Niacin for Reduction of Cardiovascular Risk

Landray, Martin J; Haynes, Richard; Armitage, Jane

doi:10.1056/nejmc1411240

Cited by 5 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… Association between the baseline plasma LDL-C level and the percentage change in LDL-C with ER niacin/laropiprant in the primary study (modified and reprinted with permission 18 ) (A) and ER niacin in the replication study (B) in univariate analysis. …”

Section: Resultsmentioning

confidence: 99%

“…It has been proposed that the failure of the 2 large outcome studies with ER niacin may be related to the changes in structural and functional complexity of HDL particles not adequately captured by changes in total HDL-C concentration 45 in groups of patients with very low baseline level of LDL-C, which as discussed above can predict a poor LDL-C response to niacin. 18 …”

Section: Discussionmentioning

confidence: 99%

“…Patients had to be naïve to all lipid-lowering therapy or taking a stable dose of lipid-modifying therapy for at least 4 weeks for statins and ezetimibe or 6 weeks for fibrates. 17 , 18 Lipid profiles and laboratory safety tests were measured before starting the treatment (week 0), after 4 weeks treatment with ER niacin/laropiprant 1000/20 mg (week 4), and after 4 and 8 weeks treatment with ER niacin/laropiprant 2000/40 mg (week 8 and week 12). Anthropometric measurements, including body weight, body height, waist circumference, hip circumference, and percentage of total body fat using an impedance device (TANITA Body Composition Analyzer BF-350, TANITA Corporation, Tokyo, Japan) were obtained at each study visit.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

Yang

et al. 2015

Medicine

View full text Add to dashboard Cite

The acyl-CoA:diacylglycerol acyltransferase (DGAT) enzymes DGAT1 and DGAT2 catalyze the final step in triglycerides biosynthesis. This study examined the relationships of baseline phenotypes and the common polymorphisms in DGAT1 and DGAT2 with the lipid responses to niacin.Lipid responses in Chinese patients with dyslipidemia treated with the extended release (ER) niacin/laropiprant combination 1000/20 mg for 4 weeks and then 2000/40 mg for 8 weeks (n = 121, the primary study) or with ER niacin 1500 mg for at least 4 weeks (n = 68, the replication study) were analyzed according to genotypes of DGAT1 rs7003945 T>C and DGAT2 rs3060 T>C polymorphisms.Treatment with ER niacin improved all lipid parameters in both studies. Absolute and percentage changes in lipids were related to their baseline levels, particularly for low-density lipoprotein cholesterol (LDL-C). The DGAT2 rs3060 T>C polymorphism was associated with lower baseline LDL-C, apoB, high-density lipoprotein cholesterol (HDL-C), and apoAI in patients on statin therapy in the primary study. Subjects with the DGAT2 rs3060 T>C variant had less reduction in LDL-C in the primary study and smaller changes in triglyceride and HDL-C in the replication study but these associations became non-significant after adjusting for baseline lipid values. The DGAT1 rs7003945 T>C polymorphism was not related to lipid baseline values or changes in either study. Concomitant statin therapy and lower body weight were also associated with greater reduction in LDL-C.Baseline lipid levels were the main determinants of lipid responses especially for LDL-C. The DGAT2 rs3060 polymorphism might influence the lipid responses depending on baseline phenotype, but this association did not persist after adjustment for the baseline lipid levels.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

Yang

et al. 2015

Medicine

View full text Add to dashboard Cite

show abstract

“…Looking at the entry lipid values (see above), one could question whether there was a need for any additional treatment of these patients. Moreover, the design used in the study “could lead to more drug interactions and, therefore, more side-effects in the group receiving multiple drugs” [ 29 ].…”

Section: Hps2-thrive Studymentioning

confidence: 99%

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

et al. 2015

View full text Add to dashboard Cite

Niacin is considered to be a powerful drug for the treatment of lipid and lipoprotein abnormalities connected with “residual cardiovascular risk”, which persist in high-risk patients even when the target goals of LDL-C are achieved with statin therapy. Recent large randomized clinical studies – AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides) and HPS2-THRIVE (Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of Vascular Events) – delivered some disappointing results, leading to the conclusion that no further benefit (decreased parameters of cardiovascular risk) is achieved by adding niacin to existing statin therapy in patients with high cardiovascular risk. Moreover, in these studies, several adverse effects of the treatment were observed; therefore, niacin treatment for hypolipidemias is not recommended. In this paper, we analyze the mechanisms underlying the hypolipidemic and antiatherogenic effects of niacin as well as some limitations of the designs of the AIM HIGH and HP2-THRIVE studies. We also provide the possibilities of rational usage of niacin for specific types of dyslipidemias.

show abstract

“…Statins raise HDLC only modestly and it is not clear whether that effect plays a role in the success of statins in CVD reduction. Niacin increases HDLC significantly, but two recent studies where niacin was added to statin treatment did not reduce CVD 3,4 . Fibrates increase HDLC moderately, depending on baseline triglycerides, but studies of fibrates and CVD reduction have produced mixed results 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling

Liu

Hernandez‐Ono

Graham

et al. 2016

ATVB

View full text Add to dashboard Cite

Objective Plasma levels of high density lipoprotein cholesterol (HDLC) and apolipoprotein A-I (ApoA-I) are reduced in individuals with defective insulin signaling. Initial studies using liver-specific insulin receptor (InsR) knockout mice (LIRKO) identified reduced expression of Type 1 Deiodinase (Dio1) as a potentially novel link between defective hepatic insulin signaling and reduced expression of the ApoA-I gene. Our objective was to examine the regulation of ApoA-I expression by Dio1. Approach and Results Acute inactivation of InsR by adenoviral delivery of Cre recombinase to InsR floxed mice reduced HDLC and expression of both ApoA-I and Dio1. Overexpression of Dio1 in LIRKO restored HDLC and ApoA-I levels and increased the expression of ApoA-I. Dio1 knockout (D1KO) mice had very low expression of ApoA-I and reduced serum levels of HDLC and ApoA-I. Treatment of C57BL/6J mice with anti-sense to Dio1 reduced ApoA-I mRNA, HDLC, and serum ApoA-I. Hepatic 3,5,3′-triiodothyronine (T3) content was normal or elevated in LIRKO or D1KO mice. Knockdown of either InsR or Dio1 by siRNA in HepG2 cells decreased expression of ApoA-I as well as ApoA-I synthesis and secretion. siRNA knockdown of InsR or Dio1 decreased activity of a region of the ApoA-I promoter lacking thyroid hormone response elements (TREs) (Region B). Electrophoretic mobility shift assay demonstrated that reduced Dio1 expression decreased the binding of nuclear proteins to Region B. Conclusions Reductions in Dio1 expression reduce expression of ApoA-I in a T3/TRE independent manner.

show abstract

Niacin for Reduction of Cardiovascular Risk

Cited by 5 publications

References 23 publications

Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

Effects of Phenotypic and Genotypic Factors on the Lipid Responses to Niacin in Chinese Patients With Dyslipidemia

Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place?

Type 1 Deiodinase Regulates ApoA-I Gene Expression and ApoA-I Synthesis Independent of Thyroid Hormone Signaling

Contact Info

Product

Resources

About