Original ArticlesEpidemiologic aspects of lipid abnormalities
Section snippets
Total cholesterol
Early studies focused on the total cholesterol (TC) in the serum or plasma and consistently showed a dose–response relation between the level of TC and the risk of coronary artery disease. For example, data from 361,662 men aged 35–57 screened for the Multiple Risk Factor Intervention Trial (MRFIT) showed that the age-adjusted death rate for coronary artery disease rose from about 3.5/1,000 men at a TC of 140 mg/dL to about 5/1,000 men at a TC of 200 mg/dL.2 The slope of the association in this
Effects of age
In contrast to the predictive value of cholesterol measured in observational analyses, where the relative and often absolute risk differences diminish sharply with age, analysis of the Lipid Research Clinic Coronary Primary Prevention Trial (LRC-CPPT)12 indicated that observational data underpredicted treatment benefit in older men. Relative treatment benefit was equal in older versus younger subjects, and absolute benefit tended to be greater in older subjects.13 This supports the proposition
LDL cholesterol
LDL cholesterol is thought to be the principal atherogenic lipoprotein in atherosclerosis. The Framingham Study15 reported in 1977 that LDL cholesterol was a better predictor than TC of coronary artery disease in both men and women. Multiple studies have confirmed this finding, although the strength of the association is sometimes greater in men than in women. For example, in the Lipid Research Clinics Follow-Up Study, whereas the association between LDL cholesterol and both cardiovascular
HDL cholesterol
Beginning with the pioneering observations of Barr in the 1950s on the inverse relation of alpha-lipoprotein to coronary artery disease,22 epidemiologic and other studies have consistently confirmed an inverse relation for HDL cholesterol; that is, as HDL cholesterol increases, coronary artery disease risk is lower (Figure 4).9 When analyzed with similar methodology, 1 British and 4 US studies were found to show a consistent protective effect for HDL cholesterol; a 1 mg/dL decrement in HDL
VLDL cholesterol and triglycerides
The amount of cholesterol carried on VLDL (VLDL cholesterol) is nearly perfectly correlated with the level of triglycerides in the blood, up to a triglyceride level of 400 mg/dL. Above this level, VLDL cannot be accurately estimated from the triglyceride level. In earlier epidemiologic studies, triglycerides and/or VLDL cholesterol were thought to have a neutral association with cardiovascular disease because, despite a consistent univariate association with cardiovascular disease, this
LDL density and pattern B
Using gel electrophoresis and other techniques, LDL particles can be separated by size.38 A predominance of smaller, denser particles—called “pattern B”—has been shown to be associated with higher coronary artery disease risk.39, 40, 41 In addition, some evidence exists that small dense LDL particles may be more easily oxidized and more atherogenic. However, LDL particle diameter is strongly and inversely correlated with the triglyceride level, with a correlation in the r = −0.7 range.40 In the
TC/HDL cholesterol ratio
Various ratios have been proposed to simplify the classification of hyperlipidemia and/or dyslipidemia to a single number. The ratios most frequently proposed are TC/HDL cholesterol, LDL cholesterol/HDL cholesterol, and recently triglyceride/HDL cholesterol.9, 13, 37, 49, 50 Each of these ratios carries composite information; that is, they have a numerator, which contains ≥1 lipid fractions with a positive association with coronary artery disease, and a denominator of HDL cholesterol, which is
Ratios and treatment benefits
Not only is the TC/HDL cholesterol ratio the best predictor of outcome in epidemiologic studies, it is also the best predictor of treatment benefit.13 In the LRC-CPPT, after considering the change in the TC/HDL-C ratio, there was no additional treatment benefit from changes in any other lipid parameter. Specifically, reduction in LDL cholesterol, the focus of the treatment with cholestyramine, added no additional benefit beyond the contribution to the TC/HDL cholesterol reduction. For example,
Conclusion
The TC/HDL cholesterol ratio is the best single measure to predict outcome in observational studies and carries nearly all of the prognostic information. Triglyceride level may add to prediction, particularly when HDL cholesterol is low and there are other manifestations of syndrome X. Change in TC/HDL cholesterol ratio is the best measure of risk reduction during therapy for dyslipidemia and should be monitored during therapy. A reasonable goal for treatment is a ratio <4, although this may
References (54)
- et al.
Serum cholesterol, blood pressure, and mortalityimplications from a cohort of 361,662 men
Lancet
(1986) - et al.
Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and Californiaincidence of myocardial infarction and death from coronary heart disease
Am J Cardiol
(1977) - et al.
Epidemiologic studies of coronary heart disease and stroke in Japanese men living in Japan, Hawaii and Californiacoronary heart disease risk factors in Japan and Hawaii
Am J Cardiol
(1977) - et al.
Blood pressure, stroke, and coronary heart diseasepart 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias
Lancet
(1990) - et al.
Total cholesterol and risk of mortality in the oldest old
Lancet
(1997) - et al.
High density lipoprotein as a protective factor against coronary heart diseasethe Framingham Study
Am J Med
(1977) - et al.
Protein-lipid relationships in human plasmaII, in atherosclerosis and related conditions
Am J Med
(1951) - et al.
HDL, its enzymes and its potential to influence lipid peroxidation
Atherosclerosis
(1995) - et al.
Inhibition of VCAM-1 expression in endothelial cells by reconstituted high density lipoproteins
Biochem Biophys Res Commun
(1997) - et al.
High-density lipoprotein inhibits the synthesis of platelet-activating factor in human vascular endothelial cells
J Lipid Mediat Cell Signal
(1996)