Cecilia Castro-Diehl1, Rebecca J Song2, Douglas B Sawyer3, Kai C Wollert4, Gary F Mitchell5, Susan Cheng6, Ramachandran S Vasan7, Vanessa Xanthakis8. 1. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. 2. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. 3. Department of Cardiovascular Medicine, Maine Medical Center, Portland, ME, USA. 4. Division of Molecular and Translational Cardiology, Department of Cardiology and Angiology, Hannover Medical School, Hannover, Germany. 5. Cardiovascular Engineering, Norwood, MA, USA. 6. Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 7. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA; Section of Cardiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA. 8. Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Boston University's and National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA, USA; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.. Electronic address: vanessax@bu.edu.
Abstract
BACKGROUND AND AIMS: Cardiac and vascular growth factors (GF) may influence myocardial remodeling through cardiac growth and angiogenic effects. We hypothesized that concentrations of circulating GF are associated with cardiac remodeling traits. METHODS: We related blood concentrations of vascular endothelial GF (VEGF), VEGFR-1 (sFlt1), angiopoietin 2 (Ang-2), soluble angiopoietin type-2 receptor (sTie2), hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, and growth differentiation factor-15 (GDF-15) to echocardiographic traits in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following measures: left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', and aortic root diameter (AoR). All biomarker values were sex-standardized. RESULTS: In multivariable-adjusted analyses, higher GDF-15 concentrations were associated with higher log-LVMi (β = 0.009 per SD, P = 0.01). Similarly, sTie2 concentrations were positively associated with log-E/e' (β = 0.011 per SD, P = 0.04). IGF-1 and Ang-2 concentrations were positively and negatively associated with GLS, respectively (βIGF-1 = 0.16 per SD and βAng-2 = -0.15 per SD, both P < 0.05), whereas higher sFlt1 and Ang-2 levels were associated with smaller log-AoR (βsFlt1 = -0.004 per SD and β Ang-2 = -0.005 per SD, respectively; P < 0.05). CONCLUSION: In our large community-based sample, we observed patterns of associations between several circulating vascular GF and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional studies are warranted to replicate our findings and assess their prognostic significance.
BACKGROUND AND AIMS: Cardiac and vascular growth factors (GF) may influence myocardial remodeling through cardiac growth and angiogenic effects. We hypothesized that concentrations of circulating GF are associated with cardiac remodeling traits. METHODS: We related blood concentrations of vascular endothelial GF (VEGF), VEGFR-1 (sFlt1), angiopoietin 2 (Ang-2), soluble angiopoietin type-2 receptor (sTie2), hepatocyte GF (HGF), insulin-like GF (IGF)-1, IGF binding protein (IGFBP)-3, and growth differentiation factor-15 (GDF-15) to echocardiographic traits in 3151 Framingham Study participants (mean age 40 years, 55% women). We evaluated the following measures: left ventricular (LV) mass index (LVMi), LV ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', and aortic root diameter (AoR). All biomarker values were sex-standardized. RESULTS: In multivariable-adjusted analyses, higher GDF-15 concentrations were associated with higher log-LVMi (β = 0.009 per SD, P = 0.01). Similarly, sTie2 concentrations were positively associated with log-E/e' (β = 0.011 per SD, P = 0.04). IGF-1 and Ang-2 concentrations were positively and negatively associated with GLS, respectively (βIGF-1 = 0.16 per SD and βAng-2 = -0.15 per SD, both P < 0.05), whereas higher sFlt1 and Ang-2 levels were associated with smaller log-AoR (βsFlt1 = -0.004 per SD and β Ang-2 = -0.005 per SD, respectively; P < 0.05). CONCLUSION: In our large community-based sample, we observed patterns of associations between several circulating vascular GF and cardiac remodeling indices that are consistent with the known biological effects of these pro- and anti-angiogenic factors on the myocardium and conduit arteries. Additional studies are warranted to replicate our findings and assess their prognostic significance.
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