The gender-specific impact of diabetes and myocardial infarction at baseline and during follow-up on mortality from all causes and coronary heart disease

OBJECTIVES: The goal of this study is to compare the magnitude of diabetes and myocardial infarction (MI) at baseline and during follow-up on cause-specific and all-cause mortality. BACKGROUND: History of both MI and diabetes are strong predictors of coronary heart disease (CHD) death. However, gender-specific data on the joint effect of diabetes and MI, and particularly on the effect of incident diabetes and MI developed during the follow-up, on CHD mortality are scarce. METHODS: The baseline cohort study included 2,416 patients with prior diabetes or MI at baseline; the follow-up cohort study included 4,315 patients with incident diabetes or MI diagnosed during the follow-up. RESULTS: In the baseline cohort study, men with prior MI had a 20% to 80% increased risk of CHD or total mortality, but women with prior MI had a 43% to 45% decreased risk of CHD or total mortality in comparison with men and women with prior diabetes. In the follow-up cohort study, men and women with incident MI had a higher risk of CHD mortality (hazard ratio [HR] 2.15 in men and 1.65 in women), and an almost similar risk of total mortality (HR 0.95 in men and 1.02 in women) in comparison with men and women with incident diabetes. CONCLUSIONS: In men, MI at baseline or during follow-up confers a greater risk on CHD mortality than diabetes does. In women, prior MI at baseline confers a lower risk on CHD mortality than prior diabetes does, but incident MI during follow-up confers a greater risk than incident diabetes does. In both men and women, total mortality is similar for incident MI and diabetes.     

Sex differences in risk for coronary heart disease mortality associated with diabetes and established coronary heart disease

BACKGROUND: The sex-specific independent effect of diabetes mellitus and established coronary heart disease (CHD) on subsequent CHD mortality is not known. METHODS: This is an analysis of pooled data (n = 5243) from the Framingham Heart Study and the Framingham Offspring Study with follow-up of 20 years. At baseline (1971-1975), 134 men and 95 women had diabetes, while 222 men and 129 women had CHD. Risk for CHD death was analyzed by proportional hazards models, adjusting for age, hypertension, serum cholesterol levels, smoking, and body mass index. The comparative effect of established CHD vs diabetes on the risk of CHD mortality was tested by testing the difference in log hazards. RESULTS: The adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for death from CHD were 2.1 (95% CI, 1.3-3.3) in men with diabetes only, and 4.2 (95% CI, 3.2-5.6) in men with CHD only compared with men without diabetes or CHD. The HR for CHD death was 3.8 (95% CI, 2.2-6.6) in women with diabetes, and 1.9 (95% CI, 1.1-3.4) in women with CHD. The difference between the CHD and the diabetes log hazards was +0.73 (95% CI, 0.72-0.75) in men and -0.65 (95% CI, -0.68 to -0.63) in women. CONCLUSIONS: In men, established CHD signifies a higher risk for CHD mortality than diabetes. This is reversed in women, with diabetes being associated with greater risk for CHD mortality. Current treatment recommendations for women with diabetes may need to be more aggressive to match CHD mortality risk.     

The impact of diabetes mellitus and prior myocardial infarction on mortality from all causes and from coronary heart disease in men

OBJECTIVES: The goal of this study was to examine the impact of diabetes and prior myocardial infarction (MI) on mortality in men. BACKGROUND: Previous studies have suggested that a history of diabetes and a prior MI confer similar risk for subsequent fatal coronary heart disease (CHD). Few studies have examined duration of diabetes in relation to mortality. METHODS: We examined type 2 diabetes and prior MI in relation to mortality among 51,316 men aged 40 to 75 years in the Health Professionals Follow-up Study. RESULTS: During 10 years of follow-up, we documented 4,150 deaths from all causes, including 1,124 deaths from CHD. Compared with men without diabetes or prior MI at baseline, the multivariate relative risks (RRs) for fatal CHD were 3.84 (95% confidence interval [CI], 3.12 to 4.71) for those with diabetes only, 7.88 (95% CI, 6.86 to 9.05) for those with MI only, and 13.41 (95% CI, 10.49 to 17.16) for those with both diabetes and MI. The corresponding RRs for total mortality were 1.91 (95% CI, 1.70 to 2.15), 2.23 (95% CI, 2.03 to 2.45), and 3.13 (95% CI, 2.56 to 3.84), respectively. Duration of diabetes was an independent risk factor for total as well as CHD mortality; the multivariate RRs of CHD mortality for increasing duration of diabetes (< or = 5 years, 6 to 10 years, 11 to 15 years, 16 to 25 years, 26+ years) were 1.63, 1.93, 2.35, 2.31, and 3.87, respectively (p for trend <0.001), compared with nondiabetic participants. CONCLUSIONS: These findings support that both diabetes and MI are associated with elevated total and CHD mortality, and having both conditions is particularly hazardous. Longer duration of diabetes is a strong predictor of death among diabetic men.     

