Dataset Information

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

ABSTRACT:

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.

SUBMITTER: Wang J

PROVIDER: S-EPMC10412535 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

Wang Juan J Han Li-Na LN Ai Dao-Sheng DS Wang Xin-Yu XY Zhang Wan-Jing WJ Xu Xiao-Rong XR Liu Hong-Bin HB Zhang Jing J Wang Pan P Li Xu X Chen Mu-Lei ML

Journal of geriatric cardiology : JGC 20230701 7

<h4>Background</h4>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.<h4>Methods</h4>A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 leve ...[more]

PMID: 37576485

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Project description:Background and aims Studies on the association between growth-differentiation factor-15 (GDF-15) level and adverse outcomes have yielded conflicting results in patients with stable coronary artery disease (CAD). This meta-analysis aimed to evaluate the association of baseline GDF-15 level with adverse outcomes in stable CAD patients. Methods Two authors independently searched PubMed and Embase databases from inception to May 31, 2021 for available studies that investigated the association of baseline GDF-15 level with all-cause mortality, cardiovascular mortality, or major adverse cardiovascular events (MACEs) in stable CAD patients. Pooled multivariable adjusted hazard ratio (HR) with 95% confidence interval (CI) was calculated for the highest vs. the lowest GDF-15 level. Results Seven studies that involved 28,765 stable CAD patients were identified and analyzed. The meta-analysis showed that the highest GDF-15 level was associated with higher risk of MACEs (HR 1.42; 95% CI 1.29–1.57; p < 0.001), cardiovascular mortality (HR 1.64: 95% CI 1.25–2.14; p < 0.001), and all-cause mortality (HR 2.01; 95% CI 1.67–2.42; p < 0.001) when compared the lowest GDF-15 level. Moreover, the values of GDF-15 level in predicting MACEs were consistently observed in each named subgroup. Conclusions Elevated blood GDF-15 level is an independent predictor of MACEs, cardiovascular mortality, and all-cause mortality in stable CAD patients. The baseline GDF-15 level may play an important role in the risk stratification of stable CAD patients. Graphical abstract Image 1 Highlights • Predictive value of GDF-15 level has not been well-established in stable CAD patients.• Stable CAD patients with the highest GDF-15 had a 42% higher risk of MACEs (p < 0.001).• Stable CAD patients with the highest GDF-15 had a 64% higher risk of cardiovascular death (p < 0.001).• Stable CAD patients with the highest GDF-15 had a 2.01-fold higher risk of all-cause death (p < 0.001).• Baseline GDF-15 level is a promising biomarker of adverse outcomes in stable CAD patients.

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: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.

Dataset Information

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

Background

Methods

Results

Conclusions

Publications

Growth differentiation factor 15 predicts cardiovascular events in stable coronary artery disease.

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