Association of Elevated Plasma Endothelin-1 Levels With Pulmonary Hypertension, Mortality, and Heart Failure in African American Individuals

Jankowich, Matthew; Wu, Wen‐Chih; Choudhary, Gaurav

doi:10.1001/jamacardio.2016.0962

Cited by 42 publications

(39 citation statements)

References 51 publications

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“…Based upon putative mechanisms, potential mediators included pulse pressure (marker of arterial stiffness), 25-hydroxy vitamin D level (associated with vascular hyper-proliferation), BNP (marker of volume overload), and plasma endothelin-1 level (marker of endothelial dysfunction). 4, 18, 19 We calculated the proportion explained by the intermediate factors as follows: 100% × [Beta-coefficient model – Beta-coefficient model+intermediate factor ]/[Beta-coefficient model ]. 20 …”

Section: Methodsmentioning

confidence: 99%

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease

Selvaraj

Shah²,

Ommerborn

et al. 2017

Circ: Heart Failure

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Background African Americans (AA) develop chronic kidney disease (CKD) and pulmonary hypertension (PH) at disproportionately high rates. Little is known whether PH heightens the risk of heart failure (HF) admission or mortality among CKD patients, including non-end stage renal disease. Methods and Results We analyzed AA participants with CKD (eGFR<60 ml/min/1.73m2 or urine albumin/creatinine >30 mg/g) and available echocardiogram-derived pulmonary artery systolic pressure (PASP) from the Jackson Heart Study (N=408). We used Cox models to assess whether PH (PASP>35 mmHg) was associated with higher rates of HF hospitalization and mortality. In a secondary, cross-sectional analysis, we examined the relationship between cystatin C (a marker of renal function) and PASP and potential mediators including b-type natriuretic peptide [BNP] and endothelin-1. In our cohort, the mean age was 63±13 years, 70% were female, 78% had hypertension, and 22% had PH. 85% had an eGFR>30 ml/min/m2. During follow-up, 13% were hospitalized for HF and 27% died. After adjusting for potential confounders, including BNP, PH was associated with HF hospitalization (HR 2.37, 95% CI: 1.15–4.86) and the combined outcome of HF hospitalization or mortality (HR 1.84, CI: 1.09–3.10). Log cystatin C was directly associated with PASP (adjusted β=2.5 [95% CI 0.8–4.1] per standard deviation change in cystatin C). Mediation analysis showed that BNP and endothelin-1 explained 56% and 40%, respectively, of the indirect effects between cystatin C and PASP. Conclusions Among AA with CKD, PH, which is likely pulmonary venous hypertension, was associated with a higher risk of HF admission and mortality.

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Section: Methodsmentioning

confidence: 99%

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease

Selvaraj

Shah²,

Ommerborn

et al. 2017

Circ: Heart Failure

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“…In addition, there are studies comparing with modern pathological study demonstrate that ET has relations with HF [15,16]. ET-1 not only has strong systolic function for blood, also promote growth of smooth muscle and ANP secretion, which is one of typical inflammatory influencing factors [17,18]. This study also analyses the influences of supplementing qi and nourishing yin formula on ET-1 simply.…”

Section: Discussionmentioning

confidence: 85%

Analysis of the influences of supplementing qi and nourishing yin formula on HR, ASP, ADP, LVSP, LVEDP and ET-1 of heart failure rats

