Correlation of neutrophil–lymphocyte ratio with carotid intima–media thickness in diabetes-an analytical cross-sectional study

Sneha Sabu George and Sumesh Raj*

*Correspondence:
Sumesh Raj,
drsumeshraj@yahoo.com

Received: 03 November 2023; Accepted: 04 December 2023; Published: 24 December 2023.

Background: Atherosclerosis, the growth of fibrofatty lesions in the arterial wall, is a major cause of illness and mortality across the world. Cardiovascular disease, stroke, and coronary heart disease risk are increased in diabetics compared to nondiabetics. Carotid intima–media thickness (CIMT), performed by radiologists has been widely regarded as a marker of atherosclerosis. Neutrophil–lymphocyte ratio (NLR) is an easily available and reproducible test and is said to be a marker of inflammation. In this study, our aim was to assess the correlation of NLR with CIMT in diabetes patients.

Methods: A total of 25 Type 2 diabetic patients (F:M = 7:18, mean age: 71.56 ± 9.63) were included. Complete blood count (CBC) was done and CIMT was measured. Depending on CIMT, the patients were divided into the following two groups: High CIMT group (>1 mm) and normal CIMT group (<1 mm).

Results: Mean NLR was found to be higher in diabetes patients with thick CIMT compared to those with normal CIMT. This was statistically significant (p < 0.05). There was no difference in mean neutrophil count and mean lymphocyte count between the two groups.

Conclusion: In this study, mean NLR was found to be higher in diabetes patients with higher CIMT than normal CIMT. Hence, NLR can be used to predict atherosclerosis in diabetes patients. Being cheaper, it can be used to predict adverse atherosclerotic events such as cerebrovascular accidents and coronary syndromes in diabetes patients, and the progression of these events in the same.

Keywords: diabetes, carotid intima–media thickness, neutrophil lymphocyte ratio, atherosclerosis

Introduction

Atherosclerosis, defined as the growth of fibrofatty lesions in the arterial wall, is a major source of morbidity and death, accounting for the majority of myocardial infarctions and strokes, as well as debilitating peripheral artery disease. The immune system is thought to be involved, and new risk factors include inflammation and clonal hematopoiesis (1).

The carotid intima–media thickness test (CIMT) is a test used to determine the degree of atherosclerotic vascular disease in the carotid arteries. The test examines the thickness of the carotid artery’s inner two layers, the intima and the media, and warns doctors to any thickening while patients are still asymptomatic.

The neutrophil–lymphocyte ratio (NLR) is the ratio between the neutrophil and lymphocyte counts measured in blood. Neutrophils contribute to innate and lymphocytes to the adaptive immune response in the body. It is an emerging biomarker with applications in diseases such as cancer, sepsis, bacteremia, COVID-19 (2).

NLR is a widely available, easily derived, and reproducible marker of inflammation (3).

NLR has been shown to predict cardiovascular events in several studies (4).

Although C-reactive protein, interleukin-6, and tumor necrosis factor-alpha are known to predict carotid atherosclerosis, obtaining them in clinical practice is problematic.

Diabetes patients and those with prediabetes have a higher risk of death from CVD, coronary heart disease, and stroke compared to those who do not have diabetes (5).

Various studies have shown a correlation of CIMT with Cardiovascular disease (6).

This study aims to find a correlation between NLR with CIMT in diabetes patients.

Objective

To study the association between NLR and CIMT in diabetes patients.

Materials and methods

This is a hospital-based analytical cross-sectional study conducted in the Department of Internal Medicine, Sree Gokulam Medical College and Research Foundation, Trivandrum. It was conducted over a period of 2 weeks (1 August 2023–14 August 2023).

The patients were known cases of type-2 diabetes mellitus who were more than 18 years of age, who had blood investigations done, who underwent a carotid Doppler and who gave consent to participate in the study.

The following categories of patients were excluded: Acute stroke, myocardial infarction, any acute or chronic infection or inflammatory condition in the last 2 weeks, hematological disease, smokers, those with cancer, and taking steroids. A total of 25 patients who matched the inclusion and exclusion criteria were selected by consecutive random sampling from 1 August 2023 to 14 August 2023 after the institutional ethics committee’s clearance was obtained. Informed written consent was taken from the participants and the study was started. The study was cross-sectional in design. The 25 adults included in the study were in the age group of 44–86 years and had undergone carotid Doppler as part of screening along with blood investigations [complete blood count (CBC)]. A questionnaire was used to get patient details such as current and past medical history, smoking history, and laboratory investigations. Patients underwent clinical examination. Carotid intima–media thickness was measured at the common carotid artery using B-mode ultrasound. Patients were divided into two groups, one with thick CIMT ≥ 1 mm and one with normal CIMT < 1 mm; 11 patients had thick CIMT and 14 normal CIMT in this study Figure 1. CBC was done on an automatic hematology analyzer, from which NLR was obtained by dividing the absolute neutrophil count (ANC) and absolute lymphocyte count (ALC). The collected data were entered into SPSS statistical data package. Quantitative data were expressed as mean ± SD and qualitative data were expressed as percentage.

FIGURE 1
www.bohrpub.com

Figure 1. Distribution of cases according to Carotid intima media thickness.

