Sex-Specific Cardiovascular Phenotypes in Marfan Syndrome

Marfan syndrome (MFS) is a heritable connective tissue disorder in which cardiovascular complications drive morbidity. Contemporary sex-based differences in vascular and rhythm manifestations remain incompletely defined.

The purpose of this study was to compare aneurysm burden, dissection prevalence, arrhythmias, valvular phenotypes, and cardiovascular interventions between men and women with confirmed MFS.

We performed a retrospective cohort study of adults with confirmed MFS evaluated from 2018 to 2024 at Mayo Clinic. Diagnoses and vascular outcomes were confirmed by manual chart and imaging report review. Outcomes reflected ever-documented history during the study period. Multivariable logistic regression estimated sex-based associations adjusted for age, hypertension, diabetes mellitus, chronic kidney disease, and heart failure. Sensitivity analyses were performed in the genetically positive subgroup.

Among 783 patients (443 men, 340 women), men more often had ascending aortic aneurysm (89.1% vs 71.1%), any aneurysm (91.0% vs 75.3%), and any extra-aortic aneurysm (36.8% vs 25.9%) (all P ≤ 0.001). Dissection prevalence was similar by sex. Men also had more atrial fibrillation (44.0% vs 30.9%), atrial flutter (18.3% vs 12.1%), sustained ventricular tachycardia (9.7% vs 5.0%), and aortic root surgery (63.4% vs 40.3%) (all P < 0.05), whereas women more often had mitral valve prolapse (45.6% vs 37.7%; P = 0.028). After adjustment, male sex remained associated with aneurysmal burden, atrial fibrillation, sustained ventricular tachycardia, and aortic root surgery.

In this multicenter Marfan cohort, men had a greater burden of aneurysmal disease, atrial arrhythmias, sustained ventricular tachycardia, and aortic intervention, whereas dissection prevalence was similar between sexes.