Incidence Of Coronary Heart Disease In Men Research Articles

Abstract P387: FOXO3 Longevity Genotype Mitigates The Risk Of Coronary Heart Disease In Men With Hypertension

Background: We have shown that the FOXO3 longevity genotype moderates the mortality risk in men with hypertension. This study aimed to test whether the FOXO3 longevity genotype moderates the risk of incident coronary heart disease (CHD) in men with hypertension. Methods: The study included 6,312 Japanese American men who were free of CHD at the baseline examination of the Kuakini Honolulu Heart Program (1965-1968, age 53.9±5.4, range 45-68 years), and had been genotyped for the FOXO3 SNP rs2802292 ( FOXO3-292 ). The minor G allele, i.e., TG or GG (TG / GG) genotype is associated with longevity vs. the common TT genotype, which is not . Hypertension was defined as systolic/diastolic BP ≥ 140/90 mmHg or taking antihypertensive medication. Incident CHD was diagnosed from hospital records and follow up examinations to 12/31/2000 (35 years of follow-up). The date of the first coronary event was defined as onset date of CHD, including myocardial infarction, coronary insufficiency, angina, coronary bypass, coronary angioplasty, silent myocardial ischemia, and CHD death. Cox proportional hazard models were used to assess the association of FOXO3-292 genotype and hypertension with incident CHD. Results: During follow-up, 1,629 men developed incident CHD. The age-adjusted incidence rate of CHD was 8.99, 8.31, and 8.62 per 1,000 person-years ( p =0.62) for FOXO3-292 genotypes TT, TG, and GG , respectively. The Cox model, adjusting for age and CVD risk factors, showed hazard ratio (95%CI) for CHD with FOXO3-292 genotypes TG / GG compared to genotype TT was 0.91 (0.82-1.00; p =0.058). The full Cox model, adjusting for age and CVD risk factors, showed a significant interaction effect of FOXO3-292 genotypes TG / GG with hypertension on incident CHD (β= -0.22, p =0.03). After stratifying for hypertension, FOXO3-292 genotypes TG / GG had no effect on incident CHD in those without hypertension HR=1.01 (0.88-1.17; p =0.84) but had a protective effect on incident CHD HR=0.82 (0.74-0.95; p = 0.0064) in those with hypertension. Conclusion: We found the longevity associated FOXO3 genotype may not independently affect the risk of CHD in all men but was associated with protection against incident CHD in men with hypertension.

Genetic Risk Score for Prediction of Coronary Heart Disease in the Korean Genome and Epidemiology Study.

Using a genetic risk score (GRS) to predict coronary heart disease (CHD) may detect disease earlier. The current study aims to assess whether GRS is associated with CHD incidence and whether it is clinically useful for improving prediction using traditional risk factors (TRFs) as well as family history. Data from a total of 48,941 participants in the Korean Genome and Epidemiology Study were analyzed in the current study. The weighted GRS was constructed using 55 single-nucleotide polymorphisms based on published genome-wide association studies. The association of GRS with incident CHD was analyzed using Cox proportional hazard model. Discrimination and reclassification were assessed to demonstrate the clinical utility of GRS. The analyses were performed separately by sex. After adjusting for family history and TRFs, GRS was significantly associated with CHD incidence in men; compared to the low GRS group, men in the high GRS group had a 2.07-fold increased risk of CHD (95% confidence interval [CI]: 1.51-2.85). In men, the combination of TRFs, family history, and GRS had better performance than TRFs alone (C statistics for TRF-only model, 0.66, 95% CI, 0.64-0.69; C statistics for combination model, 0.68, 95% CI, 0.65-0.71; category-free reclassification index, 15%). In women, however, there was no significant association between GRS and CHD and no improvement between models. GRS was associated with CHD incidence and contributed to a small improvement of CHD prediction in men. The potential clinical use of GRS may not outweigh the value of family history.

Periodontitis and risk of prevalent and incident coronary heart disease events.

To investigate periodontitis as a risk factor for prevalent and incident coronary heart disease (CHD) in a group of middle-aged men from Northern Ireland. A representative sample of 1400 dentate men had a comprehensive periodontal examination between 2001 and 2003. Prevalent and incident CHD events were validated by independent cardiologists. Logistic regression was used to assess the cross-sectional relationship between periodontitis and prevalent CHD and Cox's proportional hazards analysis to assess the longitudinal relationship between periodontitis and incident CHD. The mean age of the men at baseline was 63.7 (SD 3.0)years. Of the 1400 men examined, 126 (9%) had prevalent CHD. After adjusting for confounding variables, men with highest mean CAL (Q4) had an odds ratio of 2.15 (95% CI 1.15-4.02), p=0.02 for prevalent CHD in comparison to men with the lowest CAL (Q1). During a median follow-up of 12.7years, 137 (10.8%) of the 1274 men free of CHD at baseline had an incident CHD event. After adjusting for confounding variables, the hazard ratio for incident CHD in men in Q4 versus Q1 CAL categories was 1.36 (95% CI 0.81-2.29), p=0.24. In this group of dentate men, periodontitis was associated with prevalent CHD. However, there was no association with incident CHD.

Adiponectin gene variants and the risk of coronary heart disease: a 16-year longitudinal study

Circulating adiponectin levels have been shown to be associated with a risk of coronary heart disease (CHD). However, its primary role in protecting against the development of CHD remains controversial due to conflicting observations in prospective studies. To gain further insight into the primary role of adiponectin, our major objective was to investigate the relationship between single nucleotide polymorphisms (SNPs) of the adiponectin gene (ADIPOQ) and incident CHD in a population-based cohort with no CHD at baseline. We conducted a 16-year longitudinal study in 2196 subjects from the Hong Kong Cardiovascular Risk Factor Prevalence Study (CRISPS). During 33 862 person-years of follow-up, 184 subjects developed CHD (cumulative incidence rate=5.4 per 1000 person-years). Nine ADIPOQ SNPs with potential functional relevance or shown to be associated with adiponectin levels and/or CHD were genotyped. Among the nine ADIPOQ SNPs, +276G>T (rs1501299) was independently associated with incident CHD in men but not in women, even after adjustments for traditional cardiovascular risk factors (Padjusted=5.5×10(-3) to 0.023; hazard ratio=1.39-1.54). Furthermore, there was a significant association of the T allele of +276G>T with a lower adiponectin level (P=0.027; β (95% CI)=-0.05 (-0.10, -0.01). This study demonstrated that +276G>T may be an independent predictor of CHD development. Our findings suggest that low adiponectin levels, as may be influenced by +276G>T, confer a higher risk of CHD, in keeping with a role of hypoadiponectinaemia in the development of CHD in the general population.

Adult Height and Risk of Coronary Heart Disease: Tehran Lipid and Glucose Study

BackgroundWe assessed the relationship between height and coronary heart disease (CHD) in an urban population of Tehran.Methods4110 participants of the Tehran Lipid and Glucose Study who were 40 years of age or older (1880 men and 2230 women; mean age, 55.1 and 53.0 years, respectively) and free of CHD at baseline were followed for a mean of 9.1 years. We used Cox proportional hazards regression to evaluate the risk of a first CHD event across height tertiles.ResultsFirst CHD events occurred in 239 men and 172 women. The estimated crude HR (95% CI) for CHD events associated with an increment of 1 SD in height was 0.96 (0.28–3.33) in men and 0.84 (0.72–0.97) in women. After adjustment for age, the associations were no longer present. Further adjustment for other confounders had little impact on the results: the HR (95% CI) associated with an increase of 1 SD in height was 1.02 (0.87–1.20) in men and 0.82 (0.66–1.02) in women.ConclusionsAfter adjustment for age, height was not associated with CHD incidence in men or women.

Plasma fibroblast growth factor 23, parathyroid hormone, phosphorus, and risk of coronary heart disease

Fibroblast growth factor 23 (FGF23), parathyroid hormone (PTH), and phosphorus all have been proposed as plasma biomarkers for the development of coronary heart disease (CHD) in individuals with normal renal function. In a nested case-control study of men in the Health Professionals Follow-up Study, free of diagnosed cardiovascular disease at blood draw, we prospectively examined associations between plasma FGF23, PTH, and phosphorus and risk of CHD. During 10 years of follow-up, 422 men developed nonfatal myocardial infarction or fatal CHD. Controls were selected in a 2:1 ratio and matched for age, date of blood collection, and smoking status. Mean estimated glomerular filtration rate was 86 mL/min per 1.73 m(2) in cases and controls. At baseline, there were no statistically significant differences between cases and controls in plasma levels of FGF23, PTH, or phosphorus. After adjusting for matching factors, family history of myocardial infarction, body mass index, alcohol consumption, physical activity, history of diabetes mellitus and hypertension, ethnicity, region, plasma 25-hydroxyvitamin D, and other factors, the odds ratios for incident CHD for participants in the highest, compared with lowest, quartiles were 1.03 (95% CI 0.70-1.52, P for trend 0.84) for FGF23, 1.20 (95% CI 0.82-1.76, P trend 0.99) for PTH, and 0.72 (95% CI 0.51-1.02, P trend 0.13) for phosphorus. Plasma FGF23, PTH, and phosphorus are not associated with the development of incident CHD in men without chronic kidney disease.

