Primary Aldosteronism Influences Cardiac Structure, Function, and Disease Risk: Evidence From Mendelian Randomization...

Area of Science:

• Cardiovascular Research
• Endocrinology
• Genetic Epidemiology

Background:

• Observational studies suggest a link between primary aldosteronism (PA) and cardiovascular diseases (CVDs), but causal evidence is lacking.
• Primary aldosteronism is associated with increased cardiovascular morbidity and mortality.
• Understanding the causal relationship is crucial for clinical management and public health strategies.

Purpose of the Study:

• To investigate the causal association between primary aldosteronism (PA) and the risk of various cardiovascular diseases (CVDs).
• To examine the causal effect of PA on cardiac magnetic resonance (CMR) parameters indicative of cardiac remodeling.
• To employ the Mendelian randomization (MR) method for robust causal inference.

Main Methods:

• Utilized Mendelian randomization (MR) analysis with genome-wide significant single nucleotide polymorphisms (SNPs) for PA.
• Extracted genetic association data for CVDs and CMR parameters from large-scale genome-wide association studies (GWAS).
• Applied the inverse-variance weighted (IVW) method and conducted multiple sensitivity analyses (MR-Egger, weighted median, MR-PRESSO, Cochran's Q, leave-one-out) to ensure result validity.

Main Results:

• Genetically predicted PA showed significant causal associations with atrial fibrillation, myocardial infarction, heart failure, any stroke, any ischemic stroke, and small vessel stroke.
• PA was causally linked to adverse cardiac remodeling, including increased ventricular and atrial volumes, higher ventricular stroke volume, and reduced left atrial emptying fraction.
• Sensitivity analyses confirmed the robustness of the observed causal relationships.

Conclusions:

• Primary aldosteronism (PA) plays a causal role in increasing the risk of cardiovascular diseases (CVDs).
• PA contributes to adverse cardiac remodeling, impacting heart structure and function.
• Increased attention to PA screening and treatment is warranted to mitigate cardiovascular outcomes.