Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease

doi:10.1016/j.diabet.2015.01.001

Diabetes & Metabolism

Volume 41, Issue 4, September 2015, Pages 304-311

https://doi.org/10.1016/j.diabet.2015.01.001 Get rights and content

Abstract

Background

Coronary artery disease (CAD) is the leading cause of mortality among diabetic patients, and the neutrophil-to-lymphocyte ratio (NLR) has recently emerged from among inflammatory parameters as a potential indicator of vascular complications and poorer outcome in patients with diabetes. This study aimed to evaluate: 1) the impact of diabetes on NLR; and 2) the role of NLR on the extent of CAD among diabetic patients undergoing coronary angiography.

Methods

Consecutive patients undergoing coronary angiography were included. Diabetic status and main chemistry parameters were assessed at the time of admission. Significant CAD was defined as at least one vessel with stenosis > 50%, while severe CAD was left main and/or three-vessel disease, as evaluated by quantitative coronary angiography (QCA).

Results

Diabetes was observed in 1377 of 3756 patients (36.7%); they were older, and displayed higher-risk cardiovascular profile and more complex CAD. Diabetic status was also associated with a significant increase in NLR (P = 0.004). Among diabetics, higher NLR tertile values were related to ageing (P < 0.001), dyslipidaemia (P < 0.001), renal failure (P < 0.001), body mass index (P < 0.001), previous percutaneous coronary revascularization (P = 0.004) and cerebrovascular events (P = 0.003), acute presentation (P < 0.001), treatment at admission with beta-blockers/statins/ASA (all P < 0.001), diuretics (P = 0.01) or clopidogrel (P = 0.04), platelet count (P = 0.03), white blood cell count, creatinine, glycaemia and C-reactive protein (P < 0.001), and inversely related to haemoglobin, triglyceride levels (P < 0.001) and smoking (P = 0.03). NLR was associated with multivessel disease (P < 0.001), degree of stenosis (P = 0.01), type C lesions (P = 0.02), coronary calcifications and intracoronary thrombus (P < 0.001), but inversely with in-stent restenosis (P = 0.003) and TIMI flow grade (P = 0.02). Also, NLR was directly related to CAD prevalence (P < 0.001; adjusted OR [95% CI]: 1.62 [1.27–2.07], P < 0.001) and CAD severity (P < 0.001; adjusted OR [95% CI]: 1.19 [1.00–1.43], P = 0.05).

Conclusion

NLR is increased among diabetic patients and, in such patients, is independently associated with the prevalence and severity of CAD. Further studies are now needed to confirm present results and to evaluate the underlying pathophysiological mechanisms behind our findings.

Introduction

Various efforts have been made in the last few years to deal with the diabetes ‘epidemic’, and to treat and prevent coronary artery disease (CAD) among these patients [1], [2]. However, despite the introduction of more potent antiplatelet agents and new techniques for percutaneous revascularization, the results have, so far, proven unsatisfactory, with diabetic patients still experiencing a higher rate of cardiovascular events and poorer outcomes, especially in the setting of acute coronary syndromes [3], [4], [5]. For this reason, considerable attention has been directed towards the identification of new markers of cardiovascular risk in such patients [6], [7].

Chronic inflammation plays a central role in the development and progression of diabetes, and in the pathogenesis of its complications [8]. In particular, white blood cells are leading actors in the processes of vascular wall degeneration in patients with diabetes, being involved in the evolution of atherosclerosis and in the destabilization and rupture of plaque, resulting in thrombotic events [9], [10].

Moreover, growing interest has been directed towards leukocyte subtypes and especially the neutrophil-to-lymphocyte ratio (NLR), an inexpensive and convenient way to identify inflammatory parameters, and potentially an even more accurate indicator of cardiovascular risk than absolute blood cell counts [11], [12].

However, until now, few reports have evaluated the relationship between diabetes and NLR and its impact on CAD in diabetic patients, this was the aim of the present study.

