Cardiovascular Death In Men Research Articles

Nonfasting triglycerides and risk of cardiovascular death in men and women from the Norwegian Counties Study

The association between nonfasting triglycerides and cardiovascular disease (CVD) has recently been actualized. The aim of the present study was to investigate nonfasting triglycerides as a predictor of CVD mortality in men and women. A total of 86,261 participants in the Norwegian Counties Study 1974–2007, initially aged 20–50 years and free of CVD were included. We estimated hazard ratios (HRs) for deaths from CVD, ischemic heart disease (IHD), stroke and all causes by level of nonfasting triglycerides. Mean follow-up was 27.0 years. A total of 9,528 men died (3,620 from CVD, 2,408 IHD, 543 stroke), and totally 5,267 women died (1,296 CVD, 626 IHD, 360 stroke). After adjustment for CVD risk factors other than HDL-cholesterol, the HRs (95% CI) per 1 mmol/l increase in nonfasting triglycerides were 1.16 (1.13–1.20), 1.20 (1.14–1.27), 1.26 (1.19–1.34) and 1.09 (0.96–1.23) for all cause mortality, CVD, IHD, and stroke mortality in women. Corresponding figures in men were 1.03 (1.01–1.04), 1.03 (1.00–1.05), 1.03 (1.00–1.06) and 0.99 (0.92–1.07). In a subsample where HDL-cholesterol was measured (n = 40,144), the association between CVD mortality and triglycerides observed in women disappeared after adjustment for HDL-cholesterol. In a model including the Framingham CHD risk score the effect of triglycerides disappeared in both men and women. In conclusion, nonfasting triglycerides were associated with increased risk of CVD death for both women and men. Adjustment for major cardiovascular risk factors, however, attenuated the effect. Nonfasting triglycerides added no predictive information on CVD mortality beyond the Framingham CHD risk score in men and women.

Neo-Adjuvant Androgen Deprivation Therapy Does Not Increase the Risk of Cardiovascular Death in Men Treated for Prostate Cancer with Curative Intent

Neo-Adjuvant Androgen Deprivation Therapy Does Not Increase the Risk of Cardiovascular Death in Men Treated for Prostate Cancer with Curative Intent

Effect of Conventional Risk Factors for Excess Cardiovascular Death in Men

The present study examined how sex differences in conventional risk factors for cardiovascular disease (CVD), especially smoking, account for excess male mortality from CVD in Japan. In a 14-year follow-up study, causes of death were ascertained among 10,546 Japanese aged 30 years or older at the baseline. The proportion of the excess male risk of CVD explained by the differences in risk factors was estimated as (HR0-HR1)/(HR0-1), where HR0 is the age-adjusted hazard ratio (men vs women) and HR1 is the age and risk factor-adjusted hazard ratio. The age-adjusted male:female ratios were 1.60 (95% confidence interval (CI), 1.32-1.94) for CVD, 1.75 (95% CI, 1.33-2.30) for stroke, and 1.55 (95% CI, 0.97-2.49) for coronary heart disease. The proportion of excess male risk of CVD explained by smoking was 46% and excess risk explained by all risk factors including smoking was 36%. In men, drinking habits decreased the excess risk of CVD. Except for the association between drinking habits and CVD, the impact of the hazard ratios of conventional risk factors had no sex difference. Smoking contributes substantially to excess male mortality from CVD when the smoking rates vary substantially by sex.

Effect of Age on Blood Pressure Parameters and Risk of Cardiovascular Death in Men

Elevated blood pressure (BP) is a risk factor for cardiovascular disease (CVD), but it remains unclear which component-alone or in combination-is the best predictor. We sought to determine which BP parameters are important predictors of CVD death across a wide age range. We used a prospective cohort study design with 53,163 men followed for cause-specific death during a median of 5.7 years in the Physicians' Health Study enrollment cohort. Baseline age, systolic BP and diastolic BP were collected. We calculated relative risks (RRs) and their 95% confidence intervals using Cox proportional hazard models adjusting for major risk factors for CVD, and then stratified by age (39 to 49, 50 to 59, 60 to 69, and 70 to 84 years). There were 459 CVD deaths during follow-up. For each 10 mm Hg increase in systolic BP, the multivariable RRs by ascending age group were 1.46, 1.43, 1.24, and 1.13. The multivariable RRs for each 10 mm Hg increase in diastolic BP were 1.25, 1.20, 1.28, and 1.07. Compared with systolic BP, pulse pressure and mean arterial pressure were not consistent predictors across age ranges, and combining systolic BP with another parameter did not improve the model compared with using systolic BP alone in any age group (all P > .05). In this large cohort of healthy men with no history of hypertension, systolic BP was the most consistent and significant predictor of CVD death across all ages. Diastolic BP was not as strongly associated with risk. Our results support the continuing emphasis on using systolic BP in predicting cardiovascular risk.

