High density lipoprotein cholesterol and the risk of stroke in elderly men: the Honolulu heart program

High density lipoprotein (HDL) cholesterol has been inversely associated with coronary heart disease. Associations with stroke are less clear, particularly among the elderly. In this study, the authors examined the relation between HDL cholesterol levels and the risk of stroke in elderly men. Levels of HDL cholesterol were measured in 2,444 Honolulu Heart Program men aged 71-93 years at the 1991-1993 examinations. The participants, who were free of prevalent stroke, coronary heart disease, and cancer at baseline, were followed to the end of 1998 for thromboembolic and hemorrhagic stroke. While HDL cholesterol was unrelated to hemorrhagic events, incidence of thromboembolic stroke declined consistently with increasing HDL cholesterol level (p = 0.003). There was a nearly threefold excess of thromboembolic stroke in men with low HDL cholesterol levels (<1.0 mmol/liter (<40 mg/dl)) compared with men with high levels (> or =1.6 mmol/liter (> or =60 mg/dl)) (10.6/1,000 person-years vs. 3.6/1,000 person-years; p = 0.001). Adjustment for other risk factors had little effect on these findings, although associations appeared strongest in elderly men with "desirable" total cholesterol levels, hypertension, or diabetes mellitus. These findings suggest that HDL cholesterol level is inversely related to the risk of thromboembolic stroke in elderly men. Whether HDL cholesterol alters the effect of other factors on stroke risk in elderly men warrants further study.     

Coronary risk factor levels: differences between educational groups in 1972-87 in eastern Finland.

STUDY OBJECTIVE--To compare differences in coronary heart disease (CHD) risk factor levels between educational groups in the 1970s and 1980s in eastern Finland. DESIGN AND PARTICIPANTS--Independent, cross sectional population surveys were undertaken in 1972, 1977, 1982, and 1987 of randomly selected men and women aged 30-59 living in two provinces in eastern Finland. Altogether 20,096 subjects participated. The lowest observed level of participation in either sex or province in any year was 77%. Serum cholesterol values and blood pressure measurements, body mass index, smoking, and the level of education were determined in each survey using comparable methodology. MAIN RESULTS--More poorly educated men and women had higher levels of all risk factors at the end of the study period (1987). There was no change between 1972 and 1987 in differences between educational groups in mean serum cholesterol values and the diastolic blood pressure level in either sex, and in smoking in men. In women, the proportion of smokers was highest in the better educated in the 1970s but lowest in this group in the 1980s (interaction between year of examination and educational level p < 0.01). Differences between educational groups in mean body mass index increased with time in both men (p < 0.001) and women (p = 0.06). CONCLUSIONS--Relative differences between socioeconomic groups in CHD mortality have increased in Finland in the 1970s and 1980s. Present results from eastern Finland show no reduction in differences between educational groups in risk factor levels, and even some evidence of increasing differences. Although a comparison between mortality trends and risk factor trends is problematic, trends in the risk factors analysed do not seem to be a major cause for the increasing differences in CHD mortality in Finland, at least in men. On the other hand, the risk factor trends analysed show no progress towards reducing inequalities in health, a major goal of public health policy.     

Hypercholesterolemia predicts early death from coronary heart disease in elderly men but not women. The Rancho Bernardo Study.

In a 3-year follow-up study of 761 elderly men and 983 elderly women, total plasma cholesterol levels predicted fatal coronary heart disease (CHD) in men but not women. Low-density lipoprotein level was no better a predictor of fatal CHD than total cholesterol in either sex. Women had higher levels of high-density lipoprotein than men, which explains most of their usual higher total cholesterol levels. These data suggest that cholesterol screening of elderly women would have little value without a lipoprotein evaluation.     

