Circulating GDF-15 levels predict future secondary manifestations of cardiovascular disease explicitly in women but not men with atherosclerosis
International Journal of Cardiology, 2017
Gohar A., Gonçalves I., Vrijenhoek J., Haitjema S., van Koeverden I., Nilsson J., de Borst G., de Vries J., Pasterkamp G., den Ruijter H., Björkbacka H., de Jager S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD | Pathophysiology Patient Stratification | Plasma |  Olink Target 96 |
Abstract
GDF-15 is an established risk biomarker for a range of cardiovascular diseases. This hypothesis-driven study looked at the predictive value of plasma GDF-15 as a biomarker for secondary cardiovascular events (CVE) in patients with atherosclerosis undergoing carotid endarterectomy (CEA). In the study cohort (>1000 subjects), a Luminex assay was used to specifically measure GDF-15, using major cardiovascular events (CVE), death and peripheral vascular intervention as a composite endpoint.
Surprisingly, no significant association was found between GDF-15 and secondary CVE. When the influence of gender was examined closely, however, GDF-15 was found to be strongly and independently associated with secondary CVE in women, but not in men. This result was then confirmed using a validation cohort of 473 CEA patients from Sweden, using the Olink CVD I panel. The female-specific association of GDF-15 with secondary CVE was repeated in this independent cohort, and using a different technology. Interestingly, the multiplexed analysis with Olink also revealed that if eGFR levels were added to the analysis, the significance of GDF-15 was lost, indicating that the predictive value of GDF-15 was dependent on renal function.
The sex-dependent predictive value of GDF-15 is interesting in the context of accumulating evidence that the disease process underlying atheroscleros is significantly different between men and women (e.g. differences in plaque composition). The biology behind these difference remains unexplained, but solving this is of great importance for any future implementation of serum GDF-15 as a marker for secondary CVE in clinical practice.