Basil M. Rifkind

High-Density Lipoprotein — The Clinical Implications of Recent Studies

DESPITE early observations suggesting an inverse relation between serum levels of high-density lipoprotein (HDL) cholesterol and coronary disease,1 2 3 the possible protective role of HDL in athero...

ALTERED PLASMA LIPID AND LIPOPROTEIN LEVELS ASSOCIATED WITH ORAL CONTRACEPTIVE AND ŒSTROGEN USE: Report from the Medications Working Group of the Lipid Research Clinics Program

In a study of women attending ten North American Lipid Research Clinics plasma total cholesterol, triglyceride, low density (L.D.L.), very low density (V.L.D.L.), and high density (H.D.L.) lipoprotein levels in those taking oral contraceptives (O.C.) and in those taking oestrogens for menopausal symptoms were compared with those in women not taking gonadal hormones, after adjustment for age, educational attainment, and body-mass index, O.C. and oestrogen users were leaner than non-users. Compared with controls, O.C. users showed increased cholesterol, triglyceride, and L.D.L.-cholesterol and V.L.D.L.-cholesterol levels, but H.D.L.-cholesterol levels were similar. Cholesterol, triglyceride, and H.D.L.-cholesterol and V.L.D.L.-cholesterol levels were positively associated with the quantity of the oestrogen component of the O.C. preparations. Compared with non-users, menopausal oestrogen users had slightly lower cholesterol and triglyceride levels, significant decreases in L.D.L.-cholesterol and V.L.D.L.-cholesterol, and a significant increase in H.D.L.-cholesterol.

The Lipid Research Clinics Coronary Primary Prevention Trial

SummaryThe Lipid Research Clinics Coronary Primary Prevention Trial tested the efficacy of cholesterol lowering in reducing the risk of coronary heart disease in 3806 asymptomatic, middle-aged men with primary hypercholesterolaemia. The cholestyramine group experienced 8.5 and 12.6% greater reductions in total and low density lipoprotein (LDL), respectively, than those obtained in the placebo group. The cholestyramine group experienced a 19% reduction in risk (p < 0.05) of the primary end-point of definite coronary heart disease death and/or definite non-fatal myocardial infarction. Corresponding and significant reductions were also seen for angina, development of a positive exercise test, and coronary bypass surgery. All-cause mortality was only slightly, and not significantly, reduced in the cholestyramine group, reflecting more violent and accidental deaths in the cholestyramine subjects.When the cholestyramine group was analysed separately, a 19% reduction in coronary heart disease risk was also associated with each decrement of 8% in total cholesterol. Moreover, coronary heart disease incidence in men in sustaining a fall of 25% in total cholesterol, a typical response to the prescribed dosage (24 g/day) of cholestyramine resin, was half that of men who remained at pretreatment level.The Lipid Research Clinics Coronary Primary Prevention Trial findings show that reducing total cholesterol by lowering LDL cholesterol levels, can diminish the incidence of coronary heart disease morbidity and mortality in men at high risk for the disease because of raised LDL cholesterol levels. These results have considerable importance for the prevention of coronary heart disease through cholesterol lowering, at both the clinical and public health levels.

Plasma cholesterol and triglyceride distributions in 13,665 children and adolescents: the prevalence study of the Lipid Research Clinics Program.

Summary: The age-, race-, and sex-specific distributions for plasma cholesterol (CH) and triglyceride (TG) are described for the 13,655 individuals under 20 years of age who were examined at the first visit (visit I) of the Prevalence Study of the Lipid Research Clinics (LRC) Program. Composite findings are presented from the seven North American LRCs where children were included in the target population. Cholesterol values are higher for blacks than for whites, but triglyceride values are higher for whites than for blacks. In both the CH and TG distributions for the combined races, the mean values for females are generally higher than for males. For cholesterol, consistent age-associated differences occur. On average, the CH values peak in late childhood and decline during adolescence. The decrease in mean values for CH is most marked for white males. The values for TG tend to increase in early adolescence. This report expands the available information about lipid distributions in young populations and describes the extent of the variation in plasma lipids associated with race and sex for each year of age, 0 to 19 years.Speculation: The pattern of age-associated differences found in these population-based, cross-sectional surveys points to the need for prospective studies of lipid levels in cohorts examined before puberty and followed throughout adolescence and into early childhood. Such longitudinal studies may reveal the biological explanation for the age-curve of the mean values for lipids.

Lipid and lipoprotein distributions in white children ages 6–19 yr. The lipid research clinics program prevalence study☆

Abstract Cross-sectional age- and sex-specific distributions of plasma lipids and lipoproteins are described for 1402 white children ages 6–19 yr. These children were part of a random sample examined at seven lipid research clinics (LRC) during the LRC Prevalence Study, which was established to determine the prevalence of hyperlipidemias and to describe the distribution of lipids and lipoproteins in diverse populations. These populations were not selected to be representative of the entire North American pediatric population. Nonetheless, the large numbers of children in the seven LRC populations and their socioeconomic and geographic diversity do permit analytical and comparative studies of physiological and sociodemographic variables in school-age children. This report of their lipid and lipoprotein levels is one in a series of such studies. Examination of the distribution of plasma lipids and lipoproteins showed that total cholesterol (TCH) and low-density lipoprotein cholesterol (LDL-c) were lower in males than females in most age groups studied. The difference in LDL-c is most marked in the younger age group (ages 6–9 yr) and accounts for most of the difference in TCH concentration at this age. During the adolescent period (ages 10–14 yr) a decline in high-density lipoprotein cholesterol (HDL-c) concentration occurs in the males, but not in the females. This decline continues throughout the postadolescent (ages 16–19 yr) period. The resulting difference in HDL-c mainly accounts for the higher TCH observed in the 16–19 yr-old females. Our study confirms the fall in TCH concentration at about adolescence described previously. However, it highlights the different mechanisms responsible in the two sexes. Whereas in the males the decline in TCH is mainly the result of reduction in the concentration of HDL-c, in the females it is due mainly to a gradual decline in LDL-c.

Distribution of high density and other lipoproteins in selected LRC prevalence study populations: a brief survey.

Selected lipid and lipoprotein data from the Lipid Research Clinics (LRC) Prevalence Study are presented, with particular emphasis given to high-density lipoprotein (HDL) values. Cross-sectional age-and sex-specific mean values are shown for 7007 white participants in the ten North American LRCs. Comparisons are drawn for males and females (including the pediatric group) and for females using or not using sex hormones. The US-USSR Collaborative Program is summarized, and selected comparisons are noted for the Soviet and United States samples.

Lipid research clinics coronary primary prevention trial: Results and implications

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

Treating high blood cholesterol in the older patient

Although the general importance of treating high blood cholesterol to prevent coronary heart disease (CHD) is now widely accepted, its application to the older patient has not been well-defined. The association between total blood cholesterol levels and CHD morbidity and mortality weakens with age. However, because age itself is a major risk factor for CHD, treatment of hypercholesterolemia in the elderly may bring about a greater reduction in absolute risk than is obtained in younger persons. More research that directly addresses the benefits of the treatment of hypercholesterolemia in the elderly is needed.

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

Abstract 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. Our ability to increase low HDL levels by hygienic means is uncertain, and there is insufficient information regarding the use of drugs for such a purpose. The recent report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, while not advocating universal screening for HDL, did assign a risk-factor status to a low HDL level, and recommended HDL measurement in a large proportion of persons classified initially on the basis of total cholesterol levels. The results of the Helsinki Heart Study support the use of gemfibrozil in patients with high-risk LDL levels who also have borderline hypertriglyceridemia and low HDL levels.

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.