Next Article in Journal
Clinical Course and Conservative Strategy for Persistent De Novo Stress Urinary Incontinence After Pelvic Organ Prolapse Repair with Transvaginal Mesh
Previous Article in Journal
Novel Therapeutic Strategies for Squamous Cell Carcinoma of the Head and Neck: Beyond EGFR and Checkpoint Blockade
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biomedicines
Volume 13
Issue 8
10.3390/biomedicines13081976
biomedicines-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis

by
Yan Li
1,*,
Han Cao
2,
Lei Ding
1,
Xiaotian Shi
3,
Tuge Naren
1,
Qingqing Zhang
1 and
Zhong Wang
4
1
Department of Health Management, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
2
Medical Data Science Center, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
3
Department of Information Administration, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
4
Department of General Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, Beijing 102218, China
*
Author to whom correspondence should be addressed.
Biomedicines 2025, 13(8), 1976; https://doi.org/10.3390/biomedicines13081976
Submission received: 27 May 2025 / Revised: 17 July 2025 / Accepted: 8 August 2025 / Published: 14 August 2025
(This article belongs to the Section Molecular and Translational Medicine)
Browse Figures
Versions Notes

Abstract

Background: this retrospective cohort study aimed to identify risk factors and establish cutoff values for the initial development of carotid atherosclerosis (CAS) in middle-aged adults. Methods: from an initial cohort of 3583 participants, we finally analyzed 1141 individuals. The observation group comprised subjects who developed CAS without concomitant fatty liver disease (FLD), using their last normal clinical measurements as predictors. The control group consisted of participants who remained free of both CAS and FLD throughout the follow-up period. Statistical analyses included Student’s t-test, Mann–Whitney U test, and chi-square test for group comparisons, along with logistic regression, COX regression, ROC curve analysis, and Kaplan–Meier survival analysis to identify risk factors and determine optimal cutoff values. Repeated-measures ANOVA assessed longitudinal changes. Results: over a mean follow-up of 1.09 years, elevated leukocyte count (AUC: 0.622, 95% CI: 0.540–0.704) and LDL-C (AUC 0.600, 95% CI: 0.516–0.683) were associated with CAS development in middle-aged adults (mean age 49.6 ± 8.0 years). ROC analysis established leukocyte count >5.00 × 109/L and LDL-C >125.1 mg/dL as optimal predictive thresholds. Conclusions: leukocyte count and LDL-C are early warning indicators for CAS development within approximately one year, with leukocyte count showing a slightly stronger correlation with arteriosclerosis progression than LDL-C.

1. Introduction

Subclinical atherosclerosis in asymptomatic individuals demonstrates a significant independent association with all-cause mortality [1,2,3]. Chronic inflammation and dyslipidemia emerge as established risk factors for acute coronary syndrome [4]. While lifestyle interventions and lipid-lowering therapies can mitigate CAS progression in hyperlipidemic populations [5,6], risk factors for CAS in individuals remain poorly characterized. This study aimed to identify novel predictive biomarkers for early CAS detection to guide timely preventive strategies.

2. Materials and Methods

2.1. Study Design and Participants

This retrospective analysis enrolled 3583 participants from Beijing Tsinghua Changgung Hospital (2015–2024) with normal baseline carotid and liver ultrasounds. Exclusion criteria included cardiovascular events, pregnancy, and rheumatoid immune diseases [7]. Among these participants, 2761 had undergone at least three carotid artery and liver ultrasound examinations. After excluding those with FLD, a total of 1141 participants completed at least one follow-up examination to assess clinically significant outcomes (presence or absence of CAS), with up to nine follow-up visits conducted to confirm these findings. Access to the data was restricted and was granted under license specifically for this research.
The study was approved by the hospital ethics committee (No. 25295-6-01). Due to the retrospective nature of the study, the ethics committee waived the need of obtaining informed consent. All procedures were performed in accordance with relevant guidelines and regulations.

2.2. Clinical and Biological Evaluation

Participants’ age, gender, smoking/drinking status, BMI, blood pressure, and laboratory results (fasting glucose, lipids, leukocyte count, etc.) were recorded. Missing data (<1%) were imputed using adjacent values.

