Risk Factors And Biomarkers Of Late Saphenous Vein Graft Disease

Objectives:This study sought to investigate the risk factors of late saphenous vein graft disease by analyzing clinical data and to explore the relationship between serum biomarkers and late saphenous vein graft disease,such as Hs-CRP,Interleukin-6,Platelet-derived growth factors-B,Adropin and Proprotein Convertase Subtilisin/Kexin Type 9.Moreover,We also want to find its predictive value for advanced saphenous vein graft disease.Methods:From March 2015 to October 2017,606 patients which is hospitalized in Tianjin Chest Hospital because of recurrent chest pain were reviewed,and all of them underwent primary isolated coronary artery bypass grafting more than 1 year.Clinical laboratory,angiographic data,previous CABG and coronary angiography of patients were colleted.SVGD was defined as at least 1 SVG stenosis?50%without distal anastomosis obstruction.All selected persons were divided into two groups:SVGD group?n=421?and non-SVGD group?n=185?.Logistic regression analysis was applied to analyze the risk factors of late saphenous vein graft disease.258 patients randomly selected for the detection of the biomakers,such as CRP,IL-6,PDGF-B,Adropin,PCSK9.Logistic regression analysis and receiver operating characteristic?ROC?curves were used to explore the relationship between biomakers and late SVGDand the predictive value for the occurrence of late SVGD.Results:First,risk factors of late saphenous vein graft diseaseTotal of 606 patients?n=421 SVGD,n=185 non-SVGD?were enrolled.1.Comparison of clinical baseline data?1?Age of patients with bridging:The bridging age of patients in the SVGD group was lower than the non-SVGD group[59.00?53.00-64.00?vs 61.00?54.00-67.00?,P=0.021].?2?Age of SVG:The SVGD group had a longer SVG age than the non-SVGD group[8.00?6.00-11.00?vs 5.00?3.00-8.00?,P=0.000].?3?The type of coronary heart disease:The proportion of ACS patients in SVGD group was higher than non-SVGD group?91.92%vs.79.56%,P=0.000?.?4?Native lesion vessel number:The proportion of three-vessel disease in the SVGD group was higher than that in the non-SVGD group[327?77.70%?vs 114?61.60%?,P=0.000].?5?Bridge vessel number:SVGD group has more bridge vessel counts than non-SVGD group[3.00?2.00-3.00?vs 2.00?2.00-3.00?,P=0.000].2.Comparison of cardiac ultrasound related indicators?1?LVED:LVED in SVGD group was higher than non-SVGD group[54.00?51.00-56.50?vs 51.00?48.00-53.25?,P=0.000].?2?LVEF:LVEF in SVGD group was lower than non-SVGD group[56.00?49.00-60.00?vs 58.00?53.00-60.75?,P=0.006].3.Comparison of laboratory indicators?1?VLDL:VLDL level in SVGD group was higher than non-SVGD group[0.46?0.37-0.61?vs 0.40?0.29-0.50?,P=0.000].?2?LP?a?:LP?a?levels in SVGD group was higher than those in non-SVGD group[34.35?12.13-117.85?vs 26.45?11.40-74.20?,P=0.042].?3?Hcy:The Hcy level in SVGD group was higher than that in non-SVGD group?17.56±10.89 vs 15.39±7.97,P=0.008?.4.Analysis of risk factors for late SVGD?1?Univariate regression analysis found that the following 11 indicators were statistically significant:age of patients with bridging[OR=0.976,95%CI?0.955-0.997?,P=0.000];age of SVG[OR=1.263,95%CI?1.191-1.339?,P=0.000];LP?a?[OR=1.003,95%CI?1.001-1.005?,P=0.009];VLDL[OR=9.760,95%CI?3.750-25.398?,P=0.000];Hcy[OR=1.026,95%CI?1.004-1.049?,P=0.020];LVED[OR=1.179,95%CI?1.124-1.236?,P=0.000];LVEF[OR=0.972,95%CI?0.950-0.994?,P=0.014];ACS[OR=3.937,95%CI?2.128-7.284?,P=0.000]?SAP as reference?;two native lesion vessel[OR=2.617,95%CI?1.204-5.888?,P=0.015],there native lesion vessel[OR=5.634,95%CI?2.247-9.556?,P=0.000]?single native lesion vessel as reference?were risk factors for lateSVGD.?2?Multivariate logistic regression analysis found that five indicators entered the regression model and were statistically significant:age of SVG[OR=1.219,95%CI?1.136-1.310?,P=0.000],VLDL[OR=5.278,95%CI?1.585-17.569?,P=0.010],LVED[OR=1.128,95%CI?1.070-1.189?,P=0.000],ACS[OR=3.937,95%CI?2.128-7.284?,P=0.000],two native lesion