Total but not high-density lipoprotein cholesterol is consistently associated with coronary heart disease mortality in elderly men in Finland, Italy, and The Netherlands

We studied the relation between serum total and high-density lipoprotein (HDL) cholesterol and 10-year coronary heart disease mortality in elderly men in different European countries. The Finland, Italy and the Netherlands Elderly (FINE) Study is a prospective follow-up study in 2,132 elderly men ages 65-84 years in Finland, the Netherlands, and Italy. We estimated relative risks using Cox proportional hazard analysis with time-dependent covariates. Total cholesterol was positively related to coronary heart disease mortality in all three countries. The combined relative risk for the total population of the FINE Study was 1.17 (95% confidence interval = 1.06-1.29) for each 1.00 mmol/liter increase in total cholesterol. HDL cholesterol was inversely related to coronary heart disease mortality in Finland, but not in the Netherlands and Italy. In Italy we noted an interaction among HDL cholesterol, body mass index, and alcohol intake, with an inverse association for HDL cholesterol in lean men who drank <40 gm of alcohol daily and a positive association for HDL cholesterol among overweight men who drank > or =40 gm of alcohol per day. Serum total cholesterol remains an important predictor of coronary heart disease mortality in elderly men in different European countries. The effect of HDL cholesterol differed among the three countries.     

Physical activity and coronary heart disease in middle-aged and elderly men: the Honolulu Heart Program.

The relationship of physical activity to the development of definite coronary heart disease was examined separately in middle-aged (45-64 years) and elderly men (65-69 years) participating in the Honolulu Heart Program. After 12 years of follow-up, results indicate that increased levels of physical activity reported at study entry were inversely related to the risk of definite coronary heart disease in both age groups. In particular, among those aged 45 to 64 years, the rate of definite coronary heart disease in men who led active life styles was 30 per cent lower than the rate experienced by those who were less active (relative risk, 0.69; 95% confidence interval, 0.53, 0.88). In those older than 64 years, the rate of definite coronary heart disease in active men was less than half the rate experienced by those who led more sedentary life styles (relative risk, 0.43; 95% CI, 0.19, 0.99). These results continued to hold up when controlling for several cardiovascular risk factors and potentially confounding variables, supporting earlier observations that physical activity is beneficial in middle-age, and further suggesting that benefits may extend to the elderly male population as well.     

Cholesterol and coronary artery disease: age as an effect modifier.

An elevation of serum cholesterol has been one of the more frequently cited risk factors for coronary heart disease, found in both case-control and cohort studies. As a result, this country has undertaken massive screening of adults older than 20 years of age in an attempt to identify those persons with cholesterol levels greater than 200 mg/dl, and follow up with an active approach for intervention. The suggested cutpoints for borderline (200-240 mg/dl), and definite (> or = 240 mg/dl) hypercholesterolemia have been applied to all age groups despite suggestions of a diminution of risk conferred by cholesterol in the elderly. This study of 2544 white men undergoing coronary angiography shows that for all men, aged 25-84 years, plasma cholesterol levels were associated with an increase in coronary artery occlusion (rs = 0.15, p < 0.01). However, when stratified by age, this association held only for the younger men, the association diminishing to near zero in the oldest age group. The negative interaction between cholesterol levels and age in predicting coronary artery disease proved highly significant (p < 0.001) in multivariable linear regression analysis, suggesting that cholesterol levels are much less predictive of coronary artery disease in the elderly as compared to the young. These results point to the need for a more finely tuned set of criteria for the evaluation of hypercholesterolemia, one that takes into account the age of the screenee.     

Change in survival from out-of-hospital cardiac arrest and its effect on coronary heart disease mortality, Minneapolis-St. Paul. The Minnesota Heart Survey

Emergency medical services with advanced life support systems were implemented in the Minneapolis-St. Paul, Minnesota, area in the mid-1970s. To assess the impact of emergency medical services on coronary heart disease mortality, the authors reviewed ambulance records and hospital emergency room logs for possible out-of-hospital cardiac arrest cases in the period 1972-1982. Potential cases, and their survival to discharge, were validated by hospital record review and were checked against Minnesota death certificates for the year of cardiac arrest and the year following cardiac arrest. Age-adjusted rates of survival to 1 year after cardiac arrest (per 100,000 population) for survivors of out-of-hospital cardiac arrest aged 30-74 years increased significantly from 1972 to 1982 for men (1.8 vs. 11.7; p less than 0.00001) and for women (0.5 vs. 3.5; p less than 0.01). Coronary heart disease mortality rates declined in that period by 34.9% for men (from 527.5 per 100,000 to 343.3 per 100,000) and by 41.7% for women (from 168.6 per 100,000 to 98.3 per 100,000). The authors estimate that improved survival from out-of-hospital cardiac arrest contributed 5.4% (9.9 of 184.2) of the mortality decline for men and 4.3% (3.0 of 70.3) of the decline for women. This was a significant contribution to the decline in coronary heart disease mortality, but it explains only a small part of it.     