Thoracic aortic calcification and coronary heart disease events: The multi-ethnic study of atherosclerosis (MESA)

BackgroundThe presence and extent of coronary artery calcium (CAC) is an independent predictor of coronary heart disease (CHD) morbidity and mortality. Few studies have evaluated interactions or independent incremental risk for coronary and thoracic aortic calcification (TAC). The independent predictive value of TAC for CHD events is not well-established. MethodsThis study used risk factor and computed tomography scan data from 6807 participants in the multi-ethnic study of atherosclerosis (MESA). Using the same images for each participant, TAC and CAC were each computed using the Agatston method. The study subjects were free of incident CHD at entry into the study. ResultsThe mean age of the study population (n=6807) was 62±10 years (47% males). At baseline, the prevalence of TAC and CAC was 28% (1904/6809) and 50% (3393/6809), respectively. Over 4.5±0.9 years, a total of 232 participants (3.41%) had CHD events, of which 132 (1.94%) had a hard event (myocardial infarction, resuscitated cardiac arrest, or CHD death). There was a significant interaction between gender and TAC for CHD events (p<0.05). Specifically, in women, the risk of all CHD event was nearly 3-fold greater among those with any TAC (hazard ratio: 3.04, 95% CI: 1.60–5.76). After further adjustment for increasing CAC score, this risk was attenuated but remained robust (HR: 2.15, 95% CI: 1.10–4.17). Conversely, there was no significant association between TAC and incident CHD in men. In women, the likelihood ratio chi square statistics indicate that the addition of TAC contributed significantly to predicting incident CHD event above that provided by traditional risk factors alone (chi square=12.44, p=0.0004) as well as risk factors+CAC scores (chi square=5.33, p=0.02). On the other hand, addition of TAC only contributed in the prediction of hard CHD events to traditional risk factors (chi-square=4.33, p=0.04) in women, without contributing to the model containing both risk factors and CAC scores (chi square=1.55, p=0.21). ConclusionOur study indicates that TAC is a significant predictor of future coronary events only in women, independent of CAC. On studies obtained for either cardiac or lung applications, determination of TAC may provide modest supplementary prognostic information in women with no extra cost or radiation.

Gender differences in the association between education and the incidence of cardiovascular events in Northern Italy

The educational differences in the incidence of major cardiovascular events are under-studied in Southern Europe and among women. The study sample includes n = 5084 participants to 4 population-based Northern Italian cohorts, aged 35-74 at baseline and with no previous cardiovascular events. The follow-up to ascertain the first onset of coronary heart disease (CHD) or ischaemic stroke ended in 2002. At baseline, major cardiovascular risk factors were investigated adopting the standardized MONICA procedures. Two educational classes were obtained from years of schooling. Age- and risk factors-adjusted hazard ratios of first CHD or ischaemic stroke were estimated through sex-specific separate Cox models (high education as reference). Median follow-up time was 12 years. Event rates were 6.38 (CHD) and 2.12 (ischaemic stroke) per 1000 person-years in men; and 1.59 and 0.94 in women. In men, low education was associated with higher mean Body Mass Index and prevalence of diabetes and cigarette smokers; but also with higher HDL cholesterol and a more favourable alcohol intake pattern. Less-educated women had higher mean systolic blood pressure, Body Mass Index and HDL cholesterol and were more likely to have diabetes. Men and women in the low educational class had a 2-fold increase in ischaemic stroke and CHD incidence, respectively, after controlling for major risk factors. Education was not associated with CHD incidence in men. Higher ischaemic stroke rates were observed among more educated women. In this northern Italian population, the association between education and cardiovascular risk seems to vary by gender.

