Growth differentiation factor-15, a novel systemic biomarker of oxidative stress, inflammation, and cellular aging: Potential role in cardiovascular diseases.

Growth differentiation factor-15 (GDF-15) is a cytokine upregulated in multiple pathological conditions where oxidative stress, endothelial dysfunction, tissue aging, and chronic inflammation are the hallmarks. GDF-15 has many sources of production, including cardiac and vascular myocytes, endothelial cells, adipocytes and macrophages in response to metabolic stress, oncogenic transformation and the burden of proinflammatory cytokines or reactive oxygen species. Although the main sources of GDF-15 are extracardiac tissues, it has been shown to be elevated in many cardiac disorders. In experimental models of heart disease, GDF-15 release is induced after an ischemic insult and in pressure overload scenarios. Likewise, in recent years, an increasing body of evidence has emerged linking GDF-15 to the risk of mortality in acute coronary syndromes, atrial fibrillation and heart failure. Additionally, GDF-15 has been shown to add prognostic information beyond other conventional biomarkers such as natriuretic peptides and cardiac troponins. Further studies are needed to assess whether the incorporation of GDF-15 into clinical practice can improve cardiovascular outcomes.

Liver stiffness as measured by transient elastography is a predictor of outcomes in patients with chronic heart failure with reduced, mid-range, and recovered left-ventricular ejection fraction.

Background: Transient elastography is a noninvasive method for assessing liver stiffness (LS), which can reflect right-sided filling pressure associated with passive liver congestion in patients with HF. Methods: A prospective, single-center observational study in which LS was measured in consecutive ambulatory patients with heart failure with reduced, mid-range, and recovered left ventricular ejection fraction, between March 2018 and June 2019. Mean follow up was 219 ± 86 days. The primary endpoint was time to first event, which was defined as a composite of cardiovascular death or HF hospitalization. Results: Eighty-five patients were included in the final analysis. Mean age was 62 ± 10 and 68% were male. Mean ejection fraction and median NT-proBNP were, respectively, 38.7 ± 14.3% and 1140 pg/mL (interquartile range 224.3-2810.3). The median LS for the entire population was 6.3 (2.5-41.2) kPa. LS correlated with NT-proBNP (r = 0.46; p < 0.0001), total bilirubin (r = 0.47; p < 0.001), direct bilirubin (r = 0.43; p = 0.0001), gama-glutamyl-transpeptidase (r = 0.54; p < 0.0001), and alkaline phosphatase (r = 0.39; p = 0.0004). A Receiver Operating Characteristic (ROC) curve was performed and a cut point of 5.9 kPa showed sensitivity of 80% and specificity of 64.1% with area under the curve of 0.73. Using Cox proportional hazard model (independent variables: LS as a continuous variable, age, gender, NT-proBNP, LVEF, and creatinine), only LS was independently associated with the primary endpoint (hazard ratio 1.05, 95% confidence interval 1.01-1.09; for each increment of one unit of LS). Conclusion: LS correlates with biomarkers of myocardial stretch and several liver function tests and is an independent predictor of outcomes in ambulatory patients with HF.