| BackgroundsPCI (percutaneous coronary intervention) is one of the major interventional treatments for CHD (coronary heart diseases) now. PCI will not only alleviate the clinical symptoms but also lead to injure coronary artery, through promoting the release of reactive inflammatory factors of body tissue cell which are closely related to RS (in-stent restenosis) in vivo. The prevention of RS after PCI should be emphasised on the role of inflammation.Glucose and lipid metabolic disorders, inflammation play an important role in the process of CHD, among which T2DM (type 2 diabetes) patients are mild. IR (insulin resistance) is the central link in the occurrence of restenosis after PCI. It is found that more than 80% of RS patients complicated with T2DM and the incidence of restenosis in patients with T2DM is twice than that in patients with non-T2DM. The impact of diabetes on RS may be secondary to insulin on SMC(smooth muscle cell) proliferation. RSG (Rosiglitazone) which belongs to the TZDs (thiazolidine dione) drugs is a PPAR-γ(peroxisome proliferator-activated receptor-γ) specific agonist. As an insulin-sensitizing agent by enhancing insulin sensitivity, RSG improves the IR and accelerates the decomposition of sugar and lipolysis in the target tissue such as muscle, liver and adipose, RSG is not only for clinical treatment of T2DM, but also its anti-inflammatory, anti-atherosclerosis effect paid attention. RSG may be as a preventive medication RS after PCI by elevating serum APN(adiponectin) level.The choice of coronary stent implantation in patients with diabetes and the intervention effect of RSG in T2DM patients with in-stent RS may vary from individual to individual, because not all patients with T2DM have IR. It requires clinical data arguments. All of these require the demonstration of clinical datas.Objective1,In order to understand the blood biochemical status in CHD patients with T2DM, the laboratory parameters, plasma specimens of vasoactive substances (APN, ET) of patients during the preoperative and postoperative followed-up would be detected. Plasma adiponectin and endothelin before and after PCI would also be given the observation using correlation-analysis.2,Observe the insulin sensitizer RSG whether or not can intervene to the protection of the vascular endothelial damaged, inhibit the excessive proliferation of smooth muscle cells through improving the expression level of plasma APN and so on in PCI patients. We explore the RSG intervention of RS possible mechanism.3,Patients were followed up by recording the period of clinical cardiovascular events. It is analyzed whether the RSG's intervention played a positive role.Methods1,Object of Study and GroupingThe CHD patients combined with T2DM meeting the PCI indication for surgery were selected from December 2008 to July 2009 in Wuhan General Hospital Cardiology, except for the patients with varieties of infections, other immune dysfunctions, severe heart, lung, liver, kidney illness, and incomplete clinical data during hospitalization and postoperative lost to be followed-up.All the patients were given selective CAG (coronary arteriongraphy) after admission. PCI was given according to the coronary artery lesions. Patients were randomly divided into two groups:RSG intervention group of 40 patients, male 22 cases, female 18 cases, with an average age of 69.03±9.44; control group of 32 patients, male 23 cases,9 female cases, with an average age of 64.13±9.76.2,Diagnostic Criteria(1) CHD conforms to the developed WHO diagnostic criteria:compared with the adjacent diseased-vascular reference-vessel, and at least one major coronary artery or branch diameter stenosis≥50%, diagnosed with CHD; (2) Diabetes is diagnosed according to the ADA2007 version of standard treatment:Patients with past use of oral hypoglycemic agents and insulin or secondary insulin fasting plasma glucose≥7.0mmol/L, then diagnosed diabetes; (3) Diagnostic criteria for Hypertension adopted in 1999 the World Health Organization/International Society of Hypertension League (WHO/ISH) standard:Without the use of antihypertensive drugs, the systolic blood pressure≥140mmHg, diastolic blood