This paper is only available as a PDF. To read, Please Download here.
Introduction
Recent studies suggested that growth differentiation factor 15 (GDF-15) may indicate
heart failure and a constellation of cardiovascular co-morbidities in diabetic patients.
Whereas N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) is a cardiac-specific
biomarker, GDF-15 is non-tissue-specific and may be a useful marker of global cardiovascular
disease (CVD) burden, particularly in diabetes. In this systematic review and meta-analysis,
we summarized the effects of elevated GDF-15 on the composite outcome of cardiovascular
disease, events, and/or death in diabetic patients.
Methods
MEDLINE, EMBASE, CINAHL and Cochrane Library were queried for articles published from
inception until February 2020. Longitudinal studies that reported data about the relationship
between GDF-15 levels and CVD outcomes in diabetic patients were included. Pooled
hazard ratios (HRs) for mortality were calculated and presented with 95% confidence
intervals (CIs). Prespecified I2 threshold values of 25%, 50%, and 75% were used to indicate low, moderate, and high
levels of heterogeneity, respectively. The risk of bias in the included studies was
evaluated according to the criteria established by the Cochrane collaboration. Publication
bias was assessed using funnel plot analysis.
Results
Seven studies with a total 15,805 diabetic patients were included (Fig. 1). The median
follow-up ranged from 1.5 to 7.9 years. Pooled effect estimate suggested that elevated
GDF-15 levels at baseline was associated with an increased risk for composite CVD-related
outcome(s) (per standard deviation (SD) increase in log(GDF-15): HR 1.26, 95% CI 1.12-1.42,
P = 0.0001, I2 for heterogeneity 85%, n = 15,651 patients) (Fig. 2a). When an unadjusted study was
excluded, the pooled effect estimate remained statistically significant, with improvement
in heterogeneity (per SD increase in log(GDF-15): HR 1.16, 95% CI 1.11-1.20, P <0.00001; I2 16%, n = 14,732 patients) (Fig. 2b). In four studies that reported an association
between GDF-15 and all-cause mortality, the pooled analysis suggested that per SD
increase in log(GDF-15) concentration, there was a significant increase in the risk
for all-cause death (HR 1.76, 95% CI 1.23-2.53, P = 0.002); however, marked study heterogeneity (I2 92%, P <0.001) was observed (Fig. 2c). The pooled HR for all-cause death and GDF-15 remained
significant even after excluding the unadjusted study.
Conclusion
Findings from this systematic review and meta-analysis suggest that elevated GDF-15
levels are associated with increased risk for incident cardiovascular endpoint(s)
including acute cardiovascular events, heart failure and/or all-cause death in diabetic
patients.
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Cardiac FailureAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
Article info
Identification
Copyright
© 2020 Published by Elsevier Inc.
