Relation of serum lipoprotein cholesterol levels to presence and severity of angiographic coronary artery disease

doi:10.1016/0002-9149(91)90007-8

The American Journal of Cardiology

Volume 67, Issue 6, 1 March 1991, Pages 479-483

https://doi.org/10.1016/0002-9149(91)90007-8 Get rights and content

Abstract

To assess the relation of lipid levels to angiographic coronary artery disease (CAD), lipid profiles were obtained on 125 men and 72 women undergoing diagnostic coronary angiography. CAD, defined as ≥25% diameter narrowing in a major coronary artery, was present in 106 men (85%) and 54 women (75%). Multiple regression analyses revealed that only high-density lipoprotein (HDL) cholesterol level in men, and age and total/HDL cholesterol ratio in women, were independently associated with the presence of CAD after adjustment for other risk factors. HDL cholesterol level and age were significantly correlated with both extent (number of diseased vessels) and severity (percent maximum stenosis) of CAD in men. In women, age was the only independent variable related to severity, whereas age and total/HDL cholesterol ratio were related to extent.

Of 71 patients with total cholesterol < 200 mg/ dl, 79% had CAD. With multiple regression analyses, HDL cholesterol was the only variable independently related to the presence and severity of CAD in these patients after adjustment for age and gender; extent was significantly associated with age and male gender, and was unrelated to any of the lipid parameters.

With use of multiple logistic and linear regression analyses of the group of 197 patients, HDL cholesterol was the most powerful independent variable associated with the presence and severity of CAD after adjustment for age and gender. HDL cholesterol was also an independent predictor of extent. Age was independently associated with each of the end points examined, and was the variable most significantly related to extent. These data add to the growing body of information demonstrating an important association between HDL and CAD.

