Major lipids and lipoprotein levels and risk of blood pressure elevation: a Mendelian Randomisation study

作者：Weifang Liu, Chengzhang Yang, Fang Lei, Xuewei Huang, Jingjing Cai, Shaoze Chen, Zhi‐Gang She, Hongliang Li · 发表于：EBioMedicine · 年份：2024 · DOI：10.1016/j.ebiom.2023.104964 · 被引用次数：53 · 研究领域：Genetic Associations and Epidemiology、Metabolomics and Mass Spectrometry Studies、Diabetes, Cardiovascular Risks, and Lipoproteins

BACKGROUND: Quantitative nuclear magnetic resonance (NMR) metabolomics techniques provide detailed measurements of lipoprotein particle concentration. Metabolic dysfunction often represents a cluster of conditions, including dyslipidaemia, hypertension, and diabetes, that increase the risk of cardiovascular diseases (CVDs). However, the causal relationship between lipid profiles and blood pressure (BP) remains unclear. We performed a Mendelian Randomisation (MR) study to disentangle and prioritize the potential causal effects of major lipids, lipoprotein particles, and circulating metabolites on BP and pulse pressure (PP). METHODS: We employed single-nucleotide polymorphisms (SNPs) associated with major lipids, lipoprotein particles, and other metabolites from the UK Biobank as instrumental variables. Summary-level data for BP and PP were obtained from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. Two-sample MR and MR Bayesian model averaging approaches (MR-BMA) were conducted to analyse and rank causal associations. FINDINGS: Genetically predicted TG was the most likely causal exposure among the major lipids to increase systolic blood pressure (SBP) and diastolic blood pressure (DBP), with marginal inclusion probabilities (MIPs) of 0.993 and 0.847, respectively. Among the majority of lipoproteins and their containing lipids, including major lipids, genetically elevated TG in small high-density lipoproteins (S_HDL_TG) had the strongest association...