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.     

The impact of diabetes mellitus on mortality from all causes and coronary heart disease in women: 20 years of follow-up

BACKGROUND: Few data are available on the long-term impact of type 2 diabetes mellitus on total mortality and fatal coronary heart disease (CHD) in women. METHODS: We examined prospectively the impact of type 2 diabetes and history of prior CHD on mortality from all causes and CHD among 121 046 women aged 30 to 55 years with type 2 diabetes in the Nurses' Health Study who were followed up for 20 years from 1976 to 1996. RESULTS: During 20 years of follow-up, we documented 8464 deaths from all causes, including 1239 fatal CHD events. Compared with women with no diabetes or CHD at baseline, age-adjusted relative risks (RRs) of overall mortality were 3.39 (95% confidence interval [CI], 3.08-3.73) for women with a history of diabetes and no CHD at baseline, 3.00 (95% CI, 2.50-3.60) for women with a history of CHD and no diabetes at baseline, and 6.84 (95% CI, 4.71-9.95) for women with both conditions at baseline. The corresponding age-adjusted RRs of fatal CHD across these 4 groups were 1.0, 8.70, 10.6, and 25.8, respectively. Multivariate adjustment for body mass index and other coronary risk factors only modestly attenuated the RRs. Compared with nondiabetic persons, the multivariate RRs of fatal CHD across categories of diabetes duration (< or =5, 6-10, 11-15, 16-25, >25 years) were 2.75, 3.63, 5.51, 6.38, and 11.9 (P< .001 for trend), respectively. The combination of prior CHD and a long duration of clinical diabetes (ie, >15 years) was associated with a 30-fold (95% CI, 20.7-43.5) increased risk of fatal CHD. CONCLUSIONS: Our data indicate that among women, history of diabetes is associated with dramatically increased risks of death from all causes and fatal CHD. The combination of diabetes and prior CHD identifies particularly high-risk women.     

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.     

Risk of coronary heart disease in subjects with chest discomfort: the Framingham Heart Study

PURPOSE: To examine the risk of coronary heart disease (CHD) events in subjects of the Framingham Study reporting new chest discomfort. SUBJECTS AND METHODS: Original cohort subjects with chest discomfort were classified by their history into three groups: definite angina, possible angina, or nonanginal chest discomfort. Subjects were followed for 2 years for CHD events, including coronary insufficiency, myocardial infarction, or CHD death. RESULTS: Compared to that in subjects without chest discomfort, the relative odds of a CHD event was 3.7 (95% confidence interval [CI] 2.11, 6.60) in men with definite angina and 3.0 (95% CI 1.33, 6.69) in men with possible angina. Comparable increased CHD risk was also observed in women with definite or possible angina, with relative odds of 5.4 (95% CI 3.08, 9.30) and 2.9 (95% CI 1.13, 7.17), respectively. The increase in CHD risk associated with definite or possible angina persisted after adjustment for cardiac risk factor profile. There was no increase in risk associated with nonanginal chest discomfort. CONCLUSION: CHD risk is increased in subjects with new chest discomfort that on the basis of history is consistent with definite or possible angina, whereas CHD risk is not increased in subjects with nonanginal chest discomfort. The presence of chest discomfort and its characteristics facilitate the classification of subjects into meaningful categories that offer prognostic information beyond that provided by traditional CHD risk factors.     

Smoking and risk of coronary heart disease among women with type 2 diabetes mellitus

BACKGROUND: Although the association between smoking and increased risk of coronary heart disease (CHD) is well established in the general population, this relationship is less well-defined among individuals with diabetes. OBJECTIVE: To assess the relationship between cigarette smoking and risk of CHD among women with type 2 diabetes mellitus in the Nurses' Health Study cohort. METHODS: The Nurses' Health Study, a prospective cohort study of 121,700 US female registered nurses surveyed in 11 states and followed up from July 1, 1976, through July 1, 1996, involved a total of 6547 women diagnosed as having type 2 diabetes mellitus. Incident cases of CHD were our main outcome measure in this study. RESULTS: We documented 458 incident cases of CHD (200 fatal CHD-related cases and 258 nonfatal myocardial infarctions) during 20 years (68,227 person-years) of follow-up. We found a dose-response relationship between current smoking status and risk of CHD among diabetic women. Compared with never smokers, the relative risks (RRs) for CHD were 1.21 (95% confidence interval [CI], 0.97-1.51) for past smokers, 1.66 (95% CI, 1.10-2.52) for current smokers of 1 to 14 cigarettes per day, and 2.68 (95% CI, 2.07-3.48) for current smokers of 15 or more cigarettes per day in multivariate analyses (P<.001 for trend). The multivariate RR of CHD among diabetic women who had stopped smoking for more than 10 years was similar to that among diabetic women who were never smokers (RR, 1.01; 95% CI, 0.73-1.38). In secondary analyses involving diabetic and nondiabetic women, the multivariate-adjusted RR of CHD for those with diabetes who currently smoked (> or = 15 cigarettes per day) compared with those who never smoked was 7.67 (95% CI, 5.88-10.01). CONCLUSIONS: Cigarette smoking is strongly associated with an increased risk of CHD among women with type 2 diabetes mellitus. Furthermore, quitting smoking seems to decrease this excess risk substantially; women with diabetes should be strongly advised against smoking.CK     

