Serum GDF15, a Promising Biomarker in Obese Patients Undergoing Heart Surgery

Abstract

Background: Obesity is a risk factor that negatively impacts outcomes in patients undergoing heart surgery by mechanisms that are not well-defined nor predicated on BMI alone. This knowledge gap has fuelled a search for biomarkers associated with cardiovascular diseases that could provide clinical insight to surgeons. One such biomarker is growth differentiation factor15(GDF15), associated with inflammation, metabolism, and heart failure outcomes but not yet examined in the context of obesity and cardiac surgery outcomes. Methods: Patients undergoing open-heart surgery were consented and enrolled for blood and tissue (atria) sampling at the time of surgery. Biomarker analysis was carried out using ELISA and western blot/qPCR, respectively. Biomarker screening was classified by inflammation(NLR, GDF15, Galectin3, ST2, TNFR2), heart failure(HF)/remodeling(NT-proBNP) and metabolism(glycemia, lipid profile). Patients were categorized based on BMI: obese group (BMI ≥30.0) and non-obese group(BMI 20.0-29.9). Subsequent stratification of GDF15 high patients was conservatively set as being in the 75th percentile. Results: A total of 80 patients undergoing any open-heart surgical interventions were included in the study. Obese (mean BMI = 35.8, n = 38) and non-obese (mean BMI = 25.7, n = 42) groups had no significant differences in age, sex, or co-morbidities. Compared to other biomarkers, plasma GDF15 (mean 1,736 vs. 1,207 ng/l, p < 0.001) was significantly higher in obese patients compared to non-obese. Plasma GDF15 also displayed a significant linear correlation with BMI (R 2 = 0.097; p = 0.0049). Atria tissue was shown to be a significant source of GDF15 protein and tissue levels significantly correlated with plasma GDF15 (R 2 = 0.4, p = 0.0004). Obesity was not associated with early/late mortality at median follow-up >2years. However, patients with high GDF15 (>1,580 ng/l) had reduced survival (65%) compared to the remaining patients with lower GDF15 levels (95%) by Kaplan Meier Analysis (median >2 years; p = 0.007). Conclusions: Circulating GDF15 is a salient biomarker likely sourced from heart tissue that appears to predict higher risk obese patients for adverse outcomes. More Sarkar et al. GDF15, Obesity and Heart Surgery importantly, elevated GDF15 accounted for more sensitive outcome association than BMI at 2 years post-cardiac surgery, suggesting it heralds links to pathogenicity and should be actively studied prospectively and dynamically in a post-operative follow-up. Trial number: NCT03248921.

The Clinical Value of GDF15 and Its Prospective Mechanism in Sepsis

“…Studies suggest that the increase of serum GDF15 concentration is related to the development and progress of cardiovascular disease (29). The analysis of more than 100 original studies (30)(31)(32)(33)(34) shows that GDF15 has higher value in predicting all-cause mortality in patients with heart failure than traditional cardiovascular risk factors and biomarkers. Other studies have proposed that the expression of GDF15 in the whole nephron is weak in physiological state, but the concentration of plasma GDF15 rises sharply before acute kidney injury (35), scholars believe that it may be an early sign of subclinical kidney injury, but it cannot be detected using conventional clinical parameters.…”

Overexpression of NAG-1/GDF15 prevents hepatic steatosis through inhibiting oxidative stress-mediated dsDNA release and AIM2 inflammasome activation

“…Elevated plasma NAG-1/GDF15 levels have been reported in human subjects with these diseases [ [16] , [17] , [18] , [19] ] and chronic liver diseases [ 20 , 21 ], suggesting NAG-1/GDF15 may serve as a potential diagnostic biomarker for these diseases. It has been reported that the plasma level of NAG-1/GDF15 was significantly higher in human subjects with obesity or higher body mass index (BMI) [ 17 , 22 , 23 ].…”

GDF15 Supports the Inflammatory Response of PdL Fibroblasts Stimulated by P. gingivalis LPS and Concurrent Compression

“…Growth differentiation factor 15 (GDF15), which belongs to the transforming growth factor (TGFB) superfamily [1], is strongly associated with several diseases such as obesity, cancer and cardiovascular diseases as well as with aging [2][3][4]. Under physiological conditions, GDF15 is only weakly expressed in most tissues, whereas pathological states and cellular stress strongly increase GDF15 levels [5][6][7], suggesting it as potential biomarker.…”