Plasma Lipids: Optimal Levels for Health

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WORKSHOPS

Workshop Report: Epidemiological Section

APRIL 11 AND 12, 1979

AMERICAN HEALTH FOUNDATION,     320 East 43rd Street, New York, New York 10017,

PARTICIPANTS

Chairman HENRY BLACKBURN,     Laboratory of Physiological Hygiene School of Public Health University of Minnesota

GERALD S. BERENSON,     Department of Medicine Louisiana State University Medical Center

GEORGE CHRISTAKIS,     MRFIT Clinical Center School of Medicine University of Miami

JOE C. CHRISTIAN,     Department of Medical Genetics Indiana University Medical School

FREDERICK EPSTEIN,     Institute of Social and Preventive Medicine University of Zurich

MANNING FEINLEIB,     Division of Heart and Vascular Diseases National Heart, Lung and Blood Institute

STEPHEN HAVAS,     National Heart, Lung and Blood Institute

G. HEISS,     Department of Epidemiology University of North Carolina at Chapel Hill

SIEGFRIED HEYDEN,     Department of Community and Family Medicine Duke University Medical Center

DAVID JACOBS,     Laboratory of Physiological Hygiene School of Public Health University of Minnesota

JOSEPH V. JOOSENS,     Department of Epidemiology Academisch Ziekenhuis Saint-Rafael Leuven, Belgium

ABRAHAM KAGAN,     Honolulu Heart Study Honolulu, Hawaii

WILLIAM B. KANNEL,     Heart Disease Epidemiology Study NHLBI, Framingham

JOHN A. MORRISON,     Department of Internal Medicine University of Cincinnati Medical Center

NORBERT J. ROBERTS,     Exxon Corporation

LIONEL TIGER,     Harry Frank Guggenheim Foundation

ERNST L. WYNDER,     American Health Foundation

Publisher Summary

The epidemiological section examined evidence from population studies that bears directly on the main issue of the conference, that is, optimal blood lipid levels for whole populations. It considered the relevance of lipid distributions and disease risk as found in adults in affluent, high-coronary heart disease (CHD)-incidence countries, adults in rural farming, fishing, and low-CHD-incidence populations, special adult groups of hunter-gatherers and vegetarians, and children and young adults in high- and low-CHD-incidence countries, and also the relevance of population time trends in lipid distributions and CHD incidence. The epidemiological section considers population data an important, indeed an essential, source of evidence and guidelines related to optimal blood lipid levels for populations. It reviewed the salient facts in the epidemiology of blood lipoproteins, CHD, and atherosclerosis. This chapter presents the outline of epidemiology of blood lipids and CHD and a summary of the epidemiological section report. It further discusses the epidemiological evidences from lipid–CHD relationships, comparative childhood lipid distributions, and changes in lipid levels and CHD rates.

I INTRODUCTION AND SUMMARY FOR THE EPIDEMIOLOGICAL SECTION

A Sources

The Epidemiological Section examined evidence from population studies which bears directly on the main issue of the conference, that is, optimal blood lipid levels for whole populations. We considered the relevance of lipid distributions and disease risk as found in adults in affluent, high-CHD-incidence¹ countries; adults in rural farming, fishing, and low-CHD-incidence populations; special adult groups of hunter-gatherers and vegetarians; children and young adults in high- and low-CHD-incidence countries; and population time trends in lipid distributions and CHD incidence.

Definitions

A definition of optimal lipid levels for populations includes: lipid levels compatible with freedom from mass atherosclerosis and premature vascular disease; lipid levels also compatible with freedom from excess noncardiovascular diseases and all-cause mortality; lipid levels compatible with optimal neuromental and physical growth and development in children and with good general health for all; and lipid levels compatible with a varied and attractive diet and life-style.

Nature of the Evidence

The Epidemiological Section considers population data an important, indeed an essential, source of evidence and guidelines related to optimal blood lipid levels for populations. Direct epidemiological evidence for these levels derives first from longitudinal studies. Within different cultures the relationship between blood lipid levels and the subsequent individual risk of disease is examined. The strength and independence of such individual correlations is enhanced by statistical adjustments for the contributions of other characteristics and also by the congruence of these findings with data from other disciplines. The second main source of epidemiological evidence is from cross-cultural comparisons of blood lipid distributions in populations having different CHD incidence. These population comparisons, and the associations of lipid levels and CHD, are relevant when they confirm or negate hypotheses derived from clinical–experimental findings.

Finally, other epidemiological information bearing on optimal population levels of blood lipids is found in time trends in population lipid levels and in the rates of CHD. However, in trend data, as in population comparisons, it is not always possible to adjust adequately for simultaneous changes in other factors related to CHD risk. Further, detailed data on lipoprotein fractions are unavailable in most studies where the relationship of total serum cholesterol (TC) to CHD incidence is well established. Despite these and other limits in the nature of the epidemiological evidence, information on lipid levels from population studies provides powerful evidence confirming clinical–pathological and laboratory–experimental information.

When the findings from all are congruent, the Epidemiological Section considers that lipid distributions in populations having lower CHD rates provide reasonable guidelines for preventive practice and for public health policy concerning optimal levels.

B Outline of Epidemiology of Blood Lipids and CHD

The Section reviewed these salient facts in the epidemiology of blood lipoproteins, CHD, and atherosclerosis:

Clinical, experimental, and epidemiological evidence of the relationship between blood lipoproteins, atherosclerosis, and disease rate in different cultures is strong, consistent, and congruent (5, 33, 45, 46, 83, 84, 91).

