Kosmala, W and Przewlocka-Kosmala, M and Szczepanik-Osadnik, HH and Mysiak, A and O'Moore-Sullivan, T and Marwick, TH, A randomized study of the beneficial effects of aldosterone antagonism on LV function, structure, and fibrosis markers in metabolic syndrome, JACC: Cardiovascular Imaging, 4, (12) pp. 1239-1249. ISSN 1936-878X (2011) [Refereed Article]
Copyright 2011 THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
Background Myocardial fibrosis may be an important contributor to myocardial impairment in MS, and aldosterone antagonism may reduce fibrosis.
Methods Eighty patients (age 59 ± 11 years) with MS, already being treated with angiotensin II inhibition, were randomized to spironolactone 25 mg/day or placebo for 6 months. Each patient underwent baseline and follow-up conventional echocardiography and color tissue Doppler imaging. Raw data files were used to measure calibrated integrated backscatter and to calculate radial and longitudinal strain. 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]).
Results 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. No analogous changes were seen in the placebo group. Baseline strain (β = 0.47, p < 0.0001), spironolactone therapy (β = −0.38, p < 0.0001), and change in PICP level (β = −0.19, p < 0.03) were independently associated with LV systolic function improvement (increase in strain). Correlates of LV diastolic function improvement (increase in early diastolic mitral annular velocity) were baseline early diastolic mitral annular velocity (β = 0.47, p < 0.0001), spironolactone therapy (β = −0.21, p < 0.03), change in PICP level (β = −0.23, p < 0.02), and age (β = 0.22, p < 0.04). Favorable effects of spironolactone on cardiac function were not demonstrated in patients with less fibrosis (the lower baseline PICP tertile) or preserved function (the upper baseline strain tertile).
Conclusions Addition of spironolactone to standard angiotensin II inhibition improved myocardial abnormalities and decreased fibrotic markers in MS. The magnitude of benefit on cardiac performance is determined mainly by baseline LV dysfunction and collagen turnover as well its response to intervention.
|Item Type:||Refereed Article|
|Keywords:||collagen, echocardiography, hypertension, metabolic syndrome, obesity|
|Research Division:||Biomedical and Clinical Sciences|
|Research Group:||Cardiovascular medicine and haematology|
|Research Field:||Cardiology (incl. cardiovascular diseases)|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Marwick, TH (Professor Tom Marwick)|
|Web of Science® Times Cited:||77|
|Deposited By:||Menzies Institute for Medical Research|
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