Abstract 15205: Reactive Oxygen Metabolites Are Elevated in Relation to Severity of Heart Failure and Predict Cardiovascular Events in Heart Failure with Reduced Ejection Fraction
Background: Reactive oxygen species (ROS) is known to contribute to the development of left ventricular (LV) dysfunction in patients with heart failure (HF). Derivative of reactive oxygen metabolites (DROM), reflecting blood hydroperoxide levels, is a new and easier-to-assay marker of ROS. We investigated the role of DROM in patients with HF with reduced LV ejection fraction (HFrEF).
Methods: (1) We enrolled consecutive 142 HFrEF patients admitted Kumamoto University Hospital and measured serum DROM levels at the stable condition after standard therapy. We classified HFrEF patients by New York Heart Association (NYHA) functional class for evaluation of the severity of HF. HFrEF patients were prospectively followed until occurrence of cardiovascular events (CVE). (2) To investigate whether serum DROM levels are associated with DROM produced in coronary circulation, we measured at the aortic root and the coronary sinus in HFrEF patients.
Results: (1) DROM values were significantly higher in HFREF patients (n=142) compared to risk-matched control subjects (n=81) (366.7±81.6 U.CARR vs 320.3±51.8 U.CARR, p<0.01). Furthermore, DROM was associated with the severity of HF (NYHA I/II:338.9±57.2 U.CARR vs. NYHA III/IV:424.9±93.5 U.CARR, p<0.01). Also DROM was independently associated with the severity of HF by multivariate logistic regression analysis (odds ratio 1.014, p <0.01). DROM values significantly correlated with other biomarkers (high-sensitivity CRP, BNP and sodium levels) and echo-parameters of LV dysfunction (LVEF, LVDd and TRPG). Kaplan-Meier analysis demonstrated significantly higher probability of CVE in high-DROM group (>348U.CARR; median value in HFrEF patients) than in low-DROM group (log-rank test, P<0.01). (2) DROM levels at the coronary sinus were significantly higher than those at the aortic root in HFrEF patients, but not different in non-HF patients (p=0.037). The data indicated that ROS are produced in the coronary circulation in HFrEF patients.
Conclusion: Serum DROM levels associated with their production in coronary circulation, were significantly elevated in relation to severity of HF and could predict future CVE in HFrEF patients. DROM may provide clinical benefits for risk stratification in HFrEF patients.
Author Disclosures: T. Tokitsu: None. E. Yamamoto: None. Y. Hirata: None. K. Fujisue: None. K. Sugamura: None. M. Yamamuro: None. K. Kaikita: None. S. Hokimoto,: None. S. Sugiyama: None. H. Ogawa: Other Research Support; Modest; AstraZeneca, Astellas, Boehringer lngelheim, Bristol-Myers Squibb, Daiichi Sankyo, Dainippon Sumitomo Pharma, Kowa, MSD, Novartis, Pfizer, Sanofi, Takeda. Other Research Support; Significant; Bayer, Chugai, Otsuka. Honoraria; Modest; AstraZeneca, Bayer, Pfizer, Sanofi, Takeda. Honoraria; Significant; Daiichi Sankyo, MSD.
- © 2014 by American Heart Association, Inc.