Abstract 19189: Aldosterone and Diabetic Heart Disease: Relevance to Diffuse Myocardial Fibrosis and Coronary Microvascular Dysfunction

Abstract

BACKGROUND: Early diabetic heart disease is characterized by expansion of the cardiac interstitial matrix and impaired myocardial blood flow. Aldosterone is implicated in the pathophysiology of cardiac fibrosis and vascular injury. We hypothesized that aldosterone is associated with interstitial expansion and microcirculatory dysfunction in Type 2 diabetes mellitus (T2DM).

METHODS: We studied 53 subjects with T2DM (68% male; age [mean±SD] 53±7 years, body mass index 32.2±4.3 kg/m2) without evidence of infarction or ischemia by cardiac magnetic resonance (CMR) and PET. After ≥3 months ACE inhibition (enalapril 20 mg daily ± amlodipine for BP control) and optimal glycemic and lipid control, subjects consumed 5 days of high salt diet. 24-hr urinary aldosterone excretion and angiotensin II-stimulated increase in serum aldosterone were measured. CMR to assess extracellular volume fraction (ECV), cardiac PET to assess coronary flow reserve (CFR) and echocardiography were performed. RESULTS: T2DM subjects (HbA1c 6.8±0.7%, BP-systolic 126±14, diastolic 76±9 mmHg) had normal left ventricular structure by CMR and normal diastolic function (transmitral E/A 1.13±0.28, tissue Doppler e’ 0.11±0.03 m/s). CFR (2.51±0.83) was not associated with aldosterone. Myocardial ECV (0.36±0.05) was positively associated with 24-hr urinary aldosterone excretion (r=0.37, P=0.01) and angiotensin II-stimulated increase in aldosterone (r =0.35, P=0.02). In a best-overall stepwise multivariate model (with age, BMI, HbA1c, systolic BP and CFR as covariates), 24-hr urinary aldosterone excretion was still associated with myocardial ECV (P=0.004).

CONCLUSIONS: Aldosterone is associated with CMR measures of interstitial matrix expansion in individuals with T2DM without evidence of epicardial coronary artery disease or diastolic dysfunction and on chronic ACE inhibition. These results implicate aldosterone in early myocardial remodeling in T2DM.