Effects of blood lipids and lipid‐modifying drugs on intracranial aneurysms. (5th July 2022)

• Record Type: Journal Article
• Authors: Zhang, Baorui; Dong, Siyuan; Miao, Yan; Song, Guangrong; Yuan, Fei; Liu, Lang; Xia, Saide; Qin, Yongkai; Huo, Xiaochuan; Wu, Zhongxue; Miao, Zhongrong; Mo, Dapeng; Liu, Aihua
• Is Part Of: European journal of neurology. Volume 29:Number 10(2022)
• Page Start: 2967
• Page End: 2975
• Publication Date: 2022-07-05
• Subjects: apolipoproteins -- genetics -- intracranial aneurysm -- lipids -- Mendelian randomization; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.15471
• Languages: English
• ISSNs: 1351-5101

Abstract

Abstract: Background and purpose: We used two‐sample Mendelian randomization (MR) to examine the effects of blood lipids and lipid‐modifying drugs on intracranial aneurysm (IA). Methods: Genetic variants for the effects of high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A1, low‐density lipoprotein cholesterol (LDL‐C), apolipoprotein B, and triglycerides and targets for lipid‐modifying drugs were selected from the genome‐wide discovery analyses of the UK Biobank. Summary‐level data on IAs were obtained from the International Stroke Genetics Consortium. Univariate and multivariate MR analyses were performed. Results: Univariate MR analyses showed that the HDL‐C was negatively correlated with IA (odds ratio [OR] = 0.816, 95% confidence interval [CI] = 0.715–0.932, p = 0.003) and ruptured IA (rIA; OR = 0.775, 95% CI = 0.663–0.906, p = 0.001). The multivariate MR–inverse variance weighted analysis showed that the HDL‐C was negatively correlated with IA (OR = 0.655, 95% CI = 0.434–0.988, p = 0.043) and rIA (OR = 0.563, 95% CI = 0.347–0.913, p = 0.02), and the LDL‐C was negatively correlated with IA (OR = 0.402, 95% CI = 0.191–0.848, p = 0.017) and rIA (OR = 0.376, 95% CI = 0.160–0.883, p = 0.025). Using genetic proxies of known lipid‐modifying drugs, we found that the increased HDL‐C with cholesterol ester transfer protein proxies was associated with a decreased risk of rIA (OR = 0.852, 95% CI = 0.747–0.973, p = 0.018), and the decreased LDL‐C with 3‐hydroxy‐3‐methylglutaryl‐coenzyme A reductase proxies was associated with increased risk of IA (OR = 1.772, 95% CI = 1.080–2.908, p = 0.024) and rIA (OR = 1.856, 95% CI = 1.022–3.371, p = 0.042). Conclusions: Genetically determined HDL‐C and LDL‐C reduce the risk of IA and rIA. The effects of different lipid‐modifying drugs on IA need to be further investigated. Abstract : We used two‐sample Mendelian randomization to examine the effects of blood lipids and lipid‐modifying drugs on intracranial aneurysm. Genetically determined high‐density lipoprotein cholesterol and low‐density lipoprotein cholesterol reduce the risk of intracranial aneurysm and intracranial aneurysm rupture.