Abstract

Introduction: Growth differentiation factor (GDF)-15, a novel biomarker of cardiac stress, has been recently studied as a tool in predicting cardiovascular outcomes in patients with acute chest pain, when compared against high-sensitivity troponin T (hs-TnT). However, GDF-15 is not approved for cardiac indications in the United States, with limited nationwide data evaluating subpopulations by key demographic and clinical characteristics. Hypothesis: GDF-15 levels demonstrate sex-specific differences and serve as an independent predictor of 90-day acute myocardial infarction (MI) and all-cause death in patients presenting to the emergency department (ED) with acute chest pain and normal hs-TnT levels. Methods: This study was a secondary analysis of the STOP-CP (High Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification) trial, which prospectively enrolled adults ≥ 21 years presenting to eight EDs in the US with suspected acute MI over a twenty-month period. Blood sampling was performed at presentation, with hs-TnT and GDF-15 assays performed at a central laboratory. The outcomes of interest were the composite of acute MI and all-cause death at 90 days. Multiple logistic regression models were fitted for timepoint with multiple independent variables including the following: age, sex, ischemic electrocardiogram, hs-TnT, GDF-15, and creatinine. Results: We studied 1,428 patients; median age was 58 years and 54% (765) were male. The composite outcome of acute MI or death occurred in 3% (37) at 90 days. In multivariable regression models in patients with baseline normal hs-TnT levels, GDF-15 was associated with acute MI or all-cause death at 90 days (Odds Ratio 1.03, 95% Confidence Interval 1.01-1.05). Median GDF-15 levels were 1266 pg/mL in males (25th percentile-75th percentile, 914-2038 pg/mL), and 1504 pg/mL in females (25th percentile-75th percentile, 987-2197 pg/mL). Conclusions: Among adult ED patients presenting with acute chest pain with normal troponin levels, the novel biomarker GDF-15 was independently associated with 90-day acute MI or death, with higher median GDF-15 levels in females compared to males. These data suggest a role for GDF-15 in short-term cardiac risk stratification.

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