Abstract 465: High Circulating Levels of 8-OHdG are an Independent Predictor of Subsequent MACE

Abstract

Objective: Oxidative stress is associated with several cardiovascular risk factors and cardiovascular disease. Damaged cells release cell-free DNA (cfDNA) into the circulation; oxidized cfDNA presence in the plasma indicates a pathological process in the context of oxidative stress. We hypothesized that biomarker of oxidative DNA damage 8-hydroxy- 2’deoxyguanosine (8-OHdG) may be associated with incident major adverse cardiovascular events (MACE). Methods: Plasma samples from 84 consenting patients undergoing coronary angiography at Intermountain Healthcare were obtained at the time of the procedure and tested for 8-OHdG by ELISA. Study endpoints were subsequent myocardial infarction (MI), stroke and all-cause death (determined by electronic medical records and death certificates) within median follow-up of 10 years (IQR: 8.8, 10.6). Cox-proportional hazard analysis was used for examining MACE rate association by quartile of 8-OHdG. Results: Mean 8-OHdG was significantly higher for individuals with a subsequent MACE vs those without (124.8 and 98.7 nM, respectively; p<0.006, t-test). No other baseline demographic was significantly associated with 8-OHdG. MACE rates by 8-OHdG quartiles revealed a significant trend (p = 0.0346) (Figure). Hazard ratio increased by 1.653 for every 42 unit increase in 8-OHdG, p=0.006. Conclusion: High 8-OHdG plasma levels independently predict subsequent MACE. Whether 8-OHdG is contributes etiologically to event causation needs to be determined.