Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome

Abstract

ImportanceStudies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population.ObjectiveTo evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS).Design, Setting, and ParticipantsThis is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022.Main Outcomes and MeasuresThe outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses.ResultsOf 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change.Conclusions and RelevanceAmong stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT00202878

Acute Coronary Syndrome Subphenotypes Based on Repeated Biomarker Measurements in Relation to Long‐Term Mortality Risk

“…In fact, only 3% of our patients showed a relative hs‐cTnT increase of >25% during the 30‐day to 1‐year study period (based on the linear mixed‐effects model; data not shown). The findings in BIOMArCS contrast with previous reports by White et al, 30 Everett et al, 31 Cavender et al, 32 and Patel et al, 33 who reported a meaningful increase in cardiac troponin in up to 23% of patients with coronary artery disease and increasing concentrations were associated with a worse prognosis in all 4 studies. Indeed, increasing cardiac troponin concentrations are disconcerting, as these are potentially related to ongoing myocyte necrosis, chronic processes related to left ventricular hypertrophy, 34 , 35 increasing renal dysfunction, 36 or poor diabetes control.…”

“…On the other hand, we consider the regression to the mean phenomenon a serious limitation of previous studies that investigated change based on 2 measurements only. 30 , 31 , 32 , 33 …”

“…Most biomarker studies classifying patients following ACS have explored 1 cross‐sectional measurement only, or studied changes using just 2 repeated measurements several months apart. 30 , 31 , 32 , 33 , 40 Our data in combination with the statistical techniques (ie, based on linear mixed‐effect models) overcomes the regression to the mean phenomenon, a well‐known limitation of observational studies investigating change. 41 Second, complete follow‐up for >10 years enabled linking the ACS subphenotypes to long‐term prognosis.…”

Four high sensitivity troponin assays and mortality in US adults with cardiovascular disease: The national health and nutrition examination survey, 1999–2004

“…Hs-cTn may be an important tool to measure residual CVD risk in secondary prevention [4] , [5] , [6] . The current NHANES results are important as this cohort is designed to be representative of the diverse US adult population and because of the ability to test for any differences in important subgroups (including by sex and race/ethnicity).…”

“…Originally designed to expedite the diagnosis of myocardial infarction, high-sensitivity cardiac troponin (hs-cTn) assays have since emerged as prognostic biomarkers associated with cardiovascular disease (CVD) outcomes in a range of settings [1] , [2] , [3] . One of these settings is in the care of adults with a history of CVD who are being managed for secondary prevention [4] , [5] , [6] .…”