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 Ͼ35%. 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 ␤-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, Pϭ0.03). 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, Pϭ0.01) in a model that included previous cardiovascular events, pulse pressure, age, diabetes, smoking, and use of sympathicoplegic agents and ␤-blockers. The adjusted relative risk for cardiovascular complications in patients with plasma NE Ͼ75th percentile was 1.92 (95% CI 1.20 to 3.07) times higher than in those below this threshold (Pϭ0.006). 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.

Abstract. Patients with end-stage renal disease (ESRD) are at high risk for heart failure, but the prevalence and the prognostic value of asymptomatic systolic dysfunction in these patients are unknown. In this prospective cohort study, the authors have therefore assessed by echocardiography the prevalence and the prognostic value of systolic function as estimated by ejection fraction (EF), fractional shortening at endocardial level (endoFS), and at midwall (mwFS), in a cohort of 254 asymptomatic dialysis patients. Systolic dysfunction had a prevalence rate of 26% by endoFS and of 48% by mwFS. During the follow-up period, 125 patients had one or more fatal and nonfatal CV events. On multivariate COX regression analysis, the three LV systolic function indicators were independently associated with incident fatal and nonfatal CV events, and there were no differences in the predictive power of these indicators (P Ͼ 0.30). The prediction power of LV function indicators was largely independent of traditional and novel risk factors in ESRD such as C-reactive protein and asymmetric dimethyl arginine (ADMA). ADMA was significantly related with LV function indicators as well as with mortality and incident CV events, but these links were much reduced (P ϭ NS) in models including LV function indicators. Of note, the risk of CV events was minimal in patients with normal LV mass and function, intermediate in patients with either LVH or systolic dysfunction, and maximal in patients displaying both alterations. The study of myocardial contractility by echocardiography provides prognostic information independently of LV mass and other risk factors in ESRD. Risk stratification by simple systolic function parameters may prove useful in secondary prevention strategies in these patients.Cardiac disease is the major cause of death in patients with end-stage renal disease (ESRD). The detection of echocardiographic abnormalities associated with subclinical cardiac disease is considered to be an important step for the characterization of individuals at risk for heart failure in the general population (1). Although the problem is now felt to be of paramount importance, there are very few studies examining the prognostic power of echocardiographic abnormalities in ESRD. Landmark observations by Parfrey and Foley (2-5) in the 1990s showed that alterations of left ventricular (LV) mass and function are exceedingly frequent in patients with ESRD, and the prediction value of LVH in the dialysis population is now firmly established (3,5-7). In contrast, the prognostic power of systolic function in ESRD has been scarcely studied. The issue is important because systolic function was a marker of shorter survival in a series of patients studied on the eve of renal transplantation (8) and because associations between changes in fractional shortening and subsequent cardiac failure (9) or between systolic function and survival were reported in a population with a high prevalence of heart failure (4). Yet the prevalence of systolic dysfunction in asym...

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