Enhanced Risk Assessment With Dual Marker Strategies in Combination With Troponin

CRP and Troponin

CRP has been an independent predictor of short- and/or long-term outcome among patients with NSTEACS in at least nine studies that have included multivariable analysis (11,23-31). Specifically, measurement of hsCRP appears to yield additional prognostic value in patients with negative testing of cardiac troponins (10,11) and adds to information obtained from the clinical history and electrocardiogram. With this background, my colleagues and I evaluated a strategy that combined testing for hsCRP and cardiac troponin T (cTnT) in patients with NSTEACS (10). We found that the dual marker strategy provided more comprehensive risk assessment. Stratified by both CRP and a qualitative assay for cTnT, patients with both an early positive cTnT and an elevated CRP were at highest risk of death by 14 d, followed by those who had either an elevated CRP or a positive cTnT. Patients with negative results for both assays were at very low risk of mortality (Fig. 3). These results were subsequently confirmed and extended with respect to cardiac mortality through 2 yr of follow-up in 917 patients with non-STEACS, among whom CRP was associated with a higher 2-yr risk of death regardless of troponin strata (Fig. 4) (11).

BNP/NT-proBNP and Troponin

BNP and NT-proBNP are strongly associated with prognosis in patients with ACS (1419,32-36). The concentrations of BNP and NT-proBNP are elevated in 10-30% of patients with unstable angina (i.e., without myonecrosis) (15,18,37) and are also associated with survival in this group (see Chapter 24). When assessed in 1676 patients with NSTEACS, BNP offered significant prognostic information independently of cTnl, identifying patients at greater than fourfold higher risk of mortality among those with either negative (odds ratio [OR]: 6.9; 95% confidence interval [CI]: 1.9-25.8) or positive (OR: 4.1; 95% CI: 1.9-9.0) baseline troponin results (Fig. 5, left). Thus, the combined use of BNP and cTnI enhanced risk assessment, enabling discrimination of patients with negative BNP or troponin who were at increased risk of death or MI (Fig. 5, right). Among patients with a

Fig. 4. Risk of cardiac death at 2 yr stratified by cTnT and high-sensitivity testing for CRP among patients with NSTEACS (n = 917) enrolled in Fragmin During Instability in Coronary Artery Disease trial. (Data are from ref. 11.)

Fig. 4. Risk of cardiac death at 2 yr stratified by cTnT and high-sensitivity testing for CRP among patients with NSTEACS (n = 917) enrolled in Fragmin During Instability in Coronary Artery Disease trial. (Data are from ref. 11.)

Fig. 5. Risk of death or MI at 30 d stratified by BNP and cTnl results among patients (n = 1676) enrolled in the Treat with Aggrastat and Determine the Cost of Therapy with an Invasive or Conservative Strategy (TACTICS)-TIMI 18 Trial. (Used with permission from ref. 18.)

negative cTnl who had elevated BNP, the risk of death or MI was 7.5%, whereas in those with a negative BNP detected as being at higher risk only by cTnl, the risk of death or MI through 30 days was 6.4%. Patients with both a negative BNP and cTnl were at very low risk of death (0.7%) or death or MI (2.0%). Similar observations were made with NT-proBNP in more than 6000 patients with NSTEACS, among whom the quantile ofbaseline concentration of NT-proBNP showed a graded relationship with the risk of mortality through 1 yr (19). Notably, patients with a level of NT-proBNP <237 pg/mL were at low risk of death regardless of troponin result.

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