Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan

Vizza, Carmine Dario; Letizia, Claudio; Badagliacca, Roberto; Poscia, Roberto; Pezzuto, Beatrice; Gambardella, Cristina; Nona, Alfred; Papa, Silvia; Marcon, Serena; Mancone, Massimo; Iacoboni, Carlo; Riccieri, Valeria; Volterrani, Maurizio; Fedele, Francesco

doi:10.1016/j.ijcard.2011.12.104

Cited by 14 publications

(12 citation statements)

References 20 publications

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“…Furthermore, HE4 had a weak but significant positive correlation with RAP and ET-1, and elevated RAP indicates right ventricular dysfunction, predicts poor outcome in PAH patients [17], and is usually triggered by cardiac fibrosis [18]. Elevated ET-1 levels could also independently predict clinical worsening in IPAH patients treated with Bosentan, and ET-1 played a crucial role in vascular and tissue fibrosis [19,20]. In addition, HE4 had a strong positive correlation with galectin-3, a biomarker of cardiac fibrosis, indicating that HE4 might function in cardiac fibrosis [7].…”

Section: Discussionmentioning

confidence: 99%

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study

Jin

Tang

Liu

et al. 2020

BMC Cardiovasc Disord

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Background: Human epididymis protein 4 (HE4) was proved to be a novel biomarker for left heart failure. The purpose of this exploratory study was to evaluate the role of HE4 in patients with idiopathic pulmonary arterial hypertension (IPAH) who usually have concurrent right heart failure. Methods: 55 patients with newly diagnosed IPAH were continuously enrolled and serum HE4 levels were assessed at baseline. All patients were followed up from the date of blood sampling, and a composite endpoint of clinical worsening was detailedly recorded. Results: Serum levels of HE4 were significantly higher in IPAH patients than healthy controls (6.9 ± 2.2 vs 4.4 ± 0.9 ng/ml, p < 0.05) and increased as cardiac function deteriorated. HE4 levels correlated with endothelin-1 (r = 0.331, p < 0.01) and right atrial pressure (r = 0.30, p < 0.03). After a mean follow-up of 20 ± 10 months, 13 patients experienced clinical worsening. Receiver operating characteristic analysis showed that HE4 levels > 6.5 ng/ml discriminated clinical worsening with a sensitivity of 92.31% and a specificity of 59.52% (area under the curve [AUC] = 0.81). Multivariate Cox regression analysis demonstrated that HE4 (χ 2 : 5.10; hazard ratio [HR] = 1.26; 95% confidence interval: 1.03 to 1.55, p < 0.02) and pulmonary vascular resistance (χ 2 : 4.19; HR = 1.14; 95% confidence interval: 1.00-1.29, p < 0.04) were independently predictive of clinical worsening. Patients with HE4 > 6.5 ng/ml had a worse 2-year survival rate than those with HE4 ≤ 6.5 ng/ml (58.9% vs 96.2%, p < 0.001).Conclusions: Serum levels of HE4 were elevated in IPAH patients and correlated with disease severity. HE4 was an independent predictor of clinical worsening in IPAH patients.

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Section: Discussionmentioning

confidence: 99%

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study

Jin

Tang

Liu

et al. 2020

BMC Cardiovasc Disord

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“…ET-1 is released and accumulates when vascular endothelial cells are damaged due to ischemia and hypoxia (39,40). Furthermore, high concentrations of ET-1 may cause severe damage to the blood-retinal barrier, impaired endothelial cell function, increased vascular permeability and consequent retinal capillary leakage (41)(42)(43). Therefore, the vessel wall shear force changed with high blood pressure, which caused elevated plasma ET-1 levels.…”

Section: Discussionmentioning

confidence: 99%

Risk factors for hypertensive retinopathy in a Chinese population with hypertension: The Beijing Eye study