Improved outcomes for women undergoing contemporary percutaneous coronary intervention: a report from the National Heart,Lung, and Blood Institute Dynamic registry

OBJECTIVES: The goal of this study was to determine whether women undergoing contemporary percutaneous coronary intervention (PCI) remain at increased risk in comparison with men and whether the outcomes in women have improved. BACKGROUND: Previous studies have shown that women treated with coronary angioplasty have a higher incidence of procedural morbidity and mortality than men. METHODS: Gender differences in wave 1 of the National Heart, Lung and Blood Institute (NHLBI) Dynamic registry were evaluated. Baseline characteristics and outcomes in women in the Dynamic registry were compared with those in women in the 1985-1986 and 1993-1994 NHLBI Percutaneous Transluminal Coronary Angioplasty (PTCA) registries. RESULTS: Women were older with a higher prevalence of diabetes mellitus, hypertension, congestive heart failure, unstable angina and single vessel disease in comparison with men. Although procedural success and in-hospital death (2.2% vs. 1.3%), myocardial infarction (MI) (2.3% vs. 3.0%) and coronary artery bypass graft surgery (CABG) (1.3% vs. 1.4%) were similar in women and men, respectively, one-year mortality (6.5% vs. 4.3%, p = 0.02) and combined end point of death/MI/CABG (18.3% vs. 14.4%, p = 0.03) were higher in women than in men. After controlling for other factors, gender was not a significant predictor of death or death plus MI at one year. Despite a higher risk profile in women in the Dynamic registry in comparison with women in the 1985-1986 NHLBI PTCA registry, in-hospital death/MI/CABG was lower (6.0% vs. 11.6%, p < 0.001). CONCLUSIONS: Despite persistent high-risk characteristics in women, gender differences in outcomes in patients undergoing contemporary PCI have decreased, and outcomes in women have improved.     

Coronary events in persons aged 75 years or older in Finland from 1995 to 2002: the FINAMI study

The authors used population-based myocardial infarction (MI) register data to examine trends in incidence, case fatality, treatment strategies of MI, and coronary heart disease (CHD) mortality in persons aged 75 to 99 years in 4 areas of Finland during 1995 through 2002. This age group contributed 53% (n=13,977) of all CHD events, and 65% occurred in women. CHD mortality declined among men annually by 3.5% and 1.0% in the 75- to 84-year-old and 85- to 99-year-old age groups, respectively. Among women, it declined by 2.2% per year in the 75- to 84-year-old age group but increased by 1.3% per year in the 85- to 99-year-old age group. MI attack rate did not change in men but increased significantly in women aged 85 to 99 years. Clinical management of MI in elderly patients was more conservative than in middle-aged patients. In conclusion, one-half of all CHD events occur among persons aged 75 years or older, and elderly patients with CHD represent an increasing burden to the health care system.     

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.     