2.3. Assessment of CAS

CAS was diagnosed by five trained physicians, each with over 10 years of experience, using Doppler ultrasound systems (Siemens Acuson X700 (Siemens Healthineers, Erlangen, Germany) or Mindray DC-90Pro (Mindray, Shenzhen, China)). The scanning protocol included longitudinal and cross-sectional views, covering the proximal common carotid artery to the distal internal carotid artery bilaterally. CAS was defined by the presence of either carotid intima-media thickening (C-IMT) or carotid atherosclerotic plaque (CAP): C-IMT was diagnosed when the carotid artery intima measured ≥1.0 mm or the bifurcation intima measured ≥1.2 mm. CAP was defined as an intima-media thickness (IMT) ≥1.5 mm that either protruded into the vascular lumen or showed localized thickening exceeding 50% of the adjacent IMT [8,9,10].

2.4. Statistical Analysis

Baseline characteristics were compared using t-test, Mann–Whitney U tests, or chi-square tests. Logistic regression identified risk factors. ROC curves determined cutoff values. Kaplan–Meier analysis/Cox regression assessed survival rates. Repeated-measures ANOVA evaluated longitudinal changes. A p-value less than 0.05 was considered statistically significant.

3. Results

3.1. Participant Characteristics

As shown in Figure S1, the study included 1141 participants. Among them, 117 individuals (aged 32–85 years at baseline) were classified into the CAS group. No significant differences in clinical characteristics or outcomes were observed between the CAS group and healthy controls(Table 1). As shown in Table 2, the distribution of C-IMT and CAP showed no significant differences between the time of CAS diagnosis and follow-up evaluation (p = 0.561). The mean duration from baseline assessment to initial CAS detection was 1.09 years (range: 0.52–3.40 years), with a similar interval of 1.04 years (range: 0.58–4.23 years) observed between initial detection and ultrasound validation.

3.2. CAS and Healthy Controls Comparison Before and After PSM for Age and Gender

Compared with healthy controls, participants with CAS were older and more likely to be male. They also exhibited a higher prevalence of smoking and alcohol consumption. Additionally, the CAS group had significantly elevated levels of BMI, systolic and diastolic blood pressure (SBP/DBP), fasting glucose, total cholesterol, triglycerides, LDL-C, ALT, AST, GGT, uric acid, creatinine, leukocyte count, hemoglobin, and platelet count, but lower HDL-C levels (all p < 0.05). However, the rates of cardiovascular disease family history did not differ significantly between groups. After PSM for age and gender, CAS patients continued to demonstrate a higher prevalence of elevated levels of LDL-C and leukocyte count (Table 1 and Table S1). Subsequent binary logistic regression analysis confirmed that only LDL-C and leukocyte count remained independently associated with CAS (Table 3).

3.3. Cutoff Points of Meaningful Factors with CAS Using ROC Curves and Kaplan–Meier Analysis

ROC curve analysis was performed to evaluate the predictive value of significant factors for CAS. The areas under the curves (AUCs) were 0.622 (95% CI: 0.540–0.704, p = 0.005) for leukocyte count and 0.600 (95% CI: 0.516–0.683, p = 0.022) for LDL-C. No significant differences were observed between the AUCs of leukocyte count and predicted values (p = 0.285), LDL-C and predicted values (p = 0.285), or between LDL-C and leukocyte count (p = 0.291) (Figure 1). Optimal cutoff values were established at 125.1 mg/dL for LDL-C and 5.00 × 109/L for leukocyte count, with values above these thresholds classified as high-level groups.
Kaplan–Meier analysis (Figure 2) revealed that the high leukocyte count group showed significant association with CAS progression (log-rank p = 0.01), while LDL-C groups demonstrated borderline significance (log-rank p = 0.055). Stratification analysis showed the following: (1) For leukocyte count, 60.2% of high-risk and 37.5% of low-risk individuals developed CAS. (2) For LDL-C, 60.5% of high-risk and 42.2% of low-risk individuals developed CAS. The high leukocyte count group exhibited significantly increased risk of CAS progression (HR 1.766, 95% CI 1.138–2.743), as did the high LDL-C group (HR 1.570, 95% CI 1.056–2.084). Multivariable analysis (Table 4) confirmed these associations.
The leukocyte subclass Cox model (Table S2) significantly improved upon the null model, with two key predictors: (1) Neutrophils demonstrated a dose-dependent relationship (aHR 1.29 per 109/L increase, 95% CI 1.01–1.64; p = 0.043). (2) Eosinophils showed the strongest association (aHR 7.47 per 109/L, 95% CI 1.36–40.94; p = 0.021), suggesting clinically meaningful risk even at minimal elevations.

