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Circulating growth factors and cardiac remodeling in the community: The Framingham Heart Study
Cecilia Castro-Diehl1, Rebecca J Song2, Douglas B Sawyer3
1Section of Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Insights
Circulating growth factors (GF) are linked to cardiac remodeling. Specific GF like GDF-15, sTie2, IGF-1, Ang-2, and sFlt1 show associations with left ventricular mass, strain, and aortic root size in a large study.
Area of Science:
- Cardiology
- Vascular Biology
- Biomarkers
Background:
- Cardiac and vascular growth factors (GF) play roles in myocardial remodeling and angiogenesis.
- Understanding the relationship between circulating GF and cardiac remodeling is crucial for cardiovascular health.
Purpose of the Study:
- To investigate the association between blood concentrations of various circulating GF and cardiac remodeling traits.
- To explore how specific GF relate to measures of left ventricular structure and function, and aortic root diameter.
Main Methods:
- Analysis of blood concentrations of 8 key GF in 3151 participants from the Framingham Study.
- Correlation of GF levels with echocardiographic measures including left ventricular mass index (LVMi), ejection fraction (LVEF), global longitudinal strain (GLS), mitral E/e', and aortic root diameter (AoR).
- Multivariable-adjusted analyses were performed on sex-standardized biomarker values.
Main Results:
- Higher growth differentiation factor-15 (GDF-15) associated with increased left ventricular mass.
- Soluble Tie2 (sTie2) positively correlated with mitral E/e' ratio, indicating potential diastolic dysfunction.
- Insulin-like growth factor-1 (IGF-1) and angiopoietin 2 (Ang-2) showed associations with global longitudinal strain.
- Soluble fms-like tyrosine kinase 1 (sFlt1) and Ang-2 were linked to smaller aortic root diameter.
Conclusions:
- Observed associations between circulating vascular GF and cardiac remodeling indices align with their known biological functions.
- Findings suggest a role for these pro- and anti-angiogenic factors in myocardial and arterial remodeling.
- Further research is needed to confirm these findings and evaluate their prognostic implications in cardiovascular disease.
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.