Sex differences in the effect of diabetes duration on coronary heart disease mortality

BACKGROUND: It is not known whether the coronary heart disease (CHD) mortality risk associated with recent (RDM; <10 years) or long-standing diabetes mellitus (LDM; > or =10 years) varies by sex. METHODS: The relationship between diabetes duration and CHD mortality was evaluated among 10 871 adults (aged 35-74 years at baseline) using the 1971-1992 National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. RESULTS: The CHD mortality rates per 1000 person-years in men with no myocardial infarction (MI) or diabetes, MI only, RDM only, LDM only, MI and RDM, and MI and LDM were 5.5 (95% confidence interval, 4.8-6.2), 15.2 (11.6-20.0), 13.2 (7.9-22.1), 11.4 (6.4-20.3), 36.0 (16.7-77.7), and 35.4 (14.0-89.7), respectively. The corresponding rates in women were 2.9 (2.5-3.3), 7.3 (5.0-10.8), 5.2 (3.5-7.7), 10.7 (7.5-15.5), 9.3 (4.3-19.9), and 21.6 (6.1-76.0), respectively. Compared with MI, the multivariate hazard ratios and their 95% confidence intervals (adjusted for age, race, smoking, hypertension, total cholesterol level, and body mass index) for fatal CHD in men with RDM, LDM, MI and RDM, and MI and LDM were 0.7 (0.3-1.3), 0.8 (0.4-1.4), 3.2 (1.4-7.4), and 2.4 (0.8-6.7), respectively. The corresponding ratios in women were 0.9 (0.6-1.3), 1.8 (1.1-3.2), 1.3 (0.5-3.5), and 1.6 (0.2-10.9), respectively. CONCLUSIONS: In men, RDM and LDM were associated with as high a risk for CHD death as MI. In women, although RDM had a CHD mortality risk similar to MI, LDM had an even greater risk. Because women with LDM are at very high risk for CHD mortality, current guidelines may need to be further refined to match intensity of treatment to risk in these women.     

Ten-year predicted coronary heart disease risk in HIV-infected men and women.

BACKGROUND: Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS: Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS: Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income < $10,000 vs. > $40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS: Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.     

Depression as an antecedent to heart disease among women and men in the NHANES I study. National Health and Nutrition Examination Survey

BACKGROUND: Depression predicts morbidity and mortality among individuals who have coronary heart disease (CHD), and there is increasing evidence that depression may also act as an antecedent to CHD. The studies that have reported a relationship between depression and CHD incidence or mortality either were restricted to men only or analyzed women and men together. The present investigation was conducted to evaluate the differential effect depression may have on CHD incidence and mortality in women and men. RESEARCH METHODS: We analyzed data from 5007 women and 2886 men enrolled in the first National Health and Nutrition Examination Survey (NHANES I) who were free of CHD at the 1982-1984 interview and who had completed the Center for Epidemiologic Studies Depression Scale (CES-D). Participants were evaluated from the 1982 interview date either until the end of the study (1992 interview date) or until the occurrence of a CHD event. Using CHD incidence and CHD mortality (International Classification of Disease, Ninth Revision, codes 410-414) as the outcome variables, Cox proportional hazards regression models were developed to evaluate the relative risk (RR) of CHD incidence and mortality in the depressed women and men separately, controlling for standard CHD risk factors. RESULTS: The women experienced 187 nonfatal and 137 fatal events, compared with 187 nonfatal and 129 fatal events among the men. The adjusted RR of CHD incidence among depressed women was 1.73 (95% confidence internal [CI], 1.11-2.68) compared with nondepressed women. Depression had no effect on CHD mortality in the women (RR, 0.74; 95% CI, 0.40-1.48). The adjusted RR of CHD incidence among depressed men was 1.71 (95% CI, 1.14-2.56) compared with nondepressed men. Depressed men also had an increased risk of CHD mortality compared with their nondepressed counterparts, with an adjusted RR of 2.34 (95% CI, 1.54-3.56). CONCLUSIONS: In this sample, while controlling for possible confounding factors, depression was associated with an increased risk of CHD incidence in both men and women, as well as CHD mortality in men. Depression had no effect on CHD mortality in women.     

