Insulin sensitivity, proinsulin and insulin as predictors of coronary heart disease. A population-based 10-year, follow-up study in 70-year old men using the euglycaemic insulin clamp

Aims/hypothesis The association between CHD and insulin sensitivity (Si) measured by the euglycaemic insulin clamp has not been examined previously. Earlier studies found a relationship between CHD and elevated plasma insulin, an analysis that may have been confounded by co-determination of proinsulin, which has evolved as a stronger predictor of CHD. The aim was to determine the longitudinal relationships between Si, intact proinsulin, 32–33 split proinsulin, specific insulin and subsequent CHD.Methods This was a population-based cohort study of 815 men in Uppsala, Sweden, aged 70 years at baseline with a follow-up of up to 10 years. Baseline insulin sensitivity was determined by euglycaemic insulin clamp. Fasting proinsulin, 32–33 split proinsulin and specific insulin concentrations were analysed using specific two-site immunometric assays. CHD was taken as diagnosed, if stated (in the event of death) on the Cause of Death Registry, or for subjects hospitalised for the first time with CHD, if CHD was recorded in the Hospital-Discharge Registry. The associations were analysed using Coxs proportional hazards, presented as hazard ratios (HRs) with their 95% CIs for a one-SD increase in the predictor.Results In multivariate analysis, Si (HR:0.80, CI:0.65–0.97) adjusted for serum cholesterol, systolic blood pressure, fasting plasma glucose, BMI and smoking predicted CHD. Intact proinsulin (HR:1.18, CI:1.01–1.38), adjusted as the model above, predicted CHD, whereas 32–33 split proinsulin (HR:1.13, CI:0.95–1.35) or specific insulin (HR:1.07, CI:0.89–1.30) did not.Conclusions/interpretation Insulin resistance measured by the euglycaemic insulin clamp predicts subsequent CHD in elderly men. Proinsulin provides a better prediction of CHD than insulin.     

The relationship of age, blood pressure, serum cholesterol and smoking habits with the risk of typical and atypical coronary heart disease death in the European cohorts of the Seven Countries Study

OBJECTIVE: To explore whether "typical" coronary heart disease (CHD) such as fatal myocardial infarction and sudden death relate to major cardiovascular risk factors in the same way as the "atypical" CHD, such as fatal heart failure and chronic arrhythmias. DESIGN AND SETTING: Ten cohorts (6633 cardiovascular disease-free men, aged 40-59) in five European countries were examined, age and three major risk factors were measured (systolic blood pressure, serum cholesterol, and smoking habits) and 35-year mortality data were collected. Proportional hazard models were solved with typical and atypical CHD deaths treated separately. RESULTS: Death rates from typical and atypical CHD were inversely related among the five countries. Mean age at death was significantly higher for atypical than typical (75.8 versus 71.6 years; p < 0.001). In the multivariate analysis conducted on pools of 5 countries (adjusted for countries), the relationship of risk factors with typical CHD was direct and significant for age (hazard ratio-HR-for 5 years of age 1.44 (95% CI 1.36-1.52)), systolic blood pressure (HR for 20 mm Hg, 1.39 (95% CI 1.32-1.47)), serum cholesterol (HR for 1 mmol/l of 1.22 (95% CI 1.16-1.27)) and smoking habits (HR smokers versus non-smokers of 1.39 (95% CI 1.24-1.57)). For atypical CHD, age had a larger HR of 2.27 (95% CI 2.05-2.52), systolic blood pressure had a smaller HR of 1.28 (95% CI 1.16-1.41), serum cholesterol had an inverse non-significant HR of 0.90 (0.58-1.58) and smoking habits had a larger HR of 1.54 (95% CI 1.26-1.89). CONCLUSIONS: Age and serum cholesterol were differently related with typical and atypical CHD deaths, suggesting different etiologies for these coronary diseases.     

