Estimated aortic pulse wave velocity predicts adverse events in females with thoracic aortic aneurysms
Authors: Coutinho T , Beauchesne L , Chan K L , Dennie C , Wells G A , Boodhwani M 
Published: October 2024

Abstract

Introduction
Despite being more common in males, thoracic aortic aneurysms (TAAs) have worse prognosis in females. Females with TAA are 3x more likely to experience acute aortic syndromes, and 40% more likely to die than their male counterparts, but mechanisms underlying this paradox are incompletely understood. The estimated aortic pulse wave velocity (e-PWV) is a marker of aortic stiffness that can be used widely due to its simplicity, as it does not require specialized equipment. We have previously shown that e-PWV was independently associated with faster TAA growth,(1) and that this association was twice as strong in females than males, but the role of e-PWV as a predictor of adverse outcomes in TAA remains unknown.

Purpose
We sought to evaluate the sex-specific association of e-PWV with adverse outcomes in patients with TAA.

Methods
We performed a prospective study of 102 males and 48 females with TAA. e-PWV was calculated according to validated equations utilizing age, mean arterial pressure, and presence/absence of cardiovascular risk factors.(2) The primary outcome was a composite of acute aortic syndromes, death, or elective aortic surgery. We used a Cox proportional hazard model to determine the independent association of e-PWV with the primary outcome, adjusted for age, BSA, aneurysm size and location, hypertension, and pulse pressure. Sex-specific models were performed if the interaction of sex*e-PWV was significant (P≤0.05). Univariate logistic regression models were performed to determine the c-statistic for e-PWV in predicting adverse outcomes, and the best e-PWV cutoff for this prediction was established based on sensitivity and specificity. Kaplan-Meier curves were performed using this cut-off.

Results
A summary of study design and results is presented in Picture 1. Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and e-PWV was 9.5±1.9 m/s (not different between sexes, P&gt;0.07 for each). Mean follow-up was 4.6±2.4 years in females and 5.5±2.3 years in males, P=0.031. The primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 11 deaths - 3 of which followed surgery). The interaction term sex*e-PWV was significant (P=0.0001), so sex-specific models were performed. e-PWV independently predicted the primary outcome in females (HR for 1m/s increase in e-PWV: 3.4; 95% confidence interval (CI): 1.1-14.7, P=0.033), but not in males (HR: 0.87; 95% CI: 0.50-1.51, P=0.622). In females, e-PWV had a c-statistic of 0.860 for the detection of the primary outcome, with a best e-PWV cutoff of 11.58 m/s (73% sensitivity, 92% specificity). Kaplan-Meier curves for the primary outcome in females using this cutoff are shown in Picture 2.

Conclusion
e-PWV independently predicts adverse outcomes in females with TAA, highlighting a novel marker for risk stratification and therapeutic targeting.Study summaryKaplan-Meier curves