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Electrocardiographic Abnormalities and Cardiovascular Disease Risk In Diabetes Care Volume 40, June 2017 793 Elsayed Z. Soliman,1 Jye-Yu C. Backlund,2 Electrocardiographic Ionut Bebu,2 Trevor J. Orchard,3 Bernard Zinman,4 John M. Lachin,2 and the Abnormalities and Cardiovascular DCCT/EDIC Research Group* Disease Risk in Type 1 Diabetes: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study Diabetes Care 2017;40:793–799 | https://doi.org/10.2337/dc16-2050 OBJECTIVE We examined the association between the prevalence and incidence of electro- cardiographic (ECG) abnormalities and the development of cardiovascular disease (CVD) in patients with type 1 diabetes, among whom these ECG abnormalities are common. 1Epidemiological Cardiology Research Center RESEARCH DESIGN AND METHODS (EPICARE), Department of Epidemiology and Pre- We conducted a longitudinal cohort study involving 1,306 patients with type 1 vention, and Department of Medicine, Section on 6 Cardiology, Wake Forest School of Medicine, CARDIOVASCULAR AND METABOLIC RISK diabetes (mean age 35.5 6.9 years; 47.7% female) from the Diabetes Control and Winston-Salem, NC Complications Trial/Epidemiology of Diabetes Interventions and Complications 2The Biostatistics Center, The George Washing- (DCCT/EDIC) Study. ECG abnormalities were defined by the Minnesota Code ton University, Rockville, MD 3 ECG classification as major, minor, or no abnormality. CVD events were defined University of Pittsburgh Graduate School of fi fi Public Health, Pittsburgh, PA as the rst occurrence of myocardial infarction, stroke, con rmed angina, coro- 4Lunenfeld Tanenbaum Research Institute, nary artery revascularization, congestive heart failure, or death from any CVD. Mount Sinai Hospital, University of Toronto, Toronto, Canada RESULTS Corresponding author: Elsayed Z. Soliman, esoliman@ During a median follow-up of 19 years, 155 participants (11.9%) developed CVD wakehealth.edu. events. In multivariable Cox proportional hazard models adjusted for demograph- Received 23 September 2016 and accepted 25 ics and potential confounders, the presence of any major ECG abnormalities as a February 2017. time-varying covariate was associated with a more than twofold increased risk of This article contains Supplementary Data online CVD events (hazard ratio [HR] 2.10 [95% CI 1.26, 3.48] vs. no abnormality/normal at http://care.diabetesjournals.org/lookup/ suppl/doi:10.2337/dc16-2050/-/DC1. ECG, and 2.19 [1.46, 3.29] vs. no major abnormality). Also, each visit (year) at *A complete list of participants in the DCCT/EDIC which the diagnosis of major ECG abnormality was retained was associated with a Research Group can be found at http://www 30% increased risk of CVD (HR 1.30 [95% CI 1.14, 1.48]). The presence of minor ECG .nejm.org/doi/suppl/10.1056/NEJMoa1409463/ abnormalities was not associated with a significant increase in CVD risk. suppl_file/nejmoa1409463_appendix.pdf. © 2017 by the American Diabetes Association. CONCLUSIONS Readers may use this article as long as the work The presence of major ECG abnormalities is associated with an increased risk of is properly cited, the use is educational and not for profit, and the work is not altered. More infor- CVD in patients with type 1 diabetes. This suggests a potential role for ECG screen- mation is available at http://www.diabetesjournals ing in patients with type 1 diabetes to identify individuals at risk for CVD. .org/content/license. 794 Abnormal ECG and CVD Risk in Type 1 Diabetes Diabetes Care Volume 40, June 2017 Type 1 diabetes is known to be associated years old; 726 participants were as- left [MC 7.1] and right [MC 7.2] bundle with a higher incidence and prevalence of signed to the primary prevention cohort branch block, major intraventricular cardiovascular disease (CVD) (1), the pri- (diabetes duration 1–5years,noreti- conduction delay [MC 7.4], and bifascic- mary cause of death in patients with nopathy, and urinary albumin excretion ular block [MC 7.8]), major Q-wave ab- type 1 diabetes (2–4). Increased CVD rate [AER] ,40 mg/day), and 715 to the normalities (MC 1.1.x, MC 1.2.x), minor risk is not, however, uniform in all pa- secondary intervention cohort (diabetes Q-wave abnormalities plus major ST/ tients with type 1 diabetes; it varies ac- duration 1–15 years, very mild to mod- T-wave abnormalities (MC 1.3.x plus cording to individual characteristics and erate nonproliferative retinopathy, and [MC4.1.x,MC4.2,MC5.1,MC5.2]), risk profile (1,5). Identifying these predic- AER #200 mg/day). Intensive therapy isolated major ST/T-wave abnormalities tive characteristics and risk markers is (n = 711) aimed to achieve levels of gly- (MC 4.1.x, MC 4.2, MC 5.1, MC 5.2), left necessary to improve our ability to iden- cemia as close to the nondiabetic range ventricular hypertrophy with strain pat- tify patients with type 1 diabetes who are as safely possible, whereas conventional tern (MC 3.1 and [MC 