他汀类药物、贝特类药物、载脂蛋白C3抑制剂和血管生成素样蛋白3抑制剂降低残余胆固醇所致的动脉粥样硬化性心血管疾病风险降低：一项队列研究

Risk reduction of ASCVD attributed to lowering of remnant cholesterol from statins, fibrates, APOC3 inhibitors, and ANGPTL3 inhibitors: a cohort study.

作者信息

Balling Mie, Roepstorff Otto Grøn, Gerds Thomas Alexander, Varbo Anette, Mortensen Martin Bødtker, Langsted Anne, Nordestgaard Børge Grønne, Afzal Shoaib

机构信息

Department of Clinical Biochemistry, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; The Copenhagen General Population Study, Copenhagen University Hospital - Herlev and Gentofte, Herlev, Denmark; Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

出版信息

Atherosclerosis. 2025 Oct;409:120471. doi: 10.1016/j.atherosclerosis.2025.120471. Epub 2025 Aug 6.

DOI:10.1016/j.atherosclerosis.2025.120471

PMID:40839980

Abstract

BACKGROUND AND AIMS

Randomized clinical trials of remnant cholesterol lowering drugs show 50 % and 80 % reduction in remnant cholesterol with apolipoprotein C3 (APOC3) and angiopoietin-like 3 (ANGPTL3) inhibitors. However, how many of atherosclerotic cardiovascular disease(ASCVD) cases that could be prevented lowering remnant cholesterol by these therapies is unknown. The aim of the study was to estimate the potential of APOC3 and ANGPTL3 inhibitors to reduce the ASCVD burden through lowering of remnant cholesterol.

METHODS

Of 98,311 individuals from the Copenhagen General Population Study without ASCVD at study entry 8,506 were statin users and 89,805 were statin non-users. Cause-specific Cox regression was used to model rates of ASCVD and non-cardiovascular death conditional on remnant cholesterol and risk factors. Based on these models the potential 10-year absolute risk reduction of ASCVD in individuals with remnant cholesterol >1 mmol/L (>39 mg/dL) for 15 %, 30 %, 50 %, and 80 % lower remnant cholesterol was predicted.

RESULTS

The predicted average 10-year absolute risk of ASCVD was 20 % for statin users and 11 % for statin non-users with remnant cholesterol >1 mmol/L (>39 mg/dL). The predicted 10-year absolute risk reduction of ASCVD in individuals with remnant cholesterol >1 mmol/L (>39 mg/dL) for 50 % and 80 % lower remnant cholesterol were 2.7 % (95 % confidence interval: 2.2-3.2 %), and 4.1 % (3.4-4.8 %) for statin users and 1.4 % (1.3-1.5 %), and 2.1 % (2.0-2.3 %) for statin non-users.

CONCLUSION

We have shown that significant ASCVD risk reductions are expected for remnant cholesterol lowering drugs in at-risk populations, if intervention trials with novel remnant cholesterol lowering drugs show expected reductions in remnants in large cardiovascular outcomes trials.

摘要

背景与目的

残余胆固醇降低药物的随机临床试验表明，载脂蛋白C3（APOC3）和血管生成素样3（ANGPTL3）抑制剂可使残余胆固醇降低50%和80%。然而，通过这些疗法降低残余胆固醇可预防多少例动脉粥样硬化性心血管疾病（ASCVD）尚不清楚。本研究的目的是评估APOC3和ANGPTL3抑制剂通过降低残余胆固醇来减轻ASCVD负担的潜力。

方法

在哥本哈根一般人群研究的98311名入组时无ASCVD的个体中，8506人使用他汀类药物，89805人未使用他汀类药物。采用特定病因的Cox回归模型，根据残余胆固醇和危险因素对ASCVD和非心血管死亡发生率进行建模。基于这些模型，预测了残余胆固醇>1 mmol/L（>39 mg/dL）的个体，残余胆固醇降低15%、30%、50%和80%时，10年ASCVD的潜在绝对风险降低情况。

结果

残余胆固醇>1 mmol/L（>39 mg/dL）的他汀类药物使用者和非使用者，预测的10年ASCVD平均绝对风险分别为20%和11%。残余胆固醇>1 mmol/L（>39 mg/dL）的个体，残余胆固醇降低50%和80%时，预测的10年ASCVD绝对风险降低率，他汀类药物使用者分别为2.7%（95%置信区间：2.2 - 3.2%）和4.1%（3.4 - 4.8%），非使用者分别为1.4%（1.3 - 1.5%）和2.1%（2.0 - 2.3%）。