PMID- 36260325 OWN - NLM STAT- MEDLINE DCOM- 20221216 LR - 20231020 IS - 2380-6591 (Electronic) IS - 2380-6583 (Print) VI - 7 IP - 12 DP - 2022 Dec 1 TI - Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome: A Secondary Analysis From IMPROVE-IT. PG - 1199-1206 LID - 10.1001/jamacardio.2022.3627 [doi] AB - IMPORTANCE: Studies 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. OBJECTIVE: To 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 PARTICIPANTS: This 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 MEASURES: The 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. RESULTS: Of 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 RELEVANCE: Among 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 REGISTRATION: ClinicalTrials.gov Identifier: NCT00202878. FAU - Patel, Siddharth M AU - Patel SM AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Qamar, Arman AU - Qamar A AD - Section of Interventional Cardiology & Vascular Medicine, NorthShore University Health System, University of Chicago Pritzker School of Medicine, Evanston, Illinois. FAU - Giugliano, Robert P AU - Giugliano RP AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Jarolim, Petr AU - Jarolim P AD - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. FAU - Marston, Nicholas A AU - Marston NA AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Park, Jeong-Gun AU - Park JG AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Blazing, Michael A AU - Blazing MA AD - Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina. FAU - Cannon, Christopher P AU - Cannon CP AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Braunwald, Eugene AU - Braunwald E AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. FAU - Morrow, David A AU - Morrow DA AD - Thrombolysis in Myocardial Infarction Clinical Trials (TIMI) Study Group, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. AD - Cardiovascular Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. LA - eng SI - ClinicalTrials.gov/NCT00202878 GR - K08 HL153950/HL/NHLBI NIH HHS/United States GR - T32 HL007604/HL/NHLBI NIH HHS/United States PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - JAMA Cardiol JT - JAMA cardiology JID - 101676033 RN - 0 (Troponin T) RN - 0 (Ezetimibe, Simvastatin Drug Combination) RN - EOR26LQQ24 (Ezetimibe) RN - 0 (Biomarkers) SB - IM MH - Humans MH - Female MH - Middle Aged MH - Male MH - *Troponin T MH - *Acute Coronary Syndrome/drug therapy MH - Ezetimibe, Simvastatin Drug Combination/therapeutic use MH - Ezetimibe/therapeutic use MH - Biomarkers PMC - PMC9582963 COIS- Conflict of Interest Disclosures: Dr Patel reported grants from National Heart, Lung and Blood Institute during the conduct of the study. Dr Qamar reports receiving institutional grant support from Idorsia Pharmaceuticals, Novo Nordisk, NorthShore Auxiliary Research Scholar Fund, NorthShore CardioDiabetes Pilot Grant, and fees for educational activities from the American College of Cardiology, the Society for Vascular Medicine, the Society for Cardiovascular Angiography and Interventions, Janssen and Janssen, Pfizer, Medscape, and Clinical Exercise Physiology Association. Dr Giugliano reported grants from Akcea, Amgen, Anthos Therapeutics, Daiichi Sankyo, Ionis, and Merck (to his institution); institutional research grants to the TIMI Study Group at Brigham and Women's Hospital for research in which he is not directly involved from AstraZeneca, Bayer, Eisai, GlaxoSmithKline, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Novartis, Poxel, Pfizer, Quark Pharmaceuticals, and Takeda; and serving as a consultant or lecturer for Amarin, Amgen, American College of Cardiology, Angel Med, Beckman-Coulter, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Caladrius, Centrix, CryoLife, CSL Behring, CVS Caremark, Daiichi Sankyo, Dr Reddy's Laboratories, Esperion, Gilead, GlaxoSmithKline, Hengrui, Inari, Janssen, Lexicon, Medical Education Resources, Medscape, Menarini, Merck, Novartis, Paratek, Pfizer, PhaseBio Pharmaceuticals, Portola, St. Jude, St. Luke's Hospital System, SAJA Pharmaceuticals, Samsung, Servier, Shanghai Medical Telescope, Stealth Peptide, and Voxmedia outside the submitted work. Dr Jarolim reported research support from Abbott Laboratories, Amgen, AstraZeneca, Daiichi-Sankyo, Eisai, GlaxoSmithKline, Merck, Regeneron, Roche Diagnostics Corporation, and Siemens Healthineers, Takeda Global Research and Development Center, and Waters Technologies Corp as well as consulting fees from Roche Diagnostics. Dr Marston reported speaking honoraria from Amgen; clinical trial involvement with Ionis; grant support from the National Institutes of Health; and involvement in clinical trials with Amgen, Pfizer, Ionis, Novartis, and AstraZeneca without personal fees, payments, or increase in salary. Dr Park reported institutional research grants from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Daiichi-Sankyo, Eisai, Intracia, MedImmune, Merck, Novartis, Pfizer, Regeneron Pharmaceuticals, Roche, The Medicines Company, and Zora Biosciences during the conduct of the study. Dr Blazing has received research support from Merck, consulting fees from Espirion, and indirect support from Sanofi through Duke Clinical Research Institute. Dr Cannon reported grants and personal fees from Merck during the conduct of the study as well as grants from Amgen, Better Therapeutics, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, Janssen, Merck, Novo Nordisk, and Pfizer and personal fees from Aegerion/Amryt, Alnylam, Amarin, Amgen, Applied Therapeutics, Ascendia, Boehringer Ingelheim, Bristol Myers Squibb, Corvidia, Eisai, Eli Lilly, Innovent, Janssen, Kowa, Lexicon, Merck, Pfizer, Regeneron, Rhoshan, and Sanofi outside the submitted work. Dr Braunwald reported grants from Merck during the conduct of the study as well as research grants to institution from AstraZeneca, Daiichi Sankyo, Merck, and Novartis and consulting fees from Amgen, Boehringer Ingelheim, Eli Lilly, Cardurion, Bristol Myers Squibb, MyoKardia, NovoNordisk, and Verve outside the submitted work. Dr Morrow reported grants from Merck and Roche Diagnostics during the conduct of the study; grants from Abbott, Anthos Therapeutics, AstraZeneca, Novartis, Pfizer, Regeneron, and Siemens and consulting fees from Arca Bipharma, Merck, InCarda, Inflammatix, Merck, Novartis, and Roche Diagnostics outside the submitted work; and is a member of the TIMI Study Group, which has received institutional research grant support through Brigham and Women's Hospital from Abbott, Amgen, Anthos Therapeutics, AstraZeneca, Bayer HealthCare Pharmaceuticals, BRAHMS, Daiichi-Sankyo, Eisai, Intarcia, GlaxoSmithKline, MedImmune, Merck, Novartis, Pfizer, Quark Pharmaceuticals, Regeneron Pharmaceuticals, Roche, Siemens Healthcare Diagnostics, Takeda, The Medicines Company, and Zora Biosciences. No other disclosures were reported. EDAT- 2022/10/20 06:00 MHDA- 2022/12/17 06:00 PMCR- 2023/10/19 CRDT- 2022/10/19 11:34 PHST- 2022/10/20 06:00 [pubmed] PHST- 2022/12/17 06:00 [medline] PHST- 2022/10/19 11:34 [entrez] PHST- 2023/10/19 00:00 [pmc-release] AID - 2797195 [pii] AID - hoi220061 [pii] AID - 10.1001/jamacardio.2022.3627 [doi] PST - ppublish SO - JAMA Cardiol. 2022 Dec 1;7(12):1199-1206. doi: 10.1001/jamacardio.2022.3627.