John Öhrvik

The results of retrospective and prospective case-control studies have clearly established that mild elevations of the plasma homocysteine level are associated with increased risk of coronary, cerebral, and peripheral vascular disease. Recently, a mutation (677C-->T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene that results in reduced folate-dependent enzyme activity and reduced remethylation of homocysteine to methionine. Mutant homozygotes (TT genotype) constitute approximately 12% of the white population and frequently have mildly elevated circulating homocysteine. Therefore, it seems likely that they would also be at increased risk of vascular disease. A number of studies have investigated this during the past 3 years, and the present article evaluates the results in a meta-analysis.We identified 13 studies in which there were measurements of plasma homocysteine in relation to the 3 genotypes (TT, CT, and CC) and 23 case-control studies comprising 5869 genotyped cardiovascular disease patients (mostly coronary artery disease) and 6644 genotyped control subjects. Those bearing the TT genotype had plasma homocysteine concentrations 2.6 micromol/L (25%) higher than those with the CC genotype. However, there was no difference between patients and control subjects either in the frequency of mutant alleles (T) (34.3% versus 33.8%) or the TT genotype (11.9% versus 11.7%). In the analysis of the 23 studies, the relative risk (OR) of vascular disease associated with the TT genotype was 1.12 (95% CI, 0.92 to 1.37).We conclude that although the C677T/MTHFR mutation is a major cause of mild hyperhomocysteinemia, the mutation does not increase cardiovascular risk. Our findings suggest that the mild hyperhomocysteinemia found frequently in vascular disease patients is not causally related to the pathogenesis of the vascular disease.

Proinsulin is a precursor of mature insulin and C-peptide. Higher circulating proinsulin levels are associated with impaired β-cell function, raised glucose levels, insulin resistance, and type 2 diabetes (T2D). Studies of the insulin processing pathway could provide new insights about T2D pathophysiology.We have conducted a meta-analysis of genome-wide association tests of ∼2.5 million genotyped or imputed single nucleotide polymorphisms (SNPs) and fasting proinsulin levels in 10,701 nondiabetic adults of European ancestry, with follow-up of 23 loci in up to 16,378 individuals, using additive genetic models adjusted for age, sex, fasting insulin, and study-specific covariates.Nine SNPs at eight loci were associated with proinsulin levels (P < 5 × 10(-8)). Two loci (LARP6 and SGSM2) have not been previously related to metabolic traits, one (MADD) has been associated with fasting glucose, one (PCSK1) has been implicated in obesity, and four (TCF7L2, SLC30A8, VPS13C/C2CD4A/B, and ARAP1, formerly CENTD2) increase T2D risk. The proinsulin-raising allele of ARAP1 was associated with a lower fasting glucose (P = 1.7 × 10(-4)), improved β-cell function (P = 1.1 × 10(-5)), and lower risk of T2D (odds ratio 0.88; P = 7.8 × 10(-6)). Notably, PCSK1 encodes the protein prohormone convertase 1/3, the first enzyme in the insulin processing pathway. A genotype score composed of the nine proinsulin-raising alleles was not associated with coronary disease in two large case-control datasets.We have identified nine genetic variants associated with fasting proinsulin. Our findings illuminate the biology underlying glucose homeostasis and T2D development in humans and argue against a direct role of proinsulin in coronary artery disease pathogenesis.

Background— The secreted protein proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular disease (CVD). The relationship between circulating PCSK9 and incident CVD in the general population is unknown. We investigated whether serum PCSK9 concentration is associated with incident CVD in a prospective cohort study of 4232 men and women 60 years of age at the time of recruitment. Methods and Results— Incident CVD was recorded by matching to national registries. After 15 years of follow-up, a total of 491 incident events (fatal and nonfatal myocardial infarctions, unstable angina, deaths from coronary heart disease, fatal and nonfatal ischemic strokes) were recorded. Cox proportional hazards model was used to calculate hazard ratios with 95% confidence intervals. Baseline serum PCSK9 concentration predicted incident CVD; concentration in quartile 4 compared with quartile 1 was associated with a hazard ratio of 1.69 (95% confidence interval, 1.30–2.19) after adjustment for sex. Further adjustment for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, lipoprotein(a), triglycerides, hypertension, diabetes mellitus, smoking, overweight, obesity, physical inactivity, and statin use resulted in a decrease in the hazard ratio to 1.48 (95% confidence interval, 1.12–1.95). Conclusions— Serum PCSK9 concentration is associated with future risk of CVD even after adjustments for established CVD risk factors. Further studies are needed to confirm this observation.

Recent data revealed that patients with myocardial infarction (MI) have a high prevalence of previously unknown diabetes mellitus (DM) and impaired glucose tolerance (IGT). The added prognostic importance of this finding has not been prospectively explored. To investigate whether a newly detected abnormal glucose tolerance (IGT or DM) assessed early after an MI, is related to long-term prognosis.Patients (n=168; age 63.5+/-9.3 years) with MI, no previous DM and admission blood glucose <11.0 mmol/l were followed for major cardiovascular events defined as the composite of cardiovascular death, non-fatal MI, non-fatal stroke or severe heart failure (HF). According to an oral glucose tolerance test (OGTT) before hospital discharge, 55 patients had normal and 113 abnormal glucose tolerance (GT). During the follow-up of median 34 months there were eight cardiovascular deaths, 15 patients had a recurrent MI, six had a stroke and ten severe HF. All patients who died from cardiovascular causes had abnormal GT. The composite cardiovascular event occurred in 31 (18%) patients. The probability of remaining free from cardiovascular events was significantly higher in patients with normal than abnormal GT (p=0.002). Together with previous MI, abnormal GT was the strongest predictor of future cardiovascular events (hazard ratio 4.18; CI 1.26-13.84; p=0.019).Abnormal glucose tolerance is a strong risk factor for future cardiovascular events after myocardial infarction. Since it is common and possible to detect even during the hospital phase it may be a target for novel secondary preventive efforts.

Although diabetes is known to be a major contributor to cardiovascular diseases, as well as an independent predictor for adverse outcomes in patients with coronary artery disease (CAD), information on the prognosis of patients with CAD and newly diagnosed diabetes or impaired glucose regulation (IGR) is scarce. The objective of this study was to explore 1-year outcome in relation to different glucometabolic states of patients participating in the Euro Heart Survey on diabetes and the heart.In 4676 out of 4961 patients, information on the relation between 1-year outcome and glucometabolic state, which was based on oral glucose tolerance test (OGTT) or fasting glucose plasma, was available. A normal glucose metabolism was identified in 947 patients, IGR (impaired fasting glucose or impaired glucose tolerance) in 1116 patients, and diabetes in 1877 patients of whom 1425 were previously diagnosed and 452 newly diagnosed. In total, 736 patients could not be classified, as no OGTT or fasting plasma glucose was performed. Previously recognized and newly detected diabetes was associated with an increased risk of 1-year mortality when compared with patients with normal glucose regulation [hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.5-3.8 and HR 2.0, 95% CI 1.1-3.6, respectively)]. IGR, however, could not be identified as an independent predictor for 1-year mortality (HR 1.1, 95% CI 0.6-1.9).This study confirmed that patients with CAD and known diabetes are at high risk for mortality and cardiovascular events and demonstrated that patients with newly diagnosed diabetes are at intermediate risk for adverse outcomes. IGR, however, could not be identified as an independent predictor for adverse outcomes during the 1-year follow-up period.

Prospective studies indicate that apolipoprotein measurements predict coronary heart disease (CHD) risk; however, evidence is conflicting, especially in the US. Our aim was to assess whether measurements of apolipoprotein B (apoB) and apolipoprotein A-I (apoA-I) can improve the ability to predict CHD death beyond what is possible based on traditional cardiovascular (CV) risk factors and clinical routine lipid measurements.We analysed prospectively associations of apolipoprotein measurements, traditional CV risk factors, and clinical routine lipid measurements with CHD mortality in a multi-ethnic representative subset of 7594 US adults (mean age 45 years; 3881 men and 3713 women, median follow-up 124 person-months) from the Third National Health and Nutrition Examination Survey mortality study. Multiple Cox-proportional hazards regression was applied. There were 673 CV deaths of which 432 were from CHD. Concentrations of apoB [hazard ratio (HR) 1.98, 95% confidence interval (CI) 1.09-3.61], apoA-I (HR 0.48, 95% CI 0.27-0.85) and total cholesterol (TC) (HR 1.17, 95% CI 1.02-1.34) were significantly related to CHD death, whereas high density lipoprotein cholesterol (HDL-C) (HR 0.68, 95% CI 0.45-1.05) was borderline significant. Both the apoB/apoA-I ratio (HR 2.14, 95% CI 1.11-4.10) and the TC/HDL-C ratio (HR 1.10, 95% CI 1.04-1.16) were related to CHD death. Only apoB (HR 2.01, 95% CI 1.05-3.86) and the apoB/apoA-I ratio (HR 2.09, 95% CI 1.04-4.19) remained significantly associated with CHD death after adjusting for CV risk factors.In the US population, apolipoprotein measurements significantly predict CHD death, independently of conventional lipids and other CV risk factors (smoking, dyslipidaemia, hypertension, obesity, diabetes and C-reactive protein). Furthermore, the predictive ability of apoB alone to detect CHD death was better than any of the routine clinical lipid measurements. Inclusion of apolipoprotein measurements in future clinical guidelines should not be discarded.

Patients with coronary artery disease (CAD) and abnormal glucose regulation (AGR) are at high risk for subsequent cardiovascular events, underlining the importance of accurate glucometabolic assessment in clinical practice.To investigate different methods to identify glucose disturbances among patients with acute and stable coronary heart disease.Consecutive patients referred to cardiologists were prospectively enrolled at 110 centres in 25 countries (n = 4961). Fasting plasma glucose (FPG) and glycaemia 2 h after a 75-g glucose load were requested in patients without known glucose abnormalities (n = 3362). Glucose metabolism was classified according to the World Health Organization and American Diabetes Association (ADA; 1997, 2004) criteria as normal, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or diabetes.Data on FPG and 2-h post-load glycaemia were available for 1867 patients, of whom 870 (47%) had normal glucose regulation, 87 (5%) had IFG, 591 (32%) had IGT and 319 (17%) had diabetes. If classification had been based on the ADA criterion from 1997, the proportion of misclassified (underdiagnosed) patients would have been 39%. The ADA 2004 criterion would have overdiagnosed 8% and underdiagnosed 33% of the patients, resulting in a total misclassification rate of 41%. For ethical concerns and practical reasons, oral glucose tolerance test (OGTT) was not conducted in 1495 of eligible patients. These patients were more often women, had higher age and waist circumference, and were therefore more likely to have AGR than those who were included. A model based on easily available clinical and laboratory variables, including FPG, high-density lipoprotein cholesterol, age and the logarithm of glycated haemoglobin A1c, misclassified 44% of the patients, of whom 18% were overdiagnosed and 26% were underdiagnosed.An OGTT is still the most appropriate method for the clinical assessment of glucometabolic status in patients with coronary heart disease.

