Prognostic value of serum biomarkers in association with TIMI risk score for acute coronary syndromes

Background: Markers of neurohormonal activation and inflammation play a pivotal role in non-ST-elevation acute coronary syndromes (NSTE-ACS). Hypothesis: We hypothesized that other biochemical markers could add prognostic value on Thrombolysis In Myocardial Infarction (TIMI) risk score to predict major cardiovascular events in patients with NSTE-ACS. Methods: In a cohort of 172 consecutive patients with NSTE-ACS, TIMI score was assessed in the first 24 h, and blood samples were collected for measurement of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein. CD40 ligand, and creatinine. Major clinical outcomes (death and cardiovascular hospitalization) were accessed at 30 days and 6 months. Multivariate logistic regression was applied to identify markers significantly associated with outcomes and, based on individual coefficients, an expanded score was developed. Results: Of 172 patients, 42% had acute myocardial infarction. The unadjusted 30-day event rate increased with age (odds ratio [OR] = 1.03; 95% confidence interval [CI] 1.00-1.06). creatinine (OR = 2.4; 1.4-4.1), TIMI score (OR = 1.6; 1.2-2.2), troponin I (OR = 3.4; 1.5-7.7), total CK (OR = 2.7; 1.2-6.1), and NTproBNP (OR = 2.9;1.3-6.3) levels. In multivariate analysis, TIMI risk score, creatinine, and NTproBNP remained associated with worse prognosis. Multimarker Expanded TIMI Risk Score [TIMI score + (2 X creatinine [in mg/dl]) + (3, if NT-proBNP > 400 pg/ml)] showed good accuracy for 30-day (c statistic 0.77; p < 0.001) and 6-month outcomes (c statistic 0.75; p < 0.001). The 30-day event rates according to tertiles of expanded score were 7, 26, and 75%, respectively (p < 0.01). Conclusion: In NSTE-ACS, baseline levels of NT-proBNP and creatinine are independently related to cardiovascular events. Both markers combined with TIMI risk score provide a better risk stratification than either test alone.