Coagulation, Inflammation, and Vascular Tone: identifying axes of endothelial dysfunction in Young Women with Normal Weight Obesity

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Abstract

Individuals with the Normal Weight Obesity (NWO) phenotype are characterized by excessive body fat despite normal Body Mass Index (BMI), often leading to underestimated cardiovascular risk.The mechanisms linking this specific body composition to early vascular damage remain unclear. The aim of this study was to evaluate endothelial dysfunction biomarkers in young women with NWO, and to identify the main axes of vascular impairment. The study included 176 young women (median age 20) with normal BMI (18.5–24.9 kg/m²). Based on dual-energy X-ray absorptiometry (DXA), participants were classified into an NWO group (n = 88; body fat ≥ 35.78%) and a healthy control group (NW; n = 88). Serum levels of tissue-type plasminogen activator (tPA), von Willebrand factor (vWF), Angiopoietin-1 (Ang-1), Nitric Oxide (NO), and high-sensitivity C-reactive protein (hs-CRP) were analyzed. Principal Component Analysis (PCA) was employed to identify latent patterns of endothelial function. Women with NWO exhibited significantly higher levels of tPA (1.86 vs. 1.48 ng/ml; p = 0.038), vWF (72.24 vs. 63.62 ng/ml; p = 0.038), and Ang-1 (515.3 vs. 491.63 pg/ml; p = 0.008) compared to controls. PCA identified three principal components explaining 71.68% of the total variance: Coagulation (tPA, vWF), Inflammation/Angiogenesis (hs-CRP, Ang-1), and Vasodilation (NO). Young women with NWO exhibit subclinical endothelial dysfunction, which is characterised primarily by a pro-thrombotic state and disturbed angio-inflammatory balance. These changes occur even before the onset of overt clinical symptoms.

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