Risk Factors for First and Subsequent CVD Events in Type 1 Diabetes: The DCCT/EDIC Study

Abstract

Objective: The Diabetes Control and Complications Trial (DCCT) and its observational follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) demonstrated the dominant role of glycemia, second only to age, as a risk factor for a first cardiovascular event in type 1 diabetes (T1D). We now investigate the association between established risk factors and the total cardiovascular disease (CVD) burden, including subsequent (i.e., recurrent) events.

Research design and methods: CVD events in the 1,441 DCCT/EDIC participants were analyzed separately by type (CVD death, acute myocardial infarction [MI], stroke, silent MI, angina, percutaneous transluminal coronary angioplasty/coronary artery bypass graft [PTCA/CABG], and congestive heart failure [CHF]) or as composite outcomes (CVD or major adverse cardiovascular events [MACE]). Proportional rate models and conditional models assessed associations between risk factors and CVD outcomes.

Results: Over a median follow-up of 29 years, 239 participants had 421 CVD events, and 120 individuals had 149 MACE. Age was the strongest risk factor for acute MI, silent MI, stroke, and PTCA/CABG, while glycemia was the strongest risk factor for CVD death, CHF, and angina, second strongest for acute MI and PTCA/CABG, third strongest for stroke, and not associated with silent MI. HbA1c was the strongest modifiable risk factor for a first CVD event (CVD: HR 1.38 [95% CI 1.21, 1.56] per 1% higher HbA1c; MACE: HR 1.54 [1.30, 1.82]) and also for subsequent CVD events (CVD: incidence ratio [IR] 1.28 [95% CI 1.09, 1.51]; MACE: IR 1.89 [1.36, 2.61]).

Conclusions: Intensive glycemic management is recommended to lower the risk of initial CVD events in T1D. After a first event, optimal glycemic control may reduce the risk of recurrent CVD events and should be maintained.

Trial registration: ClinicalTrials.gov NCT00360893 NCT00360815.

© 2020 by the American Diabetes Association.

Figures

Figure 1

z scores for the association between the five most important risk factors (largest z values) and individual CVD outcomes in proportional rate models adjusted for age and mean HbA1c. The gray circles describe z scores with values between 1 and 6, and risk factors with z scores >1.96 in absolute value (outside the black circle) are considered nominally significant. For example, mean HbA1c was the strongest risk factor for CVD death, CHF, and angina (z = 5.20, 4.82, and 4.75, respectively), while age was the strongest risk factor for acute MI, silent MI, and PTCA/CABG (z = 6.04, 4.18, and 6.02, respectively).