Objective Biological evidence suggests that inflammation might induce type 2 diabetes (T2D), and epidemiological studies have shown an association between higher white blood cell count (WBC) and T2D. However, the association has not been systematically investigated. Research Design and Methods Studies were identified through computer-based and manual searches. Previously unreported studies were sought through correspondence. 20 studies were identified (8,647 T2D cases and 85,040 non-cases). Estimates of the association of WBC with T2D were combined using random effects meta-analysis; sources of heterogeneity as well as presence of publication bias were explored. Results The combined relative risk (RR) comparing the top to bottom tertile of the WBC count was 1.61 (95% CI: 1.45; 1.79, p = 1.5*10−18). Substantial heterogeneity was present (I2 = 83%). For granulocytes the RR was 1.38 (95% CI: 1.17; 1.64, p = 1.5*10−4), for lymphocytes 1.26 (95% CI: 1.02; 1.56, p = 0.029), and for monocytes 0.93 (95% CI: 0.68; 1.28, p = 0.67) comparing top to bottom tertile. In cross-sectional studies, RR was 1.74 (95% CI: 1.49; 2.02, p = 7.7*10−13), while in cohort studies it was 1.48 (95% CI: 1.22; 1.79, p = 7.7*10−5). We assessed the impact of confounding in EPIC-Norfolk study and found that the age and sex adjusted HR of 2.19 (95% CI: 1.74; 2.75) was attenuated to 1.82 (95% CI: 1.45; 2.29) after further accounting for smoking, T2D family history, physical activity, education, BMI and waist circumference. Conclusions A raised WBC is associated with higher risk of T2D. The presence of publication bias and failure to control for all potential confounders in all studies means the observed association is likely an overestimate.

Plasminogen activator inhibitor type 1 (PAI-1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAI-1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAI-1 on CHD risk.To evaluate the association between PAI-1 and CHD, we applied a 3-step strategy. First, we investigated the observational association between PAI-1 and CHD incidence using a systematic review based on a literature search for PAI-1 and CHD studies. Second, we explored the causal association between PAI-1 and CHD using a Mendelian randomization approach using summary statistics from large genome-wide association studies. Finally, we explored the causal effect of PAI-1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic meta-analysis, the highest quantile of blood PAI-1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an age- and sex-adjusted model. The effect size was reduced in studies using a multivariable-adjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAI-1 level on CHD risk (odds ratio=1.22 per unit increase of log-transformed PAI-1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAI-1 on elevating blood glucose and high-density lipoprotein cholesterol.Our study indicates a causal effect of elevated PAI-1 level on CHD risk, which may be mediated by glucose dysfunction.

Systemic lupus erythematosus (SLE), is a heterogeneous disease which predominantly affects young females (90%). SLE is associated with a shorter life expectancy than in the general population. Standardized mortality ratios (SMR) of 2.4 have been reported, which is comparable to diabetes. In modern societies cardiovascular disease (CVD) is the major cause of premature mortality. Accelerated atherosclerosis is generally assumed to be the underlying cause for SLE related CVD. However, previous studies diverge regarding whether atherosclerosis is more common in SLE than in controls. With this in mind and based on own clinical experience we hypothesized that accelerated atherosclerosis is not a general feature of SLE, but prevails in SLE subgroups.281 SLE patients and 281 individually age and sex matched population controls, were investigated clinically. Fasting blood samples and risk factor data were collected. All participants were subject to B-mode ultrasonography of the carotid arteries. Carotid plaque occurrence and mean intima media thickness (mIMT) were recorded. Two SLE subgroups previously described to be at high CVD risk; 1) patients with nephritis and 2) patients with anti-phospholipid antibodies (aPL), and one subgroup reported to be at comparatively lower CVD risk; patients positive for Sjögren´s syndrome antigens A/B (SSA/SSB) antibodies were analyzed separately in comparison with their respective matched controls.Median age was 49 (IQR 36-59) years, 93% were females. Manifest CVD; ischemic heart, cerebro- and peripheral vascular disease, prevailed in patients (12% vs. 1%, p<0.0001). Overall plaque prevalence did not differ (20% vs. 16%), but patients had slightly higher mIMT than controls (0.56 vs. 0.53 mm, p<0.0033). After age adjustment plaques, but not mIMT, remained associated with previous CVD events. Therefore we focused further analyses on plaques, a more robust measure of atherosclerosis. Patients with nephritis (40%), but neither aPL (25%) nor SSA/SSB (40%) positive patients, had more plaques than their respective controls (23% vs. 11%, p = 0.008). Notably, patients with nephritis were younger than other SLE patients (45 vs.49 years, p = 0.02). To overcome the confounding effect of age we performed an age-matched nested case-control analysis, which demonstrated that patients with nephritis had twice as often plaques (23%) as both non-nephritis patients (11%, p = 0.038) and controls (12%, p = 0.035).In SLE excess carotid plaques are essentially confined to the SLE subgroup with nephritis. This subgroup had plaques twice as often as age-matched non-nephritis SLE patients and population controls. Non-nephritis SLE patients, including the aPL positive subgroup, which has a high CVD risk, had similar prevalence of plaques as controls. To prevent later CVD events, this novel observation calls for risk factor screening and initiation of anti-atherosclerotic treatment selectively in SLE nephritis patients. Preferably at nephritis onset, which is often at a young age. In a general perspective this study demonstrates the importance to perform careful clinical subgroup analyses when investigating heterogeneous, hitherto not clearly defined, conditions like SLE.

Abstract The effects of soil warming and nitrogen availability on root production, longevity and mortality were studied using minirhizotrons in irrigation (C), fertilized (F), heated (H), and heated‐fertilized (HF) plots in a Norway spruce stand in northern Sweden from October 1996 to October 1997. Irrigation was included in all treatment plots. Heating cables were used to maintain the soil temperature in heated plots at 5°C above that in unheated plots during the growing season. A Kaplan–Meier approach was used to estimate the longevity of fine roots and Cox proportional hazards regression to analyze the effects of the H, F, and HF treatments on the risk of root mortality. The proportion of annual root length production contributed by winter–spring production amounted to 52% and 49% in heated plots and heated‐fertilized plots, respectively. The annual root length production in C plots was significantly higher than in other treatments, while the HF treatment gave significantly greater production compared with the F treatment. The risk of mortality (hazard ratio) relative to C plots was higher in H plots (358%) and F plots (191%). The interaction between heating and fertilizing was strongly significant. The increase in the risk of root mortality in combined fertilization and heating (103%) was lower than that in the H or F plots. The results show that nitrogen addition combined with warmer temperatures decreases the risk of root mortality, and fine root production is a function of the length of the growing season. In the future, fertilization combined with the warmer temperatures expected to follow predicted climatic change may increase root production in boreal forests at low fertility sites.

Glucose lowering (GL) therapy in patients with diabetes mellitus (DM) and coronary artery disease (CAD) is prognostically important. This report from the Euro Heart Survey on Diabetes and the Heart describes present practice in relation to 1 year prognosis.The survey enrolled 4676 patients with CAD from 110 centres out of whom 1425 had known and 452 newly detected DM. The impact of different GL modalities on cardiovascular events (CVE: death, myocardial infarction, or stroke) was followed. Insulin treated patients with known DM (n = 378) had an adjusted 1 year hazard ratio (HR) for mortality of 2.23 (95% CI 1.24-4.03; P = 0.006) and for CVE of 1.27 (95% CI 0.85-1.87; P = 0.230) compared with those on oral GL drugs (n = 675). Of patients with newly detected DM 77 (17%) were started on GL drugs. None of them died compared with 25 (P = 0.002) among those without such treatment and their 1 year CVE HR was 0.22 (95% CI 0.05-0.97; P = 0.041) compared with untreated subjects.Insulin therapy may relate to a more serious prognosis in CAD-patients with DM. There was a pronounced decrease in cardiovascular events in patients with newly detected DM prescribed GL drugs compared with those not receiving such treatment.

To study the association between socio-economic factors, lifestyle habits, and self-reported recurrent headache/migraine (RH/M) in a general population.The study population comprised a random sample of men and women aged 18-79 years. The data were obtained using a postal survey questionnaire during March-May 2000. The overall response rate was 65%. The area investigated covers 58 municipalities with about one million inhabitants in central part of Sweden. The study is based on 43,770 respondents. Odds ratios for RH/M were calculated for a set of variables using multiple logistic regression models.The overall prevalence of self-reported RH/M during the last 3 months was 10% among men and 23% among women and decreased with increasing age. Physically inactive subjects were more likely to suffer from headache disorders than physically active subjects. Smoking was only moderately associated with RH/M. There was an inverse relationship between heavy alcohol use and RH/M. Underweight and obesity were not associated with headache disorders when adjusted for socio-economic factors. Subjects with frequent economic problems had almost twice the risk of RH/M compared with subjects with no economic problems. Poor social support was associated with headache disorders and subjects who had been belittled during the last 3 months were more than twice as likely to suffer from RH/M as subjects who had not been belittled. The effect of educational level was modest. Marital status and country of origin were not associated with headache disorders after adjustment for other socio-economic factors. Dissatisfaction with work, worry about losing one's job, and absenteeism due to illness were strongly associated with headache disorders. Physical working conditions and working hours were not associated with RH/M.Headache disorders mainly affect young and middle-aged adults. There are, however, socio-economic disparities in self-reported recurrent headache and migraine. The relationship was particularly evident for economic hardship and psychosocial factors. Of lifestyle factors, physical inactivity was strongly associated with headache disorders independent of economic and psychosocial factors.

We examined whether antibodies against peptides 45 and 210 of apoB-100 are related to myocardial infarction (MI) and severity of coronary atherosclerosis.Three hundred and eighty-seven survivors of a first MI (aged <60 years) and 387 sex- and age-matched controls were characterized in detail. IgG and IgM autoantibodies against native and malondialdehyde (MDA)-modified peptides 45 and 210 of apoB-100 (amino acids 661-680 and 3136-3155) were quantified in plasma and quantitative coronary angiography was performed in 243 patients. Post-infarction patients had significantly lower IgG against the native peptide 210 (IgG-p210(nat)) and higher IgM against the MDA-modified peptide 210 (IgM-p210(MDA)) compared with controls, whereas no differences were found for other antibodies. Plasma concentrations of IgG-p210(nat), but not IgM-p210(MDA), were independently and inversely related to the degree of coronary atherosclerosis in patients. In multiple logistic regression analysis (including established risk indicators), MI risk was 0.55 (95%CI: 0.37-0.81) for individuals in the IgG-p210(nat) upper quartile compared with the remaining individuals.Circulating IgG antibodies against the native peptide 210 of apoB-100 are inversely related to the severity of coronary atherosclerosis and associated with lower risk of MI. Epitope 210 of apoB-100 emerges as a target for immunization against atherosclerosis in humans.

Abstract We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P &lt; 5 × 10−8) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 × 10−10); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 × 10−8); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 × 10−8). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P &lt; .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.

Abstract. Background. A high prevalence of newly detected diabetes and impaired glucose tolerance (abnormal glucose tolerance) was recently reported in patients with acute myocardial infarction. It is important to verify whether this finding is specific for the patients or attributable to the population, from which they were recruited. Objective. To verify whether abnormal glucose tolerance is more prevalent in patients than in controls chosen from the same population and to compare metabolic characteristics between the two groups. Design and subjects. The metabolic state was assessed in patients ( n = 181) admitted with acute myocardial infarction and no history of diabetes before discharge and after 3 months. Sex‐ and age‐matched controls ( n = 185) without previously known diabetes or cardiovascular disease except hypertension were recruited from the general population. Main outcome measures. Oral glucose tolerance test, glucosylated haemoglobin A1c (HbA1c), insulin, proinsulin, lipid profile, fibrinolytic function and inflammatory markers. Results. Abnormal glucose tolerance was more common (number/all classified) in patients at discharge 113/168 (67%) and after 3 months 95/145 (66%) than in controls 65/185 (35%) ( P &lt; 0.001). Dyslipidaemia (70% vs. 29%; P &lt; 0.001) and previously treated hypertension (32% vs. 18%; P = 0.028) were more frequent amongst patients whilst obesity (18% vs. 24%) did not differ significantly. Blood glucose, HbA1c, proinsulin, proinsulin/insulin ratio, triglycerides, insulin resistance (by HOMA) and fibrinogen were consistently higher in patients than controls ( P &lt; 0.01). Conclusions. Abnormal glucose tolerance was almost twice as common amongst patients with acute myocardial infarction as in matched controls. Impaired glycaemic control accompanied by insulin resistance, dyslipidaemia, hypertension, together with increased plasma fibrinogen and proinsulin levels were main features characterizing patients.