Forty-year follow-up of coronary heart disease mortality and its predictors: the Corfu cohort of the seven countries study

The authors examined the effect of several risk factors in relation to coronary heart disease (CHD) mortality in the Corfu cohort of the Seven Countries Study. The population studied in this analysis consisted of 529 rural men (age 40-59 years) enrolled in 1961. Multivariate analysis was performed with CHD death as the end point; age, blood pressure, heart rate, serum total cholesterol, smoking, physical activity, body mass index, skinfold thickness, vital capacity, and forced expiratory volume were the predictors. The 40-year CHD survival rate was 63% (108 deaths). Age (hazard ratio [HR]=1.093; p<0.001), smoking (HR=1.79; p<0.05), body mass index (HR=1.05; p<0.1), and serum total cholesterol (HR=1.004; p<0.2) were independently associated with 40-year CHD mortality. Conclusively, in men from the Corfu cohort, age, lifestyle habits (expressed as smoking and body mass index), and serum cholesterol levels were consistently associated with 40-year CHD mortality. In addition, the current status of men in the Corfu cohort is marked by long-term adoption of a Mediterranean type of diet, physical activity, and optimism.     

Serum concentrations of adiponectin and risk of type 2 diabetes mellitus and coronary heart disease in apparently healthy middle-aged men: results from the 18-year follow-up of a large cohort from southern Germany.

OBJECTIVES: We sought to assess the association between serum concentrations of adiponectin and long-term risk of type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD) in initially healthy middle-aged men within the same representative population in Augsburg, southern Germany. BACKGROUND: It has been postulated that high serum concentrations of adiponectin, an emerging biomarker that is linked to insulin resistance and endothelial dysfunction, may be protective against T2DM and CHD. METHODS: Serum concentrations of adiponectin were determined in apparently healthy middle-aged men, sampled from the general population in 1984/1985 and followed until 2002. During this period, 115 of 887 men had a newly diagnosed T2DM, and 126 of 937 men suffered from a CHD event. RESULTS: In a Cox model, after multivariable adjustment for cardiovascular risk factors, the hazard ratio of incident T2DM, comparing extreme tertiles of the adiponectin distribution, was 0.55 (95% confidence interval [CI], 0.35 to 0.89), and for incident CHD it was 0.62 (95% CI, 0.39 to 0.98). Further adjustment for high-density lipoprotein cholesterol (HDL-C) attenuated the association, which became formally non-significant. In joint analysis, men with low adiponectin and low HDL-C values showed a 2.63 times (95% CI, 1.66 to 4.15) increased incidence of T2DM and a 1.91 times (95% CI, 1.20 to 3.04) increased incidence of CHD after multivariable adjustment in comparison with men with high HDL-C and high adiponectin. CONCLUSIONS: For patients with low HDL-C values, additional measurement of adiponectin may be helpful to identify individuals at very high risk for T2DM and CHD.     

Relative importance of atherosclerotic risk factors for coronary heart disease in Taiwan.

BACKGROUND: The relative importance of atherosclerotic risk factors, such as hypertension, dyslipidemia, diabetes and smoking, was associated with cardiovascular events and varied among different ethnic groups. For a population with relatively low coronary heart disease (CHD) such as Asian-Pacific countries, it is crucial to differentiate the roles of these risk factors. METHODS: We examined the relative importance of various risk factors for CHD in a community-based cohort in Taiwan, consisting of 3602 adults aged 35 and older with a median follow-up time of 9.0 years since 1990. Regular death certificate verification and medical record reviews were performed in the follow-up activities. RESULTS: There were 85 cases defined as CHD. In the Cox proportional hazard analysis, men were at higher risk than women [hazard risk (HR)=2.22, 95% confidence interval (CI)=1.39-3.56]. Hypertension was the most common risk factor for CHD. Dyslipidemia, especially lowered high-density lipoprotein cholesterol, also played an important role (HR=2.09, 95% CI=1.33-3.29) in CHD events. Hypertension had a greater influence in males (HR=6.08, P<0.001) than in females (HR=2.80, P<0.001). No independent association was found for smoking or body mass index in cardiovascular events. CONCLUSION: This study found that in a community-based cohort, hypertension, and dyslipidemia attribute an important role to cardiovascular events.     

