Factorial Mendelian randomization of lipoprotein (a) lowering, low-density lipoprotein cholesterol lowering, and lifestyle improvements: joint associations with cardiovascular risk.

ABSTRACT:

Background

High levels of lipoprotein(a) [Lp(a)] have been associated with an increased risk of cardiovascular disease (CVD); however, the effects of Lp(a)-lowering therapy in combination with low-density lipoprotein cholesterol (LDL-C)-lowering treatment or lifestyle improvements on CVD risk remain unexplored.

Methods

We conducted a factorial Mendelian randomization study among 385 917 participants in the UK Biobank. Separate genetic scores were constructed to proxy the effects of Lp(a) lowering, LDL-C lowering through different targets [HMG-CoA reductase, NPC1-like intracellular cholesterol transporter 1, proprotein convertase subtilisin/kexin Type 9, and low-density lipoprotein receptor (LDLR)], as well as improvements in body mass index (BMI), systolic blood pressure (SB

SUBMITTER: Wang L 

PROVIDER: S-EPMC11893152 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature