Mendelian Randomization Study of Heart Failure and Stroke Subtypes

Area of Science:

• Cardiovascular Science
• Epidemiology
• Genetics

Background:

• The relationship between heart failure (HF) and stroke risk, including ischemic stroke (IS) and hemorrhagic stroke, remains debated.
• Previous studies have yielded controversial results regarding HF as an independent risk factor for stroke.

Purpose of the Study:

• To investigate the potential causal effect of heart failure (HF) on the risk of ischemic stroke (IS) and hemorrhagic stroke using a multivariable Mendelian randomization (MR) approach.
• To explore the direct causal association, independent of mediating factors, between HF and various stroke subtypes.

Main Methods:

• Utilized a multivariable Mendelian randomization (MR) design, employing genetically predicted HF as an instrumental variable.
• Extracted stroke outcome data from large genome-wide association studies (GWAS) meta-analyses.
• Applied the inverse variance-weighted (IVW) method and conducted sensitivity analyses, adjusting for potential mediators like atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP).

Main Results:

• Univariable MR indicated significant associations between genetically predicted HF and any IS, large artery stroke (LAS), and cardioembolic stroke (CES).
• No significant association was found for small vessel stroke (SVS) or intracerebral hemorrhage (ICH) in univariable MR.
• After adjusting for mediating factors (AF, CHD, SBP) in multivariable MR, all significant associations between HF and stroke subtypes were attenuated to the null.

Conclusions:

• Heart failure (HF) does not appear to have a direct causal effect on the risk of ischemic stroke (IS) or hemorrhagic stroke.
• The observed association between HF and IS is likely mediated by other cardiovascular risk factors, specifically atrial fibrillation (AF), coronary heart disease (CHD), and systolic blood pressure (SBP).