Targeted discovery proteomics to identify clinical phenotypes in heart failure with preserved ejection fraction: a proteomics substudy of VITALITY-HFpEF
Notice bibliographique
Résumé
Abstract Background Heart failure with preserved ejection fraction (HFpEF) is a heterogenous syndrome that may emerge from overlapping systemic processes associated with several medical co-morbidities, often within an inflammatory milieu. Identification of unique proteins associated with distinct phenotypes may yield insight into novel therapeutics. Purpose Determine if unique clusters of circulating proteins are associated with specific clinical characteristics in patients with HFpEF. Methods A targeted discovery proteomics approach with 358 unique proteins associated with cardiovascular disease and inflammation (Olink) was used at baseline in VITALITY-HFpEF among 789 participants with documented left ventricular EF ≥45% and recent decompensation (<6 mos). Proteins were clustered applying the weighted correlation network analysis (WCNA). The associations of the clinical characteristics and frailty and clusters were estimated with linear regression adjusted for age and eGFR. Frailty was characterized as normal, pre-frail, and frail using the Fried criteria. KCCQ was the primary and 6-minute walk distance (6MWD) the secondary endpoint of VITALITY-HFpEF. Results Four unique clusters were identified containing 24, 66, 197, and 81 proteins, respectively. Figure 1 shows the adjusted association of the 4 protein clusters, shown with their hub proteins, with the clinical characteristics. The color (red: positive, green: negative relationship) and intensity indicate the magnitude of the standardized difference (relative to the variation [i.e., T-value]); p-value shown in boxes. Cluster 3, with tumor necrosis factor receptor 1 as a hub protein that mediates apoptosis and inflammation, was associated with greater frailty and physical limitation along with shorter 6MWD. In contrast, cluster 4, with protein C as a hub protein that regulates anticoagulation and exerts a protective function on endothelial cells, is associated with less frailty and younger age, and more frequently male sex. Cluster 2 was associated with only younger age and cluster 1 with no clinical characteristics. Conclusions Proteomics appear to identify specific clinical phenotypes associated with HFpEF. Further exploration of this approach may provide insight into the diverse pathophysiology characterizing this disorder and a more targeted approach to therapy. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): VITALITY-HFpEF was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA and Bayer AG, Wuppertal, Germany.
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,003 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 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 tête enseignante, 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 ».