderate to high category should be evaluated and monitored for subclinical or overt cardiovascular (including coronary) disease.

We studied the relation between frequent hangovers and cardiovascular mortality in a representative population sample of middle-aged Finnish men who participated in the Kuopio Ischemic Heart Disease Risk Factor Study. Complete data on alcohol consumption, hangover frequency, prior cardiovascular diseases, and risk factors were obtained for 2,160 non-abstinent men. Frequent hangovers were rare in the three lowest alcohol consumption quartiles, but in the highest quartile, a total of 239 men (43.6%) reported having a hangover at least monthly. During an average follow-up time of 6.7 years, these men had a 2.36-fold (95% confidence interval = 1.02-5.48) risk of cardiovascular death compared with men with fewer hangovers, with adjustment for age and total alcohol consumption. The association was somewhat attenuated after adjustments for smoking, income, and prior cardiovascular diseases. Systolic blood pressure, body mass index, resting heart rate, or serum lipids had no appreciable role in the relation, but plasma fibrinogen concentration appeared as one possible pathway to increased risk of cardiovascular death in men who frequently experience hangovers. The findings underline the importance of preventive actions regarding not only the amount but also the way people consume alcohol.

The effect of citalopram and placebo in the treatment of alcoholism was studied in a sample of 62 patients with a follow-up period of four months. The results imply that the new 5-HT re-uptake inhibitor citalopram is significantly more effective than placebo in the treatment of alcoholism. The present study indicates that even severe alcoholism may be treated effectively with a generally available psychopharmacological agent.

Alterations in monoamine oxidase A (MAOA) expression and enzyme activity may be associated with alcoholism and impulsive behavior. Therefore, functional polymorphisms in the MAOA gene would be good candidates to consider in the interindividual differences that exist in the susceptibility to alcoholism. One variant that has been considered as a candidate in alcoholism is a repeat polymorphism in the MAOA gene promoter. We analyzed a cohort of Finnish males with either type 1 or type 2 alcoholism, as well as controls, for differences in the distribution of MAOA promoter alleles. Based on other studies, we postulated that type 2 alcoholism, which is associated with antisocial behavior, but not type 1 alcoholism, would be correlated with the inheritance of the low promoter activity allele. However, we failed to find a difference in allele distribution in type 1 and type 2 alcoholics. In addition, there was no difference in the allele distribution when each group of alcoholics was compared with controls. However, when both groups of alcoholics were pooled and compared with controls, the difference in allele distribution reached a trend towards significance. Our results suggest a minimal association between the MAOA low activity promoter alleles and alcoholism, regardless of the presence or absence of antisocial behavior. Interestingly, approximately 3% of type 2 alcoholics were found to be heterozygous for the MAOA promoter polymorphism. Since MAOA is X-linked, the heterozygotes are probable cases of Klinefelter's syndrome (47,XXY) suggesting that X-chromosome aneuploidy may increase the risk for developing type 2 alcoholism.

Despite recognition of the health risks of binge drinking, its life-course precursors have not been widely examined. Data from the Kuopio Ischemic Heart Disease Risk Factor Study (1984-1989) were used to investigate the association between socioeconomic and psychosocial exposures across the life course and binge drinking in a population-based sample of 2,316 middle-aged men. Binge drinking was defined as drinking at least four bottles of beer, one bottle of wine, one bottle of strong wine, or six servings of spirits on a single occasion. A composite indicator of childhood socioeconomic position was based on parental education, occupation, and number of rooms and divided into tertiles. Low childhood socioeconomic position increased the odds of binge drinking (odds ratio = 1.70, 95% confidence interval: 1.26, 2.31) when other early life exposures were adjusted. Additional adjustment of adult socioeconomic and psychosocial factors attenuated the odds of bingeing associated with low childhood socioeconomic position (odds ratio = 1.29, 95% confidence interval: 0.93, 1.79). Adult socioeconomic conditions, marital status, hostility, and organizational membership were independently associated with bingeing. This study shows that both early and later life characteristics including socioeconomic conditions and adult psychosocial factors contribute to adult binge drinking in this population, but the effects of adult characteristics are stronger.

Excellent palliative care is available for patients with advanced lung cancer. Whether the same services are available for those with nonmalignant respiratory disease is less clear. A questionnaire was sent to 210 named respiratory physicians, each representing a major hospital in England, Wales, and Northern Ireland. A total of 107 replies were received; the response rate was 51.0%. Respondents cared for patients with chronic obstructive pulmonary disease, asbestosis, and diffuse parenchymal lung disease but only a third had responsibility for cystic fibrosis. Physicians were supported by a mean of 3.4 respiratory nurse specialists per department and 73.8% had a specialist lung cancer nurse. In only 16 cases (20.3%) did that nurse extend care to those with nonmalignant disease. Only a minority reported easy access to hospice in-patient care or day care. About 21.5% of the respondents had formal policies in place for care of patients with chronic respiratory disease nearing the end of life, but 87.9% of respondents had no formal process for initiating end of life discussions with those with terminal respiratory illness. Patients with advanced nonmalignant respiratory disease have less universal access to specialist palliative care services than do those with malignant lung disease, and in the majority of hospitals there is no formalized approach to end of life care issues with patients with chronic lung disease.