4.1.x, MC 4.2, MC at a higher risk. therapy (n = 730) aimed to maintain clin- 5.1, MC 5.2]), atrial fibrillation/flutter Electrocardiography (ECG) is the most ical well-being, with no specificglucose (MC 8.3), major atrioventricular block widely used noninvasive tool for cardiac targets. At the end of the DCCT (1993), (complete atrioventricular block [MC investigation. We recently showed that participants in the conventional treat- 6.1] and second-degree atrioventric- developing new ECG abnormalities is ment group were instructed in intensive ular block [MC 6.2]), major QT prolon- common in the course of type 1 diabe- diabetes therapy. In 1994, all surviving gation (QT index .116%), electronic tes; about three of every four partici- DCCT participants were invited to join pacemaker (MC 6.8), and others (atrio- pants in the Diabetes Control and the EDIC observational study. The study ventricular dissociation [MC 8.6], ven- Complications Trial (DCCT)/Epidemiol- was approved by the institutional re- tricular tachycardia [MC 8.2], and ogy of Diabetes Interventions and Com- view board at each study site. All par- Wolf-Parkinson-White syndrome/ plications (EDIC) study developed at ticipants provided written informed pre-excitation [MC 6.4]). Minor ECG least one new ECG abnormality, and consent. abnormalities included minor isolated about one of every six developed at For the purpose of this analysis, we Q-wave abnormalities (MC 1.3.x), minor least one new major ECG abnormality included EDIC participants with a good- isolated ST/T-wave abnormalities (MC during 16 years of follow-up in EDIC quality ECG at the EDIC year 1 visit (re- 4.3, MC 4.4, MC 5.3, MC 5.4), high R (6). Prior reports have shown that the ferredtoas“baseline” in this article) waves/increased QRS voltage denoting presence of these ECG abnormalities in and at least one follow-up visit thereaf- left or right ventricular hypertrophy with- populations without diabetes is associ- ter. Patients who had CVD events before outstrainpattern(MC3.1,MC3.2,MC3.3, ated with an increased risk of CVD EDIC year 1 were eliminated from this MC 3.4), nonischemic ST segment eleva- events and all-cause mortality (7–11). analysis. Supplementary Fig. 1 shows tion (MC 9.2), incomplete bundle branch Similarly, in a small study with a relative- the inclusion and exclusion criteria ap- blocks (left [MC 7.6] and right [MC 7.3] ly short follow-up, the presence of ECG plied and how the analysis sample was bundle branch blocks and left anterior markers of myocardial ischemia in pa- achieved. hemiblock [MC 7.7]), minor QT prolonga- tients with type 1 diabetes was predic- tion (QT index .112% but ,116%), short tive of future coronary heart disease ECG PR interval (MC 6.5), axis deviation (left (12). However, no comprehensive re- EDIC participants underwent resting axis deviation [MC 2.1], right axis deviation ports have described the prognostic 12-lead ECG recording annually. ECG [MC 2.2]), ventricular premature beats significance of ECG abnormalities in pa- tracings were centrally read at an ECG (MC 8.1.2, MC 8.1.3), and others (low tients with type 1 diabetes, in whom core facility, initially (EDIC years 1–11) at QRS voltage [MC 9.1], premature atrial ec- CVD develops at least a decade sooner the University of Minnesota ECG Read- topic beats [MC 8.1.1], wandering atrial compared with the general population ing Center (Minneapolis, MN), then at pacemaker [MC 8.1.4], abnormal P-wave (1). Therefore, the purpose of this study the Epidemiological Cardiology Re- amplitude [MC 9.3], prolonged PR interval/ was to examine the association between search Center (EPICARE) of Wake Forest first-degree atrioventricular block [MC the presence of ECG abnormalities and School of Medicine (Winston-Salem, 6.3], marked sinus bradycardia [MC 8.8], incident CVD events in patients with NC). The change in the ECG reading and marked sinus tachycardia [MC 8.7]) type 1 diabetes enrolled in the EDIC center did not affect the rate of devel- (14). Study, providing observational follow-up oping new ECG abnormalities (interac- of the DCCT cohort. tion P values between the reading Cardiovascular Events center and the DCCT treatment group All events were adjudicated by a mortal- RESEARCH DESIGN AND METHODS for any ECG abnormalities and major ity and morbidity review committee The EDIC observational component of ECG abnormalities were 0.98 and 0.65, whose members were blinded to the the DCCT/EDIC Study started in 1994, respectively). DCCT treatment group and level of gly- after completion of the DCCT, which ECG abnormalities were classified as cemia. CVD events used in this analysis consisted of a comparison of the effects major and minor abnormalities using occurred through December 2013 and of intensive versus conventional diabe- the standards of the Minnesota Code were defined using methods described tes therapy on long-term diabetes com- (MC) for ECG classification (14).
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