Is Italy losing the "Mediterranean advantage?" Report on the Gubbio population study: cardiovascular risk factors at baseline. Gubbio Collaborative Study Group

The coronary heart disease mortality rate in Italy--lower than in many other industrialized countries--has changed little in the last 20 years, whereas in the United States, a major decline in deaths resulting from coronary heart disease has occurred. These differing trends have reduced considerably the gap between the two countries in coronary mortality rates. Several recent population studies in Italy have found a change in the previously more favorable risk factor profile. In the northern hill town of Gubbio, studied in 1983-1985, median serum cholesterol level of men ages 40-59 was 223 mg/dl, considerably higher than was found in the 1960 Italian population samples of the Seven Countries Study (197-206 mg/dl). In the earlier study, the cholesterol levels in the Italian men who were still mainly consuming the traditional Mediterranean diet were 30-40 mg/dl lower than in the U.S. sample. The 1980 Gubbio levels, however, were at least as high as those of their U.S. contemporaries. Cigarette smoking was much higher among the middle-aged men of Gubbio than among a similar U.S. population sample (56% vs 36%). Hypertension prevalence was high, and several risk factors for hypertension--obesity, high salt intake, and alcohol--were common in the Gubbio as well as in other recent Italian population studies. The changing coronary risk profile in Italy, which now includes higher population levels of serum cholesterol as well as the other major coronary heart disease risk factors of cigarette smoking and hypertension, threatens to reduce markedly the "Mediterranean advantage" enjoyed by Italy in the past.     

Fifteen-year trends in coronary risk factors in Finland, with special reference to North Karelia

The North Karelia Project, a major demonstration programme for coronary heart disease (CHD) prevention, was begun in an eastern province of Finland in 1972. A number of national CHD prevention activities have been undertaken, quite a few of them since 1977. This paper reports the 15-year changes in CHD risk factors (serum cholesterol, blood pressure, and smoking) in North Karelia and in the original reference area of the project, and more recent changes in a third area in southwestern Finland. The results are based on well-standardized, comparable surveys of cross-sectional populations, aged 30 to 59 years. The results indicate that risk factors reduced markedly in North Karelia from 1972-1977, to a lesser extent from 1977-1982, and only a little from 1982-1987. There was also a decline in the reference area during the first ten years (1972-1982) but the changes did not exceed those in North Karelia and during the second phase, from 1982-1987, risk factor changes were minor. Risk factor levels in the third area in southwestern Finland changed little from 1982-1987. Present serum cholesterol and blood pressure levels in North Karelia are still higher than in southwestern Finland, but smoking is less common among North Karelian men. These findings are discussed in the light of the recent information on Finnish dietary changes and CHD mortality; their bearing on the need for new cardiovascular disease prevention activities in Finland is also discussed.     

Ten-year changes in the obesity, abdominal adiposity, and serum lipoprotein cholesterol measures of Western Samoan men

Previously reported associations between abdominal adiposity and coronary heart disease (CHD) may be mediated through serum lipids. In the present longitudinal study, 43 Western Samoan men who participated in a 1982 study were recontacted for a second determination of anthropometric and serum lipoprotein cholesterol levels. The men showed dramatic increases in weight (mean change ± SD: 10.5 ± 8.8 kg), abdominal circumference (10.0 ± 7.6 cm), total cholesterol (49.5 ± 26.4 mg/dl), and non-HDL cholesterol (53.1 ± 26.6 mg/dl). A new indicator was used to estimate changes in abdominal adiposity: the residual from the regression of change in the abdominal circumference on change in body weight (the AR). The AR was significantly correlated with changes in total (r = 0.38) and non-HDL cholesterol (r = 0.39). Changes in HDL cholesterol were correlated with changes in weight only (r = −0.37). These bivariate relations remained significant in multiple linear regression analyses. These longitudinal results are the first to suggest changes in abdominal adiposity are related to changes in total and non-HDL cholesterol levels.     