Lecithin:cholesterol acyltransferase (LCAT) is the enzyme responsible for cholesterol esterification in plasma. LCAT is a major factor in HDL remodeling and metabolism, and it has long been believed to play a critical role in macrophage reverse cholesterol transport (RCT). The effect of LCAT on human atherogenesis is still controversial. In the present study, the plasma LCAT concentration was measured in all subjects (n = 540) not on drug treatment at the time of enrollment in the multicenter, longitudinal, observational IMPROVE study. Mean and maximum intima-media thickness (IMT) of the whole carotid tree was measured by B-mode ultrasonography in all subjects. In the entire cohort, LCAT quartiles were not associated with carotid mean and maximum IMT (<i>P</i> for trend 0.95 and 0.18, respectively), also after adjustment for age, gender, HDL-cholesterol (HDL-C), and triglycerides. No association between carotid IMT and LCAT quartiles was observed in men (<i>P</i>=0.30 and <i>P</i>=0.99 for mean and maximum IMT, respectively), whereas carotid IMT increased with LCAT quartiles in women (<i>P</i> for trend 0.14 and 0.019 for mean and maximum IMT, respectively). The present findings support the concept that LCAT is not required for an efficient reverse cholesterol transport and that a low plasma LCAT concentration and activity is not associated with increased atherosclerosis.

The epidemiological part of the Huume tietokanta (HUUTI) consortium research project is the first large-scale longitudinal study of treatment-seeking illicit drug abusers in Finland. The objective of this report was to describe the sociodemographic characteristics and drug abuse patterns of treatment-seeking clients at their first visit. This study analysed baseline data of 4817 clients (3365 men and 1452 women) aged 11–65 years who sought treatment for drug abuse between 1997 and 2008 at Helsinki Deaconess Institute. Data were collected using a structured questionnaire. The majority (56%) of clients were between 15 and 24 years, educated at elementary school level (75%), and unemployed (57%). Opiates (30%) were the primary drugs of abuse. The primary drugs were mostly injected (45%) and were abused daily during the past month (44%). Cannabis was the most common secondary drug of abuse (34%). The secondary drugs were predominantly smoked (39%) or taken orally (38%) and were abused once per week or less frequently during the past month (33%). Age at initiation of illicit drug abuse ranged from 5 to 49 years. Polydrug abuse was common, with a mean consumption of 3.5 concurrent polydrug use, which were combined from 3 or more drug classes. The prevalence of lifetime/ever intravenous drug abuse was 64% and past month intravenous drug abuse was 64%, respectively, and 13% reported sharing injecting equipment during the past month. Early initiation, polydrug abuse, and risky consumption of illicit drugs were major areas of concern among the study population. Injecting drug use could place considerable burden on health services in view of complications and transmission of infectious diseases.

Several previous epidemiologic studies have shown that high blood levels of carotenoids may be protective against early atherosclerosis, but results have been inconsistent. We assessed the association between atherosclerotic progression, measured by intima-media thickness of the common carotid artery wall, and serum levels of carotenoids.We studied the effect of carotenoids on progression of early atherosclerosis in a population-based study. The association between concentrations of serum carotenoids, and intima-media thickness of the common carotid artery wall was explored in 840 middle-aged men (aged 46-65 years) from Eastern Finland. Ultrasonography of the common carotid arteries were performed at baseline and 7-year follow-up. Serum levels of carotenoids were analyzed at baseline. Changes in mean and maximum intima media thickness of carotid artery wall were related to baseline serum carotenoid levels in covariance analyses adjusted for covariates.In a covariance analysis with adjustment for age, ultrasound sonographer, maximum intima media thickness, examination year, body mass index, systolic blood pressure, smoking, physical activity, serum LDL cholesterol, family history of coronary heart disease, antihypertensive medication and serum high sensitivity C-reactive protein, 7-year change in maximum intima media thickness was inversely associated with lycopene (p = 0.005), α-carotene (p = 0.002) and β-carotene (p = 0.019), respectively.The present study shows that high serum concentrations of carotenoids may be protective against early atherosclerosis.

Accruing evidence suggests that inflammation plays a role in prostate carcinogenesis. However, studies evaluating this association using C‐reactive protein (CRP) and interleukin‐6 as markers of inflammation have reported conflicting results. We investigated the associations of three common markers of inflammation (CRP, fibrinogen and leukocyte count) with the risk of prostate cancer in a prospective cohort of 2,571 men from Finland. During an average follow‐up period of 24 years (21–26 years), 203 men from the cohort who developed prostate cancer were identified via linkage to the nationwide Finnish Cancer Registry. We investigated the associations between the markers and the risk of prostate cancer using Cox proportional hazards model, adjusting for potential confounders. Elevated prediagnostic leukocyte count was associated with an increased risk of prostate cancer. In multivariable adjusted model, the relative risk of prostate cancer among men in the highest tertile of leukocyte count compared to men in the lowest tertile was 1.60 (95% confidence interval [CI] = 1.10–2.29, p ‐trend = 0.01). Circulating CRP and fibrinogen were not associated with increased risk. The corresponding relative risks for elevated CRP and fibrinogen concentrations were 1.08 (95% CI: 0.74–1.60, p ‐trend = 0.56) and 1.25 (95% CI: 0.87–1.81, p ‐trend = 0.14), respectively. Men with elevated leukocyte counts had a 2.57‐fold (95% CI: 0.99–6.79) increased risk of prostate cancer mortality. The increased risk associated with elevated leukocyte counts warrants confirmation in other studies. Larger studies should consider combining at least two markers or using an inflammation score derived from many inflammatory markers to evaluate prostate cancer risk.

Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT).We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline.IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women.Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease.

OBJECTIVE: To systematically review the prevalence of concomitant alcohol and sedative-hypnotic use among middle-aged and older persons. DATA SOURCES: A bibliographic search of English-language literature was performed using MEDLINE, EMBASE, and PsycINFO (January 1990-August 2012). The reference lists of all included articles were screened for additional relevant articles not identified by any of the bibliographic searches. STUDY SELECTION AND DATA EXTRACTION: Population-based studies in which the mean age of participants was 40 years or older were included. For a study to be included in the review, alcohol use had to be reported in terms of the quantity or frequency consumed. Data from included articles were extracted using a standardized data extraction tool. DATA SYNTHESIS: Five population-based studies conducted in North America, 10 in Europe, and 1 in Australia were included in the review. Up to 88% of men and 79% of women who used sedative-hypnotics also consumed alcohol. Up to 28% of those who consumed alcohol were concomitant users of sedative-hypnotics. Alcohol was consumed at higher levels among middle-aged than older persons. Risky drinking (eg, binge drinking, heavy drinking) was more prevalent among middle-aged than older persons. In contrast, sedative-hypnotic use was more prevalent among older persons. CONCLUSIONS: Our review identified a higher prevalence of alcohol consumption among middle-aged than older persons. However, middle-aged persons may experience harm from alcohol/sedative-hypnotic drug interactions due to risky drinking behavior. Despite lower levels of alcohol consumption, older persons may be more susceptible to addictive central nervous system effects than younger persons because of physiologic changes in psychotropic drug and alcohol metabolism. Clinicians should consider patients' alcohol consumption patterns before prescribing sedative-hypnotic drugs.

