This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Lee, J. M.S. Articles by Choudhury, R. P. Search for Related Content PubMed PubMed Citation Articles by Lee, J. M.S. Articles by Choudhury, R. P. Related Collections Related Articles

CLINICAL RESEARCH: VASCULAR EFFECTS OF NICOTINIC ACID

Effects of High-Dose Modified-Release Nicotinic Acid on Atherosclerosis and Vascular Function

A Randomized, Placebo-Controlled, Magnetic Resonance Imaging Study

Justin M.S. Lee, MB, BCh^_*, Matthew D. Robson, PhD^_*, Ly-Mee Yu, MSc, Cheerag C. Shirodaria, MD^_*, Colin Cunnington, MBBS^_*, Ilias Kylintireas, MD^_*, Janet E. Digby, PhD^_*, Thomas Bannister, BA^_*, Ashok Handa, MB, BS, Frank Wiesmann, MD^_*, Paul N. Durrington, MD, Keith M. Channon, MD^_*, Stefan Neubauer, MD^_* and Robin P. Choudhury, DM^_*,_*

^_* Department of Cardiovascular Medicine, University of Oxford and Oxford Centre for Clinical Magnetic Resonance Research (OCMR), Oxford, United Kingdom
Centre for Statistics in Medicine, University of Oxford, Oxford, United Kingdom
Nuffield Department of Surgery, University of Oxford, Oxford, United Kingdom
Cardiovascular Research Group, University of Manchester, Manchester, United Kingdom

Manuscript received February 3, 2009; revised manuscript received May 26, 2009, accepted June 18, 2009.

^_* Reprint requests and correspondence: Dr. Robin P. Choudhury, Department of Cardiovascular Medicine, Level 6, West Wing, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom (Email: robin.choudhury{at}cardiov.ox.ac.uk).

Objectives: Our aim was to determine the effects of high-dose (2 g) nicotinic acid (NA) on progression of atherosclerosis and measures of vascular function.

Background: NA raises high-density lipoprotein cholesterol (HDL-C) and reduces low-density lipoprotein cholesterol and is widely used as an adjunct to statin therapy in patients with coronary artery disease. Although changes in plasma lipoproteins suggest potential benefit, there is limited evidence of the effects of NA on disease progression when added to contemporary statin treatment.

Methods: We performed a double-blind, randomized, placebo-controlled study of 2 g daily modified-release NA added to statin therapy in 71 patients with low HDL-C (<40 mg/dl) and either: 1) type 2 diabetes with coronary heart disease; or 2) carotid/peripheral atherosclerosis. The primary end point was the change in carotid artery wall area, quantified by magnetic resonance imaging, after 1 year.

Results: NA increased HDL-C by 23% and decreased low-density lipoprotein cholesterol by 19%. At 12 months, NA significantly reduced carotid wall area compared with placebo (adjusted treatment difference: –1.64 mm² [95% confidence interval: –3.12 to –0.16]; p = 0.03). Mean change in carotid wall area was –1.1 ± 2.6 mm² for NA versus +1.2 ± 3.0 mm² for placebo. In both the treatment and placebo groups, larger plaques were more prone to changes in size (r = 0.4, p = 0.04 for placebo, and r = –0.5, p = 0.02 for NA).

Conclusions: In statin-treated patients with low HDL-C, high-dose modified-release NA, compared with placebo, significantly reduces carotid atherosclerosis within 12 months. (Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function; NCT00232531 [ClinicalTrials.gov] )

Key Words: carotid • atherosclerosis • HDL cholesterol • magnetic resonance imaging

Abbreviations and Acronyms   CI = confidence interval   CRP = C-reactive protein   HDL-C = high-density lipoprotein cholesterol   IMT = intima-media thickness   LDL-C = low-density lipoprotein cholesterol   MRI = magnetic resonance imaging   NA = nicotinic acid

Related Articles

Assessing Niacin as an Atherosclerosis Therapeutic Agent: Valuable Insights Provided by High-Resolution Vascular Magnetic Resonance Imaging

Farouc A. Jaffer
J. Am. Coll. Cardiol. 2009 54: 1795-1796. [Full Text] [PDF]

This article has been cited by other articles:

