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Placental abruption and cardiovascular disease (CVD) have common etiological underpinnings, and there is accumulating evidence that abruption may be associated with future CVD. We estimated associations between abruption and coronary heart disease (CHD) and stroke. The meta-analysis was based on the random-effects risk ratio (RR) and 95% confidence interval (CI) as the effect measure. We conducted a bias analysis to account for abruption misclassification, selection bias, and unmeasured confounding. We included 11 cohort studies comprising 6,325,152 pregnancies, 69,759 abruptions, and 49,265 CHD and stroke cases (1967-2016). Risks of combined CVD morbidity-mortality among abruption and nonabruption groups were 16.7 and 9.3 per 1,000 births, respectively (RR = 1.76, 95% CI: 1.24, 2.50; I2 = 94%; τ2 = 0.22). Women who suffered abruption were at 2.65-fold (95% CI: 1.55, 4.54; I2 = 85%; τ2 = 0.36) higher risk of death related to CHD/stroke than nonfatal CHD/stroke complications (RR = 1.32, 95% CI: 0.91, 1.92; I2 = 93%; τ2 = 0.15). Abruption was associated with higher mortality from CHD (RR = 2.64, 95% CI: 1.57, 4.44; I2 = 76%; τ2 = 0.31) than stroke (RR = 1.70, 95% CI: 1.19, 2.42; I2 = 40%; τ2 = 0.05). Corrections for the aforementioned biases increased these estimates. Women with pregnancies complicated by placental abruption may benefit from postpartum screening or therapeutic interventions to help mitigate CVD risks., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Research on mortality associated with exposure to the Holocaust is relevant for a better understanding of the effects of genocides on survivors. To our knowledge, previous studies have not investigated the long-term cause-specific mortality of Holocaust survivors. We compared mortality rates among Israelis born in European countries controlled by the Nazis during World War II with those among Israelis of European descent who did not have this exposure. Records of 22,671 people (45% women; 5,042 survivors) from the population-based Jerusalem Perinatal Study (1964-1976) were linked to the Israeli Population Registry, which was updated through 2016. Cox models were used for analysis, with 2-sided tests of statistical significance. Risk of all-cause mortality was higher among exposed women (hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.05, 1.27) than in unexposed women. No association was found between Holocaust exposure and male all-cause mortality. In both sexes, survivors had higher cancer-specific mortality (HR = 1.17 (95% CI: 1.01, 1.35) in women and HR = 1.14 (95% CI: 1.01, 1.28) in men). Exposed men also had excess mortality due to coronary heart disease (HR = 1.39, 95% CI: 1.09, 1.77) and lower mortality from other known causes combined (HR = 0.86, 95% CI: 0.75, 0.99). In summary, experiencing the Holocaust was associated with excess all-cause and cancer-specific mortality in women and cancer- and coronary heart disease-specific mortality in men., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The concept of a multiple risk-factor intervention trial (MRFIT) originated in mid-20th century efforts to determine whether modifying the "risk factors" established by cardiovascular disease epidemiology would prevent heart attacks. The term "MRFIT" probably first appeared in the 1968 report to the National Heart Institute from investigators of the National Diet-Heart Feasibility Study. Based on their pilot experience, they recommended a trial of diet alone. Aware, however, that authorities might agree with the rationale but not the implementation of such a massive and risky undertaking, they also proposed an alternative: whether coronary heart disease was preventable at all by simultaneous intervention on several risk factors; that is, a multiple risk-factor intervention trial. After some years agonizing by serial expert committees, the National Heart Institute opted against an explanatory diet trial and for a pragmatic multiple risk-factor intervention, one designed by Institute staff and operated under contract. Meanwhile, an impatient community of investigators met together in the Makarska Conference, outlined a broad cardiovascular disease prevention policy, and submitted their idealized version of a multiple risk-factor trial, called JUMBO. But the National Heart Institute, because of the plan for its own trial, had no funds left for an investigator-initiated proposal. Hence, this background and story of the MRFIT that wasn't., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Life satisfaction is increasingly recognized as an important determinant of health; however, prospective population-based studies on this topic are limited. We estimated the risk of chronic disease and death according to life satisfaction among a population-based cohort in Ontario, Canada (n = 73,904). The cohort included 3 pooled cycles of the Canadian Community Health Survey (2003-2008) linked to 6 years of follow-up (to 2015), using population-based health databases and validated disease-specific registries. The databases capture incident and prevalent cases of diabetes, cancer, chronic obstructive pulmonary disease, heart disease, and death. Multivariable Cox proportional hazard models were used to estimate hazards of incident chronic disease and death, and were adjusted for sociodemographic, behavioral, and clinical confounders, including age, sex, comorbidity, mood disorder, smoking, alcohol consumption, physical activity, body mass index, immigrant status, education, and income. In the fully adjusted models, risk of both death and incident chronic disease was highest for those most dissatisfied with life (for mortality, hazard ratio = 1.59, 95% confidence interval: 1.15, 2.19; for chronic disease, hazard ratio = 1.70, 95% confidence interval: 1.16, 2.51). In this population-based cohort, poor life satisfaction was an independent risk factor for incident chronic disease and death, supporting the idea that interventions and programs that improve life satisfaction will affect population health.

When a risk factor affects certain categories of a multinomial outcome but not others, outcome heterogeneity is said to be present. A standard epidemiologic approach for modeling risk factors of a categorical outcome typically entails fitting a polytomous logistic regression via maximum likelihood estimation. In this paper, we show that standard polytomous regression is ill equipped to detect outcome heterogeneity and will generally understate the degree to which such heterogeneity may be present. Specifically, nonsaturated polytomous regression will often a priori rule out the possibility of outcome heterogeneity from its parameter space. As a remedy, we propose to model each category of the outcome as a separate binary regression. For full efficiency, we propose to estimate the collection of regression parameters jointly using a constrained Bayesian approach that ensures that one remains within the multinomial model. The approach is straightforward to implement in standard software for Bayesian estimation., (© The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

