Association Between Human Cartilage Glycoprotein 39 And Cardiovascular Dysfunction In Early Essential Hypertension

BackgroundEssential hypertension is a clinical syndrome which is characterized by high systemic circulation arterial pressure.It can be caused by a certain genetic background and a variety of acquired environmental factors.A long-term high blood pressure can damage multiple target organs such as heart,brain and kidney,which can lead to organ failure finally.And also it can affect the patient’s life span and life quality.The effect of high blood pressure on the cardiovascular system is mainly manifested in hypertrophy of left ventricle and atherosclerotic plaque.However,prior to the above-mentioned damage,the cardiac diastolic dysfunction and vascular endothelial dysfunction have already occurred.Regrettably,the recognition of its importance is not enough.So early identification has important implications in the abnormalities of cardiovascular function caused by essential hypertension,which can achieve early detection,early intervention and early benefit.Human cartilage glycoprotein-39,also called YKL-40,is a biomarker of acute and chronic inflammation,which participates in the extracellular matrix remodeling and angiogenesis.YKL-40 plays an important role in endothelial dysfunction,tissue fibrosis and atherosclerosis,and it is a potential biomarker for cardiovascular disease.It can determine the prognosis of cardiovascular disease.It was found that YKL-40 had a clear increase in the patients with essential hypertension,and YKL-40 was associated with atherosclerosis and reconfiguration of the left ventricle in the patients.A large case-control study showed that YKL-40 was associated with the incidence of hypertension.However,there are few studies about the cardiovascular system dysfunction in the early stage of hypertension.ObjectiveThis study examined the YKL-40 concentration in serum of patients with early onset of essential hypertension and measured the left ventricular diastolic function and vascular endothelium diastolic function by ultrasound.We want to explore the relationship between YKL-40 and early cardiovascular dysfunction in patients with essential hypertension.Methods1.Study populations and groupsThis study includes 60 patients(female 27,male 33)with essential hypertension.All cases were recruited from out-patient and ward,the Shandong University Second Hospital,between March 2017 and December 2017.According to the Chinese guidelines for the management of hypertension in 2010,the diagnostic criteria is the systolic blood pressure≥140mmHg and/or the diastolic blood pressure is>90mmHg.And the exclusion criteria is:secondary hypertension,heart disease,kidney disease,metabolic disease,autoimmune disease,severe infection,malignancy,etc.At the same time,50 adults(female 22,male 28)from the physical examination center were enrolled in the healthy control group.Their physical indicators were normal and the written informed consent was obtained from all participants.All the subjects were given detailed information about past medical history,as well as drinking and smoking history.All the subjects were taken comprehensive physical examination and recorded the height,weight,blood pressure etc.Body mass index(BMI)and surface area(BSA)were calculated by the formula:BMI=weight/height2(kg/m2),BSA(m2)=0.0061 x height(cm)+0.0128xweight(kg)-0.1529.2.The determination of various biochemical indexesSubjects were drawn venous blood in the morning after fasting for 6 hours.Fasting blood glucose(FBG),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),high density lipoprotein cholesterol(HDL-C),creatinine(Cr),urea nitrogen(BUN)were tested by an automatic biochemical analyzer in the medical laboratory department.3.Ultrasonic measurementLeft ventricular diastolic internal diameter(LVDd),left ventricular interventricular septal thickness(VST),posterior wall thickness of left ventricle(PWT),and left atrial volume(LAV)were measured by the 2D echocardiography.The peak early diastolic velocity(E),the late diastolic velocity(A),and the ratio of E to A(E/A)were measured by pulse doppler(PW).The peak early diastolic motion velocity(E’)of the septum walls of the mitral annulus were measured by tissue doppler(TDI).The ratio of E to E’(E/E’)was measured.Left atrial volume index(LAVI)was calculate by the formula:LAVI=LAV/BSA(mL/m2).The flow-mediated vasodilation(FMD)in brachial artery and Intima-media thickness(IMT)in carotid artery were measured by vascular ultrasound.4.The determination of serum YKL-40All the subjects were taken venous blood samples in the morning after fasting for 6 hours.The blood samples were centrifuged and placed in a sterile EP tube.Then place them in the refrigerator at-80 degrees.Serum concentration of YKL-40 were determined by enzyme-linked immunosorbent assay(ELISA)in the central laboratory.5.Statistical analysisAll data were analyzed by IBM SPSS Statistics 20.0 software.Before the analysis,all data were tested for normality.Normal distribution data expressed in mean±standard deviation.We used t-test to compare the mean values between two groups.Non-normal groups expressed by median(25%quantile,75%quantile).The rank and inspection test was used to compare the mean values between the two non-normal groups.Pearson correlation analysis was used to analyze the correlation between two groups.Both test models were tested with bilateral test,and P<0.05 was considered statistically significant.Results1.There was no significant difference between the essential hypertension group and the healthy control group in age,gender,height,TG,BUN,Cr(P>0.05).There was statistically significant between the two groups in weight,BMI,FBG,TC,LDL-C,HDL-C(P<0.05).2.YKL-40 was increased significantly in essential hypertension group compared with the control group(P<0.05).3.There was no significant difference between the two groups in the left ventricular internal diameter(LVDd),inter ventricular septal thickness(VST)and posterior wall of ventricle thickness(PWT)(P>0.05).The ratio of E to A(E/A)were lower than the normal control group.The ratio of E to E’(E/E’),the left atrial volume(LAV)and the left atrial volume index(LVAI)were higher than the normal control group,the difference was statistically significant(P<0.05).4.The FMD was markedly impaired in essential hypertensive subjects compared to normal controls.5.YKL-40 was positively correlated with SBP,DBP,E/E’,LAV,LVAI,IMT,while negatively correlated with E/A,FMD by Pearson correlation analysis.Conclusion1.The levels of YKL-40 were elevated in essential hypertension patients.YKL-40 maybe involved in the development of essential hypertension.2.1n the early stage of patients with essential hypertension,vascular endothelial dysfunction and left ventricular diastolic dysfunction have occurred.3.YKL-40 was associated with endothelial dysfunction and left ventricular diastolic dysfunction in patients with early stage of essential hypertension.YKL-40 has a certain predictive value for early cardiovascular dysfunction in patients with essential hypertension.