Abstract 16318: Niacin Dramatically Raises the Endothelial Inflammatory Marker Lp-PLA2: The Reason the AIM-HIGH Trail Failed Despite Improvements in HDL and Triglycerides
The recent cancellation of the AIM-HIGH Niaspan/Simvastatin trial, despite increased HDL levels and decreased Triglyceride levels, throws into question the entire paradigm of HDL elevation in preventing heart disease. On the other hand, an alternative explanation of the null results of the trial is that Niacin caused a problem that negated the otherwise beneficial effect of HDL elevation. We believe we have discovered that reason, as a result of serial examinations of the endothelial inflammatory marker LpPLA2 (Lipoprotein-associated Phospholipase A2 in a patient population with CAD started on extended release niacin.
986 pts, aged 38-92, M:F ratio 1:1 with either documented CAD, or risk factors for CAD, Lp(a), hypercholesterolemia with low HDL, were started on dietary intervention (a limited grain, Mediterranean type diet) coupled with 500-1,500mg slow release Niacin. As part of a comprehensive lipid panel, (BerkeleyHeartLabs, Alameda, CA) LpPLA2 levels were measured at baseline and every 3 months; pts have been followed for 1-8 years, mean 6+/−2 yrs. As reported elsewhere, if LpPLA2 levels rose above 200 ng/ml, pts were started on Fish Oil, Spirolina, Grape Seed Extract and Pycnogenol.
LpPLA2 levels increased in all pts begun on a Niacin regimen. Baseline levels of 167+/−50 ng/ml increased to 212+/−43ng/ml (p<0.001). Mean individual increase was 62+/−30ng/ml. Sixty-five % of pts started on Niacin, had LpPLA2 levels increase above the normal upper level of 200ng/ml. There was no corresponding increase in hs-CRP or fibrinogen levels. The addition of Fish Oil, Spirolina, Grape Seed Extract and Pycnogenol reduced LpPLA2 levels but did not return them to baseline.
We conclude that extended release Niacin dramatically increases the endothelial inflammatory molecule Lp-PLA2, which attracts oxidized LDL into endothelial cells. This finding probably explains why despite elevated HDL's in the AIM-HIGH trial, no favorable results were obtained. We strongly recommend that pts on Niacin should have Lp-PLA2 levels checked and if elevated, started on Fish Oil, Spirolina, Grape Seed Extract, and Pycnogenol.
- © 2011 by American Heart Association, Inc.