Abstract
Peripheral arterial disease (PAD) is one of the most common manifestations of systemic atherosclerosis. The prevalence of unrecognized PAD is high, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular events. Inflammatory processes play an important role in the disease initiation as well as in the disease progression. Vascular cell adhesion molecule 1 (VCAM-1), a biomarker of endothelial dysfunction, appears to be an important mediator in inflammatory processes. Therefore, we hypothesized that in patients with PAD, circulating VCAM-1 might be elevated due to its function in mediating adhesion of immune cells to the vascular endothelium in the process of endothelial dysfunction and inflammation, and, therefore, applicable as a diagnostic biomarker. A total of 126 non-consecutive patients were enrolled in this study, of whom 51 patients had typical clinical manifestations of PAD and as controls 75 patients with no history of PAD or cardiovascular disease. All serum samples were obtained either during hospitalization or during out-patient visits and analyzed for VCAM-1 by the ELISA. Compared with controls, median levels of VCAM-1 were significantly elevated in patients suffering from PAD (953 vs. 1352 pg/ml; p < 0.001). Furthermore, VCAM-1 appeared to be highly discriminative for the detection of PAD (AUC = 0.76; CI 0.67–0.83). We could not observe dynamics related to increasing disease stages according to Rutherford classes in patients with apparent PAD. VCAM-1 was shown to be a potential discriminator and biomarker for the severity of systemic atherosclerosis. In a logistic regression analysis, VCAM-1 was robustly associated with the diagnosis of PAD, even after correction for clinically relevant cofounders (namely age, arterial hypertension, diabetes and LDL levels). Thusly, VCAM-1 might serve as a biomarker for PAD screening and detection.
Highlights
One of the most common manifestations of atherosclerosis is peripheral artery disease (PAD), with a prevalence of around 10–25% in population aged over 55 years and an estimated total number of about 27 millions of affected patients within the industrialized world
A total of 126 patients were enrolled; all were admitted to the Department of Internal Medicine I at the University hospital of Jena. 51 of these patients were diagnosed with PAD by clinical examination, apparative diagnostic (Doppler ultrasound) and functional tests (6-min walk test). 75 patients served as controls after exclusion of coronary artery disease and PAD
Compared to coronary artery disease (CAD) and other cerebrovascular diseases, individuals suffering from PAD have the highest 1-year rate of atherothrombotic events [28]
Summary
One of the most common manifestations of atherosclerosis is peripheral artery disease (PAD), with a prevalence of around 10–25% in population aged over 55 years and an estimated total number of about 27 millions of affected patients within the industrialized world. PAD is considered to be an independent predictor of cardiac or cerebrovascular events and requires aggressive medical management [1,2,3]. A significant higher mortality of individuals suffering from PAD has been shown in the past [4, 5]. Many major clinical studies on pathogenesis of PAD focus on the role of inflammatory processes [7]. In patients with elevated inflammatory markers [e.g., CRP, lipoprotein (a), Interleukin-6 (IL-6) and soluble intercellular adhesion molecule-1 (SICAM1)], an increased risk for the development of PAD could impressively be shown in the Edinburgh Artery Study [8]. The role of inflammatory parameters is still not fully unraveled, especially when it comes to potential diagnostic use or therapeutic target for medical treatments
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