Zhang

Zhao

et al. 2018

Exp Ther Med

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Hypertensive retinopathy (HRP) is a clinical feature and systemic manifestation of hypertension. There have been few reports on the risk factors for hypertensive retinopathy in China. The aim of the present study was to describe risk factors associated with HRP in a population-based sample of Chinese patients with hypertension in Beijing. The clinical data of 228 hypertensive patients was retrospectively studied, including 112 patients with retinopathy for the HRP group and 116 patients without retinopathy for the NO-HRP group. Basic clinical data and plasma clinical indicators of the two groups were compared. Logistic regression models were used to assess risk factors associated with HRP. Duration of hypertension, smoking habits, family history of hypertension, plasma level of endothelin-1 (ET-1) and systolic and diastolic blood pressure were significantly increased in the HRP group compared with the NO-HRP group (P<0.05). No significant differences were identified between the two groups for other factors. Logistic regression models indicated that hypertension duration (P<0.001, 95% CI: 0.962-0.988) and ET-1 level (P<0.001, 95% CI: 1.144-1.278) were significantly associated with HRP. The diagnostic threshold of ET-1 to diagnosis HRP was 43.5 ng/l. Of the factors studied, longer hypertension duration and elevated ET-1 level were identified to be risk factors for HRP in patients with hypertension from Beijing. Detecting the plasma level of ET-1 in patients with hypertension may be a useful diagnostic indicator for HRP.

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“…ET-1 is a potent vasoconstrictor that also stimulates proliferation of pulmonary artery smooth muscle cells. Elevated plasma ET-1 levels previously predicted clinical worsening in idiopathic PAH patients on bosentan therapy (22), but it is unknown whether ET-1 levels predict therapeutic response in a broader PAH cohort. Interestingly, plasma levels of ET-1 and BNP have been signi cantly correlated in patients with PAH, generating the hypothesis that increased levels of ET-1 may result from systemic neurohormonal activation (21).…”

Section: Discussionmentioning

confidence: 99%

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

Swaminathan

Zhu

Tapson

et al. 2020

Preprint

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Background: Multiple classes of oral therapy are available for the treatment of pulmonary arterial hypertension (PAH), but there is little to guide clinicians in choosing a specific regimen or therapeutic class. We aimed to investigate whether treatment-relevant blood biomarkers can predict therapy response in prevalent PAH patients.Methods: This prospective cohort study longitudinally assessed biomarkers along the endothelin-1 (ET-1) and nitric oxide (cGMP, ADMA, SDMA, nitrite, and S-nitrosohemoglobin) pathways along with the cGMP/NT-proBNP ratio over 12 months in patients with WHO Group 1 PAH on oral PAH-specific therapies. The relationship between biomarkers and 6MWD at the same and future visits was examined using mixed linear regression models adjusted for age. As cGMP can be elevated when NT-proBNP is elevated, we also tested the relationship between 6MWD and the cGMP/NT-pro BNP ratio. Patients with PAH with concomitant heart or lung disease or chronic thromboembolic pulmonary hypertension (CTEPH) were included in a sensitivity analysis.Results: The study cohort included 58 patients with PAH treated with either an endothelin receptor antagonist (27.6%), phosphodiesterase-5 inhibitor (29.3%) or a combination of the two (43.1%). Among biomarkers along the current therapeutic pathways, ET-1 and the cGMP/NT-proBNP ratio associated with same visit 6MWD (p = 0.02 and p=0.03 respectively), and ET-1 predicted future 6MWD (p=0.02). ET-1 (p=0.01) and cGMP/NT-proBNP ratio (p=0.04) also predicted future 6MWD in the larger cohort (n = 108) of PAH patients with concomitant left heart disease (n = 17), lung disease (n = 20), or CTEPH (n = 13). Finally, in the larger cohort, SDMA associated with 6MWD at the same visit (p = 0.01) in all subgroups and ADMA associated with 6MWD in PAH patients with concomitant lung disease (p=0.03) and PAH patients on ERA therapy (p = 0.01).Conclusions: ET-1, cGMP/NTproBNP ratio, and dimethylarginines ADMA and SDMA are mediators along pathways targeted by oral PAH therapies that associate with or predict 6MWD.

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Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan

Cited by 14 publications

References 20 publications

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study

Serum human epididymis protein 4 level as a predictor of clinical worsening in idiopathic pulmonary arterial hypertension: a pilot study

Risk factors for hypertensive retinopathy in a Chinese population with hypertension: The Beijing Eye study

Treatment-related biomarkers in pulmonary hypertension patients on oral therapies

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