Anger expression and risk of coronary heart disease: Evidence from the Nova Scotia Health Survey

Whereas some studies have found that anger increases the risk of incident coronary heart disease (CHD), others found anger to be protective. Prior studies did not account for different types of anger expression, which may be associated with opposing levels of cardiovascular risk. This study examines whether distinct types of anger expression differentially predict incident CHD. We conducted a population-based, observational prospective study of 785 randomly selected Canadian men and women (50% each) aged 46 to 92 years and free of CHD in 1995. Using videotaped interviews, trained coders rated 3 types of anger expression: constructive anger (discussing anger to resolve the situation), destructive anger justification (blaming others for one's anger), and destructive anger rumination (brooding over an anger-inducing incident). The association between anger expression type per SD and incident CHD was estimated using Cox proportional hazards models adjusted for sex, age, cardiovascular risk factors, depressive symptoms, hostility, and anxiety. Interactions of anger expression type and gender were also tested. There were 115 incident CHD events (14.6%) during 6,584 person-years of follow-up. The association between clinically assessed constructive anger expression and CHD varied by gender (P for interaction = .02); higher levels were associated with a lower risk of incident CHD in men only (hazard ratio 0.58, 95% CI 0.43-0.80, P < .001), whereas higher levels of destructive anger justification was associated with a 31% increased risk of CHD in both sexes (hazard ratio 1.31, 95% CI 1.03-1.67, P = .03) and predicted CHD incidence independent of covariates and depressive symptoms, hostility, and anxiety. Decreased constructive anger in men and increased destructive anger justification in men and women are associated with increased risk of 10-year incident CHD.

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.

Comparison of the Prognostic Significance of the Electrocardiographic QRS/T Angles in Predicting Incident Coronary Heart Disease and Total Mortality (from the Atherosclerosis Risk In Communities Study)

Spatial QRS/T angle and spatial T-wave axis were shown to be strong independent predictors of incident coronary heart disease (CHD) and total mortality, but they are not routinely available. We evaluated whether frontal plane QRS/T angle, easily obtained as the difference between frontal plane axes of QRS and T, provides a suitable substitute for spatial QRS/T angle as a risk predictor. Our study consisted of 13,973 participants from the ARIC Study. Outcome variables were incident CHD and total mortality during a median follow-up of 14 years. Electrocardiographic variables were categorized as abnormal (>/=95th percentile), borderline (>/=75th and <95th percentile), and normal (<75th percentile) separately for men and women. Cox regression was used to assess the effect of electrocardiographic variables on risk of each outcome. The normal category was considered the reference cell. With adjustment for demographic and clinical characteristics, both QRS/T angles were approximately equally strong predictors of total mortality with >50% increased risk. Spatial QRS/T angle was a stronger predictor of incident CHD in women, with a 114% increased risk, but it was not significantly associated with risk of incident CHD in men. Similarly, frontal plane QRS/T angle was statistically significant for only women with a 74% increased risk of incident CHD. In conclusion, frontal plane QRS/T angle as an easily derived risk measure is a suitable clinical substitute for spatial QRS/T angle for risk prediction.

Explaining gender differences in coronary heart disease: hunting for clues with the ophthalmoscope.

JAMA Retinal Arteriolar Narrowing and Risk of Coronary Heart Disease in Men and Women: The Atherosclerosis Risk in Communities Study Tien Yin Wong, MD, MPH; Ronald Klein, MD, MPH; A. Richey Sharrett, MD, Dr PH; Bruce B. Duncan, MD, PhD; David J. Couper, PhD; James M. Tielsch, PhD; Barbara E. K. Klein, MD, MPH; Larry D. Hubbard, MAT Context Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited. Objective To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men. Design, Setting, and Participants The Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. Main Outcome Measure Risk of CHD associated with retinal arteriolar narrowing. Results During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocardial infarction (RR, 1.08; 95% CI, 0.85-1.38). Conclusion Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings. Corresponding Author and Reprints: Tien Yin Wong, MD, MPH, Department of Ophthalmology, National University of Singapore, 10 Kent Ridge Crescent, Singapore 119260 (e-mail:ophwty@nus.edu.sq).

Retinal arteriolar narrowing and risk of coronary heart disease in men and women: The Atherosclerosis Risk in Communities Study. Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BEK, Hubbard LD. JAMA 2002;287:1153–1159.

Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited. The authors examined the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men. The Atherosclerosis Risk in Communities Study is an ongoing prospective, population-based cohort study in four US communities initiated in 1987 to 1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993–1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous six years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each standard deviation decrease in the AVR was associated with an increased risk of any incident CHD and of acute myocardial infarction. In contrast, AVR was unrelated to any incident CHD in men or to acute myocardial infarction. The authors conclude that retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men.—Thomas J. Liesegang

Retinal arteriolar narrowing and risk of coronary artery disease in men and women. The Atherosclerosis Risk in Communities Study.Wong TY, Klein R, Sharrett AR, Duncan BB, Couper DJ, Tielsch JM, Klein BEK, Hubbard LD. JAMA 2002;287:1153–1159.