Background Patients with diabetes mellitus (DM) and coronary artery disease (CAD) have a poor prognosis. Underutilization and reduced efficacy of evidence-based medications (EBM) or revascularization are among suggested explanations. This report compares the impact of EBM and revascularization on mortality and cardiovascular events (CVE = mortality, myocardial infarction or stroke) in CAD patients with and without DM.

Abstract Aims Myocardial diastolic dysfunction (MDD) and impaired coronary flow reserve (CFR) are early signs of myocardial involvement in patients with diabetes. The important question of whether this may be reversed by glucose normalization has not been tested in a controlled clinical trial. We hypothesized that strict glycaemic control, particularly if insulin based, will improve MDD and CFR. Methods and results Thirty‐nine type 2 diabetes patients (mean age 61.0 ± 7 years) with signs of diastolic dysfunction were randomly assigned to strict metabolic control by insulin (I‐group; n = 21) or oral glucose lowering agents (O‐group; n = 18). MDD and CFR were studied with Doppler‐echocardiography including Tissue Doppler Imaging and myocardial contrast enhanced echocardiography. Fasting glucose (I‐group = −2.2 ± 2.1; O‐group −1.5 ± 0.8 mmol/L) and HbA 1c were normalized (−0.6 ± 0.4 and −0.7 ± 0.4%, respectively) in both groups, but this did not significantly improve MDD in either of the groups ( P = 0.65). There was no difference in CFR before and after improved glycaemic control. Conclusion The hypothesis that strict glycaemic control would reverse early signs of MDD and improve CFR in patients with type 2 diabetes could not be confirmed, despite achieved normalization. Whether it is possible to influence a more pronounced diastolic dysfunction, particularly in less well‐controlled diabetic patients, remains to be established.

During anesthesia oxygenation is impaired, especially in the elderly or obese, but the mechanisms are uncertain.Pooled data were examined from 80 patients studied with multiple inert gas elimination technique and computed tomography. Oxygenation was impaired by anesthesia, more so with greater age or body mass index. The key contributors were low ventilation/perfusion ratio (likely airway closure) in the elderly and shunt (atelectasis) in the obese.Anesthesia is increasingly common in elderly and overweight patients and prompted the current study to explore mechanisms of age- and weight-dependent worsening of arterial oxygen tension (PaO2).This is a primary analysis of pooled data in patients with (1) American Society of Anesthesiologists (ASA) classification of 1; (2) normal forced vital capacity; (3) preoxygenation with an inspired oxygen fraction (FIO2) more than 0.8 and ventilated with FIO2 0.3 to 0.4; (4) measurements done during anesthesia before surgery. Eighty patients (21 women and 59 men, aged 19 to 69 yr, body mass index up to 30 kg/m2) were studied with multiple inert gas elimination technique to assess shunt and perfusion of poorly ventilated regions (low ventilation/perfusion ratio [(Equation is included in full-text article.)]) and computed tomography to assess atelectasis.PaO2/FIO2 was lower during anesthesia than awake (368; 291 to 470 [median; quartiles] vs. 441; 397 to 462 mm Hg; P = 0.003) and fell with increasing age and body mass index. Log shunt was best related to a quadratic function of age with largest shunt at 45 yr (r2 =0.17, P = 0.001). Log shunt was linearly related to body mass index (r2 = 0.15, P < 0.001). A multiple regression analysis including age, age2, and body mass index strengthened the association further (r2 = 0.27). Shunt was highly associated to atelectasis (r2 = 0.58, P < 0.001). Log low (Equation is included in full-text article.)showed a linear relation to age (r2 = 0.14, P = 0.001).PaO2/FIO2 ratio was impaired during anesthesia, and the impairment increased with age and body mass index. Shunt was related to atelectasis and was a more important cause of oxygenation impairment in middle-aged patients, whereas low(Equation is included in full-text article.), likely caused by airway closure, was more important in elderly patients. Shunt but not low(Equation is included in full-text article.)increased with increasing body mass index. Thus, increasing age and body mass index impaired gas exchange by different mechanisms during anesthesia.

epidemiological studies suggest that resting heart rate (RHR) is an independent predictor of cardiovascular and all-cause mortality. Still, this parameter has never been specifically assessed in patients with diabetes mellitus (DM). This study describes the association between RHR and cardiovascular events (CVE) in patients with coronary artery disease (CAD) with and without DM.the Euro Heart Survey on Diabetes and the Heart enroled 2608 patients with stable CAD, of these 780 (30%) had known DM. Resting heart rate was registered in 2507 (96%) patients: 1756 (96%) without and 751 (96%) with DM. Patients were followed with respect to CVE (all-cause mortality, non-fatal myocardial infarction, and stroke) for 1 year. Overall, median RHR was 70 (62-78) b.p.m. The RHR quartile stratification was significantly associated with outcome in the overall population (P = 0.002 and P = 0.021 for survival and CVE, respectively), whereas it was not in patients without DM. In patients with DM, the RHR quartiles correlated with survival (P = 0.032). In an adjusted regression model performed in patients without DM, RHR associated with neither survival [hazard ratio (HR): 0.97, 95% confidence interval (CI): 0.74-1.27; P = 0.804] nor CVE (HR: 0.85, 95% CI: 0.71-1.01, P = 0.068). In contrast, a 10-b.p.m. increase in RHR was independently associated with survival (HR: 1.34, 95% CI: 1.06-1.69, P = 0.015), but not with CVE (HR: 0.99, 95% CI: 0.84-1.18; P = 0.359) in patients with DM.the present report, based on patients with stable CAD, is the first to reveal that the association between RHR and CVE seems to subsist in those with DM, however, not in those without DM.

Heart failure with preserved ejection fraction (HFPEF) is common but not well understood. Electrical dyssynchrony in systolic heart failure is harmful. Little is known about the prevalence and the prognostic impact of dyssynchrony in HFPEF.We have designed a prospective, multicenter, international, observational study to characterize HFPEF and to determine whether electrical or mechanical dyssynchrony affects prognosis. Patients presenting with acute heart failure (HF) will be screened so as to identify 400 patients with HFPEF. Inclusion criteria will be: acute presentation with Framingham criteria for HF, left ventricular ejection fraction>or=45%, brain natriuretic peptide (BNP)>100 pg/mL or NT-proBNP>300 pg/mL. Once stabilized, 4-8 weeks after the index presentation, patients will return and undergo questionnaires, serology, ECG, and Doppler echocardiography. Thereafter, patients will be followed for mortality and HF hospitalization every 6 months for at least 18 months. Sub-studies will focus on echocardiographic changes from the acute presentation to the stable condition and on exercise echocardiography, cardiopulmonary exercise testing, and serological markers.KaRen aims to characterize electrical and mechanical dyssynchrony and to assess its prognostic impact in HFPEF. The results might improve our understanding of HFPEF and generate answers to the question whether dyssynchrony could be a target for therapy in HFPEF.

Carotid intima-media thickness (cIMT) is a widely accepted marker of subclinical atherosclerosis. To date, large-scale investigations of genetic determinants of cIMT are sparse.To identify cIMT-associated genes and genetic variants, a discovery analysis using the Illumina 200K CardioMetabochip was conducted in 3430 subjects with detailed ultrasonographic determinations of cIMT from the IMPROVE (Carotid Intima Media Thickness [IMT] and IMT-Progression as Predictors of Vascular Events in a High Risk European Population) study. Segment-specific IMT measurements of common carotid, bifurcation, and internal carotid arteries, and composite IMT variables considering the whole carotid tree (IMT(mean), IMT(max), and IMT(mean-max)), were analyzed. A replication stage investigating 42 single-nucleotide polymorphisms for association with common carotid IMT was undertaken in 5 independent European cohorts (total n=11,590). A locus on chromosome 16 (lead single-nucleotide polymorphism rs4888378, intronic in CFDP1) was associated with cIMT at significance levels passing multiple testing correction at both stages (array-wide significant discovery P=6.75 × 10(-7) for IMT(max); replication P=7.24×10(-6) for common cIMT; adjustments for sex, age, and population substructure where applicable; minor allele frequency 0.43 and 0.41, respectively). The protective minor allele was associated with lower carotid plaque score in a replication cohort (P=0.04, n=2120) and lower coronary artery disease risk in 2 case-control studies of subjects with European ancestry (odds ratio [95% confidence interval] 0.83 [0.77-0.90], P=6.53 × 10(-6), n=13 591; and 0.95 [0.92-0.98], P=1.83 × 10(-4), n=82 297, respectively). Queries of human biobank data sets revealed associations of rs4888378 with nearby gene expression in vascular tissues (n=126-138).This study identified rs4888378 in the BCAR1-CFDP1-TMEM170A locus as a novel genetic determinant of cIMT and coronary artery disease risk in individuals of European descent.

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.

Patients with acute myocardial infarction (AMI) but without previously known type 2 diabetes have a high prevalence of undiagnosed IGT and type 2 diabetes. Such perturbations have dismal prognostic implications. The aim of this study was to characterise AMI patients in terms of insulin resistance and beta cell function.A total of 168 consecutive AMI patients were classified by means of an OGTT before hospital discharge as having NGT, IGT or type 2 diabetes. The homeostasis model assessment (HOMA-IR) was used to estimate insulin resistance. Beta cell responsiveness was quantified as insulinogenic index (IGI) at 30 min (DeltaI(30)/DeltaG(30)).According to the HOMA-IR, patients with type 2 diabetes were more insulin resistant than those with IGT or NGT (p=0.003). Beta cell responsiveness deteriorated with decreasing glucose tolerance as measured by the IGI (median [quartile 1, quartile 3] in pmol/mmol: NGT, 70.1 [42.7, 101.4]; IGT, 48.7 [34.7, 86.8], type 2 diabetes, 38.1 [25.7, 61.6]; p<0.001). The IGI was significantly related to admission capillary blood glucose (r=-0.218, p=0.010) and to the area under the curve for glucose (r=-0.475, p<0.001).Glucose abnormalities are very common in patients with AMI but without previously known type 2 diabetes. To a significant extent, this seems to be related to impaired beta cell function and implies that dysglycaemia immediately after an infarction is not a stress epiphenomenon but reflects stable disturbances of glucose regulation preceding the AMI. Early beta cell dysfunction may have important pathophysiological implications and may serve as a future target for treatment strategies.

There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes.The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available.During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8-25.7]), age (+5 years) (1.5 [1.4-1.7]), ln IGFBP-1 (1.4 [1.1-1.8]), and ln serum creatinine at admission (2.4 [1.3-4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0-1.4]).High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.

The effect of exercise training and acarbose on glycemic control, insulin sensitivity, and phenotype was investigated in mild type 2 diabetes.Sixty-two men and women with type 2 diabetes were randomized to 12 weeks of structured exercise training with or without acarbose treatment or to acarbose alone. Glycemic control was determined by HbA(1c) (A1C), insulin sensitivity (M value) by euglycemic-hyperinsulinemic clamp, and regional fat distribution by computerized tomography and dual X-ray absorptiometry. Physical fitness was determined as maximal oxygen uptake (Vo(2max)). All investigations were performed before and after the intervention.Forty-eight subjects completed the study. Exercise improved M value by 92% (P = 0.017) and decreased total and truncal fat (P = 0.002, 0.001) and systolic blood pressure (P = 0.01) but had no significant effect on Vo(2max) or A1C level. The combination of exercise and acarbose significantly decreased fasting plasma glucose, A1C, lipids, and diastolic blood pressure and increased Vo(2max), whereas effects on M value and body composition were comparable with that of exercise alone. Acarbose alone had no significant effect on either M value or A1C but decreased systolic (P = 0.001) and diastolic blood pressure (P = 0.001) and fasting proinsulin level (P = 0.009). Multiple regression analysis showed that addition of acarbose to exercise improved glycemic control.In subjects with mild type 2 diabetes, exercise training improved insulin sensitivity but had no effect on glycemic control. The addition of acarbose to exercise, however, was associated with significant improvement of glycemic control and possibly cardiovascular risk factors.

