## 3 Is the COP a New and Reliable Marker?
Studies have reported average values ranging from 24 to 26 in healthy individuals [17; 19; 24]. However, when analyzing the average values of patients with HF, an increase in these values was observed from 29 to 36 [18; 22; 23; 25; 26; 29]. Previous studies have shown that higher COP values are associated with a higher risk of death (see Table 2). \begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Author, Year** & **Sample** & **Number Size** & **Age, Years** & **VO2** & **Results and Cut-Off Point Values** \\ \hline [PERSON] et al. & Adult patients with & 442 & 56.2 \(\pm\) 12.5 & 17.9 \(\pm\) 6.1 & COP had the highest predictive power of all parameters analyzed in submaximal CPET, with a value \(\geq\)36 achieving a sensitivity of 100\% and a specificity of 89\% for the primary outcome (death and heart transplantation) & \\ [PERSON] et al. & Adult patients with & 442 & 56.2 \(\pm\) 12.5 & 17.9 \(\pm\) 6.1 & \\ [PERSON] et al. & HfrEF & HfrEF & (80\% male) & & 17.9 \(\pm\) 6.1 & \\  & & & & mL/kg.min\({}^{-1}\) & &  
Significantly higher COP values represent an imbalance between the cardiac and respiratory systems, directly impacting the efficiency of these mechanisms, compromising the ventilatory response during exercise, and, consequently, culminating in an increase in the \(V^{\prime\prime}\)E-\(V^{\prime}\)CO\({}_{2}\) intercept, as well as ventilation variability, which may be associated with a higher incidence of periodic breathing [30; 31]. Additionally, changes in central mechanisms, such as cardiac output (SV \(\times\) HR), and peripheral mechanisms, such as peripheral extraction rate, can compromise cardiopulmonary interactions. This has been observed in patients with HF and chronic obstructive pulmonary disease [32; 33; 34]. These adaptations could lead to changes in the COP values. [PERSON] et al. [22] demonstrated that the COP is associated with classic risk factors and that a cardiac rehabilitation program can significantly reduce COP values and improve the clinical prognosis of patients with HF. Several studies have investigated differences in the COP between men and women [19; 23; 24]. [PERSON] et al. [17] analyzed COP behavior in 624 middle-aged individuals (387 men and 237 women) and observed differences between the sexes, which were mainly attributed to lower \(V^{\prime}\)O\({}_{2}\) max, \(V^{\prime}\)E, and body dimensions. Additionally, age and sex significantly predicted the COP variable based on linear regression analysis (\(p<0.001\)), explaining 18% and 13% of COP variations in healthy men and women, respectively. [PERSON] et al. [19] added that, in trained individuals, the COP also differed significantly by sex, being lower in male athletes (COP between 22 and 30; \(p<0.001\)). The authors also highlighted that such differences seem to be independent of the training regime, which corroborates the previously described points [19]. We believe that other factors may also influence the COP and should be investigated, such as general health status, the type of ergometer used, and the force generation capacity of the inspiratory muscles. Regarding the force generation capacity of inspiratory muscles, no studies have examined the relationship between inspiratory muscle weakness (maximal inspiratory pressure  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Author, Year** & **Sample** & **Number Size** & **Age, Years** & **VO\({}_{2}\)** & **Results and Cut-Off Point Values** \\ \hline  & & & & & During a median follow-up of 288 years, there were 40 CHD deaths, and risk of CHD mortality increased continuously with increasing COP from 26. During the follow-up period, there were 607 CVD deaths and the risk of CVD mortality increased continuously with increasing COP from 25. A total of 138 481 cause deaths occurred during the follow-up period, and the risk of all-cause mortality increased continuously with increasing COP from 25 onwards, all causes in dose-response modes. COP during exercise may improve long-term risk prediction for CVD mortality.