JNC 7 Category and Risk of Cardiovascular Death in Men: Are There Differences by Age?

The authors evaluated the seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) blood pressure classification scheme on the risk of cardiovascular disease death and whether the association varies by age. In a prospective cohort study, 53,163 apparently healthy participants aged 39-85 years were followed for 5.7 years. The authors calculated relative risks and 95% confidence intervals for cardiovascular disease death, adjusting for major risk factors, then stratified by age (39-49, 50-59, 60-69, and 70-84 years) and performed a test of heterogeneity. Compared with men with normal blood pressure, those with prehypertension had a multivariate-adjusted relative risk of 1.02 (95% confidence interval, 0.73-1.42) and those with hypertension had a relative risk of 1.54 (95% confidence interval, 1.08-2.19). There was no strong age-related effect (P(interaction), 0.22). In this large cohort, the JNC 7 categorization of prehypertension was not associated with a significantly increased risk of cardiovascular disease death, and there was no significant effect modification by age.

Epidemiology of Heart Failure

Of all persons aged over 40 years, approximately 1% have heart failure. The prevalence of heart failure doubles with each decade of life, and is around 10% in persons over 70 years of age. In Spain, heart failure causes nearly 80,000 hospital admissions every year. As in other developed countries, heart failure is the most frequent cause of hospitalization among persons 65 years of age and over, and is responsible for 5% of all hospitalizations. The incidence of heart failure increases with age, and reaches 1% per year in those over 65. Heart failure is a progressive, lethal disorder, even with adequate treatment. Five-year survival is around 50%, which is no better than that for many cancers. In Spain, heart failure is the third leading cause of cardiovascular mortality, after coronary disease and stroke. In 2000, heart failure caused 4% of all deaths and 10% of cardiovascular deaths in men; the corresponding figures for women were 8% and 18%. In recent decades the prevalence and number of hospitalizations due to heart failure have increased steadily in developed countries. Heart failure will probably continue to increase in coming years: although its incidence has not materially decreased, survival is increasing due to better treatment. The control of risk factors for hypertension and ischemic heart disease, the main causes of heart failure in Spain, is the only method to halt the foreseeable increase in heart failure in the near future.

Determinants of adult mortality in Russia: estimates from sibling data.

It would be useful to have a quick and cost-effective method to study individual-level determinants of mortality in countries where reliable data are not available. We have modified indirect demographic methods and applied them to a population sample to investigate predictors of mortality in Russia. A national sample of the Russian population was interviewed in a cross-sectional survey. The participants were asked about characteristics of their eldest siblings, including their vital status, year of birth, and year of death (if deceased). The association between personal characteristics and mortality risk was estimated for 682 male and 698 female siblings (of whom 122 and 81, respectively, had died). In both sexes, mortality was strongly associated with smoking and low education. After adjustment for smoking and education, mortality was elevated in men and women who drank alcohol at least once a month. Mortality was also higher among in men who had been binge drinking (more than half a bottle of vodka per drinking session) at least once a week (adjusted risk ratio [RR] = 2.5; 95% confidence interval [CI] = 1.2-4.9) and in women who were binging at least once a month (RR = 3.9; CI = 1.1-14.5) compared with nonbinging. Similar associations with drinking were seen for cardiovascular deaths in men. Childhood social circumstances were not associated with mortality. The study of siblings appears to be a cost-effective alternative for estimating risk factors for mortality in literate populations. This study identified smoking, low education, and alcohol consumption (especially binge drinking) as risk factors for mortality in Russia.

Androgens and cardiovascular disease.

