Sympathetic activation and heart rate thresholds for cardiovascular risk in chronic kidney disease

AIM: The current study was designed at assessing whether the sympathetic cardiovascular drive (SNS) is differently activated in chronic kidney disease (CKD) patients displaying less or more elevated resting heart rate (HR) values. It was also designed at determining at which HR cutoff value the SNS displays a greater activation. METHODS: In 95 CKD middle-age patients we evaluated muscle sympathetic nerve activity (MSNA, microneurography) and venous plasma norepinephrine (HPLC assay), subdividing the patients in different groups according to their resting clinic and 24-h HR. RESULTS: In CKD progressively greater values of clinic or 24-h HR were associated with a progressive increase in both MSNA and norepinephrine. HR cutoff values indicated by large-scale clinical trials for determining cardiorenal risk, that is more than 80 bpm, were associated with MSNA values significantly greater than the ones detected in patients with lower HR, this being the case also for norepinephrine. Both MSNA and norepinephrine were significantly related to clinic ( r  = 0.47, P  < 0.0001 and r  = 0.26, P  < 0.0001, respectively) and 24-h ( r  = 0.42, P  < 0.0001 and r  = 0.27, P  < 0.0001, respectively) HR. MSNA, norepinephrine, but not HR, were significantly and inversely related to estimated glomerular filtration rate (eGFR) values ( r  = -0.47, r  = -0.23, P  < 0.0001 and P  < 0.02, respectively). CONCLUSION: In CKD both clinic and 24-h HR values greater than 80 bpm are associated with an enhanced sympathetic activation, which parallelles for magnitude the HR elevations. The sensitivity of HR as sympathetic marker is limited; however, no significant relationship being detected between HR and eGFR or left ventricular mass index.