Six-Year Change in High-Sensitivity Cardiac Troponin T and Risk of Subsequent Coronary Heart Disease, Heart Failure, and Death

Abstract

Importance: High-sensitivity cardiac troponin T (hs-cTnT) is a biomarker of cardiovascular risk and could be approved in the United States for clinical use soon. However, data linking long-term temporal change in hs-cTnT to outcomes are limited, particularly in primary prevention settings.

Objective: To examine the association of 6-year change in hs-cTnT with incident coronary heart disease (CHD), heart failure (HF), and all-cause mortality.

Design, setting, and participants: This prospective observational cohort study, performed from January 1, 1990, to December 31, 2011, included 8838 participants with biracial representation from the Atherosclerosis Risk in Communities Study who were initially free of CHD and HF and who had hs-cTnT measured twice, 6 years apart. Data analysis was performed from October 28, 2014, to March 9, 2016.

Main outcome and measures: Risk factor and temporal hs-cTnT data were collected. Using Cox proportional hazards regression, we examined the association of hs-cTnT change with subsequent CHD, HF, and death during a maximum of 16 years. Improvement in discrimination was determined by the Harrell C statistic.

Results: Of the 8838 participants (mean age, 56 years; 5215 female [59.0%]; 1891 black [21.4%]) there were 1157 CHD events, 965 HF events, and 1813 deaths overall. Incident detectable hs-cTnT (baseline, <0.005 ng/mL; follow-up, ≥0.005 ng/mL) was independently associated with subsequent CHD (hazard ratio [HR], 1.4; 95% CI, 1.2-1.6), HF (HR, 2.0; 95% CI, 1.6-2.4), and death (HR, 1.5; 95% CI, 1.3-1.7), relative to an hs-cTnT level less than 0.005 ng/mL at both visits. In addition, HRs as high as 4 for CHD and death and 8 for HF were recorded among individuals with the most marked hs-cTnT increases (eg, baseline, < 0.005 ng/mL; follow-up, ≥0.014 ng/mL). Risk for subsequent outcomes was lower among those with relative hs-cTnT reductions greater than 50% from baseline. Furthermore, information on hs-cTnT change improved discrimination for HF and death when added to a model that included traditional risk factors, N-terminal pro-brain natriuretic peptide, and baseline hs-cTnT level. Among individuals with adjudicated HF hospitalizations, hs-cTnT change appeared to be similarly associated with HF with reduced and preserved ejection fraction.

Conclusions and relevance: Temporal increases in hs-cTnT, suggestive of progressive myocardial damage, are independently associated with incident CHD, death, and, above all, HF. Serial determination of hs-cTnT trajectory adds clinically relevant information to baseline testing and may be useful in prognostic assessments and the targeting of prevention strategies to high-risk individuals, especially among persons with stage A or B HF.

Figure 1. Relative Risk for CHD, Heart Failure, or Death; According to 6 year change in high-sensitivity Troponin-T

Adjusted* hazard ratios (95% confidence intervals) for incident coronary heart disease (CHD), heart failure hospitalization (HF), or death were incrementally higher according to categories of increasing 6-year change in high sensitivity cardiac troponin T (hs-cTNT) between ARIC Visit 2 (1990–1992) and Visit 4 (1996–1998)† *Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/L), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmHg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dL), HDL-cholesterol (mg/dL), triglycerides (mg/dL), and current use of cholesterol-lowering medication (yes or no), estimated GFR (mL/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria). † Note that the visit 2 <5ng/L and visit 4 <5ng/L category is the reference group throughout. Further, the visit 2 ≥14ng/L and visit 4 <5 ng/L category has been removed due to low numbers (6 participants). Square Markers= Baseline hs-cTnT <5 ng/L, Round Markers= Baseline hs-cTnT 5–13 ng/L, Diamond Markers= Baseline hs-cTnT ≥14 ng/L

Figure 1. Relative Risk for CHD, Heart Failure, or Death; According to 6 year change in high-sensitivity Troponin-T

Adjusted* hazard ratios (95% confidence intervals) for incident coronary heart disease (CHD), heart failure hospitalization (HF), or death were incrementally higher according to categories of increasing 6-year change in high sensitivity cardiac troponin T (hs-cTNT) between ARIC Visit 2 (1990–1992) and Visit 4 (1996–1998)† *Adjusted for age, sex, race-center, body mass index (kg/m3), C-reactive protein (mg/L), smoking (current; former; never), drinking (current; former; never), systolic blood pressure (mmHg), current use of blood pressure-lowering medication (yes or no), diagnosed diabetes (yes or no), LDL-cholesterol (mg/dL), HDL-cholesterol (mg/dL), triglycerides (mg/dL), and current use of cholesterol-lowering medication (yes or no), estimated GFR (mL/min/1.73m2), and left ventricular hypertrophy (yes or no, by Cornell criteria). † Note that the visit 2 <5ng/L and visit 4 <5ng/L category is the reference group throughout. Further, the visit 2 ≥14ng/L and visit 4 <5 ng/L category has been removed due to low numbers (6 participants). Square Markers= Baseline hs-cTnT <5 ng/L, Round Markers= Baseline hs-cTnT 5–13 ng/L, Diamond Markers= Baseline hs-cTnT ≥14 ng/L