Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts
Background Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome, likely stemming from comorbidity‐induced inflammation resulting in endothelial dysfunction. Endothelial glycocalyx degradation's role in the development and prognosis of HFpEF remains largely unexplore...
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Wiley
2025-06-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.040179 |
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| author | Jeremy Lagrange Mohammad Jahangiri Guillaume Baudry Nathalie Mercier Luca Monzo Zohra Lamiral Kévin Duarte Jozine M ter Maaten Faiez Zannad Adriaan A. Voors Nicolas Girerd |
| author_facet | Jeremy Lagrange Mohammad Jahangiri Guillaume Baudry Nathalie Mercier Luca Monzo Zohra Lamiral Kévin Duarte Jozine M ter Maaten Faiez Zannad Adriaan A. Voors Nicolas Girerd |
| author_sort | Jeremy Lagrange |
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| description | Background Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome, likely stemming from comorbidity‐induced inflammation resulting in endothelial dysfunction. Endothelial glycocalyx degradation's role in the development and prognosis of HFpEF remains largely unexplored. Our study aimed at exploring the association between glycocalyx degradation and diastolic dysfunction and determining whether glycocalyx degradation can predict clinical outcomes in patients with HFpEF. Methods Perlecan and thrombomodulin concentrations were assessed in individuals deemed healthy (STANISLAS [Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux (Annual Noninvasive Temporary Monitoring of the Health of Insured Lorrainers)] cohort, n=1705) and patients with HFpEF (MEDIA‐DHF [Metabolic Road to Diastolic Heart Failure], n=460 and BIOSTAT‐CHF [Biology Study to Tailored Treatment in Chronic Heart Failure], n=556) to evaluate endothelial glycocalyx degradation. Results In patients with HFpEF, perlecan but not thrombomodulin was increased compared with controls (P<0.0001 versus P=0.73). In adjusted analysis, perlecan was associated with peak early mitral inflow velocity/peak early diastolic mitral annular velocity ratio and thrombomodulin with peak early diastolic mitral annular velocity in control individuals, whereas perlecan and thrombomodulin were associated with peak early mitral inflow velocity/peak early diastolic mitral annular velocity and left atrial volume index in patients with HFpEF (all P<0.03). Perlecan was significantly associated with cardiovascular hospitalization and death in the MEDIA‐DHF (adjusted hazard ratio [HR] for highest tertile versus first tertile, 2.44 [95% CI, 1.11–5.34]; P=0.026) and BIOSTAT‐CHF cohorts (adjusted HR, 2.12 [95% CI, 1.49–3.03]; P<0.0001). Thrombomodulin was associated with a worse outcome in BIOSTAT‐CHF (P=0.004) but not in MEDIA‐DHF. Conclusions Higher circulating levels of the endothelial glycocalyx degradation biomarkers like perlecan and, to a lesser extent, thrombomodulin are associated with features of diastolic dysfunction in population and HFpEF settings and predict poor outcome in patients with HFpEF. These results suggest that glycocalyx degradation may be an early step in the pathological processes leading to HFpEF and gain further prognostic value in later stages (ie, overt HFpEF). Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT01391442, https://clinicaltrials.gov/study/NCT01391442?cond=stanislas&rank=1; NCT02446327; URL: https://cordis.europa.eu; BIOSTAT‐CHF ID: 242209. |
| format | Article |
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| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
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| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-0d99fd3ff1114b29aef82efe05280bc62025-08-20T03:28:41ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-06-01141110.1161/JAHA.124.040179Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF CohortsJeremy Lagrange0Mohammad Jahangiri1Guillaume Baudry2Nathalie Mercier3Luca Monzo4Zohra Lamiral5Kévin Duarte6Jozine M ter Maaten7Faiez Zannad8Adriaan A. Voors9Nicolas Girerd10Université de Lorraine, INSERM, DCAC Nancy FranceUniversité de Lorraine, INSERM, DCAC Nancy FranceUniversité de Lorraine, INSERM, DCAC Nancy FranceUniversité de Lorraine, INSERM, DCAC Nancy FranceUniversité de Lorraine, INSERM, DCAC Nancy FranceCentre d’Investigation Clinique‐Plurithématique (CIC‐P) 14‐33, CHRU Nancy, INSERM