Comparison of prognostic usefulness of coronary artery calcium in men versus women (results from a meta- and pooled analysis estimating all-cause mortality and coronary heart disease death or myocardial infarction)

Women with coronary heart disease (CHD) have higher mortality compared with men. Atherosclerotic imaging risk markers are associated with higher mortality and relative risk of CHD events in women compared with men. However, data on the predictive accuracy of coronary artery calcium (CAC) in women are scarce. We performed a systematic review of the published literature from 2003 to 2006 on the prognostic value of CAC in women and men. Two investigators reviewed Medline for prospective registries on annual rates of CHD death or myocardial infarction (MI) by CAC results. Three studies in 6,481 women and 13,697 men reported results by gender. We also analyzed 2 observational registries for annual all-cause death rates by CAC scores in women (n = 17,779) and men (n = 17,850). Summary relative risk ratios and 95% confidence intervals were calculated using a random effects model. For all-cause mortality, rates were 0.1% to 1.6% per year for women and 0.1% to 2.6% for men with CAC scores from 0 to 10 to > or =1,000, respectively (p <0.0001). For CHD death or MI, annual rates were 0.2% to 1.3% in women and 0.3% to 2.4% for men with low- to high-risk CAC scores. For women with a CAC score of 0, annual CHD death or MI rates were 0.16%, similar to that of men (p = 0.55). Summary relative risk ratios increased 4.9-fold (p = 0.006), 5.5-fold (p = 0.002), and 8.7-fold (p <0.0001) for mild-, moderate-, and high-risk CAC scores, respectively. A comparative analysis of gender differences showed no significant differences between women and men for mild- to high-risk CAC scores (p = 0.66), suggesting an equivalent ability to risk stratify by gender. In conclusion, this meta- and pooled analysis revealed that CAC screening is equally accurate in stratifying risk in women and men.     

Does NIDDM increase the risk for coronary heart disease similarly in both low- and high-risk populations?

Summary Finland has marked regional differences in the occurrence of coronary heart disease (CHD). Although the causes for these differences in CHD mortality and morbidity in the Finnish population are unknown, it offers an excellent opportunity to investigate the effects of non-insulin-dependent diabetes mellitus (NIDDM) on CHD risk in two populations differing significantly with respect to the occurrence of CHD. Therefore, we carried out a 7-year prospective population-based study including a large number of patients with NIDDM (East Finland: 253 men and 257 women; West Finland: 328 men, 221 women) and corresponding non-diabetic subjects (East Finland: 313 men, 336 women; West Finland: 325 men, 399 women). In both study populations the presence of NIDDM increased significantly the risk for CHD events (CHD mortality or all CHD events including CHD mortality or non-fatal myocardial infarction). Diabetic men had 3–4 fold higher and diabetic women 8–11-fold higher risk for CHD than corresponding non-diabetic subjects. Both non-diabetic and diabetic subjects had odds ratios (East vs West) for CHD events of about 2 indicating a similar East-West difference in the CHD risk. Regional difference was quite similar in men and women. These results imply that factors related to NIDDM, independently of conventional risk factors and the occurrence of atherothrombosis in the background population, must play a major role in the pathogenesis of atherosclerotic vascular disease in NIDDM diabetes.Abbreviations CHD Coronary heart disease - NIDDM non-insulin dependent diabetes mellitus - MI myocardial infarction     

Explaining the sex difference in coronary heart disease mortality among patients with type 2 diabetes mellitus: a meta-analysis

BACKGROUND: Most studies suggest that diabetes is a stronger coronary heart disease (CHD) risk factor for women than men, but few have adjusted their results for classic CHD risk factors: age, hypertension, total cholesterol level, and smoking. OBJECTIVE: To establish an accurate estimate of the odds ratio for fatal and nonfatal CHD due to diabetes in both men and women. METHODS: We compared the summary odds ratio for CHD mortality and the absolute rates of CHD mortality in men and women with diabetes. We searched the MEDLINE and Cochrane Collaboration databases and bibliographies of relevant articles and consulted experts. Studies that included a nondiabetic control group and provided sex-specific adjusted results for CHD mortality, nonfatal myocardial infarction, and cardiovascular or all-cause mortality were included. Of 4578 articles identified, 232 contained primary data, and 182 were excluded. Two reviewers recorded data on study characteristics, quality, and outcomes from 50 studies. RESULTS: Sixteen studies met all inclusion criteria. In unadjusted and age-adjusted analyses, odds of CHD death were higher in women than men with diabetes. From 8 prospective studies, the multivariate-adjusted summary odds ratio for CHD mortality due to diabetes was 2.3 (95% confidence interval, 1.9-2.8) for men and 2.9 (95% confidence interval, 2.2-3.8) for women. There were no significant sex differences in the adjusted risk associated with diabetes for CHD mortality, nonfatal myocardial infarction, and cardiovascular or all-cause mortality. Absolute CHD death rates were higher for diabetic men than women in every age strata except the very oldest. CONCLUSIONS: The excess relative risk of CHD mortality in women vs men with diabetes was absent after adjusting for classic CHD risk factors, but men had more CHD deaths attributable to diabetes than women.     