Section snippets

Methods

Our study population comprised consecutive patients undergoing coronary angiography between April 2007 and December 2013 at the Ospedale Maggiore della Carità in Novara, Italy. Informed consent was obtained from all patients before angiography, and the study protocol was approved by the Local Ethics Committee. All demographic and clinical data were prospectively collected in a dedicated database. Hypertension was defined as a systolic blood pressure > 140 mmHg and/or diastolic blood

Results

The study population included 3756 subjects undergoing coronary angiography. Among them, 1377 (36.7%) had diabetes. Table 1 shows the main clinical and demographic features of the study population according to diabetic status, which was related to ageing, hypertension, higher body mass index (BMI) scores, dyslipidaemia, renal failure, history of myocardial infarction, percutaneous and surgical coronary revascularization, cerebrovascular accidents, and treatment at admission with

Discussion

The present study represents the largest cohort study thus far to evaluate the impact of diabetes on NLR and its relationship to angiographically proven CAD. The main finding was that diabetic patients have higher NLR values, and that this NLR increase is an independent predictor of the extent and severity of coronary lesions in diabetic patients.

Cardiovascular disease still represents the leading cause of mortality in people with diabetes, with abnormalities of glucose metabolism being

Conclusion

The NLR is increased in diabetes patients and, in such patients, this increase is independently associated with both the prevalence and severity of CAD. Further studies are now needed to evaluate the underlying pathophysiological mechanism(s) driving our present findings.

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

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The ideal biomarker would be measurable in the blood using a simple and widely available test and would predict prognosis and potentially response to therapy. The Neutrophil-Lymphocyte Ratio (NLR) is easily and inexpensively measured from a complete blood count (CBC), and has indicated severity in studies of diabetes,3,4 cardiovascular5 and renal disease,6 COPD,3 malignancy7 and COVID-19.8,9 NLR can also predict development and severity of lung fibrosis in patients with systemic sclerosis,10 dermatomyositis/polymyositis11 and a composite endpoint of ‘absolute decline in 6MWD ≥50 m or death’ at 12 months in IPF.12
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We demonstrated that lower levels of vitamin D are associated with a more atherogenic lipid profile, being similarly observed in statin treated and naïve patients and potentially contributing to increase their cardiovascular risk. Coronary artery disease still represents the leading cause of mortality in developed countries, and large efforts have been focused in the last decades on the identification of new risk factors for primary and secondary prevention [16,17]. Vitamin D (25(OH)D) is a hormonal precursor, whose hydroxylated form, calcitriol (1,25(OH)2D) is the regulator of several processes, mainly calcium and bone homeostasis but also including the modulation of the immune system, metabolism and cardiovascular health [5,18].
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Original articleImpact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease

Abstract

Background

Methods

Results

Conclusion

Introduction

Section snippets

Methods

Results

Discussion

Conclusion

Disclosure of interest

Diabetes Res Clin Pract

Atherosclerosis

Am J Cardiol

Diabetes Res Clin Pract

Am J Cardiol

Nutr Metab Cardiovasc Dis

Atherosclerosis

Diabetes Res Clin Pract

Diabetes Res Clin Pract

Clin Chim Acta

Am J Cardiol

Diabetes prevention and treatment strategies: are we doing enough?

Diabetes Care

Impact of diabetes on long-term outcome after primary angioplasty: insights from the DESERT cooperation

Diabetes Care

The association of diabetes mellitus with clinical outcomes after coronary stenting: a meta-analysis

PLoS One

Low-grade chronic inflammation in the relationship between insulin sensitivity and cardiovascular disease (RISC) population: associations with insulin resistance and cardiometabolic risk profile

Diabetes Care

Neutrophilic granulocytes promiscuous accelerators of atherosclerosis

Thromb Haemost

Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis

Circ Res

Neutrophil to lymphocyte ratio predicts short and long term mortality following revascularization therapy for ST elevation myocardial infarction

Cardiol J

Diagnosis and classification of diabetes mellitus

Diabetes Care

Eur Heart J

Original article
Impact of diabetes on neutrophil-to-lymphocyte ratio and its relationship to coronary artery disease