Globally, cardiovascular disease will continue causing most human deaths for the foreseeable future. The consistent gender gap in life span of approximately 5.6 yr in all advanced economies must derive from gender differences in age-specific cardiovascular death rates, which rise steeply in parallel for both genders but 5-10 yr earlier in men. The lack of inflection point at modal age of menopause, contrasting with unequivocally estrogen-dependent biological markers like breast cancer or bone density, makes estrogen protection of premenopausal women an unlikely explanation. Limited human data suggest that testosterone exposure does not shorten life span in either gender, and oral estrogen treatment increases risk of cardiovascular death in men as it does in women. Alternatively, androgen exposure in early life (perinatal androgen imprinting) may predispose males to earlier onset of atherosclerosis. Following the recent reevaluation of the estrogen-protection orthodoxy, empirical research has flourished into the role of androgens in the progression of cardiovascular disease, highlighting the need to better understand androgen receptor (AR) coregulators, nongenomic androgen effects, tissue-specific metabolic activation of androgens, and androgen sensitivity. Novel therapeutic targets may arise from understanding how androgens enhance early plaque formation and cause vasodilatation via nongenomic androgen effects on vascular smooth muscle, and how tissue-specific variations in androgen effects are modulated by AR coregulators as well as metabolic activation of testosterone to amplify (via 5alpha-reductase to form dihydrotestosterone acting on AR) or diversify (via aromatization to estradiol acting upon estrogen receptor alpha/beta) the biological effects of testosterone on the vasculature. Observational studies show that blood testosterone concentrations are consistently lower among men with cardiovascular disease, suggesting a possible preventive role for testosterone therapy, which requires critical evaluation by further prospective studies. Short-term interventional studies show that testosterone produces a modest but consistent improvement in cardiac ischemia over placebo, comparable to the effects of existing antianginal drugs. By contrast, testosterone therapy has no beneficial effects in peripheral arterial disease but has not been evaluated in cerebrovascular disease. Erectile dysfunction is most frequently caused by pelvic arterial insufficiency due to atherosclerosis, and its sentinel relationship to generalized atherosclerosis is insufficiently appreciated. The commonality of risk factor patterns and mechanisms (including endothelial dysfunction) suggests that the efficacy of antiatherogenic therapy is an important challenge with the potential to enhance men's motivation for prevention and treatment of cardiovascular diseases.

Principal component analysis of the T wave and prediction of cardiovascular mortality in American Indians: the Strong Heart Study.

Increased QT interval dispersion (QTd) is a proposed ECG marker of vulnerability to ventricular arrhythmias and of cardiovascular (CV) mortality. However, principal component analysis (PCA) of the T-wave vector loop may more accurately represent repolarization abnormalities than QTd. Predictive values of QTd and PCA were assessed in 1839 American Indian participants in the first Strong Heart Study examination. T-wave loop morphology was quantified by the ratio of the second to first eigenvalues of the T-wave vector by PCA (PCA ratio); QTd was quantified as the difference between maximum and minimum QT intervals. After 3.7+/-0.9 years mean follow-up, there were 55 CV deaths. In univariate analyses, an increased PCA ratio predicted CV mortality in women (chi2=7.8, P=0.0053) and men (chi2=9.5, P=0.0021). In contrast, increased QTd was a significant predictor of CV mortality in women (chi2=30.6, P<0.0001) but not in men (chi2=2.0, P=NS). In multivariate Cox analyses controlling for risk factors and rate-corrected QT interval, the PCA ratio remained a significant predictor of CV mortality in women (chi2=4.0 P=0.043) and men (chi2=6.4, P=0.011); QTd was a significant predictor in women only (chi2=11.0, P=0.0009). PCA ratios >90th percentile (32% in women and 24.6% in men) identified women with a 3.68-fold increased risk of CV mortality (95% CI, 1.54 to 8.83) and men with a 2.77-fold increased risk (95% CI, 1.18 to 6.49). Abnormalities of repolarization measured by PCA of the T-wave loop predict CV death in men and women, supporting use of PCA for quantifying repolarization abnormalities.

