Phenotype-specific associations of circulating adipokine levels with carotid atherosclerosis: a systematic review and meta-analysis

Background Atherosclerosis (AS) is driven by inflammatory and metabolic dysregulation. Carotid atherosclerosis (CA), assessable by ultrasonographic carotid intima–media thickness (cIMT) and plaque, provides a noninvasive window into AS. Adipose tissue–derived adipokines are involved in AS. Aim We conducted a phenotype-specific systematic review and meta-analysis of observational studies to quantify associations between circulating adipokines and CA. Methods Following a preregistered protocol, PubMed, Embase, and Web of Science were searched. Adults with ultrasound-defined CA (increased cIMT and/or carotid plaque) and controls were included. Mean and standard deviation (SD) of circulating adipokines were extracted and converted to standardized mean difference (SMD) for pooled analysis. Results Nineteen studies (n = 5860; Asia/Europe/Americas; 8 cross-sectional, 8 case-control, 3 cohort) were included for quantitative analysis. In the increased cIMT phenotype, adiponectin was lower in CA [SMD = −0.72 (−1.00, −0.44), P < 0.05], whereas in the plaque phenotype it was higher [SMD = 0.29 (0.11, 0.47), P < 0.05]. Leptin was higher in CA, reaching significance in the plaque phenotype [SMD = 0.70 (0.13, 1.28), P = 0.02]. Omentin was consistently lower in CA across phenotypes [SMD = −1.43 (−2.20, −0.66), P < 0.001]. Sensitivity analysis supported robustness for adiponectin (stronger effects after excluding healthy cohorts), and publication-bias assessment was feasible only for adiponectin and were negative. Conclusions This study indicated that circulating adipokine levels can serve as phenotype-specific biomarkers in CA.