A common nonsynonymous single nucleotide polymorphism (SNP) in the CD93 gene (rs3746731, Pro541Ser) has been associated with risk of coronary artery disease (CAD). CD93 is a transmembrane glycoprotein, which is detectable in soluble form in human plasma. We investigated whether the concentration of soluble CD93 in plasma is related to risk of myocardial infarction (MI) and CAD, using a case-control study of premature MI (n = 764) and a nested case-control analysis of a longitudinal cohort study of 60-year-old subjects (analysis comprising 844 of 4232 subjects enrolled at baseline). In addition, SNPs in the CD93 gene were studied in relation to plasma CD93 concentration and CD93 mRNA expression.A sensitive and specific enzyme-linked immunosorbent assay was established for determination of the plasma CD93 concentration. Subjects were divided into three groups according to tertiles of the distribution of CD93 concentration. Lower odds ratios for risk of MI and incidence of CAD were observed in the middle CD93 tertile (142-173 μg L(-1) ): odds ratio (95% confidence interval), 0.69 (0.49-0.97) and 0.61 (0.40-0.94), respectively. These associations were independent of traditional CAD risk factors. The minor allele of a SNP in the 3' untranslated region of CD93 (rs2749812) was associated with increased plasma CD93 concentrations (P = 0.03) and increased CD93 mRNA expression levels (P = 0.02).The results of the present study suggest that the concentration of soluble CD93 in plasma is a potential novel biomarker for CAD, including MI.

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.

Introduction. White blood cell (WBC) count is often included in routine clinical checkups. We determined the prognostic impact of WBC count on all-cause, cardiovascular, and noncardiovascular mortality during an 11-year followup in a general population of 75-year-olds. Study Population. The study included 207 men and 220 women comprising 69% of the invited 75-year-olds in a defined geographical area. Main Results. The median WBC count (in 10(9)/L) was 6.3 (interquartile range 5.4-7.2) for men and 5.7 (4.9-6.8) for women, P < 0.001 for sex difference. The hazard ratio (HR) for all-cause mortality per 10(9)/L increase in WBCs was 1.16 (95% confidence interval, 1.03-1.32; P = 0.016) in men and 1.28 (1.10-1.50; P = 0.002) in women. These HRs were essentially unchanged by adjustment for established risk factors (current smoking, known hypertension, prior myocardial infarction, known diabetes, total cholesterol, high-density lipoprotein cholesterol, and body mass index). Furthermore, increased WBC count was significantly associated with cardiovascular mortality in both sexes and with noncardiovascular mortality in women. Conclusions. The WBC count deserves attention as a potentially clinical useful predictor of survival in the 75-year-olds, especially among women.

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.

Patients with diabetes are known to have a worse prognosis after an acute myocardial infarction (AMI) compared with non-diabetic patients. The primary aim of this study was to investigate the effect of glucometabolic status on long-term prognosis in non-diabetic patients with an AMI. The second aim was to evaluate the extent to which blood glucose levels at admission depended on acute stress, assessed as serum cortisol, previous glucometabolic status, measured as haemoglobin A1c (HbA1c), or both.In a prospective study of patients with an AMI, blood glucose, HbA1c and cortisol were measured at admission. Fasting blood glucose was determined before discharge and also afterwards, if necessary, for classification. Patients were followed-up for 5.5 years.Of the 305 consecutive patients 24% were diagnosed as diabetic and 76% as non-diabetic.Death or non-fatal myocardial re-infarction.In non-diabetic patients, a Cox regression model was used. With death or re-infarction as endpoint, the following prognostic factors had an impact on event-free survival: age (P<0.001), HbA1c (P=0.002), cortisol (P<0.001) and thrombolytic treatment (P=0.001). There was a correlation between cortisol and blood glucose at admission (r=0.44, P<0.001). Fasting blood glucose day 5 showed no association with event-free survival.In non-diabetic patients with AMI, admission HbA1c and cortisol were predictors for 5.5-year survival without recurrent non-fatal myocardial infarction. The glucometabolic status of importance for prognosis was detected by HbA1c but not by fasting blood glucose or admission blood glucose, of which the latter was influenced by cortisol.

Purpose. There is a paucity of long-term evaluations on rehabilitation of musculoskeletal disorders, e.g., neck, shoulder or back pain. The aim of this study was to assess quality of life and the effect of early multimodal rehabilitation on 91 patients with musculoskeletal pain and disability at a 5-year follow-up.

Background Insulin resistance (IR) is a risk factor for diabetes and atherosclerotic diseases. The metabolic syndrome (MetS) reflects IR. Waist circumference (WC) is the most easily registered component of MetS. The objective was to compare WC alone with MetS as defined by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) for their abilities to predict IR in elderly without known diabetes. Methods The study included 223 women and 210 men comprising 70% of a random sample of 75-year-olds from a general population. IR was conventionally defined as the gender-specific upper quartile of the Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) index in individuals without known diabetes. Results 1) The positive association between WC and IR is stronger in women than in men. 2) WC >88 cm alone is nearly as good as MetS, using NCEP criteria, in predicting IR in women. 3) According to the ROC curve, the optimal cut-off point for WC predicting IR was between 96 and 97 cm (men) and between 88 and 89 cm (women). The relative risk of IR was 5.6 (95% CI: 3.1–11.9) for women with WC >88 cm and 1.9 (1.5–2.8) for men with WC >96 cm. 4) The NCEP criteria predicts IR significantly better than the IDF criteria. Conclusion WC >88 cm in women indicates a high likelihood of IR and is almost as good as MetS defined using the NCEP criteria in predicting IR. MetS defined using the NCEP criteria predicts IR better than MetS defined using the IDF criteria.

<h3>Objective:</h3> Studies on the prognostic importance of the systolic blood pressure (SBP) response during exercise report ambiguous results. Most research focuses on younger and middle-aged selected patient groups and rarely includes women. We investigated the prognostic value of SBP response during exercise testing in 75-year-olds. <h3>Design:</h3> Prospective observational cohort study. <h3>Setting:</h3> A community-based random sample of 75-year-old men and women (n = 382). <h3>Main outcome measures:</h3> The prognostic value of SBP change from rest to peak exercise during a symptom-limited cycle test was evaluated for the endpoints all-cause mortality and cardiovascular mortality during long-term follow-up. <h3>Results:</h3> After a median follow-up of 10.6 years, 140 (37%) of the participants had died, 64 (17%) from cardiovascular causes. The all-cause mortalities for exercise SBP changes of ⩽30 mm Hg, 31–55 mm Hg and &gt;55 mm Hg were 5.1, 4.2 and 2.6 per 100 person-years, respectively (logrank 9.6; p = 0.008). For every 10 mm Hg increase in SBP during exercise the relative hazard for all-cause mortality was reduced by 13% (p = 0.030) and for cardiovascular mortality by 26% (p = 0.004) after adjustment for sex, smoking, waist circumference, total/HDL cholesterol ratio, prevalent ischaemic heart disease, hypertension, diabetes, cardiovascular medication, pre-exercise SBP, exercise capacity, resting left ventricular ejection fraction and left ventricular mass index. <h3>Conclusions:</h3> Our findings suggest that an augmented SBP response during exercise is associated with an improved long-term survival among community-living 75-year-old individuals.

OBJECTIVE To determine whether C-terminal provasopressin (copeptin) explains the prognostic importance of insulin growth factor binding protein-1 (IGFBP-1) in patients with myocardial infarction and type 2 diabetes. RESEARCH DESIGN AND METHODS Copeptin and IGFBP-1 were analyzed in 393 patients participating in the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial. RESULTS Copeptin was associated with IGFBP-1 (Spearman rank correlation test, r = 0.53; P &amp;lt; 0.001). During follow-up there were 138 cardiovascular events (cardiovascular death, myocardial infarction, and stroke). In univariate Cox proportional hazard regression analyses both biomarkers were predictors of events: the hazard ratio for log copeptin was 1.59 (95% CI 1.41–1.81; P &amp;lt; 0.001) and for log IGFBP-1 was 1.49 (1.26–1.77; P &amp;lt; 0.001). In the final model, adjusting for age and renal function, copeptin was the only independent predictor (1.35 [1.16–1.57]; P &amp;lt; 0.001). CONCLUSIONS Copeptin is an independent predictor of cardiovascular events and appears to at least partly explain the prognostic impact of IGFBP-1 in patients with type 2 diabetes and myocardial infarction. Copeptin may be a pathogenic factor to address to improve outcome in these patients.

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.

BackgroundGeneral anaesthesia is increasingly common in elderly and obese patients. Greater age and body mass index (BMI) worsen gas exchange. We assessed whether this is related to increasing atelectasis during general anaesthesia.MethodsThis primary analysis included pooled data from previously published studies of 243 subjects aged 18–78 yr, with BMI of 18–52 kg m−2. The subjects had no clinical signs of cardiopulmonary disease, and they underwent computed tomography (CT) awake and during anaesthesia before surgery after preoxygenation with an inspired oxygen fraction (FIO2) of >0.8, followed by mechanical ventilation with FIO2 of 0.3 or higher with no PEEP. Atelectasis was assessed by CT.ResultsAtelectasis area of up to 39 cm2 in a transverse scan near the diaphragm was seen in 90% of the subjects during anaesthesia. The log of atelectasis area was related to a quadratic function of (age+age2) with the most atelectasis at ∼50 yr (r2=0.08; P<0.001). Log atelectasis area was also related to a broken-line function of the BMI with the knee at 30 kg m−2 (r2=0.06; P<0.001). Greater atelectasis was seen in the subjects receiving FIO2 of 1.0 than FIO2 of 0.3–0.5 (12.8 vs 8.1 cm2; P<0.001). A multiple regression analysis, including a quadratic function of age, a broken-line function of the BMI, and dichotomised FIO2 (0.3–0.5/1.0) adjusting for ventilatory frequency, strengthened the association (r2=0.23; P<0.001). PaO2 decreased with both age and BMI.ConclusionsAtelectasis during general anaesthesia increased with age up to 50 yr and decreased beyond that. Atelectasis increased with BMI in normal and overweight patients, but showed no further increase in obese subjects (BMI ≥30 kg m−2). Therefore, greater age and obesity appear to limit atelectasis formation during general anaesthesia.

We examined the relationships of serum 25-hydroxyvitamin D (25(OH)D) concentration to established and emerging cardiovascular risk factors and risk of myocardial infarction (MI) in a population-based case-control study of MI before the age of 60 years.A total of 387 survivors of a first MI and 387 sex- and age-matched controls were included. Fasting blood samples drawn three months after the MI in cases and at the same time in the matched controls were used for biochemical analyses.Serum concentrations of 25(OH)D, adjusted for seasonal variation, were lower in cases than controls (55.0 (40.0-71.0) nmol/L vs 60.5 (47.0-75.0) nmol/L; median (interquartile range); standardized odds ratio (OR) for MI with 95% confidence interval in univariable analysis: 0.80 (0.69-0.93); p = 0.003). The 25(OH)D association with MI disappeared after adjustment for established and emerging risk factors (OR: 1.01 (0.82-1.25)). Current smoking and plasma levels of proinsulin and PAI-1 activity were independently associated with 25(OH)D in controls, whereas waist circumference, plasma triglycerides, proinsulin, PAI-1 activity and cystatin C, and non-Nordic ethnicity were independently associated with 25(OH)D in patients. Serial measurements of 25(OH)D (samples drawn <4 h and 3 months after the onset of MI) in 57 patients showed no systematic differences between sampling times.Vitamin D insufficiency, which is associated with a multitude of metabolic, procoagulant and inflammatory perturbations, is not independently related to premature MI. This suggests that vitamin D insufficiency either constitutes an epiphenomenon or increases the risk of MI by promoting established risk factor mechanisms that predispose to atherothrombosis.

