Abstract 439: Niacin Does Not Accelerate Reverse Cholesterol Transport in Man

Abstract

Background HDL may be atheroprotective by accelerating reverse cholesterol transport (RCT). Niacin raises HDL cholesterol (HDL-c) and niacin monotherapy up to 3g/d prevented coronary events, possibly by accelerating RCT. However, up to 2g/d niacin did not prevent outcomes beyond aggressive LDL lowering including statins, arguing against RCT-mediated atheroprotection. We developed a novel method to assess macrophage-to-lipoprotein RCT in vivo. Preliminary studies in mice demonstrate that albumin-bound tritiated cholesterol (3H-Chol) is rapidly removed ( 95% in 30min) by resident macrophages. We monitored subsequent reappearance over 8d by macrophage-to-lipoprotein RCT as 3H-Chol rate of appearance (RA pre-post therapy, %3H-Chol injected/mol cholesterol/h) and tracer fecal excretion (%3H-Chol injected/g feces), and further analyzed RCT by multi-compartmental modeling. Results Niacin raised HDL-c 44% vs 17% on placebo (p=0.02) and dropped non HDL-c 40% (p<0.0001). Niacin and placebo did not differ by HDL 3H-Chol RA (placebo: 4.16-3.72, niacin: 3.24-2.61, p=0.8), total plasma 3H-Chol RA (placebo: 2.70-2.42, niacin: 2.35-2.14, p=0.9), macrophage-to-HDL transfer rate (placebo: 4.8-4.2, niacin: 5.1-4.7 fractional transfer/h, p=0.7), ex vivo cholesterol efflux capacity ratio (placebo: 0.73-0.82, niacin: 0.91-0.95, p=0.2), or tracer fecal excretion (placebo: 34.1-37.4, niacin: 21.2-28.0, p=0.6). Conclusion Despite potently raising HDL-c, high-dose niacin had no benefit on in vivo or ex vivo macrophage-to-lipoprotein RCT or fecal excretion in man, suggesting niacin’s atheroprotective potential lies elsewhere.