Women with marfan syndrome, are they truly at a lower risk of cardiovascular events? Natural history of cardiovascular outcomes in women with marfan syndrome

Background Cardiovascular (CV) complications in patients with Marfan syndrome (MFS) remain the leading causes of increased morbidity and early mortality. Previous studies have reported a higher prevalence of cardiovascular events (CVE) in men compared to women, however, data on sex-related differences in the natural history of CVE and prevalence of repeat events is scarce. Purpose To study the impact of sex in the natural history of CVE, repeat events and death Methods We collected demographics, clinical characteristics, aortic dimensions, and CVE data in patients seen in our Marfan clinic from 2000 to 2021. CVE were defined as the presence of aortic dissection, prophylactic aortic surgery, valvular surgery and/or CV death Results We identified 308 patients (152 women, 49.4%) with a mean age at diagnosis of 25±16 years old. The mean follow-up (FU) was 11±9 years and mean age at the end of FU was 39±15 years old. When comparing men vs women, there were no differences in age at diagnosis, age at the end of follow up, genetic status or family history of aortic dissection. Systemic score was similar between both groups, however, women had a higher prevalence of varicose veins (9.9% vs 3.8%, p=0,036). On the contrary, men had higher prevalence of stretch marks (42.9% vs 29.6%, p=0,015), pectus excavatum (25.6% vs 13.2%, p=0,003) and pectus carinatum (21.2% vs 12.5%, p=0,043, table 1). At the start of FU, 41% of the patients presented aortic dilatation and 11% had experienced a CVE. After a mean FU of 11 years, aortic dilatation increased to 53.6% and CVE to 36%. Aortic dilatation was similar between men and women (47.3% vs 52.7%, p=0,785), however, CVE were higher in men (43.6% vs 29.6%; p=0,013). The type of event and age at CVE were similar between both groups (table 2). Despite a higher prevalence of CVE in men, the risk of CVE in women remained significant over time. The prevalence of repeat CVE (30.9% vs 17.8%, p=0,123) and CV death (4.4% vs 2.2%, p=0,542) were similar between both groups. Moreover, when studying women diagnosed after menopause (12 women), 58.3% presented aortic dilatation and almost 42% of them underwent cardiovascular surgery (4 elective aortic surgery and 1 valvular surgery). Furthermore, 13 women experienced uneventful pregnancies before the diagnosis of MFS and experienced CVE years after pregnancy (9 elective aortic surgery, 4 aortic dissection). Conclusions In our large longitudinal cohort of patients with Marfan syndrome followed for a mean of 11 years, the prevalence of CVE was higher in men. Despite this, women were at a significant risk of experiencing CVE during their lifetime, including after uncomplicated pregnancies or menopause, and presented repeat events or need for re-intervention and CV death in a similar proportion to men. These findings highlight the importance of long-term follow-up and support individualised CV surveillance in men and women with Marfan syndrome.