Investigating the Role of Growth Differentiation Factor-15 as a Biomarker of Inflammation in Patients with Atherosclerotic Vascular Disease

Abstract Introduction: Inflammatory pathways in vascular disease are the focus of intense interest. Multiple studies have shown that interleukin-6 (IL-6) is strongly implicated in the atherosclerotic process. Accumulating evidence suggests a similar role for growth differentiation factor-15 (GDF-15). 

Methods: In this study, we measured and compared circulating levels of IL-6 and GDF-15 in a cohort of 20 vascular surgical patients with atherosclerotic disease presenting for surgical revascularization (carotid endarterectomy or common femoral artery endarterectomy) and in a similar number of age-matched healthy volunteers. A cross-sectional analysis of prospectively collected data was performed, with serum GDF-15 and IL-6 levels measured and assessed using enzyme-linked immunosorbent assays (ELISAs). 

Results: We observed substantial circulating levels of GDF-15 in most patients (17/20) compared to the reference range upper limit of 1,500 pg/mL, irrespective of the type of vascular disease and revascularization procedure they were undergoing. In contrast, only 1 healthy control participant had a borderline high GDF-15 of 1,572 pg/mL. Indeed, the mean serum GDF-15 level between patients (2,515 pg/mL, SD 906) and healthy controls (1,016 pg/mL, SD 219) was highly significant (p value <0.001). On the other hand, although IL-6 levels between patients (mean 3.6, SD 2.54 pg/mL) and healthy controls (mean 2.2, SD 0.67 pg/mL) were significantly different (p = 0.020), only 7 patients had values above the reference range upper limit of 3.4 pg/mL. 

Conclusion: These results suggest that serum GDF-15, but not IL-6, is a strong candidate for use as a biomarker of atherosclerotic vascular disease and may allow for earlier risk factor modification to help prevent disease onset and progression. Large-scale studies aimed at determining whether a rising GDF-15 is an indication of worsening outcome in a wider spectrum of patients with vascular disease are clearly warranted.