Inflammatory and Matrix Remodeling Proteomic Signatures Are Associated With Arterial Stiffness in Patients With Hypertension

Objective: Arterial stiffness, assessed by carotid–femoral pulse wave velocity (PWV), is a key determinant of cardiovascular risk in arterial hypertension. Low-grade inflammation and extracellular matrix remodeling are recognized contributors to vascular stiffening; however, their combined proteomic profiles in hypertensive populations remain incompletely defined. To evaluate the associations between circulating interleukins, matrix metalloproteinases, and arterial stiffness in patients with hypertension using high-throughput proteomic profiling. Design and method: We studied 817 patients with diagnosed arterial hypertension. Carotid–femoral PWV was measured using a validated non-invasive method in accordance with current European guidelines. Circulating proteins were quantified using the OLINK® proximity extension assay (PEA) technology. Correlations between individual biomarkers and PWV were assessed. To capture cumulative biological effects, composite indices were constructed based on standardized biomarker concentrations: an IL-score (IL-6, IL-16, IL-17D, IL-27) reflecting inflammatory activity, and an MMP-score (MMP-7, MMP-12) reflecting extracellular matrix remodeling. Results: Several interleukins demonstrated significant positive associations with PWV, including IL-17D (r∼ 0.18, p < 0.0001), IL-6 (r ∼ 0.13, p < 0.01), IL-16 (r ∼ 0.11, p < 0.01), and IL-27 (r∼ 0.10, p < 0.01). While individual correlations were modest, the composite IL-score showed a stronger positive association with PWV, indicating that aggregated inflammatory burden is more closely related to arterial stiffness than single cytokines. Markers of matrix remodeling were strongly associated with PWV. MMP-7 (r ∼0.17, p < 0.0001) and MMP-12 (r∼ 0.23, p < 0.0001) were among the most robust correlates. The derived MMP-score exhibited a pronounced positive relationship with PWV, consistent with enhanced elastin and collagen degradation in stiffer arteries. Conclusions: In a large hypertensive cohort, arterial stiffness was associated with distinct proteomic signatures of inflammation and extracellular matrix remodeling. Composite interleukin- and metalloproteinase-based scores demonstrated stronger associations with PWV than individual biomarkers, supporting a multifactorial biological basis of vascular stiffening in hypertension. Integrated proteomic indices may improve mechanistic understanding and risk stratification in hypertensive patients