Causal association between heart failure and bone mineral density: Insights from a two-sample bidirectional Mendelian...

Area of Science:

• Cardiovascular Science
• Bone Metabolism
• Genetic Epidemiology

Background:

• The relationship between heart failure (HF) and bone mineral density (BMD) is of significant scientific interest but remains inconclusive.
• Published epidemiological studies have yielded inconsistent findings regarding the association between HF and BMD.

Purpose of the Study:

• To investigate the potential causal association between heart failure (HF) and bone mineral density (BMD) using a bidirectional Mendelian randomization (MR) approach.
• To analyze the causal effect of HF on BMD and the reverse causality of BMD on HF.

Main Methods:

• A two-sample bidirectional Mendelian randomization (MR) study was conducted using summary-level GWAS data.
• Instrumental variables (SNPs) were rigorously selected and quality-controlled.
• Various MR methods, including IVW, weighted median, MR-Egger, and sensitivity analyses (MR-PRESSO, leave-one-out), were employed to assess causality, heterogeneity, and pleiotropy.

Main Results:

• A significant causal association was found between heart failure (HF) and lower total body bone mineral density (TB-BMD) (IVW: OR=0.78, 95% CI: 0.68-0.87, p=0.00588).
• No significant causal relationships were observed between HF and femoral neck (FN-BMD), lumbar spine (LS-BMD), or forearm (FA-BMD).
• The reverse causality, where BMD influences HF risk, was not supported by the analysis.

Conclusions:

• Heart failure (HF) has a causal effect on reducing total body bone mineral density (TB-BMD).
• No significant causal link was detected between BMD and HF, nor between HF and other specific BMD sites (FN, LS, FA).
• Further research into preventing and treating TB-BMD decline in heart failure patients is warranted.