| Title: | Efficacy and safety of low levels of low-density lipoprotein cholesterol: trans-ancestry linear and non-linear Mendelian randomization analyses |
| Journal: | European Journal of Preventive Cardiology |
| Published: | 12 Apr 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/37040432/ |
| DOI: | https://doi.org/10.1093/eurjpc/zwad111 |
| Citations: | 11 (11 in last 2 years) as of 8 Aug 2024 |
Publication 11331
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Abstract
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.</p>
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 × 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).</p>
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.</p>
12 Authors
- Hongwei Liu
- Jianxin Li
- Fangchao Liu
- Keyong Huang
- Jie Cao
- Shufeng Chen
- Hongfan Li
- Chong Shen
- Dongsheng Hu
- Jianfeng Huang
- Xiangfeng Lu
- Dongfeng Gu
1 Application
| Application ID | Title |
|---|---|
| 69815 | Improving risk prediction of cardiometabolic diseases by integrating ethnic-specific genetic variants and environmental predictors |
Enabling scientific discoveries that improve human health