Moderate alcohol intake is associated with survival in the elderly: the Dubbo Study

To examine the relationship between alcohol intake and survival in elderly people. A prospective study over 116 months of non-institutionalised subjects living in Dubbo, a rural town (population, 34,000) in New South Wales. 1235 men and 1570 women aged 60 years and over who were first examined in 1988-89. All-causes mortality; gross cost of alcohol per life-year gained. Death occurred in 450 men and 392 women. Intake of alcohol was generally moderate (i.e., less than 14 drinks/week). Any intake of alcohol was associated with reduced mortality in men up to 75 years and in women over 64 years. In a proportional hazards model, the hazard ratio for mortality in men taking any alcohol was 0.63 (95% CI, 0.47-0.84) and in women was 0.75 (95% CI, 0.60-0.94). Cardiovascular deaths in men were reduced from 20/100 (95% CI, 14-26) to 11/100 (95% CI, 9-13) and in women from 16/100 (95% CI, 13-19) to 8/100 (95% CI, 6-10). The reduction in mortality occurred in men and women taking only 1-7 drinks/week--hazard ratios, 0.68 (95% CI, 0.49-0.94) and 0.78 (95% CI, 0.61-0.99), respectively, with a similar protective effect from intake of beer or other forms of alcohol. After almost 10 years' follow-up, men taking any alcohol lived on average 7.6 months longer, and women on average 2.7 months longer, compared with non-drinkers. The gross cost for alcohol per life-year gained if consuming 1-7 drinks/week was $5700 in men, and $19,000 in women. Moderate alcohol intake in the elderly appears to be associated with significantly longer survival in men 60-74 years and in all elderly women.

High heart rate: a risk factor for cardiovascular death in elderly men.

To examine the association between heart rate and 12-year incidence rates of total and cardiovascular death in a cohort of elderly subjects stratified by sex. The study was carried out in 763 white men and 1175 women aged 65 years or older who were participating in the Cardiovascular Study in the Elderly. Subjects were divided into quintiles of heart rate; the top quintile comprised those with a heart rate of greater than 80/min and the bottom quintile, those with a heart rate of less than 64/min. In the men, the number of deaths from cardiovascular causes was significantly increased in those in the top quintile of heart rate (crude relative risk, 1.55) but decreased in those in the bottom quintile (crude relative risk, 0.65). Similar relationships were found in the women, but the associations did not reach statistical significance (all-cause, P = .11; cardiovascular, P = .15). After adjustment for baseline age, body mass index, hypertension, diabetes mellitus, angina or previous myocardial infarction (coronary heart disease), regular medication, lipid levels, smoking, alcohol intake, forced expiratory volume in 1 second, and other confounders, the relative risk for cardiovascular death in the men was 1.38 (95% confidence interval, 0.94-2.03) for the subjects in the top quintile of heart rate and 0.82 (95% confidence interval, 0.52-1.28) for those in the bottom quintile. In the Cox analysis, predictors of time to cardiovascular death were heart rate (P < .001), age (P < .001), coronary heart disease (P < .001), clinical heart failure (P = .001), diabetes mellitus (P = .001), hypertension (P = .02), and triglyceride levels (P = .04), whereas total (P = .20) and high-density lipoprotein-cholesterol (P = .21) levels and smoking (P = .74) were found to be nonsignificant by the model. The heart rate-cardiovascular death association held true when subjects who died in 2 years after enrollment were excluded (P = .008). An elevated heart rate may be a strong predictor of cardiovascular death in elderly men. Conversely, a low heart rate is related to a better outcome in these subjects.

QT interval as a cardiac risk factor in a middle aged population.

OBJECTIVE: To evaluate the value of QT interval as a cardiac risk factor in middle aged people. METHODS: The association between QT interval and cardiac risk factors and mortality in...

Frequent hangovers and cardiovascular mortality in middle-aged men.

We studied the relation between frequent hangovers and cardiovascular mortality in a representative population sample of middle-aged Finnish men who participated in the Kuopio Ischemic Heart Disease Risk Factor Study. Complete data on alcohol consumption, hangover frequency, prior cardiovascular diseases, and risk factors were obtained for 2,160 non-abstinent men. Frequent hangovers were rare in the three lowest alcohol consumption quartiles, but in the highest quartile, a total of 239 men (43.6%) reported having a hangover at least monthly. During an average follow-up time of 6.7 years, these men had a 2.36-fold (95% confidence interval = 1.02-5.48) risk of cardiovascular death compared with men with fewer hangovers, with adjustment for age and total alcohol consumption. The association was somewhat attenuated after adjustments for smoking, income, and prior cardiovascular diseases. Systolic blood pressure, body mass index, resting heart rate, or serum lipids had no appreciable role in the relation, but plasma fibrinogen concentration appeared as one possible pathway to increased risk of cardiovascular death in men who frequently experience hangovers. The findings underline the importance of preventive actions regarding not only the amount but also the way people consume alcohol.

