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Endothelin-1, cardiac morphology, and heart failure: the MESA angiogenesis study
Peter J Leary1, Nancy S Jenny2, David A Bluemke3
1University of Washington, Department of Medicine, Seattle, Washington.
Insights
Elevated endothelin-1 (ET1) levels in individuals without heart disease are linked to a healthier heart structure. Higher ET1 may be associated with a reduced risk of heart failure or cardiovascular death, though not entirely independent of lifestyle factors.
Area of Science:
- Cardiovascular Research
- Biomarker Discovery
- Clinical Epidemiology
Background:
- Circulating endothelin-1 (ET1) is elevated in heart failure and indicates poor prognosis.
- The precise role of ET1 in heart failure pathogenesis remains unclear.
- Investigating ET1's relationship with cardiac structure and cardiovascular events in asymptomatic individuals is crucial.
Purpose of the Study:
- To examine the association between circulating ET1 levels and cardiac morphology.
- To determine the relationship between ET1 levels and the incidence of heart failure or cardiovascular death in individuals without pre-existing cardiovascular disease.
Main Methods:
- Utilized data from 1,361 participants in the Multi-Ethnic Study of Atherosclerosis Angiogenesis Sub-Study.
- Employed linear regression to assess ET1 associations with demographic and lifestyle factors.
- Applied Cox Proportional Hazards models to evaluate ET1's impact on cardiovascular outcomes.
Main Results:
- Higher ET1 levels correlated with smaller left ventricular end-diastolic volumes and increased left ventricular ejection fraction.
- Elevated ET1 was associated with a reduced risk of heart failure or cardiovascular death in unadjusted and partially adjusted models.
- The protective association of ET1 with outcomes was attenuated when health behaviors were included in the model.
Conclusions:
- Elevated circulating ET1 may be associated with a more favorable cardiac phenotype in individuals without clinical cardiovascular disease.
- The findings suggest ET1's role in cardiovascular health warrants further investigation.
- The relationship between ET1 and cardiovascular outcomes is not fully independent of covariates, including health behaviors.
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.
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