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Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients.

ABSTRACT: Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts adverse stroke outcomes. However, the association of GDF-15 with first-ever stroke in hypertensive patients has not yet been evaluated. The objective of this study was to evaluate the clinical implications of plasma GDF-15 on the development of first-ever stroke in patients with hypertension.In total, 254 patients with hypertension without a history of stroke were included from March 2010 to August 2010 and followed up until June 2013. The baseline circulating GDF-15 was determined by enzyme-linked immunosorbent assays.During a follow-up of 3.0 ± 0.6 years, 22 (8.7%) first-ever strokes were identified, including 12 ischemic strokes and 10 intracerebral hemorrhages (ICH). According to tertiles of GDF-15, survival free of first-ever stroke was lower in the highest tertile of GDF-15 (log-rank P = 0.001). By backward stepwise Cox-regression analysis, adjusted for age, gender, diabetes mellitus, hyperlipidemia, hypertension stage, body mass index, cigarette smoking, anti-hypertensive drugs, and uric acid, every 100 pg/mL-increase in plasma of GDF-15 predicted an 11% greater risk of first-ever stroke (hazard ratios [HR]: 1.11, 95% confidence interval [CI]: 1.03-1.20, P = 0.010) and an 18% increase in ischemic stroke risk (HR: 1.18, 95% CI: 1.07-1.30, P = 0.001). Receiver operating characteristic analysis indicated that GDF-15 had reasonable accuracy to predict first-ever stroke (area under curve = 0.73, 95% CI: 0.62-0.83, P < 0.001).This study identifies that GDF-15 is an independent predictor of first-ever stroke, especially for ischemic stroke in the patients with hypertension.

SUBMITTER: Wang X

PROVIDER: S-EPMC5265855 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients.

Wang Xiaojian X Zhu Ling L Wu Yan Y Sun Kai K Su Ming M Yu Liping L Chen Jingzhou J Li Weiju W Yang Jing J Yuan Zuyi Z Hui Rutai R

Medicine 20160701 30

Growth differentiation factor 15 (GDF-15) is a relatively new biomarker that predicts adverse stroke outcomes. However, the association of GDF-15 with first-ever stroke in hypertensive patients has not yet been evaluated. The objective of this study was to evaluate the clinical implications of plasma GDF-15 on the development of first-ever stroke in patients with hypertension.In total, 254 patients with hypertension without a history of stroke were included from March 2010 to August 2010 and fol ...[more]

PMID: 27472718

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Project description:Background Growth differentiation factor-15 (GDF-15) has emerged as a novel biomarker to predict all-cause death in community-dwelling individuals and patients with cardiovascular disease. We evaluated the prognostic value of GDF-15 in outpatients with cardiovascular risk factors. Methods and Results GDF-15 levels were measured in 3562 outpatients with cardiovascular risk factors in the J-HOP (Japan Morning Surge-Home Blood Pressure) study, a nationwide prospective study. Participants were stratified according to tertiles of GDF-15 and followed up for all-cause death and cardiovascular disease. During a mean follow-up period of 6.6 years, there were 155 all-cause deaths, 81 stroke events including cerebral infarction and intracranial hemorrhage, and 141 cardiac events including cardiac artery disease and heart failure. Patients with higher GDF-15 levels were associated with risks of all-cause death and stroke events (except for cardiac events) after adjustment for traditional risk factors and other prognostic biomarkers (NT-proBNP [N-terminal pro-B-type natriuretic peptide], high-sensitivity troponin T; all-cause death, hazard ratio, 2.38; 95% CI, 1.26-4.48; P=0.007; stroke events, hazard ratio, 2.93; 95% CI, 1.31-6.56, P=0.009; compared with the lowest tertile). Furthermore, incorporating GDF-15 to the predictive models for all-cause death improved discrimination and reclassification significantly. For stroke events, GDF-15 showed similar diagnostic accuracy to NT-proBNP and high-sensitivity troponin T. Conclusions In Japanese outpatients with cardiovascular risk factors, GDF-15 improves risk stratification for all-cause death when compared with NT-proBNP and high-sensitivity troponin T. GDF-15 was associated with increased risks of stroke events beyond conventional risk factors and other prognostic markers; however, the predictive ability for stroke events was equivalent to NT-proBNP and high-sensitivity troponin T. Registration URL: http://www.umin.ac.jp/ctr.; Unique identifier: UMIN000000894.