Université de Lorraine Nancy FranceCentre d’Investigation Clinique‐Plurithématique (CIC‐P) 14‐33, CHRU Nancy, INSERM Université de Lorraine Nancy FranceDepartment of Cardiology University of Groningen, University Medical Centre Groningen Groningen NetherlandsUniversité de Lorraine, INSERM, DCAC Nancy FranceDepartment of Cardiology University of Groningen, University Medical Centre Groningen Groningen NetherlandsUniversité de Lorraine, INSERM, DCAC Nancy FranceBackground Heart failure with preserved ejection fraction (HFpEF) is a multifaceted syndrome, likely stemming from comorbidity‐induced inflammation resulting in endothelial dysfunction. Endothelial glycocalyx degradation's role in the development and prognosis of HFpEF remains largely unexplored. Our study aimed at exploring the association between glycocalyx degradation and diastolic dysfunction and determining whether glycocalyx degradation can predict clinical outcomes in patients with HFpEF. Methods Perlecan and thrombomodulin concentrations were assessed in individuals deemed healthy (STANISLAS [Suivi Temporaire Annuel Non‐Invasif de la Santé des Lorrains Assurés Sociaux (Annual Noninvasive Temporary Monitoring of the Health of Insured Lorrainers)] cohort, n=1705) and patients with HFpEF (MEDIA‐DHF [Metabolic Road to Diastolic Heart Failure], n=460 and BIOSTAT‐CHF [Biology Study to Tailored Treatment in Chronic Heart Failure], n=556) to evaluate endothelial glycocalyx degradation. Results In patients with HFpEF, perlecan but not thrombomodulin was increased compared with controls (P<0.0001 versus P=0.73). In adjusted analysis, perlecan was associated with peak early mitral inflow velocity/peak early diastolic mitral annular velocity ratio and thrombomodulin with peak early diastolic mitral annular velocity in control individuals, whereas perlecan and thrombomodulin were associated with peak early mitral inflow velocity/peak early diastolic mitral annular velocity and left atrial volume index in patients with HFpEF (all P<0.03). Perlecan was significantly associated with cardiovascular hospitalization and death in the MEDIA‐DHF (adjusted hazard ratio [HR] for highest tertile versus first tertile, 2.44 [95% CI, 1.11–5.34]; P=0.026) and BIOSTAT‐CHF cohorts (adjusted HR, 2.12 [95% CI, 1.49–3.03]; P<0.0001). Thrombomodulin was associated with a worse outcome in BIOSTAT‐CHF (P=0.004) but not in MEDIA‐DHF. Conclusions Higher circulating levels of the endothelial glycocalyx degradation biomarkers like perlecan and, to a lesser extent, thrombomodulin are associated with features of diastolic dysfunction in population and HFpEF settings and predict poor outcome in patients with HFpEF. These results suggest that glycocalyx degradation may be an early step in the pathological processes leading to HFpEF and gain further prognostic value in later stages (ie, overt HFpEF). Registration URL: https://clinicaltrials.gov/; Unique identifiers: NCT01391442, https://clinicaltrials.gov/study/NCT01391442?cond=stanislas&rank=1; NCT02446327; URL: https://cordis.europa.eu; BIOSTAT‐CHF ID: 242209.https://www.ahajournals.org/doi/10.1161/JAHA.124.040179endothelial cellsglycocalyxheart failure with preserved ejection fractionperlecanthrombomodulin |
| spellingShingle | Jeremy Lagrange Mohammad Jahangiri Guillaume Baudry Nathalie Mercier Luca Monzo Zohra Lamiral Kévin Duarte Jozine M ter Maaten Faiez Zannad Adriaan A. Voors Nicolas Girerd Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease endothelial cells glycocalyx heart failure with preserved ejection fraction perlecan thrombomodulin |
| title | Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts |
| title_full | Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts |
| title_fullStr | Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts |
| title_full_unstemmed | Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts |
| title_short | Association Between Endothelial Alterations, Cardiac Function, and Outcomes From Health to Heart Failure: Insight From the STANISLAS, MEDIA‐DHF, and BIOSTAT‐CHF Cohorts |
| title_sort | association between endothelial alterations cardiac function and outcomes from health to heart failure insight from the stanislas media dhf and biostat chf cohorts |
| topic | endothelial cells glycocalyx heart failure with preserved ejection fraction perlecan thrombomodulin |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.040179 |
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