Relationship between platelet-lymphocyte ratio and carotid atherosclerosis in middle-aged and elderly patients with type 2 diabetes mellitus

Jing Hu ,Kun Zhao ,Shao-Ling Yang ,Feng-Ling Wang ,Qiao-Na Zhang ,Lin-Yan Fan ,Hong-Zhen Zhang,Wen-Hua Lin,Jia-Hong Gu

1.Anhui University of Science and Technology,Huainan 232000,China

2.Shanghai Eighth People's Hospital Ultrasonics,Shanghai 200030,China

Keywords:Type 2 diabetes mellitus Middle-aged and elderly PLR Carotid artery intima-media thickness Atherosclerotic plaque

ABSTRACT Objective:To investigate the relationship between platelet-lymphocyte ratio (PLR) and carotid atherosclerosis (CAS) in middle-aged and elderly patients with T2DM.Methods:A total of 420 middle-aged and elderly patients with T2DM who were hospitalized in the Endocrinology Department of our hospital from September 2018 to September 2020 and were examined by ultrasound were selected as the subjects.The carotid artery intima-media thickness (CIMT)was examined by color Doppler ultrasonography,including normal CIMT group (n=111),CIMT thickening group (n=103) and CAS plaque group (n=206).The differences of serum PLR levels among the three groups were compared.Multivariate Logistic regression was used to analyze the relationship between PLR and CAS plaque formation.The receiver operating curve (ROC) was used to evaluate the value of multivariate Logistic regression model (Logit P) in the diagnosis of CAS lesions.Results:The mean value of PLR in CAS plaque group(127.86±48.54) was significantly higher than that in CIMT normal group (109.15±48.35).Multivariate Logistic regression analysis showed that after adjusting for other confounding factors,the increase of PLR was an independent risk factor for the occurrence of CAS plaque.ROC showed that the efficacy of multivariate Logit P model in the diagnosis of CAS plaque was (AUC=0.807,95%CI=0.759-0.858).Conclusions:PLR is one of the important risk factors for the occurrence of CAS lesions.At the same time,the multivariate Logistic regression model established in this study has clinical reference value in predicting CAS lesions in middle-aged and elderly patients with T2DM.

1.Introduction

According to the International Diabetes Federation (IDF),human beings are facing a global trend of diabetes epidemic[1].Diabetes has become a non-infectious disease that seriously threatens human health[2].The prevention and control situation of diabetes is not optimistic in both developed and developing countries[3].Patients with diabetes are prone to develop large vascular lesions,of which carotid atherosclerosis (CAS) has a high incidence of complications,rapid development of the disease and high severity,which is one of the main causes of death and disability of patients[4].Diabetes is a chronic inflammatory disease,and platelet-to-lymphocyte ratio(PLR),as a new inflammatory marker,is closely related to diabetic nephropathy and cardiovascular and cerebrovascular diseases[5,6].Carotid atherosclerosis is characterized by carotid intima-media thickening and the formation of atherosclerotic plaques,especially in middle-aged and elderly T2DM patients with high incidence of carotid atherosclerosis.This study investigated the relationship between PLR and atherosclerotic lesions in middle-aged and elderly T2DM patients,providing evidence for the early prevention of atherosclerosis complications in T2DM patients.

2.Data and methods

2.1 Research object

A total of 420 middle-aged and elderly T2DM patients who were hospitalized in the Department of Endocrinology,Fengxian District Central Hospital affiliated to Anhui University of Technology from September 2018 to September 2020 and examined by ultrasound were selected as subjects,including 249 males (59.3%) and 171 females (40.7%),aged from 40 to 88 years old,with an average age of (62.60±11.34) years.All the subjects met the T2DM diagnostic criteria of the Chinese guidelines for the prevention and treatment of type 2 diabetes (2013 edition)[7].There were 111cases with normal CIMT (CIMT normal group),103cases with CIMT thickening(CIMT thickening group) and 206cases with carotid atherosclerotic plaque (CAS plaque group).Exclusion criteria:(1) patients with lifethreatening acute metabolic disorders at admission,patients with acute complications of diabetes (2) patients with symptoms such as acute and chronic infection (3) patients with severe heart,liver and other organ dysfunction (4) patients with tumors,autoimmune diseases,allergic diseases and blood system diseases.All patients signed the informed consent form.

