Background. Many women remain at risk for cardiac events despite treatment to reduce low-density lipoprotein cholesterol (LDL-C). We hypothesized that for postmenopausal women treated with niacin in addition to statin vascular function will improve. Methods. We conducted a randomized, double-blind, placebo-controlled trial of 16 weeks of niacin (N) versus placebo (PL) in 43 women (mean age, years) previously on statin therapy. Study outcomes included lipoprotein levels, vascular inflammation assessed by high sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and endothelial function, assessed as brachial artery flow mediated dilation (FMD). Results. The N group significantly increased HDL-C and decreased LDL-C cholesterol relative to PL (both ). FMD improved in both groups ( ) irrespective of niacin ( ). Age influenced change in FMD ( ) such that improved FMD (before to after) with lipid lowering therapy was greater with older age ( Pearson correlation = 0.34), independent of treatment group. Conclusions. Lipid lowering therapy with combination of niacin and statin does not improve inflammation or endothelial function compared to statin alone. However, older women demonstrate relatively greater endothelial benefit of lipid lowering therapy over 4 months. This trial is registered with Clinicaltrials.gov NCT00590629. 1. Introduction Cardiovascular disease (CVD) remains the most common cause of death in women, yet our current fund of CVD knowledge in women is relatively limited [1]. While total cholesterol and LDL-C cholesterol (LDL-C) have the same risk potency for CVD among women and men, women face a relatively higher risk associated with elevated triglycerides, compared to men [2–5]. Lipid modification, primarily in the form of LDL-C lowering, has been demonstrated to result in significant 30% reduction in cardiac events [6, 7], although possibly with relatively less benefit in women [8]. A majority of women and men remain at risk for cardiac events despite LDL-C lowering, indicating that additional opportunities for risk reduction exist. Recent evidence suggests that additional lipid fractions, specifically high levels of small dense LDL-C, triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), and low HDL-C identify a group at risk for progression of atherosclerosis and future cardiac events [9–12]. The Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Cholesterol Intervention Trial (VA-HIT) demonstrated that HDL-C elevation via the use of gemfibrozil resulted in a significant
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