Early growth and death from cardiovascular disease in women.

To determine whether the link suggested between growth in utero and during infancy and death from cardiovascular disease in men is also present in women. Follow up study of women and men whose birth weight and weight at 1 year of age had been recorded. Hertfordshire, England. 5585 women and 10,141 men born during 1911-30. Standardised mortality ratios for cardiovascular disease. Among women and men death rates from cardiovascular disease fell progressively between the low and high birth weights groups (chi 2 = 4.3, p = 0.04 for women, chi 2 = 8.5, p < 0.005 for men). Cardiovascular deaths in men but not women were also strongly related to weight at 1 year, falling progressively between the low and high weight groups (chi 2 = 27.5, p < 0.0001). The highest cardiovascular death rates in women were among those with below average birth weight but above average weight at 1 year. In men the highest rates were among those with below average birth weight and below average weight at 1 year. Relations between cardiovascular disease and birth weight are similar in men and women. In men cardiovascular disease is also related to weight gain in infancy.

Prediction of cardiovascular death in men undergoing noninvasive evaluation for coronary artery disease.

To develop prediction rules from clinical and exercise test data identifying patients at high and low risk for cardiovascular events among a group of male veterans. Prognostic study with prospective gathering of data and routine follow-up of consecutive patients referred for exercise testing. Patients only underwent noninvasive evaluation for coronary artery disease. No validation cohort is yet available. A 1200-bed Veterans Affairs Medical Center. Of 3609 men referred for exercise testing between 1984 and 1990, 2546 patients remained evaluable after exclusion of those who underwent subsequent cardiac catheterization, those with significant valvular heart disease, and those who had previous coronary artery bypass surgery. Evaluation included recording of clinical data on a standardized form and a standard treadmill test followed by assessment of cardiovascular events. During a mean follow-up period (+/- SD) of 2.75 (+/- 18) years, 119 cardiovascular deaths and 44 nonfatal myocardial infarctions occurred in 2546 patients. The Cox proportional hazards model showed the following characteristics to be statistically independent predictors of time until cardiovascular death: history of congestive heart failure or digoxin use, exercise-induced ST depression, change in systolic blood pressure during exercise, and exercise capacity. Using a simple score based on one item of clinical information (history of congestive heart failure or digoxin use) and three exercise test responses (ST depression, exercise capacity, and change in systolic blood pressure), 77% of patients were categorized as low risk (annual cardiac mortality rate, less than 2%), 18% as moderate risk (annual cardiac mortality rate, 7%), and 6% as high risk (annual cardiac mortality rate, 15%; hazard ratio, 10; 95% confidence interval, 6 to 17). This model has not yet been validated. Variables available from the usual non-invasive work-up of patients with known or suspected coronary artery disease can be used to predict future risk for cardiovascular death.

Epidemiology of heart failure

Analysis of 34 years of follow-up of Framingham Study data provides clinically relevant insights into the prevalence, incidence, secular trends, prognosis, and modifiable risk factors for the occurrence of heart failure in a general population sample. Heart failure was found to be highly prevalent, affecting about 1% of persons in their 50s and rising progressively with age to afflict 10% of persons in their 80s. The annual incidence also increased with age, from about 0.2% in persons 45 to 54 years, to 4.0% in men 85 to 94 years, with the incidence approximately doubling with each decade of age. Women lagged slightly behind men in incidence at all ages. Male predominance was because of a higher rate of coronary heart disease, which confers a fourfold increased risk of heart failure. Heart failure, once manifest, was highly lethal, with 37% of men and 33% of women dying within 2 years of diagnosis. The 6-year mortality rate was 82% for men and 67% for women, which corresponded to a death rate fourfold to eightfold greater than that of the general population of the same age. Sudden death was a common mode of exitus and accounted for 28% of the cardiovascular deaths in men and 14% in women with heart failure. Hypertension and coronary disease were the predominant causes for heart failure and accounted for more than 80% of all clinical events. Factors reflecting deteriorating cardiac function were associated with a substantial increase in risk of overt heart failure. These include low vital capacity, sinus tachycardia, and ECG evidence of left ventricular hypertrophy. Modifiable predisposing risk factors for heart failure include hypertension, impaired glucose tolerance, an elevated total to high-density lipoprotein cholesterol ratio, obesity, and cigarette smoking. In subjects with coronary disease risk increases progressively from angina to recognized myocardial infarctions to unrecognized infarctions in men. In women angina also carried half the failure risk of a myocardial infarction, and in both sexes unrecognized infarctions were at least as dangerous as symptomatic ones. Using simple office procedures and laboratory tests, it is possible to identify high-risk candidates for heart failure early in its course for preventive management before irreversible myocardial damage has occurred.

