Cardiorespiratory optimal point during exercise testing is related to cardiovascular and all‐cause mortality

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.

Cardiorespiratory Optimal Point Is a Submaximal Exercise Test Variable and a Predictor of Mortality Risk

“…Within males, as hypothesized, COP had a significant positive association with all-cause mortality, similar to findings of previous research on different cohorts. 10 , 13 , 14 However, contrary to our hypothesis, significant relationships between COP and mortality were not observed in females following adjustments for potential confounders. In addition, the concordance index values indicated that V˙ o 2peak was not a better discriminant of risk compared with COP.…”

“…Thus, the present study examined the prognostic utility of COP in apparently healthy males and females. Within males, as hypothesized, COP had a significant positive association with all-cause mortality, similar to findings of previous research on different cohorts 10,13,14. However, contrary to our hypothesis, significant relationships between COP and mortality were not observed in females following adjustments for potential confounders.…”

“…Other studies have reported COP to be significantly associated with mortality in patients with heart failure11 or have reported statistically nonsignificant trends between COP and mortality in patients with transposition of the great arteries 12. Finally, studies on Finnish males with and without CVD found COP to be a significant predictor of sudden cardiac death, CVD mortality, and all-cause mortality 13,14…”

“…12 Finally, studies on Finnish males with and without CVD found COP to be a significant predictor of sudden cardiac death, CVD mortality, and all-cause mortality. 13,14 Previous research highlights the potential prognostic utility of COP; however, additional research with larger sample sizes of males and females is needed to substantiate this relationship in apparently healthy adults. To date, previous research has focused primarily on the relationship between COP and mortality in males and/or those with CVD.…”

“… 12 Finally, studies on Finnish males with and without CVD found COP to be a significant predictor of sudden cardiac death, CVD mortality, and all-cause mortality. 13 , 14 …”