title: Biomarkers of activation of renin-angiotensin-aldosterone system in heart failure: how useful, how feasible?
abstract: Renin-angiotensin-aldosterone system (RAAS), participated by kidney, liver, vascular endothelium, and adrenal cortex, and counter-regulated by cardiac endocrine function, is a complex endocrine system regulating systemic functions, such as body salt and water homeostasis and vasomotion, in order to allow the accomplishment of physiological tasks, such as orthostasis, physical and emotional stimuli, and to react towards the hemorrhagic insult, in tight conjunction with other neurohormonal axes, namely the sympathetic nervous system, the endothelin and vasopressin systems. The systemic as well as the tissue RAAS are also dedicated to promote tissue remodeling, particularly relevant after damage, when chronic activation may configure as a maladaptive response, leading to fibrosis, hypertrophy and apoptosis, and organ dysfunction. RAAS activation is a fingerprint of systemic arterial hypertension, kidney dysfunction, vascular atherosclerotic disease, and is definitely an hallmark of heart failure, which rapidly shifts from organ disease to a disorder of neurohormonal regulatory systems. Chronic RAAS activation is an indirect or direct target of most effective pharmacological treatments in heart failure, such as beta-blockers, inhibitors of angiotensin converting enzyme, angiotensin receptor blockers, direct renin inhibitors, and mineralocorticoid receptor blockers. Biomarkers of RAAS activation are available, with different feasibility and accuracy, such as plasma renin activity, renin, angiotensin II, and aldosterone, which all accompany the increasing clinical severity of heart failure disease, and are well recognized prognostic factors, even in patients with optimal therapy. Polymorphisms influencing the expression and activity of RAAS pathways have been recognized as clinically relevant biomarkers, likely influencing either the individual clinical phenotype, or the response to drugs. This solid, growing evidence strongly suggests the rationale for the use of biomarkers of the RAAS activation, as a guide to tailor individual therapy in the current practice, and their implementation as a rule-in marker for future trials on novel drugs in the heart failure setting.
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy. Electronic address: emdin@ftgm.it.
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.affiliation: Department of Medical and Surgical Critical Care, University of Florence, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Fatini
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Mirizzi
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Poletti
authors.affiliation: Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Borrelli
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Prontera
authors.affiliation: Istituto Mario Negri, Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Latini
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Aldo
authors.initials: A
authors.lastname: Clerico
authors.affiliation: Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy; Scuola Superiore Sant'Anna, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vergaro
mesh_terms: D000450:Aldosterone / Q000032:analysis / Q000378:metabolism*; D000809:Angiotensins / Q000032:analysis / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D006333:Heart Failure / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D012083:Renin / Q000032:analysis / Q000378:metabolism*; D015203:Reproducibility of Results
chemical_list: D000809:Angiotensins; D015415:Biomarkers; D000450:Aldosterone; D012083:Renin
keywords: Aldosterone; Angiotensin; Biomarkers; Heart failure; Renin