3.4. Longitudinal Changes in Leukocyte Count

Elevated leukocyte count was observed exclusively prior to CAS diagnosis. However, no significant intergroup differences were observed at subsequent time points (Table S3, Figure S2). Leukocyte count decreased post-CAS diagnosis (baseline: 5.56 ± 1.22; follow-up: 5.35 ± 1.31, p = 0.037), suggesting its role as an early warning marker.

4. Discussion

In this retrospective cohort study of 1141 Chinese adults evaluated by carotid ultrasound, we identified elevated leukocyte counts and LDL-C levels in CAS patients prior to disease onset. Notably, both biomarkers demonstrated predictive value for CAS, with leukocyte count showing superior predictive performance after adjustment for age and gender (AUC 0.622 vs. 0.600 for LDL-C). Our findings revealed that both C-IMT and CAP can manifest as initial presentations in newly diagnosed CAS cases. Importantly, longitudinal follow-up (median 1.04 years, range 0.58–4.23 years) showed no evidence of progression from C-IMT to CAP, suggesting that these may represent distinct phenotypic manifestations rather than sequential stages of carotid atherosclerosis.

4.1. The Significance of CAS

Previous studies have established associations between leukocytosis and both FLD [11] and immune disorders [7,12]. To minimize confounding effects, we excluded participants with FLD (confirmed by ultrasound) and those reporting immune diseases (via standardized questionnaire). Our findings align with existing studies in the literature showing peak CAS progression in adults aged 50–59 years [13], as our PSM CAS cohort had a mean age of 49.6 years [14]. Current evidence suggests that while C-IMT and CAP serve as markers of CAS, they may not fully reflect disease severity, with mixed or soft plaques frequently observed even in individuals with normal C-IMT [15]. Our longitudinal data extend these observations by demonstrating stable lesion characteristics during follow-up, with neither isolated C-IMT nor CAP showing significant progression over the median 1.04-year observation period. Importantly, concurrent C-IMT and CAP lesions remained similarly stable, and newly developed CAS lesions exhibited no distinctive morphological patterns. These findings collectively suggest that early-stage CAS may follow an indolent course, with lesion characteristics remaining relatively stable in the short-to-medium term.

4.2. Association Between Leukocyte Counts, LDL-C, and CAS

Leukocyte count serves as a key inflammatory marker that participates in both the initiation and progression of atherosclerosis [16,17]. Our findings align with existing evidence showing significant associations between leukocyte count and lipid profiles (HDL-C, LDL-C, TG, and TC) [18,19]. The potential mechanism may involve VLDL receptor (VLDLR) mRNA expression in peripheral leukocytes, which appears to contribute to CAS development in healthy individuals, particularly in patients exhibiting low VLDL-C but high VLDLR mRNA expression [20]. This process may be mediated through VLDLR-fibrin βN-domain (β40-66) interactions that promote endothelial permeability and leukocyte transmigration [21], a pathway that can be inhibited by β15-42 interactions with endothelial receptors [22] or through anti-VLDLR monoclonal antibodies (1H10, 1H5) [23].
Neutrophil count serves as an independent predictor of all-cause and cardiovascular mortality in neurologically asymptomatic carotid stenosis patients [24], while eosinophil-specific LNK (SH2B3) deficiency promotes both eosinophilia and arterial thrombosis [25]. Although monocytes may drive CAP development without significantly affecting carotid C-IMT [26], our findings demonstrate that early CAS progression is predominantly associated with acute inflammatory responses mediated by neutrophils and eosinophils, with no observed transition from C-IMT to CAP during short-term follow-up. Conversely, monocytes appear to orchestrate the chronic phase of lesion progression toward advanced CAP. These observations collectively suggest the leukocyte subtypes in CAS pathogenesis—with neutrophils and eosinophils potentially initiating early pathological changes, while monocytes may orchestrate subsequent arterial remodeling.
This discrepancy may reflect population differences, as our PSM cohort primarily comprised apparently healthy middle-aged women with low LDL-C levels. Notably, our data confirm that elevated leukocyte count occur specifically before CAS diagnosis but not thereafter, reinforcing its potential as an early warning indicator. These findings contrast with reports of faster arterial deterioration in young Caucasian males, where atherosclerosis typically progresses from the abdominal aorta to other vascular beds [27], and highlight the importance of sex-specific interactions between leukocyte count and plaque stability [28].
These results underscore the clinical importance of monitoring leukocyte count as part of early CAS risk assessment, particularly in middle-aged female populations without conventional lipid risk factors. The findings advocate for enhanced clinical vigilance and targeted early interventions in these demographic groups.

