Cholesterol lowering in the elderly population. Coordinating Committee of the National Cholesterol Education Program.

The incidence of coronary heart disease (CHD) peaks in the elderly population. In secondary and primary prevention trials, cholesterol-lowering therapy reduces risk for CHD in both older and younger participants. This benefit, therefore, can be extended to the elderly.

Clinical trials of reducing low-density lipoprotein concentrations.

Much diverse evidence suggests that the plasma levels of low-density lipoprotein (LDL) cholesterol play a causal role in the pathogenesis of atherosclerotic coronary heart disease. Until recently, clinical trials of LDL lowering, while showing significant reductions in coronary heart disease (CHD) rates, were not entirely convincing and left some questions of long-term toxicity unresolved. The results of a series of new trials using members of the powerful statin class of drugs are now being reported. Whether they are primary or secondary prevention studies, they have been uniformly successful in reducing mortality and morbidity from CHD and even total mortality, and have decreased the need for revascularization procedures. Their effectiveness is apparent in many different subgroups such as women, diabetics, hypertensives, and in stroke prevention. Statin drugs also have proven to be remarkably safe over the duration of the studies. Angiographic studies show an impact on coronary or carotid lesions.

Distributions and trends of serum lipid levels among United States children and adolescents ages 4-19 years: data from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Atherosclerosis begins in childhood and progresses into adulthood. The reduction of cardiovascular risk factors, such as elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels, in childhood may reduce cardiovascular morbidity and mortality in adulthood. Lipid distributions among children and adolescents were examined using the most recent nationally representative data. METHODS: Data from 7,499 examinees in NHANES III (1988-1994) were used to estimate mean and percentile distributions of serum total cholesterol, LDL-C, high-density lipoprotein cholesterol (HDL-C), and triglycerides in children and adolescents aged 4 to 19 years. The estimates were analyzed by age, sex, and race/ethnic groups. Trends in mean total cholesterol were examined for 12- to 17-year-olds using data from NHES III (1966-1970), NHANES I (1971-1974), and NHANES III (1988-1994). RESULTS: For children and adolescents 4 to 19 years of age, the 95th percentile for serum total cholesterol was 216 mg/dL and the 75th percentile was 181 mg/dL. Mean age-specific total cholesterol levels peaked at 171 mg/dL at 9-11 years of age and fell thereafter. Females had significantly higher mean total cholesterol and LDL-C levels than did males (P < 0.005). Non-Hispanic black children and adolescents had significantly higher mean total cholesterol, LDL-C, and HDL-C levels compared to non-Hispanic white and Mexican American children and adolescents. The mean total cholesterol level among 12- to 17-year-olds decreased by 7 mg/dL from 1966-1970 to 1988-1994 and is consistent with, but less than, observed trends in adults. Black females have experienced the smallest decline between surveys. CONCLUSIONS: The findings provide a picture of the lipid distribution among U.S. children and adolescents and indicate that, like adults, adolescents have experienced a fall in total cholesterol levels. Total cholesterol levels in U.S. adolescents declined from the late 1960s to the early 1990s by an average of 7 mg/dL. This information is useful for planning programs targeting the prevention of cardiovascular disease beginning with the development of healthy lifestyles in childhood.

Declining serum total cholesterol levels among US adults. The National Health and Nutrition Examination Surveys.

OBJECTIVE: To examine the secular trend in serum total cholesterol levels of the US adult population. DESIGN: Nationally representative cross-sectional surveys with both an in person interview and a medical examination that included the measurement of blood lipid levels. SETTING/PARTICIPANTS: Between 6000 and 13,000 adults aged 20 through 74 years examined in each of four separate national surveys during 1960 through 1962, 1971 through 1974, 1976 through 1980, and 1988 through 1991. RESULTS: Mean serum total cholesterol levels in US adults aged 20 through 74 years have consistently declined over the time period 1960 through 1991. More than half of the decline occurred during the time period 1976 through 1991. This decline occurred across the entire distribution of serum cholesterol levels and in all age-sex groups. High-density lipoprotein cholesterol and very low-density lipoprotein cholesterol levels have not changed, suggesting that the decline in total cholesterol levels is due to a decline in low-density lipoprotein cholesterol levels. CONCLUSIONS: These results document a continuing and substantial decline in serum cholesterol levels among US adults. They suggest that public health programs, designed to reduce cholesterol levels, are proving successful. The observed downward trend in serum cholesterol levels has coincided with a continuing decline in coronary heart disease mortality. These observations suggest that the Healthy People 2000 goal of reducing the mean serum cholesterol level of US adults to no more than 200 mg/dL (5.17 mmol/L) is attainable.

