Minimally elevated cardiac troponin T and elevated N-terminal pro-B-type natriuretic peptide predict mortality in older adults: results from the Rancho Bernardo Study

Abstract

Objectives: This study investigated the prognostic value of detectable cardiac troponin T (TnT) and elevated N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in a population of community-dwelling older adults.

Background: Minimally elevated levels of TnT, a marker of cardiomyocyte injury, have been found in small subsets of the general population, with uncertain implications. A marker of ventricular stretch, NT-proBNP has clinical utility in many venues, but its long-term prognostic value in apparently healthy older adults and in conjunction with TnT is unknown.

Methods: Participants were 957 older adults from the Rancho Bernardo Study with plasma NT-proBNP and TnT measured at baseline (1997 to 1999) and followed up for mortality through July 2006.

Results: Participants with detectable TnT (>/=0.01 ng/ml, n = 39) had an increased risk of all-cause and cardiovascular death (adjusted hazard ratio [HR] by Cox proportional hazards analysis: 2.06; 95% confidence interval [CI]: 1.29 to 3.28, p = 0.003 for all-cause mortality; HR: 2.06, 95% CI: 1.03 to 4.12, p = 0.040 for cardiovascular mortality); elevated NT-proBNP also predicted an increased risk of all-cause and cardiovascular mortality (adjusted HR per unit-log increase in NT-proBNP: 1.85, 95% CI: 1.36 to 2.52, p < 0.001 for all-cause mortality; HR: 2.51, 95% CI: 1.55 to 4.08, p < 0.001 for cardiovascular mortality). Those with both elevated NT-proBNP and detectable TnT had poorer survival (HR for high NT-proBNP and detectable TnT vs. low NT-proBNP and any TnT: 3.20, 95% CI: 1.91 to 5.38, p < 0.001). Exclusion of the 152 participants with heart disease at baseline did not materially change the TnT mortality or NT-proBNP mortality associations.

Conclusions: Apparently healthy adults with detectable TnT or elevated NT-proBNP levels are at increased risk of death. Those with both TnT and NT-proBNP elevations are at even higher risk, and the increased risk persists for years.

Figure 1. NT-proBNP Levels and Creatinine Clearance Levels by Troponin T Category

Troponin T categories: undetectable, n = 917; low, n = 30; high, n = 9. Boxes depict interquartile range, and whiskers represent 10th and 90th percentiles. *p < 0.001 versus undetectable. †p < 0.001 versus undetectable and p = 0.03 versus low. ‡p < 0.001 versus low and p = 0.02 versus high. NT-proBNP = N-terminal pro-B-type natriuretic peptide.

Figure 2. Prevalence of Baseline CHD and Distribution of TnT and NT-proBNP

(A) Prevalence of baseline coronary heart disease (CHD) in participants with undetectable and detectable TnT levels (left), and distribution of TnT among those with detectable levels (right). (B) Prevalence of baseline CHD in participants with low versus high NT-proBNP levels (left), and distribution of NT-proBNP among all subjects (right). NT-proBNP = N-terminal pro-B-type natriuretic peptide; prior CHD = myocardial infarction or revascularization; TnT = troponin T.

Figure 3. Kaplan-Meier Survival Plots by TnT or NT-proBNP Levels

(A) Survival in participants with undetectable versus detectable TnT levels. n = 196 deaths in the undetectable TnT group (of 917 participants with undetectable TnT) and n = 23 deaths in the detectable TnT group (of 39 participants with detectable TnT). (B) Survival in participants with undetectable versus detectable TnT levels, with analysis limited to those participants without baseline coronary heart disease (CHD). n = 143 deaths in the undetectable TnT group (of 781 participants with undetectable TnT) and n = 13 deaths in the detectable TnT group (of 24 participants with detectable TnT). (C) Survival in participants with low (< 450 pg/ml) versus high (≥450 pg/ml) NT-proBNP levels. n = 132 deaths in the low NT-proBNP group (of 758 participants with low NT-proBNP) and n = 88 deaths in the high NT-proBNP group (of 199 participants with high NT-proBNP). (D) Survival in participants with low versus high NT-proBNP levels, with analysis limited to those participants without baseline CHD. n = 106 deaths in the low NT-proBNP group (of 667 participants with low NT-proBNP) and n = 51 deaths in the high NT-proBNP group (of 139 participants with high NT-proBNP). Abbreviations as in Figure 2.

Figure 4. Kaplan-Meier Survival Plots by Combined TnT and NT-proBNP Levels

(A) n = 132 deaths in the high NT-proBNP/detectable TnT group, n = 68 deaths in the high NT-proBNP/undetectable TnT group, and n = 19 deaths in the low NT-proBNP group. (B) Analysis limited to those participants without baseline coronary heart disease (CHD). n = 106 deaths in the high NT-proBNP/detectable TnT group, n = 40 deaths in the high NT-proBNP/undetectable TnT group, and n = 10 deaths in the low NT-proBNP group. Abbreviations as in Figure 2.

Figure 5. Framingham Risk Score and Incremental Prognostic Value of Troponin T or NT-proBNP for Predicting Death

Reference group in (A) is the group with low Framingham risk score (< 10%) and undetectable troponin T. Reference group in (B) is the group with low Framingham risk scores and NT-proBNP < 450 pg/ml. Framingham risk score was calculated as low risk (< 10% risk of events over 10 years), moderate risk (10% to 20%), and high risk (>20%). Abbreviations as in Figure 2.