High-Sensitivity Cardiac Troponin T, Age, and Outcome in Non-ST-Elevation Myocardial Infarction.

The magnitude of cardiac troponin (cTn) release in myocardial infarction (MI) reflects the size of the ischemic insult and is a strong predictor of poor prognosis. Little is known, however, about the relation between cTn concentrations and age in MI and the prognostic implications thereof. This is clinically important given increasing longevity in the general population and increasing MI incidence with higher age. We here investigated this issue in a large registry-based cohort of patients with non-ST-elevation MI (NSTEMI). This analysis is part of the Tailoring Of Treatment in All comers with Acute Myocardial Infarction (TOTAL-AMI) project (1). TOTAL-AMI aims to characterize different MI types (2) using data from the SWEDEHEART registry and mandatory registries, held by Swedish authorities. Patients included in this analysis had been admitted to Swedish coronary care units from January 2009, and were followed regarding all-cause mortality until May 2018, and regarding major adverse events (MAE), defined as the composite of all-cause mortality, rehospitalizations for recurrent MI, heart failure, or stroke until December 2017. We restricted this analysis to patients with available results for high-sensitivity cardiac troponin T (hs-cTnT) concentrations. SWEDEHEART provides only data on the highest measured cTn value during the hospitalization. We thus excluded patients with ST-elevation MI since serial cTn measurements are not usually performed in this condition. The study population consisted of 49 318 patients with NSTEMI [64.0% males, median age 72 (25th, 75th percentiles 64–81) years]. Median hs-cTnT concentrations were 262 (99–740) ng/L overall, and 216 (80–625) ng/ L, 235 (88–675) ng/L, 268 (101– 761) ng/L, and 331 (130–892) ng/L respectively, across increasing age quartiles. In total, 12 297 (24.9%) patients died [median follow-up of 2.8 (1.1–4.8) years], and 15 822 patients (33.4%) suffered a MAE [median follow-up of 2.2 (0.8–4.2) years]. All-cause mortality rates increased in stepwise fashions from 4.4% (n1⁄4 156/3576) in patients with age and hs-cTnT in the lowest quartiles to 62.0% (n1⁄4 2301/ 3711) in patients with age and hs-cTnT in the highest quartiles. Similarly, MAE rates increased from 10.1% (n1⁄4 344/3392) to 68.8% (n1⁄4 2474/3598). Hs-cTnT (ln) independently predicted all-cause mortality and MAE with hazard ratios (HR) of 1.16 [95% confidence interval (CI) 1.14–1.17] and 1.13 (95% CI 1.12–1.14), respectively (adjustments described in Fig. 1). Likewise, age per 10-year increments predicted all-cause mortality [HR 2.16 (95% CI 2.11– 2.21)] and MAE [HR 1.75 (95% CI 1.72–1.79)]. The interactions of age on the association of hs-cTnT (ln) with outcome was significant regarding MAE (Pinteraction1⁄4 0.007) but not for all-cause mortality (Pintercation1⁄4 0.484). The HR regarding all-cause mortality in patients with hs-cTnT 99 ng/L and using those aged <64 years as reference were 1.60 (95% CI 1.30–1.96), 2.66 (95% CI 2.18–3.24), and 6.53 (95% CI 5.34–7.98) across increasing age quartiles, respectively. Corresponding HR regarding MAE were 1.35 (95% CI 1.16–1.55), 2.07 (95% CI 1.80–2.39), and 3.70 (95% CI 3.19–4.30). Risk estimates per quartiles of hs-cTnT and age are also presented Fig. 1. Using patients with hs-cTnT 99 ng/L in each respective age quartile as reference, relative risk gradients across higher hs-cTnT quartiles were similar in all age groups, as indicated by largely nonoverlapping 95% CI of the HR. The only exception were patients aged <64 years in whom no significant risks were noted unless hs-cTnT concentrations exceeded 740 ng/L. Adjusting for the angiographic extent of coronary disease (defined as normal/nonocclusive vessels, 1–2 vessel disease, 3vessel/left main disease, inconclusive findings), an important predictor of adverse outcome, attenuated these findings slightly without affecting the overall associations of hs-cTnT and age with risk (data not shown). In total, 43 405 (90.4%) patients had type 1 NSTEMI and 4607 (9.6%) had type 2 NSTEMI (missing information on NSTEMI type: n1⁄4 1306). Patients with type 2 NSTEMI had higher rates of all-cause mortality (45.7 vs 22.4%; P< 0.001) and MAE (53.8 vs 30.9%; P< 0.001) that increased across higher age and hs-cTnT quartiles (data not shown). However, in part, small event numbers in some quartile groups precluded further in-depth analyses. Our findings indicate that increases in the magnitude of cTn release imply more severe prognostic consequences in older (i.e., 64 y) patients. This may be due to loss of endogenous cardioprotection with increasing susceptibility to myocardial ischemia/reperfusion damage in the elderly (3). Ischemic tolerance decreases with aging, likely as a consequence of enhanced oxidative stress. Age-related affection of signaling cascades mediating ischemic preconditioning may contribute (3). Our analysis is potentially limited by its retrospective approach using registry data, the lack of formal adjudication of index diagnoses