## 4 Does COP Have Independent Prognostic Value? Several studies have evaluated the prognostic relevance of the COP for adverse cardiovascular disease outcomes and mortality [17, 18, 21, 23, 24, 25, 29]. A study of healthy individuals found that the COP was associated with fatal mortality outcomes and that high COP values were associated with a higher risk of mortality [29]. The authors demonstrated a strong and independent association between the COP and coronary disease, general cardiovascular disease, and all-cause mortality when the COP was greater than 25, following a dose-response relationship. [PERSON] et al. [23], in a prospective study with a mean follow-up of 28 years, demonstrated the existence of a linear relationship between the COP and the risk of sudden cardiac death following a dose-response relationship in middle-aged men. Figure 3: Illustrative examples of cardiopulmonary exercise test responses in patients with HF without IMW. A multi-panel graphic display to represent metabolic (**C**,**E**), cardiovascular response (**B**,**E**), ventilatory (**A**,**D**,**F**), gas exchange (**F**,**H**,**I**), and breathing pattern (**G**) variables during an incremental CPET. In a 56-year-old heart failure patient with inspiratory muscle strength preserved (PImax = 98 cmH2O), with a severely reduced ejection fraction. The authors further stated that the COP could potentially be used to predict the established cardiovascular disease risk factors. Consequently, these studies posited that the COP is a variable capable of detecting cardiovascular risk and mortality in both healthy individuals and those with HF, as previously noted. However, they did not compare its predictive capacity for mortality with those of other variables commonly used in the literature. This constitutes a critical consideration because, while the COP may demonstrate significant values in a univariate analysis model, its performance may differ in a multivariate logistic regression model, implying that it may not independently influence mortality. In contrast, [PERSON] et al. [PERSON] et al. (2018) have incorporated several variables into the multivariate model, such as age, smoking status, history of type 2 diabetes, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, body mass index, fasting plasma glucose, alcohol consumption, prevalent coronary heart disease, family history of coronary heart disease, use of cholesterol medication, total physical activity, and socioeconomic status, highlighting the crucial role of the COP as a predictor of mortality. We analyzed the data collected by our group on patients with HF ([PERSON], 2016), examining the ROC curve behavior of various non-invasive prognostic variables such as the COP, \(V^{\prime}\)O\({}_{2}\), PImax, \(V^{\prime}\)E-\(V^{\prime}\)CO\({}_{2}\) slope, 6 min walk test, OUES, and circulatory power (Table 3). The COP had the lowest area under the ROC curve, demonstrating a lower sensitivity than the other variables (Figure 4). The OUES significantly outperformed the reference line, exhibiting a larger area than all other variables. This appears to be a unique finding, suggesting that the OUES variable may be a better predictor of mortality than the COP. However, further studies are required to confirm these results. Consequently, the COP may represent an essential index for the risk of mortality, demonstrating an inverse and dose-dependent relationship. The higher the COP value, the greater the risk of mortality from cardiovascular disease and all-cause mortality. Finally, the determination of the COP could also have prognostic utility, being relevant when a test of maximum effort is not feasible or desirable. However, further research is needed to confirm its prognostic relevance, with more comprehensive studies in different populations, particularly in patients with HF.