Cost and health implications of cholesterol lowering.

BACKGROUND: A broad, scientific consensus supports the role of cholesterol as a risk factor for coronary heart disease and agrees that lowering cholesterol levels will reduce coronary heart disease incidence. Cost-effectiveness analysis is a potentially powerful method for measuring the benefits to be achieved by expenditures of health care dollars. METHODS AND RESULTS: The literature related to the effectiveness and cost-effectiveness of cholesterol lowering was reviewed. Application of cost-effectiveness methodology to the question of cholesterol reduction generally supports the use of population-wide educational programs and the aggressive use of cholesterol-lowering therapy for the secondary prevention of subsequent coronary events in persons with preexisting coronary heart disease. For primary prevention, however, therapy with medication has a favorable cost-effectiveness ratio only in identifiable high-risk persons, and the different costs of the various available medications should be taken into account. Therapy with medications, especially for primary prevention, would be more appealing if the price of the available medications were lower. CONCLUSIONS: High priority should be given to research that could validate these cost-effectiveness projections as well as to further studies of the elderly and women, in whom direct data on the precise costs, risks, and benefits of interventions to lower cholesterol remain sparse.

Serum total cholesterol: HDL cholesterol ratios in US white and black adults by selected demographic and socioeconomic variables (HANES II).

BACKGROUND: Framingham Study findings suggest that total cholesterol (TC):High density lipoprotein cholesterol (HDL-C) ratio is a useful summary of the joint contribution of TC and HDL-C to coronary heart disease (CHD) risk. Information on the distribution of TC:HDL-C in the US population is limited to selected populations and the relationship of the ratio distribution and its correlates has received little attention. METHOD: TC/HDL-C ratios were examined in a representative sample of the United States adult population ages 20 to 74 years, between February 1976 and February 1980 during NHANES II, using stratification and multivariate regression analyses. RESULTS: Age-adjusted mean ratios were higher in men compared with women and were higher in Whites compared with Blacks. White men had the highest TC/HDL-C mean ratios. These relationships remained after stratification by age, education, body mass index, alcohol use, cigarette smoking, and physical activity. Using multivariate analyses, the ratios were positively related to BMI, age, and smoking; and negatively related to female sex, alcohol use, being Black, and physical activity. CONCLUSIONS: Using a ratio reference point of greater than or equal to 4.5 from the Framingham study, at least an estimated 44 million persons ages 25 to 74 years in the US were found to be at higher risk of developing coronary heart disease.

Change in cholesterol awareness and action. Results from national physician and public surveys.

The National Heart, Lung, and Blood Institute, Bethesda, Md, sponsored national telephone surveys of practicing physicians and the adult public in 1983, 1986, and 1990 to assess attitudes and practices regarding high serum cholesterol levels. Each time, approximately 1600 physicians and 4000 adults were interviewed. Trends show continuing change in medical practice and public health behavior relating to serum cholesterol. In 1990, physicians reported treating serum cholesterol at considerably lower levels than in 1986 and 1983. The median range of serum cholesterol at which diet therapy was initiated was 5.17 to 5.66 mmol/L (200 to 219 mg/dL) in 1990, down from 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1986 and 6.72 to 7.21 mmol/L (260 to 279 mg/dL) in 1983. The median ranges for initiating drug therapy were 6.21 to 6.70 mmol/L (240 to 259 mg/dL) in 1990, 7.76 to 8.25 mmol/L (300 to 319 mg/dL) in 1986, and 8.79 to 9.28 mmol/L (340 to 359 mg/dL) in 1983. The number of adults who reported having had their cholesterol level checked rose from 35% to 46% to 65% in 1983, 1986, and 1990, respectively. Between 1983 and 1990, the number of adults reporting a physician diagnosis of high serum cholesterol increased from 7% to 16%; the number reporting a prescribed cholesterol-lowering diet increased from 3% to 9%. Reports of self-initiated diet efforts reached a high of 19% in 1986 and decreased to 15% in 1990 compared with 1% in earlier years. In 1990, over 90% of physicians reported awareness and use of the recommendations from the Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, and the public reported marked increases in awareness of dietary methods to lower serum cholesterol. These changes suggest educational gains; the data also suggest areas for continued cholesterol educational initiatives.

The Lipid Research Clinics Coronary Primary Prevention Trial: design, results, and implications.

