Sandeep Bansal, MD, MPH, is clinical fellow, Division of Cardiology, Johns Hopkins Hospital, and Roger S. Blumenthal, MD, (above) is director, Ciccarone Center for the Prevention of Heart Disease, and professor of medicine, Division of Cardiology, Johns Hopkins Hospital, Baltimore, Maryland.

The fasting lipid profile plays an integral role in preventive cardiology. By obtaining total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, and low-density lipoprotein (LDL) cholesterol levels, we are provided a snapshot of the atherosclerotic risk of our patients and can use these values as targets for therapy directed by national guidelines.¹ Yet, the need for a return visit after an overnight fast remains a considerable inconvenience for both patients and providers.

Traditionally, we have requested lipid assessment in the fasting state for 2 basic reasons. First, fasting triglycerides can be used to calculate LDL cholesterol using the Friedewald equation,² and LDL cholesterol is a well-established target for therapy.1 Second, in contrast to total cholesterol and directly measured LDL cholesterol and HDL cholesterol, triglycerides obtained in the nonfasting state can vary substantially based on the contentof a recent meal. Hence, fasting triglycerides are thought to provide a more reliable estimate of cardiovascular risk.

In this issue of Cardiology Review, Nordestgaard and colleagues summarize the results of their study of nonfasting triglycerides in the Copenhagen City Heart Study.³ They followed 7587 women and 6394 men for a mean of 26 years for cardiovascular endpoints and mortality. In age-adjusted analyses, nonfasting triglycerides were strongly associated with myocardial infarction (MI), ischemic heart disease, and all-cause mortality; in multivariate analyses, these associations were attenuated but persistent.

This study underscores the potential benefits of measuring nonfasting lipids. However, a major limitation of the study is that the multivariable model does not account for HDL cholesterol, which is strongly and negatively correlated with triglycerides. Previous studies have demonstrated that adjustment for HDL cholesterol substantially reduces the association between triglycerides and cardiovascular disease risk.⁴ Although the authors suggest that multifactorial adjustment “masks the effects of triglycerides,” the true clinical utility of a novel risk factor is its ability to provide additional, independent risk information beyond established risk factors.

Another recent study also analyzed the effect of nonfasting triglycerides on cardiovascular disease. Bansal and colleagues⁵ reported the results of more than 26,000 women followed for 11 years for MI, ischemic stroke, coronary revascularization, and cardiovascular death. In multivariable analyses adjusted for traditional risk factors as well as total cholesterol, HDL cholesterol, and markers of insulin resistance, fasting triglycerides were not independently associated with the primary endpoint; however, women in the top third of nonfasting triglycerides had nearly twice the risk of cardiovascular events as those in the bottom third. In secondary analyses, triglycerides were most associated with cardiovascular risk in women who had eaten 2 to 4 hours prior to their blood draw, a time frame that corresponds to the peak in triglyceride levels after a meal.^3,6

The association of nonfasting lipids with cardiovascular disease can be explained by 2 phenomena. First, pathophysiologically, elevated postprandial triglyceride levels signify a large burden of triglyceride-rich atherogenic remnant lipoproteins, particles that have been strongly implicated in atherosclerosis.⁷ Second, the exaggerated triglyceride response to a meal may be indirectly associated with cardiovascular risk because it is a manifestation of insulin resistance and the metabolic syndrome.^8,9

The results of these studies have provocative clinical implications for the practice of assaying lipids after an overnight fast. Direct measurement of LDL cholesterol is now widely available, and in contrast to calculated LDL cholesterol, it does not change substantially after a meal. Furthermore, both apolipoprotein B, a measure of the total number of atherogenic particles, and non-HDL cholesterol, already a secondary target in national guidelines, are stable regardless of prandial state and are established risk factors for atherosclerosis.¹⁰ Finally, the observation in these studies that the nonfasting triglyceride level is the stronger independent predictor of cardiovascular risk than the fasting triglyceride level obviates the reason for measuring lipids in the fasting state.

So can we finally begin measuring nonfasting lipids in all our patients? Unfortunately, before the results of these epidemiologic studies can be translated into clinical practice, further studies are needed to identify clinical cutpoints for triglycerides after a standardized meal. Based on these recent studies, however, clinicians might not be so cavalier about disregarding high triglyceride values because they were not reliably easured in the fasting state. And as further evidence accrues regarding the importance of nonfasting lipids, we may someday, at long last, do away with the fasting lipid profile.

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