Project description:BackgroundCancer-related weight loss is associated with increased inflammation and decreased survival. The novel inflammatory mediator growth differentiation factor (GDF)15 is associated with poor prognosis in cancer but its role in cancer-related weight loss (C-WL) remains unclear. Our objective was to measure GDF15 in plasma samples of cancer subjects and controls and establish its association with other inflammatory markers and clinical outcomes.MethodsWe measured body weight, appetite, plasma GDF15, and other inflammatory markers in men with cancer-related weight loss (C-WL, n = 58), weight stable patients with cancer (C-WS, n = 72), and non-cancer controls (Co, n = 59) matched by age and pre-illness body mass index. In a subset of patients we also measured handgrip strength, appendicular lean body mass (aLBM), Eastern Cooperative Oncology Group (ECOG), and Karnofsky performance scores.ResultsGDF15, interleukin (IL)-6 and IL-8 were increased in C-WL versus other groups. IL-1 receptor antagonist, IL-4, interferon-gamma, tumour necrosis factor alpha, and vascular endothelial growth factor A were increased in C-WL versus C-WS, and Activin A was significantly downregulated in Co versus other groups. C-WL patients had lower handgrip strength, aLBM, and fat mass, and Eastern Cooperative Oncology Group and Karnofsky performance scores were lower in both cancer groups. GDF15, IL-6, and IL-8 significantly correlated with weight loss; GDF15 negatively correlated with aLBM, handgrip strength, and fat mass. IL-8 and Activin A negatively correlated with aLBM and fat mass. GDF15 and IL-8 predicted survival adjusting for stage and weight change (Cox regression P < 0.001 for both).ConclusionGDF15 and other inflammatory markers are associated with weight loss, decreased aLBM and strength, and poor survival in patients with cancer. GDF15 may serve as a prognostic indicator in cancer patients and is being evaluated as a potential therapeutic target for cancer-related weight loss.

Project description:BACKGROUND Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS Baseline GDF-15 levels for 3699 patients were grouped by quartile (≤ 1153, 1153–1888, 1888–3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro B-type natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF-15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52–3.11)], including: MI [HR = 2.83 95% CI: (1.03–7.74)], heart failure [HR = 2.71 95% CI: (1.18–6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49–4.11)] during the median follow up of 3.1 years. CONCLUSIONS Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD.

