title: Increased pasma S-nitrosothiol concentrations predict cardiovascular outcomes among patients with end-stage renal disease: a prospective study.
abstract: The plasma concentrations of S-nitrosothiols, which are circulating nitric oxide metabolites with potential biologic activity, are increased among patients undergoing chronic hemodialysis (HD). However, the ability of S-nitrosothiols to release nitric oxide at physiologically relevant sites may be reduced among HD patients, because of impaired availability and/or activity of factors involved in S-nitrosothiol breakdown. The resultant lack of S-nitrosothiol bioavailability could contribute to the high cardiovascular risk for such patients. A possible relationship between plasma S-nitrosothiol levels and cardiac outcomes, as well as all-cause mortality rates, was investigated in a cohort of 250 chronic HD patients and who were undergoing regular dialysis three times per week were monitored for 1 yr. During that follow-up period, major cardiac events and all-cause deaths were prospectively recorded. At baseline, high plasma S-nitrosothiol levels (>2 micro M, corresponding to the top quartile of all measured values) were independently associated with pulse pressure in an adjusted multivariate analysis (odds ratio, 1.03; 95% confidence interval, 1.01 to 1.05; P = 0.007). During the follow-up period, 36 patients died (16 as a result of cardiac causes) and 33 patients experienced major adverse cardiac events. In an adjusted Cox proportional-hazards model, high plasma S-nitrosothiol concentrations (i.e., the top quartile versus the three other quartiles) were an independent predictor of cardiac events (hazard ratio, 3.30; 95% confidence interval, 1.61 to 6.76; P = 0.001) but not of all-cause death. Therefore, among chronic HD patients, markedly elevated plasma S-nitrosothiol levels are associated with pulse pressure and predict cardiovascular outcomes. These findings support the hypothesis that impaired S-nitrosothiol bioavailability in uremia is an important factor for the excessive cardiovascular risk among HD patients.
authors.affiliation: INSERM U507, Necker Hospital, Paris, France. massy@necker.fr
authors.forename: Ziad A
authors.initials: ZA
authors.lastname: Massy
authors.forename: Christine
authors.initials: C
authors.lastname: Fumeron
authors.forename: Didier
authors.initials: D
authors.lastname: Borderie
authors.forename: Philippe
authors.initials: P
authors.lastname: Tuppin
authors.forename: Thao
authors.initials: T
authors.lastname: Nguyen-Khoa
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Benoit
authors.forename: Christian
authors.initials: C
authors.lastname: Jacquot
authors.forename: Claude
authors.initials: C
authors.lastname: Buisson
authors.forename: Tilman B
authors.initials: TB
authors.lastname: Drüeke
authors.forename: Ohvanesse G
authors.initials: OG
authors.lastname: Ekindjian
authors.forename: Bernard
authors.initials: B
authors.lastname: Lacour
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Iliou
mesh_terms: D002318:Cardiovascular Diseases / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000150:complications*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D026403:S-Nitrosothiols / Q000097:blood*; D015996:Survival Rate; D013997:Time Factors
chemical_list: D026403:S-Nitrosothiols