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.     

Proteinuria as a risk factor for cardiovascular disease and mortality in older people: a prospective study

BACKGROUND: The prognostic significance of proteinuria in older people is not well defined. We examined the associations between proteinuria and incident coronary heart disease, cardiovascular mortality, and all-cause mortality in older people.SUBJECTS AND METHODS: Casual dipstick proteinuria was determined in 1,045 men (mean [+/- SD] age 68 +/- 7 years) and 1,541 women (mean age 69 +/- 7 years) attending the 15th biennial examination of the Framingham Heart Study. Participants were divided by grade of proteinuria: none (85.3%), trace (10.2%), and greater-than-trace (4.5%). Cox proportional hazards analyses were used to determine the relations of baseline proteinuria to the specified outcomes, adjusting for other risk factors, including serum creatinine level.RESULTS: During 17 years of follow-up, there were 455 coronary heart disease events, 412 cardiovascular disease deaths, and 1,214 deaths. In men, baseline proteinuria was associated with all-cause mortality (hazards ratio [HR] = 1.3, 95% confidence interval [CI] 1.0 to 1.7 for trace proteinuria; HR = 1.3, 95% CI 1.0 to 1.8 for greater-than-trace proteinuria; P for trend = 0.02). In women, trace proteinuria was associated with cardiovascular disease death (HR = 1. 6, 95% CI 1.1 to 2.4), and all-cause mortality (HR = 1.4, 95% CI 1.1 to 1.7).CONCLUSION: Proteinuria is a significant, although relatively weak, risk factor for all-cause mortality in men and women, and for cardiovascular disease mortality in women.     

Framingham risk score and prediction of lifetime risk for coronary heart disease

We investigated whether the Framingham risk score, which was designed to estimate the 10-year risk of coronary heart disease (CHD), differentiates lifetime risk for CHD. All subjects in the Framingham Heart Study examined from 1971 to 1996 who were free of CHD were included. Subjects were stratified into age- and gender-specific tertiles of Framingham risk score, and lifetime risk for CHD was estimated. We followed 2,716 men and 3,500 women; 939 developed CHD and 1,363 died free of CHD. At age 40 years, in risk score tertiles 1, 2, and 3, respectively, the lifetime risks for CHD were 38.4%, 41.7%, and 50.7% for men and 12.2%, 25.4%, and 33.2% for women. At age 80 years, risks were 16.4%, 17.4%, and 38.8% for men and 12.8%, 22.4%, and 27.4% for women. The Framingham risk score stratified lifetime risk well for women at all ages. It performed less well in younger men but improved at older ages as remaining life expectancy approached 10 years. Lifetime risks contrasted sharply with shorter term risks: at age 40 years, the 10-year risks of CHD in tertiles 1, 2, and 3, respectively, were 0%, 2.2%, and 11.6% for men and 0%, 0.7%, and 2.3% for women. The Framingham 10-year CHD risk prediction model discriminated short-term risk well for men and women. However, it may not identify subjects with low short-term but high lifetime risk for CHD, likely due to changes in risk factor status over time. Further work is needed to generate multivariate risk models that can reliably predict lifetime risk for CHD.     

Haptoglobin phenotype and prevalent coronary heart disease in the Framingham offspring cohort

BACKGROUND: The haptoglobin (Hp) locus is polymorphic with two major alleles denoted 1 and 2. Several recent prospective longitudinal studies have demonstrated conflicting results regarding whether there is an increase or decrease in the relative risk of coronary heart disease (CHD) conferred on individuals homozygous for the haptoglobin 1 allele (Hp 1-1). METHODS: We sought to examine the relationship between Hp type and prevalent coronary heart disease in a cross-sectional study from a large community-based cohort, the Framingham Heart Offspring Study (n = 3273). RESULTS: Overall we found no relation between Hp type and CHD prevalence. In secondary analyses we found a different pattern of Hp type and CHD prevalence by diabetes status. In nondiabetics, compared with Hp 1-1, Hp 2-1 (OR 1.71, 95% CI 1.03, 2.83) was associated with excess prevalence of CHD. In contrast in diabetic individuals we observed the opposite pattern; Hp 2-1 (OR 0.49, 95% CI 0.24, 0.99) and Hp 2-2 (OR 0.46, 95% CI 0.22, 0.96) were associated with diminished prevalence of CHD. CONCLUSIONS: These data are consistent with an interaction between Hp type and diabetes in the prevalence of CHD. These findings will need to be confirmed in other cohorts and in longitudinal studies.     

