Sex-specific VO2peak reference values and their association with major adverse cardiovascular events in Norwegian cardiac rehabilitation patients

AIMS: The aim of this study was to present sex-specific reference data for peak oxygen uptake (V̇O2peak) in Norwegian patients with coronary artery disease (CAD) undergoing cardiac rehabilitation and examine its association with major adverse cardiovascular events (MACEs). METHODS AND RESULTS: We retrospectively analysed treadmill cardiopulmonary exercise test (CPET) data from 1651 CAD patients (21% women; mean (SD) age 61 (9) years) attending inpatient cardiac rehabilitation (2004-2022). Patients were categorized by index event: myocardial infarction (MI), coronary artery bypass grafting (CABG), or percutaneous coronary intervention/pharmacologically treated CAD (PCI/CAD). Age-, sex-, and diagnosis-specific V̇O2peak reference data were generated. Associations between V̇O2peak and a combined MACE endpoint (all-cause mortality, acute coronary syndrome, stroke, or heart failure) were assessed using Cox proportional hazards models, including natural cubic splines for assessing non-linear patterns. Men had higher V̇O2peak than women (26.9 (6.7) vs. 23.2 (5.3) mL·kg-1·min-1; P < 0.001). V̇O2peak was on average 2.5 and 1.7 mL·kg-1·min-1 lower per decade of age in men and women, respectively. Patients with a previous MI had the highest V̇O2peak, followed by CABG and PCI/CAD (P < 0.001). During 7880 person-years, 510 patients (36%) experienced MACE. Each 1 mL·kg-1·min-1 higher V̇O2peak was associated with a 7% lower MACE risk (HR [95% CI]; 0.93 [0.92-0.95]) in men and 5% (HR [95% CI]; 0.95 [0.91-0.99]) in women. Patients in the highest cardiorespiratory fitness quartile had a 55% lower risk compared to the lowest quartile. Associations were consistent across CAD subcategories. Sex-specific natural cubic spline models revealed inverse, non-linear associations. CONCLUSION: This study provides novel sex- and diagnosis-specific V̇O2peak reference values for Norwegian CAD patients and confirms V̇O2peak as a strong prognostic marker, supporting its integration into routine secondary prevention and individualized care.