Development and Clinical Validation of a Novel Inflamm-Aging Score in Cardiovascular Disease

Aiad Gaber Arean; Amenh Mohammed Abdulrahman; Abdullah Ali Mohammed; Waleed Khalid Ahmed; Youssef Shakuri Yasin; Azal Hamoody Jumaa

doi:10.24017/

Authors

Aiad Gaber Arean Department of Medical Chemistry, College of Medicine , Al-Muthanna University, Al-Muthanna , Iraq. https://orcid.org/0009-0003-6258-2026
Amenh Mohammed Abdulrahman Department of Pharmacology , College of medicine. Al-Iraqia university, Baghdad, Iraq. https://orcid.org/0009-0008-2596-2560
Abdullah Ali Mohammed Department of Medical Chemistry, College of Medicine , Al-Muthanna University, Al-Muthanna , Iraq. https://orcid.org/0000-0002-5717-6694
Waleed Khalid Ahmed Department of Medical Chemistry, College of Medicine, University of Fallujah, Al-Fallujah, Iraq. https://orcid.org/0009-0000-8683-541X
Youssef Shakuri Yasin Bilad Alrafidain University, Diyala, Iraq. https://orcid.org/0000-0003-1433-1858
Azal Hamoody Jumaa Iraqi National Cancer Research Center/the University of Baghdad, Baghdad, Iraq. https://orcid.org/0000-0001-8497-0001

Abstract

Chronic low-grade inflammation associated with aging "inflamm-aging" contributes to cardiovascular disease (CVD), yet traditional risk assessment relies on single biomarkers. This cross-sectional study aims to evaluate and validate a composite inflamm-aging score in 65 patients with CVD and 55 age-matched healthy controls. The score was derived from three biomarkers of interleukin 6 (IL-6), high-sensitivity c-reactive protein (hsCRP), and matrix metalloproteinase-9 (MMP9)- using principal component analysis (PCA). The PCA yielded one component with an eigenvalue of 2.172 (72.4% variance), and the second component's eigenvalue was 0.52 (<1.0, Kaiser criterion). The biomarker loadings were IL-6 (0.58), hsCRP (0.54), and MMP9 (0.61). The weighted composite was adjusted for age (β = 0.045/year, p=0.002) and sex (β = 0.31 female vs. male, p = 0.018) using multiple linear regression among the controls (R² = 0.246). The final score was calculated as the residual. The score distinguished CVD from the controls with an area under the curve of 0.89 (an optimal cutoff of >1.20) with 81.5% sensitivity and 87.3% specificity. The score correlated strongly with N-terminal pro-B-type natriuretic peptide (ρ=0.71) and the soluble suppression of tumorigenicity 2 (ρ=0.58), independent of traditional risk factors including hypertension, diabetes, and dyslipidemia. A significant age-by-disease interaction (p=0.008) indicated accelerated inflamm-aging in older CVD patients. The inflamm-aging score is a promising novel biomarker of CVD severity beyond traditional assessments, potentially guiding individualized anti-inflammatory therapy. Independent external validation is required before clinical implementation.

Keywords:

Inflamm-aging score, Cardiovascular disease, IL-6, hs-CRP, MMP9, Pleiotropic effects

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