PT  - JOURNAL ARTICLE
AU  - Ferreira, João Pedro
AU  - Rossignol, Patrick
AU  - Pizard, Anne
AU  - Machu, Jean-Loup
AU  - Collier, Timothy
AU  - Girerd, Nicolas
AU  - Huby, Anne-Cécile
AU  - Gonzalez, Arantxa
AU  - Diez, Javier
AU  - López, Begoña
AU  - Sattar, Naveed
AU  - Cleland, John G
AU  - Sever, Peter S
AU  - Zannad, Faiez
TI  - Potential spironolactone effects on collagen metabolism biomarkers in patients with uncontrolled blood pressure
AID  - 10.1136/heartjnl-2018-313182
DP  - 2019 Feb 01
TA  - Heart
PG  - 307--314
VI  - 105
IP  - 4
4099  - http://heart.bmj.com/content/105/4/307.short
4100  - http://heart.bmj.com/content/105/4/307.full
SO  - Heart2019 Feb 01; 105
AB  - Background An increase in myocardial collagen content may contribute to the development of heart failure; this might be inhibited or reversed by mineralocorticoid receptor antagonists (MRAs). We investigated changes in serum concentrations of the collagen synthesis biomarkers N-terminal propeptide of procollagen type III (PIIINP) (primary outcome) and C-terminal propeptide of procollagen type I (PICP) (secondary outcome) after non-randomised initiation of spironolactone as add-on therapy among patients with resistant hypertension enrolled in the ‘Anglo-Scandinavian Cardiac Outcomes’ trial (ASCOT).Methods An age/sex matching plus propensity-scored logistic regression model incorporating variables related to the outcome and spironolactone treatment was created to compare patients treated with spironolactone for a 9-month period versus matched controls. A within-person analysis comparing changes in serum biomarker concentrations in the 9 months before versus after spironolactone treatment was also performed.Results Patients included in the between-person analysis (n=146) were well matched: the mean age was 63±7 years and 11% were woman. Serum concentrations of PIIINP and PICP rose in ‘controls’ and fell during spironolactone treatment (adjusted means +0.52 (−0.05 to 1.09) vs −0.41 (−0.97 to 0.16) ng/mL, p=0.031 for PIIINP and +4.54(−1.77 to 10.9) vs −6.36 (−12.5 to −0.21) ng/mL, p=0.023 for PICP). For the within-person analysis (n=173), spironolactone treatment was also associated with a reduction in PICP (beta estimate=−11.82(−17.53 to −6.10) ng/mL, p<0.001) but not in PIIINP levels.Conclusions 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.