Key result
Composite inflammatory-lipid indices outperform static lipids for detecting atherosclerosis with AUC up to ~0.85.
Why the study?
Conventional lipid testing alone fails to identify a substantial proportion of individuals at risk for atherosclerosis. This review aimed to systematically compile and appraise traditional lipid, oxidative LDL-modification, inflammatory, composite, and emerging molecular biomarkers for atherosclerosis diagnosis and risk stratification.
Does a tiered strategy combining oxidative LDL-modification products, inflammatory mediators, and composite haematological/lipid indices improve diagnostic accuracy and risk stratification for atherosclerosis compared to conventional static lipid measurements in adult patients?
Systematic Review
Does a tiered strategy combining oxidative LDL-modification products, inflammatory mediators, and composite haematological/lipid indices improve diagnostic accuracy and risk stratification for atherosclerosis compared to conventional static lipid measurements in adult patients?
A tiered biomarker strategy integrating conventional lipids with oxidative LDL products, plaque-specific inflammatory enzymes, and composite leukocyte-lipid ratios (AUC 0.75-0.85) provides superior diagnostic accuracy for identifying vulnerable atherosclerotic plaque compared to static lipid panels alone.
Answers are grounded in this paper and cite their sources.
Composite indices may aid atherosclerosis detection beyond lipids; leaves open need for prospective outcome validation before adoption.
Background: Atherosclerosis remains the principal substrate for ischaemic heart disease and stroke, yet conventional lipid testing alone fails to identify a substantial proportion of at-risk individuals (1,2).Oxidative modification of LDL and downstream inflammatory activation are now recognised as central, biomarker-rich processes driving plaque initiation, progression, and rupture (3,4).Objective: To systematically compile and appraise biomarkers used in atherosclerosis diagnosis and risk stratification -traditional lipid markers, oxidative LDL-modification products, inflammatory mediators, composite ratios, and emerging molecular markers -classifying each by structure, mechanism, estimation method, reference range, and temporal (early versus late) predictive utility, individually and in combination.Methods: A narrative-systematic search of PubMed/MEDLINE, Scopus, Embase, Cochrane Library, and Web of Science (January 2000 -June 2026) identified original studies, meta-analyses, and reviews reporting biomarker biology, methodology, or diagnostic performance in atherosclerosis.Data were extracted and synthesised thematically across five predefined biomarker domains.Results: Oxidative products of LDL modification (oxLDL, malondialdehyde, 4-hydroxynonenal, oxysterols, modified apoB-100) (3-6) and plaque-specific inflammatory enzymes (Lp-PLA2, myeloperoxidase, MMP-9) (7-9) consistently outperformed static lipid values in identifying biologically active and vulnerable plaque.Composite indices integrating lipid and leukocyte-derived parameters (NLR, MHR, SII, SIRI) achieved the highest reported diagnostic accuracy (AUC generally 0.75-0.85)(10,11), exceeding any single marker in isolation.Conclusion: No single biomarker captures the full biology of atherosclerosis.A tiered strategy combining lipid, oxidative, and inflammatory markers offers the most evidence-supported approach to early detection and risk stratification, pending further assay standardisation.
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A 2026 study conducted a systematic review in Atherosclerosis. Oxidative LDL-modification products, inflammatory mediators, and composite lipid/leukocyte indices (NLR, MHR, SII, SIRI) vs. Traditional static lipid markers (TC, LDL-C, HDL-C, TG) was evaluated on Diagnostic accuracy for biologically active and vulnerable atherosclerotic plaque (AUC 0.75-0.85). Composite inflammatory and lipid indices (NLR, MHR, SII, SIRI) achieved the highest diagnostic accuracy for atherosclerosis (AUC 0.75–0.85), outperforming single static lipid markers.
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