The Current State of Niacin in Cardiovascular Disease Prevention A Systematic Review and Meta-Regression
ABSTRACT OBJECTIVES: This study sought to assess the efficacy of niacin for reducing cardiovascular disease (CVD) events, as indicated by the aggregate body of clinical trial evidence including data from the recently published AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial. BACKGROUND: Previously available randomized clinical trial data assessing the clinical efficacy of niacin has been challenged by results from AIM-HIGH, which failed to demonstrate a reduction in CVD event incidence in patients with established CVD treated with niacin as an adjunct to intensive simvastatin therapy. METHODS: Clinical trials of niacin, alone or combined with other lipid-altering therapy, were identified via MEDLINE. Odds ratios (ORs) for CVD endpoints were calculated with a random-effects meta-analyses. Meta-regression modeled the relationship of differences in on-treatment high-density lipoprotein cholesterol with the magnitude of effect of niacin on CVD events. RESULTS: Eleven eligible trials including 9,959 subjects were identified. Niacin use was associated with a significant reduction in the composite endpoints of any CVD event (OR: 0.66; 95% confidence interval: 0.49 to 0.89; p = 0.007) and major coronary heart disease event (OR: 0.75; 95% confidence interval: 0.59 to 0.96; p = 0.02). No significant association was observed between niacin therapy and stroke incidence (OR: 0.88; 95% confidence interval: 0.5 to 1.54; p = 0.65). The magnitude of on-treatment high-density lipoprotein cholesterol difference between treatment arms was not significantly associated with the magnitude of the effect of niacin on outcomes. CONCLUSIONS: The consensus perspective derived from available clinical data supports that niacin reduces CVD events and, further, that this may occur through a mechanism not reflected by changes in high-density lipoprotein cholesterol concentration.
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- ". These changes were associated with reductions in risk of major coronary events by 25% and 20%, respectively, with fibrates and niacin. A more recent meta-analysis of the niacin trials suggested overall benefit from the drug, but the benefit did not correlate with magnitude of change in HDL-C . A meta-analysis of 4 prospective randomized statin IVUS trials revealed that increases in HDL-C independently predicted atheroma regression . "
ABSTRACT: The first observations linking a low serum level of HDL-C to increased risk for cardiovascular disease were made over 50 years ago. High serum levels of HDL-C appear to protect against the development of atherosclerotic disease, while low serum levels of this lipoprotein are among the most important predictors of atherosclerotic disease in both men and women and people of all racial and ethnic groups throughout the world. It has long been assumed that therapeutic interventions targeted at raising HDL-C levels would lower risk for such cardiovascular events as myocardial infarction, ischemic stroke, and death. Even after five decades of intensive investigation, evidence to support this assumption has been fleeting. A number of post hoc analyses of randomized controlled trials and meta-analyses suggest that HDL-C raising, particularly when coupled with aggressive LDL-C reduction, impacts risk for cardiovascular events and rates of progression of atherosclerotic disease. Unfortunately, four recent prospective trials performed with the intent of testing the "HDL hypothesis" (ILLUMINATE, dal-OUTCOMES, AIM-HIGH, and HPS2-THRIVE) failed to meet their primary composite endpoints. These results have lead many clinicians and investigators to question the validity of the assumption that HDL-C raising reduces risk for cardiovascular events. Additional trials with other drugs are underway. In the meantime, HDL-C cannot be considered a target of therapy. Given the complexity of the HDL proteome and lipidome, there is biological plausibility for how HDL particles might exert atheroprotection. We explore the evidence supporting the inverse relationship between HDL-C and cardiovascular disease risk, documented mechanisms by which HDL particles may exert atheroprotection, and the findings either supporting or negating specific therapeutic interventions in patients afflicted with low HDL-C.Best Practice & Research: Clinical Endocrinology & Metabolism 06/2014; 28(3):353-368. DOI:10.1016/j.beem.2013.11.002 · 4.91 Impact Factor
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- "As is well known, niacin has long been employed in the treatment of patients at risk for vascular disease. A recent metaanalysisdadmittedly conducted before release of the HPS2- THRIVE (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 factorsdincluding low-density lipoprotein cholesterol (LDL-C) reductiondmay have been primarily responsible for the observed benefit . 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 . "
ABSTRACT: Increased fasting serum phosphate within the normal physiological range has been linked to increased cardiovascular risk in prospective epidemiology; increased production of fibroblast growth factor 23 (FGF23), and direct vascular effects of phosphate, may mediate this risk. Although dietary phosphate intake does not clearly influence fasting serum phosphate in those with normal renal function, increased phosphate intake can provoke an increase in FGF23, and in diurnal phosphate levels, and hence may adversely influence vascular health. Dietary phosphate absorption can be moderated by emphasizing plant-based dietary choices (which provide phosphate in less-bioavailable forms), avoidance of processed foods containing inorganic phosphate food additives, and by ingestion of phosphate-binder drugs, magnesium supplements, or niacin, which precipitate phosphate or suppress its gastrointestinal absorption. The propensity of dietary phosphate to promote vascular calcification may be opposed by optimal intakes of magnesium, vitamin K, and vitamin D; the latter should also counter the tendency of phosphate to elevate parathyroid hormone.Nutrition 01/2013; 30(7-8). DOI:10.1016/j.nut.2013.12.010 · 3.05 Impact Factor
- Anesthesiology 12/2012; 117(6):1159-61. DOI:10.1097/ALN.0b013e318272d8ac · 6.17 Impact Factor