Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure

Abstract

Treatment with spironolactone was associated with a reduction in serum biomarkers of collagen synthesis independently of blood pressure in patients with hypertension, suggesting that spironolactone might exert favourable effects on myocardial collagen synthesis and fibrosis. Whether this effect might contribute to slowing the progression to heart failure is worth investigating.

Effects of spironolactone on serum markers of fibrosis in people at high risk of developing heart failure: rationale, design and baseline characteristics of a proof‐of‐concept, randomised, precision‐medicine, prevention trial. The Heart OMics in AGing (HOMAGE) trial

“…14,32,33 Trials of patients with obesity and/or hypertension have more consistently shown reductions in both PIIINP and PICP, as well as improvement in Doppler indices of left ventricular diastolic dysfunction. [34][35][36] Overall, the trials suggest that MRAs lead to more consistent reductions in serum PIIINP than PICP, markers of synthesis, with little effect on CITP, a marker of collagen degradation ( Table 1). 14,[27][28][29][30][32][33][34][35][36][37][38][39][40] The above observations provide the rationale for the Heart OMics in AGing (HOMAGE) trial, investigating whether spironolactone favourably alters markers of extra-cellular matrix remodelling for patients at increased risk of developing HF.…”

“…Median LVEF was normal at 63% (IQR 58-67%) and median plasma concentrations of NT-proBNP were 214 (IQR 137-356) ng/L ( Table 5). 36,[38][39][40][44][45][46][47][48][49][50] Left atrial volume and the ratio of E/E ′ were increased and left ventricular mass was at the upper limit of normal. On a symptom questionnaire (Appendix), the median score in response to the question 'Do you get breathless on moderate exertion (e.g.…”

Determinants of anti-fibrotic response to mineralocorticoid receptor antagonist therapy: insights from the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) and Early Eplerenone Treatment in Patients with Acute ST-elevation Myocardial Infarction without Heart Failure (REMINDER) trials

“…Previous reports showed that MRA treatment was associated with a decrease in collagen biomarkers, PIIINP in particular 4,10,14 . Hence, a decrease in PIIINP was used as a surrogate of anti-fibrotic response in the present study.…”

Roles of Biomarkers in Myocardial Fibrosis

“…A cross-sectional study demonstrated that plasma PICP levels in HCM patients were positively correlated with myocardial PICP content and the histological myocardial collagen volume fraction [10]. Similarly, Ferreira et al also confirmed that the serum levels of PICP were significantly higher in patients with hypertension before drug treatment [11]. In contrast, in heart failure rats, Adamcova et al observed that collagen content in the left ventricle was increased, whereas plasma PICP levels were reduced by 42% as compared to the control group [12].…”