Increased pasma S-nitrosothiol concentrations predict cardiovascular outcomes among patients with end-stage renal disease: a prospective study.
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.
Massy
Ziad A
ZA
INSERM U507, Necker Hospital, Paris, France. massy@necker.fr
Fumeron
Christine
C
Borderie
Didier
D
Tuppin
Philippe
P
Nguyen-Khoa
Thao
T
Benoit
Marie-Odile
MO
Jacquot
Christian
C
Buisson
Claude
C
Drüeke
Tilman B
TB
Ekindjian
Ohvanesse G
OG
Lacour
Bernard
B
Iliou
Marie-Christine
MC
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
D026403:S-Nitrosothiols