Relationship Between Pregnancy-associated Plasma Protein A,Insulin-like Growth Factor-1 And Coronary Heart Disease And Their Changes After Percutaneous Coronary Intervention

BackgroundCoronary heart disease (CHD) has been the first fatal disease threatening people's health in the world. The incidence of CHD is gradually increasing yearly. Acute coronary syndrome (ACS ) is one of the severe clinical manifestation of CHD, The pathology basis of ACS is the rupture or erosion of vulnerable plaque, on which platelet accumulation and thrombus that can cause complete or incomplete block in coronary artery. ACS include unstable angina pectoris (UAP) , non-ST-segment elevation myocardial infarction (NSTAMI) and ST-segment elevation myocardial infarction (STAMI) and sudden death. Pathology studies indicate that most of patients with ACS were not caused by critical stenosis of coronary artery, but by rupture of the vulnerable plaque and subsequent thrombus formation in the coronary arteries in which there are only slight or medium stenosis. The occurrence of ACS was not associated with the severity of coronary artery stenosis. Rupture of vulnerable plaque and subsequent thrombus formation in the coronary artery are considered to be responsible for the pathogenesis of ACS. Therefore, it is important signification to identify vulnerable plaque early, forecast the risk of ACS in order to give early intervention to prevent the rupture of vulnerable plaque. With the rapid development of interventional cardiology, percutaneous coronary intervention(PCI)has been one of the main measures for CHD. But restenosis after PCI lowers its long-term effect, it is an important issue to prevent and cure restenosis after PCI.Recent studies have demonstrated that pregnancy-associated plasma protein-A (PAPP-A) is associated with the rupture of vulnerable plaque. It may play an important role in the occurrence and development of ACS. Many studies showed that insulin-like growth factor-l(IGF-l) is relative to atherosclerosis (AS) and CHD. It can make plague vulnerable and lead to ACS. Some experimental studies have confirmed that PAPP-A and IGF-1 participate in the progress of restenosis after PCI.ObjectiveThis study measured the serum levels of PAPP-A and IGF-1, at the same time, coronary angiography (CAG) were conducted in patients with CHD and normal subjects without CHD. To investigate the relationship between PAPP-A, IGF-1 and the severity of coronary lesions, the effect of PCI on PAPP-A, IGF-1. To search the biomarkers of high sensitivity and specificity that can reflect the vulnerable plaque characteristic. With the help of these markers, we can evaluate the risk degrees of patients with CHD to outbreak ACS and interfere with vulnerable plaque earlier, Meanwhile, provide the rationale for prevention and cure restenosis after PCI.Materials and MethodsAll subjects come from the inpatient of the department of cardiology and emergency, the first affiliated hospital of Zhengzhou University during January 2006 and October 2006.①42 patients with CHD diagnosed by CAG, were divided three sub-groups according to clinical type. 12 patients in acute myocardial infarction (AMI) group, 7 men and 5 women, mean age (62.5±12.5) years; 15 patients in UAP group, 10 men and 5 women, mean age (58.3±11.7) years; 15 patients in SAP group, 10 men and 5 women, mean age (58.1±9.2) years. 16 normal subjects without CHD diagnosed by CAG served as the control group, 10 men and 6 women, mean age(56.1±10.3) years. 24 patients with CHD received PCI;②The CHD group was divided into the single, double and three vessel lesions group by the numbers of vessels with percent stenosis of≥50% diameter;③The severity scale of coronary artery stenosis was quantitatively assessed according to CAG by Gensini scoring system;④The coronary artery lesions was divided into typeⅠ,ⅡandⅢplaque group by the morphology of atherosclerotic plaque. Enzyme linked immuoserbent assay(ELISA)was used to measure the serum levels of PAPP-A, IGF-1 in the patients with CHD and control group. The change of the serum levels of PAPP-A, IGF-1 before and after PCI and the relationship to stability of coronary artery, the severity of stenosis, stenosis number and the morphology of atherosclerotic plaque were assessed.Statistic analysisAll statistic work was carried out with software of