Increased levels of triglycerides, BMI and blood pressure and low physical activity increase the risk of diabetes in Swedish women. A prospective 18-year follow-up of the BEDA study.

AIM: To investigate risk factors for the development of diabetes in middle-aged women. METHODS: A random population sample of 1351 women without prior diabetes or cardiovascular disease, aged 39-65 years, took part in a screening study in 1979-1981 with questionnaires, physical examination and blood sampling. Development of diabetes up to 1998 was identified at a second examination in 1997-1998. RESULTS: Seventy-three women (5.4%) were diagnosed with diabetes during follow-up. As expected, obesity resulted in a rising age-adjusted risk with hazards ratio 3.2 [95% confidence interval (CI) 1.3, 8.1] at body mass index (BMI) 24-27 kg/m(2), and 8.3 (3.5, 19.7), at BMI > or = 27, compared with BMI < 22 kg/m(2). S-triglycerides (TG) carried a steeply increasing age-adjusted risk with hazards ratio 4.0 (95% CI 2.1, 7.6) already at s-TG 1.0-1.4 mmol/l, 7.1 (3.6, 14.0) at s-TG 1.5-1.9 mmol/l and 9.3 (4.3, 20.2) at s-TG > or = 2.0 mmol/l compared with s-TG < 1.0 mmol/l. Increasing systolic blood pressure (SBP) to 130-144, 145-159 and > or = 160 mmHg escalated the hazards ratio of diabetes to 1.6 (0.8, 3.3), 3.6 (1.7, 7.4) and 5.6 (2.7, 11.4), respectively, compared with SBP < 130 mmHg. Also, low physical activity predicted diabetes, with hazards ratio 2.1 (1.3, 3.3) for sedentary compared with non-sedentary activity. Smoking was not associated with increased risk of diabetes. After adjustment for BMI, SBP and physical activity, increasing TG level remained a strong and significant risk factor for diabetes [hazards ratio 3.0 (1.6, 5.7), 3.7 (1.8, 7.7) and 4.5 (2.0, 10.0), P < 0.001]. CONCLUSIONS: Among middle-aged Swedish women even very slightly elevated s-TG resulted in a considerably enhanced risk of developing diabetes, which was independent of age, BMI, blood pressure and physical activity.     

Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease.

AIMS: To evaluate the joint associations of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the incidence of coronary heart disease (CHD) and CHD mortality. METHODS AND RESULTS: Study cohorts included 49 775 Finnish subjects aged 25-74 without history of CHD and stroke. The multivariable-adjusted hazard ratios (HRs) of CHD incidence were 1.25, 1.69, 1.25, 1.83, 1.85, 2.39, 2.15, and 3.31 (P-value for trend <0.001), respectively, among men with hypertension I (blood pressure 140-159/90-94 mmHg or using antihypertensive drugs at baseline but blood pressure <160/95 mmHg) only, with hypertension II (blood pressure > or =160/95 mmHg) only, with incident diabetes during follow-up only, with both hypertension I and incident diabetes, with both hypertension II and incident diabetes, with history of diabetes at baseline only, with both hypertension I and history of diabetes, and with both hypertension II and history of diabetes compared with men without either of these diseases. The corresponding HRs of CHD incidence among women were 1.52, 2.37, 2.45, 3.78, 4.56, 5.63, 6.10, and 7.41 (P-value for trend <0.001), respectively. The impact on CHD mortality associated with the different strata of hypertension and diabetes was almost the same or a little stronger compared with that on the CHD incidence. CONCLUSION: Hypertension and type 2 diabetes increase the CHD risk independently, and their combination increases the risk dramatically, particularly in women.     