Risk prediction of coronary heart disease based on retinal vascular caliber (from the Atherosclerosis Risk In Communities [ARIC] Study)

Recent studies showed that such retinal vascular signs as quantitative retinal vascular caliber were associated with increased risk of incident coronary heart disease (CHD), but whether these retinal vascular signs add to the prediction of CHD over and above traditional CHD risk factors was not addressed. Whether these signs add to the prediction of CHD over and above the Framingham risk score in people (n = 9,155) without diabetes selected from the ARIC Study was investigated. Incident CHD was ascertained using standardized methods, and retinal vascular caliber and other retinal signs were measured from retinal photographs. After a mean of 8.8 years of follow-up, there were 700 incident CHD events. Women with wider retinal venular caliber (hazard ratio 1.27/1-SD increase, 95% confidence interval 1.08 to 1.50) and narrower retinal arteriolar caliber (hazard ratio 1.31/1-SD decrease, 95% confidence interval 1.10 to 1.56) had a higher risk of incident CHD after adjusting for Framingham risk score variables. Area under the receiver operator characteristic curve increased from 0.695 to 0.706 (1.7% increase) with the addition of retinal vascular caliber to the Framingham risk model. Risk prediction models with and without retinal vascular caliber both fitted the data and were well calibrated for women. In men, retinal vascular caliber was not associated with CHD risk after adjustment. Other retinal vascular signs were not associated with 10-year incident CHD in men or women. In conclusion, although retinal vascular caliber independently predicted CHD risk in women, the incremental predictive ability over that of the Framingham model was modest and unlikely to translate meaningfully into clinical practice.     

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.     

Comparison of estimated glomerular filtration rates and albuminuria in predicting risk of coronary heart disease in a population with high prevalence of diabetes mellitus and renal disease

Improved accuracy in predicting coronary heart disease (CHD) risk in patients with diabetes and kidney disease is needed. The addition of albuminuria to established methods of CHD risk calculation was reported in the Strong Heart Study (SHS) cohort. In this study, the addition of estimated glomerular filtration rate (eGFR) was evaluated using data from 4,549 American Indian SHS participants aged 45 to 74 years. After adjustment for Framingham CHD risk factors, hazard ratios for eGFR as a predictor of CHD were 1.69 (95% confidence interval 1.34 to 2.13) in women and 1.41 (95% confidence interval 0.94 to 2.13) in men. Models including albuminuria, eGFR, or both scored higher in discriminatory power than models using conventional risk factors alone in women; in men, the improvement was seen only for albuminuria and the combination of albuminuria and eGFR. Hosmer-Lemeshow assessments showed good calibration for the models using eGFR alone in both genders, followed by models including albuminuria alone in both genders. Adding eGFR improved the net reclassification improvement (NRI) in women (0.085, p = 0.0004) but not in men (0.010, p = 0.1967). NRI and integrated discrimination improvement (IDI) were improved in both genders using albuminuria and eGFR (NRI 0.135, p <0.0001, and IDI 0.027, p <0.0001 in women; NRI 0.035, p <0.0196, and IDI 0.008, p <0.0156 in men). Therefore, a risk calculator including albuminuria enhances CHD prediction compared to a calculator using only standard risk factors in men and women. Including eGFR alone improves risk prediction in women, but for men, it is preferable to include eGFR and albuminuria. In conclusion, this enhanced calculator should be useful in estimating CHD risk in populations with high prevalence of diabetes and renal disease.     