SPSS 10.0. The measurement data were shown by (mean±SD), analysis between groups by least significant difference-t test and chi square test. Statistic analysis among four groups were performed by analysis of variance of univariate. The relationship between variables was analyzed by univariate linear relation. Correlation coefficient was tested by T-test, A vaule of P<0.05 was considered as statistical significant.Results1. Compared with AMI, UAP, SAP and the control group, the difference of sex, age, smoking history, family history, diabetes, hypertension and blood fat was not significant (P>0.05) .2. Compared with AMI, UAP and SAP group, the difference of the numbers of coronary artery vessels was not significant (P>0.05) . 3. The Gensini score of coronary artery in AMI, UAP and the SAP group was (71.75±22.69), (73.47±24.26) and (70.27±23.90) respectively, there wasnot significant differences among them (P>0.05) .4. The incidence of typeⅡplaque increased, typeⅠ,Ⅲplaque decreased in AMI, UAP group, compared with that in SAP group, the difference was significant (P<0.01).5. In AMI, UAP, SAP and the control group, the mean level of serum PAPP-A was (16.85±10.30) mIU/L, (15.24±10.51) mIU/L, (8.51±3.10) mIU/L and(8.35±2.01) mIU/L respectively; the concentration of IGF-1 was (132.28±40.88)μg/L, (127.31±36.04)μg/L, (44.88±18.47)μg/L and (67.69±24.54)μg/L respectively; The serum levels of PAPP-A and IGF-1 were obviously higher in AMI and UAP group than that in SAP and control group (P<0.01) , The mean level of serum IGF-1 in SAP group was significantly lower than that in control group (P <0.01) , The mean level of serum PAPP-A in SAP group was not different significantly, compared with that in control group (P>0.05) .6. In single, double and triple-vessel lesions and control group, the mean level of serum PAPP-A was (15.09±10.15)mIU/L,(16.07±10.81)mIU/L,(17.30±10.01) mlU/L and (8.35±2.01) mlU/L respectively; the concentration of IGF-1 was(91.54±49.04)μg/L, ( 90.46±51.08)μg/L, (92.40±50.02)μg/L and (67.69±24.54)μg/L respectively; The serum levels of PAPP-A and IGF-1 in single, double and three vessel lesions group were obviously higher than that in control group (P<0.05) , but the serum levels of PAPP-A and IGF-1 among single, double and three vessel lesion group were not significant differences (P>0.05) .7. In typeⅠ,ⅡandⅢplaque and control group, the level of serum PAPP-A was (12.01±7.18) mIU/L, (17.67±9.81) mIU/L, (13.33±6.01) mIU/L and (8.35±2.01) mIU/L respectively; the concentration of IGF-1 was (49.54±29.24)μg/L,(110.42±31.08)μg/L, (50.42±20.12)μg/L and(67.69±24.54)μg/L respectively;The serum level of PAPP-A in typeⅠ,ⅡandⅢplaque group were obviously higherthan that in control group (P<0.01) , The level of serum PAPP-A in typeⅡplaque group was highest than that in others group; the concentration of IGF-1 in typeⅡplaque group was also highest than that in others group. But the concentration of IGF-1 in typeⅠ,Ⅲplaque group were lower than that in control group, the difference was significant (P<0.05) .8. The serum level of PAPP-A before and after PCI was (15.07±10.02) mIU/L, (19.91±10.05 ) mIU/L respectively; The serum level of IGF-1 before and after PCIwas (91.42±51.02)μg/L, (153.22±52.36)μg/L respectively, the serum levels of PAPP-A, IGF-1 were higher after PCI than that of before PCI, the difference was significant (P<0.01) .9. A significant positive correlation was found between the serum levels of PAPP-A and IGF-1 in AMI and UAP group (r=0.48, P<0.01) .Conclusion1. The serum levels of PAPP-A and IGF-1 are obviously higher in AMI and UAP group than in SAP and control group, but the serum levels of PAPP-A and IGF-1 among single, double and three vessel lesion group are not significant differences, which suggests that PAPP-A and IGF-1 may act as one of the biomarkers of vulnerable plaques, but may not reflect the severity of coronary artery stenosis.2. The serum levels of PAPP-A and IGF-1 in typeⅡplaque group are higher than that in typeⅠandⅢplaque group, which suggests that typeⅡplaque is more vulnerable plaque, typeⅡplaque is more commonly in patients with AMI and UAP, but typeⅠandⅢplaque are more in patients with SAP.3. The serum levels of PAPP-A and IGF-1 after PCI are higher than that before PCI. This suggests that PAPP-A and IGF-1 may play an important role in the restenosis after PCI.