Circulating growth factors and cardiac remodeling in the community: The Framingham Heart Study

Cecilia Castro-Diehl, Rebecca J. Song, Douglas B. Sawyer, Kai C. Wollert, Gary F. Mitchell, Susan Cheng, Ramachandran S. Vasan, Vanessa Xanthakis

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)217-224
Number of pages8
JournalInternational Journal of Cardiology
StatePublished - Apr 15 2021
Externally publishedYes


  • Biomarkers
  • Cardiac remodeling
  • Community-based study
  • Vascular remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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