Author + information
- Received January 16, 2018
- Revision received July 22, 2018
- Accepted July 23, 2018
- Published online October 1, 2018.
- Paulo C. Rezende, MD, PhDa,
- Brendan M. Everett, MD, MPHb,
- Maria Mori Brooks, PhDc,
- Helen Vlachos, MSc,
- Trevor J. Orchard, MD, MSc,
- Robert L. Frye, MDd,
- Deepak L. Bhatt, MD, MPHb@DLBhattMD and
- Mark A. Hlatky, MDe,∗ (, )@MarkHlatky_MD@Stanford
- aHeart Institute, University of São Paulo, São Paulo, Brazil
- bDepartment of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
- cGraduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania
- dDepartment of Medicine, Mayo Clinic, Rochester, Minnesota
- eDepartment of Health Research and Policy, Stanford University School of Medicine, Stanford, California
- ↵∗Address for correspondence:
Dr. Mark A. Hlatky, Stanford University School of Medicine, HRP Redwood Building, Room T150, 259 Campus Drive, Stanford, California 94305-5405.
Background Diabetic medications can cause hypoglycemia, which may lead to myocardial damage.
Objectives This study sought to determine whether hypoglycemia is associated with higher levels of high-sensitivity cardiac troponin T (hsTnT).
Methods The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial randomized patients with type 2 diabetes mellitus and stable coronary artery disease, and closely followed them for hypoglycemia over the first year. Hypoglycemia was classified by maximum severity and frequency. hsTnT was measured at baseline and 1 year, and analyzed using multivariable regression.
Results Of 1,984 patients, follow-up hypoglycemia was absent in 1,026 (52%) patients, mild in 875 (44%), and severe in 83 (4%), and occurred less than weekly in 561 (28%) and greater than or equal to weekly in 397 (20%). hsTnT levels were associated with hypoglycemia: a median of 11.4 ng/l (interquartile range [IQR]: 8.1 to 17.3 ng/l) for none, 12.5 ng/l (IQR: 8.3 to 19.3 ng/l) for mild, and 13.7 ng/l (IQR: 9.9 to 24.9 ng/l) for severe hypoglycemia (p = 0.0001); and 12.5 ng/l (IQR: 8.3 to 18.1 ng/l) for less than weekly and 13.0 ng/l (IQR: 8.8 to 21.1 ng/l) for greater than or equal to weekly hypoglycemia (p = 0.0013). Severe hypoglycemia was associated with 34% higher 1-year hsTnT levels (p < 0.0001) in unadjusted analysis, 17% higher (p = 0.006) after adjustment for baseline factors unrelated to diabetes, and 6% higher (p = 0.23) after further adjustment for the duration and severity of diabetes. Hypoglycemia greater than or equal to weekly was associated with 14% higher hsTnT (p = 0.0003) in unadjusted analysis, 12% higher (p = 0.0002) after adjustment for baseline factors unrelated to diabetes, and 4% higher (p = 0.16) after adjustment for diabetes related factors.
Conclusions Hypoglycemia was associated with elevated hsTnT levels, but this may be due to more severe diabetes in patients who developed hypoglycemia, rather than the direct result of hypoglycemia. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI2D]; NCT00006305)
Supported by grants from the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and Roche Diagnostics (U01HL061744, U01HL061746, U01HL061748, U01HL063804, and R21HL121495). The study sponsors had no role in the design, data collection, data analysis, or interpretation of this study, and no role in writing this report or the decision to submit the manuscript. Dr. Everett has received grant support from Novartis Pharmaceuticals; and has served as a consultant for Roche Diagnostics and Abbott Laboratories. Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the Board of Directors of the Boston VA Research Institute and Society of Cardiovascular Patient Care; has served as the chair of American Heart Association Quality Oversight Committee; has served on the data monitoring committees of the Cleveland Clinic, Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (Chief Medical Editor, Cardiology Today Intervention), Society of Cardiovascular Patient Care (Secretary/Treasurer), and WebMD (CME steering committees); has served as the Deputy Editor for Clinical Cardiology; has served as the chair of the NCDR-ACTION Registry Steering Committee and VA CART Research and Publications Committee; has received research funding from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Chiesi, Eisai, Ethicon, Forest Laboratories, Ironwood, Ischemix, Lilly, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (Editor, Cardiovascular Intervention: A Companion to Braunwald Heart Disease); has served as a site co-investigator for Biotronik, Boston Scientific, and St. Jude Medical (now Abbott); has served as a trustee of American College of Cardiology; and has performed unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Hlatky has served as the Medical Advisor for the Office of Clinical Affairs of the Blue Cross Blue Shield Association; served an associate editor for Journal of the American College of Cardiology; served a consultant to the George Institute and Acumen, Inc.; and received research funding from HeartFlow, Inc., Milestone Pharmaceuticals, St. Jude Medical, and Sanofi. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Received January 16, 2018.
- Revision received July 22, 2018.
- Accepted July 23, 2018.
- 2018 American College of Cardiology Foundation
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