Epidemiological and clinical intervention data have consistently shown that low levels of
HDL-cholesterol (HDL-C) are associated with an increased risk of
cardiovascular disease. In contrast, data for gene variants associated with changes in HDL-C are more conflicting, potentially reflecting the complexity of HDL metabolism. Indeed reverse
cholesterol transport and HDL functionality cannot be appreciated by HDL-C level alone. In clinical practice, low HDL-C is frequently combined with other metabolic abnormalities, particularly with
type 2 diabetes,
metabolic syndrome and
abdominal obesity. These circumstances are usually associated with the presence of an atherogenic
dyslipidemia characterized by the
lipid triad low HDL-C, elevated
triglycerides and excess of small dense
LDL particles. The first step in the management of low HDL-C is lifestyle interventions:
weight loss, physical activity and smoking cessation are effective in increasing HDL-C. The residual cardiovascular risk among high risk patients who are treated with
statins, have triggered intense interest in
therapies raising HDL-C. Until now,
nicotinic acid is the most effective
drug. All the new therapeutic strategies acting on HDL should be validated by cardiovascular clinical trials.