Cholesterol knowledge and practices among patients compared with physician management in a university primary care setting

Lowering elevated serum cholesterol has been shown to reduce the risk of symptomatic coronary heart disease. The National Institute of Health and National Cholesterol Education Program recommend that all adults obtain a cholesterol screening and state that desirable adult levels are less than 200 mg/dl. This study examined the knowledge and practices regarding cholesterol among patients and physicians in a university-based primary care clinic that serves a large proportion of elderly and indigent patients. One hundred fifty-nine patients were interviewed and their medical records were examined. Twenty-four percent of patients were aware of their elevated cholesterol levels, 60% were aware of the health risks associated with hypercholesterolemia, and 83% were able to state methods of lowering cholesterol levels. Approximately 50% stated that they were making considerable efforts to lower fat and cholesterol consumption. Physicians listed cholesterol as a problem in 29% of patients with elevated values (greater than 200 mg/dl) and counseled 17%. Results indicate a good level of knowledge and interest in cholesterol as a health risk even in this group of patients with the multiple problems associated with low socioeconomic status. Knowledge of personal risk status, however, was poor. Physicians need to improve documentation, counseling, and monitoring of patients with elevated cholesterol levels. Long-term follow-up is needed to evaluate efficacy.     

Trends in educational inequalities in cardiovascular risk factors: A longitudinal study among 48,000 middle-aged Norwegian men and women

The aim of the study was to compare educational and gender specific trends in the classical cardiovascular risk factors body mass index (BMI), cholesterol, systolic blood pressure and smoking in a Norwegian population during a period when the coronary heart disease mortality had just reached its peak in the late 1970s and 1980s. We used The Norwegian Counties study: a longitudinal study with three screenings on the same individuals in Oppland, Sogn␣og Fjordane and Finnmark counties in Norway in the period 1974–1988. All residents aged 35–49 were invited and 48,422 participated (89%) in the baseline screening. To estimate the cardiovascular␣risk factor change in individuals over time longitudinal statistical methods were used. BMI, cholesterol and blood pressure levels increased with age, while the amount of daily smokers decreased. The higher the educational level the lower the level of BMI, blood pressure, smoking and cholesterol. This pattern persisted through the whole study period. In men, however, the educational gradient in cholesterol diminished in the last screening. Among women there was an increase in inequality in systolic blood pressure, and for smoking there was a steeper decrease for men than women across all educational groups. The educational differences in classical cardiovascular risk factors persisted, except for BMI, cholesterol and daily smokers in men which tended to decrease.     

Pulmonary function as a predictor of coronary heart disease

The role of pulmonary function as an independent predictor of coronary heart disease was examined in 1965-1983 in a cohort of Japanese-American men. As part of the Honolulu Heart Program, the authors measured pulmonary function in 5,924 men aged 45-68 years who were free of coronary heart disease at baseline examination and followed them for 15-18 years for the development of nonfatal myocardial infarction and fatal coronary heart disease. Per cent predicted forced expiratory volume in one second (%PFEV1) was significantly inversely related to coronary heart disease incidence in the total cohort after adjusting for age (p less than 0.0001) and then for all known coronary heart disease risk factors (p = 0.0004). However, when examined by smoking status, %PFEV1 was a predictor of coronary heart disease only among past and current smokers, and not for men who had never smoked cigarettes (p = 0.36). The association between pulmonary function and coronary heart disease can be explained by cigarette smoking, which leads to both lung impairment and coronary heart disease incidence.     

Coronary risk factors in various occupational groups: the Oslo study.

