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Systematic Review

Evaluating Immune-Inflammatory Indices for Risk Stratification in Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta-Analyses

by
Hanxin Liu
1,2,3,
Pingwu Wang
4,
Lik Hang Wu
1,2,3,†,
Fan Wu
5,
Xinya Zhou
5,
Yuhan Li
6,
Hui Su
5,
Jiayi Zang
1,
Xinchen Ji
1,‡,
Xueling Xiao
4,*,
Ya-Ke Wu
7,8,*,
Leroy Sivappiragasam Pakkiri
1,2,3,§ and
Chester Lee Drum
1,2,3,9,§
1
Yong Loo Lin School of Medicine, National University of Singapore (NUS), NUHS Tower Block, 1E Kent Ridge Road Level 11, Singapore 119228, Singapore
2
Cardiovascular Research Institute (CVRI), National University Health System (NUHS), 14 Medical Drive, MD6 Level 8, Singapore 117599, Singapore
3
Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore (NUS), Singapore 119228, Singapore
4
Xiangya School of Nursing, Central South University, 172 Tongzipo Road, Changsha 410013, China
5
College of Medicine and Health Science, Wuhan Polytechnic University, 68 Xuefu South Road, Changqing Garden, Wuhan 430023, China
6
Department of Operating Room, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China
7
School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
8
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
9
Department of Biochemistry, National University of Singapore (NUS), 8 Medical Drive, MD7, Singapore 117596, Singapore
*
Authors to whom correspondence should be addressed.
†
Current address: School of Frontier Engineering, Kitasato University, 1-15-1, Kitazato, Minami-ku, Sagamihara-shi 252-0373, Japan.
‡
Current address: Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, China.
§
The last two authors are joint senior authors.
Diagnostics 2025, 15(22), 2862; https://doi.org/10.3390/diagnostics15222862
Submission received: 26 September 2025 / Revised: 3 November 2025 / Accepted: 5 November 2025 / Published: 12 November 2025
(This article belongs to the Special Issue Recent Advances in Biomarkers for Cardiovascular Disease)
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Abstract

Background/Objectives: Although systematic reviews and meta-analyses have examined immune-inflammatory indices in cardiovascular disease (CVD), the evidence remains scattered and inconsistent. This umbrella review aims to synthesize findings and evaluate the overall predictive value of these indices for clinical outcomes. Methods: We systematically searched PubMed, Cochrane Library, Web of Science, Embase, Scopus, and Medline for systematic reviews with meta-analyses assessing neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI) in patients with CVD. Study quality and certainty of evidence were appraised using AMSTAR-2 and GRADE, respectively. Results: A total of 35 meta-analyses covering 106 unique outcomes were included, of which 87 showed significant associations. Elevated NLR and SII were consistently linked to higher risks of CVD mortality, major adverse cardiovascular events, myocardial infarction, heart failure, and stroke. PLR and SIRI were primarily associated with poor recovery from stroke and increased mortality in ST-elevation myocardial infarction. Specifically, the methodological quality of the included reviews was generally moderate to high according to AMSTAR-2, whereas none of the associations reached high certainty based on GRADE, with most rated as low or very low and about one-quarter as moderate certainty. Conclusions: The overall certainty of evidence remains limited according to GRADE, alongside methodological heterogeneity, population variability, and inconsistent thresholds that further restrict the direct applicability of these findings in clinical practice. Nevertheless, available evidence indicates that elevated immune-inflammatory indices are likely associated with worse clinical outcomes in patients with CVD. Future research should prioritize establishing standardized cutoffs, improving methodological consistency, and validating these indices across diverse populations to support their integration into clinical risk-stratification frameworks.
Keywords: immune-inflammatory indices; cardiovascular diseases; prognostic biomarkers; umbrella review immune-inflammatory indices; cardiovascular diseases; prognostic biomarkers; umbrella review
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MDPI and ACS Style

Liu, H.; Wang, P.; Wu, L.H.; Wu, F.; Zhou, X.; Li, Y.; Su, H.; Zang, J.; Ji, X.; Xiao, X.; et al. Evaluating Immune-Inflammatory Indices for Risk Stratification in Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta-Analyses. Diagnostics 2025, 15, 2862. https://doi.org/10.3390/diagnostics15222862

AMA Style

Liu H, Wang P, Wu LH, Wu F, Zhou X, Li Y, Su H, Zang J, Ji X, Xiao X, et al. Evaluating Immune-Inflammatory Indices for Risk Stratification in Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta-Analyses. Diagnostics. 2025; 15(22):2862. https://doi.org/10.3390/diagnostics15222862

Chicago/Turabian Style

Liu, Hanxin, Pingwu Wang, Lik Hang Wu, Fan Wu, Xinya Zhou, Yuhan Li, Hui Su, Jiayi Zang, Xinchen Ji, Xueling Xiao, and et al. 2025. "Evaluating Immune-Inflammatory Indices for Risk Stratification in Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta-Analyses" Diagnostics 15, no. 22: 2862. https://doi.org/10.3390/diagnostics15222862

APA Style

Liu, H., Wang, P., Wu, L. H., Wu, F., Zhou, X., Li, Y., Su, H., Zang, J., Ji, X., Xiao, X., Wu, Y.-K., Pakkiri, L. S., & Drum, C. L. (2025). Evaluating Immune-Inflammatory Indices for Risk Stratification in Cardiovascular Disease: An Umbrella Review of Systematic Reviews and Meta-Analyses. Diagnostics, 15(22), 2862. https://doi.org/10.3390/diagnostics15222862

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