Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses

医学 孟德尔随机化 内科学 随机化 胆固醇 随机对照试验 基因型 遗传学 基因 生物 遗传变异
作者
Hongwei Liu,Jianxin Li,Fangchao Liu,Keyong Huang,Jie Cao,Shufeng Chen,Hongfan Li,Chong Shen,Dongsheng Hu,Jianfeng Huang,Xiangfeng Lu,Dongfeng Gu
出处
期刊:European Journal of Preventive Cardiology [Oxford University Press]
卷期号:30 (12): 1207-1215 被引量:18
标识
DOI:10.1093/eurjpc/zwad111
摘要

LDL cholesterol (LDL-C) is a well-established risk factor for coronary artery disease (CAD). However, the optimal LDL-C level with regard to efficacy and safety remains unclear. We aimed to investigate the causal relationships between LDL-C and efficacy and safety outcomes.We analyzed 353 232 British from the UK Biobank and 41 271 Chinese from the China-PAR project. Linear and non-linear Mendelian randomization (MR) analyses were performed to evaluate the causal relation between genetically proxied LDL-C and CAD, all-cause mortality, and safety outcomes (including haemorrhagic stroke, diabetes mellitus, overall cancer, non-cardiovascular death, and dementia). No significant non-linear associations were observed for CAD, all-cause mortality, and safety outcomes (Cochran Q P > 0.25 in British and Chinese) with LDL-C levels above the minimum values of 50 and 20 mg/dL in British and Chinese, respectively. Linear MR analyses demonstrated a positive association of LDL-C with CAD [British: odds ratio (OR) per unit mmol/L increase, 1.75, P = 7.57 × 10-52; Chinese: OR, 2.06, P = 9.10 × 10-3]. Furthermore, stratified analyses restricted to individuals with LDL-C levels less than the guideline-recommended 70 mg/dL demonstrated lower LDL-C levels were associated with a higher risk of adverse events, including haemorrhagic stroke (British: OR, 0.72, P = 0.03) and dementia (British: OR, 0.75, P = 0.03).In British and Chinese populations, we confirmed a linear dose-response relationship of LDL-C with CAD and found potential safety concerns at low LDL-C levels, providing recommendations for monitoring adverse events in people with low LDL-C in the prevention of cardiovascular disease.We used the Mendelian randomization method to estimate the causal relationships between LDL-C and efficacy and safety outcomes in the UK Biobank and the China-PAR project.We found a linear rather than a non-linear relationship between genetically proxied LDL cholesterol and coronary artery disease.There are potential safety concerns (including haemorrhagic stroke and dementia) for people who have low LDL-C levels.
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