Abstract
Cardiorespiratory optimal point (COP) during exercise may be a potentially clinically useful cardiopulmonary exercise testing (CPET) variable, but its prognostic relevance for adverse cardiovascular disease (CVD) outcomes is unknown. We aimed to assess the association of COP during exercise with fatal mortality outcomes and the extent to which COP could improve the prediction of CVD mortality. Cardiorespiratory optimal point, the minimum value of the ventilatory equivalent for oxygen (VE/VO2) in a given minute of a CPET, was defined in 2,205 men who underwent CPET. Hazard ratios (HRs) (95% confidence intervals [CIs]) for outcomes and measures of risk discrimination for CVD mortality were calculated. During a median follow-up of 28.8 years, 402 fatal CHDs, 607 fatal CVDs, and 1,348 all-cause mortality events occurred. COP was continually associated with each outcome in a dose-response manner. On adjustment for established and emerging risk factors, the HRs (95% CIs) for fatal CHD, fatal CVD, and all-cause mortality were 3.05 (1.94-4.81), 2.82 (1.91-4.18) and 2.46 (1.85-3.27), respectively, per standard deviation increase in COP. After further adjustment for high sensitivity C-reactive protein, the HRs were 2.82 (1.78-4.46), 2.57 (1.73-3.81), and 2.27 (1.70-3.02), respectively. Addition of COP to a CVD mortality risk prediction model containing established risk factors was associated with a C-index change of 0.0139 (0.0040 to 0.0238; p = 0.006) at 25 years. COP during exercise is directly associated with fatal cardiovascular and all-cause mortality events in dose-response fashions. COP during exercise may improve the prediction of the long-term risk for CVD mortality.