Associations of adiponectin with metabolic and vascular risk parameters in the British Regional Heart Study reveal stronger links to insulin resistance-related than to coronory heart disease risk-related parameters

BACKGROUND AND AIM: Adiponectin is considered by many to be part of the 'common soil' linking type 2 diabetes and coronary heart disease (CHD). We examined the relationship between adiponectin and insulin resistance, metabolic, inflammatory and haemostatic risk factors and hepatic function. METHODS AND RESULTS: The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Adiponectin was associated with waist circumference (inversely), alcohol intake (positively) and physical activity (nonlinearly); no association was seen with cigarette smoking, prevalent CHD or stroke. After adjustment for these factors, adiponectin was significantly inversely associated with insulin resistance, triglyceride, C-reactive protein (but not interleukin 6), tissue plasminogen activator and alanine aminotransferase and positively associated with high-density lipoprotein cholesterol (HDL-cholesterol) and Factor VIII, factors associated with diabetes. No association was seen with cholesterol, smoking, systolic blood pressure or coagulation factors. Risk of the metabolic syndrome decreased significantly with increasing adiponectin. CONCLUSION: Adiponectin is inversely associated with factors strongly associated with the development of diabetes. Limited associations with the established major risk factors for CHD suggest adiponectin may be a stronger marker of risk for diabetes than for CHD.     

Primary risk factors influence risk of recurrent myocardial infarction/death from coronary heart disease: results from the Stockholm Heart Epidemiology Program (SHEEP).

BACKGROUND: Prognosis after a first myocardial infarction (MI) is influenced by primary risk factors as well as secondary risk factors. There is still a lack of follow-up studies of well-characterized patient cohorts assessing the relative importance of these factors. DESIGN: A cohort of 1635 patients (aged 45-70 years) surviving at least 28 days after a first MI were followed for 6-9 years with regard to recurrent MI/fatal coronary heart disease (CHD). Data were collected through questionnaires, physical examinations, and medical records. METHODS: Hazard ratios (HR) with 95% confidence intervals (CI) for different risk factors were calculated using the Cox proportional hazard model. RESULTS: Of the primary risk factors, diabetes in both sexes was the most important predictor of recurrent MI/fatal CHD, multivariate-adjusted HR in men 1.6 (95% CI; 1.0-2.4) and in women 2.5 (95% CI; 0.9-6.9). Other primary risk factors with prognostic influence were job strain, HR 1.5 (95% CI; 1.0-2.1), and central obesity, HR 1.4 (95% CI; 1.0-2.0), in men and a low level of apolipoprotein A1, HR 2.3 (95% CI; 1.1-5.0), and high-density lipoprotein cholesterol, HR 1.9 (95% CI; 0.9-4.1), in women. The secondary risk factors most detrimental for prognosis were heart failure in men, HR 2.2 (95% CI; 1.2-4.0), and a high peak acute cardiac enzyme level in women, HR 4.4 (95% CI; 2.0-9.7). CONCLUSIONS: Long-term follow-up of patients who survived at least 28 days after a first MI shows that several primary cardiovascular risk factors, particularly diabetes, contribute to the increased risk of recurrent MI/fatal CHD.     

不同类型冠心病患者血清脂联素水平及冠心病危险因素的变化

目的探讨不同类型冠心病患者血清脂联素水平和冠心病危险因素的变化及两者的相关性。方法冠心病患者90例:稳定型心绞痛组(SAP)22例,不稳定型心绞痛组(UAP)32例,急性心肌梗死组(AMI)36例;对照组(CG)30例。测定身高、体重、腰围、臀围、空腹血糖(FPG)、胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和血清脂联素(APN)水平,并计算体重指数(BMI)、腰臀比(WHR)及胰岛素敏感性指数(ISI)。结果冠心病组血清APN水平明显降低,且SAP、UAP、AMI三组血清APN水平依次降低。SAP组FINS升高、ISI降低;UAP组FINS、TC、TG升高,吸烟年限长,ISI降低;AMI组BMI、WHR、FINS、TC、TG、LDL-C升高,吸烟年限长,ISI、HDL-C降低。冠心病患者血清APN与BMI、WHR、FINS、TG、LDL-C呈负相关,与ISI、HDL-C呈正相关。结论冠心病患者血清APN水平降低,SAP、UAP、AMI三组血清APN水平依次降低,冠心病危险因素依次增多。冠心病患者血清APN水平与冠心病危险因素密切相关。     

