Physicians' Academy for Cardiovascular Education

T2DM-related microvascular disease associated with incident HF

Microvascular Disease and Incident Heart Failure Among Individuals With Type 2 Diabetes Mellitus

Literature - Kaze AD, Santhanam P, Erqou S, et al. - J Am Heart Assoc. 2021;10:e018998. doi: 10.1161/JAHA.120.018998.

Introductions and methods

Evidence suggests that patients with T2DM have a 2-4 fold increased risk of developing HF, independently of additional CV risk factors such as high BP, hypercholesterolemia, or CAD [1,2]. Data from animal studies suggest that microvascular dysfunction, amongst several other pathways, might link diabetes mellitus to HF [3,4]. However, epidemiological data on the relationship between microvascular disease (MVD) with incident HF in individuals with T2DM are limited. This study analyzed the association of MVD in multiple vascular beds with incident HF in patients with T2DM.

The Look AHEAD (Action of Health in Diabetes) study was a randomized, multicentered, double-blind trial that included 5145 participants from the US from August 2001 to April 2004. Inclusion criteria were: BMI ≥25 kg/m² (or ≥27 kg/m² if patients were on insulin), HbA1c ≤11%, SBP <160 mm Hg, DBP <100 mm Hg, TG levels <600 mg/dL. Individuals (45-76 years) were randomized to participate in an intensive lifestyle intervention (intervention group) or to receive diabetes mellitus support and education (control group). For the current analysis, people with a history of HF or atherosclerotic CVD defined as prior MI or stroke at baseline or with missing data on MVD were excluded. This resulted in a dataset with data from 4095 participants (mean age 58.3 [SD 6.6] years, 61.9% were women). Diabetic MVD was defined as the presence of nephropathy, retinopathy, and/or neuropathy at baseline. First hospitalization for definite or possible acute decompensated HF was prospectively assessed to determine incident HF. Median (IQR) follow-up was 9.7 (8.9-10.3) years.

Main results


This study showed that MVD was associated with an elevated risk of developing HF in adults with T2DM. This association was independent of traditional risk factors, including CAD.


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