Associations between cardiorespiratory fitness, sex and long term mortality amongst adults undergoing exercise treadmill testing

Background: Cardiorespiratory fitness (CRF) varies with sex and is an independent predictor of mortality. We sought to investigate sex differences in the exercise protocol selected, CRF levels, and their relationships with long term all-cause mortality.

Methods: In a 25-year stress testing registry spanning from 1991 to 2014, consecutive all-comer patients who underwent exercise stress testing at Cleveland Clinic were categorized by sex, stress protocol and imaging modality. All tests were conducted by one or more of stress test technicians, sonographers and nuclear medicine technologists, and interpreted by cardiologists. The primary outcome all-cause mortality was analyzed in using multivariable Cox regression.

Results: In 120,705 patients, the mean age was 53.3 ± 12.5 years, and 41% were female. Females were more commonly referred for non-Bruce exercise protocols (modified Bruce, Cornell 0, 5 and 10, Naughton and modified Naughton) with odds ratio of 2.62; 95% confidence interval (95%CI) (2.54-2.70) after adjusting for age and comorbidities. When also adjusting for the protocol chosen, females achieved lower CRF with beta -1.40, 95% CI (-1.43, -1.37). There were 8426 (6.9%) deaths during a mean follow-up of 8.7 years. Both female sex and CRF were independently associated with lower all-cause mortality with hazards ratio (95%CI) of 0.44 (0.41-0.46) and 0.41 (0.39-0.42) respectively, after adjusting for age, co-morbidities and protocol chosen.

Conclusions: Women were more likely referred for less demanding exercise protocols, more imaging protocols and achieved lower CRF than men. Despite this, female sex was associated with significantly lower long term mortality for equivalent CRF level in adjusted analyses.