Plasma Norepinephrine Predicts Survival and Incident Cardiovascular Events in Patients With End-Stage Renal Disease
Abstract
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 β-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 β-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.
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Ongoing systemic sympathetic activation has long been thought to be noxious in heart failure and renal failure.
“Ongoing systemic sympathetic activation has long been thought to be noxious, in heart failure 18,19 and renal failure.113”
From Obesity Paradox in Hypertension: Is This Because Sympathetic Activation in Obesity-Hypertension Takes a Benign Form? (2018) · cites this paper as [113]
The plasma concentration of norepinephrine predicts the incidence of cardiovascular events, and survival, in patients with end-stage renal disease.
“A striking observation is that of Zoccali and colleagues, who demonstrated the plasma concentration of norepinephrine to predict the incidence of cardiovascular events, and survival, in patients with end-stage renal disease10.”
From The Sympathetic Nervous System Alterations in Human Hypertension (2015) · cites this paper as [10]
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- Authors
- Zoccali, C., Mallamaci, F., Parlongo, S., Cutrupi, S., Benedetto, F. A., Tripepi, G., Bonanno, G., Rapisarda, F., Fatuzzo, P., Seminara, G., Cataliotti, A., Stancanelli, B., & Malatino, L. S.
- Affiliations
- University of Catania (IT)
- ORCID
- Venue
- Circulation
- Published
- 2002-03-19
- Volume
- 105
- Issue
- 11
- Pages
- 1354-1359
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2166904705
- Cited by
- 519
- References
- 36
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 12 · 2023: 16 · 2022: 15 · 2021: 14 · 2020: 20 · 2019: 11 · 2018: 20 · 2017: 29 · 2016: 31 · 2015: 30 · 2014: 38 · 2013: 27 · 2012: 31
- FWCI
- 12.27
- Type
- journal article
- Language
- en
- Update notices
- correction (2002-05-07)
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Regione Calabria
- Topics
- Health Sciences › Medicine › Nephrology › Dialysis and Renal Disease Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Failure Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- plasma norepinephrine, end-stage renal disease, hemodialysis, sympathetic activation, cardiovascular mortality, cardiovascular events, beta-blockers, cardiovascular risk prediction
- MeSH terms
- Cardiovascular Diseases, Chronic Disease, Female, Renal Dialysis, Humans, Kidney Failure, Chronic, Male, Middle Aged, Norepinephrine, Predictive Value of Tests, Risk Factors, Stroke Volume, Sympathetic Nervous System, Cohort Studies, Comorbidity, Survival Rate, Proportional Hazards Models, Survival Analysis, Ventricular Function, Left
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