White blood cell (WBC) count appears to predict total mortality and coronary heart disease (CHD) mortality, but it is unclear to what extent the association reflects confounding by smoking, underlying illness, or comorbid conditions. We used data from the Women's Health Initiative to examine the associations of WBC count with total mortality, CHD mortality, and cancer mortality. WBC count was measured at baseline in 160,117 postmenopausal women and again in year 3 in 74,375 participants. Participants were followed for a mean of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline WBC count and of the mean of baseline + year 3 WBC count. High deciles of both baseline and mean WBC count were positively associated with total mortality and CHD mortality, whereas the association with cancer mortality was weaker. The association of WBC count with mortality was independent of smoking and did not appear to be influenced by previous disease history. The potential clinical utility of this common laboratory test in predicting mortality risk warrants further study., (© The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The personality domains of extraversion and neuroticism are regarded as being stable individual psychological characteristics, yet it remains unclear whether they are associated with chronic disease over an extended period of time. In a randomized controlled trial of smoking cessation nested within the original prospective Whitehall Study (1967-2012), the Eysenck Personality Questionnaire was administered to 832 male self-declared smokers who had undergone a medical examination during which their levels of extraversion and neuroticism were quantified. In the 42-year follow-up period, there were 781 deaths. In analyses in which participants from both trial arms were pooled, there was little evidence of a robust relation of either personality domain with death from all causes, coronary heart disease, stroke, respiratory disease, or cancer in any of our analyses. We therefore found no support for a role of either extraversion or neuroticism as determinants of long-term mortality risk., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Anemia and low and high levels of hemoglobin have been associated with increased mortality and morbidity. However, most studies have measured hemoglobin at only 1 time point, and few studies have considered possible reverse causation. We used data from the Women's Health Initiative, in which baseline hemoglobin was measured in 160,081 postmenopausal women and year 3 hemoglobin was measured in 75,658 participants, to examine the associations of hemoglobin concentration with total mortality, coronary heart disease mortality, and cancer mortality. Women were enrolled from 1993 to 1998 and followed for a median of 16 years. Cox proportional hazards models were used to estimate the relative mortality hazards associated with deciles of baseline hemoglobin and the mean of baseline + year 3 hemoglobin. Both low and high deciles of baseline hemoglobin were positively associated with all 3 outcomes in the total cohort. In analyses restricted to women with 2 measurements, a low mean hemoglobin level was robustly and positively associated with all 3 outcomes, after exclusion of the early years of follow-up. High mean hemoglobin was also associated with increased risk of total mortality, whereas associations with heart disease mortality and cancer mortality were weaker and inconsistent. Our results provide evidence that low and high levels of hemoglobin are associated with increased risk of mortality in otherwise healthy women., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The association between socioeconomic status (SES) and subclinical cardiovascular disease is not well understood. Using data from the Atherosclerosis Risk in Communities Study, we sought to evaluate the cross-sectional and prospective associations of SES, measured by annual income and educational level, with elevated high-sensitivity cardiac troponin T (hs-cTnT) concentrations (≥14 ng/L) using Poisson and multinomial logistic regressions, respectively. We used Cox proportional hazard models to compare the risks of coronary heart disease, heart failure, and mortality according to SES, stratified by baseline hs-cTnT concentration. Our study baseline was 1990-1992, with follow-up through 2011. We found an independent association between SES and hs-cTnT. When comparing participants in the lowest educational level group to those in the highest, the adjusted prevalence ratios for elevated hs-cTnT were 1.36 (95% confidence interval: 1.05, 1.75) overall, 1.83 (95% confidence interval: 1.23, 2.71) in blacks, and 1.05 (95% confidence interval: 0.73, 1.52) in whites (P for interaction = 0.08). Among participants with nonelevated hs-cTnT concentrations, when comparing those in the lowest income groups to those in the highest, the adjusted hazard ratios were strongest for heart failure and death. Having elevated baseline hs-cTnT doubled the risk of heart failure and death. Persons with low SES and elevated hs-cTnT concentrations have the greatest risk of cardiovascular events, which suggests that this group should be aggressively targeted for cardiovascular risk reduction., (© The Author 2016. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Unhealthy lifestyle habits are a major contributor to coronary artery disease. The purpose of the present study was to investigate the associations of smoking, weight maintenance, physical activity, and diet with coronary calcium, cardiovascular events, and mortality. US participants who were 44-84 years of age (n = 6,229) were followed in the Multi-Ethnic Study of Atherosclerosis from 2000 to 2010. A lifestyle score ranging from 0 to 4 was created using diet, exercise, body mass index, and smoking status. Coronary calcium was measured at baseline and a mean of 3.1 (standard deviation, 1.3) years later to assess calcium progression. Participants who experienced coronary events or died were followed for a median of 7.6 (standard deviation, 1.5) years. Participants with lifestyle scores of 1, 2, 3, and 4 were found to have mean adjusted annual calcium progressions that were 3.5 (95% confidence interval (CI): 0.0, 7.0), 4.2 (95% CI: 0.6, 7.9), 6.8 (95% CI: 2.0, 11.5), and 11.1 (95% CI: 2.2, 20.1) points per year slower, respectively, relative to the reference group (P = 0.003). Unadjusted hazard ratios for death by lifestyle score were as follows: for a score of 1, the hazard ratio was 0.79 (95% CI: 0.61, 1.03); for a score of 2, the hazard ratio was 0.61 (95% CI: 0.46, 0.81); for a score of 3, the hazard ratio was 0.49 (95% CI: 0.32, 0.75); and for a score of 4, the hazard ratio was 0.19 (95% CI: 0.05, 0.75) (P < 0.001 by log-rank test). In conclusion, a combination of regular exercise, healthy diet, smoking avoidance, and weight maintenance was associated with lower coronary calcium incidence, slower calcium progression, and lower all-cause mortality over 7.6 years.

In metropolitan areas, road traffic is a major contributor to ambient air pollution and the dominant source of community noise. The authors investigated the independent and joint influences of community noise and traffic-related air pollution on risk of coronary heart disease (CHD) mortality in a population-based cohort study with a 5-year exposure period (January 1994-December 1998) and a 4-year follow-up period (January 1999-December 2002). Individuals who were 45-85 years of age and resided in metropolitan Vancouver, Canada, during the exposure period and did not have known CHD at baseline were included (n = 445,868). Individual exposures to community noise and traffic-related air pollutants, including black carbon, particulate matter less than or equal to 2.5 μm in aerodynamic diameter, nitrogen dioxide, and nitric oxide, were estimated at each person's residence using a noise prediction model and land-use regression models, respectively. CHD deaths were identified from the provincial death registration database. After adjustment for potential confounders, including traffic-related air pollutants or noise, elevations in noise and black carbon equal to the interquartile ranges were associated with 6% (95% confidence interval: 1, 11) and 4% (95% confidence interval: 1, 8) increases, respectively, in CHD mortality. Subjects in the highest noise decile had a 22% (95% confidence interval: 4, 43) increase in CHD mortality compared with persons in the lowest decile. These findings suggest that there are independent effects of traffic-related noise and air pollution on CHD mortality.

