Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Leary PJ

PROVIDER: S-EPMC6942224 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Publications

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

Leary Peter J PJ Jenny Nancy S NS Bluemke David A DA Kawut Steven M SM Kronmal Richard A RA Lima Joao A JA Maron Bradley A BA Ralph David D DD Rayner Samuel G SG Ryan John J JJ Steinberg Zachary L ZL Hinckley Stukovsky Karen D KD Tedford Ryan J RJ

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation 20190810 1

<h4>Background</h4>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.<h4>Methods and results ...[more]

PMID: 31515065

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Project description:BackgroundAlthough small elevations of high-sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy.MethodsWe measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models.ResultsLate gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus <limit of detection [<3 ng/L]; adjusted odds ratio, 2.87; 95% confidence interval, 1.38-5.94). Higher hs-cTnT was also associated with a greater probability of an increase in LV mass >12% (highest category versus <limit of detection; odds ratio, 1.50; 95% confidence interval, 1.09-2.07), but not with decline in left ventricular ejection fraction. The risk of incident HF was greater for higher hs-cTnT (≥8.81 ng/L versus <limit of detection; adjusted hazards ratio, 5.59; 95% CI, 2.97-10.68).Conclusionshs-cTnT levels are associated with replacement fibrosis and progressive changes in left ventricular structure in CVD-free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions.

Project description:ObjectivesThis study sought to compare various measures of adiposity with risk for incident hospitalized heart failure (HF) with preserved ejection fraction (HFpEF) and reduced ejection fraction (HFrEF).BackgroundObesity is a risk factor for HF, particularly HFpEF. It is unknown which measures of adiposity, including anthropometrics and computed tomography (CT)-measured fat area, are most predictive of HF subtypes.MethodsThe authors studied 1,806 participants of the MESA (Multi-Ethnic Study of Atherosclerosis) study without baseline cardiovascular disease who underwent anthropometrics (body mass index [BMI] and waist circumference) and an abdominal CT. Subcutaneous and visceral adipose tissue (VAT) were measured from a single CT slice at L2-L3. Cox hazard models were used to examine associations of adiposity with incident hospitalized HFpEF and HFrEF events. Fully adjusted models included demographics, HF risk factors, and N-terminal pro-B-type natriuretic peptide.ResultsOver a mean follow-up of 11 years, there were 34 HFpEF and 36 HFrEF events. The fully adjusted hazard ratio (95% confidence interval [CI]) per 1-SD higher of each anthropometric and CT-measured adiposity measures for incident HFpEF were as follows: BMI HR: 1.66; 95% CI: 1.12 to 2.45; waist circumference HR: 1.59; 95% CI: 1.05 to 2.40; and VAT HR: 2.24; 95% CI: 1.44 to 3.49. None of these adiposity measures were associated with HFrEF. Even among overweight/obese adults (BMI ≥25 kg/m2), assessment of VAT (per 1-SD) was strongly associated with HFpEF (HR: 2.78; 95% CI: 1.62 to 4.76). Subcutaneous adipose tissue was neither associated with HFpEF nor HFrEF.ConclusionsIn a multiethnic cohort free of cardiovascular disease, CT-measured VAT was independently associated with incident hospitalized HFpEF but not HFrEF. Measuring visceral fat at the time of CT imaging for other indications may offer additional prognostication of HF risk. (Multi-Ethnic Study of Atherosclerosis [MESA]; NCT00005487).

Dataset Information

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

Background

Methods and results

Conclusions

Publications

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

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