Association of markers of endothelial dysfunction with depression in middle-aged patients with cerebral microangiopathy

Abstract

To assess the ratio of levels of peripheral markers of inflammation and biomarkers of endothelial dysfunction (ED) with the severity of depression in middle-aged patients with cerebral microangiopathy. In an observational study of outpatients (n=262, 42.1% of men, 57.9% of women, average age 54.2±7 years), the severity of depressive disorders was assessed with HADS. Levels of peripheral markers of endothelial inflammation (C-reactive protein (CRP), monocytic chemoattractant protein-1 (MCP-1)) and ED biomarkers (endothelin-1, endothelial NO synthase, vascular endothelial growth factor, desquamated endotheliocytes, S100 protein, von Willebrand factor, fibrinogen) were determined by enzyme immunoassay. The initial sample of patients is divided into two groups: with clinical (n=146) and subclinical (n=116) depression. Based on the indicators of the ED biomarkers, a factor analysis was performed to calculate the integrative indicator of endothelial function (IIEF). Patients with clinically defined depression compared with patients with subclinical depression had an increased level of peripheral markers of inflammation (CRP 6.11 vs 2.03 mg/L; p<0.05; MCP-1 2.02 vs 0.66 ng/ml; p<0.05). The severity of depression was directly correlated with the level of peripheral markers of inflammation (CRP, r=0.85, p<0.05; MCP-1, r=0.8, p<0.05, respectively). Patients with clinically expressed depression were characterized by a lower IIEF compared with patients with subclinical depression (0.12±0.04 vs 1.14±0.3; p<0.05, respectively). Odds ratios adjusted for age, obesity, type 2 diabetes mellitus were as follows: 1.5; 95% CI (1.3-1.8), p<0.001 for CRP; 1.67; 95% CI (0.63-2.85), p<0.001 for MCP-1; 1.21; 95% CI (1.19-1.35), p<0.001 for IIEF. Pro-inflammatory ED contributes to the development of depression in middle-aged patients with cerebral microangiopathy associated with arterial hypertension. The severity of depression depends on the degree of ED. The association between the degree of ED, the pro-inflammatory activity of the endothelium and the severity of depression is relatively independent of age, obesity, type 2 diabetes mellitus.