A genetic risk score based on direct associations with coronary heart disease improves coronary heart disease risk prediction in the Atherosclerosis Risk in Communities (ARIC), but not in the Rotterdam and Framingham Offspring, Studies

ObjectiveMultiple studies have identified single-nucleotide polymorphisms (SNPs) that are associated with coronary heart disease (CHD). We examined whether SNPs selected based on predefined criteria will improve CHD risk prediction when added to traditional risk factors (TRFs).MethodsSNPs were selected from the literature based on association with CHD, lack of association with a known CHD risk factor, and successful replication. A genetic risk score (GRS) was constructed based on these SNPs. Cox proportional hazards model was used to calculate CHD risk based on the Atherosclerosis Risk in Communities (ARIC) and Framingham CHD risk scores with and without the GRS.ResultsThe GRS was associated with risk for CHD (hazard ratio [HR] = 1.10; 95% confidence interval [CI]: 1.07–1.13). Addition of the GRS to the ARIC risk score significantly improved discrimination, reclassification, and calibration beyond that afforded by TRFs alone in non-Hispanic whites in the ARIC study. The area under the receiver operating characteristic curve (AUC) increased from 0.742 to 0.749 (Δ = 0.007; 95% CI, 0.004–0.013), and the net reclassification index (NRI) was 6.3%. Although the risk estimates for CHD in the Framingham Offspring (HR = 1.12; 95% CI: 1.10–1.14) and Rotterdam (HR = 1.08; 95% CI: 1.02–1.14) Studies were significantly improved by adding the GRS to TRFs, improvements in AUC and NRI were modest.ConclusionAddition of a GRS based on direct associations with CHD to TRFs significantly improved discrimination and reclassification in white participants of the ARIC Study, with no significant improvement in the Rotterdam and Framingham Offspring Studies.     

Action levels for obesity treatment in 40 to 42-y-old men and women compared with action levels for prevention of coronary heart disease.

BACKGROUND: Guidelines for treating overweight and obesity have been suggested by the World Health Organization and other expert groups. We asked whether most men and women targeted in obesity guidelines would already be included in existing clinical recommendations for the prevention of coronary heart disease (CHD) or whether a new group of patients would be added to current workloads. SUBJECTS AND METHODS: In 1997 the Norwegian National Health Screening Service examined CHD risk factors in subjects aged 40-42 y living in three counties. We studied 6911 men and 7992 women who did not report treatment for diabetes, hypertension or the presence of cardiovascular disease. Estimated 10 y risk of CHD was calculated using the Framingham equation. RESULTS: The prevalence of single risk factors (systolic blood pressure > or =160 mmHg, diastolic blood pressure > or =95 mmHg, total cholesterol level > or =7.8 mmol/l and nonfasting glucose > or =11.1 mmol/l) ranged between 0 and 11% among subjects with body mass index > or =25 kg/m2. Adding low HDL cholesterol (<1.0 mmol/l for men, <1.1 mmol/l for women) and 10 y risk CHD risk to the classical risk factors increased prevalence to 16-50% (one or more risk factors or 10 y risk > or =10%). Sensitivities and specificities of using body mass index (BMI) or BMI and waist circumference as a screen for elevated CHD risk ranged between 22 and 91%. Screening for 10 y CHD risk of > or =10% or one or more risk factors among men and screening for one or more risk factors among women gave positive predictive values of 19-50%; however, the positive predictive value of screening for 10 y CHD risk of > or =10% was only 1-2% among women. Compared with men with BMI<30 kg/m2 or waist circumference <102 cm, those with measurements equal to or above these levels had statistically significantly higher adjusted odds ratios of elevated CHD risk (1.49, 95% CI 1.24-1.79 and 1.48, 95% CI 1.22-1.80, respectively); these associations were not observed among women. CONCLUSION: Using BMI and waist circumference to screen for CHD risk yields low positive prediction values, thus doubling the number of men and adding even more to the number of women seen by the practitioner for prevention of CHD.     

Fibrinogen, angina and coronary heart disease in a Chinese population

Although fibrinogen is an established risk factor of coronary heart disease (CHD), whether fibrinogen is associated with CHD in Chinese is not clear. This population-based cross-sectional study aimed to analyse this relationship in Hong Kong Chinese. Fibrinogen was measured by the Clauss method in 1348 men and 1385 women aged 25-74 years. Severity of CHD was defined as most serious if the subjects had medically diagnosed CHD, as less serious if they had angina only, and as normal if they had neither. The prevalence of angina and CHD was respectively 2.4% and 2.2% in men and 3.2% and 2.7% in women. In men the age-adjusted mean fibrinogen concentration was 2.47 (95% confidence interval (CI) 2.43-2.51) g/l in the normal group, 2.65 (95% CI 2.45-2.85) g/l in the angina group, and 2.78 (95% CI 2.56-3. 00) g/l in the CHD cases (P<0.01); in women it was respectively 2.61 (95% CI 2.59-2.63), 2.66 (95% CI 2.50-2.82), 2.90 (95% CI 2.72-3.08) g/l (P<0.01). The differences were significant after adjustment of other significant risk factors. We conclude that fibrinogen should be considered as a risk factor in Chinese.     