Background Little is known about the relationship between metabolic syndrome and sudden cardiac death (SCD). We examined the association of metabolic syndrome, as defined by World Health Organization (WHO), International Diabetes Federation (IDF), National Cholesterol Education Program (NCEP) and American Heart Association (AHA) — IDF interim criteria, with incident SCD. We also assessed the association of a continuous metabolic risk score with SCD. Methods A total of 1466 middle-aged men participating in a prospective population-based cohort study from eastern Finland with no history of coronary heart disease or diabetes at baseline were included. Results During the average follow-up of 21 years 85 SCDs occurred. Men with the metabolic syndrome as defined by the WHO, NCEP, IDF and interim criteria had a 2.2–2.6 fold, increased risk for SCD, after adjusting for lifestyle and traditional cardiovascular risk factors not included in the metabolic syndrome definition (P < 0.001–0.011). A one-standard deviation increase in the metabolic risk score (composed of the sum of Z-scores for waist circumference, insulin, glucose, high-density lipoprotein (HDL) cholesterol, triglycerides, and blood pressure) was associated with a 1.68-fold higher (95% CI 1.33-2.11) risk of SCD. Even when adjusting further for systolic blood pressure, HDL cholesterol and body mass index, the association remained significant for the interim criteria and the metabolic risk score, but not for WHO, NCEP, or IDF definitions. Conclusions Men with metabolic syndrome are at increased risk for SCD. Incident SCD associated with the IDF/AHA interim criteria and metabolic risk clustering estimated by a score is not explained by obesity or traditional cardiovascular risk factors. Key messages Men with metabolic syndrome are at increased risk for sudden cardiac death. Incident sudden cardiac death associated with metabolic risk clustering estimated by a score in not explained by obesity or traditional cardiovascular risk factors. Prevention of the metabolic syndrome may help reduce the health burden of SCD.

The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations.Meta-analysis of individual participant data.From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression.Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values.The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Inflammation is associated with cancer but there are conflicting reports on associations of biomarkers of inflammation with cancer risk and mortality. We investigated the associations of C-reactive protein (CRP) and leukocyte count with cancer risk and mortality using individual biomarkers, and an inflammatory score derived from both biomarkers.We conducted this analysis among 2,570 men enrolled in the population-based, prospective Kuopio Ischemic Heart Disease Risk Factor Study in Finland. During an average follow-up period of 26 years, 653 cancer cases and 287 cancer deaths occurred. We computed a z-score for each participant, with the combined z-score being the sum of each individual's CRP and leukocyte z-scores. Multivariable-adjusted Cox proportional hazard model was used to evaluate associations with cancer risk and mortality.Using individual biomarkers, elevated leukocyte count was associated with an increased risk of cancer (RR = 1.31, 95% CI 1.04-1.66), and cancer mortality (RR=, 95% CI 1.39, 0.98-1.97). The corresponding results for CRP were (RR = 1.23, 95% CI 0.97-1.55) for risk and (RR = 1.15, 95% CI 0.81-1.64) for cancer mortality. Associations of the biomarkers with cancer appeared to be more robust using the combined z-score. HRs comparing men within the highest z-score quartile to those within the lowest z-score quartiles were 1.47 (95% CI 1.16-1.88, p-trend < 0.01) for cancer risk, and 1.48 (95% CI 1.03-2.14, p-trend = 0.09) for cancer mortality.Our study suggests that inflammation is associated with cancer risk and mortality, and combining inflammatory biomarkers into a score is a robust method of elucidating this association.

This study explores the effects of occupational (OPA) and leisure time physical activity (LTPA) on mortality relative to cardiorespiratory fitness and pre-existing coronary heart disease (CHD).Associations between OPA, measured as energy expenditure (kcal/day) and relative aerobic workload (%VO2 max), LTPA, and 22-year mortality among 1891 Finnish men were assessed by Cox regression models stratified by CHD and adjusted for 19 confounders.In fully adjusted models, each 10% of relative aerobic workload increased all-cause mortality by 13% and CHD mortality 28% (P < 0.01). Compared to healthy subjects, men with CHD experienced lower mortality risks due to OPA and higher risks due to LTPA. While LTPA had no effect among healthy men, in men with CHD each weekly hour of conditioning LTPA increased all-cause mortality risks by 10% and CHD mortality by14%.OPA was positively associated with both all-cause and CHD mortality. LTPA was not protective. Among men with CHD, LTPA increased mortality risks.

