Low high-density lipoprotein cholesterol is not a risk factor for recurrent vascular events in patients with vascular disease on intensive lipid-lowering medication

Objectives: This study sought to evaluate the vascular risk of low high-density lipoprotein-cholesterol (HDL-C) in relation to the use and intensity of lipid-lowering medication in patients with clinically manifest vascular diseases.

Background: Low levels of HDL-C are associated with an increased risk for vascular diseases and may contribute to residual vascular risk in patients already treated for other risk factors. However, post-hoc analyses from statin trials indicate that the vascular risk associated with low HDL-C may be low or even absent in patients using intensive statin therapy.

Methods: We performed a prospective cohort study of 6,111 patients with manifest vascular disease. Cox proportional hazards models were used to evaluate the risk of HDL-C on vascular events in patients using no, usual dose, or intensive lipid-lowering therapy.

Results: New vascular events (myocardial infarction, stroke, or vascular death) occurred in 874 subjects during a median follow-up of 5.4 years (interquartile range: 2.9 to 8.6 years). In patients not using lipid-lowering medication at baseline (n = 2,153), a 0.1 mmol/l increase in HDL-C was associated with a 5% reduced risk for all vascular events (hazard ratio [HR]: 0.95; 95% confidence interval [CI]: 0.92 to 0.99). In patients on usual dose lipid-lowering medication (n = 1,910) there was a 6% reduced risk (HR: 0.94; 95% CI: 0.90 to 0.98). However, in patients using intensive lipid-lowering treatment (n = 2,046), HDL-C was not associated with recurrent vascular events (HR: 1.02; 95% CI: 0.98 to 1.07) irrespective of low-density lipoprotein cholesterol level.

Conclusions: In patients with clinically manifest vascular disease using no or usual dose lipid-lowering medication, low plasma HDL-C levels are related to increased vascular risk, whereas in patients using intensive lipid-lowering medication, HDL-C levels are not related to vascular risk.