Randomized clinical trials (RCTs) are usually the preferred strategy with which to generate evidence of comparative effectiveness, but conducting an RCT is not always feasible. Though observational studies and RCTs often provide comparable estimates, the questioning of observational analyses has recently intensified because of randomized-observational discrepancies regarding the effect of postmenopausal hormone replacement therapy on coronary heart disease. Reanalyses of observational data that excluded prevalent users of hormone replacement therapy led to attenuated discrepancies, which begs the question of whether exclusion of prevalent users should be generally recommended. In the current study, the authors evaluated the effect of excluding prevalent users of statins in a meta-analysis of observational studies of persons with cardiovascular disease. The pooled, multivariate-adjusted mortality hazard ratio for statin use was 0.77 (95% confidence interval (CI): 0.65, 0.91) in 4 studies that compared incident users with nonusers, 0.70 (95% CI: 0.64, 0.78) in 13 studies that compared a combination of prevalent and incident users with nonusers, and 0.54 (95% CI: 0.45, 0.66) in 13 studies that compared prevalent users with nonusers. The corresponding hazard ratio from 18 RCTs was 0.84 (95% CI: 0.77, 0.91). It appears that the greater the proportion of prevalent statin users in observational studies, the larger the discrepancy between observational and randomized estimates.

The authors compared trends in and levels of coronary heart disease (CHD) risk factors between the Minneapolis-St. Paul, Minnesota, metropolitan area (Twin Cities) and the entire US population to help explain the ongoing decline in US CHD mortality rates. The study populations for risk factors were adults aged 25-74 years enrolled in 2 population-based surveillance studies: the Minnesota Heart Survey (MHS) in 1980-1982, 1985-1987, 1990-1992, 1995-1997, and 2000-2002 and the National Health and Nutrition Examination Survey (NHANES) in 1976-1980, 1988-1994, 1999-2000, and 2001-2002. The authors found a continuous decline in CHD mortality rates in the Twin Cities and nationally between 1980 and 2000. Similar decreasing rates of change in risk factors across survey years, parallel to the CHD mortality rate decline, were observed in MHS and in NHANES. Adults in MHS had generally lower levels of CHD risk factors than NHANES adults, consistent with the CHD mortality rate difference. Approximately 47% of women and 44% of men in MHS had no elevated CHD risk factors, including smoking, hypertension, high cholesterol, and obesity, versus 36% of women and 34% of men in NHANES. The better CHD risk factor profile in the Twin Cities may partly explain the lower CHD death rate there.

Meta-analyses of psychological interventions typically find a pooled effect of "psychological intervention" compared with usual care. This answers the research question, "Are psychological interventions in general effective?" In fact, psychological interventions are usually complex with several different components. The authors propose that mixed treatment comparison meta-analysis methods may be a valuable tool when exploring the efficacy of interventions with different components and combinations of components, as this allows one to answer the research question, "Are interventions with a particular component (or combination of components) effective?" The authors illustrate the methods using a meta-analysis of psychological interventions for patients with coronary heart disease for a variety of outcomes. The authors carried out systematic literature searches to update an earlier Cochrane review and classified components of interventions into 6 types: usual care, educational, behavioral, cognitive, relaxation, and support. Most interventions were a combination of these components. There was some evidence that psychological interventions were effective in reducing total cholesterol and standardized mean anxiety scores, that interventions with behavioral components were effective in reducing the odds of all-cause mortality and nonfatal myocardial infarction, and that interventions with behavioral and/or cognitive components were associated with reduced standardized mean depression scores.

Serum phosphorus levels in the general population have been reported to be associated with cardiovascular morbidity and mortality and increased carotid intima-media thickness. The authors examined gender heterogeneity in the association of phosphorus with all-cause mortality and incident coronary artery disease using data from the Atherosclerosis Risk in Communities Study (1987-2001). Baseline phosphorus levels were higher in women and were associated differently among men and women with traditional atherosclerosis risk factors such as age, low density lipoprotein cholesterol, diabetes mellitus, and hypertension. In a multivariable-adjusted model, men in the highest quintile of serum phosphorus level (>3.8 mg/dL) had an increased mortality rate (hazard ratio = 1.45, 95% confidence interval: 1.12, 1.88), while women did not (hazard ratio = 1.18, 95% confidence interval: 0.89, 1.57). The multivariable likelihood ratio test of effect modification by gender was significant at alpha = 0.1 (P = 0.085) for all-cause mortality. Although the associations of phosphorus with coronary artery disease also appeared to differ substantially by gender, the multivariable test for effect modification suggested that the difference was consistent with random variation (P = 0.195). These results suggest the need for further investigation into gender differences in the contribution of mineral metabolism to cardiovascular disease in the general population.

While some studies have found a positive association between both short and long sleep durations and cardiovascular disease (CVD), others have found an association only with a long or short sleep duration. In addition, there are limited data from non-Western populations on this topic. The authors examined the association between sleep duration and coronary heart disease (CHD) mortality among Chinese adults in Singapore (1993-2006), performing a prospective cohort study among 58,044 participants aged > or =45 years (55.9% women) without preexisting CVD. The main outcome of interest was CHD mortality (n = 1,416). The authors found both short and long sleep durations to be positively associated with CHD mortality, independent of smoking, alcohol intake, and body mass index. Compared with persons with a sleep duration of 7 hours (referent), the multivariable relative risk of CHD mortality for a sleep duration of < or =5 hours was 1.57 (95% confidence interval: 1.32, 1.88); for a sleep duration of > or =9 hours, it was 1.79 (95% confidence interval: 1.48, 2.17). This association persisted in subgroup analyses by sex and body mass index. In a population-based cohort of Chinese adults from Singapore, sleep durations of < or =5 hours and > or =9 hours (versus 7 hours) were modestly associated with CHD mortality. These results suggest that sleep duration may be an important marker for CVD.