Diabetes,plasma insulin,and cardiovascular disease: subgroup analysis from the Department of Veterans Affairs high-density lipoprotein intervention trial (VA-HIT)

BACKGROUND: Diabetes mellitus, impaired fasting glucose level, or insulin resistance are associated with increased risk of cardiovascular disease. OBJECTIVES: To determine the efficacy of gemfibrozil in subjects with varying levels of glucose tolerance or hyperinsulinemia and to examine the association between diabetes status and glucose and insulin levels and risk of cardiovascular outcomes. METHODS: Subgroup analyses from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial, a randomized controlled trial that enrolled 2531 men with coronary heart disease (CHD), a high-density lipoprotein cholesterol level of 40 mg/dL or less (/=271 pmol/L) was associated with a 31% increased risk of events (P =.03). Gemfibrozil was effective in persons with diabetes (risk reduction for composite end point, 32%; P =.004). The reduction in CHD death was 41% (HR, 0.59; 95% CI, 0.39-0.91; P =.02). Among individuals without diabetes, gemfibrozil was most efficacious for those in the highest fasting plasma insulin level quartile (risk reduction, 35%; P =.04). CONCLUSION: In men with CHD and a low high-density lipoprotein cholesterol level, gemfibrozil use was associated with a reduction in major cardiovascular events in persons with diabetes and in nondiabetic subjects with a high fasting plasma insulin level.     

Plasma adiponectin levels are associated with insulin resistance, but do not predict future risk of coronary heart disease in women

CONTEXT: Low adiponectin levels predict type 2 diabetes, and one prospective study in men reported its independent prediction of vascular events. Many observers thus already consider adiponectin to be a major part of the "common soil" underpinning diabetes and vascular disease. OBJECTIVE: The objective of this study was to assess the association between adiponectin and incident coronary heart disease (CHD) risk in the British Women's Heart and Health Study. DESIGN: This was a prospective (4 yr) case (n = 167) control (n = 334) study nested within the 4286 women in British Women's Heart and Health Study. SETTING: The study was performed in a primary care setting. PARTICIPANTS: The study consisted of women (n = 4286) randomly selected from 23 British towns between 1999 and 2001, who were 60-79 yr of age at baseline. MAIN OUTCOME MEASURES: Association of adiponectin with CHD risk factors and incident CHD events were the main outcome measures. RESULTS: Among both cases and controls, adiponectin positively correlated with age and high-density lipoprotein cholesterol and inversely correlated with waist to hip ratio, fasting insulin, fasting glucose, homeostasis model assessment of insulin resistance scores, C-reactive protein, and triglycerides. However, despite adequate power and these associations with CHD risk factors, adiponectin did not predict CHD events in unadjusted or adjusted analyses. The relative risk ratio for a doubling of adiponectin was 0.93 (95% confidence interval, 0.78, 1.11). CONCLUSIONS: It is premature to consider adiponectin as a root for vascular disease in women despite its association with insulin resistance and diabetes. Additional prospective studies are required to determine whether there is a true sex difference in the effect of adiponectin on CHD.     

Association of circulating levels of leptin and adiponectin with metabolic syndrome and coronary heart disease in patients with various coronary risk factors

The aim of this study was to investigate the associations of adiponectin and leptin with metabolic syndrome (MetS) and coronary heart disease (CHD) in patients with various coronary risk factors. We determined serum adiponectin, leptin, and metabolic syndrome components in 104 patients (59 men and 45 women; aged 40-86 years) with various coronary risk factors at a cardiovascular out-patient clinic. Natural logarithmic transformed (ln) leptin was lower in men and smokers, and positively correlated with body mass index (BMI) (r = 0.59, P < 0.0001), waist circumference (r = 0.60, P < 0.0001), and homeostasis model assessment of insulin resistance (HOMA-IR) levels (r = 0.24, P < 0.02). Ln adiponectin was higher in women and nonsmokers, and was correlated with age and high-density lipoprotein cholesterol (HDL-C). Patients with MetS (n = 69) had significantly higher BMI, HOMA-IR, and ln leptin and lower ln adiponectin than those without Mets (Ln leptin, 2.14 ± 0.08 versus 1.30 ± 0.11; Ln adiponectin, 2.29 ± 0.06 versus 2.54 ± 0.09). In contrast, patients with coronary heart disease (CHD: n = 40) had significantly lower serum ln adiponectin concentrations than non-CHD patients (n = 64) (1.79 ± 0.12 versus 1.91 ± 0.10) as well as lower HDL-C and a higher smoking percentage. Consistent results were obtained by multivariate analyses. In conclusion, this study disclosed factors associated with the increase in serum leptin and adiponectin. Serum levels of leptin may be associated positively with MetS, whereas adiponectin levels are associated negatively with MetS and CHD, even in patients with various coronary risk factors.     

The association of alcohol consumption with coronary heart disease mortality and cancer incidence varies by smoking history

OBJECTIVE: To evaluate the effect of alcohol on coronary heart disease (CHD), cancer incidence, and cancer mortality by smoking history. DESIGN/SETTING: A prospective, general community cohort was established with a baseline mailed questionnaire completed in 1986. Participants: A population-based sample of 41,836 Iowa women aged 55-69 years. MEASUREMENTS: Mortality (total, cancer, and CHD) and cancer incidence outcomes were collected through 1999. Relative hazard rates (HR) were calculated using Cox regression analyses. MAIN RESULTS: Among never smokers, alcohol consumption (> or =14 g/day vs none) was inversely associated with age-adjusted CHD mortality (HR, 0.40; 95% confidence interval [CI], 0.19 to 0.84) and total mortality (HR, 0.71; 95% CI, 0.55 to 0.92). Among former smokers, alcohol consumption was also inversely associated with CHD mortality (HR, 0.45; 95% CI, 0.23 to 0.88) and total mortality (HR, 0.78; 95% CI, 0.62 to 0.97), but was positively associated with cancer incidence (HR, 1.25; 95% CI, 1.03 to 1.51). Among current smokers, alcohol consumption was not associated with CHD mortality (HR, 1.05; 95% CI, 0.73 to 1.50) or total mortality (HR, 1.07; 95% CI, 0.92 to 1.25), but was positively associated with cancer incidence (HR, 1.30; 95% CI, 1.10 to 1.54). CONCLUSIONS: Health behavior counseling regarding alcohol consumption for cardioprotection should include a discussion of the lack of a decreased risk of CHD mortality for current smokers and the increased cancer risk among former and current smokers.     

Lipoprotein particles, insulin, adiponectin, C-reactive protein and risk of coronary heart disease among men with metabolic syndrome

We tested the hypotheses whether nuclear magnetic resonance (NMR) determined lipoprotein particles, insulin and adiponectin, and C-reactive protein (CRP) and white blood cell (WBC) count as markers of inflammation predicted risk of coronary heart disease (CHD) death among 428 men age 35-57 years with metabolic syndrome (MetSyn) in a matched case control study within the multiple risk factor intervention trial. Blood samples collected at entry into the study and stored at -60 degrees C were obtained from central storage for blood analyte analysis. Two hundred and fourteen men with MetSyn who died of CHD were matched with 214 men with MetSyn who did not die of CHD during 18 years of follow-up. Cases were matched to controls on age, study group, number of factors present in the MetSyn, and presence or absence of a nonfatal CVD event during the trial. Mortality follow-up was determined using the National Death Index. Higher levels of high density lipoprotein particles (HDL-P), especially medium-sized HDL-P [hazard ratio (95% confidence interval) 0.45 (0.25-0.83, P<0.01), quartile 1 as compared to quartile 4], were associated with lower risk of CHD death. Low density lipoprotein (LDL) particles were not associated with increased risk of CHD. Elevated LDL cholesterol (LDL-C), smoking and WBC count were, but levels of adiponectin, insulin and CRP were not significantly related to CHD death. In multivariate models adjusting for smoking and LDL-C, medium HDL-P and WBC count remained independent predictors of CHD death. Number of HDL particles, especially medium-sized HDL particles and WBC count were independent predictors of CHD death among men with MetSyn.     

