Dataset Information

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A meta-analysis of prospective studies.

ABSTRACT:

Background and aim

Previous studies have documented that the association between growth differentiation factor-15 (GDF-15) the risk of patients with cardiovascular diseases (CVDs). In this meta-analysis, our main objective is to explore the associations between GDF-15 and the risk of CVD or all-cause mortality.

Methods

PubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard ratio (HR) with 95% confidence interval (CI), with regard to the association between GDF-15 levels and subsequent risk of CVDs or all-cause mortality. A random-effect model was applied to pool the HR and 95% CI.

Results

Thirty-one prospective studies met the eligibility criteria involving 53?706 subjects with 7020 adverse outcome events. It was concluded that GDF-15 levels were associated with an incremental risk of CVDs or all-cause mortality. Highest GDF-15 category was associated with greater risk of cardiovascular mortality (HR, 2.66; 95% CI, 1.69-3.63), all-cause mortality (HR, 2.52; 95% CI, 2.06-2.97), and complex adverse outcome (HR, 1.81; 95% CI, 1.42-2.21). As each log-unit increment in GDF-15 concentration, the corresponding risk of adverse events also escalated, cardiovascular mortality (HR, 2.11; 95% CI, 1.57-2.66), all-cause mortality (HR, 2.70; 95% CI, 2.29-3.12), and complex adverse outcome (HR, 1.96; 95% CI, 1.64-2.29).

Conclusions

Judging from the results of the data analysis, GDF-15 levels may increase the risk of CVDs or all-cause mortality.

SUBMITTER: Xie S

PROVIDER: S-EPMC6523003 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Publications

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A meta-analysis of prospective studies.

Xie Shanhui S Lu Liping L Liu Liwei L

Clinical cardiology 20190326 5

<h4>Background and aim</h4>Previous studies have documented that the association between growth differentiation factor-15 (GDF-15) the risk of patients with cardiovascular diseases (CVDs). In this meta-analysis, our main objective is to explore the associations between GDF-15 and the risk of CVD or all-cause mortality.<h4>Methods</h4>PubMed and ISI Web of Science (up to January 2018) electronic databases were browsed for eligible studies. The studies provided relevant data depicted as hazard rat ...[more]

PMID: 30697778

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Project description:BACKGROUND:Growth differentiation factor 15 (GDF-15), a stress responsive cytokine, belongs to transforming growth factor ? cytokine superfamily. Some evidence support that it's involved in inflammation, coagulation, oxidative stress, endothelial dysfunction, and hemostasis. However, it's still controversial whether GDF-15 directly contributes to the morbidity and mortality of patients suffered with cardiovascular disease (CVD). Besides prospective cohort study and randomized controlled trial, Mendelian randomization (MR) is a genetic epidemiological method that exploits genetic variants as unbiased proxies for modifiable to determine the causal relationships between exposures and health outcomes. Herein, we introduced a two-sample MR approach to evaluate the causal relationships of circulating GDF-15 levels with major CVDs incidence. METHODS:Genetic instruments and summary statistics for two-sample MR analysis were obtained from 5 independent large genome-wide association studies (GWAS) to investigate the causal correlation between circulating GDF-15 levels and 9 CVDs, respectively. Conventional inverse variance weighted method was adopted to evaluate the causality of GDF-15 with different outcomes; weighted median and MR egger were used for sensitivity analyses. RESULTS:Among 9 SNPs identified from 5 GWASs in 2.6 million individuals, 5 SNPs (rs1227731, rs3195944, rs17725099, rs888663, rs749451) coming from chromosome 19 and containing the PGPEP1 and GDF-15 genes were employed. Based on the instruments, circulating GDF-15 levels significantly linked to the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction. However, no significant causal association was observed for circulating GDF-15 levels with the incidence of any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. CONCLUSIONS:The MR study provides with genetic evidence for the causal relationship of circulating GDF-15 levels with the increased risk of cardioembolic stroke, atrial fibrillation, coronary artery disease and myocardial infarction, but not any ischemic stroke, large-artery atherosclerotic stroke, small vessel stroke, heart failure and nonischemic cardiomyopathy. It indicates that GDF-15 might be a promising biomarker or potential therapeutic target for some CVDs.

Project description:BackgroundGrowth 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.MethodsA 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.ResultsBaseline 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.ConclusionsHigher 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.

Dataset Information

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A meta-analysis of prospective studies.

Background and aim

Methods

Results

Conclusions

Publications

Growth differentiation factor-15 and the risk of cardiovascular diseases and all-cause mortality: A meta-analysis of prospective studies.

Similar Datasets

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