The Coronary Primary Prevention Trial (CPPT) was the major clinical investigation conducted in the Lipid Research Clinics (LRC) Program. There were 12 North American clinics involved in this joint double-blind protocol. The hypothesis tested was: lowering plasma cholesterol in middle-aged men with primary hypercholesterolemia [plasma total cholesterol greater than or equal to 265 mg/dl (6.88 mm/l)] who are otherwise healthy leads to a reduction in coronary heart disease (CHD) as manifest by a reduction in definite myocardial infarction (fatal and nonfatal) over a 7-year follow-up of all participants. The trial was conducted in 3806 male volunteers between the ages of 35 and 59, who were randomly assigned to two equal groups. The treatment group received a moderate cholesterol-lowering diet plus cholestyramine: the placebo group received an identical diet plus a placebo. The study medication was administered at 24 g daily in divided doses. The participants were followed up bimonthly for an average of 7.4 years. The diet (daily cholesterol intake of about 400 mg and a polyunsaturated fat/saturated fat ratio of 0.8) lowered plasma cholesterol by an average of 4%, as designed. The cholestyramine group experienced average plasma total cholesterol (TC) lowering and plasma low-density lipoprotein cholesterol (LDC-C) lowering 8.5% and 12.6% greater than the placebo group, respectively. This resulted in a 19% reduction in definite myocardial infarction (P less than 0.05). The trial results for CHD deaths, nonfatal myocardial infarction,new positive exercise stress tests (P less than 0.001) new-onset angina (P less than 0.01) and coronary artery bypass surgery (P less than 0.06) and coronary artery bypass surgery ((p less than 0.06) were consistent with and supportive of the main findings of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

A single cholesterol measurement underestimates the risk of coronary heart disease. An empirical example from the Lipid Research Clinics Mortality Follow-up Study.

In prospective epidemiologic studies of coronary heart disease, a single measurement of cholesterol is made to assess its relationship to the risk of coronary disease. Statistical theory states that if this measurement is subject to within-individual variability, the strength of the relationship will be underestimated. This is empirically shown for the example of plasma cholesterol. For the Lipid Research Clinics Follow-up Study population (comprising 2170 white men over 30 years of age), the age-adjusted coronary heart disease mortality regression coefficient increases from .453 to .496 if the average of two cholesterol measurements is used instead of a single measurement. Since the correlation between the two repeated cholesterol measurements is .815, an increase in the regression coefficient up to .556 would be expected if the true cholesterol values were available. Thus, epidemiologic studies have substantially underestimated the strength of the relationship between cholesterol levels and the risk of coronary disease by calculating the relationship on the basis of a single cholesterol determination.

The association of corneal arcus with coronary heart disease and cardiovascular disease mortality in the Lipid Research Clinics Mortality Follow-up Study.

The relationship between corneal arcus (arcus senilis) and mortality from coronary heart disease (CHD) and cardiovascular disease (CVD) is examined in a prospective study of White men (n = 3,930) and women non-hormone users (n = 2,139), ages 30-69, followed for an average of 8.4 years as part of the Lipid Research Clinics Mortality Follow-up Study. After excluding those with clinically manifest CHD at baseline, corneal arcus was strongly associated with CHD and CVD mortality only in hyperlipidemic men ages 30-49 years, for whom the relative risk for CHD and CVD death was 3.7 and 4.0, respectively, after adjusting for age, total cholesterol, HDL cholesterol, and smoking status using a Cox proportional hazards model. Among 30-49 year old males, corneal arcus appears to be a prognostic factor for CHD, independent of its association with hyperlipidemia in this age-group, of about the same magnitude as other common risk factors, underscoring the usefulness of corneal arcus as a prognostic factor to the practicing clinician.

Policies for the prevention of coronary heart disease through cholesterol-lowering.

Policies for coronary heart disease prevention through cholesterol-lowering have been advocated by groups in the UK, the US and Continental Europe. Such policies are based on studies of the atherosclerotic plaque, experimental animals, genetic disorders, and lipoprotein metabolism, and from different epidemiological studies and clinical trials. Surveys of physicians and the public indicate a growing awareness of the importance of cholesterol. Expert groups advocate mutually compatible high-risk and population-based strategies. Selective or whole adult population screening is being discussed as is whether it should be done exclusively in the doctor's office or should also include mass public screening. Improved standards for public screening are necessary. The US National Cholesterol Education Program has developed or is developing reports on: (1) the detection, evaluation and treatment of high blood cholesterol in (a) adults and (b) children and adolescents; and on (2) standardization of cholesterol measurement and (3) population-based strategies for controlling cholesterol.

High-density lipoprotein cholesterol and coronary artery disease: survey of the evidence.