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2013, Journal of Clinical Lipidology
Citation Excerpt :
To further explore the role of HDL-C in subjects with desirable cholesterol concentrations, the FHS found incident CVD risk to be increased in subjects with low levels of HDL-C, independent of other cardiovascular risk factors.26 This was followed by arteriographic evidence consistently showing that low HDL-C was the most common lipoprotein abnormality in patients with established CVD, irrespective of total-C levels27–30 and that a low HDL-C in the absence of elevated cholesterol was also predictive of future CVD events.31 The validity of the inverse association generated in observational studies extended to randomized clinical trials in which it was observed in both placebo- and drug-treated groups.
For >4 decades it has been recognized that elevated serum levels of high-density lipoprotein cholesterol (HDL-C) are associated with reduced risk of cardiovascular disease (CVD) and its sequelae. Many prospective observational studies performed around the world have confirmed an inverse relationship between HDL-C and cardiovascular risk in people irrespective of sex, race, or ethnicity. Consequently, it was assumed that, by extension, raising HDL-C through lifestyle modification and pharmacologic intervention would reduce risk of CVD. Animal studies are consistent with this assumption. Lipid treatment guidelines around the world promoted the recognition of HDL-C as a therapeutic target, especially in high-risk patients. Some post hoc analyses from randomized controlled trials also suggest that raising HDL-C beneficially affects the risk of CVD. However, a number of recent randomized studies putatively designed to test the “HDL hypothesis” have failed to show benefit. The results of these trials have caused many clinicians to question whether HDL-C is a legitimate therapeutic target. In response to the many questions and uncertainties raised by the results of these trials, the National Lipid Association convened an expert panel to evaluate the current status of HDL-C as a therapeutic target; to review the current state of knowledge of HDL particle structure, composition, and function; and to identify the salient questions yet to be answered about the role of HDL in either preventing or contributing to atherosclerotic disease. The expert panel's conclusions and clinical recommendations are summarized herein. The panel concludes that, although low HDL-C identifies patients at elevated risk, and much investigation suggests that HDL may play a variety of antiatherogenic roles, HDL-C is not a therapeutic target at the present time. Risk stratified atherogenic lipoprotein burden (low-density lipoprotein cholesterol and non–HDL-C) should remain the primary and secondary targets of therapy in patients at risk, as described by established guidelines. The National Lipid Association emphasizes that rigorous research into the biology and clinical significance of low HDL-C should continue. The development of novel drugs designed to modulate the serum levels and functionality of HDL particles should also continue. On the basis of an enormous amount of basic scientific and clinical investigation, a considerable number of reasons support the need to continue to investigate the therapeutic effect of modulating HDL structure and function.
High-density lipoprotein subclasses and their relationship to cardiovascular disease
2012, Journal of Clinical Lipidology
To assess the clinical utility of measuring high-density lipoprotein (HDL) subfractions to assess coronary heart disease (CHD) risk.
Literature review of 80 published investigations.
Measurements of HDL2b by gradient gel electrophoresis provided more consistent evidence of CHD risk than measurement of HDL2 cholesterol. Five of the seven studies that compared the extent or progression of atherosclerosis with gradient gel electrophoresis estimates of HDL subclasses (71%) assigned statistical significance to HDL2b. Ten of the 11 case-control comparisons (91%) reported lower HDL2b in cases. In contrast, of the 16 association studies relating HDL2 cholesterol and HDL3 cholesterol to extent of disease, five reported no significant relationships with either subfraction, two reported significant relationships with both HDL2 and HDL3 cholesterol, four reported significant relationships with HDL2 but not HDL3 cholesterol, and five reported relationships with HDL3 but not HDL2 cholesterol. Forty-five percent of the case-control comparisons reported that both HDL2 cholesterol and HDL3 cholesterol were significantly lower in cases than controls, 17% failed to find significance for either subfraction, and the remainder reported significantly lower values in cases for HDL2 cholesterol only (26%) or HDL3 cholesterol only (11%). On average, the case-control differences were similar for HDL2 (−0.12 ± 0.01 mmol/L) and HDL3 cholesterol (−0.10 ± 0.02 mmol/L), although relative to controls, the percent reduction was twice as great for HDL2 (−25.7 ± 2.9%) than HDL3 cholesterol (−12.1 ± 1.5%). Eight prospective studies were identified and four reported that both HDL2 and HDL3 predicted lower risk for CHD, one reported reductions in risk for HDL2 but not HDL3 cholesterol, and three reported reductions in risk for HDL3 but not HDL2 cholesterol. None of the prospective studies show that measurements of HDL cholesterol subfractions improve the identification of persons at risk.
HDL2 and HDL3 cholesterol do not distinguish cardioprotective differences between HDL subclasses. More extensive characterization of HDL particles by one or two dimensional gel electrophoresis, ion mobility, or ultracentrifugation may provide more specific information about CHD risk than the measurement of HDL cholesterol, HDL3 cholesterol, or HDL2 cholesterol.