4.3. Strengths and Limitations

To our knowledge, this represents the first study to identify early warning indicators for CAS and characterize their temporal relationship with disease onset. However, several limitations should be acknowledged. First, while we cross-validated available electronic medical records, the majority of participants’ medical and family histories relied on self-reporting, which may introduce recall bias. Second, our cohort consisted predominantly of Han Chinese (over 50% female), potentially limiting the generalizability of our findings to other ethnic and gender groups. Third, the regional confinement of our study population may further restrict the external validity of our results. Existing evidence underscores the pivotal role of immune–inflammatory mechanisms in arteriosclerosis pathogenesis, particularly through systemic inflammation [29], monocyte–macrophage activity [30], and coagulation–fibrinolysis imbalances [31]. Unfortunately, our study was constrained by the available clinical data, with limited inflammatory markers collected during follow-up. While these limitations were inherent to our study design, we intend to address them in future multicenter collaborative studies to validate our findings.

5. Conclusions

Elevated leukocyte count (>5.00 × 109/L) and LDL-C (>125.1 mg/dL) serve as clinically practical early warning indicators for CAS development. The strong association between leukocytosis and CAS progression particularly underscores the potential involvement of immune–inflammatory mechanisms in the pathogenesis of arteriosclerosis, a finding that merits further mechanistic investigation.

Supplementary Materials

The following supporting information can be downloaded at: https://www.mdpi.com/article/10.3390/biomedicines13081976/s1, Table S1: Baseline characteristics between healthy controls and CAS group after PSM for age and gender; Table S2 Leukocyte subclass mul-tivariable Cox Regression results for CAS; Table S3 Leukocyte count comparisons between and within groups after propensity score matching for age and gender. Figure S1. Study flowchart depicted total number of subjects enrolled and reasons for exclusion; Figure S2. Leukocyte count differences of within CAS group and between groups at three time points.

Author Contributions

Conceptualization, Y.L.; methodology, H.C.; software, H.C.; validation, Z.W.; formal analysis, Y.L.; investigation, Y.L.; resources, L.D., X.S. and Q.Z.; data curation, T.N.; writing—original draft preparation, Y.L.; writing—review and editing, Z.W.; visualization, Y.L.; supervision, Z.W.; project administration, Y.L. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki, and approved by Ethics Committee of Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University (No. 25295-6-01 and 28 March 2025).

Informed Consent Statement

Due to the retrospective nature of the study, the ethics committee waived the need of obtaining informed consent.

