A Randomized Study of the Beneficial Effects of Aldosterone Antagonism on LV Function, Structure, and Fibrosis Markers in Metabolic Syndrome

Study Questions:

What are the effects of spironolactone on biomarkers of fibrosis and left ventricular (LV) function in subjects with the metabolic syndrome (MS)?


Eighty patients with MS were randomized to spironolactone 25 mg/day or placebo for 6 months. Each patient underwent baseline and follow-up echocardiography and color tissue Doppler imaging. Blood was obtained at baseline and follow-up to measure fibrosis markers (procollagen type III amino-terminal propeptide and procollagen type I carboxy-terminal propeptide [PICP]).


The spironolactone group showed significant improvement of LV function, myocardial reflectivity, and LV hypertrophy, with a parallel decrease in levels of PICP and procollagen type III amino-terminal propeptide. Baseline strain, spironolactone therapy, and change in PICP level were independently associated with LV systolic function improvement. Correlates of LV diastolic function improvement were baseline early diastolic mitral annular velocity, spironolactone therapy, change in PICP level, and age. Favorable effects of spironolactone on cardiac function were not demonstrated in patients with less fibrosis or preserved LV function.


The authors concluded that addition of spironolactone to standard angiotensin II inhibition improved myocardial abnormalities and decreased fibrotic markers in MS.


The benefits of aldosterone blockade may extend to a broad population of patients with early myocardial disease. This paper provides additional support for the use of spironolactone in MS patients with abnormalities in systolic and diastolic function, and also provides a potential mechanistic correlate with the changes in fibrosis biomarkers. These measures may be used to identify MS patients who would derive benefit from aldosterone blockade. Additional data are needed in this group of patients to determine if these changes will lead to improved outcomes.

Clinical Topics: Diabetes and Cardiometabolic Disease, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Acute Heart Failure, Heart Failure and Cardiac Biomarkers, Echocardiography/Ultrasound

Keywords: Follow-Up Studies, Mineralocorticoid Receptor Antagonists, Risk Factors, Spironolactone, Metabolic Syndrome X, Heart Diseases, Cardiovascular Agents, Biological Markers, Cardiomyopathies, Cardiology, Heart Failure, Ventricular Function, Hypertrophy, Fibrosis, Echocardiography

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