Razavi Journal of Medicine

Razavi Journal of Medicine

Comparison of the Utility of New Putative Inflammatory Biomarkers for Predicting the Incidence of All-cause and Cause-Specific Mortality

Articles in Press

Document Type : Original Article

Authors
Rana kolahi Ahari 1, 2
Niloofar Shabani 3
Reza Nejad Shahrokh Abadi 4
Hossein Hatamzadeh 5
Bahareh Khajehpour 6
Seyed Kazem Farahmand 7
Mohsen Mouhebati 8
Reza Eftekhar 2, 9
Muhammad Islampanah 10
Habibollah Esmaily 11, 12
Gordon A Ferns 13
Sara Saffar Soflaei 2, 9
Majid Ghaour-Mobarhan 2, 9
1 Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
2 International UNESCO center for Health-Related Basic Sciences and Human Nutrition, Mashhad University of Medical Sciences, Mashhad, Iran.
3 Department of Biostatistics, School of Health, Tehran University of Medical Sciences, Tehran, Iran
4 Clinical Research Development Unit, Ghaem Hospital, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
5 Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
6 Faculty of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran
7 School of Persian and Complementary Medicine, Mashhad University of Medical Science, Mashhad, Iran.
8 Department of Cardiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
9 Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
10 Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
11 Department of Biostatistics, School of Health, Mashhad University of Medical Sciences, Mashhad, Iran
12 Social Determinants of Health Research center, Mashhad University of Medical Sciences, Mashhad, Iran.
13 Brighton and Sussex Medical School, Division of Medical Education, Brighton, United Kingdom.
10.30483/rjm.2026.254732.1506
Abstract
Background: Inflammation and dyslipidemia have significant roles in the pathophysiology of cardiovascular disease (CVD). Recently, leukocyte subtypes to high-density lipoprotein cholesterol (HDL-C) ratios have been proposed as potential indicators of inflammation. However, their value for the mortality incidence remains unclear.

Objectives: We investigated and compared the association of neutrophil /HDL-C (NHR), lymphocyte /HDL-C (LHR), white blood cell (WBC) /HDL-C, and mixed cell /HDL-C (defined as the sum of monocyte, basophil, and eosinophil counts divided by HDL-C) with all-cause and cause-specific mortality.

Methods: Data from the Mashhad stroke and heart atherosclerotic disorder (MASHAD) study was analyzed. Cumulative hazard analysis and log-rank test were utilized to evaluate the differences in mortality within different indices tertiles. The associations of baseline indices with mortality were investigated using Cox proportional hazard regression among various models. Predictive performance was evaluated utilizing c-statistic, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI).

Results: 8702 subjects were recruited. During 10 years of follow-up, 343 deaths from all-cause, 140 from CVD, and 106 from coronary heart disease (CHD) were identified. Using multivariable models, mixed cell /HDL-C showed the strongest association, although non-significant, with total mortality compared to the other indices, with hazard ratios (HRs) and 95% confidence intervals (95%CI) of 1.264 (0.992-1.610). For CVD and CHD mortality, the HRs (95% CI) were 1.070 (0.683-1.676) and 1.221 (0.791-1.887), respectively. Based on the c-statistic and IDI, WBC/HDL-C showed a non-significant improvement in predictive performance for all-cause mortality (IDI 0.003, 95%CI 0-0.014) for all-cause mortality (IDI 0.003, 95%CI 0-0.014). Based on the c-statistic index and NRI, mixed cell/ HDL-C had better performance for CVD (cNRI 0.125, 95%CI 0.021-0.175) and CHD (cNRI 0.137, 95%CI 0.038-0.218) mortality.

Conclusion: Among the MASHAD study population, WBC/HDL-C had a greater predictive ability for all-cause mortality. However, the mixed cell/ HDL-C index was a promising predictive biomarker for the incidence of CVD and CHD mortality.
Keywords
leukocyte subtypes
high-density lipoprotein cholesterol
all-cause mortality
cardiovascular mortality
coronary heart disease mortality
Subjects

Acknowledgments: The authors thank the participants of the MASHAD study for their valuable contributions.


Ethics approval: The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study protocol was given approval by the Ethics Committee of Mashhad University of Medical Sciences (MUMS) (ethics approval code: IR.MUMS.REC.1386.250). Written informed consent was obtained from participants before the inclusion.


Funding: N/A


Conflict of interests: N/A


Availability of data and materials: The data that support the findings of this study are available from MUMS, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of MUMS.


Approval date of Registry and the Registration No: The study was given approval by the Ethics Committee of MUMS (Approval date: August 15, 2007 and registration No: 85134).


Consent for publication: Not applicable.


Author contributions: The final version of the manuscript has been reviewed and approved by all the authors. Authors agreed to be responsible for all aspects of the work. Details of contributions: Study concept and design: MG, SKF, and MM; data collection: SSS, BKH, and RE; Analysis and interpretation of data: NS, RKA, SSS, and HE; Drafting of the manuscript and critical revision: RKA, RNS, HH, MI, SSS and GAF

Open Access Policy: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/

 
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Available Online from 07 October 2026