Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes
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posted on 2021-05-12, 18:52 authored by Rose Gubitosi-Klug, Xiaoyu Gao, Rodica Pop-Busui, Ian H de Boer, Neill White, Lloyd P Aiello, Ryan Miller, Jerry Palmer, William Tamborlane, Amisha Wallia, Mikhail Kosiborod, John M Lachin, Ionut Bebu, DCCT/EDIC Research Group<b>Objective:</b> We examined whether the presence of
microvascular complications was associated with increased subsequent risk of cardiovascular
disease (CVD) among participants with type 1 diabetes in the Diabetes Control
and Complications Trial and Epidemiology of Diabetes Interventions and
Complications (DCCT/EDIC) Study followed for over 35 years.
<p><b>Research
Design and Methods:</b> Standardized longitudinal
data collection included: 1) stereoscopic seven-field retinal fundus
photography centrally-graded for retinopathy stage and clinically significant
macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular
filtration rate (eGFR);
3) cardiovascular autonomic neuropathy
(CAN) reflex testing; and 4) adjudicated CVD events, including death from cardiovascular disease,
nonfatal myocardial infarction, stroke, subclinical myocardial infarction on
ECG, confirmed angina, or coronary artery revascularization. Cox
proportional hazard models assessed the association of microvascular
complications with subsequent risk of CVD. </p>
<p><b>Results:</b> 239 participants developed CVD, including 120
participants who suffered major adverse cardiovascular events (MACE) defined as
non-fatal myocardial
infarction, non-fatal stroke or cardiovascular death. The
presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN)
was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09
to 3.63, respectively); associations that remained significant after adjusting
for age and HbA1c. After adjustment for
traditional CVD risk factors, however, only sustained AER≥30 mg/24hr occurring alone and/or with
eGFR<60 ml/min/1.73m, and the presence
of both retinal and kidney disease remained associated with CVD. </p>
<p><b>Conclusions:</b> Advanced microvascular disease, especially moderate
to severe albuminuria or eGFR<60
ml/min/1.73m<sup>2</sup>, conveyed an
increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort. </p>
Funding
The DCCT/EDIC has been supported by cooperative agreement grants (1982-1993, 2012-2017, 2017-2022), and contracts (1982-2012) with the Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Disease (current grant numbers U01 DK094176 and U01 DK094157), and through support by the National Eye Institute, the National Institute of Neurologic Disorders and Stroke, the General Clinical Research Centers Program (1993-2007), and Clinical Translational Science Center Program (2006-present), Bethesda, Maryland, USA.
History
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