Measures of aortic function independently predict adverse events in females with thoracic aortic aneurysms

Abstract Background/Introduction Thoracic aortic aneurysm (TAA) is a disease associated with high morbidity and mortality. TAA is more common in males, but females with TAA experience faster aneurysm growth and a higher risk of acute aortic syndromes and death. We have previously demonstrated that measures of aortic function, correlating with abnormal aortic wall architecture and reflecting worse aortic health, are independently associated with aneurysm size and expansion, specifically among females. To date, international guidelines focus on aneurysm size to determine timing for prophylactic surgical intervention, however adverse outcomes can occur before surgical thresholds are met, highlighting the need for novel risk assessment tools in TAA. Purpose We sought to evaluate whether measures reflecting proximal aortic function (where the TAA is located) would independently predict adverse outcomes in men and women with TAA. These measures include: aortic characteristic impedance (Zc), proximal aortic compliance (PAC), proximal aortic pulse wave velocity (PAoPWV) and the aortic stiffness-thickness product (Eh). Study summary is illustrated in Picture 1. Methods We performed a prospective study of 102 males and 48 females with TAA. Measures reflecting proximal aortic function were non-invasively assessed with validated methodology combining arterial tonometry with transthoracic echocardiography at the time of enrollment. The primary outcome was a composite of acute aortic syndromes, death, or guideline-directed aortic surgery. We used Cox proportional hazard models to determine the independent associations of aortic function measures with the primary outcome. PAoPWV and Eh were log-transformed to reduce skewness. Models were adjusted for variables previously demonstrated to predict adverse outcomes in TAA: age, sex, aneurysm size and etiology, and mean arterial pressure (MAP). Sex-specific models were performed if the interaction of sex *aortic function measure was significant (P≤0.05). Results Mean age was 62±12 years, 70 (47%) had degenerative etiology, baseline aneurysm size was 46.3±4.3mm, and MAP was 90±10 mmHg (not different between and women, P>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. Our primary outcome occurred in 37 (25%) participants (3 dissections, 3 intramural hematomas, 1 aortic rupture, 22 elective surgical repairs and 8 deaths). Interaction terms of sex with each of the aortic function variables were significant (P<0.04 for each). Results of the sex-specific models are summarized in Picture 2. We observed that higher Zc, PAoPWV and Eh, and lower PAC were each independently associated with an increased risk of adverse outcomes among females only. Conclusions Among females with TAA, measures of proximal aortic function are independent predictors of adverse events, highlighting novel markers for risk stratification and therapeutic targeting.Illustrative Summary

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