Mean levels and distributions of total serum cholesterol and other blood lipids vary widely between populations (33, 45, 46).

Associations are strong between population means of TC and CHD incidence (33, 45, 46).

Associations are weak between population means of serum triglycerides and CHD incidence (5, 32).

In the few places measured, associations are weak between mean population levels of HDL and VLDL and CHD incidence (10, 41, 42, 48, 49).

Average population TC levels and distributions differ widely for children. They parallel roughly the differences in adult distributions of blood TC and CHD incidence (18).

TC levels at birth have similar means and ranges in all cultures where measured (13, 25, 102).

TC means and distributions of emigrants approach those of the adopted country, whether higher or lower than the country of origin (56).

Considerable variation in CHD incidence and TC levels is observed within countries and this has been insufficiently studied.

Longitudinal studies of adults within populations, in which blood lipids are measured in a state of health, generally show rising individual risk of CHD according to levels of TC and LDL, at least until late middle age (45, 46, 84, 91, 93).

A strong inverse relationship is found between HDL cholesterol level and CHD incidence at older ages in Framingham, Norwegian, and Israeli data (32).

Large-scale experiments indicate the feasibility and safety of lipid lowering based on changes in dietary composition and loss of weight (19, 60, 91, 92).

Results of clinical trials of lipid lowering in the primary prevention of CHD in older, high-risk populations range from negative to equivocal to positive. The relevance of such trials in high-risk adults to the issues of primary prevention in the community using educational health strategies is thought to be small (4, 19, 84, 91).

A small but significant drop in U.S. population TC means has probably occurred in the last 20 years, largely explainable by reported changes in diet composition or food consumption (4, 82–84, 90).

Downward trends in CHD mortality are generally consistent with measured population decreases in TC, decreased adult smoking, and improved care and control of hypertension (4, 83).

C Summary of the Epidemiological Section Report

The issue of optimal and feasible levels of blood cholesterol and lipoproteins for the general population is important to individuals, to the health professions, and to the public health. It was our aim to describe those population levels of blood lipoproteins compatible with optimal growth and development of a people which at the same time leave them least susceptible to premature death and disease. We assume that the general relationship of TC or LDL with CHD is causal, because of the congruent evidence from clinical and experimental observations reviewed in this conference report and elsewhere.

We considered evidence from worldwide studies bearing on the question of optimal blood lipid levels for whole populations. First, the heart attack or coronary heart disease risk for individuals living in affluent societies was considered according to the level and type of blood cholesterol. In cultures having relatively high CHD incidence and high levels of blood lipids and lipoproteins, the individual CHD risk rises with the level of total serum cholesterol and with the level of cholesterol measured in the low-density type of lipoprotein, while it diminishes with the level of cholesterol found in the high-density type. In such high-incidence societies the individual risk of CHD corresponds more strongly with serum levels of total or LDL cholesterol in younger years, below ages 50–55, while later the risk correlates more closely, and negatively, with the amount of cholesterol in the HDL fraction.

We also compared the population levels of TC to the CHD incidence and death rates in regions where each has been carefully measured. At the upper extreme of mean TC values and distributions, and higher CHD rates, are numerous societies in North America, Central and Northern Europe, New Zealand, and Australia, where average TC levels are 220–280 mg/dl and where atherosclerotic diseases are the major public health problem. At the opposite extreme are special populations characterized by largely vegetarian diets and physically active, subsistence-level societies. Among them, average adult values of TC range from 100 to 140 mg/dl. However, the uncertainties about age- and cause-specific disease and death rates in these populations, as well as their growth and development, overall nutrition, health, and disease, are such that their extremely low TC levels are not considered here as necessarily ideal population distributions. Their characteristics are cited because they are thought to approximate those of huntergathering man during the major part of evolution. They contrast with mass metabolic maladaptations of hyperlipidemia, diabetes, obesity, and hypertension found in sedentary, affluent societies.

The Epidemiological Section also reviewed evidence from a number of populations having mean TC levels around 160 mg/dl in which eating and living patterns are stable, palatable, and feasible. Such populations are found widely in rural, pastoral, and agricultural or fishing societies, in the Orient and in the Mediterranean Basin, where low rates of atherosclerotic diseases are well documented. This evidence suggests that average TC levels around 160, with a 95% population range from a low of 110 to a high of 210 mg/dl, very possibly represent the optimal lipid levels for populations in terms of overall low risk of atherosclerosis and minimal incidence of CHD. Populations in this range may or may not have relatively low rates of noncardiovascular and other causes of death. Observations in Japanese, Hawaiian, and American studies of the association of very low individual TC levels and risk of brain hemorrhage and malignancies remain to be confirmed. There is no such evidence of excess risk in all the U.S. studies of the Pooling Project nor in comparisons between populations having very low blood lipid levels. At this time there are also no mechanisms to explain any causal association between serum cholesterol levels, cerebral hemorrhage, and cancer.

A third and sizable group of populations and cultures was identified as having TC averages on the order of 180–200 mg/dl, in which CHD incidence is half or less than that in many affluent Western countries. Averages around 190 mg/dl and the 95% range of the population associated with those averages, 130–250 mg/dl, are found in most Mediterranean countries, including Greece, Yugoslavia, and Italy; in Latin America including Puerto Rico; and in urban mainland Japan among others. As Fig. 1 shows, mean levels around 190 mg/dl might therefore be considered desirable population means, compatible with feasible changes, substantially reduced risk of atherosclerosis, and low rates of premature mortality from CHD and from other