Diabetes Mellitus, Microalbuminuria, and Subclinical Cardiac Disease: Identification and Monitoring of Individuals at Risk of Heart Failure

Abstract

Background: Patients with type 2 diabetes mellitus and elevated urinary albumin:creatinine ratio (ACR) have increased risk of heart failure. We hypothesized this was because of cardiac tissue changes rather than silent coronary artery disease.

Methods and results: In a case-controlled observational study 130 subjects including 50 ACR+ve diabetes mellitus patients with persistent microalbuminuria (ACR >2.5 mg/mol in males and >3.5 mg/mol in females, ≥2 measurements, no previous renin-angiotensin-aldosterone therapy, 50 ACR-ve diabetes mellitus patients and 30 controls underwent cardiovascular magnetic resonance for investigation of myocardial fibrosis, ischemia and infarction, and echocardiography. Thirty ACR+ve patients underwent further testing after 1-year treatment with renin-angiotensin-aldosterone blockade. Cardiac extracellular volume fraction, a measure of diffuse fibrosis, was higher in diabetes mellitus patients than controls (26.1±3.4% and 23.3±3.0% P=0.0002) and in ACR+ve than ACR-ve diabetes mellitus patients (27.2±4.1% versus 25.1±2.9%, P=0.004). ACR+ve patients also had lower E' measured by echocardiography (8.2±1.9 cm/s versus 8.9±1.9 cm/s, P=0.04) and elevated high-sensitivity cardiac troponin T 18% versus 4% ≥14 ng/L (P=0.05). Rate of silent myocardial ischemia or infarction were not influenced by ACR status. Renin-angiotensin-aldosterone blockade was associated with increased left ventricular ejection fraction (59.3±7.8 to 61.5±8.7%, P=0.03) and decreased extracellular volume fraction (26.5±3.6 to 25.2±3.1, P=0.01) but no changes in diastolic function or high-sensitivity cardiac troponin T levels.

Conclusions: Asymptomatic diabetes mellitus patients with persistent microalbuminuria have markers of diffuse cardiac fibrosis including elevated extracellular volume fraction, high-sensitivity cardiac troponin T, and diastolic dysfunction, which may in part be reversible by renin-angiotensin-aldosterone blockade. Increased risk in these patients may be mediated by subclinical changes in tissue structure and function.

Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01970319.

Keywords: biomarker; cardiac magnetic resonance imaging; diabetes mellitus; diastolic dysfunction; echocardiography; extracellular volume fraction; renin angiotensin system.

Figure 1

Recruitment flowchart. ACEi indicates Angiotensin converting enzyme inhibitor; ACR, albumin:creatinine ratio; ACR+ve, albumin:creatinine ratio positive; ACR−ve, albumin:creatinine ratio negative; CI, contraindication; DM, diabetes mellitus; MRI, magnetic resonance imaging.

Figure 2

Late gadolinium enhancement (LGE) and extracellular volume (ECV) maps planned in identical imaging planes of an ACR−ve patient (A and B) and ACR+ve patient (C and D). LGE imaging (A and C) showed no focal fibrosis in either patient but ECV mapping (B and D) demonstrated the ECV to be significantly higher in the ACR+ve patient. ACR indicates albumin:creatinine ratio.