Lipids vs Lipoproteins vs Particle Number

Abstract & Commentary

By Michael H. Crawford, MD

Professor of Medicine, University of California, San Francisco, Chief of Clinical Cardiology, University of California, San Francisco Medical Center, CA

Dr. Crawford reports no financial relationships relevant to this field of study. This article originally appeared in the July issue of Clinical Cardiology Alert.

Synopsis: In this study population with a 2% average risk of a major coronary event per year, LDL cholesterol, apolipoproteins, and LDL particle concentrations had similar and strong associations for major vascular events. The independent predictive value of HDL measures is less clear.

Source: Parish S, et al. Lipids and lipoproteins and risk of different vascular events in the MRC/BHF heart protection study. Circulation 2012;125:2469-2478.

CONFLICTING RESULTS FROM PRIOR STUDIES HAVE CREATED CONTROversy regarding the value of apolipoproteins and lipid particle measures in predicting the risk of atherosclerotic vascular disease in presumably healthy individuals. Thus, these investigators from the United Kingdom analyzed the Heart Protection Study (HPS) data to address this issue. The previously reported HPS studied more than 20,000 men and women over age 40 years who either had known cardiovascular disease or were at high risk for it and had a total cholesterol > 135 mg/dL. The subjects were randomized to simvastatin 40 mg daily or a placebo and treated for 5 years. For this analysis, baseline blood cholesterol fractions, apolipoproteins A1 and B, and lipoprotein particles assessed by nuclear magnetic resonance were associated with the > 5000 vascular events in the trial. The results were adjusted for baseline vascular disease. Major coronary events were associated with all LDL measures, including particle size and number in both the statin and placebo arms. The strengths of these associations were quite similar (hazard ratios 1.15-1.35). HDL concentrations were as good or better at predicting major vascular events as any of the HDL subclasses. However, the predictive power of HDL was partly explained by LDL measures and prior vascular disease reducing the strength of the associations. Interestingly, stroke was not significantly associated with HDL measures. The authors conclude that in this population with a 2% average risk of a major coronary event per year, LDL cholesterol, apolipoproteins, and LDL particle concentrations had similar and strong associations for major vascular events. The independent predictive value of HDL measures is less clear.

Commentary

For those of us who do not routinely measure more than total cholesterol (C), LDL-C, HDL-C, and triglycerides level, this study supports the utility of this simple approach. The strengths of this study were that it was large (> 20,000), prospective, and had a large number of events (> 5000). Also, the results were adjusted for prior vascular disease and other risk factors, including BNP levels. In addition, they measured lipids almost every way possible, including apolipoproteins and particle size and number. Finally, the results agreed with the results of two large, observational studies in apparently healthy adults. A Framingham study of apolipoproteins A1 and B did not demonstrate their superiority over the standard lipid panel. The Women’s Health Study evaluated NMR derived particle size and number with the same result. Thus, I believe the weight of evidence supports that the standard lipid panel is adequate for risk stratification of adults with regard to cardiovascular disease risk. Are there patients who might benefit from a more extensive and expensive analysis of their lipids? There probably are at the extremes of our experience — for example, the patient with a terrible family history, but no apparent risk factors; or the patient with a vascular event and no evident risk factors — but such individuals are rare.

The weak predictive power of HDL was interesting in this study. This is different from that reported in the Framingham and the Women’s Health Study. The latter were primary prevention populations, whereas this study involved those with known or at high risk for cardiovascular disease. Other studies, and now this one, show that pre-existing disease attenuates the predictive power of HDL for future events. In fact, in this study elevated BNP was noted to markedly reduce the predictive power of HDL. This is perhaps good news in secondary prevention, given the paucity of treatments for low HDL. However, low HDL levels remain a concern in primary prevention. Right now I’m recommending more exercise for low HDL — it can’t hurt!