In this study of 4,188 patients with low plasma LDL cholesterol concentrations (<1.55 mmol/l (<60 mg/dl)) attending the Palo Alto Veterans Administration Medical Center, deGoma et al. investigated the clinical significance of HDL cholesterol in predicting the 1 year risk of their primary endpoint (myocardial injury or hospitalization from ischemic heart disease). Independent of statin use or previous myocardial injury, increasing HDL cholesterol levels were associated with a decreased risk of primary endpoint (quartile 1: odds ratio=1.59 (95% CI, 1.16-2.19) vs. quartile 4 as reference). When HDL cholesterol was examined as a continuous variable, a 0.26 mmol/l (10 mg/dl) decrease in HDL cholesterol levels was linked to a 10% increase in the primary endpoint. When the clinical significance of HDL cholesterol was tested for the secondary endpoint (all-cause mortality), a U-shaped association was reported. These results suggest that even with low plasma LDL cholesterol levels (either natural or achieved through statin therapy), a further decrease in HDL cholesterol increases cardiovascular disease (CVD) risk. Thus, it is important to raise HDL cholesterol independent of plasma LDL cholesterol levels in order to prevent CVD endpoints. This paper was accompanied by an editorial by Lavie and Milani who discussed the controversial issue of new HDL raising therapies (CETP inhibitors). They stressed that the disappointing results of ILLUMINATE do not mean that the medical community should abandon HDL raising therapies. In their conclusion, they suggested that lifestyle therapy, weight reduction, alcohol intake reduction, niacin, and certain fibrates should be used since, on top of raising HDL cholesterol levels, these interventions might increase reverse cholesterol transport.
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