The relative contribution of microvascular and macrovascular processes to the risk of coronary heart disease (CHD) is unknown, but evidence suggests that both contribute to some degree. Microvascular processes have been hypothesized to play a greater role in the development of CHD in women than in men, although prospective clinical data are limited. Since retinal arteriolar narrowing is a marker of microvascular damage, typically from hypertension, it was suggested that there might be an association between retinal arteriolar narrowing and CHD. As part of the Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in four US communities initiated in 1987 to 1989, retinal photographs were taken in 9,648 women and men aged 51 to 72 years without CHD at the third examination (1993–1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous six years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD and of acute myocardial infarction. In contrast, AVR was unrelated to any incident CHD in men or to acute myocardial infarction. The authors conclude that retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. However, future studies are needed to confirm these findings.—Nancy J. Newman

Retinal arteriolar narrowing and risk of coronary heart disease in men and women. The Atherosclerosis Risk in Communities Study.

Microvascular processes have been hypothesized to play a greater role in the development of coronary heart disease (CHD) in women than in men; however, prospective clinical data are limited. To examine the association between retinal arteriolar narrowing, a marker of microvascular damage from hypertension and inflammation, and incident CHD in healthy middle-aged women and men. The Atherosclerosis Risk in Communities Study, an ongoing prospective, population-based cohort study in 4 US communities initiated in 1987-1989. Retinal photographs were taken in 9648 women and men aged 51 to 72 years without CHD at the third examination (1993-1995). To quantify retinal arteriolar narrowing, the photographs were digitized, individual arteriolar and venular diameters were measured, and a summary arteriole-to-venule ratio (AVR) was calculated. Risk of CHD associated with retinal arteriolar narrowing. During an average 3.5 years of follow-up, 84 women and 187 men experienced incident CHD events. In women, after controlling for mean arterial blood pressure averaged over the previous 6 years, diabetes, cigarette smoking, plasma lipid levels, and other risk factors, each SD decrease in the AVR was associated with an increased risk of any incident CHD (relative risk [RR], 1.37; 95% confidence interval [CI], 1.08-1.72) and of acute myocardial infarction (RR, 1.50; 95% CI, 1.10-2.04). In contrast, AVR was unrelated to any incident CHD in men (RR, 1.00; 95% CI, 0.84-1.18) or to acute myocardial infarction (RR, 1.08; 95% CI, 0.85-1.38). Retinal arteriolar narrowing is related to risk of CHD in women but not in men, supporting a more prominent microvascular role in the development of CHD in women than in men. Future work is needed to confirm these findings.

Lipids and lipoproteins as risk factors for coronary heart disease in men with abnormal glucose tolerance: the Honolulu Heart Program

To evaluate lipids and lipoproteins as risk factors for coronary heart disease (CHD) in older men with non-insulin-dependent diabetes (NIDDM) or abnormal glucose tolerance compared with normoglycaemic men. A prospective, population-based cohort study based on the lipoprotein examination (1970-72) of the Honolulu Heart Program. Follow-up was through to December 1988. Honolulu, Hawaii. Japanese-American men, ages 51-72 at baseline: 2042 with 1 h glucose < 12.5 mmol l-1 (normal group); 376 on oral hypoglycaemic agents or with 1 h glucose > or = 12.5 mmol l-1 after 50 g oral glucose challenge (abnormal glucose tolerance group). None had prevalent coronary heart disease (CHD) or stroke at baseline. Incident CHD: definite non-fatal myocardial infarction (MI) or fatal CHD. There were 221 incident cases in the normal group, and 65 in the abnormal glucose tolerance group. Total and high-density lipoprotein (HDL) cholesterol were significant predictors of incident CHD in men with NIDDM or abnormal glucose tolerance after controlling for age, body-mass index, systolic blood pressure, pack-years of cigarettes and alcohol consumption (P < 0.05). Total, low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol were significant predictors in normal men, and HDL cholesterol was of borderline significance. Abnormal lipids and lipoproteins are significant, independent predictors of CHD in subjects with NIDDM or abnormal glucose tolerance. Attention to lipid and lipoproteins as CHD risk factors should be part of clinical management of these patients.