Although both low socioeconomic status (SES) and poor cardiorespiratory fitness (CRF) are associated with increased chronic disease and heightened mortality, it remains unclear whether moderate-to-high levels of CRF are associated with survival benefits in low SES populations. This study evaluated the hypothesis that SES and CRF predict all-cause mortality and cardiovascular disease mortality and that moderate-to-high levels of CRF may attenuate the association between low SES and increased mortality.This study included 2368 men, who were followed in the Kuopio Ischaemic Heart Disease Study cohort. CRF was directly measured by peak oxygen uptake during progressive exercise testing. SES was characterized using self-reported questionnaires.During a 25-year median follow-up, 1116 all-cause mortality and 512 cardiovascular disease mortality events occurred. After adjusting for potential confounders, men with low SES were at increased risks for all-cause mortality (hazard ratio 1.49, 95% confidence interval: 1.30-1.71) and cardiovascular disease mortality (hazard ratio1.38, 1.13-1.69). Higher levels of CRF were associated with lower risks of all-cause mortality (hazard ratio 0.54, 0.45-0.64) and cardiovascular disease mortality (hazard ratio 0.53, 0.40-0.69). In joint associations of SES and CRF with mortality, low SES-unfit had significantly higher risks of all-cause mortality (hazard ratio 2.15, 1.78-2.59) and cardiovascular disease mortality (hazard ratio 1.95, 1.48-2.57), but low SES-fit was not associated with a heightened risk of cardiovascular disease mortality (hazard ratio 1.09, 0.80-1.48) as compared with their high SES-fit counterparts.Both SES and CRF were independently associated with subsequent mortality; however, moderate-to-high levels of CRF were not associated with an excess risk of cardiovascular disease mortality in men with low SES.

Neuropeptide Y (NPY) plays an important role in the hypothalamic regulation of food intake and energy balance. According to recent findings in animals, NPY also seems to be a potent regulator of alcohol consumption. We used the recently identified Leu(7) to Pro(7) polymorphism in the signal peptide part of NPY to investigate whether the NPY system is associated with alcohol consumption in humans. The subjects (N = 889) were an ethnically homogeneous, nonselected population sample of middle-aged men from Eastern Finland. The gene variant producing Pro(7) substitution was associated with a 34% higher average alcohol consumption, even after adjustment for a number of covariates (P = 0.03). The proportion of heavy drinkers (over 230 g of ethanol/week) was also somewhat higher in this group (13.1% vs. 8.2%, P = 0.10). Our study provides the first evidence that alcohol preference in humans is likely to be regulated by the NPY system.

Addictive drugs, including ethanol, increase the brain's dopaminergic transmission, and catechol-o-methyltransferase (COMT) enzyme has a crucial role in dopamine inactivation. A common functional polymorphism in the COMT gene results in a three- to four-fold variation in enzyme activity. In a previous study, we found an association between type 1 (with late-onset but without prominent antisocial behavior) alcoholism and the low activity allele of the COMT gene. In this work we analyzed whether the COMT polymorphism has any effect on the development of type 2 (with early-onset and habitual impulsive violent behavior) alcoholism. The COMT genotype was determined in 62 impulsive violent recidivist offenders with early-onset (type 2) alcoholism, 123 late-onset nonviolent (type 1) alcoholics, and 267 race and gender-matched controls. The allele and genotype frequencies of these groups were compared with each other and also with previously published data from 3,140 Finnish blood donors. The type 2 alcoholics did not differ from either the blood donors or the controls. The low activity (L) allele frequency was higher among type 1 alcoholics (chi(2) = 4.98, P = 0.026) when compared with type 2 cases. The odds ratio for type 1 alcoholism as compared with type 2 alcoholism for those subjects with the LL genotype versus the HH genotype was 3.0 (95% confidence interval 1.1-8.4, P = 0.017). The results suggest that COMT genotype has no major role in the development of early-onset alcoholism with severe antisocial behavior.

A number of psychosomatic studies have suggested that alexithymia, impairment in identifying and expressing inner feelings, might somehow affect the course of various illnesses. However, none of these studies have distinguished between an impact of alexithymia on actual pathophysiological change versus an impact only on illness behavior. In the present study, a population-based random sample of 2297 middle-aged men from Eastern Finland was evaluated for alexithymia using the Finnish version of the self-report Toronto Alexithymia Scale (TAS). Although high TAS scores were associated with prior diagnosis of coronary heart disease (CHD), they were not associated with greater prevalence of ischemia on an exercise tolerance test. The results of B-mode ultrasonography of the carotid artery for those who had a CHD diagnosis showed that carotid atherosclerosis actually decreased significantly as alexithymia increased. An interaction analysis indicated that alexithymia was related to increased probability of being diagnosed with CHD only among those who had mildly or moderately progressed carotid atherosclerosis, and not among those with the most severe progression. Alexithymia was associated with higher perceived exertion, and to some extent, with more self-reported symptoms during the exercise tolerance test. The findings support the hypothesis that alexithymia relates to increased symptom reporting rather than pathophysiological changes in CHD. The results also suggest that alexithymic men may get diagnosed earlier, perhaps because of their different illness behavior.

Abstract Psychosocial correlates of alexithymia were examined in 102 healthy, older adults (ages 53-83; 76% male). Alexithymic ( n = 26) and non-alexithymic ( n = 30) groups, defined by top ( S 70) and bottom ( h 54) quartiles of the distribution of Toronto Alexithymia Scale (26-item) scores, were compared with respect to psychosocial, psychophysiological, and biomedical risk factors for cardiovascular disease. Both categorical ratings and continuous scores of alexithymia were associated with significantly greater levels of trait anxiety, anger-in, neuroticism, hostility, perceived stress, depression, and lower levels of social support. Compared to non-alexithymics, alexithymics displayed significantly greater blood pressure responses to anger provocation and tended to have a greater percent body fat. The groups did not differ in resting cardiovascular parameters, heart rate reactivity, fasting glucose and lipoprotein lipids, body mass index, waist-to-hip ratio, social desirability, or trait anger. These findings suggest several psychosocial and psychophysiological pathways by which alexithymia may confer risk for cardiovascular disease among older adults. Keywords: AlexithymiaCardiovascular ReactivityCardiovascular RiskPsychosocial FactorsOlder Adults

