Sex-related differences in the association between septal wall thickness and survival
Authors: Khoury S , Zornitzki L , Laufer-Perl M , Granot Y , Bhatia R , Tome M , Flint N , Hochstadt A , Banai S , Topilsky Y 
Published: November 2023

Abstract

Background
Septal hypertrophy is associated with increased morbidity and mortality but data regarding the effect of sex on the association between septal wall thickness and survival is limited and uniform cutoffs in men and women are often used in clinical practice and research.

Objective
To investigate the differences between men and women in the association between septal wall thickness and survival.

Methods
A retrospective analysis of consecutive unselected patients undergoing echocardiography between March 2010 and February 2021 in a large tertiary referral center. Echocardiography studies were performed according to standard protocol. Survival data was validated against the ministry of health records. Cox regression analysis was used to evaluate the association between septal thickness and mortality.

Results
A total of 71,965 individuals were included. There were 32,419 (46%) female and 38,546 (54%) male examinees. Females were older than males (65 + 18 vs. 62 + 18, p &lt; 0.001), less likely to have diabetes (16% vs. 19%, p&lt;0.001) or ischemic heart disease (11% vs. 25%, p&lt;0.001) but more frequently had atrial fibrillation (11% vs. 10%, p&lt;0.001). Females had lesser septal wall thickness than males (10.3 + 2 vs. 11.1 + 2, p &lt; 0.001), lower left ventricular mass index (89 + 29 vs. 102 + 33, p&lt;0.001), lower left ventricular end diastolic and end systolic diameter index. Men had lower ejection fraction than women (55% + 9 vs. 58% + 6, p &lt; 0.001).
Over a mean follow-up of 59.1 ± 37 months there were 9631 (25%) and 8429 (26%) deaths in the male and female groups, respectively. In multivariate cox regression analysis, septal thickness was an independent predictor for all-cause mortality in both sexes (Table). When using a uniform cutoff of 12mm for septal thickness for both sexes, the multivariate adjusted HR was 1.00 (CI 95%: 0.94-1.08, p=0.83) for males and 1.15 (CI 95%: 1.07-1.25, p&lt;0.001) for females. The Kaplan–Meier mortality-free survival curve by septal thickness and sex is shown (figure).
Septal thickness had an incremental prognostic significance in both sexes. On multivariate analysis it became statistically significant in females at 11mm with HR 1.51 (CI95%:1.06-1.24, p&lt;0.001) and in males at 13mm with HR 1.21 (CI95%: 1.12-1.36, p&lt;0.001). When using indexed septal thickness for BSA, the statistically significant cutoff was 6mm/BSA for women, HR 1.08 (CI 95%: 1-1.17, p=0.04) and 6.2mm/BSA for men, HR 1.07 (CI 95%: 1-1.15, p=0.05).

Conclusions
In an large unselected cohort of patients, septal hypertrophy had an incremental prognostic significance in both sexes and was associated with increased mortality at a lower threshold in women than in men. This may at least partially explain the delayed diagnosis and worse prognosis reported in females in many conditions characterized by septal hypertrophy. Applying a lower absolute value or using indexed measurements may facilitate early diagnosis and improve prognostication in females.