Sex differences in cardiovascular and total mortality among diabetic and non-diabetic individuals with or without history of myocardial infarction

Aims/hypothesis We investigated the associations of type 2 diabetes and a history of myocardial infarction (MI) with coronary heart disease, stroke, cardiovascular and total mortality, and whether these effects are different in men and women.Methods Study cohorts included 51,735 Finnish men and women aged 25–74 years. Smoking status and the history of MI and type 2 diabetes were recorded, and height, weight, blood pressure and serum cholesterol levels were measured at baseline. Additional data on the occurrence of diabetes and MI prior to baseline survey were obtained from national hospital discharge and drug registers through computerised register linkage. Mortality data were obtained from the national mortality register.Results During a mean follow-up period of 17.2 years, 9,201 deaths were recorded. Hazard ratios (HRs) for coronary mortality were 2.1, 4.0 and 6.4 among men with diabetes alone, men with MI alone, and men with diabetes and MI, respectively, compared with men with neither diabetes nor a history of MI. The corresponding HRs among women were 4.9, 2.5 and 9.4, respectively. The equivalent HRs for cardiovascular and total mortality were 2.2, 3.3 and 6.0, and 1.8, 2.3 and 3.7 in men, and 4.4, 2.4 and 6.5, and 3.2, 1.7 and 4.4 in women, respectively. Diabetic men and women had similar total mortality rates, whereas total mortality rates were markedly higher among men in the other three diabetes–MI categories.Conclusions/interpretation Diabetes and MI markedly increase cardiovascular and all-cause mortality. In women, the association between diabetes and mortality was stronger than that between MI and mortality, whereas the converse was true among men.     

Risk factors for myocardial infarction in women and men: insights from the INTERHEART study.

AIMS: Coronary heart disease (CHD) is a leading cause of death among men and women globally. Women develop CHD about 10 years later than men, yet the reasons for this are unclear. The purpose of this report is to determine if differences in risk factor distributions exist between women and men across various age categories to help explain why women develop acute MI later than men. METHODS AND RESULTS: We used the INTERHEART global case-control study including 27 098 participants from 52 countries, 6787 of whom were women. The median age of first acute MI was higher in women than men (65 vs. 56 years; P < 0.0001). Nine modifiable risk factors were associated with MI in women and men. Hypertension [2.95(2.66 -3.28) vs. 2.32(2.16-2.48)], diabetes [4.26(3.68-4.94) vs. 2.67(2.43-2.94), physical activity [0.48(0.41-0.57) vs. 0.77(0.71-0.83)], and moderate alcohol use [0.41(0.34-0.50) vs. 0.88(0.82-0.94)] were more strongly associated with MI among women than men. The association of abnormal lipids, current smoking, abdominal obesity, high risk diet, and psychosocial stress factors with MI was similar in women and men. Risk factors associations were generally stronger among younger individuals compared to older women and men. The population attributable risk (PAR) of all nine risk factors exceeded 94%, and was similar among women and men (96 vs. 93%). Men were significantly more likely to suffer a MI prior to 60 years of age than were women, however, after adjusting for levels of risk factors, the sex difference in the probability of MI cases occurring before the age of 60 years was reduced by more than 80%. CONCLUSION: Women experience their first acute MI on average 9 years later than men. Nine modifiable risk factors are significantly associated with acute MI in both men and women and explain greater than 90% of the PAR. The difference in age of first MI is largely explained by the higher risk factor levels at younger ages in men compared to women.     