Project description:Background: Disease-related anorexia-cachexia is associated with poor prognosis of patients with cardiovascular disease (CVD) or cancer. Growth differentiation factor-15 (GDF-15) has emerged as a central regulator of appetite and body weight. However, the exact role of GDF-15 in lean patients has not been elucidated. Aim: Our aim is to evaluate whether the association of GDF-15 with mortality, including cancer death, differs according to body mass index (BMI) level. Methods and Results: We collected blood samples from 4,061 patients with CV risk factors who were enrolled in the nationwide practice-based J-HOP (Japan Morning Surge-Home Blood Pressure) study. Serum GDF-15 levels were determined by immunoassay analysis. During a mean follow-up period of 6.6 years, we observed 174 (6.7/1000 person-year) all-cause deaths, 68 (2.6/1000 person-year) cancer deaths, and 56 (2.2/1000 person-year) CV deaths. Patients were stratified according to the cut-points of GDF-15 at 1,200 ng/L and BMI at 22.5 and 25.0 kg/m2. The association between the GDF-15/BMI based study groups and each outcome was evaluated by Cox-proportional hazard models with adjustment for established risk factors. The multivariate Cox regression model showed that patients with elevated GDF-15 (≥1,200 ng/L) and low BMI (<22.5 kg/m2) were significantly associated with increased risk of all outcomes [all-cause death, hazard ratio (HR) 3.15, 95% confidence interval (CI) 1.85-5.34, p < 0.001; cancer death, HR 3.52, 95%CI 1.64-7.57, p = 0.001; CV death, HR 2.88, 95%CI 1.20-6.92, p = 0.018, respectively] compared to a reference group with non-elevated GDF-15 and normal BMI (22.5-25.0 kg/m2). In analyses of a subgroup with low BMI (<22.5 kg/m2), patients with elevated GDF-15 had 4.79-fold increased risk of cancer death and 11-fold greater risk of CV death when compared with patients with non-elevated GDF-15 (<1,200 ng/L) after adjustment for established risk factors. Conclusion: In patients with CV risk factors, GDF-15 was associated with all-cause, cancer, and CV death. This relationship was especially remarkable in patients with low BMI. The serum GDF-15 levels in patients with low BMI might be a useful marker to identify the potential for anorexia-cachexia associated with CVD and cancer.

Project description:BackgroundGrowth-differentiation factor-15 (GDF-15) is an emerging humoral marker for risk stratification in cardiovascular disease. Cardiac-surgery-associated acute kidney injury (CSA-AKI), an important complication in patients undergoing cardiac surgery, is associated with poor prognosis. The present secondary analysis of an observational cohort study aimed to determine the role of GDF-15 in predicting CSA-AKI compared with the Cleveland-Clinic Acute Renal Failure (CC-ARF) score and a logistic regression model including variables associated with renal dysfunction.MethodsPreoperative plasma GDF-15 was determined in 1176 consecutive patients undergoing elective cardiac surgery. Patients with chronic kidney disease stage 5 were excluded. AKI was defined according to Kidney-Disease-Improving-Global-Outcomes (KDIGO) - creatinine criteria. The following variables were screened for association with development of postoperative AKI: age, gender, additive Euroscore, serum creatinine, duration of cardiopulmonary bypass, duration of surgery, type of surgery, total circulatory arrest, preoperative hemoglobin, preoperative oxygen-supplemented cerebral oxygen saturation, diabetes mellitus, hemofiltration during ECC, plasma GDF-15, high sensitivity troponin T (hsTNT), and N-terminal prohormone of B-type natriuretic peptide (NTproBNP).ResultsThere were 258 patients (21.9 %) with AKI (AKI stage 1 (AKI-1), n = 175 (14.9 %); AKI-2, n = 6 (0.5 %); AKI-3, n = 77 (6.5 %)). The incidence of AKI-1 and AKI-3 increased significantly from the lowest to the highest tertiles of GDF-15. In logistic regression, preoperative GDF-15, additive Euroscore, age, plasma creatinine, diabetes mellitus, and duration of cardiopulmonary bypass were independently associated with AKI. Inclusion of GDF-15 in a logistic regression model comprising these variables significantly increased the area under the curve (AUC 0.738 without and 0.750 with GDF-15 included) and the net reclassification ability to predict AKI. Comparably, in receiver operating characteristic analysis the predictive capacity of the CC-ARF score (AUC 0.628) was improved by adding GDF-15 (AUC 0.684) but this score also had lower predictability than the logistic regression model. In random forest analyses the predictive capacity of GDF-15 was especially pronounced in patients with normal plasma creatinine.ConclusionThis suggests that preoperative plasma GDF-15 independently predicts postoperative AKI in patients undergoing elective cardiac surgery and is particularly helpful for risk stratification in patients with normal creatinine.Trial registrationNCT01166360 on July 20, 2010.

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Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients.

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Plasma growth differentiation factor 15 predicts first-ever stroke in hypertensive patients.

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