2.2 Experimental equipment and method

2.2.1 Ultrasonic examination

Using Phillips EPIQ 7c color Doppler ultrasound diagnostic instrument,equipped with L12-5 probe with a frequency of 5-12MHz,the carotid artery was examined by doctors who had been engaged in ultrasound for more than ten years.Before the examination,the subjects at least rest 15min,remove the pillow to take the supine position,and tilt the head back to the opposite side of the examination to fully expose the anterior part of the neck.The intima-media thickness of bilateral common carotid arteries was measured and atherosclerotic plaques were recorded.CIMT thickening criteria refer to the guidelines for carotid ultrasound examination[8]CIMT＜1.0mm is regarded as intima-media normal,CIMT≥1.0mm as intima-media thickening,and local common carotid artery intima-media thickness≥1.5mm is defined as plaque.

2.2.2 Collection of clinical observation indicators

The resident workstation collected general data such as sex,age,height,weight,course of diabetes,course of hypertension,systolic blood pressure (SBP),diastolic blood pressure (DBP),drinking history,smoking history and so on.Body mass index (body mass index,BMI)=weight (kg)/ height 2 (m2) and pulse pressure difference (PP)=SBP-DBP were calculated.Fasting C peptide(F-CP) and cystatin C (Cys-C) were detected by Roche E602 analyzer,fasting blood glucose (FBG),triglyceride (TG),total cholesterol (TC),high density lipoprotein cholesterol (HDL-C),low density lipoprotein cholesterol (LDL-C),serum uric acid (UA) and glycosylated albumin (GA) were detected by AU5800-automatic biochemical analyzer.Glycosylated hemoglobin (HbAlc) was measured by high performance liquid chromatography (HPLC).Hypersensitive C-reactive protein (hs-CRP) and the ratio of platelet to lymphocyte ratio (PLR) were detected by XN-10 automatic module hematology analyzer.

2.3 Statistical treatment

SPSS23.0 statistical software was used for analysis,The measurement data conforming to normal distribution were expressed as(),and independent sample T-test was used;The measurement data of non-normal distribution were represented by median(interquartile spacing)[M(P25,P75)].And the counting data were represented by rate,using chi-square test;One-way ANOVA was used for comparison between groups,and Welch test was used for variance variance analysis.The variables assigned to influencing factors of carotid atherosclerosis in middle-aged and elderly T2DMpatients were analyzed by multi-factor binary Logistic regression,as shown in Table 1.The above statistical analysis was conducted by bilateral test,with test level α=0.05.Receiver Operating curve(ROC) was used to evaluate the effectiveness of PLR and LogitP in diagnosing CAS plaques,andP<0.05 was considered as statistically significant difference.

Table 1Variable assignment of binary Logistic regression analysis for influencing factors of CAS plaque

3.Results

3.1 Comparison of general data of three groups

The age and course of diabetes and hypertension in CIMT group were higher than those in normal CIMT group,and the differences were statistically significant(P＜0.05);The age difference of pulse pressure,proportion of smoking,proportion of alcohol consumption,course of diabetes,course of hypertension,TG,LDL-C,GA,HbA1c,HS-CRP,CYS-c PLR in CAS plaque group were higher than those in CIMT normal group,the difference was statistically significant(P＜0.05 orP＜0.01);The proportion of age smoking and alcohol consumption in CAS plaque group was higher than that in CIMT thickening group(P＜0.05 orP＜0.01);There was no significant difference in BMI,FC and FBG levels among the three groups(allP＞0.05),as shown in Table 2.Images of patients with CIMT thickening examined by color Doppler ultrasound are shown in Figure A.Images of patients with CAS plaques are shown in Figure B,C and D.

