Cardiorespiratory optimal point during exercise testing and sudden cardiac death: A prospective cohort study

Background: Cardiorespiratory optimal point (COP) during exercise, a potentially useful submaximal cardiopulmonary exercise testing (CPET) variable, may be an independent risk factor for cardiovascular disease outcomes. However, the relationship of COP with risk of sudden cardiac death (SCD) has not been previously investigated. We sought to evaluate the association between COP during exercise and SCD risk and determine whether COP improves SCD risk prediction.

Methods: COP, the minimum value of the ventilatory equivalent for oxygen (VE/VO2) in a given minute of a CPET, was ascertained in 2190 men who underwent clinical exercise testing. Hazard ratios (HRs) (95% confidence intervals [CIs]) and measures of risk discrimination for SCD were calculated.

Results: A total of 240 SCDs death occurred during a median follow-up of 28.8 years. COP was linearly associated with SCD in a dose-response manner. In a multivariable model comprising several established and emerging CVD risk factors, the HR (95% CI) for SCD was 2.51 (1.36-4.62) per standard deviation increase in COP. This was minimally attenuated to 2.36 (1.27-4.37) on further adjustment for high sensitivity C-reactive protein. The association did not vary importantly in several relevant clinical subgroups. Addition of COP to a SCD risk score was associated with a C-index change of 0.0086 (0.0005 to 0.0167; p = .038) and difference in -2 log likelihood (p = .017).

Conclusions: COP during exercise is strongly, inversely and independently associated with SCD in a graded fashion. COP during exercise may potentially be used for the prediction of the long-term risk for SCD beyond established CVD risk factors.