Plasma norepinephrine predicts survival and incident cardiovascular events in patients with end-stage renal disease.
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%.


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 beta-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 beta-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.
Zoccali
Carmine
C
CNR, Centre of Clinical Physiology and Division of Nephrology, Reggio Calabria, Italy. carmine.zoccali@tin.it
Mallamaci
Francesca
F
Parlongo
Saverio
S
Cutrupi
Sebastiano
S
Benedetto
Francesco Antonio
FA
Tripepi
Giovanni
G
Bonanno
Graziella
G
Rapisarda
Francesco
F
Fatuzzo
Pasquale
P
Seminara
Giuseppe
G
Cataliotti
Alessandro
A
Stancanelli
Benedetta
B
Malatino
Lorenzo Salvatore
LS
Cateliotti
Alessandro
A
D002318:Cardiovascular Diseases / Q000401:mortality*; D002908:Chronic Disease; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000401:mortality* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D006435:Renal Dialysis / Q000401:mortality; D012307:Risk Factors; D013318:Stroke Volume; D016019:Survival Analysis; D015996:Survival Rate; D013564:Sympathetic Nervous System / Q000378:metabolism; D016277:Ventricular Function, Left
D009638:Norepinephrine