<p>Molecular recognition and determination of vascular cell adhesion molecule-1 (VCAM-1), interleukin-6 (IL-6), and natriuretic peptide C-type (NPPC) are essential for the early prognosis and diagnosis of cardiovascular diseases, especially in young obese populations. Highly sensitive and selective devices characterized by low Limits of quantification are required for their determination in whole blood. Therefore, a 3D stochastic sensor was developed by immobilizing a chitosan hydrogel onto a carbon paste electrode (used as the support matrix for the hydrogel), which was subsequently modified with gold nanoparticles, multi-walled carbon nanotubes, and β-cyclodextrin (β-CD/AuNPs@MWCNT/CS/CPE). The sensor was designed, characterized, and validated using whole blood samples and compared with commercial enzyme-linked immunoassay (ELISA) kits for the molecular recognition and determination of IL-6, VCAM-1, and NPPC. The sensor exhibited low Limits of quantification: 4.10 × 10⁻¹⁷ g mL⁻¹ for IL-6, 5.00 × 10⁻¹⁶ g mL⁻¹ for VCAM-1, and 1.00 × 10⁻¹⁵&#xa0;g&#xa0;mL⁻¹ for NPPC, with wide Linear concentration ranges of 4.10 × 10⁻¹⁷–2.00 × 10⁻⁷ g mL⁻¹ (IL-6), 5.00 × 10⁻¹⁶–5.00 × 10⁻⁸ g mL⁻¹ (VCAM-1), and 1.00 × 10⁻¹⁵–1.00 × 10⁻⁹ g mL⁻¹ (NPPC). The recoveries for each biomarker were higher than 99.85%, with relative standard deviations below 1.00%. The sensor can be used as a screening tool for whole blood, enabling rapid molecular recognition and determination of IL-6, VCAM-1, and NPPC.</p> Graphical Abstract <p></p>