Svenningsen A;  Norwegian University of Science and Technology, Trondheim  Norway.
Hollekim-Strand SM; Sandmael JA; Engan H; Wisloff U; Letnes JM

European Journal of Preventive Cardiology. 33(13):2467-2476, 2026 Sep 22.

AIMS: The aim of this study was to present sex-specific reference data for
peak oxygen uptake (VO2peak) 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 VO2peak reference data were
generated. Associations between VO2peak 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 VO2peak
than women (26.9 (6.7) vs. 23.2 (5.3) mL.kg-1.min-1; P < 0.001). VO2peak
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
VO2peak, 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 VO2peak 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 VO2peak
reference values for Norwegian CAD patients and confirms VO2peak as a
strong prognostic marker, supporting its integration into routine
secondary prevention and individualized care.