Data Availability Statement

The data that support the findings of this study are available from Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University, but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Fuster, V.; García-Álvarez, A.; Devesa, A.; Mass, V.; Owen, R.; Quesada, A.; Fuster, J.J.; García-Lunar, I.; Pocock, S.; Sánchez-González, J.; et al. Influence of Subclinical Atherosclerosis Burden and Progression on Mortality. J. Am. Coll. Cardiol. 2024, 84, 1391–1403. [Google Scholar] [CrossRef]
  2. Fegers-Wustrow, I.; Gianos, E.; Halle, M.; Yang, E. Comparison of American and European Guidelines for Primary Prevention of Cardiovascular Disease: JACC Guideline Comparison. J. Am. Coll. Cardiol. 2022, 79, 1304–1313. [Google Scholar] [CrossRef]
  3. Martin, S.S.; Aday, A.W.; Almarzooq, Z.I.; Anderson, C.A.; Arora, P.; Avery, C.L.; Baker-Smith, C.M.; Barone Gibbs, B.; Beaton, A.Z.; Boehme, A.K.; et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association. Circulation 2024, 149, e347–e913. [Google Scholar] [CrossRef] [PubMed]
  4. Yuan, S.; Li, L.; Pu, T.; Fan, X.; Wang, Z.; Xie, P.; Li, P. The relationship between NLR, LDL-C/HDL-C, NHR and coronary artery disease. PLoS ONE 2024, 19, e0290805. [Google Scholar] [CrossRef] [PubMed]
  5. Shai, I.; Spence, J.D.; Schwarzfuchs, D.; Henkin, Y.; Parraga, G.; Rudich, A.; Fenster, A.; Mallett, C.; Liel-Cohen, N.; Tirosh, A.; et al. Dietary intervention to reverse carotid atherosclerosis. Circulation 2010, 121, 1200–1208. [Google Scholar] [CrossRef] [PubMed]
  6. Crouse, J.R., III; Raichlen, J.S.; Riley, W.A.; Evans, G.W.; Palmer, M.K.; O’Leary, D.H.; Grobbee, D.E.; Bots, M.L.; METEOR Study Group. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR Trial. JAMA 2007, 297, 1344–1353. [Google Scholar] [CrossRef]
  7. Tyrrell, P.N.; Beyene, J.; Feldman, B.M.; McCrindle, B.W.; Silverman, E.D.; Bradley, T.J. Rheumatic disease and carotid intima-media thickness: A systematic review and meta-analysis. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 1014–1026. [Google Scholar] [CrossRef]
  8. Nicolaides, A.N.; Panayiotou, A.G.; Griffin, M.; Tyllis, T.; Bond, D.; Georgiou, N.; Kyriacou, E.; Avraamides, C.; Martin, R.M. Arterial Ultrasound Testing to Predict Atherosclerotic Cardiovascular Events. J. Am. Coll. Cardiol. 2022, 79, 1969–1982. [Google Scholar] [CrossRef]
  9. Kabłak-Ziembicka, A.; Przewłocki, T. Clinical Significance of Carotid Intima-Media Complex and Carotid Plaque Assessment by Ultrasound for the Prediction of Adverse Cardiovascular Events in Primary and Secondary Care Patients. J. Clin. Med. 2021, 10, 4628. [Google Scholar] [CrossRef]
  10. Yang, H.; The Professional Committee of Vascular Ultrasound of Stroke Prevention and Treatment Expert; Committee of the National Health Commission; the Professional Committee of Superficial Organ and Peripheral Vascular Ultrasound of the Chinese Medical Ultrasound Engineering; the Professional Committee of Craniocerebral and Cervical Vascular Ultrasound of the Chinese Medical Ultrasound Engineering. Expert consencus on some problems of cerebral and carotid vascular ultrasonography (part of carotid). Clin. J. Cerebrovasc. Dis. 2020, 17, 346–352J. [Google Scholar]
