The causal relationships between body composition and heart failure: A two-sample mendelian randomization study.

Area of Science:

• Cardiovascular Genetics
• Metabolic Health
• Epidemiology

Background:

• Heart failure (HF) is a major global health concern.
• Body composition indicators like BMI, WC, and fat mass are associated with cardiovascular disease.
• Causal relationships between body composition and HF risk require robust investigation.

Purpose of the Study:

• To investigate the causal effect of various body composition indicators on heart failure (HF) risk.
• To utilize a two-sample Mendelian randomization (MR) approach for robust causal inference.
• To assess the role of BMI, WC, WHR, fat mass, and fat-free mass in HF etiology.

Main Methods:

• Employed a two-sample Mendelian randomization (MR) design.
• Utilized genome-wide significant single nucleotide polymorphisms (SNPs) from large biobanks (UK Biobank, GIANT, FinnGen) as instrumental variables.
• Applied multiple MR methods including IVW, IVW_mre, MR-PRESSO, and maximum likelihood for robust estimation.

Main Results:

• Elevated BMI, WC, and WHR showed significant causal associations with increased HF risk.
• Increased fat mass in the right arm, right leg, trunk, and whole body were all linked to higher HF risk.
• Fat-free mass, including whole-body and regional measures, also demonstrated a positive association with HF risk.

Conclusions:

• This MR study provides strong evidence for a causal link between multiple body composition indicators and HF risk.
• BMI, WC, WHR, and various fat mass and fat-free mass measures are significant risk factors for heart failure.
• These findings highlight the importance of monitoring body composition for HF risk assessment and developing targeted prevention strategies.