Do known risk factors explain the higher coronary heart disease mortality in South Asian compared with European men? Prospective follow-up of the Southall and Brent studies, UK

Aims/hypothesis We examined prospectively whether measured risk factors can explain the higher CHD mortality in South Asians compared with Europeans.Materials and methods Conventional CHD risk factors and those associated with insulin resistance were measured in 1,787 European and 1,420 South Asian men aged 40 to 69 years at baseline in the population-based Southall and Brent studies (London) between 1988 and 1990. Participants were followed up for mortality.Results By February 2006, there were 202 CHD deaths (108 Asian, 94 European). South Asian men had double the CHD mortality of European men in Cox regression analyses adjusted for age, smoking, and cholesterol (hazard ratio [HR] 2.14, 95% CI 1.56–2.94, p<0.001). Nearly half of all South Asian CHD deaths versus 13% of deaths among Europeans were among persons with diabetes. Asian men had greater CHD mortality than Europeans, both in the with- and the without-diabetes categories at baseline. CHD mortality remained significantly higher in South Asian men in multivariable models that adjusted for conventional risk factors and diabetes and/or impaired glucose regulation, features of insulin resistance, or the metabolic syndrome (HR 1.6–1.9). Accounting for co-morbidity and socio-economic status did not materially alter the findings.Conclusions/interpretation These data confirm that South Asian men have significantly higher CHD mortality than their European counterparts, while indicating that neither conventional risk factors, nor insulin resistance parameters or metabolic syndrome criteria as currently defined can account for this excess risk. The contribution of unmeasured factors to the elevated vascular risk in South Asians should be addressed in future studies.     

Forty-years (1961-2001) of all-cause and coronary heart disease mortality and its determinants: the Corfu cohort from the Seven Countries Study

AIMS: This study examined risk factors in relation to 40-year all-cause and coronary heart disease mortality in the Corfu cohort of the Seven Countries Study. METHODS: The population studied in this analysis consisted of 529 rural middle-aged men enrolled in 1961. Multivariate analysis was performed using the proportional hazards Cox model with all-cause as well as coronary heart disease death as end points and age, blood pressure, serum total cholesterol, smoking, physical activity, body mass index, skinfold thickness, vital capacity and forced expiratory volume as predictors. RESULTS: The 40-year all-cause mortality rate was 87.1% (461 deaths/529 individuals at entry), while the CHD mortality rate was 22.7% (120 deaths/529 individuals at entry). The proportion of CHD deaths varied from 16 to 28.5% of all deaths during the period investigated. Age (hazard ratio (HR)=1.08, P<0.001), smoking (HR=1.40, P<0.01), diastolic blood pressure (HR=1.01, P<0.05), and forced expiratory volume (HR=0.97, P<0.05) were independently associated with 40-year all-cause mortality. Moreover, age (HR=1.093, P<0.001), smoking (HR=1.596, P<0.05), and body mass index (HR=1.05, P<0.05) were independently associated with 40-year CHD mortality. CONCLUSION: Among the investigated cardiovascular risk factors, age, smoking, physical activity, skinfold thickness, diastolic blood pressure, and forced expiratory volume seem to be associated with all-cause mortality, while age, smoking, and body mass index were consistently associated with 40-year CHD mortality.     

Synergistic effects of depressed mood and obesity on long-term cardiovascular risks in 1510 obese men and women: results from the MONICA-KORA Augsburg Cohort Study 1984-1998

OBJECTIVE: To examine the contribution of depressed mood in obese subjects on the prediction of a future coronary heart disease event (CHD). DESIGN: A prospective population-based cohort study of three independent cross-sectional surveys with 6239 subjects, 45-74 years of age and free of diagnosed CHD, stroke and cancer. During a mean follow-up of 7 years, 179 CHD events occurred among men and 50 events among women. SUBJECTS: A total of 737 (23%) male and 773 (26%) female subjects suffering from obesity (BMI >or=30 kg/m2). MEASUREMENTS: Body weight determined by trained medical staff following a standardized protocol; standardized questionnaires to assess subsyndromal depressive mood and other psychosocial features. RESULTS: The main effect of obesity to predict a future CHD (hazard ratio, HR=1.38, 95% CI 1.03-1.84; P=0.031) and the interaction term of obesity by depression (HR=1.73, 95% CI 0.98-3.05; P=0.060) were borderline significant, both covariate adjusted for multiple risk factors. Relative to the male subgroup with normal body weight and no depression, the male obese group with no depression was not at significantly increased risk for CHD events (HR=1.17, 95% CI 0.76-1.80; P=0.473) whereas CHD risk in males with both obesity and depressed mood was substantially increased (HR=2.32, 95% CI 1.45-3.72, P>0.0001). The findings for women were similar, however, not significant probably owing to lack of power associated with low event rates. Combining obesity and depressed mood resulted in a relative risk to suffer from a future CHD event of HR 1.84 (95% CI 0.79-4.26; P=0.158). CONCLUSIONS: Depressed mood substantially amplifies the CHD risk of middle-aged obese, but otherwise apparently healthy men. The impact of depression on the obesity risk in women is less pronounced.     

