Effect of obesity on cardiovascular morphofunctional phenotype: Study of Mendelian randomization

Background:Obesity is an independent factor for cardiovascular diseases, impacting health across different age groups. cardiovascular magnetic resonance (CMR) imaging is considered the gold standard for noninvasive assessment of cardiovascular structure and function. We conducted a Mendelian randomization (MR) study to explore the associations between obesity-related traits and the clinical pre-phenotype of cardiac and aortic structure and function. Methods:Independent genetic variations significantly correlated with adult body mass index, adult waist-to-hip ratio, birth weight, child body mass index, and excess visceral fat were selected as instrumental variables. Eighty-two CMR imaging features were obtained from the UK Biobank Genome-Wide Association Study. These features served as clinical pre-phenotypes, providing early indications of the structure and function of the 4 cardiac chambers and 2 aortic slices. Preliminary analyses were conducted using MR and inverse variance-weighted methods. Causal directions were determined through Steiger filtering and testing, achieving confirmation. Sensitivity analyses were performed using weighted median, MR-Egger, and MR-PRESSO methods. Results:Adult BMI was positively correlated with left ventricular end-systolic volume, right ventricular end-diastolic volume, right ventricular end-systolic volume, and right ventricular volume per beat. The adult waist-to-hip ratio was inversely proportional to right atrial volume per beat, right atrial maximum volume, right atrial minimum volume, partial regional longitudinal strain, regional peak circumferential strain, and regional radial strain, and positively proportional to partial regional peak circumferential strain and partial end-diastolic local myocardial wall thickness characteristics. Birth weight was positively correlated with maximum right atrial volume, minimum right atrial volume, right atrial volume per beat, right ventricular end-diastolic volume, right ventricular output per beat, maximum area of the ascending aorta, minimum area of the ascending aorta, and negatively correlated with longitudinal strain in some regions. Body mass index in children is positively correlated with left ventricular end-diastolic volume, left ventricular end-systolic volume, left atrial volume per beat, right ventricular end-diastolic volume, and right ventricular volume per beat. Conclusion:This study suggests that obesity may lead to myocardial hypertrophy and dilation of the cardiac chambers and aorta, thereby exerting adverse effects on the cardiovascular system and increasing the susceptibility to HF.