High-density Lipoprotein Cholesterol in Coronary Heart Disease Risk Assessment
2009, Clinical Lipidology: A Companion to Braunwald's Heart Disease
High-Density Lipoprotein Cholesterol in Coronary Heart Disease Risk Assessment
2008, Clinical Lipidology: A Companion to Braunwald's Heart Disease Expert Consult: Online and Print
Optimal management of hyperlipidemia in primary prevention of cardiovascular disease
2004, International Journal of Cardiology
Cardiovascular disease (CVD) in the developed countries continues to grow at an epidemic proportion. There are a significant number of young adults with no clinical evidence of CVD, but who have two or more risk factors that predispose them to CV events and death. Many of these risk factors are modifiable, and by controlling these factors, the CVD burden can be decreased significantly. Recent statistics have shown that, if all major forms of CVD were eliminated, the life expectancy would rise by almost 7 years. Hence it is imperative that primary prevention efforts should be initiated at a young age to avert decades of unattended risk factors. Hyperlipidemia has been linked to CVD almost a century ago. Since then various clinical trials have not only supported this link, but have also shown the CV benefits in aggressively treating patients with hyperlipidemia. In this generation, we have various therapeutic agents that are capable of reducing the elevated lipid levels. With drugs like statins, we are able to reduce the risk of CVD by about 30% and avoid major adverse events. Newer drugs are being researched and introduced in the treatment of hyperlipidemia in humans. These can be used in combination therapy resulting in optimal levels of lipids. The new National Cholesterol Education Program (NCEP)/Adult Treatment Panel III (ATP III) guidelines have come as a wake-up call to clinicians about primary prevention of CVD through strict lipid management and multifaceted risk management approach in the prevention of CVD.
Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol
2003, American Heart Journal
Citation Excerpt :
This study shows that, in populations at risk for CHD caused by low HDL-C levels, use of the proposed guidelines based on the TC/HDL-C ratio and LDL-C values identifies more high-risk subjects for treatment than LDL-C threshold values alone. In Turkish men and women with a CHD or equivalent diagnosis, the average TC values (194 and 190 mg/dL, respectively) (Table II) were substantially below those (≥200 mg/dL) in several studies of American men with CHD.10,45–52 In the largest of these studies,10 the average TC of 2905 white men was 213 mg/dL, the average HDL-C was 38 mg/dL, and the average LDL-C was 139 mg/dL.
Current guidelines for managing dyslipidemia qualify patients for treatment based on low-density lipoprotein cholesterol (LDL-C) levels and other risk factors for coronary heart disease (CHD). However, when LDL-C is the sole lipid criterion for initiating therapy, patients with levels below the treatment initiation threshold who are at high risk because of low levels (<40 mg/dL) of high-density lipoprotein cholesterol (HDL-C) might not be identified. Twenty percent of male patients with CHD in the United States fall into this category. The total cholesterol/HDL-C (TC/HDL-C) ratio predicts CHD risk regardless of the absolute LDL-C and HDL-C.
We compared guidelines based on TC/HDL-C and LDL-C with those recommended by the National Cholesterol Education Program Adult Treatment Panel III (ATP III). Both sets of guidelines were applied to 9837 adults (>20 years of age) in the Turkish Heart Study, which has shown that 75% of men and 50% of women in Turkey have HDL-C <40 mg/dL.
ATP III guidelines identified 14% of Turkish adults, 20 years or older, as candidates for lifestyle treatment only and an additional 18% for drug treatment. In conjunction with ATP III LDL-C thresholds, the TC/HDL-C ratio (>3.5, patients with CHD; ≥6.0, 2+ risk factors, ≥7.0, 0 to 1 risk factor) assigned lifestyle therapy alone to 18% and drug treatment to an additional 36%. Among primary prevention subjects at high risk because of age (men ≥45 years; women ≥55 years), both sets of guidelines prescribed lifestyle therapy for only 5%; however, drug treatment was recommended for an additional 13% by ATP III guidelines and an additional 18% by TC/HDL-C and LDL-C.
In populations at risk for CHD caused by low HDL-C, qualification of subjects for treatment based on either the TC/HDL-C ratio or LDL-C thresholds identifies more high-risk subjects for treatment than LDL-C threshold values alone, and use of the ratio, instead of risk tables, simplifies the approach for physicians.

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Relation of serum lipoprotein cholesterol levels to presence and severity of angiographic coronary artery disease

Abstract

Lancet

Lancet

Am J Cardiol

Am J Cardiol

Atherosclerosis

Am J Med

Am J Med

Am Heart J

Serum cholesterol, lipoproteins, and the risk of coronary heart disease: the Framingham Study

Ann Intern Med

The Lipid Research Clinics Coronary Primary Prevention Trials results: II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering

JAMA

Report of the National Cholesterol Education Program Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults

Arch Intern Med

Incidence of coronary heart disease and lipoprotein cholesterol levels: the Framingham Study

JAMA

High density lipoprotein cholesterol, total cholesterol screening, and myocardial infarction: the Framingham Study

Arteriosclerosis

High-density lipoprotein cholesterol and cardiovascular disease: four prospective American studies

Circulation