Adverse health effects of exposures to acute air pollution have been well studied. Fewer studies have examined effects of chronic exposure. Previous studies used exposure estimates for narrow time periods and were limited by the geographic distribution of pollution monitors. This study examined the association of chronic particulate exposures with all-cause mortality, incident nonfatal myocardial infarction, and fatal coronary heart disease (CHD) in a prospective cohort of 66,250 women from the Nurses' Health Study in northeastern US metropolitan areas. Nonfatal outcomes were assessed through self-report and medical record review and fatalities through death certificates and medical record review. During follow-up (1992-2002), 3,785 deaths and 1,348 incident fatal CHD and nonfatal myocardial infarctions occurred. In age- and calendar-time-adjusted models, 10-microg/m(3) increases in 12-month average exposures to particulate matter <10 microm in diameter were associated with increased all-cause mortality (16%, 95% confidence interval: 5, 28) and fatal CHD (43%, 95% confidence interval: 10, 86). Adjustment for body mass index and physical activity weakened these associations. Body mass index and smoking modified the association between exposure to particulate matter <10 microm in diameter and fatal CHD. In this population, increases in such exposures were associated with increases in all-cause and CHD mortality. Never smokers with higher body mass indexes were at greatest risk of fatal CHD.

Dietary flavonols and flavones are subgroups of flavonoids that have been suggested to decrease the risk of coronary heart disease (CHD). The authors prospectively evaluated intakes of flavonols and flavones in relation to risk of nonfatal myocardial infarction and fatal CHD in the Nurses' Health Study. They assessed dietary information from the study's 1990, 1994, and 1998 food frequency questionnaires and computed cumulative average intakes of flavonols and flavones. Cox proportional hazards regression with time-varying variables was used for analysis. During 12 years of follow-up (1990-2002), the authors documented 938 nonfatal myocardial infarctions and 324 CHD deaths among 66,360 women. They observed no association between flavonol or flavone intake and risk of nonfatal myocardial infarction or fatal CHD. However, a weak risk reduction for CHD death was found among women with a higher intake of kaempferol, an individual flavonol found primarily in broccoli and tea. Women in the highest quintile of kaempferol intake relative to those in the lowest had a multivariate relative risk of 0.66 (95% confidence interval: 0.48, 0.93; p for trend = 0.04). The lower risk associated with kaempferol intake was probably attributable to broccoli consumption. These prospective data do not support an inverse association between flavonol or flavone intake and CHD risk.

The authors aimed to quantify the effects of current systolic blood pressure (SBP) and serum total cholesterol on the risk of mortality in comparison with SBP or serum cholesterol 25 years previously, taking measurement error into account. The authors reanalyzed 35-year follow-up data on mortality due to coronary heart disease and stroke among subjects aged 65 years or more from nine cohorts of the Seven Countries Study. The two-step method of Tsiatis et al. (J Am Stat Assoc 1995;90:27-37) was used to adjust for regression dilution bias, and results were compared with those obtained using more commonly applied methods of adjustment for regression dilution bias. It was found that the commonly used univariate adjustment for regression dilution bias overestimates the effects of both SBP and cholesterol compared with multivariate methods. Also, the two-step method makes better use of the information available, resulting in smaller confidence intervals. Results comparing recent and past exposure indicated that past SBP is more important than recent SBP in terms of its effect on coronary heart disease mortality, while both recent and past values seem to be important for effects of cholesterol on coronary heart disease mortality and effects of SBP on stroke mortality. Associations between serum cholesterol concentration and risk of stroke mortality are weak.

An inverse association between height and risk of coronary heart disease (CHD) is well demonstrated, but it is not known whether this association is because of genetic factors, socioeconomic background, or other environmental factors. Four population-based twin cohorts with register-based follow-up data on CHD mortality from Denmark (1966-1996), Finland (1975-2001), and Sweden (1963-2001 and 1972-2001) were used to investigate this question; response rates varied between 65% and 86%. Together, the cohorts included 74,704 twin individuals (35,042 complete twin pairs) with 5,943 CHD deaths during 1.99 million person-years of follow-up. Cox and conditional logistic regression models were used. Per 1-standard deviation decrease in height, height was inversely associated with CHD mortality in men (hazard ratio = 1.08, 95% confidence interval (CI): 1.04, 1.12) and in women (hazard ratio = 1.06, 95% CI: 1.01, 1.10). A twin who had died from CHD was on average shorter than the co-twin within monozygotic pairs (odds ratio = 1.27, 95% CI: 1.12, 1.44, with no sex difference), whereas a weaker association was found within dizygotic pairs in men (odds ratio = 1.01, 95% CI: 0.91, 1.13) and in women (odds ratio = 1.14, 95% CI: 1.01, 1.28). The inverse association between height and CHD mortality found within monozygotic discordant twin pairs suggests that this association is because of environmental factors that directly affect height and CHD risk.

In Finland since the 1980s, coronary heart disease mortality has declined more than might be predicted by risk factor reductions alone. The aim of this study was to assess how much of the decline could be attributed to improved treatments and risk factor reductions. The authors used the cell-based IMPACT mortality model to synthesize effectiveness of treatments and risk factor reductions with data on treatments administered to patients and trends in cardiovascular risk factors in the population. Cardiovascular risk factors were measured in random samples of patients in 1982 (n=8,501) and 1997 (n=4,500). Mortality and treatment data were obtained from the National Causes of Death Register, Hospital Discharge Register, social insurance data, and medical records. Estimated and observed changes in coronary heart disease mortality were used as main outcome measures. Between 1982 and 1997, coronary heart disease mortality rates declined by 63%, with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982. Improved treatments explained approximately 23% of the mortality reduction, and risk factors explained some 53-72% of the reduction. These findings highlight the value of a comprehensive strategy that promotes primary prevention programs and actively supports secondary prevention. It also emphasizes the importance of maximizing population coverage of effective treatments.

Androgen level or androgen activity is implicated in several health outcomes, but its independent role remains controversial. This study investigated the association between history of acne in young adulthood, a marker of hormone activity, and cause-specific mortality in the Glasgow Alumni Cohort Study. Male students who attended Glasgow University between 1948 and 1968 and participated in voluntary health checks reported history of acne (n = 11,232). Vital status has been traced, and risk factors in adulthood are known for about 50% of the participants. Those with a history of acne were more often nonsmokers while university students and tended to be from a lower socioeconomic position. The two groups did not differ in other adolescent (height, body mass index, blood pressure, and number of siblings) or in most adult risk factors. Students who reported a history of acne had a lower risk of all-cause (hazard ratio = 0.89, 95% confidence interval (CI): 0.76, 1.04) and coronary heart disease (hazard ratio = 0.67, 95% CI: 0.48, 0.94) mortality but had some evidence of a higher risk of prostate cancer mortality (hazard ratio = 1.67, 95% CI: 0.79, 3.55). This study shows that androgen activity during adolescence may protect against coronary heart disease but confer a higher risk of prostate cancer mortality.

