Associations of Angiopoietins With Heart Failure Incidence and Severity |
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| Authors: | Brandon S. Peplinski Brian A. Houston David A. Bluemke Steven M. Kawut Todd M. Kolb Richard A. Kronmal Joao A.C. Lima David D. Ralph Samuel G. Rayner Zachary L. Steinberg Ryan J. Tedford Peter J. Leary |
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| Affiliation: | 1. University of Washington, Department of Medicine, Seattle, WA;2. Medical University of South Carolina, Department of Medicine, Charleston, SC;3. University of Wisconsin, Department of Radiology, Madison, WI;4. Perelman School of Medicine at the University of Pennsylvania, Departments of Medicine and Epidemiology, Philadelphia, PA;5. Johns Hopkins Hospital, Department of Medicine, Baltimore, MD;6. University of Washington, Department of Biostatistics, Seattle, WA;7. Johns Hopkins Hospital, Department of Radiology, Baltimore, MD;8. University of Washington, Department of Epidemiology, Seattle, WA;1. University of Buenos Aires, School of Medicine, Institute of Medical Research A. Lanari, Ciudad Autónoma de Buenos Aires, Argentina;2. National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Cardiology, Ciudad Autónoma de Buenos Aires, Argentina;3. National Scientific and Technical Research Council (CONICET), University of Buenos Aires (UBA), Institute of Medical Research (IDIM), Department of Molecular Genetics and Biology of Complex Diseases, Ciudad Autonoma de Buenos Aires, Argentina;4. Laboratory of Experimental Medicine, Hospital Alemán, Ciudad Autonoma de Buenos Aires, Argentina;5. University of Buenos Aires (UBA), School of Medicine, Institute of Medical Research “Alfredo Lanari,” Department of Cardiology, Ciudad Autonoma de Buenos Aires, Argentina;1. Cardiovascular Center, Tufts Medical Center;2. Predictive Analytics and Comparative Effectiveness Center;3. Clinical and Translational Sciences Institute, Tufts Medical Center, Boston, Massachusetts;1. Columbia University Irving Medical Center, New York, New York;2. Cardiff School of Sport & Health Sciences, Cardiff Metropolitan University, Cardiff, UK;3. Beth Israel Deaconess Medical Center, Boston, Massachusetts |
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| Abstract: | ![]()
BackgroundAngiopoietin-1 and 2 (Ang1, Ang2) are important mediators of angiogenesis. Angiopoietin levels are perturbed in cardiovascular disease, but it is unclear whether angiopoietin signaling is causative, an adaptive response, or merely epiphenomenon of disease activity.Methods and ResultsIn a cohort free of cardiovascular disease at baseline (Multi-Ethnic Study of Atherosclerosis [MESA]), relationships between angiopoietins, cardiac morphology, and subsequent incidence of heart failure or cardiovascular death were evaluated. In cohorts with pulmonary arterial hypertension or left heart disease, associations between angiopoietins, invasive hemodynamics, and adverse clinical outcomes were evaluated. In MESA, Ang2 was associated with a higher incidence of heart failure or cardiovascular death (hazard ratio 1.21 per standard deviation, P < .001). Ang2 was associated with increased right atrial pressure (pulmonary arterial hypertension cohort) and increased wedge pressure and right atrial pressure (left heart disease cohort). Elevated Ang2 was associated with mortality in the pulmonary arterial hypertension cohort.ConclusionsAng2 was associated with incident heart failure or death among adults without cardiovascular disease at baseline and with disease severity in individuals with existing heart failure. Our finding that Ang2 is increased before disease onset and that elevations reflect disease severity, suggests Ang2 may contribute to heart failure pathogenesis. |
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