Aortic calcified plaques and cardiovascular disease (the Framingham study)

The relation between the presence of calcified plaques in the thoracic aorta, as detected on chest x-rays, and the development of cardiovascular disease is examined during 12 years of follow-up of the Framingham cohort (n = 5,209). The prevalence of aortic calcified plaques approximately doubled with each decade of age, with only a trivial male predominance. Its presence was associated with a twofold increase in risk of cardiovascular death in men and women younger than age 65, even after other risk factors were taken into account. Similar increases in risk were found for coronary artery disease, stroke and intermittent claudication among middle-aged women. In middle-aged men these risks were less marked. The predictive value of aortic calcified plaques generally diminished with age. Risk of sudden coronary death in men with calcified plaques in the thoracic aorta ranged from a sevenfold increase at age 35 to no excess risk at age 70 years. These results support the view that atherosclerosis is a generalized process. The finding of aortic calcified plaques in a relatively young subject on a routine chest x-ray should be regarded as a sign for potential development of clinically manifest atherosclerotic disease in the cardiac, cerebral and peripheral arterial circulation.

Plasma dehydroepiandrosterone and dehydroepiandrosterone sulfate in patients undergoing diagnostic coronary angiography

Serum levels of DHEA sulfate are inversely associated with cardiovascular death in men, and urinary dehydroepiandrosterone (DHEA) levels are inversely associated with clinical manifestations of coronary artery disease. These observations may be related to the antiproliferative effects of DHEA, resulting in inhibition of atherosclerotic intimal hyperplasia. To examine the relation between these steroids and a direct measure of coronary atherosclerosis, plasma DHEA and DHEA sulfate levels were determined in 206 middle-aged patients (103 men, 103 women) undergoing elective coronary angiography. Plasma DHEA sulfate levels were lower in men with at least one stenosis greater than or equal to 50% compared with those without any stenosis greater than or equal to 50% (4.9 +/- 2.7 versus 6.1 +/- 3.5 nmol/ml, p = 0.05). Levels of DHEA sulfate were also inversely related to the number of diseased coronary vessels (r = -0.20, p = 0.05) and a continuous measure of the extent of coronary atherosclerosis (r = -0.25, p = 0.01) in men. The association between DHEA sulfate levels and extent of coronary artery disease was independent of age and other conventional risk factors for coronary disease. In women, there was no association between plasma DHEA or DHEA sulfate levels and coronary disease. These data demonstrate a consistent, independent, inverse, dose-response relation between plasma DHEA sulfate levels and angiographically defined coronary atherosclerosis in men. Plasma DHEA sulfate may be another important and potentially modifiable risk factor for the development and progression of coronary atherosclerosis.

Family history of heart attack: a modifiable risk factor?

A family history of heart attack is reported to be an independent predictor of cardiovascular death in men. In a 9 year follow-up of 4014 adults from 40 to 79 years old in the Rancho Bernardo Study, men under 60 years of age with a family history of heart attack were at fivefold increased risk. In this study, we sought to determine whether modifiable risk factors, i.e., blood pressure, plasma cholesterol, obesity, and cigarette smoking, have a differential effect on cardiovascular risk in those with and without a family history of heart attack. For both sexes, cigarette smoking was a stronger predictor of cardiovascular disease in those with a family history of heart attack (relative risk of smokers vs nonsmokers was 2.5 for men and 4.0 for women) than in those with no such family history (relative risk of smokers vs nonsmokers was 1.1 for men and 1.7 for women). Conversely, an increased risk of cardiovascular mortality in men with a family history of heart attack was present predominantly in smokers (relative risk related to positive family history was 1.2 in nonsmokers, and 3.3 in smokers). An estimated 68% of the excess deaths in men with a family history of heart attack were attributable solely to the interaction of family history with smoking habit and were therefore potentially avoidable. The risk of cardiovascular disease associated with an apparently inherited predisposition appears to be profoundly affected by modifiable behavior.