Echocardiography improves prediction of major adverse cardiovascular events in a population with type 1 diabetes and without known heart disease: the Thousand & 1 Study
Cardiovascular disease is the most common comorbidity in type 1 diabetes. However, current guidelines do not include routine assessment of myocardial function. We investigated whether echocardiography provides incremental prognostic information in individuals with type 1 diabetes without known heart disease.
A prospective cohort of individuals with type 1 diabetes without known heart disease was recruited from the outpatient clinic. Follow-up was performed through Danish national registers. The association of echocardiography with major adverse cardiovascular events (MACE) and the incremental prognostic value when added to the clinical Steno T1D Risk Engine were examined.
A total of 1093 individuals were included: median (interquartile range) age 50.2 (39.2–60.3) years and HbA1c 65 (56–74) mmol/mol; 53% men; and mean (SD) BMI 25.5 (3.9) kg/m2 and diabetes duration 25.8 (14.6) years. During 7.5 years of follow-up, 145 (13.3%) experienced MACE. Echocardiography significantly and independently predicted MACE: left ventricular ejection fraction (LVEF) <45% (n = 18) vs ≥45% (n = 1075), HR (95% CI) 3.93 (1.91, 8.08), p < 0.001; impaired global longitudinal strain (GLS), 1.65 (1.17, 2.34) (n = 263), p = 0.005; diastolic mitral early velocity (E)/early diastolic tissue Doppler velocity (e′) <8 (n = 723) vs E/e′ 8–12 (n = 285), 1.59 (1.04, 2.42), p = 0.031; and E/e′ <8 vs E/e′ ≥12 (n = 85), 2.30 (1.33, 3.97), p = 0.003. In individuals with preserved LVEF (n = 1075), estimates for impaired GLS were 1.49 (1.04, 2.15), p = 0.032; E/e′ <8 vs E/e′ 8–12, 1.61 (1.04, 2.49), p = 0.033; and E/e′ <8 vs E/e′ ≥12, 2.49 (1.41, 4.37), p = 0.001. Adding echocardiographic variables to the Steno T1D Risk Engine significantly improved risk prediction: Harrell’s C statistic, 0.791 (0.757, 0.824) vs 0.780 (0.746, 0.815), p = 0.027; and net reclassification index, 52%, p < 0.001.
In individuals with type 1 diabetes without known heart disease, echocardiography significantly improves risk prediction over and above guideline-recommended clinical risk factors alone and could have a role in clinical care.
KeywordsCardiovascular Diabetes Echocardiography Heart disease Prognosis Type 1 diabetes
Coronary artery bypass graft
Early diastolic tissue Doppler velocity
Early mitral peak diastolic velocity
Global longitudinal strain
Integrated discrimination improvement
Left ventricular ejection fraction
Major adverse cardiovascular events
Net reclassification index
Percutaneous coronary intervention
We gratefully express our appreciation to the former Chair of Cardiology J. K. Madsen and the late Professor J. S. Jensen (1962–2018) both from Department of Cardiology, Copenhagen University Hospital Herlev-Gentofte, whose importance for the establishment of the Thousand & 1 Study cannot be overstated. We are indebted to the staff and patients of Steno Diabetes Center Copenhagen for their participation and contribution to the Thousand & 1 Study.
MTJ made substantial contributions to the conception and design of the work, the acquisition, analysis and interpretation of data and drafting the manuscript and revising it critically for important intellectual content. MTJ gave final approval of the version to be published. MTJ had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. PS, HUA, TA and PR made substantial contributions to the conception and design of the work and interpretation of data; they revised the manuscript critically for important intellectual content and gave final approval of the version to be published. IG, JB, TFH, TA, ST, TB-S, PGJ and SG made substantial contributions to the acquisition and interpretation of data, revised the manuscript critically for important intellectual content and gave final approval of the version to be published.
The work was supported by The European Foundation for the Study of Diabetes/Pfizer European Programme 2010 for Research into Cardiovascular Risk Reduction in Patients with Diabetes and the Danish Heart Foundation (no. 12-04-R90-A3840-22725). The funding sources had no influence on: the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review nor approval of the manuscript; nor the decision to submit the manuscript for publication.
Duality of interest
MTJ has served as consultant on advisory boards or as an invited speaker for Astra Zeneca, Novo Nordisk, Novartis and GE Healthcare. PGJ has received lecture fees from Novo Nordisk. PR has: board memberships for Astra Zeneca, Astellas, Boehringer Ingelheim, Lilly and Novo Nordisk; received grants and/or has grants pending from Novo Nordisk and Astra Zeneca; received payment for lectures (all payments to institution) from Astra Zeneca/BMS, Novartis and Sanofi Aventis; and stocks in Novo Nordisk. HUA is a member of advisory boards for Abbott, Astra Zeneca and Novo Nordisk, has received lecture fees from Nordic Infucare and has stocks in Novo Nordisk. All other authors declare that there is no duality of interest associated with their contribution to this manuscript.
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