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Published on: April 17, 2021
Heart failure causally affects the brain cortical structure: a Mendelian randomization study
Tianjiao Meng1, Qinwen Fei2, Jingying Zhu3
1Department of Neurology, Zhuji Affiliated Hospital of Wenzhou Medical University, Zhuji, China.
Insights
Heart failure (HF) may causally affect brain structure, with potential impacts on cognitive and emotional functions. This study used Mendelian randomization to explore HF
Area of Science:
- Neuroscience
- Cardiology
- Genetics
Background:
- The impact of heart failure (HF) on the brain's cortical structure is not well understood.
- Investigating the causal relationship between HF and brain structure is crucial for understanding neurological comorbidities.
Purpose of the Study:
- To investigate the causal effects of heart failure on cortical brain structures using Mendelian randomization (MR).
- To examine the influence of HF trait, left ventricular ejection fraction (LVEF), and N-terminal prohormone brain natriuretic peptide (NT-proBNP) on cortical surface area (SA) and thickness (TH).
Main Methods:
- A two-sample MR analysis was performed using large-scale genome-wide association study summary data.
- Data sources included large cohorts for HF, LVEF, NT-proBNP, and cortical SA/TH from the ENIGMA Consortium.
- Statistical methods were employed to ensure result stability by excluding heterogeneity and pleiotropy.
Main Results:
- No significant association was found between HF and overall cortical thickness or surface area.
- Elevated NT-proBNP levels were suggested to decrease cortical thickness in several brain regions, including the pars orbitalis and precuneus.
- Reduced LVEF was associated with decreased cortical SA and TH in regions like the isthmus cingulate gyrus and postcentral gyrus, with some suggested increases in other areas.
Conclusions:
- Fifteen brain regions were identified as potentially affected by heart failure.
- These structural brain changes may underlie cognitive, emotional, and sensory processing impairments observed in HF patients.
- Further research is warranted to elucidate the mechanisms linking HF to specific cortical alterations.
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.
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