title: Prognostic value of plasma renin activity in heart failure.
abstract: The prognostic role of specific biomarkers of the renin-angiotensin-aldosterone system and sympathetic activation pathways in heart failure has never been investigated in populations with current evidence-weighted treatment. To establish whether the plasma renin activity (PRA), among several neurohormonal biomarkers, is able to predict cardiac events in a population of patients with heart failure on up-to-date treatment, we selected 996 consecutive patients with systolic left ventricular dysfunction (ejection fraction <50%, mean age 65 ± 13 years), who underwent a complete clinical and humoral characterization and were then followed up (median 36 months, range 0 to 72) for cardiac death and appropriate implantable cardioverter device shock. We recorded 170 cardiac deaths and 27 shocks. On Cox multivariate analysis, only ejection fraction (hazard ratio 0.962, 95% confidence interval 0.938 to 0.986), N-terminal pro-brain natriuretic peptide (NT-proBNP; hazard ratio 1.729, 95% confidence interval 1.383 to 2.161) and PRA (hazard ratio 1.201, 95% confidence interval 1.024 to 1.408) were independent predictors of cardiac death. Receiver operating characteristic curve analysis identified a cutoff value for PRA of 2.30 ng/ml/hour that best predicted cardiac mortality. Independent predictors of PRA were ejection fraction, functional class, sodium, potassium, NT-proBNP, norepinephrine, aldosterone, C-reactive protein, and medical therapy. The association of high NT-proBNP and high PRA identified a subgroup (22% of the study population) with the greatest risk of cardiac death. In conclusion, PRA resulted an independent prognostic marker in patients with systolic heart failure additive to NT-proBNP level and ejection fraction. PRA might help to select those patients needing an enhanced therapeutic effort, possibly targeting incomplete renin-angiotensin-aldosterone system blockade.
authors.affiliation: Division of Cardiovascular Medicine, Fondazione Toscana G. Monasterio, Pisa, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vergaro
authors.forename: Michele
authors.initials: M
authors.lastname: Emdin
authors.forename: Annalisa
authors.initials: A
authors.lastname: Iervasi
authors.forename: Luc
authors.initials: L
authors.lastname: Zyw
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gabutti
authors.forename: Roberta
authors.initials: R
authors.lastname: Poletti
authors.forename: Chiara
authors.initials: C
authors.lastname: Mammini
authors.forename: Alberto
authors.initials: A
authors.lastname: Giannoni
authors.forename: Marianna
authors.initials: M
authors.lastname: Fontana
authors.forename: Claudio
authors.initials: C
authors.lastname: Passino
mesh_terms: D000368:Aged; D000450:Aldosterone / Q000097:blood; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003645:Death, Sudden; D017147:Defibrillators, Implantable; D004232:Diuretics / Q000627:therapeutic use; D004554:Electric Countershock / Q000706:statistics & numerical data; D005260:Female; D005500:Follow-Up Studies; D006333:Heart Failure / Q000097:blood* / Q000145:classification / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000401:mortality; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D011188:Potassium / Q000097:blood; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D012083:Renin / Q000097:blood*; D012680:Sensitivity and Specificity; D012964:Sodium / Q000097:blood; D013148:Spironolactone / Q000627:therapeutic use; D013318:Stroke Volume
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D015415:Biomarkers; D004232:Diuretics; D010446:Peptide Fragments; C109794:pro-brain natriuretic peptide (1-76); D020097:Natriuretic Peptide, Brain; D013148:Spironolactone; D000450:Aldosterone; D012964:Sodium; D012083:Renin; D011188:Potassium; D009638:Norepinephrine