Gender impact on prognosis of acute coronary syndrome patients treated with drug-eluting stents

Women have a higher risk of adverse outcomes after percutaneous coronary intervention (PCI) than men. However, in acute coronary syndrome (ACS), long-term outcomes after contemporary PCI with drug-eluting stent (DES) have not been fully investigated. We aimed to test the impact of gender on outcomes in patients with ACS after PCI with DES. We analyzed all patients with ACS from the prospective NOBORI-2 trial who underwent PCI with a Nobori DES from 2008 through 2009 in 125 centers worldwide. End points of the study were target lesion failure, cardiac death, myocardial infarction (MI), and clinically driven target lesion revascularization, and major adverse cardiac events (composite of cardiac death, MI, and target vessel revascularization) at 1 year and yearly up to 5 years. There were 1,640 patients with ACS, 1,268 men (77%) and 372 women (23%). Compared to men, women were 5 years older and more frequently had co-morbidities such as diabetes mellitus and hypertension. There were no gender differences for cardiac death (1.3% vs 2.7%), MI (2.1% vs 3.2%), or target lesion revascularization (2.6% vs 3.8%) at 1 year after the procedure for men and women, respectively. The trend was the same at 2 years (cardiac death 2.0% vs 2.3%, MI 2.5% vs 3.5%, target lesion revascularization 3.2% vs 4.6%). Target lesion failure rates were 4.5% and 5.9% at 1 year and 5.7% and 7.3% at 2 years in men and women, respectively (p = NS). Multivariate analysis, which included age, hypertension, diabetes mellitus, and number of diseased vessels, showed that gender was not a predictor for outcome. There were no differences in bleeding or stent thrombosis rates. Relief from anginal symptoms was similar. The same rate of adherence to dual antiplatelet therapy was observed and reached 73% at 1 year and 31% at 2 years after the ACS event and PCI. In conclusion, although women had worse baseline characteristics, no differences in outcomes were observed between men and women treated for ACS with contemporary DES.     

Left ventricular hypertrophy determined by Sokolow-Lyon criteria: a different predictor in women than in men?

The clinical usefulness of the Sokolow-Lyon voltage criteria in the assessment of electrocardiographic left ventricular hypertrophy (ECG LVH) is addressed. We prospectively studied 3,338 women and 3,330 men referred with hypertension, with an average follow-up of 11.2 years. The voltage amplitude sum SV1+max (RV5 or RV6) was calculated and ECG LVH was defined as a sum >or=3.5 mV. We adjusted survival for age, treatment status before presentation and a previous myocardial infarction or cerebrovascular accident. The risk of stroke, coronary heart disease (CHD) and cardiovascular disease (CVD) mortality increased significantly for each quantitative 0.1 mV increase in baseline electrocardiogram (ECG) voltage, in women within the range of 1.6-3.9% and in men 1.4-3.0%. After further adjustments for race, body mass index, smoking and systolic blood pressure, increasing voltage independently predicted CVD mortality in both men and women. In women, both increasing voltage and the presence of left ventricular hypertrophy (LVH) were predictors of stroke mortality, whereas in men this risk was attenuated. In men, the adjusted association between increasing voltage and CHD mortality tended to be stronger than in women. The use of different thresholds for the two genders made little difference. For stroke and CHD mortality, the population attributable fractions associated with LVH were 15.2 and 5.4% in women and 12.8 and 8.5% in men, respectively. In conclusion, the greater the baseline ECG voltage sum, the greater the associated CVD mortality risk. Women tended to have a high risk of stroke mortality owing to LVH despite adjustments.     

Diabetes and all-cause and coronary heart disease mortality among US male physicians

