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Remnant cholesterol lowering in cardiovascular disease risk reduction in statin, ezetimibe, and PCSK9 inhibitor trials: meta-regression analyses

医学 以兹提米比 PCSK9 他汀类 内科学 胆固醇 元回归 低密度脂蛋白胆固醇 动脉粥样硬化性心血管疾病 降低胆固醇 疾病 荟萃分析 心脏病学 脂蛋白 低密度脂蛋白受体
作者
Ask Tybjærg Nordestgaard,Børge G. Nordestgaard
出处
期刊:European Journal of Preventive Cardiology [Oxford University Press]
标识
DOI:10.1093/eurjpc/zwaf337
摘要

Abstract Aims We tested the hypothesis that remnant cholesterol reduction is associated with part of the cardiovascular risk reduction in statin, ezetimibe, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor trials. Methods We included statin, ezetimibe, and PCSK9 inhibitor trials of 1,000 participants or more and lipid level data. Baseline and follow-up low-density lipoprotein (LDL) and remnant cholesterol levels were extracted. LDL and remnant cholesterol reductions were differences between intervention and reference groups at year one. We calculated risk ratios for major adverse cardiovascular events per 1 mmol/L (39 mg/dL) and 1 standard deviation reductions in LDL and remnant cholesterol using meta-regressions. Results A total of 43 trials of 327,264 participants with 42,016 major adverse cardiovascular events where included. Remnant cholesterol was reduced 0.19 mmol/L per 1 mmol/L LDL cholesterol reduction, and 11% per 20% LDL cholesterol reduction. Fixed/random effects risk ratios (95% confidence intervals) for major adverse cardiovascular events per 1 mmol/L reductions were 0.84 (0.82-0.85)/0.82 (0.78-0.85) for LDL and 0.36 (0.33-0.40)/0.27 (0.20-0.36) for remnant cholesterol. Corresponding, estimates per 1 standard deviation reductions were 0.93 (0.92-0.93)/0.91 (0.90-0.93) and 0.92 (0.92-0.93)/0.90 (0.88-0.92), respectively. Fixed/random effects risk ratios per 1 mmol/L reductions were 0.88 (0.85-0.91)/0.82 (0.74-0.91) for LDL cholesterol adjusted for remnant cholesterol reductions and 0.74 (0.60-0.92)/0.92 (0.45-1.187) for remnant cholesterol adjusted for LDL cholesterol reductions. Corresponding estimates per 1 standard deviation reductions were 0.94 (0.93-0.96)/0.92 (0.88-0.96) and 0.98 (0.96-0.99)/0.99 (0.94-1.05), respectively. Conclusion Remnant cholesterol lowering is associated with part of the cardiovascular risk reduction in statin, ezetimibe, and PCSK9 inhibitor trials.
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