Evaluating the Causal Effects of ADHD and Autism on Cardiovascular Diseases and Vice Versa: A Systematic Review and Meta-Analysis of Mendelian Randomization Studies

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are neurodevelopmental disorders with lifelong functional implications. Their potential role as emerging risk factors for cardiovascular diseases (CVDs) is increasingly acknowledged. The aim of this study was to conduct a comprehensive evaluation and meta-analysis of Mendelian Randomization (MR) studies exploring the causal effects of ADHD and ASD on various cardiovascular outcomes and vice versa. Three databases were searched, study quality was evaluated using a STROBE-MR checklist, and relevant data were extracted. In total, 14 studies revealed genetic associations between ADHD or ASD susceptibility and selected CVDs and vice versa. Notably, genetic markers for ADHD were linked to an increased risk of coronary artery disease, heart failure, and various types of stroke. Genetic predisposition to ASD raised the likelihood of atrial fibrillation and heart failure. Atrial fibrillation showed a causal relationship with elevated ADHD risk. Interestingly, hypertension was not associated with ADHD or ASD at the genetic level. Further efforts are needed to fully elucidate the basis of causal links from a mechanistic perspective. Overall, the results highlight the need for cardiovascular risk assessment and management in the clinical care of individuals with ADHD and ASD.