Moderate alcohol consumption is associated with a decreased risk of cardiovascular disease. However, the impact of variation in alcohol intake over time on estimated risk relations has not been adequately addressed. In this study, 6,544 middle-aged British men without previous cardiovascular disease were followed for cardiovascular events and all-cause mortality over 20 years from 1978/1980 to 1998/2000. Alcohol intake was ascertained at regular points throughout the study. A total of 922 men had a major coronary event within 20 years, 352 men had a stroke, and 1,552 men died of all causes. Baseline alcohol intake displayed U-shaped relations with cardiovascular disease and all-cause mortality, with light drinkers having the lowest risks and nondrinkers and heavy drinkers having similarly high risks. However, the nature of these relations changed after adjustment for intake variation; risks associated with nondrinking were lowered, and risks associated with moderate and heavy drinking increased. Regular heavy drinkers had a 74% higher risk of a major coronary event, a 133% higher risk of stroke, and a 127% higher risk of all-cause mortality than did occasional drinkers (these estimates were 8%, 54%, and 44% before adjustment for intake variation). The findings suggest that considerable caution may be needed before any recommendations regarding acceptable limits of alcohol consumption are made.

Despite evidence that weight loss improves the severity of coronary heart disease (CHD) risk factors, a direct association between weight loss and CHD incidence has not been demonstrated. In 1994-2001, the authors conducted an observational study of intentional weight loss as related to CHD incidence among patients recruited from a network of clinics in Israel who received nutritional counseling from a dietitian to support the medical recommendation to lose weight. Subjects were outpatients aged 50-75 years with a body mass index of > or =27 kg/m(2), without CHD or cancer but with at least one risk factor for CHD in addition to overweight. Outcomes were documented over 4 years by repeated weight measurements and by medical record verification. Among 1,669 patients, 224 (13.4%) incidents of CHD were recorded. For subjects who underwent at least 6 months of dietetic counseling, the risk-factor-adjusted odds ratio for CHD incidence associated with a weight loss of 4.5 kg (the median level of weight loss) was 0.57 (95% confidence interval: 0.39, 0.84). In this, the largest known study of its type reported to date, intentional weight loss from a 6-month diet predicted lower incidence of CHD over 4 years.

Some weight loss diets promote protein intake; however, the association of protein with disease is unclear. In 1986, 29,017 postmenopausal Iowa women without cancer, coronary heart disease (CHD), or diabetes were followed prospectively for 15 years for cancer incidence and mortality from CHD, cancer, and all causes. Mailed questionnaires assessed dietary, lifestyle, and medical information. Nutrient density models estimated risk ratios from a simulated substitution of total and type of dietary protein for carbohydrate and of vegetable for animal protein. The authors identified 4,843 new cancers, 739 CHD deaths, 1,676 cancer deaths, and 3,978 total deaths. Among women in the highest intake quintile, CHD mortality decreased by 30% from an isoenergetic substitution of vegetable protein for carbohydrate (95% confidence interval (CI): 0.49, 0.99) and of vegetable for animal protein (95% CI: 0.51, 0.98), following multivariable adjustment. Although no association was observed with any outcome when animal protein was substituted for carbohydrate, CHD mortality was associated with red meats (risk ratio = 1.44, 95% CI: 1.06, 1.94) and dairy products (risk ratio = 1.41, 95% CI: 1.07, 1.86) when substituted for servings per 1,000 kcal (4.2 MJ) of carbohydrate foods. Long-term adherence to high-protein diets, without discrimination toward protein source, may have potentially adverse health consequences.

Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased levels of total cholesterol and low density lipoprotein cholesterol. The FH clinical phenotype has been shown to be associated with increased coronary heart disease and premature death. Mutations in the low density lipoprotein receptor gene (LDLR) can result in the FH phenotype, and there is evidence that receptor-negative mutations result in a more severe phenotype than do receptor-defective mutations. Mutations in the apolipoprotein B-100 gene (APOB) can result in a phenotype that is clinically indistinguishable from familial hypercholesterolemia, and mutations in this gene have also been shown to be associated with coronary heart disease. Preliminary research indicates that the FH phenotype is influenced by other genetic and environmental factors; however, it is not clear if these are synergistic interactions or simply additive effects.

In a 16-year follow-up study (ending in 1998) of 3,686 Danish men and women aged 30-71 years at recruitment, the association between energy intake from dietary fat and the risk of coronary heart disease was evaluated while assessing the possible modifying role of gender and age. In the models used, total energy and protein intake were fixed. Differences in intake of energy from fat thus reflected complementary differences in intake of energy from carbohydrates. A 5% higher level of energy from saturated fat intake was associated with a 36% greater risk of coronary heart disease among women (hazard ratio (HR) = 1.36, 95% confidence interval (CI): 0.98, 1.88). No overall association between saturated fat and coronary heart disease was found among men. However, age-dependent analyses showed that saturated fat was positively associated with coronary heart disease among the younger men (HR = 1.29, 95% CI: 0.87, 1.91) and the younger women (HR = 2.68, 95% CI: 1.40, 5.12) but not among the older men (HR = 0.94, 95% CI: 0.70, 1.28) and the older women (HR = 1.22, 95% CI: 0.86, 1.71). Polyunsaturated fat was inversely associated with coronary heart disease among women and men, although not significantly. In conclusion, the present study suggests that coronary heart disease risk relates to both the quantity and the quality of dietary fats.

Missing values, common in epidemiologic studies, are a major issue in obtaining valid estimates. Simulation studies have suggested that multiple imputation is an attractive method for imputing missing values, but it is relatively complex and requires specialized software. For each of 28 studies in the Asia Pacific Cohort Studies Collaboration, a comparison of eight imputation procedures (unconditional and conditional mean, multiple hot deck, expectation maximization, and four different approaches to multiple imputation) and the naive, complete participant analysis are presented in this paper. Criteria used for comparison were the mean and standard deviation of total cholesterol and the estimated coronary mortality hazard ratio for a one-unit increase in cholesterol. Further sensitivity analyses allowed for systematic over- or underestimation of cholesterol. For 22 studies for which less than 10% of the values for cholesterol were missing, and for the pooled Asia Pacific Cohort Studies Collaboration, all methods gave similar results. For studies with roughly 10-60% missing values, clear differences existed between the methods, in which case past research suggests that multiple imputation is the method of choice. For two studies with over 60% missing values, no imputation method seemed to be satisfactory., (Copyright 2004 Johns Hopkins Bloomberg School of Public Health)