The epidemiologic evidence linking high-density lipoprotein (HDL) levels with coronary artery disease (CAD) is persuasive. Case-control studies have shown CAD patients to have lower HDL levels than control subjects. Several large-scale, observational epidemiologic studies in the United States and abroad have shown a strong independent inverse relation between HDL and CAD. Women have a lower incidence of CAD than men of the same age; this has been attributed to their higher HDL levels. Postmenopausal women taking estrogen replacement therapy have higher HDL and lower low-density lipoprotein (LDL) levels, and a much lower incidence of CAD. Statistical analysis suggests that much of this is attributable to HDL levels. In several clinical trials, reduced levels of total or LDL cholesterol have been accompanied by increased HDL levels. Cox proportional hazards analysis suggests that the increment in HDL levels made an independent contribution to the reduction in CAD risk. In several angiographic studies, the increase in HDL may have contributed to the decreased progression, increased stabilization and possible regression of coronary lesions. Despite this range of impressive evidence, a number of unresolved issues have prevented the emergence of a consensus regarding the prevention of CAD by increasing HDL levels. Between-population comparisons of HDL and CAD do not match the within-population relations. Animal research on the relation between HDL, atherogenesis and CAD has been relatively scanty. Although much evidence suggests that reverse cholesterol transport partially explains the protective effect of HDL, there are still doubts as to its role. Problems with measurement of HDL have inhibited widespread recommendations for its use in prevention programs.(ABSTRACT TRUNCATED AT 250 WORDS)

Ten-year mortality from cardiovascular disease in relation to cholesterol level among men with and without preexisting cardiovascular disease.

To determine the associations of total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol with mortality from coronary heart disease and cardiovascular disease, we studied 2541 white men who were 40 to 69 years old at base line and followed them for an average of 10.1 years. Seventeen percent had some manifestation of cardiovascular disease at base line, whereas the others did not. Among the men who had cardiovascular disease at base line, we found, after multivariate adjustment, that those with "high" blood cholesterol levels (above 6.19 mmol per liter) had a risk of death from cardiovascular disease, including coronary heart disease, that was 3.45 times higher (95 percent confidence interval, 1.63 to 7.33) than that for men with "desirable" blood cholesterol levels (below 5.16 mmol per liter). The corresponding hazard ratios were 5.92 (95 percent confidence interval, 2.59 to 13.51) for LDL cholesterol levels above 4.13 mmol per liter as compared with those below 3.35 mmol per liter, and 6.02 (95 percent confidence interval, 2.73 to 13.28) for HDL cholesterol levels below 0.90 mmol per liter as compared with those above 1.16 mmol per liter. All three lipid levels were also significant predictors of death from coronary heart disease alone (P less than 0.005). Total cholesterol and LDL cholesterol levels were also significant predictors of death from cardiovascular and coronary heart disease in men without preexisting cardiovascular disease, although at a lower level of absolute risk of death. Thus, the 10-year risk of death from cardiovascular disease for a man with preexisting cardiovascular disease increased from 3.8 percent to almost 19.6 percent with increasing levels of total cholesterol from "desirable" to "high," whereas the corresponding risk for a man who was free of cardiovascular disease at base line increased from 1.7 percent to 4.9 percent. Our findings suggest that total, LDL, and HDL cholesterol levels predict subsequent mortality in men 40 to 69 years of age, especially those with preexisting cardiovascular disease.

Does lowering serum cholesterol levels lower coronary heart disease risk?

Many lines of evidence converge toward the conclusion that low-density lipoprotein cholesterol (LDLC) is indeed a causal factor in the genesis of CHD. These range from animal studies, pathology studies, inborn errors of metabolism, clinical observations, and the existence of plausible biologic mechanisms, to the vast body of epidemiologic evidence. Observations of the association of LDLC with CHD hold between different populations, in the same population at different times, and to studies of individuals within populations. Finally, the clinical trials of cholesterol lowering, together with regression studies in animals and angiographic studies in humans, provide compelling evidence that the progress of atherosclerosis can be halted and the clinical sequelae can be reduced. The newly available results from more recent intervention studies have reinforced the validity of this conclusion. The intervention studies reduced the CHD incidence rate by approximately 2% for every 1% reduction in total cholesterol (TC) even though the studies were of relatively short duration (typically 5 years). More prolonged exposure to lower TC levels can be expected to yield even greater ultimate benefit. The benefit is most clearcut for men at highest risk. The combined data indicate that both fatal and nonfatal CHD can be reduced. More data on the extremes of age, on subjects with moderate elevations of TC, and on women would be valuable, but it is reasonable to proceed with advice to the general population aimed at reducing average cholesterol levels, and also to identify and treat those at high risk. There is good reason to expect that these measures will further reduce MI events and in all likelihood also MI deaths. Whether they will also reduce overall mortality is at present a moot point; however, a reduction in the burden of nonfatal MI would in itself be a very desirable objective.