Investigating causal relations between heart failure and Alzheimer's disease: A two-sample Mendelian randomization study

Abstract

Introduction: Heart failure has been shown to be associated with an increased risk of dementia and its subtype- Alzheimer's disease in observational studies. However, whether this associations reflects the underlying causality remains controversial. This study aims to investigate the causal effects of heart failure on the risk of Alzheimer's disease. Materials and Methods: We conducted a two-sample Mendelian randomization analysis using summary data from recently published genome-wide association studies. Twelve single nucleotide polymorphisms (SNPs) associated with heart failure at a significance level of P<5 × 10−8 were extracted as instrumental variables to evaluate the causality. Results: There was no evidence of a causal association between genetically predicted heart failure and the risk of Alzheimer's disease. Effect estimates calculated by the inverse-variance weighted (IVW) method were incompatible with the causality in the primary analysis (OR: 1.073, 95% CI: 0.997–1.073, P = 0.070), and similar results were also yield in the replication analysis (OR: 1.060, 95% CI: 0.627–1.793, P = 0.828). Conclusion: Under Mendelian randomization assumptions, our analysis did not support a causal association between heart failure and the risk of Alzheimer's disease. The results should be cautiously interpreted, and further studies are warranted.

Keywords

• Heart failure
• Alzheimer's disease
• Cognitive dysfunction
• Dementia