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Published on: October 15, 2010
Endothelial activation, dysfunction, and damage in congestive heart failure and the relation to brain natriuretic
Aun Yeong Chong1, Bethan Freestone, Jeetesh Patel
1Haemostasis, Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, United Kingdom.
Insights
Acute and chronic congestive heart failure (CHF) show different endothelial markers. High von Willebrand factor (vWF) levels in CHF patients predict worse outcomes, independent of cardiac function markers like B-type natriuretic peptide (BNP).
Area of Science:
- Cardiovascular Medicine
- Endothelial Biology
- Heart Failure Pathophysiology
Background:
- Congestive heart failure (CHF) is characterized by significant endothelial dysfunction.
- Acute and chronic CHF may exhibit distinct patterns of endothelial damage, dysfunction, and activation.
- Endothelial markers and their relationship with cardiac function indices like B-type natriuretic peptide (BNP) in CHF prognosis are not fully understood.
Purpose of the Study:
- To investigate differences in plasma endothelial markers (von Willebrand factor [vWF], soluble thrombomodulin, soluble E-selectin) between acute and chronic CHF.
- To explore the relationship between these endothelial markers and BNP levels in CHF patients.
- To assess the prognostic value of endothelial markers for adverse cardiovascular outcomes in CHF.
Main Methods:
- Cross-sectional study comparing 35 acute CHF patients, 40 chronic CHF patients, and 32 healthy controls.
- Plasma levels of vWF, soluble thrombomodulin, soluble E-selectin, and BNP were measured.
- Patients with CHF were followed for a composite endpoint including cardiovascular death, myocardial infarction, stroke, thromboembolism, and hospital readmissions.
Main Results:
- All measured endothelial markers and BNP were significantly elevated in both acute and chronic CHF groups compared to controls.
- Soluble thrombomodulin was significantly higher in acute CHF compared to chronic CHF, while vWF and E-selectin showed no significant difference between CHF groups.
- High vWF levels were significantly associated with a poorer prognosis (adverse outcomes) in CHF patients during an 18-month follow-up; no correlation was found between endothelial markers and BNP.
Conclusions:
- Acute and chronic CHF present with distinct endothelial damage/activation profiles, suggesting different underlying pathophysiological mechanisms.
- Elevated von Willebrand factor (vWF) is a significant predictor of adverse outcomes in patients with congestive heart failure.
- Endothelial markers and plasma BNP levels appear to be regulated by independent mechanisms in CHF.
Abstract:
Congestive heart failure (CHF) is associated with marked endothelial dysfunction. We hypothesized that acute and chronic CHF may manifest different degrees of endothelial damage/dysfunction and activation, as reflected by different plasma endothelial markers, such as von Willebrand factor (vWF) and soluble thrombomodulin (both are indexes of endothelial damage/dysfunction) and soluble E-selectin (an index of endothelial activation). Second, we hypothesized a relation between endothelial markers and B-type natriuretic peptide (BNP, an index of cardiac function) in acute and chronic CHF that could be linked to prognosis. To test this hypothesis, we studied 35 patients with acute CHF, 40 patients with chronic CHF, and 32 healthy controls. The patients with CHF were followed up for the combined outcomes of cardiovascular death, nonfatal myocardial infarction, stroke, thromboembolism, and recurrent admissions to the hospital. vWF (p = 0.001), soluble thrombomodulin, E-selectin, and BNP (all p <0.0001) were higher in patients with acute and chronic CHF compared with controls. When the 2 CHF groups were compared, no significant differences were found in vWF or E-selectin (p = NS), but soluble thrombomodulin was significantly elevated in acute CHF (Tukey's post hoc test, p <0.05). Only high vWF was associated with a poorer outcome (log-rank test, p = 0.0188). None of the endothelial indexes correlated with plasma BNP. After a median follow-up of 18 months, only high (median or higher) vWF levels were predictive of adverse outcomes in the patients with CHF (log-rank statistic = 5.52, degree of freedom 1, p = 0.0188). In conclusion, despite similar ejection fractions, patients with acute and chronic CHF have different degrees of endothelial damage/dysfunction and activation, which may be related to differences in pathophysiology. High levels of vWF were associated with a worse short-term outcome. These endothelial markers were unrelated to plasma BNP levels and may imply a different release mechanism.
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