Importance of HDL Cholesterol in ACS

Abstract & Commentary

By Michael H. Crawford, MD, Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco. Dr. Crawford is on the speaker's bureau for Pfizer.

Synopsis: Regardless of baseline low-density lipoprotein cholesterol levels and statin therapy, additional strategies to increase HDL cholesterol should be evaluated in patients with acute coronary syndrome.

Source: Wolfram RM, et al. Impact of low high-density lipoproteins on in-hospital events and one-year clinical outcomes in patients with non-ST-elevation myocardial infarction acute coronary syndrome treated with drug-eluting stent implantation. Am J Cardiol. 2006;98:711-717.

Patients with acute coronary syndromes (ACS) are routinely put on statins, which usually do little for their high-density lipoprotein (HDL) cholesterol. Thus, Wolfram and colleagues studied the outcomes of ACS patients who underwent drug-eluting stent implantation, stratified by whether their HDL cholesterol was above or below 40 for men or 45 for women. This observational study involved 1032 consecutive patients with ACS based upon ST wave changes or elevated biomarkers of myocardial necrosis. There were 550 patients with low HDL cholesterol. Clinical outcomes at 30 days and one year were analyzed.

The end points were death, Q wave MI, target lesion revascularization (TLR) and a major adverse cardiac event (MACE) composite. Patients with low HDL cholesterol were more likely to have diabetes, obesity, and high triglycerides. In both groups, 98% were treated with statins, and LDL cholesterol was similar. Death at 30 days was higher in the low HDL group as compared to the high HDL (3% vs 0; P < .001), as was MACE at 30 days (3% vs 0.3%; P = .002). Results for one-year mortality and MACE were similar (12% vs 5%; P ≤ .033) for death and (27% vs 12%; P = .005) for MACE. Increasing HDL by one mg/dL reduced MACE and TLR by 4%. Wolfram et al concluded that HDL cholesterol is a key predictor of MACE and death after ACS treatment and drug-eluting stents and, regardless of LDL cholesterol levels and statin therapy, efforts should be made to increase low HDL levels.


Several small studies have shown that HDL cholesterol is inversely related to the development of atherosclerotic cardiovascular disease, and the recent Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial showed that after aggressive LDL lowering with atorvastatin, HDL, but not LDL, cholesterol predicted short-term events at a rate of -1.4% for every 1 mg/dL increase in HDL. Also, therapeutic HDL analogue infusions, such as apolipoprotein A-1 Milano have been shown to reduce atheroma by intravascular ultrasound. Yet in current practice, little attention is paid to HDL. In this study only, 37 of the 550 patients with low HDL (7%) were on specific therapy beyond statins to elevate their HDL after discharge.

Perhaps the lack of enthusiasm for tackling this problem is the lack of a suitable way to raise HDL levels. Exercise can raise HDL, but few patients want to take this dramatic step. Fibric acids may increase HDL, but they are mainly used in patients with high triglycerides and LDL cholesterol. Ezetimibe may increase HDL, but it is mainly used in conjunction with statins to further lower LDL. Niacin is the old standby, but flushing limits its usefulness. At this time, a synthetic HDL is not available. Perhaps physicians would like to raise HDL, but do not have good options for safely doing so. Also, there has been so much emphasis on lowering LDL with statins and the pleiotropic effects of statins, that the fact that they tend to lower HDL has been ignored. In fact, in this study, 95% of the patients were on statins before their ACS event, which may have lowered their HDL cholesterol.

One limitation to this study is that only baseline lipid levels were done. The prognostic value of low HDL is entirely based upon this value. It is possible that their HDL changed after discharge, but since only 7% were on specific therapy to raise HDL, this is unlikely. Nevertheless, it would have been interesting to assess post-discharge lipid levels. Also, this study included only patients treated by percutaneous intervention. Patients treated in other ways may have different results. At this point, the weight of evidence supports the prognostic value of HDL cholesterol in ACS patients, and there is preliminary data that shows that raising it will improve outcomes. Thus, it is prudent to try to raise HDL if it is low in ACS patients. The amount of elevation in HDL needed to change outcomes in not known, but certainly raising it to above 40 in men and 45 in women seems prudent.