The Diabetes mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Quality of Life (QoL) sub-study included 465 patients with type 2 diabetes and acute myocardial infarction (AMI) followed for 2 years. Self-rated health was reported by the rating scale (RS), graded 0 = death to 100 = perfect health. Prospective associations between RS and all-cause mortality, cardiovascular (CV) death and cardiovascular events (CVEs = CV death, non-fatal AMI, stroke) were assessed. Median age was 68 years (range 59–74), 68% male. Patients experiencing CVE ( n = 132) or death ( n = 71) had lower RS compared with patients free from events: 60 (50–79) versus 70 (55–81) ( p &lt; 0.001) and 60 (50–75) versus 70 (51–80) ( p = 0.008). The RS score predicted CVE [hazard ratio (HR); 95% confidence interval (CI): 0.87; 0.80–0.95] and all-cause mortality (0.86; 0.76–0.97), and corresponding HRs after adjustment were 0.90; 0.83–0.99 and 0.90; 0.79–1.02, respectively. A low self-rated health is of prognostic importance in patients with type 2 diabetes and AMI and may serve as an easily obtainable indicator of high risk for CVEs supplementing traditional risk factors.

Low heart rate recovery (HRR) at exercise test and the metabolic syndrome (MetS) are both predictors of cardiovascular morbidity and mortality. We studied in 75-year-old women and men, representative of the general population, the relationship between (1) HRR and the MetS, (2) HRR and the individual components of the MetS, and (3) HRR and insulin sensitivity.A cross-sectional study of randomly selected 75-year-olds from a general population was performed (191 women and 194 men). The MetS was defined according to the National Cholesterol Education Program criteria. Heart rate was measured as beats per minute immediately after exercise and at 4 minutes into recovery.Heart rate recovery (median and interquartile range, beat/min) was 48 (37-58) for women and 49 (38-58) for men. Thirty-seven percent of the women and 25% of the men had the MetS. Heart rate recovery was 52 (42-61) for women with the MetS and 42 (31-49) for those without. The corresponding values for men was 50 (39-61) and 47 (35-54); the difference between individuals with and without the MetS was significant for women (P < .001) but not for men (P = .084). The following significant correlation coefficients between HRR and MetS components were found: for women, waist circumference (-0.43, P < .001), high-density lipoprotein cholesterol (0.37, P < .001), insulin sensitivity (-0.37, P < .001), fasting plasma glucose (-0.30, P < .001), and triglycerides (-0.24, P = .001); for men, triglycerides (-0.20, P = .005). The sex disparity in the strength of correlation reached statistical significance for insulin sensitivity (P < .001) and waist circumference (P = .042).Among 75-year-olds, the MetS and related components are more strongly correlated to HRR in women than in men.

Aim: We investigated whether insulin treatment‐induced weight gain was accompanied by increased cardiovascular (CV) mortality and morbidity in the second Diabetes Insulin Glucose in Acute Myocardial Infarction (DIGAMI 2) study. Methods: We studied the 865 patients who survived during 12 months without any change in their glucose‐lowering (GL) therapy. They were divided into four subgroups according to GL treatment: group I, no pharmacological GL treatment (n = 99); group II, oral hypoglycaemic agents (n = 250); group III, new insulin treatment (n = 245) and group IV, insulin before inclusion continued during the first year of follow up (n = 271). Results: Patients who started on insulin (group III) experienced an average body weight increase of 2.3 (1.5–3.2) kg during the first year of treatment, whereas weight remained unchanged in groups I, II and IV. The incidence of non‐fatal reinfarction was higher in group III compared with the other groups (hazard ratio (HR) = 2.5, p = 0.011) and CV mortality was higher in group IV (HR = 2.4, p = 0.003). When the subjects were grouped in quartiles according to maximal body weight increase, those in the lowest quartile experienced the highest CV mortality. Each kilogram increase in weight reduced the risk for CV death with 6%. The incidence of reinfarction did not differ between quartiles. Conclusions: Initiation of insulin treatment after myocardial infarction was associated with a significant increase in weight and incidence of reinfarction. The increase in weight did, however, not explain the increased rate of reinfarction.

The present study characterizes mannose-binding lectin (MBL), an activator of the complement system and thereby important for inflammatory activation, in patients with diabetes and myocardial infarction.Serum (S)-MBL was determined at hospital admission in 387 patients with type 2 diabetes (median age 70 years; 68% male) with myocardial infarction, and genotyping was performed in 287 patients. Cardiovascular events (cardiovascular mortality and nonfatal myocardial infarction or stroke) were recorded during 2.5 years.Median S-MBL was 1,212 μg/l (interquartile range [IQR] 346-2,681 μg/l). Of the subjects, 54% in the geno- and phenotype subgroup had a high-coding MBL genotype (median S-MBL=2,658 μg/l [IQR 1,715-3,829]) and 46% a low-coding MBL genotype (373 μg/l [100-765]). S-MBL did not correlate with age, BMI, creatinine clearance, glucose, or A1C. Cardiovascular events occurred in 136 (35%) patients. S-MBL did not predict events in univariable analyses (hazard ratio 0.93 [95% CI 0.85-1.01]; P=0.09). In unadjusted analyses, the risk of events was lower in patients with a high genotype and S-MBL above the median for their genotype (0.49 [0.26-0.92]; P=0.026) than for patients with a low genotype and S-MBL below the median for their genotype. The prediction capacity of the geno- and phenotype model was of borderline significance in adjusted Cox regression.Patients with type 2 diabetes and myocardial infarction have MBL genotypes that are similar to those known in the general population. The combination of a low-coding MBL genotype with a low S-MBL appears to be prognostically unfavorable, but the association is blunted by traditional risk markers.

<h3>Objective</h3> To study the relationship between body mass index (BMI) and mortality among 75-year-olds with and without diabetes mellitus type 2 (DM) or impaired fasting glucose (IFG). <h3>Design</h3> Prospective population-based cohort study with a 10-year follow-up. <h3>Participants</h3> A random sample of 618 of the 1100 inhabitants born in 1922 and living in the city of Västerås in 1997 were invited to participate in a cardiovascular health survey; 70% of those invited agreed to participate (432 individuals: 210 men, 222 women). <h3>Outcome measures</h3> All-cause and cardiovascular mortality. <h3>Results</h3> 163 of 432 (38%) participants died during the 10-year follow-up period. The prevalence of DM or IFG was 41% (35% among survivors, 48% among non-survivors). The prevalence of obesity/overweight/normal weight/underweight according to WHO definitions was 12/45/42/1% (14/43/42/1% among survivors, 9/47/42/2% among non-survivors). The hazard rate for death decreased by 10% for every kg/m² increase in BMI in individuals with DM/IFG (HR 0.91, 95% CI 0.86 to 0.97; p=0.003). After adjustment for sex, current smoking, diagnosed hypertension, diagnosed angina pectoris, previous myocardial infarction and previous stroke/transient ischaemic attack, the corresponding decrease in mortality was 9% (HR 0.92, 95% CI 0.86 to 0.99; p=0.017). These findings remained after exclusion of individuals with BMI&lt;20 or those who died within 2-year follow-up. In individuals without DM/IFG, BMI had no effect on mortality (HR 1.01, 95% CI 0.95 to 1.07; p=0.811). The HR for BMI differed significantly between individuals with and without DM/IFG (p interaction=0.025). The increased all-cause mortality in individuals with DM/IFG in combination with lower BMI was driven by cardiovascular death. <h3>Conclusion</h3> High all-cause and cardiovascular mortality was associated with lower BMI in 75-year-olds with DM/IFG but not in those without DM/IFG. Further studies on the combined effect of obesity/overweight and DM/IFG are needed in order to assess the appropriateness of current guideline recommendations for weight reduction in older people with DM/IFG.

Low levels of IGF-I are associated with increased risk of cardiovascular disease and type 2 diabetes. The aim of this study was to investigate the IGF-I system in patients with acute myocardial infarction (AMI) without previously known diabetes.One hundred and sixty-eight AMI patients were classified before hospital discharge by means of an OGTT as having NGT, IGT or newly detected type 2 diabetes. Age- and sex-matched subjects from the background population (n=185) served as the control group. The associations between fasting levels of IGF-I and IGF binding proteins 1 and 3 (IGFBP-1, IGFBP-3) and glucose metabolism during a follow-up period of 12 months were studied.At hospital discharge, age-adjusted IGF-I (IGF-I SD) was significantly lower in patients with abnormal glucose tolerance (AGT=IGT or type 2 diabetes) compared with patients with NGT (p=0.014) and control subjects (p<0.001). IGF-I was strongly correlated with IGFBP-3 (r=0.730, p<0.001), which was significantly lower in patients with AGT compared with patients with NGT (p=0.009) and control subjects (p<0.001). Fasting levels of IGFBP-1 did not differ significantly between patients with NGT and AGT or between patients and control subjects. In a multiple logistic regression analysis in patients, IGF-I at hospital discharge was a significant predictor of AGT at discharge and after 12 months (adjusted odds ratio 0.29, p=0.022, and adjusted odds ratio 0.29, p=0.034, respectively).Low levels of IGF-I may be a useful predictor of abnormal glucose metabolism in patients with AMI.

Objective. The purpose of this study was to investigate prognostic impact of cholesterol and its subfractions among 75-year-old people from the general population. Methods and Results. The study comprised a random sample (222 women and 210 men) from the general population (participation rate 70%). During 10-year follow-up, 19% of women and 35% of men experienced a major cardiovascular event (MCVE). The all-cause mortality was 29% for women and 47% for men. After adjustment for cardiovascular risk factors, a low level of high-density lipoprotein cholesterol (HDL-C) was significantly associated with MCVE (P = .006) and mortality (P = .011) in men but not in women. The prognostic sex disparity was nearly significant (P = .051 for MCVE and .067 for mortality). The associations of adjusted HDL-C to MCVE and mortality were unchanged after excluding individuals with prevalent stroke or MI. Total cholesterol and low-density lipoprotein cholesterol (LDL-C) were not significantly related to prognosis in either sex. Main Conclusions. HDL-C was associated with dismal prognosis in men but not in women. Elderly men with HDL-C <40 mg/dL deserve particular attention for cardiovascular prevention.

Introduction We investigated whether genetic variations robustly associated with coronary artery disease are also associated with risk of venous thromboembolism in a well-defined, female case–control study (n = 2753) from Sweden. Materials and Methods 39 single nucleotide polymorphisms in 32 loci associated with coronary artery disease in genome-wide association studies were identified in a literature search and genotyped in the ThromboEmbolism Hormone Study (TEHS). Association with venous thromboembolism was assessed by logistic regression. Results Only rs579459 in the ABO locus demonstrated a significant association with VTE. A tentative association between ANRIL and VTE in the discovery analysis failed to replicate in a meta-analysis of 4 independent cohorts (total n = 7181). Conclusions It appears that only the ABO locus is a shared risk factor for coronary artery disease and VTE.

