Effects of Niacin on LDL Particle Number

Haseeb Jafri; Richard H Karas; Jeffrey T Kuvin

Disclosures

Clin Lipidology. 2009;4(5):565-571. 

In This Article

Niacin & LDL-P

The ability of niacin to influence LDL-P is under active investigation and it appears that the beneficial effects of niacin extend beyond the traditional evaluation of the 'lipid profile.'

McKenney et al. compared the effect of once-daily low-dose atorvastatin with niacin (1 g three times daily) on LDL-P in patients with atherogenic dyslipidemia, defined by elevated triglycerides, reduced HDL-C and elevated small LDL-P.[15] This was a multicenter, randomized, open-label parallel-design study. Treatment with either atorvastatin or niacin followed a 6-week lead-in period on a National Cholesterol Education Program (NCEP) step-one diet. The study enrolled 108 patients with total cholesterol values greater than 200 mg/dl, triglyceride levels 200–800 mg/dl, and ApoB levels greater than 110 mg/dl. During the 12-week study period, on average, both niacin and atorvastatin significantly decreased the number of small LDL-P (35.1 and 44.3%, respectively; p < 0.05 for both). Immediate-release niacin increased large LDL-P by 74% (p < 0.05), while atorvastatin had little effect on large LDL-P, with a nonsignificant decrease of 9.8%. It is unclear from this brief study, however, the ramifications of these alterations in LDL-P.

Superko et al. studied the effect of the immediate-release and extended-release formulations of niacin on LDL-P compared with placebo.[16] They recruited 180 men and women, aged 21–75 years, with a history of CAD or greater than two CAD risk factors and LDL-C levels of 160–190 mg/dl, or no history of CAD and LDL-C of greater than 190 mg/dl. All subjects underwent 6 weeks of a NCEP step-one diet, followed by randomization to placebo (n = 61), immediate-release niacin (3 g/day; n = 59) or ERN (1.5 g/day; n = 60) for a total of 14 weeks. LDL subparticles were defined as LDL I through LDL IVb, with LDL I being the largest of the LDL-p and LDL IVb the smallest. When compared with placebo, both ERN and immediate-release niacin influenced LDL-P. Therapy with ERN resulted in a nonsignificant 10% increase (p = 0.12) for the larger LDL I particles, whereas immediate-release niacin resulted in a significant increase of 24% (p < 0.0002). ERN therapy resulted in a significant 10% decrease (p < 0.02) for the smaller LDL IVb particles and therapy with immediate-release niacin resulted in a significant 12% decrease (p < 0.01). Of note, total LDL-P is not reported in this study. Interestingly, when these data are compared with those from the previous study by McKenney et al., immediate-release niacin significantly decreases small LDL-P, but with a potentially off-setting significant increase in large LDL-P. However, when examining ERN, there is only a significant decrease in small LDL-P, with no change in large LDL-P.[16]

Further examining ERN's effect on LDL-P, Morgan et al. compared ERN at 1 and 2 g/day with placebo (n = 21, 20 and 19, respectively[17]). This study was a multicenter, double-blinded, placebo-controlled trial where patients with CAD or greater than two CAD risk factors and an LDL-C level of 160–190 mg/dl or with LDL level greater than 190 mg/dl, were randomized to ERN 1 g/day, ERN 2 g/day or placebo for a total of 12 weeks. Patients who were randomized to ERN 1g/day and 2 g/day both had nonsignificant decreases in small LDL-P and nonsignificant increases in large LDL-P when compared with placebo. However, there was a significant 15 and 23% decrease in total LDL-P in the ERN 1 g/day and 2 g/day groups, respectively (p = 0.002 for both groups).[17]

Finally, our group has shown that the addition of ERN to existing statin therapy has favorable effects on LDL-P in patients with established CAD and well-controlled LDL-C levels (< 100 mg/dl) at baseline.[18] We enrolled 54 patients with a history of CAD into a randomized, placebo-controlled trial of ERN 1 g or active placebo added to the patient's baseline lipid-lowering therapy, over a 3-month period. At the end of the study, there was no significant change in total, large or small LDL-P in those randomized to placebo. However, those receiving ERN had a 9% decrease in total LDL-P and a 14% decrease in small LDL-P when compared from baseline to follow-up (p < 0.05 for both). Additionally, when compared with placebo at follow-up, there were 18% fewer total LDL-P in patients randomized to ERN, and 26% fewer small LDL-P in patients randomized to ERN (p < 0.05 for both). Of note, there was no significant change in large LDL-P from baseline to follow-up for patients who received ERN, or in comparison to placebo at follow-up. In light of the previously published data, this study adds further evidence that ERN favorably alters LDL-P.[18]

Taken together, these data support that ERN may have cardiovascular benefits that extend beyond the routine lipid profile. However, the trials to date have been too small and too short to suggest a definitive influence of ERN on LDL-P-mediated improvements in cardiovascular disease. Furthermore, there were no clinical events reported in any of these lipid-end point studies.[15–18]

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