Discussion

In this study, 25 participants were enrolled, of which 7 were female and 18 were male (Table 1). The baseline characteristics are represented in Table 3. The participants were divided into two groups one with normal CIMT (<1 mm) and another with high CIMT (≥1 mm).

TABLE 1
www.bohrpub.com

Table 1. Descriptive statistics.

TABLE 2
www.bohrpub.com

Table 2. Correlation between NLR, TC, age with carotid intima thickness.

TABLE 3
www.bohrpub.com

Table 3. Comparison of demographic and hematological parameters with CIMT.

In this study, no statistically significant correlation between total leucocyte count and CIMT was found (Table 2). There was no statistically significant difference in mean neutrophil or mean lymphocyte count between the two groups (Table 4).

TABLE 4
www.bohrpub.com

Table 4. Comparison of hematological parameters with CIMT.

FIGURE 2
www.bohrpub.com

Figure 2. Correlation between NLR and CIMT.

However, NLR was higher in patients with thick CIMT, which was statistically significant. In this study, a strong correlation was noticed between NLR and CIMT in diabetes patients (Table 2).

This is similar to the result obtained in the study by Mohammad et al. (7), Gu et al. (8) which showed NLR has a strong association with CIMT in diabetes.

Many epidemiological studies have found that CIMT is a measure of subclinical atherosclerosis that is linked to traditional CVD risk factors (911).

Thus, high NLR correlates with high CIMT and risk of atherosclerotic events in type 2 diabetes.

Conclusion

In this study mean NLR was higher in diabetes patients with higher CIMT compared to those with normal CIMT. This was found to be statistically significant. Hence, NLR can be used to predict atherosclerosis in diabetes patients.

Being cheaper, it can be used to predict adverse atherosclerotic events such as cerebrovascular accidents and coronary syndromes in diabetes and the progression of these events in the same.

Author contributions

Both authors have made a substantial, direct, and intellectual contribution to this work and approved it for publication.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Acknowledgments

The authors express their sincere gratitude to SR, Professor, Department of General Medicine who was a constant of guidance and encouragement, and Dr. Parvathy P, Senior Resident, Department of Radiodiagnosis for the CIMT measurements.

References

1. Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS. Atherosclerosis. Nat Rev Dis Primers. (2019) 5:56.

Google Scholar

2. Zahorec R. Neutrophil-to-lymphocyte ratio, past, present and future perspectives. Bratislava Med J. (2021) 122:474–88. doi: 10.4149/BLL_2021_078

CrossRef Full Text | Google Scholar

3. Balta S, Celik T, Mikhailidis DP, Ozturk C, Demirkol S, Aparci M, et al. The relation between atherosclerosis and the neutrophil-lymphocyte ratio. Clin Appl Thromb Hemost. (2016) 22:405–11. doi: 10.1177/1076029615569568

CrossRef Full Text | Google Scholar

4. Angkananard T, Anothaisintawee T, McEvoy M, Attia J, Thakkinstian A. Neutrophil lymphocyte ratio and cardiovascular disease risk: A systematic review and meta-analysis. Biomed Res Int. (2018) 2018:2703518. doi: 10.1155/2018/2703518

CrossRef Full Text | Google Scholar

5. Fuller JH, Shipley MJ, Rose G, Jarrett RJ, Keen H. Mortality from coronary heart disease and stroke in relation to degree of glycaemia: the Whitehall study. Br Med J (Clin Res Ed). (1983) 287:867–70. doi: 10.1136/bmj.287.6396.867

CrossRef Full Text | Google Scholar

6. Simon A, Megnien JL, Chironi G. The value of carotid intima-media thickness in predicting cardiovascular risk. Arterioscler Thromb Vasc Biol. (2010) 30:182–5.

Google Scholar

7. Ezzate S, Mohammada WH, Ahmadb AB, Al-Maghrabyb MH, Abdelrhmanc MZ. Is the neutrophil-lymphocyte ratio a new biomarker for type 2 diabetes macrovascular and microvascular complications. Egypt J Int Med. (2019) 31:1–7.

Google Scholar

8. Gu G, Guo J, Zhuo N, Yang L. Correlation between neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, mean platelet volume, and early atherosclerosis in newly diagnosed type 2 diabetes mellitus. J Chinese Phys. (2018) 12:861–4.

Google Scholar

9. Onut R, Balanescu S, Constantinescu D, Calmac L, Marinescu M, Dorobantu M. Imaging atherosclerosis by carotid intima-media thickness in vivo: How to, where and in whom? Maedica (Bucur). (2012) 7:153–62.

Google Scholar

10. Bauer M, Caviezel S, Teynor A, Erbel R, Mahabadi AA, Schmidt-Trucksäss A. Carotid intima-media thickness as a biomarker of subclinical atherosclerosis. Swiss Med Wkly. (2012) 142:w13705. doi: 10.4414/smw.2012.13705

CrossRef Full Text | Google Scholar

11. Willeit P, Tschiderer L, Allara E, Reuber K, Seekircher L, Gao L. Carotid intima-media thickness progression as surrogate marker for cardiovascular risk: Meta-analysis of 119 clinical trials involving 100 667 patients. Circulation. (2020) 142:621–6. doi: 10.1161/CIRCULATIONAHA.120.046361

CrossRef Full Text | Google Scholar