Prediction of the early response to spironolactone in resistant hypertension by the combination of matrix metalloproteinase-9 activity and arterial stiffness parameters

• Published in: European heart journal. Cardiovascular pharmacotherapy 2022-01, Vol.8 (1), p.68-76
• Main Authors: Rodríguez-Sánchez, Elena, Navarro-García, José Alberto, Aceves-Ripoll, Jennifer, González-Lafuente, Laura, Baldan-Martin, Montserrat, de la Cuesta, Fernando, Alvarez-Llamas, Gloria, Barderas, María G, Segura, Julián, Ruilope, Luis M, Ruiz-Hurtado, Gema
• Format: Article
• Language: English
• Subjects: Biochemistry; Biomarkers; Blood Pressure Monitoring, Ambulatory; Drug resistance; Enzymes; Health risks; Humans; Hypertension; Hypertension - diagnosis; Hypertension - drug therapy; Matrix Metalloproteinase 9 - therapeutic use; Pulse Wave Analysis; Spironolactone; Spironolactone - adverse effects; Vascular Stiffness
• ISSN: 2055-6837; 2055-6845
• DOI: 10.1093/ehjcvp/pvaa086

Abstract Aims The aim of this study was to determine whether arterial stiffness assessed with the biochemical parameter active matrix metalloproteinase (MMP)-9 and the clinical parameters pulse pressure (PP) and pulse wave velocity predicts the response to spironolactone in resistant hypertension (RH). Methods and results Ambulatory blood pressure (BP) and active MMP-9 (measured by zymography and ELISA) were measured at baseline, and patients were classified as having pseudo-RH or RH. Patients with RH received spironolactone and the response was determined after 8 weeks by ambulatory BP monitoring: those who achieved BP goals were considered controlled (CRH) and those who did not were considered uncontrolled (UCRH). Plasma active MMP-9 was significantly higher in patients with RH than with pseudo-RH, and correlated with 24 h systolic BP and PP. Receiver operating characteristic analysis indicated that active MMP-9 could predict the response to spironolactone, and its combination with 24 h PP and pulse wave velocity significantly improved this prediction. Moreover, plasma of patients with UCRH induced the MMP-9 expression pathway. Conclusion We propose active MMP-9 as a useful biomarker to identify patients with RH who will not respond to spironolactone. Combining MMP-9 activity with classical arterial stiffness parameters improves the prediction of the clinical response to spironolactone and might contribute to guide the most appropriate therapeutic decisions for patients with RH. Graphical Abstract