Coronary risk factors (CRF) have been recorded for nearly 15 000 men aged between 40 and 49 living in Oslo in 1972. These data are matched with the 1970 census data for Norway so as to analyse CRF within various occupational groups. A fairly good agreement between mortality statistics for Norway and CRF was found in many occupations. For instance, persons in pedagogical work have low total mortality rates consistent with their low coronary risk factors. Taxi and busdrivers, on the other hand, have been reported to have mortality rates from lung cancer and coronary heart disease consistent with their high smoking prevalence, serum triglycerides, and cholesterol levels.     

Direct measurement of low-density-lipoprotein cholesterol is more effective than total cholesterol for the purpose of lipoprotein screening

BACKGROUND: We have developed a new method for chemically measuring blood low-density-lipoprotein (LDL) cholesterol. In the present study, we simulated guidelines of the National Cholesterol Education Program (NCEP) using our LDL cholesterol measurements. METHODS: Blood samples were collected from 1,069 individuals (519 males, 550 females) who were referred to our laboratory at Niigata University Hospital for lipoprotein analysis. LDL cholesterol levels were determined according to our assay protocol, which has been published previously. Subjects were categorized by NCEP guidelines and identified "false positives" and "false negatives" on the basis of LDL cholesterol levels measured by our method. RESULTS: The sensitivity of the NCEP guidelines is 87.5% and the specificity is 87.1%, provided we assume that every individual has fewer than two risk factors for coronary heart disease. If we assume that every individual has two or more risk factors, the sensitivity and specificity of the guidelines are 99 and 56.8%, respectively. CONCLUSION: This study presents an opportunity to reevaluate guidelines for routine lipoprotein screening. The chance that individuals with higher LDL cholesterol and lower high-density-lipoprotein cholesterol levels in serum would be missed at initial classification should be zero. The chance that individuals with desirable lipid levels would undergo further lipoprotein analysis should be decreased. Since the new method can be implemented cost-effectively in routine lipoprotein screening, direct measurement of LDL cholesterol could replace total cholesterol.     

Serum triglycerides as an independent risk factor for death from coronary heart disease in middle-aged Norwegian men

The relation between nonfasting serum triglycerides and death from coronary heart disease was studied in 37,546 men aged 35-49 years who were examined during 1972-1977 in four counties in Norway. During an average follow-up period of nine years, 369 deaths from coronary heart disease occurred. In univariate analysis, log(triglycerides) were a weak, but statistically significant predictor of coronary death in the age groups 40-44 and 45-49 years. Within-area analysis showed that a high triglyceride area represented no extreme. When other coronary risk factors were adjusted for, log(triglycerides) remained a significant independent predictor at ages 45-49 years and at higher levels of serum cholesterol. The predictive strength of serum cholesterol was largely the same whether log(triglycerides) were taken into account or not, whereas the predictive strength of log(triglycerides) depended on whether serum cholesterol was accounted for. The strength of coronary death prediction of the logarithm of serum triglycerides was hardly greater than might be explained by the fact that triglycerides are an indicator of the usual cholesterol level of the subject.     

High density lipoprotein cholesterol as a predictor of cardiovascular disease mortality in men and women: the follow-up study of the Lipid Research Clinics Prevalence Study

With data from the Lipid Research Clinics Prevalence Study used as a baseline, an average of 8.4 years of mortality follow-up has been completed for 8,825 male and female participants who were at least 30 years of age at the time of the study. The participants were examined at 10 North American sites during 1972-1976. Univariate findings for high density lipoprotein (HDL) cholesterol in the 7,569 persons initially free of coronary heart disease indicate an inverse relation with cardiovascular disease mortality for men and women. Controlling for age, low density lipoprotein (LDL) cholesterol, triglycerides, body mass index, systolic blood pressure, and smoking, multivariate analysis results indicate inverse relations between HDL cholesterol and cardiovascular disease mortality. In men, the cardiovascular disease mortality rate ratio for HDL cholesterol increments of 10 mg/dl was similar to the cardiovascular disease mortality rate ratio for LDL cholesterol increments of 30 mg/dl. In women, HDL cholesterol is more closely related to cardiovascular disease than is LDL cholesterol. HDL cholesterol is inversely related to both coronary heart disease and other cardiovascular disease mortality in both sexes, though the relation of HDL cholesterol with coronary heart disease mortality in women approached statistical significance only for the combined end point of suspect and definite cases. No relation was observed in either sex group between HDL cholesterol and noncardiovascular disease mortality. This study, only the second large prospective study evaluating the role of HDL cholesterol in women, confirms both the importance and the independence in both men and women of HDL cholesterol in the epidemiology of coronary heart disease and other cardiovascular disease mortality.     

