As is well known, niacin has long been employed in the treatment of patients at risk for vascular disease. A recent meta analysisdadmittedly conducted before release of the HPS2THRIVE (Heart Protection Study-2 Treatment of HDL to Reduce the Incidence of Vascular Events) trialdhas concluded that niacin therapy reduces risk for cardiovascular events by about one-third; intriguingly, this protection was found to be independent of the extent to which high density lipoprotein cholesterol (HDL-C) was decreased, suggesting that other fac- torsdincluding low-density lipoprotein cholesterol (LDL-C) reductiondmay have been primarily responsible for the observed benefit [186]. Indeed, a Mendelian randomization analysis concludes that elevation of plasma HDL-C per se does not reduce risk for myocardial infarction ; moreover, a recent meta-regression analysis has found that the extent to which lipid-modifying agents increase HDL-C is not pertinent to their ability to decrease CVD and mortality [188]. In light of these findings, and the fact that niacin 's effect on LDL-C is modest relative to statins, it is reasonable to postulate that niacin 's ability to inhibit dietary phosphate absorption may contribute quite meaningfully to its protective utility. Perhaps further epidemio logic analysis, assessing the expected effect of LDL reduction on niacin 's clinical efficacy, could clarify whether this is a credible possibility. It should be noted, however, that direct antiinflammatory effects of niacin on vascular endothelial cells have been reported, in part reflecting nrf2-mediated induction of heme oxygenase-1; such effects could evidently also contribute to niacin 's utility in CVD .