Purpose. The high prevalence of musculoskeletal pain generates significant costs for primary health care and the whole of society. The development of appropriate interventions is therefore necessary. The aim of this effectiveness study was to assess the long-term effects of a primary health care multidisciplinary rehabilitation program in Sweden.Methods. An experimental group comprising 89 patients from two primary health care units received individualised treatment interventions after a multidisciplinary investigation. A control group of 69 patients with the same inclusion criteria from four other primary health care units were treated according to routine. All participants completed questionnaires measuring pain, sick leave, quality of life, health care utilisation, drug consumption and psychosocial factors at baseline and at 3-year follow-up.Results. After 3 years, utilisation of primary health care was significantly lower in the experimental group and work capacity was slightly but not significantly higher. The control group showed a trend of having a higher risk of high consumption after 3 years compared to the intervention group. There was no significant difference between the two groups concerning remaining variables such as function, catastrophising and pain.Conclusion. Both groups demonstrated considerable improvement over the course of 3 years. The experimental group had lower health care utilisation and a reduced risk of using large amounts of medication at the 3-year follow-up, indicating that compared with participants in the control group they were coping in a better way with pain.

Despite considerable improvements in the management of cardiovascular diseases, patients with diabetes mellitus have not benefited to the same extent as those without. Possible explanations are advanced atherosclerosis, inferior efficacy or insufficient use of evidence-based treatment, or inadequate glycemic control in these patients. The Euro Heart Survey on Diabetes and the Heart (EHS) was a multicentre prospective observational study involving 110 centres in 25 European countries. The aims of the survey were to describe the prevalence of abnormal glucose regulation to assess clinical practice in relation to existing guidelines and to compare the impact of evidence-based medication and procedures on mortality and morbidity in patients with coronary artery disease (CAD). Patient enrolment was performed between February 2003 and January 2004. Consecutive patients with established CAD were recruited when admitted to hospital cardiology wards or visiting outpatient clinics. All patients were assessed, investigated and treated at the discretion of their physician according to the institution’s practice. The present review describes the main findings of the EHS and puts them into perspective.

Low levels of free activated coagulation factor VII (VIIa) are normally present in plasma to prime the coagulation of blood in normal hemostasis and during thrombus formation. VIIa also circulates in inactive form, in complex with antithrombin (VIIaAT) formed when VIIa is bound to tissue factor (TF). This study evaluated VIIaAT in relation to cardiovascular disease (CVD).We determined the plasma VIIaAT concentration in samples from the Stockholm Coronary Atherosclerosis Risk Factor (SCARF) study, a population-based case-control study of myocardial infarction (MI) and in samples from the Stockholm study of 60-years-old individuals, a prospective study of CVD. VIIaAT was measured with a sandwich ELISA that captures the complex between a monoclonal antibody to VIIa and a polyclonal antibody to AT.In the SCARF study (200 post-MI cases, 340 controls), VIIaAT was statistically significantly associated with patient status [odds ratio (95% confidence interval (CI)] 1.51 (1.09-2.08), p=0.0126). The case-control differences were however small, with VIIaAT values that largely overlap between the two groups. When a nested case-control design (211 incident CVD cases and 633 matched controls) was applied on 5- to 7-year follow-up results of the Stockholm prospective study of 60-year-olds, plasma VIIaAT concentration was not associated with incident CVD (odds ratio (95% CI) 1.001 (0.997-1.005), p=0.5447).Plasma VIIaAT concentration had no predictive value for future CVD in our study population. Slightly increased plasma VIIaAT concentrations observed after MI may reflect processes that occur in connection with the acute event when TF and VIIa availability is increased.

IL-5 is a Th2 cytokine which activates eosinophils and is suggested to have an atheroprotective role. Genetic variants in the IL5 locus have been associated with increased risk of CAD and ischemic stroke. In this study we aimed to identify genetic variants associated with IL-5 concentrations and apply a Mendelian randomisation approach to assess IL-5 levels for causal effect on intima-media thickness in a European population at high risk of coronary artery disease. We analysed SNPs within robustly associated candidate loci for immune, inflammatory, metabolic and cardiovascular traits. We identified 2 genetic loci for IL-5 levels (chromosome 5, rs56183820, BETA=0.11, P=6.73E(-5) and chromosome 14, rs4902762, BETA=0.12, P=5.76E(-6)) and one for eosinophil count (rs72797327, BETA=-0.10, P=1.41E(-6)). Both chromosome 5 loci were in the vicinity of the IL5 gene, however the association with IL-5 levels failed to replicate in a meta-analysis of 2 independent cohorts (rs56183820, BETA=0.04, P=0.2763, I(2)=24, I(2)-P=0.2516). No significant associations were observed between SNPs associated with IL-5 levels or eosinophil count and IMT measures. Expression quantitative trait analyses indicate effects of the IL-5 and eosinophil-associated SNPs on RAD50 mRNA expression levels (rs12652920 (r2=0.93 with rs56183820) BETA=-0.10, P=8.64E(-6) and rs11739623 (r2=0.96 with rs72797327) BETA=-0.23, P=1.74E(-29), respectively). Our data do not support a role for IL-5 levels and eosinophil count in intima-media thickness, however SNPs associated with IL-5 and eosinophils might influence stability of the atherosclerotic plaque via modulation of RAD50 levels.

We studied Psychological General Well-Being (PGWB) and its relation to 10-year survival in 75-year-olds from the general population. The PGWB global score (sum of six subscale scores) and the subscale scores were transformed to 0–100 scales. Ten-year survival in relation to PGWB global and subscale scores was studied in a cohort of 204 men and 213 women. Global PGWB score (median) was 83 in men and 79 in women (for difference p = 0.001). Significantly higher male scores were found for most PGWB subscales. Global PGWB score was significantly related to better 10-year survival in men (relative risk per ten points of score was 0.80; p = 0.001 and 0.85; p = 0.022 adjusting for chronic diseases and living alone) but not in women (relative risk 0.94; p = 0.478 unadjusted). Among 75-year-olds, PGWB score was significantly higher for men. A high PGWB score was significantly related to better survival in men but not in women.

The crossover design is often used in biomedical trials since it eliminates between subject variability. This paper is concerned with the statistical analysis of data arising from such trials when assumptions like normality do not necessarily apply. Nonparametric analysis of the two-period, two-treatment design was first described by Koch in a paper 1972. The purpose of this paper is to study nonparametric methods in crossover designs with three or more treatments and an equal number of periods. The proposed test for direct treatment effects is based on within subject comparisons after removing a possible period effect. With only two treatments this test reduces to the twosided Wilcoxon signed rank test. By simulation experiments the validity of the significance level of the test when using the asymptotic distribution of the test statistic are manifested and the power against different alternatives illustrated. A test for first order carryover effects can be constructed by a straightforward generalization of the test proposed by Koch in 1972. However, since this test is based on between subject comparisons its power will be low. Our recommendation is to consider the crossover design rather than the parallel group design if the carryover effects are assumed to be neglible or positive and smaller then the direct treatment effects.

A positive relation between the metabolic syndrome (MetS) and inflammatory activity has been reported. The purpose of this investigation was to study the relationships between 1) white blood cell (WBC) count and MetS, 2) WBC count and the individual components of MetS and 3) WBC count and insulin sensitivity in 75-year-old women and men from the general population.The study included 200 women and 196 men comprising 64% of the 75-year old people from the city of Västerås in Sweden. MetS was defined according to the National Cholesterol Education Program (NCEP).WBC count (10(9)/L; median and interquartile range) was 5.7 (4.9-6.8) for women and 6.3 (5.4-7.2) for men, P < .001 for gender difference. For women with and without MetS, WBC count was 6.3 (5.3-7.3) and 5.4(4.7-6.3), respectively. For men the corresponding figures were 6.7 (5.9-7.6) and 6.1 (5.4-7.1).The difference in WBC count between individuals with and without MetS was significant (P < .001 for women; P = .014 for men). All individual components of MetS (with exception of blood pressure) were more strongly associated with WBC count for women than for men. Insulin sensitivity, measured as HOMA-IR (HOmeostasis Model Assessment-Insulin Resistance) index, was significantly associated with WBC count in women but not in men.In this elderly population, individuals with MetS had a higher WBC count than those without. Women had a lower WBC count and stronger relationship between WBC count and insulin sensitivity than did men.

The aim of the present study was to examine how a personal experience of illness and a family history of cardiovascular disease (CVD), adjusted for sex, level of education and nationality, affect risk behaviour. Participants were 1,011 and 1,043, 50-year-old men and women from Sweden and Poland, respectively, who were recruited from a primary health care screening programme. Family history, personal experience of illness and risk behaviour (smoking and exercise habits, BMI level) were self-reported. The results showed that smoking behaviour was affected by a personal experience of illness but not by a family history of CVD. No effects of these variables were found on the remaining risk-related variables tested in this study. These results suggest that individuals with a personal experience of illness may be more inclined to change smoking behaviour than the average person. Smoking prevention strategies may therefore benefit from targeting this group in particular.

To investigate the prevalence of diabetes and impaired glucose regulation (IGR) in a large cohort of men and women with coronary artery disease (CAD), and to describe the effect of abnormal glucose regulation by sex on symptoms, clinical course, and diagnosis.A total of 4855 patients with CAD (median age 66 years; 29% women) were analysed within the framework of the Euro Heart Survey on Diabetes and the Heart. In all, 967 (28.1%) men and 528 (37.5%) women had diabetes. Of 3185 patients with unknown glucose regulation, 1835 (57.6%; 1400 men and 435 women) underwent an oral glucose tolerance test revealing that 17% of the men and 18% of the women had diabetes and 35 and 39% impaired glucose tolerance or impaired fasting glucose, respectively. Thus, only 19% of the women and 27% of the men had a normal glucose regulation. Women were more likely to have diabetes than men with an odds ratio (OR) of 1.32 (1.13-1.54). The corresponding OR for abnormal glucose regulation was 1.34 (1.11-1.62). Gender did not influence differences in clinical presentation between patients with diabetes or IGR and those with a normal glucose metabolism.Abnormal glucose regulation was more common in women than men with CAD. However, the influence of diabetes on presenting symptoms and clinical course was similar in men and women.

Background: Obesity is an important biological risk factor for cardiovascular disease (CVD). Aims: The main aim of this study was to answer the question whether obese individuals differ from individuals with normal weight with regard to knowledge about risk factors for CVD. A further aim was to replicate previous findings that obese individuals are at higher risk of developing other biological risk factors for CVD. Method: Normal weights, BMI <25 kg/m2 (n = 385), and obese, BMI ≥ 30 kg/m2 (n = 159), individuals were identified from a screening program conducted among 50-year-old inhabitants of the County of Västmanland, Sweden. Participants answered questions regarding their gender, level of education, and items relating to knowledge about cardiovascular risk factors. Total cholesterol and blood glucose levels, height, weight and blood pressure were measured. Results: Obese individuals did not differ significantly from individuals with a normal weight regarding knowledge of cardiovascular risk factors when education was controlled for. Obesity and low level of education are associated with other risk factors for CVD such as high blood pressure and high serum cholesterol. Conclusion: Obese individuals are at an increased risk of developing other risk factors for CVD but are just as knowledgeable about risk factors for CVD as normal weighting individuals.

Aims The study concerns the relationship of the corrected QT (QTc) interval to 6.4 years of survival and to measures of cardiac function, such as echocardiographic variables and plasma levels of brain natriuretic peptide (BNP), in 75-year-old people.

Information on trends in healthy and unhealthy habits among children are important for the development of programmes intended to foster and consolidate a healthy lifestyle. This report studied the importance of time and age on the health behaviour of Swedish school children.A comparison between health behaviours derived from repeated evaluations of Swedish school children aged 11-13 years was performed.Significant positive time trends were found in the form of increased physical activity and decreased sedentary behaviours, whereas negative time trends were observed in dietary habits and smoking. An analysis of the impact of increasing age demonstrated a negative influence including less physical activity and deteriorating dietary habits and increased smoking at the young age groups in this study.Time trends and age are both important determinants of health behaviour in pre-teen children. Even the small age increase from 11 to 13 years had an important negative influence. The results of the present study underline that the window of opportunities to promote a healthy lifestyle in children is narrow. It is evident that a successful health intervention programme must be initiated at an early age, continued and repeated over time, and structured to counteract trends in age as well as time.

