Simplifying lipid assessment: non-fasting total and HDL cholesterol

A report from the Emerging Risk Factors Collaboration concludes that measurement of total and high-density lipoprotein cholesterol (HDL cholesterol) or apolipoproteins provides a simple, reliable and practical approach to assessment of vascular risk. Neither fasting lipid levels nor triglycerides provides additional information. The study was reviewed by HDL Forum Editor Professor Philip Barter.

 

The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease. JAMA 2009;302:1993-2000.

 

This analysis was based on 68 prospective population-based studies of cardiovascular risk involving 302,430 participants without known history of coronary heart disease (CHD), mainly from western Europe (60%) and North America (32%). Over 2.79 million person-years of follow-up, there were 18,368 first-ever outcomes (12,785 CHD events), as summarised in Figure 1.

 

Hazard ratios were calculated for 1 standard deviation higher values of triglycerides (1 SD = 0.52 loge), HDL cholesterol (15 mg/dL), non-HDL cholesterol (43 mg/dL), apolipoproteins (apo) AI or B (29 mg/dL each) and directly measured LDL cholesterol (33 mg/dL).  Adjustment was made for age, sex, systolic blood pressure, smoking status, diabetes history, body mass index and lipid measures. 

 HDL cholesterol and non-HDL cholesterol levels were strongly associated with CHD risk, albeit in opposite directions, with risk increasing in a log-linear manner, independently of each other.  An increase in HDL cholesterol by 15 mg/dL was associated with 22% reduction in CHD risk. Triglyceride levels did not impact on CHD risk (hazard ratio 0.99, 95% CI 0.94-1.05) (Table 1).

 Hazard ratios were at least as strong in individuals who fasted compared with those who did not. Adjustment for lipid or non-lipid risk factors did not appear to influence hazard ratios for CHD risk (Table 2).

 

Based on these findings, the authors suggest that a therapeutic approach aimed at raising HDL cholesterol, as well as lowering non-HDL cholesterol may provide additional clinical benefit. For example, in this epidemiological analysis subjects with 15 mg/dL higher HDL cholesterol levels and 80 mg/dL lower non-HDL cholesterol levels have 65% reduction in CHD risk (hazard ratio 0.35, 95% CI 0.30-0.42). Clearly long-term outcomes trials are needed to test this hypothesis.

 

Another point to note was that hazard ratios for CHD risk associated with HDL and non-HDL cholesterol levels were similar to those reported for apolipoproteins (Table 3).

 

This finding contrasts with other studies. For example, in the International Studies of Infarct Survival (ISIS), recently reported in HDL Forum, the ratio of apoB/apoA1 was a stronger, reproducible risk factor than any other lipid measure (1). It is possible that this discrepancy between case-control studies such as ISIS and the current epidemiological analysis may arise as a result of distortion of lipid levels following heart attack, a bias which is minimised in prospective analysis of subjects without prior cardiovascular disease.

 

On the basis of their findings, the authors conclude that measuring non-fasting total and HDL cholesterol levels or apolipoproteins provide simple, practical approaches to assessment of CHD risk. Measurement of triglycerides does not add to risk assessment.

 

Reference

1. Parish S, Peto R, Palmer A et al. The joint effects of apoliprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls. Eur Heart J 2009;30:2137-46.


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