pressure≥90mmHg; past history of high blood pressure, antihypertensive drugs currently in use are not up to the level of blood pressure should be diagnosed as having hypertension; (4) Diagnostic criteria of Hyperlipidemia adopted the Dyslipidemia Control Strategies Thematic Group "proposed standard for prevention and treatment of dyslipidemia":TC≥5.72 mmol/ L, TG≥1.7 mmol/L, LDL≥3.64 mmol/L, HDL≤0.91 mmol/L; (5) RS is divided into clinical and angiographic RS two main categories:clinical restenosis may lead to recurrence of angina or objective evidence of myocardial ischemia occur; angiography restenosis is common, according to the vascular lesions appeared at expanding segment of more than 50% stenosis.3,All patients admitted to hospital were timely collected their disease history, and for the underlying disease state the corresponding symptomatic supportive care was given (expanding coronary artery, reducing arterial pressure, anticoagulating, antiplatelet, hypoglycemic, hypolipidemic, nurturing myocardium, improving microcirculation, etc). The preoperative blood pressure, blood glucose and blood lipid were controled in the optimal level. Surgery indications were filtered. The appropriate patients signed a surgery agreement.4,All the relevant indicators should be completly tested preoperative:blood glucose, blood lipids, blood biochemistry, and blood coagulation. The plasma samples were acquired from centrifugal cubital vein,-80℃preservated, uniform tested. The renal toxicity of drugs (certain antibiotics, nonsteroidal anti-inflammatory drugs, cyclosporine, etc.) should be stoped using in 24-48 hours before surgery to 48 hours after surgery in order to avoid the occurrence and development of diabetic nephropathy.The postoperative patients were randomly divided into two groups:RSG intervention group and control group. The sex, underlying disease characteristics, vascular lesions acording to CAG, disease nature, extent and type of stent-used [Drug-eluting stent(DES)] match in two groups.Patients with diabetes should be treated by controlling the FPG (fasting plasma glucose) to near normal and glycosylated HbAjc (hemoglobin)<7%, in order to prevent the development of coronary artery disease and adverse events.RSG Intervention Group:patients were given the conventional medicine according to basic diseases (expanding coronary artery, reducing arterial pressure, anticoagulating, antiplatelet, hypoglycemic, hypolipidemic, nurturing myocardium, improving microcirculation, etc), plus rosiglitazone 4mg oral tablets once a day, consecutively taking 6 months.The Control Group:patients were given the conventional medicine acording to their basic disease situation (expanding of coronary artery, reducing blood pressure, anticoagulant, anti-platelet, reducing blood sugar and fat, nutrition cardiac muscle, improve microcirculation, etc), without rosiglitazone.5,Percutaneous Coronary Intervention Surgical MethodsPCI is completed by cardiology specialist according to the American Heart Association and the American Heart Association (ACC/AHA) guidelines coronary angiography using Judkins method, conventional multi-position (left anterior oblique, right anterior oblique, and axial position cephalopods) projection, in order to make the paragraphs of coronary fully display. Vascular will be judged as target lesion vessel when visually diameter stenosis>75%. usually through the femoral artery approach, according to standard methods of drug-eluting coronary stent implantation.It is compared to a successful operation when the residual stenosis<20% by visual after stenting and the blood level was TIMI3 (CAG assessment).6,Follow-up and Criterion of DiseasePatients were given the routine out-patient referral at the first 1,3 months, reviewed of blood pressure, blood glucose, blood lipids, blood biochemistry, and blood coagulation function, etc. Venous blood specimened from the cubital vein through the anticoagulant, centrifuged treatment, the supernatant was plasma samples,-80℃preservation, uniform testing. Every time echocardiography and normal ECG were chosed to give the patients, CAG was reviewed when conditions were in 6-8 months, or evidence of recurrence