Comparison of endothelial vasodilator function, inflammatory markers, and N-terminal pro-brain natriuretic peptide in patients with or without chronotropic incompetence to exercise test

Objective: To investigate the role of endothelial function, inflammatory markers, and N-terminal pro-brain natriuretic peptide (NT-proBNP) in patients with impaired chronotropic response during exercise test. Methods: 86 subjects were enrolled. Treadmill exercise test was conducted according to the modified Bruce protocols. Brachial ultrasound was used to measure endothelium dependent flow mediated vasodilatation (FMD). Chronotropic incompetence was defined as either failure to achieve 85% of the age predicted maximum heart rate or a low chronotropic index (<0.8). Results: Of the 86 patients, 20 (23%) exhibited chronotropic incompetence. The patients were divided into three groups according to chronotropic index: group 1, <0.8 (n = 20); group 2, 0.8-1.0 (n = 26); and group 3, >1.0 (n = 40). Patients with impaired chronotropic response had significantly lower FMD than those with higher chronotropic response (mean (SD) 2.8 (1.9)% v 5.0 (2.8)% v 5.3 (2.5)%, p = 0.002, for groups 1, 2, and 3, respectively). Serum concentrations of high-sensitivity C reactive protein (hsCRP), monocyte chemoattractant protein-1 (MCP-1), and NT-proBNP were significantly higher in group 1 than in groups 2 and 3 (hsCRP: 19 (12) v 9 (6) v 9 (6) mg/l, p < 0.05; MCP-1: 140 (51) v 133 (60) v 108 (46) pg/ml, p = 0.046; NT-proBNP: 4760 (1980) v 3710 (850) v 3910 (1060) mg/l, p = 0.019, respectively). In addition, chronotropic index was significantly related to FMD (r = 0.380, p = 0.001) and inversely related to hsCRP (r = 20.267, p = 0.013). By multivariate analysis, impaired chronotropic response was significantly related to endothelial dysfunction (p = 0.012). Conclusion: Patients with impaired chronotropic response to graded exercise had endothelial dysfunction, enhanced systemic inflammation, and higher NT-proBNP concentrations. These findings may partly explain the mechanism of chronotropic incompetence as a predictor of cardiovascular risk and increased mortality.