Levels of adiponectin, C-reactive protein and interleukin-1 receptor antagonist are associated with insulin sensitivity: a population-based study

BACKGROUND: We evaluated the relationship of insulin sensitivity (assessed with the quantitative insulin sensitivity check index, QUICKI) to adiponectin and pro-inflammatory markers, levels of high-sensitivity C-reactive protein (hs-CRP) and interleukin-1 receptor antagonist (IL-1 Ra). METHODS: Cross-sectional study. Study population (N=923, i.e 411 men and 512 women) included five different population-based age groups (born in 1942, 1947, 1952, 1957 and 1962), [mean age 46 years and mean body mass index (BMI) 26 kg/m(2)]. Study protocol included an interview and measurements of anthropometric parameters and glucose, insulin, adiponectin, hs-CRP and IL-1 Ra. RESULTS: Correlation (r) between QUICKI and adiponectin level was 0.334 [95% confidence intervals (CI), 0.275-0.392] and partial correlation adjusted for gender, BMI, smoking status, physical activity and age was 0.247 (95% CI, 0.185-0.308). There was negative correlation between QUICKI and IL-1 Ra (r= -0.385; 95% CI, -0.440 to -0.328) which remained statistically significant after the adjustment for confounding factors (r= -0.178; 95% CI, -0.240 to -0.113). Similarly, QUICKI was negatively correlated with hs-CRP (r= -0.241; 95% CI, -0.302 to -0.178), but after the adjustment it lost its statistical significance. There was a statistically significant gender difference (p=0.018) in correlation between QUICKI and IL-1 Ra levels (men: r= -0.348; 95% CI, -0.436 to - 0.261; women r= -0.500; 95% CI, -0.537 to -0.398). CONCLUSIONS: Our results show that adiponectin level and markers of low-grade inflammation are related to insulin sensitivity. Adiponectin and IL-1 Ra levels might be better markers of the risk of obesity and type 2 diabetes than hs-CRP.     

Male pattern baldness and coronary heart disease: the Physicians' Health Study

OBJECTIVE: To examine the association between male pattern baldness and the risk of coronary heart disease (CHD) events. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study among 22,071 US male physicians aged 40 to 84 years enrolled in the Physicians' Health Study. Of these, 19,112 were free of CHD at baseline and completed a questionnaire at the 11-year follow-up concerning their pattern of hair loss at age 45 years. Response options included no hair loss, frontal baldness only, or frontal baldness with mild, moderate, or severe vertex baldness. MAIN OUTCOME MEASURES: Coronary heart disease events defined as nonfatal myocardial infarction (MI), angina pectoris, and/or coronary revascularization. RESULTS: During 11 years of follow-up, we documented 1446 CHD events in this cohort. Compared with men with no hair loss, those with frontal baldness had an age-adjusted relative risk (RR) of CHD of 1.09 (95% confidence interval [CI], 0.94-1.25), while those with mild, moderate, or severe vertex baldness had RRs of 1.23 (95% CI, 1.05-1.43), 1.32 (95% CI, 1.10-1.59), and 1.36 (95% CI, 1.11-1.67), respectively (P for trend, <.001). Multivariate adjustment for age, parental history of MI, height, body mass index (weight in kilograms divided by the square of the height in meters as a continuous variable), smoking, history of hypertension, diabetes, high cholesterol level, physical activity, and alcohol intake did not materially alter these associations. Results were similar when nonfatal MI, angina, and coronary revascularization were examined separately, and when events were analyzed among men older and younger than 55 years at baseline. Vertex baldness was more strongly associated with CHD risk among men with hypertension (multivariate RR, 1.79; 95% CI, 1.31-2.44) or high cholesterol levels (multivariate RR, 2.78; 95% CI, 1.09-7.12). CONCLUSION: Vertex pattern baldness appears to be a marker for increased risk of CHD events, especially among men with hypertension or high cholesterol levels.     