Yingni¹

2018

biomedicalresearch

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Objective: To explore influences of supplementing qi and nourishing yin formula on death rate, cardiac function, haemodynamics and ET-1 of heart failure rats. Methods: This study used ADR to establish heart failure model, they were divided into model control group, Shexiang Baoxin pill positive control group, high dose, medium dose and low dose experimental group of supplementing qi and nourishing yin formula, blank healthy control group. There were 12 rats in each group, half male and half female. They were given intragastric administration twice one day for 6 w continuously. Then we observed death conditions of rats, measured cardiac function of rats, including HR, ASP, ADP, LVSP, LVEDP and ET-1 level in serum. Results: After administration of the last time, average weight and HR of rats in different doses of supplementing qi and nourishing yin formula lower than the healthy control group, but LVEDP higher than the healthy control group, P<0.05. ASP, ADP, LVSP, ET-1 level in serum of rats in high dose group were in accordance with healthy control group, P>0.05; but average weight, HR, ASP, LVSP, LVEDP and ET-1 level in serum all higher than model control group and positive control animal, P<0.05. Average weight, various parameter of haemodynamics and ET-1 level in serum in medium and low dose group were in accordance with positive control group, P>0.05; but it higher than model control group, P<0.05. Conclusion: Supplementing qi and nourishing yin formula can enhance myocardial function of HF rats, improve abnormal haemodynamics, lower ET level in serum, which has good clinical application prospect.

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“…Although they did not report on right ventricular dilation, this hypothesis was reinforced by the Jackson Heart Study, which observed that elevated ET1 was associated with increased pulmonary artery systolic pressure, heart failure, and death. 7 The key difference between the previous studies and this analysis is the absence of clinical cardiovascular disease at the time ET1 was assayed.…”

Section: Discussionmentioning

confidence: 97%

Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study

Leary

Jenny

Bluemke

et al. 2020

The Journal of Heart and Lung Transplantation

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BACKGROUND: Circulating levels of endothelin-1 (ET1) are elevated in heart failure and predict poor prognosis. However, it is not clear whether ET1 elevation is an adaptive response, maladaptive response, or an epiphenomenon of heart failure. In this study, we evaluated the relationships between ET1, cardiac morphology, and incident heart failure or cardiovascular death in participants with no evidence of clinical cardiovascular disease at the time ET1 was measured. METHODS AND RESULTS: ET1 was measured in 1,361 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis Sub-Study. As suggested by linear regression, participants with lower circulating ET1 levels tended to be older, non-white, more likely to have smoked heavily, and less likely to report intentional exercise. Participants with higher ET1 levels had smaller left ventricular end-diastolic volumes (8.9 ml smaller per log increase in ET1, 95% confidence interval 17.1−0.7, p = 0.03) with an increased left ventricular ejection fraction (2.8% per log increase in ET1, 95% confidence interval 0.5%−5.2%, p = 0.02). As suggested by Cox Proportional Hazards estimates, participants with higher ET1 levels had a lower risk for the composite outcome of heart failure or cardiovascular death in models that were unadjusted or had limited adjustment (p = 0.03 and p = 0.05, respectively). Lower risk for heart failure with higher ET1 levels could not be clearly shown in a model including health behaviors. CONCLUSIONS: These results suggest, but do not confirm, that elevated levels of circulating ET1 are associated with a more favorable cardiac phenotype. The relationship between ET1 and outcomes was not fully independent of one or more covariates.Endothelin signaling is a treatment target in pulmonary arterial hypertension. 1 Endothelin-receptor antagonists lower pulmonary vascular resistance, improve right heart function, and reduce morbidity and mortality in patients with pulmonary arterial hypertension. 2−4 Endothelin signaling has

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Association of Elevated Plasma Endothelin-1 Levels With Pulmonary Hypertension, Mortality, and Heart Failure in African American Individuals

Abstract: Elevated plasma endothelin-1 levels, especially associated with an elevated pulmonary artery systolic pressure on echocardiogram, may identify an at-risk population that could be evaluated for targeted prevention and management strategies in future studies.

Cited by 42 publications

References 51 publications

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease

Pulmonary Hypertension Is Associated With a Higher Risk of Heart Failure Hospitalization and Mortality in Patients With Chronic Kidney Disease

Analysis of the influences of supplementing qi and nourishing yin formula on HR, ASP, ADP, LVSP, LVEDP and ET-1 of heart failure rats

Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study

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