Table 2Comparison of general conditions among three groups[,M(P25,P75)n(%)]

Table 2Comparison of general conditions among three groups[,M(P25,P75)n(%)]

CIMT normal group,* P＜0.05,# P＜0.01;CIMT thicken group,△P＜0.05,▲P＜0.01.BMI:body mass index;PP:pulse pressure;FBG:fasting blood glucose;FC:fasting c peptide;TG:triacylglycerol;TC:total cholesterol;HDL-C:high density lipoprotein cholesterol;LDL-C:low density lipoprotein cholesterol;hs-CRP:high sensitivity c reactive protein;GA:glycated albumin;HbA1c:glycosylated hemoglobin;Cys-C.cystatin C;PLR:platelet to lymphocyte ratio.

Table 3Multivariate Logistic regression analysis of influencing factors of CAS plaque in middle-aged and elderly patients with T2DM

Figure 1 Color doppler ultrasonography

3.2 Multivariate

Logistic regression analysis of influencing factors of CAS plaquesin middle-aged and elderly T2DM patients With the occurrence of outcome variable Y1 (CAS plaque) as the dependent variable (0=non-occurrence,1=occurrence) and PLR (continuous variable)as the independent variable,the results of uncorrected Logistic regression model showed that increased PLR was a risk factor for CAS plaque in middle-aged and elderly T2DM patients.Logistic regression results after adjusting for gender,age,body mass index,pulse pressure difference,diabetes course,hypertension course,smoking,alcohol consumption,fasting blood glucose,fasting C-peptide,cystatin C,TG,TC,HDL-C,LDL-C,HbAlc,GA and hypersensitive C-reactive protein showed that,Elevated PLR is a risk factor for CAS plaques in middle-aged and elderly T2DM patients.PLR (PLR classification variable,PLR mean=115,0=PLR＜115 as reference,1=PLR≥115) was incorporated into the multivariate Logistic regression Model (Model 3),which showed that patients with PLR≥115 were 2.678 times more CAS plaques than those with PLR <115 (OR=2.678,95%CI=1.672-4.687,P=0.000),suggesting that elevated PLR is still a risk factor for CAS plaques in middle-aged and elderly T2DM patients.As shown in table 3.

3.3 ROC evaluation of the effectiveness of PLR and LogitP in diagnosing CAS plaques

ROC results showed that The effectiveness of PLR in diagnosing CAS plaques (AUC=0.642,95%CI=0.578-0.707,P=0.000).Multifactor Logit P model was used to diagnose CAS plaque efficiency(AUC=0.807,95%CI=0.759-0.858,P=0.000),as shown in Figure 2.

Figure 2 Evaluation of the effciacy of PLR and LogitP in the diagnosis of CAS plaque by ROC

4.Discussion

With the deepening of the research on diabetes,people have gradually realized that the essence of diabetes is vascular disease.Diabetic vascular disease is the main factor of coronary heart disease,stroke and other cardiovascular and cerebrovascular adverse events in diabetic patients,as well as the main cause of death in diabetic patients,while atherosclerosis is the pathological basis of diabetic macrovascular disease[9].Especially in middle-aged and elderly patients with high incidence of carotid atherosclerosis,finding the risk factors of carotid atherosclerosis in middle-aged and elderly patients with T2DM and early intervention is expected to effectively prevent coronary heart disease,stroke and other cardiovascular and cerebrovascular adverse events as carotid ultrasound examination as a window to evaluate systemic atherosclerosis,can accurately measure CIMT and detect the formation of CAS plaque,which has important clinical significance for the risk assessment and prediction of cardiovascular and cerebrovascular events[10,11].This study mainly investigated the relationship between PLR and carotid atherosclerosis in middle-aged and elderly T2DM patients.The results showed that the mean PLR in CAS plaque group was significantly higher than that in CIMT normal group.Multivariate Logistic regression analysis showed that elevated PLR was an independent risk factor for CAS plaque formation in T2DM patients,which was consistent with the results of Dong Rongjing et al[12].Monitoring the changes of PLR value in T2DM patients may be an effective method for early prevention of atherosclerosis complications in T2DM patients.