of myocardial ischemia.The critical nature of restenosis (target lesion vessel diameter 50%-70% stenosis) without angina symptoms and objective evidence of ischemia can only give medical treatment without routine PCI, but it should be noted that the objective evidence of ischemia and clinical follow-up. Research had showed that the luminal diameter of critical rhetoric of coronary artery restenosis would been improved over time.All of the patients having a CAG reviewed must have the first PCI-patient clinical data. The standards of review medical records, and meet the following criteria for excluding records:(1) graft vascular disease; (2) in-stent restenosis lesions; (3) except for simple balloon angioplasty, rotary grinding, peeling, and other treatment before stenting; (4) coronary angiography images is not clear; (5) operation is unsuccessful.7,Detection of the Serum Samples IndicatorsFasting cubital vein blood was collected preoperative and then immediately sent to our hospital medical laboratory subjects. Automatic biochemical analyzer which quality control are qualified were used to detect serum TC (total cholesterol), TG (triglyceride), HDL-C (high-density lipoprotein cholesterol), LDL-C (low-density lipoprotein cholesterol), FPG (fasting plasma glucose), Fibrinogen, Insulin, hs-CRP (high-sensitivity C-reactive protein) levels and so on.Plasma samples which-80℃stored were defrosted at room temperature, while unified by ELISA determined the expression plasma level of APN (adiponectin) and ET (endothelin). Conduct the light kit instructions of the specific steps.8,Statistical AnalysisDatas processing analysis use SPSS13.0 statistical software. All measurement datas are expressed by mean±SD. Two independent sample t-testing were used a few more. Factorial design ANOVE was used to analyze the main effects and interaction of two groups. P<0.05 indicates that the difference was statistically significant. Tabulation and describe the experimental results. Results1,the average level of plasma APN and ET in all selected patients before PCIThe plasma APN mean level was 2.06±2.36μg/ml and the ET mean level was 129.90±144.74ng/L in all selected patients before PCI.2,comparison of clinical datas between the RSG group and the control group before PCIThe age, sex, blood glucose (BG), plasma high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), cholesterol (TC), triglyceride (TG), C-reactive protein (CRP) and fibrinogen (Fib) were not significantly different between the two groups before PCI (P>0.05). The RSG group were male 22 cases, female 18 cases: the control group were male 23 cases, female 9 cases. The RSG group vs the control group:mean age (69.03±9.44 vs 64.13±9.76, P>0.05), HDL-C (1.11±0.29mmol/L vs 1.07±0.20mmol/L, P>0.05), LDL-C(2.29±0.86mmol/L vs 2.09±0.57mmol/L, P>0.05), TC (4.45±1.20mmol/L vs 4.26±0.89mmol/L, P>0.05), TG (1.64±0.79mmol/L vs 1.40±1.15mmol/L, P>0.05), CRP (5.04±3.63mg/L vs 4.84±4.21mg/L, P>0.05), Fib (4.29±1.42mg/L vs 4.14±1.34mg/L, P>0.05). The two random-grouping groups of patients can be compared.3,comparison of APN and ET changes between the RSG group and the control group at different time points(1) the comparison between the RSG group and the control groupThe 3th month after PCI, the plasma APN levels in the RSG group significantly increased than that in the control group (4.79±1.96μg/ml vs 3.64±2.35μg/ml, P<0.05), the elevated levels of the plasma APN between the 6th month and the 3th month were not significantly different (4.84±1.59μg/ml,3.89±2.24μg/ml vs 4.79±1.96μg/ml,3.64±2.35μg/ml, P>0.05); the 1st and 3th month after PCI, the plasma ET levels decreased in the RSG group than that in the control group, but having no significant difference (106.40±39.04ng/L vs 116.68±70.23ng/L,93.70±34.29ng/L vs 116.12±71.96ng/L, P>0.05), the 6th month, there were significant differences (87.67±30.06 ng/L vs 113.93±71.17ng/L, P<0.05).