  11. Tang, A.S.P.; Chan, K.E.; Quek, J.; Xiao, J.; Tay, P.; Teng, M.; Lee, K.S.; Lin, S.Y.; Myint, M.Z.; Tan, B.; et al. Non-alcoholic fatty liver disease increases risk of carotid atherosclerosis and ischemic stroke: An updated meta-analysis with 135,602 individuals. Clin. Mol. Hepatol. 2022, 28, 483–496. [Google Scholar] [CrossRef]
  12. Rodriguez, T.; Lehker, A.; Mikhailidis, D.P.; Mukherjee, D. Carotid Artery Pathology in Inflammatory Diseases. Am. J. Med. Sci. 2022, 363, 209–217. [Google Scholar] [CrossRef] [PubMed]
  13. Song, P.; Fang, Z.; Wang, H.; Cai, Y.; Rahimi, K.; Zhu, Y.; Fowkes, F.G.R.; Fowkes, F.J.I.; Rudan, I. Global and regional prevalence, burden, and risk factors for carotid atherosclerosis: A systematic review, meta-analysis, and modelling study. Lancet Glob. Health 2020, 8, e721–e729. [Google Scholar] [CrossRef] [PubMed]
  14. Sebastian, S.A.; Co, E.L.; Tidd-Johnson, A.; Chowdhury, S.; Jain, E.; Davidson, M.; Johal, G. Usefulness of Carotid Ultrasound Screening in Primary Cardiovascular Prevention: A Systematic Review. Curr. Probl. Cardiol. 2024, 49 Pt C, 102147. [Google Scholar] [CrossRef] [PubMed]
  15. Boulos, N.M.; Gardin, J.M.; Malik, S.; Postley, J.; Wong, N.D. Carotid Plaque Characterization, Stenosis, and Intima-Media Thickness According to Age and Gender in a Large Registry Cohort. Am. J. Cardiol. 2016, 117, 1185–1191. [Google Scholar] [CrossRef]
  16. Liao, M.; Liu, L.; Bai, L.; Wang, R.; Liu, Y.; Zhang, L.; Han, J.; Li, Y.; Qi, B. Correlation between novel inflammatory markers and carotid atherosclerosis: A retrospective case-control study. PLoS ONE 2024, 19, e0303869. [Google Scholar] [CrossRef]
  17. Tsai, K.Z.; Huang, W.C.; Chang, Y.C.; Kwon, Y.; Sui, X.; Lavie, C.J.; Lin, G.-M. Localized periodontitis severity associated with carotid intima-media thickness in young adults: CHIEF atherosclerosis study. Sci. Rep. 2023, 13, 10523. [Google Scholar] [CrossRef]
  18. Liu, Y.; Kong, X.; Wang, W.; Fan, F.; Zhang, Y.; Zhao, M.; Wang, Y.; Wang, Y.; Wang, Y.; Qin, X.; et al. Association of peripheral differential leukocyte counts with dyslipidemia risk in Chinese patients with hypertension: Insight from the China Stroke Primary Prevention Trial. J. Lipid Res. 2017, 58, 256–266. [Google Scholar] [CrossRef]
  19. Hu, W.; Zhang, P.; Su, Q.; Li, D.; Hang, Y.; Ye, X.; Guan, P.; Dong, J.; Lu, Y. Peripheral leukocyte counts vary with lipid levels, age and sex in subjects from the healthy population. Atherosclerosis 2020, 308, 15–21. [Google Scholar] [CrossRef]
  20. Zhao, F.; Qi, Y.; Liu, J.; Wang, W.; Xie, W.; Sun, J.; Liu, J.; Hao, Y.; Wang, M.; Li, Y.; et al. Low Very low-Density Lipoprotein Cholesterol but High Very low-Density Lipoprotein Receptor mRNA Expression in Peripheral White Blood Cells: An Atherogenic Phenotype for Atherosclerosis in a Community-Based Population. EBioMedicine 2017, 25, 136–142. [Google Scholar] [CrossRef]
  21. Yakovlev, S.; Medved, L. Dual functions of the fibrin βN-domains in the VLDL receptor-dependent pathway of transendothelial migration of leukocytes. Thromb. Res. 2022, 214, 1–7. [Google Scholar] [CrossRef] [PubMed]
  22. Yakovlev, S.; Strickland, D.K.; Medved, L. Current View on the Molecular Mechanisms Underlying Fibrin(ogen)-Dependent Inflammation. Thromb. Haemost. 2022, 122, 1858–1868. [Google Scholar] [CrossRef] [PubMed]