Zinc is an immunomodulatory trace element suggested to be beneficial in the augmentation of antidepressant therapy. Cross-sectional studies have also suggested an association between low dietary zinc and depression. This study examined the association between dietary zinc intake and depression in a prospective setting in initially depression-free men during a 20-year follow-up.The study formed a part of the population-based Kuopio Ischemic Heart Disease Risk Factor (KIHD) Study, and comprised 2317 Finnish men aged 42-61 years. Zinc intake was assessed at baseline by a 4-d food record. Baseline depression severity was recorded with the Human Population Laboratory Depression Scale. In the prospective setting, depression was defined as having received a hospital discharge diagnosis of unipolar depressive disorder. Individuals who at baseline had elevated depressive symptoms were excluded (n=283).Altogether, 60 (2.7%) individuals received a hospital discharge diagnosis of depression during the 20-year follow-up. In Cox regression analysis adjusted for age, baseline depression severity, smoking, alcohol use, physical exercise and the use of dietary supplements, belonging to the lowest tertile of energy-adjusted zinc intake was not associated with an increased depression risk (RR 1.06, 95% CI 0.59-1.90).These observations may not be generalizable to women, or to individuals with a depression level not warranting hospitalization.Our findings suggest that a low dietary zinc intake may not longitudinally precede depression in men. Dietary zinc intake may not have relevance for the prevention of depression in middle-aged men with a sufficient dietary zinc intake.

Vitamin D deficiency has been implicated in cardiovascular disease and is associated with multiple cardiovascular risk factors. We investigated the serum 25-hydroxyvitamin D (25(OH)D) concentration in relation to latitude, baseline carotid intima-media thickness (IMT), and IMT progression, the carotid IMT measures being surrogate markers of subclinical atherosclerosis and cardiovascular disease risk.Serum 25(OH)D concentration was related to high-resolution carotid IMT measures in 3430 middle-aged and elderly subjects with high cardiovascular risk but no prevalent disease, who were recruited at 7 centers in Finland, Sweden, The Netherlands, France, and Italy. Participants underwent carotid ultrasound examination at baseline and at months 15 and 30 after entry into the study, whereas blood samples, clinical data, and information about lifestyle were collected at baseline. Serum 25(OH)D levels were positively associated with latitude (Jonckheere-Terpstra χ=166.643; P<0.001) and, as previously reported, associated with a range of cardiovascular risk factors. There were no independent relationships between 25(OH)D and segment-specific or composite IMT measures in the entire cohort. In analyses stratified by sex, diabetes mellitus, and statin treatment, weak associations with some baseline and progression measures of carotid IMT were observed in males, diabetics, and nonstatin-treated individuals.Levels of 25(OH)D differed across Europe, were highest in the North, showed multiple associations with established and emerging cardiovascular risk factors but were not consistently, independently related to measures of carotid IMT. This argues against a protective role of vitamin D against subclinical atherosclerosis in high-risk individuals.

Plasma adiponectin levels have previously been inversely associated with carotid intima-media thickness (IMT), a marker of subclinical atherosclerosis. In this study, we used a sex-stratified Mendelian randomization approach to investigate whether adiponectin has a causal protective influence on IMT.Baseline plasma adiponectin concentration was tested for association with baseline IMT, IMT progression over 30 months, and occurrence of cardiovascular events within 3 years in 3430 participants (women, n=1777; men, n=1653) with high cardiovascular risk but no prevalent disease. Plasma adiponectin levels were inversely associated with baseline mean bifurcation IMT after adjustment for established risk factors (β=-0.018, P<0.001) in men but not in women (β=-0.006, P=0.185; P for interaction=0.061). Adiponectin levels were inversely associated with progression of mean common carotid IMT in men (β=-0.0022, P=0.047), whereas no association was seen in women (0.0007, P=0.475; P for interaction=0.018). Moreover, we observed that adiponectin levels were inversely associated with coronary events in women (hazard ratio 0.57, 95% CI 0.37 to 0.87) but not in men (hazard ratio 0.82, 95% CI 0.54 to 1.25). A gene score of adiponectin-raising alleles in 6 loci, reported recently in a large multi-ethnic meta-analysis, was inversely associated with baseline mean bifurcation IMT in men (β=-0.0008, P=0.004) but not in women (β=-0.0003, P=0.522; P for interaction=0.007).This report provides some evidence for adiponectin protecting against atherosclerosis, with effects being confined to men; however, compared with established cardiovascular risk factors, the effect of plasma adiponectin was modest. Further investigation involving mechanistic studies is warranted.

Fish intake and the long-chain omega-3 polyunsaturated fatty acids (PUFAs) in fish have been suggested to lower the risk of cognitive decline. We assessed whether serum long-chain omega-3 PUFAs eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) are associated with performance on neuropsychological tests in an older population and whether exposure to methylmercury, mainly from fish, or apolipoprotein-E4 (Apo-E4) phenotype can modify the associations.A total of 768 participants from the population-based Kuopio Ischaemic Heart Disease Risk Factor Study were included. Cognitive function was measured using five neuropsychological tests: the Trail Making Test, the Verbal Fluency Test, the Selective Reminding Test, the Visual Reproduction Test and the Mini Mental State Exam. Multivariate-adjusted analysis of covariance and linear regression were used to analyze the cross-sectional associations.We found statistically significant associations between serum EPA+DPA+DHA and better performance in the Trail Making Test and the Verbal Fluency Test. The individual associations with EPA and DHA were similar with the findings with EPA+DPA+DHA, although the associations with DHA were stronger. No associations were observed with serum DPA. Pubic hair mercury content was associated only with a worse performance in the Trail Making Test, and mercury had only little impact on the associations between the serum PUFAs and cognitive performance. Apo-E4 phenotype did not modify the associations with PUFAs or mercury.Higher serum long-chain omega-3 PUFA concentrations were associated with better performance on neuropsychological tests of frontal lobe functioning in older men and women. Mercury exposure or Apo-E4 phenotype had little impact on cognitive performance.