vessel[OR=2.754,95%CI?1.304-7.336?,P=0.043],there native lesion vessel[OR=5.176,95%CI?2.076-12.904?,P=0.000]?single native lesion vessel as reference?.Second,the biomarkers of late saphenous vein graft disease258 patients were tested for serum biomarkers,including 151 SVGD patients and 107 non-SVGD patients.1.Comparison of serum biomarkers level in two groups:The level of PDGF-B[303.03?236.46-371.67?vs281.14?182.82-386.04?],PCSK9[286.42?242.59-352.50 vs 266.56?216.28-312.34?],Hs-CRP[40.77?30.52-42.90?vs 27.38?22.43-36.77?]were higher than that in non-SVGD group,and Adropin[2.77?1.77-3.35?vs 3.36?3.12-4.67?]was lower than that in non-SVGD group,and the difference were statistically significant.IL-6 levels were not statistically differentbetween the two groups.2.Univariate regression analysis of biomarker quartile?1?Quartile divisionPDGF-B?pg/mL?:Q₁:?218.49;Q₂:218.49-292.03;Q₃:292.03-373.99;Q₄:?373.9.Adropin?ng/ml?:Q₁:?2.16;Q₂:2.16-3.12;Q₃:3.12-3.80;Q₄:?3.80.PCSK9?ng/mL?:Q₁:?234.54;Q₂:34.54-277.27;Q₃:277.27-338.04;Q₄:?338.04.Hs-CRP?ng/ml?:Q₁:?25.37;Q₂:25.37-33.40;Q₃:33.40-41.88;Q₄:?41.88.?2?PDGF-B:Taking Q₁ as the reference,the OR value of Q₂ and Q₃were 3.288[95%CI?1.592-6.793?,P=0.001],3.288[95%CI?1.592-6.793?,P=0.001].Adropin:Taking Q₄ as the reference,the OR value of Q₃-Q₁ were 4.032[95%CI?1.877-8.663?,P=0.000],11.667[95%CI?5.097-26.704?,P=0.000],17.208[95%CI?7.143-41.451?,P=0.000].PCSK9:Taking Q₁ as the reference,the OR value of Q₄ was 2.413[95%CI?1.176-4.950?,P=0.016].Hs-CRP:Taking Q₁ as the reference,the OR value of Q₃ and Q₄ were4.706[95%CI?2.224-9.960?,P=0.000]and 5.000[95%CI?2.340-10.682?,P=0.000].3.Correlation between biomarkers and clinical indicators?1?There was a positive correlation between PDGF-B and Lp?a??r=0.191,P=0.002?and PLT?r=0.179,P=0.004?.?2?Adropin was negatively correlated with Hcyr=-0.171,P=0.007?.?3?PCSK9 was positively correlated with FIB?r=0.215,P=0.001?,TC?r=0.184,P=0.003?,VLDL?r=0.209,P=0.001?,APOB?r=0.189,P=0.003?,WBC?r=0.222,P=0.000?,neutrophil ratio?r=0.174,P=0.005?,PLT?r=0.219,P=0.000?.?4?There was no significant correlation between Hs-CRP and clinical parameters.?5?Dividing the biomarkers into quartiles and finding that the correlation between biomarkers and clinical indicators still has statistical significance.4.Multivariate regression analysis of biomarker quartiles?1?PDGF-B:Taking Q₁ as the reference,the OR value of Q₂ and Q₃was 4.895[95%CI?1.559-15.365?,P=0.007],8.876[95%CI?2.644-29.798?,P=0.000].?2?Adropin:Taking Q₄ as the reference,the OR value of Q₃-Q₁ were3.839[95%CI?1.150-12.819?,P=0.029],6.823[95%CI?1.960-23.757?,P=0.003],18.156[95%CI?4.318-76.342?,P=0.000].?3?PCSK9:Taking Q₁ as the reference,the OR value of Q₃ and Q₄ were3.367[95%CI?1.063-10.661?,P=0.039],4.860[95%CI?1.242-19.020?,P=0.023].?4?Hs-CRP:Taking Q₁ as the reference,the OR value of Q₄ was 4.951[95%CI?1.407-17.425?,P=0.013].5.The predictive effect of biomarkers on late SVGD?1?PDGF-B:When the cut-off point was 200.80 pg/ml,its sensitivity and specificity for predicting late SVGD were 90.07%and 31.78%,and the area under the ROC curve was 0.58.?2?Adropin:When the cut-off point was 3.12ng/ml,its sensitivity and specificity for predicting late SVGD were 67.55%and 75.70%,and the area under the ROC curve was 0.75.?3?PCSK9:The cut-off point was 268.60 ng/ml,and its sensitivity and specificity for predicting late SVGD were 63.58%and 54.21%,and the area under the curve was0.59.?4?Hs-CRP:The cut-off point was 30.51 ng/ml,and its sensitivity for predicting late SVGD was 76.82%,specificity was 63.55%,and the area under the ROC curve was 0.70.Conclusions:1.Multivariate logistic regression analysis found that age of SVG,and the number of native vessel lesions,VLDL,LVED,ACS were independent risk factors for late SVGD.2.PDGF-B,Adropin,PCSK9,Hs-CRP may be related to the occurrence of late SVGD.Adropin,Hs-CRP had higher sensitivity and specificity for the prediction of late SVGD,and they may be the targets for future prevention and treatment of late SVGD.