The authors have studied whether area-level socioeconomic status predicts mortality independently of individual-level socioeconomic status in 179,383 persons in the American Cancer Society Nutrition Cohort, followed for mortality from 1992 to 2000 (17,383 deaths). They used an area-level variable based on census blocks that was an average of home value, income, education, and occupation. Education was the individual-level socioeconomic status variable. The authors studied socioeconomic status-mortality trends with each socioeconomic status variable adjusted for the other. For all causes, an individual's education was strongly and inversely associated with mortality; a weak but significant inverse trend was also present for area-level socioeconomic status. A similar pattern was seen for all-vascular disease. For all cancers, there was again a significant inverse trend with education but no trend with area-level socioeconomic status. Adjustment for conventional (non-socioeconomic status) individual-level risk factors diminished the effect of both socioeconomic status variables, although significant trends remained for men between education and all-cause, all-cancer, and all-vascular disease mortality. Study data indicate that the predictive value of area-level socioeconomic status variables varies by cause of death but is less important than individual-level socioeconomic status variables. Multivariate models that consider socioeconomic status as a potential confounder may not need to consider area-level socioeconomic status if data are available on individual-level education.

Overweight and abdominal obesity increase mortality risk, although the risk may be mediated by traditional cardiac risk factors. The authors assessed the association of baseline measures, change in overall body weight and abdominal obesity (waist circumference), and weight and waist circumference cycling with total mortality among postmenopausal women with known heart disease. They used data from 2,739 US women who participated in the Heart and Estrogen/progestin Replacement Study between 1993 and 2001. Over 6.8 years of follow-up, 498 women died. In adjusted Cox models that included either baseline waist circumference or body mass index (BMI), each was associated with mortality. However, after further adjustment for diabetes, hypertension, and lipoproteins, these associations disappeared. In models including both waist circumference and BMI, larger waist circumference (hazard ratio=1.40 per standard deviation, 95% confidence interval: 1.16, 1.68) was associated with increased risk and higher BMI (hazard ratio=0.81 per standard deviation, 95% confidence interval: 0.67, 0.97) was associated with decreased risk of total mortality, independent of cardiac risk factors. Weight and waist circumference cycling were not associated with mortality. Results show that both BMI and waist circumference are associated with mortality among postmenopausal women with established heart disease, but waist circumference may be more important than BMI, and their effects may be largely mediated by other cardiac risk factors.

The observation that Hispanics have lower all-cause and cardiovascular mortality rates despite increased rates of diabetes and obesity and lower socioeconomic status has been termed the "Hispanic paradox." The authors therefore examined the relation between ethnicity and mortality in 1,438 Mexican-American and 921 non-Hispanic White San Antonio Heart Study participants, aged 45-64 years when they enrolled between 1979 and 1988. Over an average of 14.5 years, 466 deaths occurred: 238 attributed to cardiovascular disease (death certificate International Classification of Diseases, Ninth Revision, codes 401-414 or codes 420-447 with the exception of code 427.5) and 117 attributed to coronary heart disease (codes 410-414). Age- and gender-adjusted hazard ratios for all-cause, cardiovascular, and coronary heart disease mortality comparing Mexican Americans with non-Hispanic Whites were 1.50 (95% confidence interval (CI): 1.23, 1.81), 1.70 (95% CI: 1.30, 2.24), and 1.60 (95% CI: 1.09, 2.36), respectively. After adjusting for possible confounders, among diabetic individuals not using insulin, the authors found excess risk of all-cause, cardiovascular, and coronary heart disease mortality associated with being Mexican American; however, in nondiabetic individuals and insulin-using diabetic individuals, Mexican Americans and non-Hispanic Whites appeared to be at similar risk of mortality. Contrary to the prediction of the "Hispanic paradox," in the San Antonio Heart Study, Mexican Americans were at greater risk of all-cause, cardiovascular, and coronary heart disease mortality than were non-Hispanic Whites.

In electric utility workers, occupational exposure to magnetic fields has previously been associated with mortality from acute myocardial infarction (AMI) and arrhythmia but not from chronic coronary heart disease (CCHD) or atherosclerosis. To investigate these health endpoints further, the authors examined mortality from AMI (n = 407) and CCHD (n = 369) in a cohort of 35,391 male workers at the Southern California Edison Company between 1960 and 1992. Exposure was estimated according to duration of employment in occupations associated with high levels of magnetic field exposure and was calculated as cumulative exposure to magnetic fields expressed in micro-Tesla-years. Adjustment was made for age, calendar time, socioeconomic status, race, and worker status (active or inactive). The authors found that men working longer in high-exposure occupations or working as electricians, linemen, or power plant operators had no increased risk of dying from either AMI or CCHD compared with men who never worked in high-exposure occupations. For cumulative exposure, no association was observed with mortality from AMI (rate ratio per 1 micro T-year = 1.01, 95% confidence interval: 0.99, 1.02) or CCHD (rate ratio per 1 micro T-year = 1.00, 95% confidence interval: 0.99, 1.02). These results, indicating no exposure-related risk increase for AMI mortality, do not confirm previous results.

Whole blood viscosity, plasma viscosity, hematocrit, and fibrinogen are considered independent risk factors for coronary heart disease and can be elevated by dehydration. The associations between fatal coronary heart disease and intake of water and fluids other than water were examined among the 8,280 male and 12,017 female participants aged 38-100 years who were without heart disease, stroke, or diabetes at baseline in 1976 in the Adventist Health Study, a prospective cohort study. A total of 246 fatal coronary heart disease events occurred during the 6-year follow-up. High daily intakes of water (five or more glasses) compared with low (two or fewer glasses) were associated with a relative risk in men of 0.46 (95% confidence interval (CI): 0.28, 0.75; p trend = 0.001) and, in women, of 0.59 (95% CI: 0.36, 0.97). A high versus low intake of fluids other than water was associated with a relative risk of 2.47 (95% CI: 1.04, 5.88) in women and of 1.46 (95% CI: 0.7, 3.03) in men. All associations remained virtually unchanged in multivariate analysis adjusting for age, smoking, hypertension, body mass index, education, and (in women only) hormone replacement therapy. Fluid intake as a putative coronary heart disease risk factor may deserve further consideration in other populations or using other study designs.

