The Correlation Of Serum Secreted Frizzled-related Protein 5 Level With Severity Of Coronary Artery Lesion

Objective: Secreted frizzled-related protein 5(SFPR5) is regarded as a novel adipokine which is associated with anti-inflammatory, anti-atherosclerosis and insulin resistance. Inflammation plays a crucial role in atherosclerosis which is considered as the mechanism of coronary artery disease. In our study, we measured the level of Secreted frizzled-related protein 5(SFRP5) and comprehensive quantified evaluation of extent and severity of coronary artery lesion through SYNTAX score which is according to the result of coronary angiography. We aimed to investigate the Correlation of serum secreted frizzled-related protein 5 level with severity of coronary artery lesion,thus for disease evaluation, therapeutic treatment assessment and prognosis provide theoretical foundation.Methods: 163 patients who underwent the coronary angiography(CAG) were consecutively enrolled in the cardiovascular department of Second Affiliated Hospital of He bei Medical University from June 2014 to Dec 2014. Patients with the following diseases were excluded: a previous history of coronary intervention and/or coronary artery bypass graft surgery, the function of liver and kidney of serious insufficiency, hyperthyroidism or hypothyroidism, malignant tumor, blood system diseases, rheumatoid immune system disease, infectious disease, polycystic ovary syndrome(PCOS),and other diseases that infect the serum level of SFRP5. According to the results of coronary angiography, we defined the control group as no obvious stenosis, namely negative group. Coronary artery disease(CAD) group: subjects with significant coronary stenosis defined as ≥ 30% narrowing of luminal diameter of left main coronary artery, or ≥ 50% luminal diameter stenosis of at least one of three epicardial coronary artery. The CAD group divided into two groups: acute coronary disease(ACS) group, and stable angina pectoris(SAP),on the basis of the 2014 guideline for the diagnosis and treatment of chronic stable angina pectoris syndrome, the 2014 AHA/ACC guideline for the diagnosis and treatment of non-ST segment elevation acute coronary syndrome, and the ACC/AHA guideline for the diagnosis and treatment of STEMI in 2014.Blood samples were taken in the early morning(fasting 12 hours or more),before coronary artery angiography. Extraction of brachial vein blood 5ml to coagulation promoting tubes, centrifuged at 3000r/min 10 min in 2 hours, placed the upper serum separation in the-80℃.Glucose(GLU), Fasting insulin(FINS), glycosylated hemoglobin(Hb Alc), triglycerides(TG), total cholesterol(CHOL), high-density lipoprotein cholesterol(HDL-C), low-density lipoprotein cholesterol(LDL-C), serum creatinine(Scr), High sensitivity C reactive protein(hs-CRP), and other biochemical markers were measured by Beckman AU5800 automatic biochemical analyzer. HOMA-IR=GLU(mmol/L) ×FINS(m IU/L)/22.5. e GFR(m L/min/1.73 m2) = 194×(Scr)-1.094 ×(age)-0.287(×0.739 for female).BMI= Kg / m2.The level of serum SFPR5 were detected by enzyme-labeled immunosorbent assay(ELISA). severity of coronary artery lesion was detected by SYNTAX scores, we defined ≤22 scores as low risk, 23-32 scores as average risk, and ≥33 scores as high risk.All the date were analyzed by SPSS 19.0 software. Measurement date with normal distribution expressed ad mean ± standard deviation. Enumeration date expressed as percentage. T test was used to comparison between groups. Using the one-way analysis of variance test to compare the mean of multiple groups. Enumeration date were compared withχ2 test. The interrelationships of SFRP5,clinical date, biochemical parameters, and SYNTAX scores were analyzed by Person correlation analysis. And multiple linear stepwise regression analysis