Although health strategies and policies have addressed equitable distribution of health care in Mongolia, few studies have been conducted on this topic. Rapid socio-economic changes have recently occurred; however, there is no evidence as to how horizontal inequity has changed. The aim of this paper is to evaluate income related-inequalities in health care utilizations and their changes between 2007/2008 and 2012 in Mongolia.The data used in this study was taken from the nationwide cross-sectional data sets, the Household Socio-Economic Survey, collected in 2007/2008 and 2012 by the National Statistical Office of Mongolia. We employed the Erreygers' concentration index to measure inequality in health service utilization. Horizontal inequity was estimated by a difference between actual and predicted use of health services using the indirect standardization method.The results show that the concentration indices for tertiary level, private outpatient and inpatient services were significantly positive, the contrary for family group practice/soum hospital outpatient services, in both years. After controlling for need, pro-rich inequity (p < 0.01) was observed in the tertiary level, private outpatient, and general inpatient, services in both years. Pro-poor inequity (p < 0.01) existed in family group practice/soum hospital outpatient services in both years. Degrees of inequity in tertiary level hospital and private hospital outpatient services became more pro-rich, whereas in family group practice/soum hospital outpatient services became more pro-poor from 2007/2008 to 2012. Pro-rich inequity in inpatient services remained the same from 2007/2008 to 2012.Equitable distribution of health care has been well documented in health strategies and policies; however, the degree of inequity in delivery of health services has a tendency to increase in Mongolia. Therefore, there is a need to consider implementation issues of the strategies and refocus on policy prioritizations. It is necessary to strengthen primary health care services, particularly by diminishing obstacles for lower income and higher need groups.

In Kenya, leaves and roots from Croton macrostachyus are used as a traditional medicine for infectious diseases such as typhoid and measles, but reports on possible antimicrobial activity of stem bark do not exist. In this study, the antibacterial and antifungal effects of methanol, ethyl acetate and butanol extracts, and purified lupeol of C. macrostachyus stem bark were determined against important human gram-negative pathogens Escherichia coli, Salmonella typhi, Klebsiella pneumoniae, and Enterobacter aerogenes, gram-positive Listeria monocytogenes, and a fungus Candida albicans. The most promising broad scale antimicrobial activity against all the studied pathogens was shown by the ethyl acetate extract. The ethyl acetate extract induced the zone of inhibition between 10.1 ± 0.6 mm and 16.0 ± 1.2 mm against S. typhi, E. coli, K. pneumoniae, E. aerogenes, and L. monocytogenes with weaker antimicrobial activity against C. albicans (zone of inhibition: 5.6 ± 1.0 mm). The antibiotic controls (amoxicillin, ciprofloxacin, ampicillin, benzylpenicillin, clotrimazole, and cefotaxime) showed antimicrobial activity with zones of inhibition within 13.4 ± 0.7-22.1 ± 0.9 mm. The ethyl acetate extract had MIC in the range of 125-250 mg/mL against all the studied bacteria and against C. albicans MIC was 500 mg/mL. The present results give scientific evidence and support the traditional use of C. macrostachyus stem bark as a source for antimicrobials. We show that C. macrostachyus stem bark lupeol is a promising antimicrobial agent against several important human pathogens.

To address the question of whether users of herbal products (HPs) are exposed to harmful contaminants, we evaluated six HPs mostly patronized in Kumasi for heavy metal contamination and assessed the health risk associated with their use. This study is one of the first safety evaluation studies on finished multiherbal products in the region.Three antimalarial, two antidiabetic and one antihypertensive HPs were selected after a mini-survey and coded randomly as HP A-F. The HPs were acid digested for quantitative analysis of heavy metals using Inductively Coupled Plasma Mass Spectrometer. Hg quantification was carried out using cold vapour atomic absorption spectroscopy.The cancer risk estimation values for the carcinogenic metals ranged between 1.54 × 10-9 to 3.73 × 10-4 and were all within acceptable limits. The non-cancer health risk evaluation revealed that, some of the products pose health risk to consumers. The estimated daily intake (EDI) for As in HPF was 2.48 × 10-4 mg/kg/day compared to the reference limit of 1.67 × 10-4 mg/kg/day. HPF also had high hazard index (HI) of 5.70 (HI >1) in children as compared to 1.68 (HI >1) in adults showing a 3.4 folds increase in the health risk among the former.The six polyherbal products exhibited carcinogenic risk within acceptable limits. Although, the non-carcinogenic risk assessment of products HPA to HPE suggests safety, this can only be ascertained after further characterization of their health risks in detailed chronic toxicity studies. The high HI for product HPF suggests health risk for consumers of this product.

Strong associations have been demonstrated between the American Heart Association's cardiovascular health (CVH) metrics and various cardiovascular outcomes, but the association with sudden cardiac death (SCD) is uncertain. We examined the associations between these CVH metrics and the risks of SCD and all-cause mortality among men in Finland.We used the prospective population-based Kuopio Ischaemic Heart Disease cohort study, which consists of men between 42 and 60 years of age at baseline. CVH metrics were computed for 2577 men with CVH scores at baseline ranging from 0 to 7, categorized into CVH scores of 0-2 (poor), 3-4 (intermediate) and 5-7 (ideal). Multivariate Cox regression models were used to estimate the hazards ratios (HRs) and 95% confidence intervals (CIs) of ideal CVH metrics for SCD and all-cause mortality. During a median follow-up period of 25.8 years, 280 SCDs and 1289 all-cause mortality events were recorded. The risks of SCD and all-cause mortality decreased continuously with increasing number of CVH metrics across the range 2-7 (p value for non-linearity for all <0.05). In multivariable analyses, men with an ideal CVH score had an 85% reduced risk of SCD compared with men with a poor CVH score (HR 0.15; 95% CI 0.05-0.48; p = 0.001). For all-cause mortality, there was a 67% lower risk among men with an ideal CVH score compared with those with a poor CVH score (HR 0.33; 95% CI 0.23-0.49; p <0.001).Ideal CVH metrics were strongly and linearly associated with decreased risks of SCD and all-cause mortality among middle-aged men in Finland.