The authors prospectively examined the effects of social ties and change in social ties, as measured by a well-known social network index, on total and cause-specific mortality and on coronary heart disease incidence in 28,369 US male health professionals aged 42-77 years in 1988. Over 10 years, the relative risk of total mortality for men in the lower two levels of social integration compared with more socially integrated men was 1.19 (95% confidence interval: 1.06, 1.34) after controlling for age, occupation, health behaviors, general physical condition, coronary risk factors, and dietary habits. In multivariate analysis, deaths from accidents and suicide and from other noncancer, noncardiovascular causes were significantly increased among less socially connected men. Socially isolated men also had an increased risk of fatal coronary heart disease (multivariate relative risk = 1.82, 95% confidence interval: 1.02, 3.23). An increase in the overall social network index between 1988 and 1996 was not significantly associated with subsequent 2-year mortality. In analyses of change in social network components restricted to older men, each categorical unit increase in number of close friends was significantly associated with a 29% decrease in risk of death. Increase in religious service attendance over time was also significantly predictive of decreased mortality.

Standard methods for analysis of cohort studies may give biased estimates of exposure effects in the presence of time-varying confounding. Such effects may instead be estimated by using G-estimation. This study aimed to examine the relations between important cardiovascular risk factors and all-cause mortality and risk of coronary heart disease (CHD), accounting for confounding between exposures over time using G-estimation. Results were compared with those from standard survival analyses (e.g., Weibull regression) with time-updated covariates. The dataset consisted of all participants in the Atherosclerosis Risk in Communities cohort study who had complete data on the first two of four visits, giving a sample of 13,898 people at baseline. Death and occurrence of CHD or stroke were recorded. G-estimated associations between several risk factors and mortality/CHD incidence differed from those estimated using standard survival analysis. The associations between mortality/CHD incidence and smoking, presence of diabetes, and use of antihypertensives were stronger than the standard survival estimates, while the G-estimated effect of low density lipoprotein and high density lipoprotein cholesterol on CHD incidence were more linear than the standard estimate. Complex relations between exposures over time may lead to biased exposure effect estimates in standard survival analyses. G-Estimation can be used to overcome such biases, and thus may have important implications for the analysis of observational studies.

To investigate the association between height in young, socially homogeneous males and cause-specific mortality, the authors conducted a prospective study of 8,361 male former students who underwent medical examinations while attending Glasgow University, Scotland, from 1948 to 1968. The mean age at examination was 20.5 (range, 16.1-30.0) years. The median follow-up time was 41.3 years. There were 863 deaths. In Cox proportional hazards modeling, there was no association between height and all-cause mortality with age-adjusted hazard ratios per 10-cm increase in height (hazard ratio = 0.92, 95% confidence interval: 0.83, 1.02). Height was inversely associated with all cardiovascular disease and coronary heart disease mortality, with hazard ratios per 10-cm increase in height of 0.78 (95% confidence interval: 0.66, 0.93) and 0.76 (95% confidence interval: 0.62, 0.93), respectively. Sizeable inverse associations with stroke and respiratory disease were also found, although these did not reach conventional levels of significance. There was no association with cancer or noncardiorespiratory disease mortality. There was a positive, although nonsignificant, association between height and mortality from aortic aneurysm. Controlling for confounding variables had little effect on these results. The findings suggest that factors operating in early life, and which influence height, also influence future cardiovascular health in men.

This study evaluated whether small shifts in cardiac autonomic balance with standing, as measured by heart rate variability (HRV), were prospectively associated with incident coronary heart disease (CHD) and mortality. Both Black and White men and women aged 45-64 years from the Atherosclerosis Risk in Communities Study (n = 9,267) were followed from 1987 to 1997 for myocardial infarction (n = 296), fatal CHD (n = 63), and non-CHD mortality (n = 533). HRV indices and mean R-R interval length (inverse of heart rate) were measured in the supine and standing positions for 2 minutes each; HRV shift was calculated as the difference between positions. After adjustment for demographic characteristics and medication use, HRV in each position was significantly inversely related to events in Cox proportional hazards models. With the exception of R-R interval length shift and myocardial infarction (hazard ratio = 1.42, 95% confidence interval: 1.02, 1.98 for the smallest vs. the largest quartile), there was no association between HRV shift and the other events. Despite clinical research suggesting that HRV shift with standing is a more sensitive measure of autonomic balance than is HRV in one position, simple measures such as heart rate change and supine and standing HRV were better predictors of events.

Oxidative damage to proteins in the human lens is believed to be important in the etiology of age-related cataract. Because free radical-mediated oxidative damage to lipoproteins may accelerate atherosclerosis, the authors hypothesized that the development of cataract might be a marker for such damage and therefore might be associated with future risk of coronary heart disease (CHD). The authors followed 60,657 women aged 45--63 years and without known coronary disease, stroke, or cancer in 1984. During 10 years of follow-up (674,283 person-years), the authors documented 887 incident cases of CHD and 2,322 deaths. After adjustment for age, smoking, and other coronary risk factors, cataract extraction was significantly associated with higher risk of CHD (relative risk (RR) = 1.88, 95% confidence interval (CI): 1.41, 2.50) for total CHD, 2.44 (95% CI: 1.54, 3.89) for fatal CHD, and 1.63 (95% CI: 1.14, 2.34) for nonfatal myocardial infarction). The positive association between cataract extraction and total CHD was stronger among women with a history of diabetes (RR = 2.80, 95% CI: 1.77, 4.42) than among those without reported diabetes (RR = 1.51, 95 percent CI: 1.04, 2.18). In multivariate analyses, cataract extraction was associated with significantly increased overall mortality (RR = 1.37, 95 percent CI: 1.13, 1.66), which was entirely explained by the increased mortality from cardiovascular disease (RR = 1.84, 95% CI: 1.29, 2.64). These findings are compatible with current hypotheses relating oxidative damage and tissue aging to the development of cataract and CHD.

To assess the association of fasting plasma nonesterified fatty acid (NEFA) concentration with the risk of death from coronary heart disease and cancer, the authors computed 15-year mortality rates for the 4,589 working men aged 43-53 years who were included in the Paris Prospective Study between 1967 and 1972. A total of 251 and 126 men died from cancer and coronary heart disease, respectively. For coronary heart disease death, the age- and tobacco-adjusted relative risk for men in the highest 20% of the fasting plasma NEFA concentrations compared with those in the lowest 80% was 1.54 (95% confidence interval (CI): 1.01, 2.34). It became nonsignificant after further adjustment for blood pressure, iliac/thigh ratio, and plasma insulin and cholesterol concentrations. In contrast, a high fasting plasma NEFA concentration exhibited a strong independent relation with cancer mortality (relative risk = 1.66, 95% CI: 1.25, 2.21, after adjustment for age, cigarette consumption, heart rate, and body mass index). Despite pathophysiologic mechanisms linking NEFA metabolism with visceral fat and plasma glucose, insulin, and triglyceride concentrations, the plasma NEFA concentration does not appear to be a good marker for coronary heart disease risk. In contrast, an unexpected association with cancer mortality was found that may point to the need for further investigation.

