Growth-differentiation factor-15 and functional outcome after acute ischemic stroke

Abstract

Blood biomarkers may improve the performance in predicting early stroke outcome beyond well-established clinical factors. We investigated the value of growth-differentiation factor-15 (GDF-15) to predict functional outcome after 90 days in a prospectively collected patient cohort with symptoms of acute ischemic stroke. Two hundred eighty-one patients with symptoms of acute ischemic stroke were prospectively investigated. Serial blood samples for GDF-15 analysis were obtained after the admission of the patient, after 6 and 24 h. Primary outcome was the dichotomized modified ranking scale (MRS) 90 days after the initial clinical event. Within the final study population (264 patients, mean age 70.3 ± 12.7 years, 55.3% male), National Institutes of Health Stroke Scale (NIH-SS) [odds ratio (OR) 1.269, 95% confidence interval (CI) 1.141–1.412, p < 0.001] and initial GDF-15 levels (OR 1.029, 95% CI 1.007–1.053, p = 0.011) were independently associated with a MRS ≥ 2 after day 90 after multiple regression analysis. Growth-differentiation factor-15 levels increase with higher NIH-SS-tertiles (p = 0.005). Receiver-operator characteristic curves demonstrated a discriminatory accuracy to predict unfavourable stroke outcome of 0.629 (95% CI 0.558–0.699), 0.753 (95% CI 0.693–812) and 0.774 (95% CI 0.717–0.832) for GDF-15, NIH-SS and the combination of these variables. The additional use of GDF-15 to NIH-SS ameliorates the model with a net reclassification index of 0.044 (p = 0.541) and integrated discrimination improvement of 0.034 (p = 0.443). Growth-differentiation factor-15 as an acute stroke biomarker independently predicts unfavourable functional 90 day stroke outcome. Discriminatory value in addition to NIH-SS is only modestly distinct.

High-sensitivity troponin assay improves prediction of cardiovascular risk in patients with cerebral ischaemia

“…We acknowledge, however, that our analysis is underpowered to unravel smaller increments in prediction achieved with marker combinations or comparisons with established markers such as D-dimer, CRP or fibrinogen. 14 15 GDF-15, for example, was elevated in patients with an adverse outcome, was predictive for functional outcome after 90 days in another cohort 36 as well as in our own, 37 and might well have been found to be incrementally predictive in a larger cohort with a greater number of events .…”

Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke

“…10, 11 GDF-15 has also been reported to improve prediction of the risk of incident overall cardiovascular disease (CVD), heart failure, and cancer, as well as all-cause and cancer-related mortality in community-based cohorts. 12, 13 Higher GDF-15 concentrations have been noted with increasing age and in smokers, persons with diabetes, hypertension, poor kidney function, and low high-density lipoprotein cholesterol levels.…”

Growth Differentiation Factor 15, Its 12-Month Relative Change, and Risk of Cardiovascular Events and Total Mortality in Patients with Stable Coronary Heart Disease: 10-Year Follow-up of the KAROLA Study

“…In patients with CVD atherosclerotic plaque macrophages and infarcted myocardium have been shown to express GDF-15 (5)(6). GDF-15 has also been associated with mortality and disease progression in patients with acute coronary syndromes (ACS), angina pectoris, heart failure, and stroke (7)(8)(9)(10). GDF-15 is weakly expressed in most tissues under physiological conditions and yet it is unclear whether high concentrations might just be a response to biologic stress or reflect directly a harmful pathway (3 ).…”