Prognostic value of adiponectin for cardiovascular disease and mortality

CONTEXT: Low adiponectin concentrations are associated with the presence of an adverse cardiovascular disease (CVD) risk profile. OBJECTIVE: We studied the predictive value of adiponectin levels for all-cause and CVD mortality and CVD morbidity. DESIGN, SETTING, AND PARTICIPANTS: This was a population-based cohort study in Hoorn, The Netherlands, which started in 1989 and included 2484 participants, aged 50-75 yr. MAIN OUTCOME MEASURES: Hazard ratios (HRs) with 95% confidence interval per sd change in log-adiponectin for all-cause and CVD mortality and CVD morbidity were calculated. RESULTS: Adiponectin was determined for 1077 men and 1248 women. Higher adiponectin reduced the risk of nonfatal CVD in women [HR with 95% confidence interval 0.72 (0.61-0.90) in women and 0.92 (0.79-1.06) in men], but not the risk of all-cause or CVD mortality. In contrast, after adjustment for cardiovascular risk factors, higher adiponectin was a significant predictor of all-cause and CVD mortality [HR for CVD mortality 1.45 (1.10-1.92) in women and 1.30 (1.04-1.63) in men]. Higher adiponectin was associated with an increased risk of CVD mortality in people with prevalent CVD [HR 1.27 (0.98-1.63)] and with reduced risk in people without [HR 0.90 (0.73-1.11)]. After adjustment for cardiovascular risk factors, the HRs for CVD mortality were 1.60 (1.14-2.23) for patients with and 1.38 (1.06-1.80) for patients without prevalent CVD. CONCLUSIONS: High levels of adiponectin predict mortality, in particular in patients with prevalent CVD. We hypothesize that adiponectin protects against metabolic and vascular diseases, but in patients already afflicted with CVD, adiponectin is compensatory up-regulated and, therefore, indicates a high mortality risk.     

Do lipids,blood pressure,diabetes, and smoking confer equal risk of myocardial infarction in women as in men? The Reykjavik Study

BACKGROUND: Studies on coronary risk factors in men and women are mainly based on mortality data and few compare results of both sexes with consistent study design and diagnostic criteria. This study assesses the major risk factors for coronary events in men and women from the Reykjavik Study. DESIGN: Within a prospective, population-based cohort study individuals without history of myocardial infarction were identified and the relative risk of baseline variables was assessed in relation to verified myocardial infarction or coronary death during follow-up. METHODS: Of the 9681 women and 8888 men who attended risk assessment from 1967-1991, with follow-up period of up to 28 years, 706 women and 1700 men suffered a non-fatal myocardial infarction or coronary death. RESULTS: Serum cholesterol was a significant risk factor for both sexes, with hazard ratios (HR) decreasing with age. Systolic blood pressure was a stronger risk factor for women as was ECG-confirmed left ventricular hypertrophy (women HR 2.89, 95% confidence interval [CI] 1.67-5.01; men HR 1.11 [CI 0.86-1.43]). Fasting blood glucose > or =6.7 mmol/L identified significantly higher risk for women (HR 2.65) than men (HR 2.08) as did self-reported diabetes. Triglyceride risk was significantly higher for women and decreased significantly with age. Smoking increased risk two- to five-fold, increasing with dose, for women, which was significantly higher than the doubling in risk for men. CONCLUSIONS: This large study of the major risk factors compared between the sexes demonstrates similar relative risk of myocardial infarction associated with cholesterol for both sexes, however, the relative risk is higher in women for many other risk factors such as smoking, diabetes, elevated triglycerides and left ventricular hypertrophy.