Role of angiotensin peptides in risk stratification and prognostication for heart failure: focus on plasma Ang 1–7/Ang II ratio
Notice bibliographique
Résumé
Abstract Background ACE2 and Ang 1–7 are endogenous negative regulators of the renin-angiotensin system (RAS) exerting cardioprotective effects in models of heart failure (HF). Recombinant ACE2 markedly increased plasma Ang 1–7 and lowered Ang II levels in clinical trials. Elevated plasma ACE2 activity is associated with adverse outcomes in HF patients. However, the direct effects of systemic and tissue ACE2 activation on angiotensin peptides in relation to long-term HF outcomes has yet to be examined. Purpose To generate insights into the ACE2 mediated cardioprotective arm through the relative levels of its substrates and products using the plasma Ang 1–7/Ang II ratio, and assess its prognostic utility in HF patients. Methods 110 HF patients were prospectively enrolled from outpatient clinics and the emergency department. Comprehensive circulating and equilibrium levels of plasma angiotensin peptides were assessed using novel liquid chromatography-mass spectrometry/mass spectroscopy techniques. Plasma aldosterone, BNP, active renin activity and clinical profiles were captured at baseline. Patients were stratified into above and below median cohorts based on equilibrium and circulating levels of Ang 1–7/Ang II ratio, as a surrogate for ACE2 functionality. During a median follow-up of 5.1±0.8 years, composite clinical outcomes were assessed through all-cause in-patient hospitalizations and mortality. Results Circulating and equilibrium angiotensin peptide levels strongly correlated in our patient cohort. All-cause mortality for HF patients with equilibrium Ang 1–7/Ang II ratios above the median showed higher survival rates compared to below median patients (76.4% vs. 50.9%; p=0.004); similar results were observed for circulating Ang 1–7/Ang II ratios (72.7% vs. 54.5%; p=0.041). Adjusting for covariates, elevated equilibrium (HR: 0.24; 95% CI: 0.09 to 0.69; p=0.008) and circulating (HR: 0.35; 95% CI: 0.13 to 0.94; p=0.036) Ang 1–7/Ang II ratios was associated with improved survival. Lower hospitalization duration was also associated with elevated equilibrium (p<0.001) and circulating (p=0.023) Ang 1–7/Ang II ratios. In nested models, net reclassification analysis showed considerable improvement in risk prediction for all-cause mortality at 5 years provided by both the equilibrium (+45.0% [95% CI: 7.3% to 82.7%]) and circulating Ang 1–7/Ang II ratios (+24.3% [95% CI: 0.4% to 59.6%]) respectively. Conclusions We extensively profiled plasma angiotensin peptides in HF patients and identified elevated ACE2 signature, reflected through the Ang 1–7/Ang II ratio, as an independent and incremental predictor of beneficial outcomes, higher survival rate, and decreased hospitalization duration. These findings provide important clinical evidence supporting strategies aiming to promote the beneficial ACE2/Ang 1–7/Mas receptor axis concurrent with RAS blockade therapies inhibiting the detrimental ACE/Ang II/AT1 receptor axis. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Alberta Innovates, Canadian Institute of Health Research
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».