  23. Yakovlev, S.; Belkin, A.M.; Chen, L.; Cao, C.; Zhang, L.; Strickland, D.K.; Medved, L. Anti-VLDL receptor monoclonal antibodies inhibit fibrin-VLDL receptor interaction and reduce fibrin-dependent leukocyte transmigration. Thromb. Haemost. 2016, 116, 1122–1130. [Google Scholar] [CrossRef] [PubMed]
  24. Nasr, N.; Ruidavets, J.B.; Arnal, J.F.; Sie, P.; Larrue, V. Association of neutrophil count with microembolization in patients with symptomatic carotid artery stenosis. Atherosclerosis 2009, 207, 519–523. [Google Scholar] [CrossRef]
  25. Dou, H.; Wang, R.; Tavallaie, M.; Xiao, T.; Olszewska, M.; Papapetrou, E.P.; Tall, A.R.; Wang, N. Hematopoietic and eosinophil-specific LNK(SH2B3) deficiency promotes eosinophilia and arterial thrombosis. Blood 2024, 143, 1758–1772. [Google Scholar] [CrossRef]
  26. Johnsen, S.H.; Fosse, E.; Joakimsen, O.; Mathiesen, E.B.; Stensland-Bugge, E.; Njølstad, I.; Arnesen, E. Monocyte count is a predictor of novel plaque formation: A 7-year follow-up study of 2610 persons without carotid plaque at baseline the Tromsø Study. Stroke 2005, 36, 715–719. [Google Scholar] [CrossRef]
  27. Jakab, A.E.; Bukva, M.; Maróti, Z.; Kalmár, T.; Raskó, I.; Kereszty, É.M.; Papp, V.Z.; Bereczki, C. The ASAP study: Association of atherosclerosis with pathobiology in a caucasian cohort-a study of 3400 autopsy reports. Sci. Rep. 2024, 14, 25179. [Google Scholar] [CrossRef]
  28. Gasbarrino, K.; Zheng, H.; Daskalopoulou, S.S. Circulating Sex-Specific Markers of Plaque Instability in Women and Men With Severe Carotid Atherosclerosis. Stroke 2024, 55, 269–277. [Google Scholar] [CrossRef]
  29. Song, J.E.; Hwang, J.I.; Ko, H.J.; Park, J.Y.; Hong, H.E.; Kim, A.S. Exploring the Correlation between Systemic Inflammatory Markers and Carotid Atherosclerosis Indices in Middle-Aged Adults: A Cross-Sectional Study. J. Cardiovasc. Dev. Dis. 2024, 11, 73. [Google Scholar] [CrossRef]
  30. Winkels, H.; Ehinger, E.; Vassallo, M.; Buscher, K.; Dinh, H.Q.; Kobiyama, K.; Hamers, A.A.; Cochain, C.; Vafadarnejad, E.; Saliba, A.E.; et al. Atlas of the Immune Cell Repertoire in Mouse Atherosclerosis Defined by Single-Cell RNA-Sequencing and Mass Cytometry. Circ. Res. 2018, 122, 1675–1688. [Google Scholar] [CrossRef]
  31. Gravholt, C.H.; Mortensen, K.H.; Andersen, N.H.; Ibsen, L.; Ingerslev, J.; Hjerrild, B.E. Coagulation and fibrinolytic disturbances are related to carotid intima thickness and arterial blood pressure in Turner syndrome. Clin. Endocrinol. 2012, 76, 649–656. [Google Scholar] [CrossRef]
Biomedicines 13 01976 g001
Figure 1. ROC curve analysis of the predictive effect of CAS progression predictors, based on the cutoff values of leukocyte count >5.00 × 109/L and LDL-C > 125.1 mg/dL, respectively.
Figure 1. ROC curve analysis of the predictive effect of CAS progression predictors, based on the cutoff values of leukocyte count >5.00 × 109/L and LDL-C > 125.1 mg/dL, respectively.
Biomedicines 13 01976 g001
Biomedicines 13 01976 g002
Figure 2. Kaplan–Meier analysis the survival rates, based on the classification of cutoff values of leukocyte count and LDL-C different levels, respectively.
Figure 2. Kaplan–Meier analysis the survival rates, based on the classification of cutoff values of leukocyte count and LDL-C different levels, respectively.
Biomedicines 13 01976 g002
Table 1. Baseline characteristics among healthy controls and the CAS group.
Table 1. Baseline characteristics among healthy controls and the CAS group.