Background: Factor analysis reduces a set of directly measured variables into a smaller set of underlying factors representing unique statistically independent domains termed “factors.” In middle-aged people, previous factor analyses of the components of the metabolic syndrome have identified two to four factors. Many of these analyses report blood pressure as one of these factors. Methods: We performed a factor analysis of the individual continuous components of the metabolic syndrome among 198 men and 203 women comprising 65% of all 75 year olds from the city of Västerås in Sweden. Results: The metabolic syndrome comprised two factors. Factor 1, the metabolic factor, consisted of waist circumference, high-density lipoprotein cholesterol, triglycerides, and fasting glucose, whereas factor 2, the blood pressure factor, consisted of systolic and diastolic blood pressure. These two factors explained 58% (factor 1, 31%, and factor 2, 27%) of the total variation in men. The corresponding figures for women were 63% (factor 1, 36%, and factor 2, 27%). Factor 1 was significantly related to a decreased 10 years of survival for men, with a hazard ratio (HR) of 1.30 (95% confidence interval [CI] 1.07–1.58, P = 0.008), and nearly significantly for women, with a HR of 1.27 (95% CI 0.98–1.64, P = 0.071). In a pooled analysis adjusting for sex, known cardiovascular disease, and hypertension, high blood pressure, and current smoking, the HR for factor 1 was 1.20 (95% CI 1.02–1.49, P = 0.026). Factor 2 was not significantly related to survival. Conclusions: Factor analysis of the basic variables of the metabolic syndrome among 75 year olds from a general population identified a metabolic factor and a blood pressure factor. The former factor was significantly related to 10-year survival and the relationship remained after adjusting for known cardiovascular disease and hypertension and current smoking.

The primary objective of this study was to classify patients with CAD as regards their gluco-metabolic state by easily available clinical variables. A secondary objective was to explore if it was possible to identify CAD patients at a high cardiovascular risk due to metabolic perturbations. The 1,867 patients with CAD were gluco-metabolically classified by an OGTT. Among these, 990 patients had complete data regarding all components of the metabolic syndrome, BMI, HbA1c and medical history. Only FPG and HDL-c adjusting for age significantly impacted OGTT classification. Based on these variables, a neural network reached a cross-validated misclassification rate of 37.8% compared with OGTT. By this criterion, 1,283 patients with complete one-year follow-up concerning all-cause mortality, myocardial infarction and stroke (CVE) were divided into low- and high-risk groups within which CVE were, respectively, 5.1 and 9.4% (p=0.016).Adjusting for confounding variables the relative risk for a CVE based on the neural network was 2.06 (95% CI: 1.18-3.58) compared with 1.37 (95% CI: 0.79-2.36) for OGTT.The neural network, based on FPG, HDL-c and age, showed useful risk stratification capacities; it may, therefore, be of help when stratifying further risk of CVE in CAD patients.

Background: High blood concentrations of inflammatory markers, including white blood cell (WBC) count, are closely related to the metabolic syndrome. Both conditions predict dismal survival. We determined prospective associations between mortality and factors derived by a factor analysis of WBC count and the basic components of the metabolic syndrome. Methods and Results: We performed a factor analysis of WBC count and the continuous components of the metabolic syndrome in 196 men and 200 women, comprising 64% of the originally invited 75 year olds from the Swedish city Västerås. The analysis revealed three factors in men and two in women. The first factor included fasting glucose, high-density lipoprotein cholesterol, triglycerides, and waist circumference in men and in addition WBC count in women. The second factor included diastolic blood pressure and systolic blood pressure in both sexes. In men, the third factor included fasting glucose and WBC count. These factors explained 66% (first factor, 28%; second factor, 23%; third factor, 15%) of the variation in men and 57% (first factor, 34%; second factor, 23%) in women. Prospective associations of the derived factors and all-cause mortality during 10-year follow-up were assessed by Cox regression [hazard ratio (HR)]. The first factor was significantly related to increased mortality in men: HR=1.22 [95% confidence interval (CI) 1.05–1.41; p=0.008] and women: HR=1.25 (95% CI 1.06–1.48; p=0.010). Pooling men and women adjusting for established cardiovascular risk factors gave HR=1.16 (95% CI 1.04–1.29; p=0.010). In men the third factor was significantly related to mortality; HR=1.29 (95% CI 1.07–1.57; p=0.009). Conclusions: A metabolic inflammatory factor and a blood pressure factor were identified. In men, the former was split into a metabolic and an inflammatory factor. Factors including metabolic and inflammatory components were significantly related to 10-year mortality and the relation remained after adjusting for established cardiovascular risk factors.

We compared weight, height, waist and hip circumferences (hip), body mass index (BMI), and waist-to-hip ratio in acute myocardial infarction (MI) patients and individually sex- and age-matched control subjects from the general population in the catchment area of the patients and predicted the risk of MI status by these basic anthropometric measures. The study cohort comprised 748 patients ≤80 years of age with acute MI from a major Swedish cardiac center and their individually sex- and age-matched controls. The analyses were stratified for sex and age (≤65/≥66 years). Risk of MI was assessed by conditional logistic regression. A narrow hip in men ≥66 years was the single strongest risk factor of MI among the anthropometric measures. The combination of hip and weight was particularly efficient in discriminating men ≥66 years with MI from their controls (area under the receiver operating characteristic (AUROC) curve = 0.82). In men ≤65 years, the best combination was hip, BMI, and height (AUROC = 0.79). In women ≥66 years, the best discriminatory model contained only waist-to-hip ratio (AUROC = 0.67), whereas in women ≤65 years, the best combination was hip and BMI (AUROC = 0.68). A narrow hip reasonably reflects small gluteal muscles. This finding might suggest an association between MI and sarcopenia, possibly related to deficiencies in physical activity and nutrition.

Managers and clinical directors have the ethical and administrative responsibility, and professional duty, to identify clinicians who are performing significantly better or worse than their peers. At the University of Iowa, faculty anesthesiologists (raters) working with Certified Registered Nurse Anesthetists (ratees) evaluate their clinical performance daily using a valid and reliable work habits scale. Because the evaluations are used for ongoing professional practice evaluation and performance reviews, rater bias should be reduced. However, adjustment for rater bias (leniency) causes many raters’ evaluations to have little influence on ranking of ratees. The retrospective cohort study was from a large teaching hospital. Functionally, ratings are binary: the value is 1 when all six items in the scale are scored at the maximum performance, and 0, otherwise (i.e., any item less than maximum). The 40,027 ratings over 5.8 years were sorted by rater in descending sequence of date. The Shannon information content of the ratings was quantified using binomial entropy. The most recent 6359 ratings from 2020 were analyzed using mixed effects logistic regression, with each rater as a fixed effect and ratees as random effects. Using all 74 raters, the Spearman correlation coefficient between the precisions of the raters’ coefficients in the logistic regression and the corresponding binomial entropy was 0.997 (99% confidence interval [CI] 0.992 to 0.999). Excluding the 33 raters who provided all ratings being 1’s or 0’s, the remaining 41 raters’ Spearman correlation was 0.985 (99% confidence interval 0.965 to 0.997). Those 41 raters had median binomial entropies that were 76% of the normalized maximum entropy (99% CI 62% to 86%), while the other 33 raters’ entropy was 0%. When the same rater gave the same rating >10 times in a row, there was a median of 23 more identical ratings in the run (99% CI 21 to 26, N=535). Most loss of information originates from raters who provide all ratees with the largest possible score for all items and from raters who never provide ratings with the maximum score. There should be educative feedback to raters who consistently rate all ratees the same, both for departments with quantitative evaluations using a reliable scale and departments using qualitative evaluations.

Objectives. Determine if pre-emptive daily insulin glargine surpasses regular insulin when needed for glycaemic control after cardiac surgery. Design. Prospective, randomized study of 43 patients (scheduled for coronary artery bypass grafting) with preoperatively diagnosed diabetes (DM) or pre-DM. Lantus group received insulin glargine daily from start of surgery while Actrapid group received regular insulin (sliding scale) when needed (plasma glucose (P-glu) >10 mmol/l). Primary endpoint was percent of pre- and post-prandial P-glu values within Target Intervals: Pre-prandial P-glu: 4.5–7 mmol/l; post-prandial P-glu: 4.5–9 mmol/l. Study period 1–4 days after surgery. Tissue glucose was also measured continuously. Results. More than twice as many P-glu values were within Target Interval for Lantus patients as compared with Actrapid patients (p <0.001). One of 504 timed measurements was <4 mmol/l. Area under the curve for glucose >7 mmol/l was reduced by 61% by Lantus (p <0.001). Conclusion. The routine protocol with pre-emptive glargine insulin studied here provides a major improvement in glycaemic control with a minimal incidence of hypoglycaemia and without an excessive increase in nursing burden.

The amount of information conveyed by check sums in digital sequences is conveniently measured by entropy. We determine the entropy of sums of binary digits and, more generally, r+1 digits 0,…,r for r⩾1. For finite sequences of independent identically distributed binary digits this is the entropy of a binomial distribution. We generalize to Poisson distributions and to Markovian sequences of binary digits. We also consider approximations and upper and lower bounds to the entropies.

To assess the impact of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) on long-term all-cause mortality (ACM) in patients with acute myocardial infarction (AMI) and controls.Matched case-control study with 8-year follow-up.Vastmanland County Hospital, Vasteras, Sweden.Consecutive patients with AMI admitted to the coronary care unit from March 2005 to May 2010 and age-matched and sex-matched controls from the general population.ACM.Person-year at risk among patients with AMI and controls was 11 667 (cases: 5780 and controls: 5887). During follow-up, 199 patients and 84 controls died, implying 3.4 deaths among patients and 1.4 among controls per 100 person-years at risk. Unadjusted Cox analyses showed significantly increasing mortality by decreasing TC and LDL-C levels in both patients (HR=0.70, 95% CI 0.62 to 0.79, p<0.001, and HR=0.64, 95% CI 0.56 to 0.74, p<0.001) and controls (HR=0.73, 95% CI 0.60 to 0.89, p=0.002, and HR=0.74, 95% CI 0.59 to 0.93, p=0.010). After adjusting for clinical variables, the results for the patients remained significant. Cox analyses of the relations between mortality and TC and LDL-C below and above their respective medians revealed the following pattern.below medians were TC and LDL-C levels significantly inversely related to mortality; above medians there were no relations with mortality.below medians were TC and LDL-C levels significantly inversely related to mortality; above medians were LDL-C levels significantly positively related to mortality. Mean LDL-C level in patients with blood sampled >12 hours after symptom onset was 0.41 mmol/L lower than that in patients with blood sampled ≤12 hours (p=0.030). This LDL-C decrease was reasonably caused by ongoing AMI and reflects the difference in LDL-C levels between patients and controls.In patients with AMI, lower TC and LDL-C levels independently predict higher ACM. In their controls, LDL-C levels above the median independently predict higher ACM. This study adds to the body of evidence supporting the existence of a cholesterol paradox.

Abstract Seventy‐one patients were entered into a multicentre, double‐blind randomized study to compare the efficacy and safety of remoxipride with those of haloperidol in the acute treatment of schizophrenia or schizophreniform disorder. The patients, who were well‐matched regarding demographic characteristics, were aged 18–64 years. Four patients in the remoxipride group and 6 in the haloperidol group discontinued treatment prematurely. The mean daily doses during the last week of treatment were 363 mg remoxipride and 9 mg haloperidol. At this time 22% of patients on remoxipride and 66% of those on haloperidol were taking anticholinergics (p &lt; 0.001). The clinical efficacy was similar in both groups as judged by Present State Examination (PSE) profile and Brief Psychiatric Rating Scale (BPRS) ratings. Several adverse symptoms occurred significantly more frequently during treatment with haloperidol than with remoxipride, particularly where extrapyramidal symptoms were concerned. No clinically relevant changes occurred in the laboratory tests in either group.

