Circulating growth differentiation factor-15 concentration and hypertension risk: a dose-response meta-analysis

Growing evidence suggests that growth differentiation factor-15 (GDF-15) may contribute to adverse clinical outcomes, such as major cardiovascular events and all-cause mortality. However, there is little information about its relationship to hypertension. This meta-analysis aimed to quantitatively evaluate the relationship between circulating GDF-15 and hypertension prevalence.

Databases searched included PubMed, Web of Science, and Embase, from inception to August 2024. The inclusion criteria were studies reporting hypertension prevalence in at least three GDF-15 categories.

A total of 24 studies from 21 articles with 35,904 participants and 23,925 hypertensive cases were included in this meta-analysis. Compared with individuals with a low level of circulating GDF-15, those with high GDF-15 level had a higher prevalence of hypertension [odds ratios (OR) 1.60, 95% confidence interval (CI) 1.37-1.88, P < 0.001). In the dose-response meta-analysis, the prevalence of hypertension increased by 24% with every 1 ng/ml increase in GDF-15 (OR 1.24, 95% CI 1.16-1.33, P < 0.001). However, the dose-response curve was nonlinear (P-nonlinearity < 0.001), plateauing or even decreasing slightly after GDF-15 concentrations reached approximately 5.5 ng/ml. Significant heterogeneity was detected in the pooled analysis and meta-regression analysis suggested that participants' age and the prevalence of diabetes significantly accounted for the heterogeneity.

Circulating GDF-15 is positively and non-linearly associated with the prevalence of hypertension, with a plateau or slight decline after reaching a certain GDF-15 dose. Systematic Review Registration: https://inplasy.com/inplasy-2023-3-0082/, identifier (INPLASY202330082).