Objectives Loneliness and social isolation both increase mortality and are likely to affect health via several pathways. However, information on the potential pathways remains scarce. We investigated the associations between loneliness, social isolation, and mortality, and possible mechanisms underlying these connections.Methods The analyzed data comprised a prospective population-based cohort of Finnish men (42–61 years at baseline, n = 2588) who were followed up for an average of 23.2 years. Mortality data were obtained from the national population register in 2012. Cox proportional hazards analysis with adjustments for possible confounding factors was used to examine the associations between loneliness and social isolation at baseline and all-cause, injury, cancer, and cardiovascular disease (CVD) mortality. Mediation analysis was conducted to investigate the mechanisms underlying the associations of loneliness and social isolation with mortality.Results Loneliness predicted all-cause mortality, even after adjustments for all covariates. Loneliness predicted cancer mortality, except after adjustments for lifestyle variables or Human Population Laboratory (HPL) depression scores, and also predicted CVD mortality, except after adjustments for HPL depression scores. Social isolation predicted all-cause mortality and injury mortality. The effect of social isolation on all-cause mortality was mediated by loneliness and HPL depression scores.Conclusions Our findings suggest that both loneliness and social isolation increase the risk of all-cause mortality, while they have differing effects on different causes of death. Loneliness and depressive symptoms may mediate the effect of social isolation on increased mortality.

Globally, cancer is the second leading cause of death. Loneliness has been suggested as a risk factor for cancer mortality. However, connections between loneliness, social isolation, and cancer are poorly understood. In our longitudinal study (mean follow-up: 20.44 years) of 2570 middle-aged men, loneliness, social isolation, and health-related factors were measured at baseline. Cox proportional hazards analysis was used to examine the association between cancer incidence, loneliness, and social isolation. The effect of relationship status on cancer mortality among cancer patients was tested with the Kaplan-Meier method. Loneliness was associated with total cancer incidence after adjustments for tested lifestyle and health-related covariates. Social Isolation was associated with total cancer incidence, except when adjusted for lifestyle, diet, or Human Population Laboratory (HPL) Depression Scale scores. Loneliness was associated with lung cancer incidence, except when adjusted for HPL Depression Scale scores. There was no significant association between social isolation and lung cancer. Neither loneliness nor social isolation were connected with prostate or colorectal cancer. Being single at baseline was associated with worse survival outcomes for cancer patients. Our findings suggest that regardless of the social network size, loneliness among middle-aged men is associated with an increased likelihood of cancer.

Physical inactivity and poor cardiorespiratory fitness have been found to be associated with an increased risk of coronary heart disease, hypertension, stroke, non-insulin-dependent diabetes mellitus and cancer. To characterize the least active and the least fit sociodemographic groups of middle-aged males, we investigated conditioning leisure time physical activity and maximal oxygen uptake (VO2max) in a population sample of 2589 men aged 42–60 years in Eastern Finland. In covariate models, younger (P = 0.004), rural (P < 0.001), married or engaged (P = 0.04), lower income (P = 0.009), and employed men (P < 0.001), as well as farmers (P < 0.001) had a shorter duration of physical activity, whereas older (P < 0.001), urban (P = 0.05), single (P < 0.001), less educated (P < 0.001), lower income (P < 0.001), and unemployed or retired men (P < 0.001), as well as blue-collar workers (P < 0.001) had a lower mean intensity of physical activity than others. Older (P < 0.001), single (P < 0.001), less educated (P < 0.001), lower income (P < 0.001), and unemployed or retired men (P < 0.001), as well as blue-collar workers and farmers (P < 0.001) had lower VO2max than others. On the basis of our data, for health promotion regarding physical activity, special attention should be paid to people In a lower socioeconomic position.

We studied the associations between 11 scales of social functioning and risk of death over an average follow-up time of 71 months in 42- to 60-year-old men in the Kuopio Ischemic Heart Disease Risk Factor Study. In age-adjusted analyses, men were at increased risk of death if they reported few persons to whom they gave or received social support, nonparticipation in organizations, low quality of social relationships, a small number of friends, or not currently being married. Frequency of interaction, shyness, and use of emotional support when troubled were not associated with risk of death; the use of instrumental support when troubled was associated with increased risk. There was little evidence of confounding of these associations by the presence of 31 chronic or acute conditions, perceived health status, or six risk factors. Consistent associations were found in a healthy subgroup. These data add to the growing body of literature linking mortality risk with social functioning, especially in relation to organizational participation and quality of relationships.

The role of circulating levels of total homocysteine tHcy in the development of coronary heart disease (CHD) is still under debate. One reason for conflicting results between previous studies on homocysteine and heart diseases could be consequence of different interactions between homocysteine and genes in different study populations. Many genetic factors play a role in folate-homocysteine metabolism, like functional polymorphism (Val108Met) in the Catechol-O-methyltransferase (COMT) gene.Our aim was to examine the role of COMT Val158Met polymorphism and interaction of this polymorphism with serum tHcy and folate concentration on the risk of acute coronary and events in middle-aged men from eastern Finland. A population-based prospective cohort of 792 men aged 46-64 years was examined as part of the Kuopio Ischaemic Heart Disease Risk Factor Study. During an average follow-up of 9.3 years, there were 69 acute coronary events in men with no previous history of CHD. When comparing the COMT low activity genotype with the others, we found an age and examination year adjusted hazard rate ratio (HRR) of 1.73 (95% confidence interval (CI), 1.07-2.79), and an age, examination year, serum LDL and HDL cholesterol, and triglyceride concentration, systolic blood pressure and smoking adjusted HRR of 1.77 (95% CI, 1.05-2.77). Although serum tHcy concentration was not statistically significantly associated with acute coronary events (HRR for the highest third versus others 1.52, 95% CI, 0.93-2.49), subjects with both high serum tHcy and the COMT low activity genotype had an additionally increased adjusted risk of HRR 2.94 (95% CI 1.50-5.76) as compared with other men.This prospective cohort study suggests that the functional COMT Val158Met polymorphism is associated with increased risk of acute coronary events and it may interact with high serum tHcy levels.