Serum triglycerides and risk of coronary heart disease among Japanese men and women

To examine the relation of triglycerides with coronary heart disease among populations with low mean total cholesterol, the authors conducted a 15.5-year prospective study ending in 1997 of 11,068 Japanese aged 40-69 years (4,452 men and 6,616 women with mean total cholesterol = 4.73 mmol/liter and 5.03 mmol/liter, respectively), initially free of coronary heart disease or stroke. There were 236 coronary heart disease events comprising 133 myocardial infarctions, 68 angina pectoris events, and 44 sudden cardiac deaths. The coronary heart disease incidence was greater in a dose-response manner across increasing quartiles of nonfasting triglycerides for both sexes. The multivariate relative risk of coronary heart disease adjusting for coronary risk factors and time since last meal associated with a 1-mmol/liter increase in triglycerides was 1.29 (95% confidence interval (CI): 1.09, 1.53; p = 0.004) for men and 1.42 (95% CI: 1.15, 1.75; p = 0.001) for women. The trend was similar for myocardial infarction, angina pectoris, and sudden cardiac death. The relation of triglycerides with coronary heart disease was not influenced materially by total cholesterol levels or, in a subsample analysis (51% of total sample), by high density lipoprotein cholesterol levels. Nonfasting serum triglycerides predict the incidence of coronary heart disease among Japanese men and women who possess low mean values of total cholesterol. Further adjustment for high density lipoprotein cholesterol suggests an independent role of triglycerides on the coronary heart disease risk.     

Is hypercholesterolemia a risk factor and should it be treated in the elderly?

PURPOSE: The 1993 National Cholesterol Education Program guidelines recommend cholesterol screening for elderly patients with and without known coronary heart disease. This review summarizes clinical trial evidence from the medical literature that addresses cholesterol treatment in the elderly. DATA SOURCES: References were obtained from a MEDLINE search, bibliographies, metaanalyses, and review articles. STUDY INCLUSION AND EXCLUSION CRITERIA: Randomized, controlled clinical trials, including all lipid intervention trials with elderly participants or subgroup analyses of the elderly designed to measure major cardiovascular disease endpoints, were selected. DATA EXTRACTION METHODS: A MEDLINE search of all clinical trials using key search terms yielded 1360 references. Journal titles and abstracts were reviewed for all references by one of us (K.M.H.). A full journal review was undertaken for 41 references to clinical trials. Five clinical trials fulfilled all criteria and represented unique data. DATA SYNTHESIS: A MEDLINE search (from 1966 to January 2000) and bibliography reviews yielded five important clinical trials with analyses of elderly participants. Data are presented in text form and a summary table. MAJOR CONCLUSIONS: Clinical trial evidence supports treating hyperlipidemia in elderly persons for secondary prevention of coronary heart disease. Evidence from four secondary prevention trials demonstrated that major coronary heart disease risk decreased by 25% to 30% in elderly subjects treated for 5 years. Unanswered questions include cholesterol treatment for primary prevention in the elderly, gender effect, and benefit of treatment in persons older than 70.     

Educational status and coronary heart disease in Puerto Rico: the Puerto Rico Heart Health Program

The Puerto Rico Heart Health Program is an observational epidemiological study of coronary heart disease (CHD) among 9824 Puerto Rican men conducted from 1965 to 1980. Increased level of education was associated with decreased total mortality and increased CHD incidence among the urban participants. Urban men with more education, age 45-64, also showed higher levels of blood pressure and serum cholesterol, more obesity, less physical activity and more atherogenic diets. The increased level of risk factors among those with high education could statistically account for the elevations in CHD incidence. Among rural participants there was an increase in total mortality among those at the highest and lowest levels of education.