In recent years, several studies have used the measurement of carotid intima-media thickness (IMT) as a marker of early atherosclerosis: IMT has been shown to correlate significantly with the presence of coronary artery disease (CAD) and to predict fatal and not fatal cerebro- and cardio-vascular events. These findings highlight the importance of recognizing and managing early stages of atherosclerosis for effective cardiovascular prevention. Beyond traditional established cardiovascular risk factors, inflammation has been shown to be crucial throughout atherosclerosis from endothelial dysfunction to plaque rupture and thrombosis. Several studies have shown the existence of a strong relation between CAD and fibrinogen or highly sensitive C-reactive protein (hs-CRP) levels and their predictive role has been examined through stratification or multivariable statistical analyses: levels of these markers of inflammation have been independently associated with the incidence of coronary events after adjusting for traditional cardiovascular risk factors. Recent studies have further addressed the importance of therapeutical modulation of hs-CRP levels in high-risk patients for the prevention of vascular events. The strong relationship between hs-CRP and IMT may potentially account for the complex role of hs-CRP and IMT in the pathogenesis of cardiovascular events. However, beyond the utility of measuring markers of inflammation to assess patients with subclinical carotid atherosclerosis at higher risk of vascular events, further studies are needed to evaluate the therapeutic implications in this category of patients.

Background: Cardiopulmonary exercise testing with ventilatory expired gas analysis (CPET) has proven to be a valuable tool for assessing patients with chronic heart failure (CHF). The maximal oxygen uptake (peak V02) is used in risk stratification of patients with CHF. The minute ventilation-carbon dioxide production relationship (VE/VCO2 slope) has recently demonstrated prognostic significance in patients with CHF. Methods: Between January 2006 and December 2007 we performed CPET in 184 pts (146 M, 38 F, mean age 59.8 ± 12.9 years), with stable CHF (96 coronary artery disease, 88 dilated cardiomyopathy), in NYHA functional class II (n.107) - III (n.77), with left ventricular ejection fraction (LVEF) ≤ 45%,. The ability of peak VO2 and VE/VCO2 slope to predict cardiac related mortality and cardiac related hospitalization within 12 months after evaluation was examined. Results: Peak VO2 and VE/VCO2 slope were demonstrated with univariate Cox regression analysis both to be significant predictor of cardiac-related mortality and hospitalization (p < 0.0001, respectively). Non survivors had a lower peak VO2 (10.49 ± 1.70 ml/kg/min vs. 14.41 ± 3.02 ml/kg/min, p < 0.0001), and steeper Ve/VCO2 slope (41.80 ± 8.07 vs. 29.84 ± 6.47, p < 0.0001) than survivors. Multivariate survival analysis revealed that VE/VCO2 slope added additional value to VO2 peak as an independent prognostic factor (χ2: 56.48, relative risk: 1.08, 95% CI: 1.03 – 1.13, p = 0.001). The results from Kaplan-Meier analysis revealed a 1-year cardiac-related mortality of 75% in patients with VE/VCO2 slope ≥ 35.6 and 25% in those with VE/VCO2 slope < 35.6 (log rank χ2: 67.03, p < 0.0001) and 66% in patients with peak VO2 ≤ 12.2 ml/kg/min and 34% in those with peak VO2 > 12.2 ml/kg/min (log rank χ2: 50.98, p < 0.0001). One-year cardiac-related hospitalization was 77% in patients with VE/VCO2 slope ≥ 32.5 and 23% in those with VE/VCO2 slope < 32.5 (log rank χ2: 133.80, p < 0.0001) and 63% in patients with peak VO2 ≤ 12.3 ml/kg/min and 37% in those with peak VO2 > 12.3 ml/kg/min (log rank χ2: 72.86, p < 0.0001). The VE/VCO2 slope was demonstrated with receiver operating characteristic curve analysis to be equivalent to peak VO2 in predicting cardiac-related mortality (0.89 vs. 0.89). Although area under the receiver operating characteristic curve for the VE/VCO2 slope was greater than peak VO2 in predicting cardiac-related hospitalization (0.88 vs 0.82), the difference was no statistically significant (p = 0.13). Conclusion: These results add to the present body of knowledge supporting the use of CPET in CHF patients. The VE/VCO2 slope, as an index of ventilatory response to exercise, is an excellent prognostic parameter and improves the risk stratification of CHF patients. It is easier to obtain than parameters of maximal exercise capacity and is of equivalent prognostic importance than peak VO2.