The Clinical and Experimental Study on the Relationship Between Fibrinogen and Development of Coronary Artery Disease 2

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2 The Clinical and Experimental Study on the Relationship Between Fibrinogen and Development of Coronary Artery Disease 2

3 LDL/HDL

4 fibrinogen, FIB FIB FIB 417 FIB 3 <306.9 mg/l, mg/l, >408.1 mg/l FIB FIB FIB CHOTGLDLHDL FIB CAD LDL/HDL ( vs P< vs p<0.05) LDL/HDL LDL/HDL 195 FIB CHO, TG, LDL, HDLDDimmer FIB 0.289P< 0.01 FIB 2 F

5 P< 0.01 R P< 0.01 FIB FIB FIB FIB FIB FIB 32 FIB 62PE FIB 62PE FIB 62PE BMI 62PE FIB FIB FIB FIB FIB FIB LDL/HDL FIB FIB FIB 5

6 The Clinical and Experimental Study on the Relationship Between Fibrinogen and Development of Coronary Artery Disease Abstract Recently, foreign scholars have made a great deal of studies on the relationship between FIB and the development of coronary artery disease(cad) but much less comprehensive studies have been done about it in our country. In Chinese, the mobility and motility of CAD is increasing every year, most for acute myocardial infarction and sudden death, but while part of CAD patients have been in stable condition, its mechanism particular in the relationship of FIB and the coronary artery development has not been clarified. The objectives of this study were to :evaluate the association between fibrinogen and several tradional risk factors, including age, body mass index(bmi), cigarette, total cholesterol, HDL cholesterol, triglycerides, diabetes mellitus, hypertension; determine the relationship of FIB and CAD and the predictive value of FIB on CAD;explore the association of FIB and coronary artery stenosis degree; study the relationship of FIB and platelet membrane glycoproteins expression which were platelet activation marker. 417 CAD patients were assigned into three groups basing on FIB cut-off level which was <306.9 mg/l, mg/l, >408.1 mg/l.we found that age was increasing according to advancment of FIB level whether male or female. More diabete mellitus patients were in high FIB level group, while more smoking male were found in high FIB level group. After adjusting age, smoke, diabete mellitus, CHO TG LDLHDL value, FIB of CAD patients level was still in high level. After controlling the factor of smoking and BMI, Fibrinogen and LDL/HDL ratio and its relationship with CAD in 230 cases underwent coronary angiogaphy(122 patients with CAD and 108 people as normal control were analyzed). Fibrinogen and LDL/HDL ratio were significantly higher in patients with CAD than those of the normal control group( vs P< vs P<0.05). Multivariate regression analysis showed that Fibrinogen and LDL/HDL ratio was a significant variable associated with 6

7 acute coronary events risk. When Fibrinogen and LDL/HDL ratio were both in high level, acute coronary events risk might increase highly, comparing to single index. In a collective of 195 patients suspected of coronary artery disease (CAD), coronary artery stenosis was measured by coronary angiography. The severity of coronary artery was quantified in a modified Gensini score in base of angiogrphic imaging manipulation system. After the influences of other risk factors were controlled, the relationship between fibrinogen and severity of CAD was analyzed. Partial correlation analysis showed that fibrinogen was positively associated with severity of CAD (r =0.293, P< 0.01). Multiple stepwise regression analysis indicated that fibrinogen and age was a significant variable associated with severity of coronary artery disease( F value was P< 0.01; R was P< 0.01).All patients were assigned to four groups according to fibrinogen 25%, 50%, 75% cut-off level, we found high fibrinogen level were associated with severity of coronary artery, particularly in men and in diabetes mellitus patients. 216 patients suspected CAD were divided in 3 groups in base of diabetes mellitus and angiographic image, which included normal control, non-diabetes mellitus and coronary artery disease, diabetes mellitus and coronary artery disease. After the influences of other risk factors (including CHO, TG, LDL, HDL, D-Dimmer) were controlled, the relationship between fibrinogen and severity of CAD was analyzed. ANOVA analysis showed that the difference of coronary score and fibrinogen in 3 groups was significantly(p<0.01). All patients were assigned to four groups according to fibrinogen 25%, 50%, 75% cut-off level, we found high fibrinogen level were associated with severity of coronary artery, which was more seriously in diabetes mellitus patients compare of non-diabetes mellitus in same fibrinogen level, particularly in men. In 32 CAD patients, we used monoclonal antibody to measure the alpha granule membrane protein CD62PE expression in different FIB level. It was found that 62PE expression was increasing in high FIB level. Correlation analysis showed that the relation of FIB and 62PE expression was signifcant. After other risk factors were controlled, correlation coefficient improved oberviously. It showed that 62PE 7

8 expression was related with severity of coronary artery. The high level FIB may improve platelet membrane glycoprotein activation expression and could increase the degree of coronary artery severity. Traditional cardiovascular risk factors may be through high level FIB exert their effect. The FIB of CAD patients may be in high level. FIB may be a important predictive value on CAD for its advanced level indicating the risk of thrombosis development and underlying end point event. High fibrinogen may effect on progression of coronary atherosclerosis and aggravate direct degree of stenosis. High fibrinogen level associated with high LDL/HDL ratio significantly increased the risk of coronary artery disease. High level fibrinogen may accerlerate development of coronary stenosis more seriously in diabetes mellitus patients compare of non-diabetes mellitus in same fibrinogen level, particularly in men. High level fibrinogen may increase active expression of platelet membrane glycoproteins, and it maybe main mechanism impacting incidence and development of coronary artery disease. Therefore, elevated fibrinogen level seems to be a contributing factor for the severity of coronary artery disease. Key Word: Fibrinogen CAD Risk 8

9 fibrinogen, FIB FIB [1-7] FIB FIB FIB [89] FIB 10 FIB FIB IIb/IIIa FIB FIB FIB FIB FIB FIB FIB 1113 FIB C 1417 FIB 9

10 1820 FIB FIB [21] FIB [21] FIB FIB FIB [ ] FIB FIB FIB 10

11 FIB 11

12 BECTON DICKINSON Facsort SYSMEX CA-1500 BFX5-320 ( McAb) : BD (CD63 CD41-FITC) McAb DADE BEHRING D- DADE BEHRING SPSS

13 % 5% % C, 4%9% D-Dimmer [25] 140mg/dl ACCAHA [26] <10%1 10%-49% % %4 90%-100% SPSS

14 FIB 25%50%75% 4 FIB t 1-ANOVA CAD OROR = ad/bc, 95% Woolf CAD LDL HDL 14

15 mg/dl FIB CHOTGHDL FIB 1. FIB 3 <306.9 mg/l, mg/l, >408.1 mg/l FIB -1 15

16 -1 FIB n=76 n=80 n=111 n=48 n=46 n=55 Age CHO TG HDL LDL LDL/HDL DM(%) SMOKE(%) FIB <306.9 mg/l, mg/l, >408.1 mg/l AGE DM SMOKE FIB FIB FIB 16

i ED 3 ED 3 ED ED 17 ED 17

i ED 3 ED 3 ED ED 17 ED 17 MMPs B00017140 2003 6 i 1 2 3 ED 3 ED 3 ED 5 5 6 9 10 12 12 13 13 14 14 15 16 16 16 ED 17 ED 17 CIEF-5 21 23 27 MMPs 28 29 31 31 31 31 34 MMPs 34 MMP 34 MMP 35 MMP 36 MMP 38 MMP 39 43 43 44 44 46 ii 50