BACKGROUND: While diabetes has long been associated with increased risk of coronary heart disease (CHD), the magnitude of risk of diabetes-related CHD is uncertain. OBJECTIVE: To evaluate the impact of diabetes and prior CHD on all-cause and CHD mortality. METHODS: In a prospective cohort study of 91 285 US male physicians aged 40 to 84 years, participants were divided into 4 groups: (1) a reference group of 82 247 men free of both diabetes and CHD (previous myocardial infarction and/or angina) at baseline, (2) 2317 men with a history of diabetes but not CHD, (3) 5906 men with a history of CHD but not diabetes, and (4) 815 men with a history of both diabetes and CHD. Rates of all-cause and CHD mortality were compared in these groups. RESULTS: Over 5 years (49 7952 person-years of follow-up), 3627 deaths from all causes were documented, including 1242 deaths from CHD. Compared with men with no diabetes or CHD, the age-adjusted relative risk of death from any cause was 2.3 (95% confidence interval [CI], 2.0-2.6) among men with diabetes and without CHD, 2.2 (95% CI, 2.0-2.4) among men with CHD and without diabetes, and 4.7 (95% CI, 4.0-5.4) among men with both diabetes and CHD. The relative risk of CHD death was 3.3 (95% CI, 2.6-4.1) among men with diabetes and without CHD, 5.6 (95% CI, 4.9-6.3) among men with CHD and without diabetes, and 12.0 (95% CI, 9.9-14.6) among men with both diabetes and CHD. Multivariate adjustment for body mass index, smoking status, alcohol intake, and physical activity as well as stratification by these variables did not materially alter these associations. CONCLUSIONS: These prospective data indicate that diabetes is associated with a substantial increase in all-cause and CHD mortality. For all-cause mortality, the magnitude of excess risk conferred by diabetes is similar to that conferred by a history of CHD; for mortality from CHD, a history of CHD is a more potent predictor of death. The presence of both diabetes and CHD, however, identifies a particularly high-risk group.     

Alcohol consumption, TaqIB polymorphism of cholesteryl ester transfer protein, high-density lipoprotein cholesterol, and risk of coronary heart disease in men and women.

AIMS: To investigate whether a common polymorphism in the cholesteryl ester transfer protein (CETP) gene modifies the relationship of alcohol intake with high-density lipoprotein cholesterol (HDL-C) and risk of coronary heart disease (CHD). METHODS AND RESULTS: Parallel nested case-control studies among women [Nurses' Health Study (NHS)] and men [Health Professionals Follow-up Study (HPFS)] where 246 women and 259 men who developed incident CHD were matched to controls (1:2) on age and smoking. The TaqIB variant and alcohol consumption were associated with higher HDL-C, with the most pronounced effects of alcohol among B2 carriers. In the NHS we did not find an inverse association between alcohol and CHD in B2 non-carriers (P trend: 0.5), but did among B2 carriers (P trend <0.01). Among non-carriers the odds ratio (OR) for CHD among women with an intake of 5-14 g/day was 1.4 (95% CI: 0.6-3.7) compared with non-drinkers, whereas among B2 carriers the OR was 0.4 (0.2-0.8). Results in men were less suggestive of an interaction; corresponding OR's were 1.9 (0.8-4.5) and 0.9 (0.5-1.6), for B2 non-carriers and carriers, respectively. CONCLUSIONS: The association of alcohol with HDL-C levels was modified by CETP TaqIB2 carrier status, and there was also a suggestion of a gene-environment interaction on the risk of CHD.     

Risk factors for coronary heart disease in African Americans: the atherosclerosis risk in communities study, 1987-1997

BACKGROUND: As part of the Atherosclerosis Risk in Communities Study, the race-specific incidence rates and risk factor prediction for coronary heart disease (CHD) were determined for black and white persons over 7 to 10 years of follow-up, from 1987 to 1997. METHODS: The sample included 14 062 men and women (2298 black women, 5686 white women, 1396 black men, and 4682 white men) aged 45 to 64 years who were free of clinical CHD at baseline. RESULTS: Average age-adjusted incidence rates (95% confidence intervals) for CHD per 1000 person-years were as follows: black women, 5.1 (4.2-6.2); white women, 4.0 (3.5-4.6); black men, 10.6 (8.9-12.7); and white men, 12.5 (11.5-13.7). Incidence rates (95% confidence intervals) using a definition for CHD that excluded revascularization procedures were as follows: black women, 4.9 (4.6-6.0); white women, 2.9 (2.5-3.4); black men, 9.2 (7.6-11.1); and white men, 7.9 (7.0-8.8). In a multivariable analysis, hypertension was a particularly strong risk factor in black women, with hazard rate ratios (95% confidence intervals) as follows: black women, 4.8 (2.5-9.0); white women, 2.1 (1.6-2.9); black men, 2.0 (1.3-3.0); and white men, 1.6 (1.3-1.9). Diabetes mellitus was somewhat more predictive in white women than in other groups. Hazard rate ratios (95% confidence intervals) were as follows: black women, 1.8 (1.2-2.8); white women, 3.3 (2.4-4.6); black men, 1.6 (1.1-2.5); and white men, 2.0 (1.6-2.6). Low-density lipoprotein cholesterol level was similarly predictive in all race-sex groups (hazard rate ratio, 1.2-1.4 per SD increment of low-density lipoprotein cholesterol level). High-density lipoprotein cholesterol level seemed somewhat more protective in white than in black persons. CONCLUSIONS: Findings from this study, along with clinical trial evidence showing efficacy, support aggressive management of traditional risk factors in black persons, as in white persons. Understanding the intriguing racial differences in risk factor prediction may be an important part of further elucidating the causes of CHD and may lead to better methods of preventing and treating CHD.     

Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28,838 middle-aged men and women.

AIMS: Serum gamma-glutamyltransferase (GGT) concentration may be involved in atherosclerosis. This study examined if serum GGT predicted coronary heart disease (CHD), especially differentiating non-fatal myocardial infarction (MI) and fatal CHD event, among the general population or participants with type-2 diabetes. METHODS AND RESULTS: A prospective study of 28,838 Finnish men and women aged 25-74 years was performed (1467 incident CHD cases; a median follow-up time of 11.9 years). Serum GGT cutpoints were the 25th, 50th, 75th, and 90th sex-specific percentiles. After adjustment for known cardiovascular risk factors, compared with the lowest GGT category, hazard ratios (HR) were 1.15, 1.25, 1.27, and 1.57 among men and 1.03, 1.22, 1.32, and 1.44 among women in other four GGT categories (P for trend <0.01, respectively). However, stronger associations were observed among subjects aged <60 and among alcohol drinkers. The strength of association was similar for non-fatal MI and for fatal CHD. Among subjects with type-2 diabetes, the corresponding adjusted HRs were 1.29, 1.57, 1.88, and 1.78 (P trend=0.03, men and women combined). CONCLUSION: This study suggests an independent mechanism linking serum GGT to CHD among general population. Even though the strength of association appeared to be modest among all subjects, stronger associations were observed among subjects aged <60 and among alcohol drinkers. Especially, measurement of serum GGT among type-2 diabetics may be helpful to predict the future risk of CHD.     

Impact of diabetes and previous myocardial infarction on long-term survival: 25-year mortality follow-up of primary screenees of the Multiple Risk Factor Intervention Trial

BACKGROUND: The magnitude of coronary mortality risk associated with diabetes or prior myocardial infarction (MI) is debatable. Modulating effects of age, risk factors, and duration of follow-up may explain discrepancies in previous research. Associations with noncardiovascular mortality are little explored. OBJECTIVES: To compare mortality patterns in men with a history of diabetes or MI and to assess modulating effects on mortality of age, cardiovascular risk factors, and follow-up duration. METHODS: We compared the 25-year mortality of 4809 men with diabetes only and 4625 men with MI only (all men aged 35-57 years). RESULTS: The adjusted hazard ratio (HR) for all-cause mortality for those with MI only vs those with diabetes only was 0.97 (95% confidence interval, 0.92-1.03; P =.32). The pattern of deaths was different: higher coronary mortality (HR = 1.37; P<.001) and lower mortality from noncardiovascular causes (HR = 0.66; P<.001) in those with MI only compared with those with diabetes only. This finding prevailed across all ages and levels of cardiovascular risk factors. Hazard ratios for coronary mortality significantly declined over follow-up (2.7, 1.7, 1.2, 1.1, and 1.0 for < or =5, 6-10, 11-15, 16-20, and >20 years of follow-up, respectively), whereas HRs for noncardiovascular mortality remained relatively constant. CONCLUSIONS: Overall, diabetes and MI were similarly strong predictors of total mortality. Higher mortality from noncardiovascular causes was observed in those with diabetes only, whereas prior MI was more strongly predictive of coronary mortality than diabetes at any age and level of cardiovascular risk factors. The difference in coronary mortality between the 2 groups was most evident in the first 10 years of follow-up.