Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes

Rajesh Garg, Ajay D Rao, Maria Baimas-George, Shelley Hurwitz, Courtney Foster, Ravi V Shah, Michael Jerosch-Herold, Raymond Y Kwong, Marcelo F Di Carli, Gail K Adler, Rajesh Garg, Ajay D Rao, Maria Baimas-George, Shelley Hurwitz, Courtney Foster, Ravi V Shah, Michael Jerosch-Herold, Raymond Y Kwong, Marcelo F Di Carli, Gail K Adler

Abstract

Reduced coronary flow reserve (CFR), an indicator of coronary microvascular dysfunction, is seen in type 2 diabetes mellitus (T2DM) and predicts cardiac mortality. Since aldosterone plays a key role in vascular injury, the aim of this study was to determine whether mineralocorticoid receptor (MR) blockade improves CFR in individuals with T2DM. Sixty-four men and women with well-controlled diabetes on chronic ACE inhibition (enalapril 20 mg/day) were randomized to add-on therapy of spironolactone 25 mg, hydrochlorothiazide (HCTZ) 12.5 mg, or placebo for 6 months. CFR was assessed by cardiac positron emission tomography at baseline and at the end of treatment. There were significant and similar decreases in systolic blood pressure with spironolactone and HCTZ but not with placebo. CFR improved with treatment in the spironolactone group as compared with the HCTZ group and with the combined HCTZ and placebo groups. The increase in CFR with spironolactone remained significant after controlling for baseline CFR, change in BMI, race, and statin use. Treatment with spironolactone improved coronary microvascular function, raising the possibility that MR blockade could have beneficial effects in preventing cardiovascular disease in patients with T2DM.

Trial registration: ClinicalTrials.gov NCT00865124.

© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Figures

Figure 1
Figure 1
An ANCOVA model predicting the change with treatment in CFR. Spironolactone treatment improved CFR as compared with HCTZ (*P = 0.02), placebo (†P = 0.05), and combined HCTZ/placebo groups (‡P = 0.01). HCTZ and placebo had similar effects on CFR (P = 0.79). The predicted adjusted change (95% CI) in posttreatment CFR was 0.38 (0.11, 0.65) with spironolactone, −0.10 (−0.38, 0.18) with HCTZ, and −0.05 (−0.38, 0.28) with placebo. Model adjusts for race, statin use, baseline CFR, and the change in BMI over the treatment period.

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