for SYNTAX scores and risk factors. We consider p <0.05 as statistically significant.Results:1 Comparisons of clinical data in different groups.This study include 163 patients(114 men, 49 women, mean age 59.19±7.40 years). Among the subjects,52 cases in the CON group(35 men,17 women, mean age 60.07±6.18 years),111 cases in the CAD group(79 men,32 women, mean age 58.92±7.58 years).In the subgroup of CAD,49 cases in the SAP group(31 men,18 women, mean age 60.08±6.81 years),62 cases in the ACS group(47 men,15 women, mean age 58.36±9.19 years).There was no statistically significant differences among the CON group and CAD group in age(60.07±6.18 years vs. 58.92±7.58 years), gender(M:F 35/17 vs. 79/32), hypertension(61.5% vs. 59.5%), diabetes(32.7% vs. 31.5%), smoking history(25%vs. 25.2%), Hb Alc(5.53±0.63%vs. 5.43±0.57%),GLU(5.80±1.80mmol/L vs. 5.68±1.52mmol/L), Medications(P>0.05). BMI(23.76±1.55 kg/m2 vs. 25.29±1.33 kg/m2), LDL-C(3.12±0.55mmol/L vs. 2.68±0.76mmol/L), hs-CRP(3.17±3.31 mg/L vs. 6.15±4.57 mg/L) levels in the CAD group were higher than CON group, these difference have statistical significance(P<0.05). HDL-C(1.34±0.23mmol/L vs. 1.09±0.28mmol/L) levels were significantly lower in CAD group than in CON group(P<0.05). In ACS group,hs-CRP(9.09±4.47 mg/L vs. 3.01±4.84 mg/L) levels were significantly higher than SAP group(P<0.05),and LDL-C(2.85±0.93mmol/L vs. 2.52±0.58mmol/L) levels were significantly lower than SAP group(P<0.05).2 Comparison the level of SFRP5 in different groupsIn CAD group, the level of SFRP5 was significantly lower than in CON group(37.49±4.95ng/ml vs. 49.45±4.05ng/ml, P <0.05).Serum SFRP5 levels in ACS group were significantly lower than in SAP group(33.89±5.81ng/ml vs. 40.16±4.23ng/ml, P<0.05) and CON group(33.89±5.81ng/ml vs. 49.45±4.05ng/ml, P <0.01).The level of SFRP5 was significantly lower than in CON group(40.16±4.23ng/ml vs. 49.45±4.05ng/ml, P <0.05).3 Correlative the level of SFRP5 and risk factorsAmong all the subjects, the level of serum SFRP5 was negatively correlated with body mass index(BMI)( r=-0.406,P<0.05),the homeostasis model of assessment of insulin resistance(HOMA-IR),(-0.496,P<0.05).In the CAD group, the level of SFRP5 was negatively correlated with LDL-C(r=-0.406,P<0.05),hs-CRP(r=-0.39,P<0.05),and positively correlated with HDL-C(r=-0.376,P <0.05).4 Correlative Analysis of serum SFRP5 and SYNTAX scoreIn CAD group, the level of SFRP5 was negatively correlated with SYNTAX score(r=-0.662, P <0.01). The level of SFRP5 in high risk group was lower than low risk group(31.43±3.63ng/ml vs. 43.20±3.52ng/ml, P<0.05), and CON group(31.43±3.63ng/ml vs. 49.45±4.05ng/ml, P<0.01). Serum SFRP5 levels in low risk group and average group were lower than CON group(43.20±3.52ng/ml vs. 49.45±4.05ng/ml, 38.48±3.08ng/ml vs. 49.45±4.05ng/ml, P<0.05).5 We regard SYNTAX score which represent the severity of coronary artery lesion as dependent variable, with the sex, age, history of hypertension, diabetes and HOMA-IR, HAblc, TG, CHOL, LDL-C, HDL-C, hs-CPR, SFRP5 as the dependent variable, carry on multiple linear stepwise regression analysis. The result show that serum SFRP5, hs-CRP and SYNTAX score had linear regression relation, standardization coefficient showed that SFRP5 has greater influence on the severity of coronary artery lesion than hs-CPR(β=-1.218 vs.-0.314, P<0.05). SFRP5 levels is a independent factor even if ages,BMI,LDL-C and other factors were considered.Conclusion:The level of SFRP5 in CAD group was significantly lower than in non-CAD group and negatively correlated with SYNTAX score. It represent that SFRP5 may act as a protective factor in coronary artery disease. Low level SFPR5 may play a major role in predictive the CAD, and provide a new direction for diagnosis, treatment, prevention of coronary artery disease.