Predicted risk of coronary heart disease among persons with type 2 diabetes

BACKGROUND: Diabetes is an independent risk factor for the development of coronary heart disease (CHD). We evaluated whether there are racial/ethnic differences in predicted probability of CHD among persons with type 2 diabetes from the 1999-2002 National Health and Nutrition Examination Survey. METHODS: Adults with type 2 diabetes without cardiovascular disease (n=585) were evaluated; the United Kingdom Prospective Diabetes Study (UKPDS) Risk Engine was used to develop estimates of CHD and Framingham Risk Score (FRS) was used to assess the 10-year CHD risk. Chi-square tests and analysis of variance were used to assess differences between racial/ethnic groups in risk factors and predicted probability for CHD. RESULTS: Risk factors for CHD differed significantly amongst the three racial/ethnic groups. Whites had lower mean A1C concentrations (7.3%+/-0.2) than blacks (8.1%+/-0.2, P<0.05) or Mexican Americans (8.1%+/-0.2, P<0.05). Systolic blood pressure was higher in blacks compared with whites (P<0.05) and in Mexican American men compared with white men (P<0.05). Total cholesterol differed insignificantly by race/ethnicity whereas high-density lipoprotein cholesterol was higher in blacks compared with whites and Mexican Americans. Blacks had the greatest 5, 10, 15, and 20-year predicted risks of CHD among men, whereas whites had the greatest predicted risks among women. When evaluated by the FRS, the 10-year predicted risk of CHD was estimated to be 22.5% by UKPDS and 17% using FRS. CONCLUSIONS: UKPDS estimates of probability of CHD were similar across race/ethnicities, indicating that the risk factors tended to balance out. Despite differences in individual risk factors, the estimated risk for CHD was similar for all persons with diabetes.     

Incident diabetes mellitus may explain the association between sleep duration and incident coronary heart disease

Aims/hypothesis

Sleep duration is a risk factor for incident diabetes mellitus and CHD. The primary aim of the present study was to investigate, in sex-specific analyses, the role of incident diabetes as the possible biological mechanism for the reported association between short/long sleep duration and incident CHD. Considering that diabetes is a major risk factor for CHD, we hypothesised that any association with sleep duration would not hold for cases of incident CHD occurring before incident diabetes (‘non-diabetes CHD’) but would hold true for cases of incident CHD following incident diabetes (‘diabetes-CHD’).

Methods

A total of 6966 men and 9378 women aged 45–73 years from the Malmö Diet Cancer Study, a population-based, prospective cohort, who had answered questions on habitual sleep duration and did not have a history of prevalent diabetes or CHD were included in the analyses. Incident cases of diabetes and CHD were identified using national registers. Sex-specific Cox proportional hazards regression models were stratified by BMI and adjusted for known covariates of diabetes and CHD.

Results

Mean follow-up times for incident diabetes (n = 1137/1016 [men/women]), incident CHD (n = 1170/578), non-diabetes CHD (n = 1016/501) and diabetes-CHD (n = 154/77) were 14.2–15.2 years for men, and 15.8–16.5 years for women. In men, short sleep duration (< 6 h) was associated with incident diabetes (HR 1.35, 95% CI 1.01, 1.80), CHD (HR 1.41, 95% CI 1.06, 1.89) and diabetes-CHD (HR 2.34, 95% CI 1.20, 4.55). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.35, 95% CI 0.98, 1.87). Long sleep duration (≥ 9 h) was associated with incident diabetes (HR 1.37, 95% CI 1.03, 1.83), CHD (HR 1.33, 95% CI 1.01, 1.75) and diabetes-CHD (HR 2.10, 95% CI 1.11, 4.00). Long sleep duration was not associated with incident non-diabetes CHD (HR 1.33, 95% CI 0.98, 1.80). In women, short sleep duration was associated with incident diabetes (HR 1.53, 95% CI 1.16, 2.01), CHD (HR 1.46, 95% CI 1.03, 2.07) and diabetes-CHD (HR 2.88, 95% CI 1.37, 6.08). Short sleep duration was not associated with incident non-diabetes CHD (HR 1.29, 95% CI 0.86, 1.93).

Conclusions/interpretation

The associations between sleep duration and incident CHD directly reflect the associations between sleep duration and incident diabetes. Incident diabetes may thus be the explanatory mechanism for the association between short and long sleep duration and incident CHD.