Effect Of SGLT2-i And GLP-1Ra On Peripheral Blood NLR And NGAL In Patients With Coronary Artery Disease Combined With Diabetes Mellitus

Background:Coronary heart disease(CHD)is a common cardiovascular disease with a high morbidity and mortality rate worldwide.It has long been widely accepted that coronary heart disease is caused by the narrowing and blockage of blood vessels due to atherosclerosis,and therefore the focus of treatment has been on revascularisation and thrombolysis.However,in recent years,a growing number of studies have shown that chronic inflammation also plays an important role in the development and progression of coronary heart disease.In coronary artery disease,chronic inflammation is mainly manifested by inflammatory cell infiltration in the atherosclerotic plaque,release of inflammatory factors and damage to the endothelium.These inflammatory responses lead to reduced plaque stability and ease of rupture to form thrombi,leading to serious complications such as acute coronary syndromes.As the fields of molecular biology and immunology continue to develop.Researchers have found that many inflammatory mediators such as C-reactive protein(CRP),white blood cell counts,and inflammatory factors are strongly associated with the development and severity of coronary heart disease.In conclusion,advances in the study of chronic inflammation in coronary heart disease are gradually attracting widespread attention and are important for gaining insight into the pathogenesis of coronary heart disease as well as for developing new preventive and therapeutic strategies.Objective:Chronic inflammation plays a key role in the pathogenesis of coronary heart disease and diabetes mellitus.This study focuses on the relationship among neutrophil-lymphocyte ratio(NLR),neutrophil gelatinase-associated lipocalin(NGAL)and coronary heart disease combined with diabetes mellitus.In addition,the relationship between the use of sodium dependent glucose transporters 2 inhibitors(SGLT2-i)and glucagon-like peptide-1 agonists(GLP-1Ra)on these two indicators.Methods:The subjects were those who attended the Department of Cardiovascular Medicine、Endocrinology and health check-ups at Shandong Provincial Hospital from August 2021 to August 2022.The healthy check-up patients were used as the control group of 70 cases,those diagnosed with type 2 diabetes without coronary heart disease as the diabetic group of 69 cases,those diagnosed with coronary heart disease without diabetes as the coronary heart disease group of 136 cases,and those diagnosed with coronary heart disease combined with diabetes as the group of 281 cases,a total of 556 cases.The coronary heart disease combined with diabetes group was later divided into groups according to the diagnosis of coronary heart disease,glycated haemoglobin quartiles and the presence or absence of SGLT2-i and GLP-1Ra medication during the observation and treatment period,and clinical and laboratory related data were collected according to the inclusion and exclusion criteria.SPSS 26.0 was applied for statistical analysis of the collected data.T-test,one-way ANOVA and rank sum test were used for continuous variables,and chi-square test was used for categorical variables.Logistic regression was used for univariate and multifactorial analyses,and ROC curves were plotted to assess the predictive value of NGAL and NLR for coronary artery disease combined with diabetic disease.All differences were considered statistically significant at P<0.05.Results:1.There was a significant difference(P<0.05)in the difference in NLR levels between any two of the four groups,with lower levels in the control group,followed by the diabetic group,the coronary heart disease group and the highest levels in the diabetic combined with coronary heart disease group.There was no significant difference in NGAL levels between the control group and the diabetic group(P=0.37),but they were significantly lower than those in the coronary artery disease group and the coronary artery disease combined with diabetes group(P<0.05),and the NGAL levels in the coronary artery disease combined with diabetes group were significantly higher than those in the coronary artery disease group(P<0.05).2.In grouping the coronary artery disease combined with diabetes group according to their coronary angiographic assessment records with clinical coronary diagnosis,there was a statistically significant(P<0.01)comparison of NLR values between any two of the three groups,with lower levels in the stable angina group,followed by the unstable angina group,and the highest levels in the myocardial infarction group.There was no significant difference in NGAL when comparing the unstable angina group with the myocardial infarction group(P=0.465),but both groups had significantly higher levels of NGAL than the stable angina group(P<0.01).3.When NLR and NGAL are analysed as predictors of coronary artery disease combined with type 2 diabetes,the area under the ROC curve for NLR,NGAL and their combined predictive probability curve as a diagnosis is 0.820,0.797 and 0.891 respectively(P<0.01).The sensitivity and specificity of the diagnosis are 0.491,0.698,0.822 and 0.986,0.771,0.8 when the optimal critical values of NLR,NGAL and combined predictive probability curves are 2.792,52.95 and 0.742,respectively.4.Patients with coronary heart disease and diabetes are divided into SGLT2-i group,GLP-1Ra group and basal treatment group according to their clinical data.During the observation period,NLR levels in the SGLT2-i,GLP-1Ra and basal treatment groups are significantly reduced(p<0.05),while the reduction in the SGLT2i and GLP-1Ra groups is more significant.There is no significant change in NGAL levels in the basic treatment group,but the difference between NGAL levels in the SGLT2-i and GLP-1Ra groups before and after treatment is statistically significant(P<0.05),the reduction level in the SGLT2-i group is more significant.5.The coronary heart disease combined with diabetes group is divided into four groups according to HbAlc quartile levels for comparison,and the results show that there is no significant difference in NLR and NGAL between the groups for comparison(P>0.05).6.Multi-factor logistic regression analysis showed that NGAL,NLR,HbA1c and NT-ProBNP were significant risk factors for coronary artery disease combined with type 2 diabetes.Conclusion:NLR and NGAL as inflammatory biomarkers can effectively reflect the severity of coronary artery disease in patients with coronary artery disease combined with type 2 diabetes,but not the level of glycemic control in patients.NGAL,NLR,HbA1c and NT-ProBNP are important risk factors for the disease.The use of SGLT2-i and GLP-1Ra drug therapy can effectively reduce circulating levels of NLR and NGAL and delay disease progression.