Published online before print February 25, 2002, doi: 10.1161/hc1102.105261
(Circulation. 2002;105:1354.)
© 2002 American Heart Association, Inc.
Plasma Norepinephrine Predicts Survival and Incident Cardiovascular Events in Patients With End-Stage Renal Disease
From CNR (C.Z., F.M., S.P., S.C., G.T.), Centre of Clinical Physiology and Division of Nephrology, Reggio Calabria, Italy; Division of Cardiology (F.A.B.), Morelli Hospital, Reggio Calabria, Italy; and Institute of Internal Medicine (A.C., L.S.M.), Geriatrics (G.S., B.S.), and Nephrosurgery (G.B., F.R., P.F.), University of Catania, Italy.
Reprint requests to Prof Carmine Zoccali, CNR Centro Fisiologia Clinica, Via Sbarre Inferiori 39, Reggio Cal, 89131 Italy. E-mail carmine.zoccali{at}tin.it
Background— Sympathetic tone is consistently raised in patients with end-stage renal disease (ESRD). We therefore tested the hypothesis that sympathetic activation is associated with mortality and cardiovascular events in a cohort of 228 patients undergoing chronic hemodialysis who did not have congestive heart failure at baseline and who had left ventricular ejection fraction >35%.
Methods and Results— The plasma concentration of norepinephrine (NE) was used as a measure of sympathetic activity. Plasma NE exceeded the upper limit of the normal range (cutoff 3.54 nmol/L) in 102 dialysis patients (45%). In a multivariate Cox regression model that included all univariate predictors of death as well as the use of sympathicoplegic agents and ß-blockers, plasma NE proved to be an independent predictor of this outcome (hazard ratio [1-nmol/L increase in plasma NE]: 1.07, 95% CI 1.01 to 1.14, P=0.03). Similarly, plasma NE emerged as an independent predictor of fatal and nonfatal cardiovascular events (hazard ratio [1-nmol/L increase in plasma NE] 1.08, 95% CI 1.02 to 1.15, P=0.01) in a model that included previous cardiovascular events, pulse pressure, age, diabetes, smoking, and use of sympathicoplegic agents and ß-blockers. The adjusted relative risk for cardiovascular complications in patients with plasma NE >75th percentile was 1.92 (95% CI 1.20 to 3.07) times higher than in those below this threshold (P=0.006).
Conclusions— Sympathetic nerve overactivity is associated with mortality and cardiovascular outcomes in ESRD. Controlled trials with antiadrenergic drugs are needed to determine whether interference with the sympathetic system could reduce the high cardiovascular morbidity and mortality in dialysis patients.
Key Words: nervous system, sympathetic • norepinephrine • kidney • risk factors • nervous system, autonomic
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