The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome A prospective analysis of the CETP TaqIB polymorphism on cardiovascular outcome and interaction with cholesterol-lowering therapy

AbstractObjectivesOn the basis of quantitative coronary angiography data, the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism has been postulated to predict the progression of coronary atherosclerosis and response to cholesterol-lowering therapy.BackgroundCholesteryl ester transfer protein mediates the exchange of lipids between anti-atherogenic high-density lipoprotein (HDL) and atherogenic apolipoprotein B containing lipoproteins and therefore plays a key role in human lipid metabolism. Hence, CETP gene polymorphisms may alter susceptibility to atherosclerosis.MethodsTo investigate the significance of the CETP TaqIB gene polymorphism with respect to clinical end points, we used the Cholesterol And Recurrent Events (CARE) cohort. The CARE study was designed to investigate the effect of five years of pravastatin therapy on coronary events.ResultsWe found that the odds ratios for the primary end point were not significantly different from unity for the three genetic subgroups after five years of placebo treatment. Furthermore, pravastatin induced similar changes in total cholesterol, low-density lipoprotein cholesterol, and HDL cholesterol among TaqIB genotypes, and both nonfatal myocardial infarction and deaths from coronary heart disease were reduced to the same extent in all three genotypes.ConclusionsIn the CARE cohort, the CETP TaqIB polymorphism does not predict cardiovascular events or discriminate between those who will or will not benefit from pravastatin treatment

Alirocumab in Patients With Polyvascular Disease and Recent Acute Coronary Syndrome : ODYSSEY OUTCOMES Trial

Patients with acute coronary syndrome (ACS) and concomitant noncoronary atherosclerosis have a high risk of major adverse cardiovascular events (MACEs) and death. The impact of lipid lowering by proprotein convertase subtilisin-kexin type 9 inhibition in such patients is undetermined. This pre-specified analysis from ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) determined whether polyvascular disease influenced risks of MACEs and death and their modification by alirocumab in patients with recent ACS and dyslipidemia despite intensive statin therapy. Patients were randomized to alirocumab or placebo 1 to 12 months after ACS. The primary MACEs endpoint was the composite of coronary heart disease death, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization. All-cause death was a secondary endpoint. Median follow-up was 2.8 years. Of 18,924 patients, 17,370 had monovascular (coronary) disease, 1,405 had polyvascular disease in 2 beds (coronary and peripheral artery or cerebrovascular), and 149 had polyvascular disease in 3 beds (coronary, peripheral artery, cerebrovascular). With placebo, the incidence of MACEs by respective vascular categories was 10.0%, 22.2%, and 39.7%. With alirocumab, the corresponding absolute risk reduction was 1.4% (95% confidence interval [CI]: 0.6% to 2.3%), 1.9% (95% CI: −2.4% to 6.2%), and 13.0% (95% CI: −2.0% to 28.0%). With placebo, the incidence of death by respective vascular categories was 3.5%, 10.0%, and 21.8%; the absolute risk reduction with alirocumab was 0.4% (95% CI: −0.1% to 1.0%), 1.3% (95% CI: −1.8% to 4.3%), and 16.2% (95% CI: 5.5% to 26.8%). In patients with recent ACS and dyslipidemia despite intensive statin therapy, polyvascular disease is associated with high risks of MACEs and death. The large absolute reductions in those risks with alirocumab are a potential benefit for these patients. (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab [ODYSSEY OUTCOMES]: NCT01663402

Additional file 7: of Blood lipids influence DNA methylation in circulating cells

The HDL-C PS is nominally associated with confounder neutrophil counts. (CSV 202 bytes

Additional file 11: of Blood lipids influence DNA methylation in circulating cells

Effect of lipid levels on DNA methylation corrected for nearest PS SNP within 1Â Mb. Estimate is the percentage change in DNA methylation per standard deviation change in lipid levels. (CSV 289 bytes

Additional file 10: of Blood lipids influence DNA methylation in circulating cells

Power calculations were performed for the situations where the EWAS effect size estimate is (1) the true causal effect size, (2) half the true causal effect size, and (3) double the true causal effect size. (CSV 1Â kb