Abstract 16457: Markers of Diabetes and Renal Function Extend Sudden Death Risk Assessment Beyond the Ejection Fraction
Introduction: Although diabetes and renal dysfunction are known to be associated with SCD risk, the cumulative risk of objective laboratory markers in combination with left ventricular ejection fraction (LVEF) has not been previously evaluated. Hypothesis: Addition of glycosylated hemoglobin (HbA1C) and serum creatinine levels to LVEF can improve the SCD risk stratification model. Methods: As part of a large, prospective, ongoing study of SCD in a Northwestern US metropolitan region (catchment population about 1 million), SCD cases were compared with controls with coronary artery disease (CAD) and no SCD from the same geographic location. HbA1C, serum creatinine levels and LVEF (all prior and unrelated to the SCD event for cases) were obtained for all subjects. Odds ratios for SCD associated with abnormal HbA1C (≥ 7%) and creatinine (≥ 1.5 mg/dL) levels was calculated. Cumulative odds and improvement in model performance on addition of elevated lab markers to low LVEF (≤ 35%) was assessed. Results: 243 SCD cases (68.7 ± 13.2 yrs; 62.1% male) and 159 CAD controls (66.2 ± 9.9 yrs; 65.6% male) with appropriate lab values and LVEF information were evaluated. The mean HbA1C (7.3 ± 2.3 vs. 6.6 ± 1.5%) and creatinine (1.8 ± 1.7 vs. 1.2 ± 0.7 mg/dL) levels were significantly higher in cases. Cases were significantly more likely to have HbA1C ≥ 7% (49.4 vs. 27.7%; p<0.0001) or creatinine ≥ 1.5 mg/dL (39.1% vs. 13.8%) (all p<0.0001). After adjustment for age, sex and low LVEF, high HbA1C (OR 2.3, 95% CI 1.4-3.6; p=0.001) and high creatinine (OR 3.3, 95% CI 1.9-5.7; p<0.0001) were independently associated with SCD; LVEF ≤ 35% was associated as well (OR 1.8, 95% CI 1.1-3.2; p=0.05). As compared to neither lab marker being high, elevation of one marker (OR 2.4, 95% CI 1.5-3.9) or both markers (OR 7.9, 95% CI 3.5-17.6) was associated with progressive increase in SCD odds. Addition of lab markers to a risk stratification model with only LVEF improved model discrimination significantly (AUC 0.613 vs. 0.709; p=0.01). Conclusions: HbA1C and serum creatinine improved the SCD risk stratification model when added to LVEF. Further investigation is warranted before clinical use, including consideration of competing risks that influence overall mortality.