Arterial Stiffness and Anti-NR2/GluN2 Autoantibodies to N-Methyl-D-Aspartate Receptors as Markers of Vascular Aging and Cognitive Impairment in Arterial Hypertension

Vollständiger Abstract

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Background: Arterial hypertension (HTN) is associated with accelerated vascular aging, cerebral microvascular injury, and cognitive decline. Anti-NR2/GluN2 (NR2) antibodies may be related to N-methyl-D-aspartate receptor (NMDAR)-mediated neuronal-ischemic injury, although their clinical significance in HTN requires further clarification. Objective: The aim of this study was to evaluate cross-sectional associations between arterial stiffness assessed by the cardio-ankle vascular index (CAVI), serum NR2 antibody levels, and cognitive performance assessed by the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) in patients with essential HTN and controls. Methods: This single-center study included 175 adults aged 40–70 years: 128 patients with essential HTN and 47 controls. The median age was 58 [54; 66] years in the HTN group and 55 [47; 62] years in controls (p = 0.06). Men accounted for 52 patients (40.6%) in the HTN group and 14 participants (30.0%) in the control group (p = 0.22). Arterial stiffness was assessed using CAVI. Serum NR2 antibody levels were measured by enzyme-linked immunosorbent assay. Cognitive status was evaluated using MoCA and MMSE. Between-group comparisons, correlation analysis, and exploratory classification modeling were performed. Results: Patients with HTN had higher CAVI values than controls (8.3 [7.3; 9.4] vs. 7.3 [6.9; 7.9]; p = 0.001). Cognitive impairment was more frequent in hypertensive patients by both MoCA (52.3% vs. 27.7%; p = 0.003) and MMSE (48.7% vs. 28.3%; p = 0.01). NR2 antibody levels were higher in HTN (1.6 [1.15; 2.62] vs. 1.33 [1.02; 1.84] ng/mL; p = 0.03). CAVI inversely correlated with MoCA and MMSE scores. Conclusions: CAVI was higher in patients with HTN and showed modest inverse associations with cognitive scores. NR2 antibody levels were also higher in HTN; however, their relationship with cognitive impairment should be interpreted as exploratory and hypothesis-generating. Further longitudinal studies with neuroimaging are required to determine the clinical and prognostic significance of these findings.