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.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
刚刚
科目三应助糊涂的猎豹采纳,获得10
3秒前
4秒前
风清扬应助清脆的灵煌采纳,获得30
4秒前
思源应助美好斓采纳,获得30
6秒前
成功应助hkh采纳,获得10
6秒前
酷波er应助信仰阳光快乐采纳,获得10
7秒前
Tong完成签到,获得积分10
8秒前
香蕉觅云应助克林沙星采纳,获得10
8秒前
田様应助孙成成采纳,获得10
8秒前
一把过发布了新的文献求助10
9秒前
新嘟发布了新的文献求助10
10秒前
Owen应助12采纳,获得10
11秒前
11秒前
11秒前
14秒前
开朗艳一发布了新的文献求助10
16秒前
Emily完成签到,获得积分10
16秒前
18秒前
量子星尘发布了新的文献求助10
18秒前
沉静乌龟发布了新的文献求助10
20秒前
20秒前
20秒前
21秒前
mia发布了新的文献求助20
23秒前
木乙完成签到 ,获得积分10
23秒前
23秒前
SYLH应助开朗艳一采纳,获得10
24秒前
务实的寻凝完成签到 ,获得积分10
26秒前
27秒前
Mia发布了新的文献求助30
29秒前
彭剑封发布了新的文献求助10
29秒前
pazhao完成签到,获得积分10
30秒前
冬1发布了新的文献求助10
30秒前
军帽完成签到,获得积分20
32秒前
小蘑菇应助新嘟采纳,获得10
33秒前
33秒前
111完成签到,获得积分20
34秒前
Emily发布了新的文献求助10
34秒前
34秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Picture Books with Same-sex Parented Families: Unintentional Censorship 700
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3975610
求助须知:如何正确求助?哪些是违规求助? 3519986
关于积分的说明 11200337
捐赠科研通 3256337
什么是DOI,文献DOI怎么找? 1798246
邀请新用户注册赠送积分活动 877446
科研通“疑难数据库(出版商)”最低求助积分说明 806357