Abstract Introduction The metabolic syndrome (MetS) represents a cluster of risk factors that predict cardiovascular disease (CVD) and type 2 diabetes. Early detection of MetS opens up for a successful treatment of the cardiovascular (CV) risk factors involved, hopefully leading to later advent of CVD in the general population. Purpose In this long-term, population-based study we aimed to investigate how presence of MetS, in middle-aged men and women, was associated with all-cause mortality and non-fatal CVD later in life. Methods Between 1990 -1999 a screening program was conducted among 40- and 50-year-old inhabitants in the County of Västmanland, Sweden. Data on lifestyle habits and socio-economic status were collected. Total cholesterol, fasting blood glucose, blood pressure, weight, height, waist and hip circumference were measured. Individuals that met three or more of the following risk factors were classified with MetS: waist circumference: ≥102 cm (men) and ≥88 cm (women), total cholesterol: ≥6.1 mmol/ l, blood pressure: ≥130 and/ or ≥85 mm Hg (or previous diagnosis of hypertension) or fasting plasma glucose: ≥5.6 mmol/ l (or previous diagnosis of type 2 diabetes). A control group was identified with individuals from the same population, without MetS diagnosis. Each participant with MetS was matched to two controls regarding sex, age and date for the health examination. The association between midlife MetS and all-cause mortality and non-fatal CV events (stroke and myocardial infarction) was adjusted for age, sex, smoking, physical inactivity, educational level, BMI, hip circumference and living alone or with family members. Multivariable cox regression and Kaplan-Meier analyses were used. Results A total number of 5084 individuals met the criteria for MetS and a control group of 10 168 individuals was identified. The median (Q1, Q3) follow-up time was 27 years (24.6, 30.1), corresponding to 130 820 and 269 696 person-years at risk in the MetS and the control group respectively. During follow up, 1317 MetS and 1904 control subjects died, implying 10 deaths in the MetS group and 7 deaths in the controls per 1000 person-years at risk (fig. 1). Cox analysis showed increased mortality in the MetS group compared to the controls, hazard ratio (HR) 1.30 (95% CI: 1.20-1.40); p&amp;lt;0.001. Non-fatal CV events in the MetS group and in the controls were 32.4% vs 22.8%, respectively (p&amp;lt;0.001); HR 1.35 (CI;1.25–1.46) (fig 2). Median time (Q1, Q3) for first non-fatal CV event was 16.8 years (9.9,22.3) in the MetS group and 19.1 (12.2, 23.6) for the controls. Conclusions Results from this long-term, population-based study underline that the risk of non-fatal CVD and all-cause mortality was significantly higher in individuals with asymptomatic MetS. Present results support previous studies that early identification of MetS with screening programs might open a window of opportunity for prevention of CVD and premature death in the general population.Figure 1.All-cause mortalityFigure 1.Cardiovascular events

Objective: Hyperglycaemia enhances the risk of cardiovascular events and death, while high-density lipoprotein cholesterol (HDLc) is protective. Information on these associations among the elderly population is scanty. We applied a cardiometabolic risk index (CMRI) based on HDLc and fasting plasma glucose (FPG) in an elderly Swedish population. Methods: In total, 432 75-year-olds were followed for 10-year mortality. The impact of risk factors on survival was analysed using Cox regression. Results: HDLc (mmol/l; median and interquartile range) was 1.6 (1.3–2.0) in women and 1.4 (1.2–1.5) in men, while FPG was 5.9 (5.5–6.6) and 5.9 (5.5–6.5). Some 89 persons were at high risk according to CMRI, and 163 persons died. FPG was related to mortality in women (HR; 95% CI: 1.23; 1.10–1.37) and there was a similar trend in men (1.08; 1.00–1.17; p = 0.061). Increasing HDLc was protective in men (0.38; 0.19–0.77) but not in women (0.77; 0.45–1.29). CMRI was related to mortality in both genders even after adjustment for established risk factors (1.79; 1.14–2.79; p = 0.011). Conclusions: The CMRI helps identify elderly subjects at risk and may serve as a cost-effective risk prediction tool.

One thousand and twenty Polish men and women and 1,011 Swedish men and women aged 50 and recruited through primary health care took part in a survey relating to their knowledge of health-related behaviour, attitudes to health-related behaviour and self-reported risk behaviour.The results reveal that Poles know as much about cardiovascular risk factors as Swedes, but that Swedes feel that it is more important to change their dietary habits and to influence factors in the working environment to avoid the risk of developing CVD than did Poles.Swedes also displayed less risk behaviour than Poles and more Swedes than Poles had successfully stopped smoking.These findings suggest that differences in stages of health-related behavior that have previously been observed at an individual level may sometimes also be discerned at a national level.

A comparative study of the efficacy and safety of hyaluronan viscosupplements and placebo in patients with symptomatic and artrhroscopy-verified carilage pathology

Patients and Individually Sexand Age-Matched Controls from the General Population" [1], Dr. Andreas Rosenblad was incorrectly included as an

[Interactions between genes and environment predict criminality, depression and alcohol dependence].

High exercise capacity and low white blood cell counts are determinants of survival up to 90 year : findings in a community based study of 75-year-olds

Background and aim: Cardiovascular disease (CVD) isthe global leading cause of death, albeit improved treatment, and the risk of CVD is in the rise for an aging European population. Framingham andEuro heart score are the basic guidelines for CVD risk assessment but they arestill poor predictors for future CVD events. The aim of this study was toexplore the prognostic ability of the protein biomarkers on Olink ProseekMultiplex CVD Panel.

Objectives: There is a well-known association of type 2 diabetes (T2D) with cardiovascular disease, as manifested by major cardiovascular events (CVEs) such as myocardial infarction and ischemic stroke. However, the mechanisms behind this association are not fully understood, and sensitive biomarkers for vascular risk in diabetic individuals are warranted. We aimed at identifying novel potential lipid biomarkers of incident CVEs in T2D, considering both structural lipids (e.g. triglyceride and cholesteryl ester species), as well as bioactive lipids (e.g. eicosanoids).

Accelerated Atherosclerosis In Systemic Lupus Erythematosus, - A Matter Of Renal Involvement

Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). ...

Arterial wall remodeling is a central multifactorial process in the development and progression of cardiovascular diseases. We employed an approach aimed at observing genetic variants associated with the progression of carotid intima-media thickness (cIMT) in order to identify novel pathways effecting vessel remodeling. This was achieved by conducting gene-centric analysis of 400,000 variants in 3,042 subjects with repeated cIMT measurements. Rs16997464 on chr22 intergenic between neutrophil cytosolic factor-4 ( NCF4) and colony stimulating factor 2 receptor beta ( CSF2RB ) was associated with cIMT progression at array-wide significance (p &lt;4.5x10 -7 ). The potential causative genes within this locus were investigated using a human vascular and non-vascular tissue biobank. Expression of 9 genes near rs16997464, were analyzed with the most significant association being with NCF4 in aortic adventitia. The effect of the variant on the function of the NCF4 gene product was further analyzed by comparing the oxidative burst capacity of neutrophils from subjects with different rs16997464 genotypes. We observed that neutrophils homozygous for the minor T allele, associated with slower cIMT progression, produced more extracellular ROS than neutrophils homozygous for the G allele, indicating a functional effect of rs16997464 on the NCF4 gene product p40 phox , a component of the NADPH oxidase 2 complex (NOX2). In parallel, we investigated if the chr22 locus also influenced the cellular composition of the atherosclerotic plaque, by utilizing data from the Athero-Express Biobank. Here we found that the minor T allele associated with a higher smooth muscle cell (SMC) content in the plaque. Finally, using a partial ligation model in mice where ncf4 is mutated, resulting in a reduced but not absent NOX2-associated ROS formation, we observed a reduced neointima formation in the ncf4 -mutated strain compared with wild-type littermates. Thus, this study identified rs16997464 in the NCF4-CSF2RB locus as a novel genetic determinant of cIMT progression, and provides evidence suggesting that NCF4 is involved in SMC proliferation and alteration of vessel wall pathophysiology.

Introduction: Thrombosis underlies myocardial infarction and other cardiovascular diseases (CVD). Plasminogen activator inhibitor type 1 (PAI-1) is produced by the vascular endothelium and is consi...

Patients with coronary artery disease (CAD) and newly diagnosed diabetes mellitus (NDM) are at increased risk for cardiovascular events (CVE= death, myocardial infarction or stroke). This report from the Euro Heart Survey on Diabetes and the Heart relates glucose lowering (GL) treatment to cardiovascular prognosis. Methods 3940 patients with CAD were enrolled at 110 centers in 25 countries, of whom 1425 (36%) had known DM and 2515 (64%) were glucometabolically characterized with an oral glucose tolerance test (WHO 1999) or fasting blood glucose (ADA 2004) and followed for one-year with respect to CVE. Results 452 patients had NDM of whom 77 (17%) were started on pharmaceutical GL treatment (insulin 5%, oral glucose lowering drugs 94%, both 1%) while 375 (83%) not received any GL drugs. Baseline characteristics did not differ in patients receiving pharmaceutical GL treatment or not. None of the patients receiving pharmaceutical GL treatment died compared to 25 of those who did not (p=0.002). Myocardial infarction and stroke occurred in one vs. 13 and one vs. five patients respectively. Kaplan-Meier curves for CVE in patients receiving GL drugs (full) or not (empty) are shown in the figure . Adjusting for age, sex, previous cardiovascular disease and use of evidence based medications in a Cox proportional hazard regression, patients on pharmaceutical GL treatment had a lower CVE hazard ratio during follow-up (HR 0.22, 95%CI 0.05–0.97; p=0.041) compared to those not on GL therapy. Conclusion There was a striking decrease in event free survival in NDM patients prescribed pharmacological GL therapy following diagnosis underlining the importance to detect and treat such perturbations.

Returning to work after disc surgery appears to be more heavily influenced by psychological aspects of work than by MR-identified morphological alterations. It is still not known whether psychosocial factors of importance for outcome after disc surgery are present preoperatively or develop in the postoperative phase. The aim of this study was to investigate the presence of work-related stress, life satisfaction and demanding life events, among patients undergoing first-time surgery for lumbar disc herniation in comparison with patients scheduled for arthroscopic knee surgery. Sixty-nine patients with disc herniation and 162 patients awaiting arthroscopy were included in the study, during the time period March 2003 to May 2005. Sixty-two percent of the disc patients had been on sick leave for an average of 7.8 months and 14 percent of the knee patients had been on sick leave for an average of 4.2 months. The psychosocial factors were investigated preoperatively using a questionnaire, which was a combination of the questionnaire of quality of work competence (QWC), life satisfaction (LiSat9) and life events as a modification of the social readjustment scale. There were no significant differences between the two groups in terms of work-related stress or the occurrence of demanding life events. The disc patients were significantly less satisfied with functions highly inter-related to pain and discomfort, such as present work situation, leisure-time, activities of daily living (ADL) function and sleep. Patients with disc herniation on sick leave were significantly less satisfied with their present work situation than knee patients on sick leave; this sub-group of patients with disc herniation also reported significantly higher expectations in relation to future job satisfaction than knee patients. The results indicate that psychosocial stress is not more pronounced preoperatively in this selected group of disc patients, without co-morbidity waiting for first-time disc surgery, than among knee patients awaiting arthroscopy. It was notable that the disc patients had high expectations in terms of improved job satisfaction after treatment by surgery.

Self-perceived ability to cope with stress without smoking predicts successful smoking cessation 12 months later in a quitline setting : A Randomized Trial