Association between S100A12 and risk of peripheral arterial disease in patients with dyslipidemia: a cross-sectional study

Objective: S100A12 acts as a pro-inflammatory agent in vivo, with a close relationship with plaque formation in patients with acute coronary syndrome (ACS), end-stage renal disease, and diabetes. Peripheral arterial disease (PAD) can lead to mobility difficulties and ultimately disability and amputation. The association between S100A12 and risk of peripheral arterial disease remains unclear. This study aims to investigate the association between S100A12 and the risk of PAD in patients with dyslipidemia. Methods: From March 2023 to June 2024, 478 patients were included in this cross-sectional study. They were divided into PAD group (n = 105) and control group (n = 373) according to the presence or absence of PAD (The diagnosis of PAD is a combination of the patient’s clinical symptoms, imaging evidence and ankle-brachial index). Plasma S100A12 was detected by available kit. General information, disease history, smoking history, and laboratory indicators were collected from both groups. The relationship between S100A12 and the risk of PAD was analyzed using statistical methods. Results: Levels of S100A12 were significantly higher in the PAD group of dyslipidemia [0.22 (0.13,1.49) ng/cL vs. 0.13 (0.10,0.18)ng/cL, p value < 0.001]. Univariate and multivariate logistic regression analyses suggested that the risk of PAD was significantly higher with increasing levels of S100A12 [Odd ratio (OR) (95%CI) = 2.264 (1.681, 3.047), p value < 0.05]. In addition, lower high-density lipoprotein cholesterol (HDL-C) level and diabetes mellitus (DM) were independent risk factors for PAD [OR (95%CI) = 0.388 (0.186,0.809), p value = 0.012; OR = 2.375 (1.527,3.695), p value < 0.001]. Subgroup analysis suggested that S100A12 was significantly and positively associated with the risk of PAD in all subgroups, regardless of whether HDL-C levels < 1.03 mmol/L, age > 60 years, and presence of diabetes or hypertension. Restricted cubic spline (RCS) curves suggested that the correlation between S100A12 and the risk of PAD was nonlinear (p-non-linear value < 0.05). The RCS curves showed that the positive correlation between S100A12 and the risk of PAD was stronger when the S100A12 level was less than 1.00ng/cL. Conclusion: In conclusion, elevated S100A12 level is an independent risk factor for PAD in patients with dyslipidemia. In different subgroups, S100A12 was significantly and positively associated with the risk of PAD after adjusting for different factors. There is a non-linear relationship between S100A12 and the risk of PAD, with a stronger positive correlation at S100A12 levels below 1.00ng/cL. These findings implied that S100A12 is a potential biomarker for identifying patients with dyslipidemia who are at high risk of developing PAD. They also implied that S100A12 levels can be routinely monitored in dyslipidemic populations for the early detection of PAD and to guide the management of PAD. Finally, the results of this study emphasize that inflammation in dyslipidemia patients plays an important role in the development of PAD, suggesting that lipid control and immunomodulation may be effective in the prevention of PAD. Clinical trial number: MR-35-24-038431. © The Author(s) 2025.