Niacin in cardiovascular disease: recent preclinical and clinical developments.

Digby JE, Ruparelia N, Choudhury RP.
Arterioscler Thromb Vasc Biol. 2012;32:582-8.

Background

This publication gives a re-appraisal of the use of niacin in clinical practice, based on its mechanism of action and nonlipoprotein mediated actions.

Summary

Niacin (nicotinic acid) has been used for more than 50 years to treat cardiovascular disease [1]. Niacin increases HDL-C [2] and reduces LDL-C [3], VLDL-C and lipoprotein(a) [2]. Although it is an effective therapy in raising HDL-C, the side effect of cutaneous flushing has limited its use [4]. As with treating dyslipdemias with statins a significant CV risk remains [5-7], HDL-C elevation is a rational target for lipid intervention. HDL-raising CETP inhibitors are currently evaluated in Phase III trials; niacin is still the most effective available drug. The beneficial effects may go beyond lipoprotein modulation, with direct effects on endothelial cells, immune cells, and adipocytes, which could potentially change the indications for the use of niacin. New agents may in the future be able to show pleiotropic anti-inflammatory effects without the side effects that limited the use of niacin.

Conclusion

Niacin has pleiotropic lipoprotein independent actions that might be beneficial, by anti-inflammatory effects on cell types involved in the progression of atherosclerosis. These actions might contribute to the clinical benefits of niacin treatment.

References

1. Altschul R, Hoffer A, Stephen JD. Influence of nicotinic acid on serum cholesterol in man. Arch Biochem Biophys. 1955;54:558–559
2. Carlson LA, Hamsten A, Asplund A. Pronounced lowering of serum levels of lipoprotein lp(a) in hyperlipidaemic subjects treated with nicotinic acid. J Intern Med. 1989;226:271–276.
3. Superko HR, McGovern ME, et al. Differential effect of two nicotinic acid preparations on low-density lipoprotein subclass distribution in patients classified as low-density lipoprotein pattern a, b, or i. Am J Cardiol. 2004;94:588–594.
4. Kamal-Bahl SWD, Kramer B, Markson LE. Flushing experience and discontinuation with niacin in clinical practice. J Am Coll Cardiol. 2007;49:273A.
5. LaRosa JC, Grundy SM, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425–1435.
6. Barter P, Gotto AM, et al. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301–1310.
7. Pedersen TR, Faergeman O, et al. High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial. JAMA. 2005;294:2437–2445.

Abstract

Niacin has been used for more than 50 years in the treatment of cardiovascular disease, although its use has largely been superseded by better-tolerated lipid-modulating interventions. There has been a renewed interest in the HDL-cholesterol raising properties of niacin, with the appreciation that substantial cardiovascular risk remains despite effective treatment of LDL-cholesterol. This coincides with increasing evidence that the complex functional properties of HDL are not well reflected by measurement of HDL-cholesterol alone. In addition to favorable actions on lipoproteins, it is becoming apparent that niacin may also possess lipoprotein independent or pleiotropic effects including the inhibition of inflammatory pathways mediated by its receptor GPR109A, which is expressed by adipocytes and some leukocytes. In this article we consider emerging and prior clinical trial data relating to niacin. We review recent data in respect of mechanisms of action on lipoproteins, which remain complex and incompletely understood. We discuss the recent reports of anti-inflammatory effects of niacin in adipocytes and through bone marrow derived cells and vascular endothelium. These novel observations come at an interesting time, with current imaging and outcome studies leaving outstanding questions on niacin efficacy in statin-treated patients.