The Addition of Niacin to Statin Therapy Improves High-Density Lipoprotein Cholesterol Levels but Not Metrics of Functionality

Study Questions:

Is there a reason why niacin, which raises the high-density lipoprotein cholesterol particle content (HDL-C), fails to improve outcomes when added to standard statin treatment?


The authors conducted a study designed to assess the impact of niacin added to statin therapy on HDL-C levels, cholesterol efflux capacity, and the HDL inflammatory index. Subjects were 39 patients with carotid atherosclerosis randomized to simvastatin 20 mg daily plus either placebo or extended-release niacin, titrated up to 2 g daily. HDL-C levels and functional parameters were assessed at baseline and after 6 months of therapy.


The mean age was 71 years and 64% were male, 23% had coronary artery disease, and 67% were taking a statin at baseline. Average cholesterol was 185 mg/dl, HDL-C was 46 mg/dl, and low-density lipoprotein cholesterol was 116 mg/dl. Mean normalized cholesterol efflux capacity was 0.95, and average HDL inflammatory index value was 1.15. Bivariate correlation analysis demonstrated a moderate association (r = 0.56; p = 0.002) between HDL-C and cholesterol efflux capacity, but no association between HDL inflammatory index and HDL-C. Niacin led to an increase in average HDL-C from 46 to 57 mg/dl (p = 0.001) compared to baseline and placebo, but no change was noted in either cholesterol efflux capacity or HDL inflammatory index.


The addition of niacin to statin therapy led to favorable changes in patients’ lipid profiles without a demonstrable effect on HDL functionality, thus providing one potential mechanistic hypothesis for the disappointing results in recent clinical trials.


The failure of niacin to reduce carotid plaque and coronary events and the recent failure of two novel cholesterol ester transfer protein inhibitors to reduce events despite a very large increment in HDL-C strongly supports a conclusion that it is not the HDL particle cholesterol content, but its functional characteristics that predict benefits. It is likely that the functionality of HDL particles will eventually become part of coronary risk assessment.

Clinical Topics: Dyslipidemia, Vascular Medicine, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Nonstatins, Novel Agents, Statins

Keywords: Pyrrolidinones, Coronary Artery Disease, Cholesterol Ester Transfer Proteins, Plaque, Atherosclerotic, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Vascular Diseases, Hypolipidemic Agents, Carotid Artery Diseases, Risk Assessment

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