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Brain age gap as biomarker linking cardiovascular diseases genetic susceptibility and causality
Shangying Lyu1,2, Ruixia Zhang1,2, Kai Peng3
1College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi 830017, China.
Abstract:
Cardiovascular diseases (CVDs) remain a primary cause of global mortality, underscoring the need for biomarkers that capture systemic aging risks. T1-weighted magnetic resonance imaging (MRI) data from UK Biobank (UKB) participants were utilized to develop a three-dimensional vision transformer (3D-ViT) model for predicting brain age and computing BAG, an imaging-derived indicator of biological aging. Causal BAG-CVD relationships were assessed through bidirectional Mendelian randomization (MR). The results substantiated significant brain-heart interactions, revealing that acute myocardial infarction (AMI) and chronic ischemic heart disease (CIH) were associated with decelerated brain aging (OR = 0.783; OR = 0.847), while an elevated BAG correlated with a reduced risk of AMI and CIH (OR = 0.954; OR = 0.969). These findings highlight BAG as an integrative indicator combining neuroimaging and genetic profiles. The observed bidirectional causality offers a biological framework for defining intervention strategies targeting comorbid brain and cardiovascular health.
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