In observational studies, estrogen replacement therapy is associated with decreased cardiovascular disease rates and increased breast cancer rates. Recent evidence suggests that the impact of estrogen use on disease outcomes may vary by body mass. In a prospective study of 290,827 postmenopausal US women with no history of cancer or cardiovascular disease at enrollment in 1982, the authors examined the association between postmenopausal estrogen use and all-cause, coronary heart disease, stroke, all-cancer, and breast cancer death rates and whether these associations differed by body mass. After 12 years of follow-up, results from Cox proportional hazards models showed that all-cause death rates were lower among baseline estrogen users than never users (rate ratio (RR) = 0.82, 95% confidence interval (CI): 0.78, 0.87). The lowest relative risk was found for coronary heart disease (RR = 0.66, 95% CI: 0.58, 0.77). The inverse association between estrogen use and coronary heart disease mortality was strongest for thin women (body mass index <22 kg/m2) (RR = 0.49, p for interaction = 0.02). Breast cancer mortality did not increase with estrogen use overall, and no increased risk was observed for thin or heavy women. In this population, the reduction in coronary heart disease mortality among estrogen users was greatest for thinner women. Additional studies are needed to confirm or refute these results.

The authors explored two methodological issues in the estimation of smoking-attributable mortality for the United States. First, age-specific and age-adjusted relative risk, attributable fraction, and smoking-attributable mortality estimates obtained using data from the American Cancer Society's second Cancer Prevention Study (CPS II), a cohort study of 1.2 million participants (1982-1988), were compared with those obtained using a combination of data from the National Mortality Follow-back Survey (NMFS), a representative sample of US decedents in which information was collected from informants (1986), and the National Health Interview Survey (NHIS), a nationally representative household survey (1987). Second, the potential for residual confounding of the disease-specific age-adjusted smoking-attributable mortality estimates was addressed with a model-based approach. The estimated smoking-attributable mortality based on the CPS II for the four most common smoking-related diseases-lung cancer, chronic obstructive pulmonary disease, coronary heart disease, and cerebrovascular disease-was 19% larger than the estimated smoking-attributable mortality based on the NMFS/NHIS, yet the two data sources yielded essentially the same smoking-attributable mortality estimate for lung cancer alone. Further adjustment of smoking-attributable mortality for disease-appropriate confounding factors (education, alcohol intake, hypertension status, and diabetes status) indicated little residual confounding once age was taken into account.

To determine the relation between multivitamin use and death from heart disease, cerebrovascular disease, and cancer, the authors examined a prospective cohort of 1,063,023 adult Americans in 1982-1989 and compared the mortality of users of multivitamins alone; vitamin A, C, or E alone; and multivitamin and vitamin A, C, or E in combination with that of vitamin nonusers by using multivariate Cox proportional hazard models. Multivitamin users had heart disease and cerebrovascular disease mortality risks similar to those of nonusers, whereas combination users had mortality risks that were 15% lower than those of nonusers. Multivitamin and combination use had minimal effect on cancer mortality overall, although mortality from all cancers combined was increased among male current smokers who used multivitamins alone (relative risk (RR) = 1.13, 95% confidence interval (CI): 1.05, 1.23) or in combination with vitamin A, C, or E (RR = 1.16, 95% CI: 1.06, 1.26), but decreased in male combination users who had never (RR = 0.86, 95% CI: 0.74, 0.99) or had formerly (RR = 0.90, 95% CI: 0.82, 0.98) smoked. No such associations were seen in women. These observational data provide limited support for the hypothesis that multivitamin use in combination with vitamin A, C, or E may reduce heart disease and cardiovascular disease mortality, but add to concerns raised by randomized studies that some vitamin supplements may adversely affect male smokers.

Copper, a strong prooxidant, may play a role in atherogenesis. The author examined the association between serum copper concentration and mortality from coronary heart disease using data from the Second National Health and Nutrition Examination Survey (1976-1992). Serum copper concentration was determined using atomic absorption spectroscopy. After various exclusions, 151 deaths from coronary heart disease occurred among 4,574 participants aged > or =30 years. At baseline, the age-adjusted serum copper concentration was about 5% higher among participants who died from coronary heart disease than among those who did not (p = 0.072). After adjustment for age, sex, race, education, smoking status, systolic blood pressure, serum cholesterol, serum high density lipoprotein cholesterol, body mass index, recreational activity, nonrecreational activity, history of diabetes, and white blood cell count, the hazard ratios for death from coronary heart disease for serum copper concentrations in the second, third, and fourth quartiles (versus the first quartile) were 1.84 (95% confidence interval (CI): 0.93, 3.66), 2.14 (95% CI: 1.21, 3.77), and 2.87 (95% CI: 1.57, 5.25), respectively. Several prospective studies, including the present analysis, have found elevated serum copper concentrations to be associated with cardiovascular disease. Whether copper directly affects atherogenesis or is a marker of inflammation associated with atherosclerosis remains to be established.

Fish consumption seems to protect against death from coronary heart disease (CHD). If this association is due to n-3 polyunsaturated fatty acids, especially fatty fish may be responsible for this protective effect. The association between total, lean, and fatty fish consumption and the risk of CHD mortality was examined in 1,088 Finnish, 1,097 Italian, and 553 Dutch men participants in the Seven Countries Study who were aged 50-69 years and free of CHD around 1970. After 20 years of follow-up, 242 (22.2%) men in Finland, 116 (10.6%) men in Italy, and 105 (19.0%) men in the Netherlands had died of CHD. Cox proportional hazards analysis showed no association between total fish consumption and CHD mortality. After adjustments were made for age, body mass index, smoking, energy intake, and relevant dietary variables, the pooled relative risk for the highest quartile of total fish compared with no fish consumption in the three countries was 1.08 (95% confidence interval: 0.76, 1.53). Lean fish consumption also was not associated with CHD mortality in any country. Fatty fish compared with non-fatty-fish consumption was associated with lower CHD mortality; the adjusted, pooled relative risk for fatty fish consumers was 0.66 (95% confidence interval: 0.49, 0.90). These data suggest that especially fatty fish is protective against CHD mortality.