This paper presents the results of a key, compelling post-hoc analysis of the completed Treating to New Targets (TNT) study, which examined the predictive value of HDL cholesterol in a sample of almost 10,000 patients treated with 2 doses of atorvastatin. Results clearly showed that among patients receiving statin therapy, HDL cholesterol levels predicted major cardiovascular events across the overall TNT Study cohort. Even among patients with very low LDL cholesterol, a low HDL cholesterol concentration increased risk of cardiovascular events. Interestingly, as both LDL cholesterol and HDL cholesterol were significant drivers of CVD events in this study, the authors found that the cholesterol/HDL cholesterol ratio (which is largely determined by LDL and HDL cholesterol levels) was a powerful predictor of cardiovascular events irrespective of the atorvastatin dose used. Therefore, this paper provides further evidence that low HDL cholesterol, either through direct or indirect mechanisms, is an independent predictor of cardiovascular disease risk even among patients who are treated with a high statin dose and who have very low LDL cholesterol. Now requiring additional study is the question of whether low HDL cholesterol concentrations are due to the presence of abdominal obesity, the metabolic syndrome, and the related cluster of metabolic abnormalities.
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