Control
n = 1024		CAS
n = 117		p-Value
Age, years36.4 ± 7.952.6 ± 10.0<0.001
Female, (%)729 (71.2)73 (62.4)<0.001
Alcohol status, %94 (9.2)19 (16.2)<0.001
Smoking status (former or active), %49 (4.8)9 (7.7)<0.001
Family history of cardiovascular disease, %97 (9.5)20 (17.1)0.064
Time interval, years1.06 (0.98, 1.29)1.09 (0.99, 1.84)0.076
Type2 diabetes11
Hypertension01
BMI, kg/m221.8 ± 2.522.8 ± 2.3<0.001
SBP, mmHg114.9 ± 13.2123.6 ± 15.8<0.001
DBP, mmHg69.8 ± 9.573.9 ± 10.2<0.001
MAP, mmHg84.0 (77.7, 90.3)90.0 (82.2, 99.2)<0.001
Fasting glucose, mg/dl86.0 ± 8.591.4 ± 0.72<0.001
Total cholesterol, mg/dl182.2 ± 32.8197.6 ± 33.6<0.001
Triglycerides, mg/dl73.5 (57.5, 97.4)91.2 (73.5, 129.2)<0.001
LDL cholesterol, mg/dl108.5 ± 29.3124.7 ± 29.7<0.001
HDL cholesterol, mg/dl57.1 ± 13.154.0 ± 12.0<0.001
ALT, U/L14.7 (11.2, 19.4)18.2 (13.7, 22.9)<0.001
AST, U/L 18.4 (15.9, 21.6)20.1 (18.0, 24.4)<0.001
GGT, U/L12.7 (9.3, 17.3)16.8 (12.5, 22.0)<0.001
Uric acid, mg/dl5.03 ± 1.285.27 ± 1.11<0.001
Creatinine, mg/dl0.68 ± 0.130.70 ± 0.15<0.001
Hemoglobin, g/L138.3 ± 16.0141.3 ± 15.1<0.001
Platelet count, 109/L248.6 ± 54.0232.6 ± 57.10.002
Leukocyte count, 109/L5.55 ± 1.235.56 ± 1.22<0.001
Table 2. Characteristics of CAS participants’ ultrasound results before and after propensity score matching for age and sex.
Table 2. Characteristics of CAS participants’ ultrasound results before and after propensity score matching for age and sex.
Before PS Matching After PS Matching
C-IMTCAPC-IMT+CAPTime intervals, yC-IMTCAPC-IMT+CAPTime intervals, y
Baseline000 000
CAS diagnosis49(41.9%)46(39.3%)22(18.8%)1.09(0.99,1.84)38(42.7%)44(49.4%)7(7.9%)1.03(0.91,1.53)
Follow-up44(37.6%)49(41.9%)24(20.5%)1.04(0.92,1.53)36(40.4%)39(43.8%)14(15.7%)1.04(0.93,1.53)
Table 3. Factors associated with CAS using binary logistic regression.
Table 3. Factors associated with CAS using binary logistic regression.
UnivariateMultivariate
OR95% CIp-valueAOR95% CIp-value
SBP1.0141.002–1.0260.0221.0110.999–1.0240.084
LDL-c1.3271.032–1.7060.0281.3681.062–1.7630.015
Leukocyte count1.1861.029–1.3670.0191.1721.006–1.3660.042
Table 4. Multivariable Cox regression results for CAS.
Table 4. Multivariable Cox regression results for CAS.
UnitaHR (95% CI)Wald χ2p-Value
Leukocyte Countper 109/L1.21 (1.04–1.40)6.280.012
LDL-Cper 1 mmol/L1.37 (1.06–1.77)5.970.015
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Li, Y.; Cao, H.; Ding, L.; Shi, X.; Naren, T.; Zhang, Q.; Wang, Z. Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis. Biomedicines 2025, 13, 1976. https://doi.org/10.3390/biomedicines13081976

AMA Style

Li Y, Cao H, Ding L, Shi X, Naren T, Zhang Q, Wang Z. Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis. Biomedicines. 2025; 13(8):1976. https://doi.org/10.3390/biomedicines13081976

Chicago/Turabian Style

Li, Yan, Han Cao, Lei Ding, Xiaotian Shi, Tuge Naren, Qingqing Zhang, and Zhong Wang. 2025. "Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis" Biomedicines 13, no. 8: 1976. https://doi.org/10.3390/biomedicines13081976

APA Style

Li, Y., Cao, H., Ding, L., Shi, X., Naren, T., Zhang, Q., & Wang, Z. (2025). Leukocyte Count Is Better than LDL-C as Predictor of Novel Carotid Atherosclerosis. Biomedicines, 13(8), 1976. https://doi.org/10.3390/biomedicines13081976

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop