Keyaki Sasaki1, Tetsuo Shoji2,3, Daijiro Kabata4, Ayumi Shintani4, Yujiro Okute1, Shoko Tsuchikura5, Naoko Shimomura5, Yoshihiro Tsujimoto5, Shinya Nakatani1, Katsuhito Mori6, Atsushi Shioi2,3, Masaaki Inaba1,3,6, Masanori Emoto1. 1. Department of Metabolism, Endocrinology and Molecular Medicine, Osaka City University Graduate School of Medicine. 2. Department of Vascular Medicine, Osaka City University Graduate School of Medicine. 3. Vascular Science Center for Translational Research, Osaka City University Graduate School of Medicine. 4. Department of Medical Statistics, Osaka City University Graduate School of Medicine. 5. Division of Internal Medicine, Inoue Hospital. 6. Department of Nephrology, Osaka City University Graduate School of Medicine.
Abstract
AIM: Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP). METHODS: This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events. RESULTS: A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patients died, and 190 patients experienced new CVD events. In the Kaplan-Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not. CONCLUSIONS: Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.
AIM: Both oxidative stress and inflammation are involved in the pathogenesis of cardiovascular disease (CVD). The serum level of derivatives of reactive oxygen metabolites (d-ROMs) is a measure of the total amount of hydroperoxides serving as a marker of oxidative stress. We investigated whether d-ROMs could predict the clinical outcomes in hemodialysis patients and whether the associations of d-ROMs with the outcomes are independent of a marker of inflammation, C-reactive protein (CRP). METHODS: This was a prospective cohort study in hemodialysis patients. The key exposures were the serum levels of d-ROMs and CRP. The outcome measures were all-cause mortality and new CVD events. RESULTS: A total of 517 patients were analyzed. d-ROMs correlated positively with CRP. During follow-up for 5 years, 107 patientsdied, and 190 patients experienced new CVD events. In the Kaplan-Meier analyses, both higher d-ROMs and higher CRP levels predicted higher risks for mortality and CVD events. By Cox proportional-hazard regression analysis adjusted for potential confounders excluding CRP, d-ROMs exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for CRP. Using the same model, CRP exhibited a significant association with all-cause mortality, but this association was no longer significant after further adjustment for d-ROMs. When we analyzed new CVD events as the outcome, CRP was a significant predictor, whereas the level of d-ROMs was not. CONCLUSIONS: Although d-ROMs predicted mortality and CVD events in unadjusted models, the associations of d-ROMs with these outcomes were not independent of CRP. Oxidative stress and inflammation appear to share common causal pathways.
Authors: Yang Xuan; Martin Bobak; Ankita Anusruti; Eugène H J M Jansen; Andrzej Pająk; Abdonas Tamosiunas; Kai-Uwe Saum; Bernd Holleczek; Xin Gao; Hermann Brenner; Ben Schöttker Journal: Eur J Epidemiol Date: 2018-11-07 Impact factor: 8.082
Authors: Christoph Wanner; Vera Krane; Winfried März; Manfred Olschewski; Johannes F E Mann; Günther Ruf; Eberhard Ritz Journal: N Engl J Med Date: 2005-07-21 Impact factor: 91.245
Authors: Bengt C Fellström; Alan G Jardine; Roland E Schmieder; Hallvard Holdaas; Kym Bannister; Jaap Beutler; Dong-Wan Chae; Alejandro Chevaile; Stuart M Cobbe; Carola Grönhagen-Riska; José J De Lima; Robert Lins; Gert Mayer; Alan W McMahon; Hans-Henrik Parving; Giuseppe Remuzzi; Ola Samuelsson; Sandor Sonkodi; D Sci; Gultekin Süleymanlar; Dimitrios Tsakiris; Vladimir Tesar; Vasil Todorov; Andrzej Wiecek; Rudolf P Wüthrich; Mattis Gottlow; Eva Johnsson; Faiez Zannad Journal: N Engl J Med Date: 2009-03-30 Impact factor: 91.245