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Relations of circulating GDF-15, soluble ST2, and troponin-I concentrations with vascular function in the community:
Charlotte Andersson1, Danielle Enserro2, Lisa Sullivan2
1The Boston University's and National Heart, Lung, Blood Institute's Framingham Heart Study, Framingham, MA, USA.
Insights
Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin-I (hs-TnI) are linked to vascular dysfunction. These cardiac biomarkers may explain their association with cardiovascular disease (CVD) and heart failure.
Area of Science:
- Cardiovascular Medicine
- Biomarker Research
- Vascular Biology
Background:
- Growth differentiation factor-15 (GDF-15), soluble ST2 (sST2), and high-sensitivity troponin-I (hs-TnI) are established predictors of incident cardiovascular disease (CVD) and heart failure.
- The precise mechanisms linking these cardiac stress biomarkers to CVD remain incompletely understood.
- Investigating their association with subclinical vascular dysfunction may elucidate these underlying pathways.
Purpose of the Study:
- To examine the relationship between circulating concentrations of GDF-15, sST2, and hs-TnI and measures of subclinical vascular dysfunction.
- To determine if these biomarkers are associated with arterial stiffness and endothelial function in a community-based cohort.
- To explore potential mechanisms explaining the link between these biomarkers and cardiovascular events.
Main Methods:
- The study included 1823 participants from the Framingham Heart Study (mean age 61 years, 54% women).
- Vascular function was assessed using carotid-femoral pulse wave velocity (CFPWV), augmentation index, forward pressure wave amplitude (FW), and flow-mediated dilation (FMD).
- Linear regression models, adjusted for standard cardiovascular risk factors, were used to relate GDF-15, sST2, and hs-TnI levels to vascular parameters.
Main Results:
- GDF-15 was positively associated with CFPWV and FW, and inversely related to FMD.
- sST2 showed a positive association with CFPWV.
- hs-TnI was inversely associated with hyperemic brachial flow velocity.
Conclusions:
- Individual cardiac stress biomarkers (GDF-15, sST2, hs-TnI) demonstrate differential associations with specific aspects of vascular function.
- These findings suggest that subclinical vascular dysfunction may mediate the relationship between these biomarkers and the risk of incident CVD and heart failure.
- The study provides insights into the pathophysiological links between cardiac stress markers and vascular health in the general population.
Background And Aims:
Growth differentiation factor-15 (GDF-15), soluble (s)ST2, and high-sensitivity troponin-I (hs-TnI) are associated with incident cardiovascular disease (CVD) including heart failure, yet the underlying mechanisms are not fully understood. We investigated if GDF-15, sST2, and hs-TnI are related to subclinical vascular dysfunction in the community, which may explain the relations of these biomarkers with CVD.
Methods:
We evaluated 1823 Framingham Study participants (mean age 61 ± 10 years, 54% women) who underwent routine assessment of vascular function. We related circulating GDF-15, sST2, and hs-TnI concentrations to measures of arterial stiffness (carotid-femoral pulse wave velocity, CFPWV; augmentation index; and forward pressure wave amplitude, FW), endothelial-dependent vasodilation (flow-mediated dilation, FMD), and baseline and hyperemic brachial flow velocities using linear regression adjusting for standard risk factors.
Results:
After multivariable adjustment, GDF-15 levels were positively associated with CFPWV (0.044 [95% confidence interval 0.007-0.081] standard deviation [SD] change per SD increase in loge[GDF-15], p = 0.02) and FW (0.076 [0.026-0.126] SD change per SD increase in loge[GDF-15], p = 0.003) and inversely related to FMD (-0.051 [-0.101-0.0003] SD change per SD increase in loge[GDF-15], p = 0.048). sST2 was positively associated with CFPWV (0.032 [0.0005-0.063] SD change per SD increase in loge[sST2], p = 0.046), and hs-TnI inversely associated with hyperemic flow velocity (-0.041 [-0.082-0.0004] SD change per SD increase in loge[hs-TnI], p = 0.048).
Conclusion:
In our community-based investigation, individual cardiac stress biomarkers were differentially related to select aspects of vascular function. These findings may contribute to the associations of circulating GDF-15, sST2, and hs-TnI with incident CVD and heart failure.