Lipid research clinics coronary primary prevention trial: Results and implications

The Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT) tested the efficacy of lowering cholesterol levels in reducing the risk of coronary heart disease (CHD) in 3,806 asymptomatic, middle-aged men with primary hypercholesterolemia. The group treated with cholestyramine ∗ ∗ Questran® Mead Johnson & Company, Evansville, Indiana. had 8.5% and 12.6% greater reductions in total and low-density lipoprotein levels, respectively, than those achieved in the placebo group. The cholestyramine group had a 19% reduction in risk (p <0.05) of the primary endpoint of definite CHD, death or definite nonfatal myocardial infarction. Corresponding and significant reductions were also seen for angina, development of a positive exercise test, and coronary bypass surgery. All-cause mortality was only slightly, and not significantly, reduced in the cholestyramine group, reflecting more violent and accidental deaths in the cholestyramine subjects. When the cholestyramine group was analyzed separately, a 19% reduction in CHD risk was also associated with each decrement of 8% in the total cholesterol level. Moreover, CHD incidence in men in whom a decrease of 25% in total cholesterol was sustained, a typical response to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at the pretreatment level. The LRC-CPPT findings show that reducing the total cholesterol level by lowering the LDL cholesterol level can diminish the incidence of CHD morbidity and mortality in men at high risk for CHD because of increased LDL cholesterol levels. These results have considerable importance for the prevention of CHD through cholesterol lowering, at both the clinical and public health levels.

Elevated daytime urinary excretion of testosterone glucuronide in men with the type A behavior pattern.

Urinary excretion of testosterone glucuronide was compared in 13 men with typical Type A behavior pattern (as determined by structured interviews) and 10 age-matched men with typical Type B behavior pattern. Twenty-four hour urine collections were divided into three periods: 9AM - 6PM , 6PM to bedtime, and bedtime to 9AM . Type A men showed a significantly higher excretion than Type B men in the daytime ( 9AM - 6PM ); the geometric mean value was 24 micrograms in Type A and 15 micrograms in Type B (P less than 0.05). There were no significant differences between Type A and Type B men for the other two time periods. Indicating an elevated daytime testosterone secretion in Type A men, this finding is consistent with a recent report that exposure to laboratory tests of reaction time causes an increase in plasma testosterone levels in Type A but not Type B men. Since a role for testosterone in the genesis of coronary heart disease (CHD) is suggested by the much higher incidence of CHD in men and the acceleration of murine atherogenesis by testosterone, the findings of this and the previous report may represent a mechanism for the elevated incidence of CHD in Type A men.

The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering

In the Lipid Research Clinics Coronary Primary Prevention Trial (LRC-CPPT), a 19% lower incidence of coronary heart disease (CHD) in cholestyramine-treated men was accompanied by mean falls of 8% and 12% in plasma total (TOTAL-C) and low-density lipoprotein (LDL-C) cholesterol levels relative to levels in placebo-treated men. When the cholestyramine treatment group was analyzed separately, a 19% reduction in CHD risk was also associated with each decrement of 8% in TOTAL-C or 11% in LDL-C levels (P less than .001). Moreover, CHD incidence in men sustaining a fall of 25% in TOTAL-C or 35% in LDL-C levels, typical responses to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at pretreatment levels. Adherence to medication was associated with reduced incidence of CHD only when accompanied by falls in TOTAL-C and LDL-C levels. Small increases in high-density lipoprotein cholesterol levels, which accompanied cholestyramine treatment, independently accounted for a 2% reduction in CHD risk. Thus, the reduction of CHD incidence in the cholestyramine group seems to have been mediated chiefly by reduction of TOTAL-C and LDL-C levels.

Reduced Fibrinolytic Capacity Associated with Low Ratio of Serum Testosterone to Oestradiol in Healthy Coronary High‐risk Men

In a study of 42 healthy, middle‐aged men with high risk of coronary heart disease (CHD), we found a highly significant correlation between low ratio of serum testosterone to oestradiol and delayed clot lysis after venous stasis as measured with the euglobulin clot lysis time (ECLT). The upper normal limit of ECLT was set at 60 min. Half of the examined specimen, i.e. from 21 individuals, lysed as normal; 4 specimen lysed between 60 and 90 min, whereas the remaining 17 specimen did not lyse within 2 hours. Sixteen of these 17 individuals with the most defective fibrinolytic capacity belonged to the group of individuals with the lowest ratio of serum testosterone to oestradiol. The association was highly significant (p &lt; 0.001). In comparison, the correlation between serum triglyceride concentration and the ratio of serum testosterone to oestradiol was significant at the 2% level, whereas serum cholesterol and this ratio were not associated. The significance of the findings remains obscure, but may be important for the incidence of CHD in men.