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Genetic Variants Associated With Plasma Lipids Are Associated With the Lipid Response to Niacin.
Tuteja, S, Qu, L, Vujkovic, M, Dunbar, RL, Chen, J, DerOhannessian, S, Rader, DJ
Journal of the American Heart Association. 2018;(19):e03488
Abstract
Background Niacin is a broad-spectrum lipid-modulating drug, but its mechanism of action is unclear. Genome-wide association studies have identified multiple loci associated with blood lipid levels and lipoprotein (a). It is unknown whether these loci modulate response to niacin. Methods and Results Using data from the AIM - HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL /High Triglycerides and Impact on Global Health Outcomes) trial (n=2054 genotyped participants), we determined whether genetic variations at validated loci were associated with a differential change in plasma lipids and lipoprotein (a) 1 year after randomization to either statin+placebo or statin+niacin in a variant-treatment interaction model. Nominally significant interactions ( P<0.05) were found for genetic variants in MVK , LIPC , PABPC 4, AMPD 3 with change in high-density lipoprotein cholesterol; SPTLC 3 with change in low-density lipoprotein cholesterol; TOM 1 with change in total cholesterol; PDXDC 1 and CYP 26A1 with change in triglycerides; and none for lipoprotein (a). We also investigated whether these loci were associated with cardiovascular events. The risk of coronary disease related death was higher in the minor allele carriers at the LIPC locus in the placebo group (odds ratio 2.08, 95% confidence interval 1.11-3.90, P=0.02) but not observed in the niacin group (odds ratio 0.89, 95% confidence interval 0.48-1.65, P=0.7); P-interaction =0.02. There was a greater risk for acute coronary syndrome (odds ratio 1.85, 95% confidence interval 1.16-2.77, P=0.02) and revascularization events (odds ratio 1.64, 95% confidence interval 1.2-2.22, P=0.002) in major allele carriers at the CYP 26A1 locus in the placebo group not seen in the niacin group. Conclusions Genetic variation at loci previously associated with steady-state lipid levels displays evidence for lipid response to niacin treatment. Clinical Trials Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00120289.
2.
Effect of Statin Therapy on Fibrous Cap Thickness in Coronary Plaques Using Optical Coherence Tomography: A Systematic Review and Meta-Analysis.
Zheng, G, Chen, J, Lin, C, Huang, X, Lin, J
Journal of interventional cardiology. 2015;(6):514-22
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Abstract
OBJECTIVES We conducted a systematic review and meta-analysis to evaluate the effect of statin therapy on coronary fibrous cap thickness (FCT) as assessed by optical coherence tomography (OCT) and the relationship between FCT and traditional coronary risk factors. BACKGROUND Increasing evidence has shown that statin therapy results in a marked increase in coronary FCT. However, the relationship between this increase in FCT and the lipid profile has not been clearly elucidated. METHODS A literature search of PubMed, Embase, the Cochrane Library, and Web of Science up to March 17, 2015 was performed. Studies providing data on FCT using OCT at baseline and follow-up in patients receiving statin therapy were included. Weighted mean difference (WMD) with a random-effects model was used. RESULTS Six OCT studies were included. The FCT in coronary plaques was significantly increased after statin therapy (WMD: 58.79 μm, 95% CI 33.82-83.76 μm, P < 0.001). When compared with the placebo group, the increase in FCT was also greater in the statin group (WMD: 72.28 μm, 95% CI 44.97-99.58 μm, P < 0.001). Meta regression analysis demonstrated no significant correlations between the increase in FTC and the changes in total cholesterol, low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels during follow-up. Similarly, there were no significant correlations between the increase in FCT and age, male gender, hypertension, diabetes, and smoking. CONCLUSIONS Statin therapy induced a significant increase in coronary FCT evaluated by OCT. This increase in FCT was independent of traditional coronary risk factors including the lipid profile.
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Rosuvastatin may reduce the incidence of cardiovascular events in patients with acute coronary syndromes receiving percutaneous coronary intervention by suppressing miR-155/SHIP-1 signaling pathway.
Xie, W, Li, P, Wang, Z, Chen, J, Lin, Z, Liang, X, Mo, Y
Cardiovascular therapeutics. 2014;(6):276-82
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Abstract
PURPOSE The beneficial effect of rosuvastatin against percutaneous coronary intervention (PCI) related procedural myocardial injury has been determined mostly in patients with acute coronary syndromes (ACS). However, the detailed therapeutic mechanism has not been well studied. METHODS Patients with ACS receiving PCI (n = 159) were randomized to control group (placebo treatment) or to rosuvastatin group (20 mg 12 h before PCI, and a further 20 mg 2 h preprocedure dose). Levels of INF-γ, TNF-α, IL-6, miR-155/SHIP-1, and CD4(+)FoxP3(+)Treg in peripheral blood were detected before PCI and 24 h after PCI. Clinical data of these patients were also collected in this prospective study. RESULTS Compared with placebo, rosuvastatin treatment significantly reduced the incidence of periprocedural myocardial infarction (PMI) and levels of cardiac troponin I (cTnI) associated with decreased relative expression of serum miR-155, levels of inflammatory cytokines (INF-γ, TNF-α, and IL-6), increased SHIP-1 expression and CD4(+)FoxP3(+)Treg percentage values (P < 0.05). In addition, patients with rosuvastatin pretreatment also reduced incidence of 30 days major adverse cardiac events (MACE) compared to the patients with placebo treatment (16 patients vs. 28 patients, P = 0.038). CONCLUSIONS Our study suggests that high loading dose rosuvastatin pretreatment may reduce the incidence of cardiovascular events and levels of inflammatory markers in patients with ACS receiving PCI, which may be explained at least in part, by mechanism involving suppression of miR-155/SHIP-1 signaling pathway.