The antimicrobial activity and phenolic compounds of five Finnish honey products against important human pathogens Streptococcus pneumoniae, S. pyogenes, Staphylococcus aureus, and methicillin-resistant S. aureus were analyzed. Microbroth dilution method and HPLC-DAD were used in antimicrobial testing and phenolic compound determination, respectively. Significant antimicrobial activity (p < 0.01) against all the tested pathogens was found from willow herb (Epilobium angustifolium), heather (Calluna vulgaris), and buckwheat (Fagopyrum esculentum) honeys. This is the first report on antimicrobial activity of Finnish monofloral honeys against streptococcal and staphylococcal bacteria. To our knowledge this is also the first report on the antimicrobial effect of honey against S. pneumoniae.

The role of systolic blood pressure (SBP) as an independent risk factor for sudden cardiac death (SCD) is not well defined in a general population. Thus, we assessed the association between BP at rest and risk of SCD. BP and other risk factors were measured in a representative population-based sample of 2,666 Finnish men (42 to 61 years of age). During an average follow-up period of 18.9 years (interquartile range 17.9 to 22.6), 213 SCDs occurred. Each increment 10-mm Hg of SBP at rest was associated with an increased risk of SCD (relative hazard 1.15, 95% confidence interval 1.07 to 1.25, p <0.001) after adjustment for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, body mass index, left ventricular hypertrophy, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications. Men with increased SBP of >145 mm Hg had a 2.04-fold (95% confidence interval 1.23 to 2.52, p = 0.003) adjusted risk for SCD compared to those with SBP <123 mm Hg. In conclusion, this study emphasizes the importance of the definition of SBP at rest because it provides a valuable prognostic measurement for SCD. The role of systolic blood pressure (SBP) as an independent risk factor for sudden cardiac death (SCD) is not well defined in a general population. Thus, we assessed the association between BP at rest and risk of SCD. BP and other risk factors were measured in a representative population-based sample of 2,666 Finnish men (42 to 61 years of age). During an average follow-up period of 18.9 years (interquartile range 17.9 to 22.6), 213 SCDs occurred. Each increment 10-mm Hg of SBP at rest was associated with an increased risk of SCD (relative hazard 1.15, 95% confidence interval 1.07 to 1.25, p <0.001) after adjustment for age, alcohol consumption, cigarette smoking, serum low-density lipoprotein cholesterol, type 2 diabetes, body mass index, left ventricular hypertrophy, previous myocardial infarction, family history of coronary heart disease, and use of antihypertensive medications. Men with increased SBP of >145 mm Hg had a 2.04-fold (95% confidence interval 1.23 to 2.52, p = 0.003) adjusted risk for SCD compared to those with SBP <123 mm Hg. In conclusion, this study emphasizes the importance of the definition of SBP at rest because it provides a valuable prognostic measurement for SCD.

We aimed to examine the impact of anxiety and somatic concerns on the mortality risk during a 23-year follow-up of a representative sample of men. Finnish men aged 42–61 years (n = 2388) were followed up for a median of 23.4 years. Anxiety was assessed using baseline scores for the Minnesota Multiphasic Personality Inventory Psychasthenia subscale and somatic concerns were measured with the Hypochondriasis subscale. Mortality data were obtained from the National Population Register. All-cause, injury, disease, cardiovascular, and cancer mortalities were examined as endpoints. Adjustments were performed for age, smoking, alcohol consumption, physical activity, low- and high-density lipoprotein cholesterol, body mass index, systolic blood pressure, a history of cardiovascular disease, marital status, socioeconomic status, the Framingham Type A Behavior Pattern Scale, and life events during the 12 months before the baseline examination. Anxiety and somatic concerns predicted the all-cause mortality risk after full adjustments for sociodemographic background, lifestyle factors, and descriptors of somatic health. Regarding other forms of mortality, the risk ratios were significant after full adjustments in anxiety for injury and in somatic concerns for disease death. This study supported previous findings of anxiety predicting the all-cause mortality risk in men. Somatic concerns are a novel factor that needs to be taken into account while examining associations between personality and the risk of increased mortality.

Experimental studies have suggested that autoimmunity is involved in atherosclerosis and provided evidence that both protective and pro-atherogenic immune responses exist. This concept has received support from small clinical studies implicating autoantibodies directed against apolipoprotein B-100 (apoB-100) in human atherosclerosis. We examined circulating autoantibodies directed against native and malondialdehyde (MDA)-modified epitope p210 of apoB-100 (IgG-p210nat and IgM-p210MDA) in relation to early atherosclerosis in a large, European longitudinal cohort study of healthy high-risk individuals.IgG-p210nat and IgM-p210MDA were quantified in baseline plasma samples of 3430 participants in the IMPROVE study and related to composite and segment-specific measures of severity and rate of progression of carotid intima-media thickness (cIMT) determined at baseline and after 30 months. IgM-p210MDA autoantibody levels were independently related to several cIMT measures both in the common carotid artery and in the carotid bulb, including measures of cIMT progression, higher levels being associated with lower cIMT or slower cIMT progression. Consistent inverse relationships were also found between plasma levels of IgG-p210nat and baseline composite measures of cIMT. These associations disappeared when adjusting for established and emerging risk factors, and there were no associations with rate of cIMT progression besides in certain secondary stratified analyses.The present study provides further evidence of involvement of autoantibodies against native and MDA-modified apoB-100 peptide 210 in cardiovascular disease in humans and demonstrates that these associations are present already at a subclinical stage of the disease.