Associations of Angiopoietins With Heart Failure Incidence and Severity
Section snippets
Methods
This work uses 3 cohorts to evaluate the relationship between angiopoietins and heart failure. Serum angiopoietin levels were measured in each cohort. The Multi-Ethnic Study of Atherosclerosis (MESA) Angiogenesis cohort was used to evaluate relationships between angiopoietins, cardiac morphology, and the risk of incident heart failure or cardiovascular death in individuals without CVD at the time Ang1 and Ang2 were measured. A pulmonary arterial hypertension (PAH) cohort was used to evaluate
MESA Cohort
The MESA–Angiogenesis cohort included 1383 participants selected randomly from the parent MESA cohort. In addition, 155 MESA participants outside the MESA–Angiogenesis cohort experienced incident heart failure or cardiovascular death; these participants were included in longitudinal case-cohort analyses only. In the current study, 1358 participants in the MESA-Angiogenesis cohort (81 cases, 1277 noncases) and 154 additional cases outside the cohort had all available covariates and were included
Discussion
To our knowledge, this study is the first to demonstrate that an elevation in Ang2 is associated with a higher risk of heart failure or cardiovascular death in individuals without heart disease at baseline. We also confirm and expand previous observations suggesting that Ang2 is associated with more severe disease in individuals with existing heart failure. Taken together, this suggests Ang2 elevation precedes heart disease, is unlikely to merely represent a reaction to existing disease, and
Conclusions
This study corroborates previous data identifying increased Ang2 as a biomarker for heart failure severity. Our results suggest increased Ang2 predicts increased risk of mortality in PAH and increased risk of incident heart failure or cardiovascular mortality in individuals without CVD. Because Ang2 is increased before disease onset in the MESA cohort, and increases reflect disease severity in right and left heart failure, Ang2 could be a contributor to heart failure pathogenesis and not merely
Disclosure
All authors report no direct conflict of interest related to this manuscript. Dr Leary receives research support from the NHLBI, PHA, AHA, Chest Foundation, Lung LLC, Bayer, and Actelion; salary support from the Cystic Fibrosis Therapeutic Development network; and honoraria from Bayer. Dr Tedford has consulting relationships with Medtronic, Aria CV Inc., Acceleron, Arena Pharmaceuticals, and United Therapeutics. Dr Tedford is on a steering committee for Medtronic and Abbott, and a research
Acknowledgments
The authors thank the MESA investigators, staff, and participants for their valuable contributions. A full list of participating investigators and institutions can be found at http://www.mesa-nhlbi.org.
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Presented at the online symposium: “What's new in clinical research in pulmonary hypertension: lessons from the best abstracts,” October 21, 2020, at the 2020 American Thoracic Society Annual Conference.
This research was supported by contracts from the National Heart, Lung, and Blood Institute 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, R01-HL-086719, K24-HL-103844, and R01-HL-071759, and by grants UL1-TR-000040, UL1-TR-001079 and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). The American Heart Association Mentored Award in Population Research supported the MESA-Angiogenesis Ancillary Study.
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These authors contributed equally to this work.