Abstract:Objective: test if (niacin-ER) increases apoA-I-containing HDL-C, andimproves vascular function in SCD.
Method and materials: during 12 weeks a randomized, double-blinded,placebo-controlled trial were done in 27 SCD patients with HDL-C. Thepatients were divided to two groups one treated with Niacin-ER and otherstreated with placebo. Result: after12 weeks, we noticed change in HDL-C level in Niacin-ER-treated patients compared with placebo treated at (5.1±7.7vs. 0.9±3.
8 mg/dL, one-tailed p=0.07), with improvements in the ratio oflow-density lipoprotein to HDL-C (1.24 vs. 1.95, p = 0.003), and apolipoproteinB to apoA-I (0.46 vs. 0.
58, p = 0.03) . Conclusion:we concluded that there was increasing in HDL-C and change in low-densitylipoprotein to HDL-C ratio. For, endothelium function there is no change. Introduction:Sickle celldisease patients have apparently decreased HDL-C and apoA-1 and those withlow levels of apoA-1 have damaged vasodilatory responses toacetylcholine during (FBF) plus an echocardiographic marker of pulmonaryhypertension. For low levels of HDL-C and apoA-I we use Niacin-ER astreatment to inhibits the degradation and hepatic clearance ofapoA-I-containing HDL-C, inhibits cholesterol ester transmission to low densitylipoprotein (LDL) cholesterol, and also inhibits the effects of hepatic lipase.In this study we want to know Niacin-ER effect on HDL-C and apoA-I in SCDpatients and vascular function using a randomized, double-blinded,placebo-controlled trial.
Method:We use aprospective, single-center, randomized, double-blinded trial comparingniacin-ER with placebo. Males or females 18 – 65 years of age recruitedand they have all of the certain criteria for example if the subject hadaspirin or NSAIDs within 1 week before vascular testing, or used caffeinethe day of vascular testing the subject were the subject will be excepted.Simple randomization was used to allow subjects to either 12 weeks of placeboor niacin-ER and they were eliminated if they had some clinical injuries. We measurevascular and/or endothelial function, forearm blood flow (FBF), flow-mediateddilation (FMD) of the brachial artery, and peripheral arterial tonometry wereaccomplished at baseline and after 12 weeks of treatment. Laboratoryevaluations were accomplished in the Clinical Center Department of LaboratoryMedicine at the National Institutes of Health by standard clinical laboratoryassays, containing standard complete blood counts with hemoglobin F levels,iron-binding studies, serum , lipid panels, amino terminal brain natriureticpeptide, homocysteine, and C-reactive protein. The primary result was thecomplete change in HDL-C after niacin-ER treatment, i.
e. post-treatment (week12) HDL-C minus pre-treatment (week 0) HDL-C. Result:305patients was included and 278 was excluded due to several reasons mentioned before.27adults with SCD were randomized to receive either placebo or niacin-ER dailyfor 12 weeks: 12 subjects received niacin-ER, and 15 received placebo.
2in the niacin-ER treatment group and 1 in the placebo treatment group did notfulfill the agenda. After 12 weeks, all niacin-ER-treated subjects had an risein HDL-C from baseline, mean is 5.1 ± 7.7 mg/dL and non-significantalteration in HDL-C for placebo, mean is 0.9 ± 3.
8 (Figure A). Figure B Figure A The LDL-Cto HDL-C rate reduced by niacin-ER treatment, placebo mean is 1.95 vs.niacin-ER mean is 1.24, although neither LDL-C nor HDL-C absolute changedin the niacin-ER-treatment group.
The ratio of serum apolipoprotein B to apoA-Idecreased, placebo mean is 0.58 vs. niacin-ER mean is 0.45.
For endothelialfunction, no change following niacin-ER treatment appeared. Discussion: In subjectswith the metabolic syndrome, Vaccari et al., Westphal et al., and Thoenes et alshowed elevation in HDL-C ,but Westphal et al. failed to show identifying improvements in flow mediated dilation, while Vaccariet al. and Thoenes et al.
treated subjects with niacin for 52 weeks. Insubjects with coronary artery disease already on statin therapy, Kuvin etal. showed a considerable increase in HDL-C and corresponding improvement inFMD, while Andrews et al.
were incapable to show elevated FMD for elevatingtheir subjects’ HDL-C by >25%. Other published studies in dyslipidemicpatients without SCD suggested a beneficial action of niacin 1500mg daily inboth lipid levels and endothelial function. Instead of patients with SCD may berelatively resistant to HDL-C elevation correlating with niacin administrationto other patient populations. A change in liver function will exhibit sideeffect of niacin medication. One subject was excepted from theniacin-ER-treatment group because of such liver enzyme elevations. Thehepatocellular injury side effects of niacin probable explain the slight risein alanine and aspartate aminotransferases, as well as lactate dehydrogenase, inthe niacin-ER treatment group, but these results did not otherwise reachabnormal levels. In blood flow, the expected changes in endothelial functionwere not detected, presumably because the small HDL-C/apoA-I response toniacin-ER was inadequate to improve endothelial function. Patients takinghydroxyurea, a drug known to reduce hospitalizations for vaso-occlusive crises,were not excepted from this study, but there was no marker that this designaffected the consequence of the study.
However, there were unexpectedly fewerhospitalizations for vaso-occlusive crises and small transfusions in theniacin-ER group than in the placebo group, but this was not statisticallyimportant.