Diabetes is a chronic inflammatory disease and chronic inflammation is involved in the whole process of atherosclerosis[13].Studies have shown that PLR,as a new predictor of inflammation,can more accurately and sensitively reflect the degree of inflammation in the body without being affected by confounding factors such as infection stress when chronic inflammatory autoimmune diseases occur[14].Platelet-induced inflammation plays an important role in the formation of atherosclerosis in diabetic patients.Mitotic substances and inflammatory mediators released by activated platelets can promote the recruitment of more white blood cells and platelets to the inflammatory site.As the total number of lymphocytes in T2DM patients with atherosclerosis decreases,the body's anti-inflammatory ability decreases,and lowgrade inflammation will persist[15].Studies suggest that elevated platelet count and decreased lymphocyte count may be involved in the development and progression of atherosclerosis[16].Therefore,the platelet to lymphocyte ratio (PLR) may be an early predictor of the risk of atherosclerosis.

Research Reports at home and abroad[17,18],PLR was positively correlated with the severity of coronary atherosclerosis.The more severe coronary atherosclerosis was,the higher PLR value was.By analyzing the correlation between PLR and CAS severity,Varim et al[19] found that PLR value can be used to predict severe carotid artery stenosis.Chen Yingcong et al [20] found that PLR is a marker for predicting the severity of carotid atherosclerosis in young patients with newly diagnosed T2DM.This study found that PLR is one of the important risk factors for the occurrence of CAS lesions,and the multi-factor Logistic regression model established in this study has clinical reference value in predicting CAS lesions in middleaged and elderly T2DM patients.This is consistent with the research results of Wang Yan and others[21].After adjusting for confounding factors such as gender,age,body mass index,pulse pressure difference,course of diabetes,course of hypertension,smoking,alcohol consumption,fasting blood glucose,fasting C-peptide,cystatin C,TG,TC,HDL-C,LDL-C,HbAlc,GA,and hypersensitive C-reactive protein,The results of Logistic regression model with PLR as continuous variable showed that increased PLR was a risk factor for CAS plaques in middle-aged and elderly T2DM patients.The results of multivariate Logistic regression model (Model 3) with PLR as a taxonomic variable (0=PLR <115,1=PLR≥115) showed that the number of patients with PLR≥115 was 2.678 times higher than that of patients with PLR <115(OR=2.678,95%CI=1.672-4.687),suggesting that elevated PLR is still a risk factor for CAS plaque in middle-aged and elderly patients with T2DM.ROC curve results further showed that PLR was effective in diagnosing CAS plaques (AUC=0.642,95%CI=0.578-0.707,P=0.000).The multifactor Logit P model was effective in the diagnosis of CAS plaques(AUC=0.807,95%CI=0.759-0.858,P=0.000),indicating that PLR was considered as a simple clinical indicator for the diagnosis of CAS plaques in middle-aged and elderly T2DM patients

This study also has limitations:First,this study is a retrospective cross-sectional design,failed to longitudinally observe the changes of patients' PLR indicators,and can not clarify the causal relationship between PLR and CAS lesions in middle-aged and elderly T2DM patients;Secondly,this study does not include T2DM patients under 40 years old,which may make the results biased.Therefore,more large-sample,multicenter prospective clinical studies are needed in the future to further confirm the role of PLR in the formation of CAS plaques in patients with T2DM.

In conclusion,this study found that elevated PLR is a risk factor for CAS plaques in middle-aged and elderly T2DM patients.PLR indicators are easy to obtain and low in price,suggesting that clinicians should further conduct vascular ultrasound examination for middle-aged and elderly T2DM patients with PLR≥115,and early prevention and screening of carotid intimedia lesions is the key to improve the prognosis of diabetic patients.There is no conflict of interest in this article.

Author's contribution

Hu Jing conceives articles and designs,writes papers and makes statistical analysis;Yang Shaoling analyzed and revised the feasibility of the article.Zhao Kun for data collection and analysis;Wang Fengling,Zhang Qiaona,Fan Linyan,Zhang Hongzhen,Lin Wenhua and Gu Jiahong collected data.