Abstract
BACKGROUND: The effects of heart failure (HF) on cortical brain structure remain unclear. Therefore, the present study aimed to investigate the causal effects of heart failure on cortical structures in the brain using Mendelian randomization (MR) analysis. METHODS: We conducted a two-sample MR analysis utilizing genetically-predicted HF trait, left ventricular ejection fraction (LVEF), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) levels to examine their effects on the cortical surface area (SA) and thickness (TH) across 34 cortical brain regions. Genome-wide association study summary data were extracted from studies by Rasooly (1,266,315 participants) for HF trait, Schmidt (36,548 participants) for LVEF, the SCALLOP consortium (21,758 participants) for NT-proBNP, and the ENIGMA Consortium (51,665 participants) for cortical SA and TH. A series of MR analyses were employed to exclude heterogeneity and pleiotropy, ensuring the stability of the results. Given the exploratory nature of the study, p-values between 1.22E-04 and 0.05 were considered suggestive of association, and p-values below 1.22E-04 were defined as statistically significant. RESULTS: In this study, we found no significant association between HF and cortical TH or SA (all p > 1.22E-04). We found that the HF trait and elevated NT-proBNP levels were not associated with cortical SA, but were suggested to decrease cortical TH in the pars orbitalis, lateral orbitofrontal cortex, temporal pole, lingual gyrus, precuneus, and supramarginal gyrus. Reduced LVEF was primarily suggested to decrease cortical SA in the isthmus cingulate gyrus, frontal pole, postcentral gyrus, cuneus, and rostral middle frontal gyrus, as well as TH in the postcentral gyrus. However, it was suggested to causally increase in the SA of the posterior cingulate gyrus and medial orbitofrontal cortex and the TH of the entorhinal cortex and superior temporal gyrus. CONCLUSION: We found 15 brain regions potentially affected by HF, which may lead to impairments in cognition, emotion, perception, memory, language, sensory processing, vision, and executive control in HF patients.