Sex-Specific Cardiovascular Phenotypes in Marfan Syndrome

Q: What are the key findings of this study?

Male sex in Marfan syndrome was associated with a greater burden of ascending aortic aneurysm (aOR 3.11), atrial fibrillation, and aortic root surgery compared to female sex, while dissection prevalence was similar.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Marfan syndrome (n=783). Intervention: Male sex vs. Female sex. Primary outcome: Ascending aortic aneurysm (aOR 3.11, 95% CI 2.10-4.60, p=<0.001).

Q: What does this research mean for the field?

Male patients with Marfan syndrome have a significantly higher burden of aneurysms, atrial and ventricular arrhythmias, and aortic root interventions than female patients, despite similar rates of aortic dissection. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To compare aneurysm burden, dissection prevalence, arrhythmias, valvular phenotypes, and cardiovascular interventions between men and women with confirmed Marfan syndrome.

Luke Dreher; Hussein Abdul Nabi; Hunter VanDolah; Jack Hartnett; Yuxiang Wang; Christine Firth; Linnea M. Baudhuin; Hicham El Masry; Chadi Ayoub; Fadi Shamoun

doi:10.1016/j.jacadv.2026.103034

July 20, 2026JACC AdvancesOpen Access

Sex-Specific Cardiovascular Phenotypes in Marfan Syndrome

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Key result

Male sex in Marfan syndrome linked to ~3-fold higher odds of ascending aortic aneurysm.

aOR 3.11
95% CI 2.10-4.60
P<0.001
n=783

Figures

Graphical abstract published by JACC Advances — Graphical abstract · Published by JACC Advances · CC BY

Why the study?

Cardiovascular complications drive morbidity in Marfan syndrome, but contemporary sex-based differences in vascular and rhythm manifestations remain incompletely defined.

Does male sex increase the risk of adverse cardiovascular phenotypes in adults with Marfan syndrome?

Key Points

To compare aneurysm burden, dissection prevalence, arrhythmias, valvular phenotypes, and cardiovascular interventions between men and women with confirmed Marfan syndrome.
Retrospective cohort study evaluating 783 adult patients (443 men and 340 women; 353 genetically positive) with confirmed Marfan syndrome from 2018 to 2024 at Mayo Clinic.
Diagnoses, imaging results, and surgical histories were manually abstracted from medical records, and multivariable logistic regression estimated sex-based associations adjusted for age, hypertension, diabetes mellitus, chronic kidney disease, and heart failure.
Men had a higher prevalence of ascending aortic aneurysm (89.1% vs 71.1%; aOR 3.11, 95% CI 2.10–4.60; P < 0.001), any aneurysm (91.0% vs 75.3%; aOR 3.18, 95% CI 2.09–4.85; P < 0.001), and any extra-aortic aneurysm (36.8% vs 25.9%; aOR 1.65, 95% CI 1.18–2.29; P = 0.003), whereas dissection prevalence did not differ by sex (aOR 0.92, 95% CI 0.65–1.29; P = 0.624).
Men experienced higher rates of atrial fibrillation (44.0% vs 30.9%; P < 0.05), sustained ventricular tachycardia (9.7% vs 5.0%; P < 0.05), and aortic root surgery (63.4% vs 40.3%; P < 0.001), while women had a higher prevalence of mitral valve prolapse (45.6% vs 37.7%; P = 0.028).

Study Design

Type

Cohort (n=783)

Multicenter

Yes

Structured PICO

Does male sex increase the risk of adverse cardiovascular phenotypes in adults with Marfan syndrome?

P

Population

783 adults with confirmed Marfan syndrome, mean age 52.6 years and 43.4% female, evaluated across Mayo Clinic sites with a mean follow-up of 12.7 years.

E

Exposure

Male sex

C

Comparator

Female sex

O

Outcome

Prevalence of cardiovascular manifestations including aneurysms, dissections, arrhythmias, valvular abnormalities, and cardiovascular interventionshard clinical

Main Result

Odds Ratio: 3.11 (95% CI 2.1–4.6)

Absolute Event Rate: 89.1% vs 71.1%

p-value: p=<0.001

Male patients with Marfan syndrome exhibit a distinct, more severe cardiovascular phenotype characterized by greater aneurysmal and arrhythmic burden, necessitating sex-aware surveillance.

Limitations

Retrospective design dependent on clinical documentation
Vascular imaging was clinically driven and not standardized
Outcomes reflect cumulative disease burden rather than temporal sequence
Molecular confirmation not uniformly available across full cohort
Residual confounding from unmeasured variables
Retrospective design depends on completeness of clinical documentation
Vascular imaging was clinically driven and not standardized across vascular beds
Molecular confirmation not uniformly available

Implication

Male sex linked to greater aneurysm and arrhythmia burden in Marfan syndrome; leaves open whether sex-specific surveillance improves outcomes.

Abstract

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Discussion

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Cite This Study

Dreher et al. (2026) conducted a cohort in Marfan syndrome (n=783). Male sex vs. Female sex was evaluated on Ascending aortic aneurysm (aOR 3.11, 95% CI 2.10-4.60, p=<0.001). Male sex in Marfan syndrome was associated with a greater burden of ascending aortic aneurysm (aOR 3.11), atrial fibrillation, and aortic root surgery compared to female sex, while dissection prevalence was similar.

synapsesocial.com/papers/6a61aea0faa9903c51169d62 https://doi.org/10.1016/j.jacadv.2026.103034

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Sex-Specific Cardiovascular Phenotypes in Marfan Syndrome

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Sex-Specific Cardiovascular Phenotypes in Marfan Syndrome

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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