The relationship between lipoprotein(a) and risk of cardiovascular disease: a Mendelian randomization analysis

作者：Shiyue Wang, Li Zha, Jian Chen, Dongjie Du, Danyang Liu, Ming Zhong, Rongfang Shang, Dongxue Sun, Chang Sun, Enze Jin · 发表于：European journal of medical research · 年份：2022 · DOI：10.1186/s40001-022-00825-6 · 被引用次数：53 · 研究领域：Genetic Associations and Epidemiology、Lipoproteins and Cardiovascular Health、Atherosclerosis and Cardiovascular Diseases

BACKGROUND: Lipoprotein(a) [Lp(a)] is one of the residual risk factors for cardiovascular disease (CVD) in the setting of optimal low-density lipoprotein cholesterol (LDL-C). The association between Lp(a) and CVD is still in the exploratory phase, with few studies indicating a causal connection between Lp(a) and various CVD. METHODS: Lp(a) (n = 377,590) was a genome-wide association study (GWAS) based on European populations from Neale Lab. Large GWAS datasets for CVD, including aortic aneurysm(AA) (n = 209,366), atrial fibrillation(AF) (n = 1,030,836), coronary heart disease(CHD) (n = 361,194), secondary hypertension(HBP) (n = 164,147), heart failure(HF) (n = 208,178), ischemic stroke (IS) (n = 218,792), large artery atherosclerosis stroke(ISL) (n = 150, 765), small vessel stroke(ISS) (n = 198,048), lacunar stroke(LIS) (n = 225,419), and pulmonary embolism(PE) (n = 218,413) were also based on European populations. We performed separate univariate two-sample Mendelian randomization (MR) analysis for Lp(a) and CVD as described above. We evaluated this connection mainly using the random-effects inverse variance weighted technique(IVW1) with a 95% confidence interval (CI) for the odds ratio (OR). This was supplemented by MR-Egger, weighted median, maximum likelihood, penalized weighted median, and fixed-effects inverse variance weighted methods. MR-PRESSO offers another means of statistical detection. RESULTS: Our two-sample MR, which was predominately based on IVW1, revealed a ...