				F. R. Joshi, A. C. Lindsay, D. R. Obaid, E. Falk, and J. H. F. Rudd Non-invasive imaging of atherosclerosis Eur Heart J Cardiovasc Imaging, January 24, 2012; (2012) jer319v1. [Abstract] [Full Text] [PDF]

				W. Hochholzer, D. D. Berg, and R. P. Giugliano The facts behind niacin Therapeutic Advances in Cardiovascular Disease, October 1, 2011; 5(5): 227 - 240. [Abstract] [PDF]

				C. M. Kramer, V. Mani, and Z. A. Fayad MR Imaging-Verified Plaque Delipidation With Lipid-Lowering Therapy: Important Questions Remain J. Am. Coll. Cardiol. Img., September 1, 2011; 4(9): 987 - 989. [Full Text] [PDF]

				A. Pitcher, D. Ashby, P. Elliott, and S. E. Petersen Cardiovascular MRI in clinical trials: expanded applications through novel surrogate endpoints Heart, August 15, 2011; 97(16): 1286 - 1292. [Abstract] [Full Text] [PDF]

				I. J. Goldberg, R. H. Eckel, and R. McPherson Triglycerides and Heart Disease: Still a Hypothesis? Arterioscler Thromb Vasc Biol, August 1, 2011; 31(8): 1716 - 1725. [Abstract] [Full Text] [PDF]

				Developed with the special contribution of: Europe, Authors/Task Force Members, Z. Reiner, A. L. Catapano, G. De Backer, I. Graham, M.-R. Taskinen, O. Wiklund, S. Agewall, E. Alegria, et al. ESC/EAS Guidelines for the management of dyslipidaemias: The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) Eur. Heart J., July 2, 2011; 32(14): 1769 - 1818. [Full Text] [PDF]

				M. J. Chapman, H. N. Ginsberg, P. Amarenco, F. Andreotti, J. Boren, A. L. Catapano, O. S. Descamps, E. Fisher, P. T. Kovanen, J. A. Kuivenhoven, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management Eur. Heart J., June 1, 2011; 32(11): 1345 - 1361. [Abstract] [Full Text] [PDF]

				J.-C. Tardif, F. Lesage, F. Harel, P. Romeo, and J. Pressacco Imaging Biomarkers in Atherosclerosis Trials Circ Cardiovasc Imaging, May 1, 2011; 4(3): 319 - 333. [Full Text] [PDF]

				S. J. Hamilton, G. T. Chew, T. M. Davis, and G. F. Watts Niacin improves small artery vasodilatory function and compliance in statin-treated type 2 diabetic patients Diabetes and Vascular Disease Research, October 1, 2010; 7(4): 296 - 299. [Abstract] [PDF]

				M. Vergeer, A. G. Holleboom, J. J. P. Kastelein, and J. A. Kuivenhoven The HDL hypothesis: does high-density lipoprotein protect from atherosclerosis? J. Lipid Res., August 1, 2010; 51(8): 2058 - 2073. [Abstract] [Full Text] [PDF]

				S. J. Nicholls, P. Lundman, and J.-C. Tardif Diabetic dyslipidemia: extending the target beyond LDL cholesterol European Journal of Cardiovascular Prevention & Rehabilitation, May 1, 2010; 17(1_suppl): s20 - s24. [Abstract] [Full Text] [PDF]

				J. Sanz, P. R. Moreno, and V. Fuster The Year in Atherothrombosis J. Am. Coll. Cardiol., April 6, 2010; 55(14): 1487 - 1498. [Full Text] [PDF]

				A. N. DeMaria, J. J. Bax, O. Ben-Yehuda, G. K. Feld, B. H. Greenberg, J. Hall, M. Hlatky, W. Y.W. Lew, J. A.C. Lima, A. S. Maisel, et al. Highlights of the Year in JACC 2009 J. Am. Coll. Cardiol., January 26, 2010; 55(4): 380 - 407. [Full Text] [PDF]

				F. A. Jaffer Assessing Niacin as an Atherosclerosis Therapeutic Agent: Valuable Insights Provided by High-Resolution Vascular Magnetic Resonance Imaging J. Am. Coll. Cardiol., November 3, 2009; 54(19): 1795 - 1796. [Full Text] [PDF]