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

Liu, Hongwei1,2; Li, Jianxin1,2; Liu, Fangchao1,2; Huang, Keyong1,2; Cao, Jie1,2; Chen, Shufeng1,2; Li, Hongfan1,2; Shen, Chong3; Hu, Dongsheng4,5; Huang, Jianfeng1,2; Lu, Xiangfeng1,2; Gu, Dongfeng1,2,6

2023-04-01

10.1093/eurjpc/zwad111

EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY   影响因子和分区

2047-4873

2047-4881

["Lay Summary 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.","Aims 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. Methods and results 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 x 10(-52); Chinese: OR, 2.06, P = 9.10 x 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). Conclusion 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."]

Low-density lipoprotein cholesterol Cardiovascular disease Haemorrhagic stroke Dementia Mendelian randomization

SCI

英语

通讯

Cardiovascular System & Cardiology

Cardiac & Cardiovascular Systems

WOS:000975493600001

OXFORD UNIV PRESS

Web of Science

1.Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Key Lab Cardiovasc Epidemiol, 167 Beilishi Rd, Beijing 100037, Peoples R China
2.Chinese Acad Med Sci & Peking Union Med Coll, Fuwai Hosp, Natl Ctr Cardiovasc Dis, Dept Epidemiol, 167 Beilishi Rd, Beijing 100037, Peoples R China
3.Nanjing Med Univ, Sch Publ Hlth, Dept Epidemiol & Biostat, Nanjing 211166, Peoples R China
4.Zhengzhou Univ, Coll Publ Hlth, Dept Epidemiol & Hlth Stat, Zhengzhou 450001, Peoples R China
5.Shenzhen Univ, Sch Publ Hlth, Dept Biostat & Epidemiol, Hlth Sci Ctr, Shenzhen 518060, Peoples R China
6.Southern Univ Sci & Technol, Sch Med, 1088 Xueyuan Ave, Shenzhen 518055, Peoples R China

Liu, Hongwei,Li, Jianxin,Liu, Fangchao,et al. Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses[J]. EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY,2023,30(12).

Liu, Hongwei.,Li, Jianxin.,Liu, Fangchao.,Huang, Keyong.,Cao, Jie.,...&Gu, Dongfeng.(2023).Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses.EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY,30(12).

Liu, Hongwei,et al."Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses".EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY 30.12(2023).