(2) the respectively plasma levels of APN in the RSG group and in the control group before and after PCIIn the RSG group, the plasma levels of APN concentration the 1st month postoperative compared with preoperative had a higher trendence, but having no significant difference (2.72±2.25μg/ml vs 1.99±2.16μg/ml, P>0.05), the 3th and 6th month after PCI there were significantly higher than that before PCI, having significant differences (4.79±1.96ng/L,4.84±1.59ng/L vs 1.99±2.16ng/L, P<0.01); in the control group the plasma APN concentrations had increasing tendency after PCI compared with preoperative, but having no significant difference (2.60±2.56μg/ml,3.64±2.35μg/ml,3.89±2.24μg/ml vs 2.15±2.64μg/ml, P>0.05).(3) the respectively plasma levels of APN concentration in the RSG group and in the control group before and after PCIIn the RSG group, the plasma levels of ET concentration the 1st month after surgery compared with preoperative decreased, having difference (106.40±39.04 ng/L vs 125.02±40.99ng/L, P<0.05), the 3th and 6th month after PCI, the plasma levels of ET concentration was significantly lower than that before PCI, having significant differences (93.70±34.29ng/L,87.67±30.06 ng/L vs 125.02±40.99ng/L, P<0.01); in the control group the 1st,3th and 6th month after PCI, the plasma levels of ET concentrations had no significant differences (116.68±70.23ng/L,116.12±71.96ng/L,113.93±71.17ng/L vs 123.95±71.90ng/L,P>0.05).4,The levels of patients'fasting blood glucose, glycosylated hemoglobin, serum insulin before and after PCI between the two groups(1) the comparison between the RSG group and the control groupFPG had no significant difference (6.83±4.21 mmol/L,6.54±4.03mmol/L vs 6.92±4.16mmol/L,6.68±4.17mmol/L,P>0.05)compared with the control group before and 1 month,3 months after PCI.It was different(6.23±3.85mmol/L vs 6.56±4.07mmol/L,P<0.05)6 months after PCI compared with the control group;HbA1c 1 month,3 month,6 months after PCI compared with the control group,there were no significant difference(6.92±1.64%,6.55±1.46%,6.35±1.43% vs 6.82±1.53%, 6.83±1.41%,6.75±1.42%,P>0.05)；serum insulin levels 1 month after PCI compared with the control group,had no significant difference(10.18±4.27mU/L vs 12.58±4.26mU/L,P>0.05),3 months,6 months after PCI compared with the control group had down,there were differences(9.85±3.89mU/L vs 12.38±4.16mU/L,9.86±3.65mU/L vs 11.97±4.31mU/L,P<0.05).(2)the concentration changes of fasting plasma glucose,glycosylated hemoglobin,serum insulin before and after PCI in RSG group and the control groupIn the RSG group,FBG 1 month,3 months after PCI had a decline compared with preoperative,but having no significant difference(6.83±4.21mmol/L,6.54±4.03mmol/L vs 7.61±5.48mmol/L,P>0.05),6 months after PCI compared with preoperative significantly decreased.There was a significant difference(6.23±3.85 mmol/L vs 7.61±5.48mmol/L,P<0.05)；HbA1c compared with that before surgery there was a decreasing trend,but no significant difference(6.92±1.64%,6.55±1.46%,6.35±1.43% vs 6.99±1.66%,P>0.05)；serum insulin levels than 6 months after surgery was significantly decreased when there was significant difference(9.86±3.65mU/L vs 12.83±5.49mU/L,P<0.05)In the control group,FBG,HbA1c,serum insulin 1 month,3 months,6 months after PCI,compared with preoperative decreased,but no significant difference(6.92±4.16mmol/L,6.68±4.17mmol/L,6.56±4.07mmol/L vs 7.37±5.18mmol/L；6.82±1.53%,6.83±1.41%,6.75±1.42% vs 6.94±1.61>%；12.58±4.26mU/L,12.38±4.16mU/L,11.97±4.31mU/L vs 12.97±4.81mU/L,0.05). 5,During the two groups of patients were followed up for restenosis (the clinical restenosis and the angiographic restenosis) and the major occurrence of clinical adverse eventsThere was 1 case of subacute thrombosis.in the RSG group and there were 4 cases of unstable angina occurred in the control group. There were no other clinical adverse cardiovascular events(subacute thrombosis, Q-wave acute myocardial infarction, sudden cardiac death) in the follow-up period.6,the adverse reactions of RSG in the postoperative follow-up periodPatients does not appear edema, weight gain and(or) the clinical manifestations of congestive heart failure, and the toxicity of liver and kidney during treatment.ConclusionThe CHD patients combined with T2DM had low-fat APN hyperlipidemia. Coronary intervention may increase plasma levels of ET. The repair process of injuryed vascular after stenting can be reflected from endothelial injury, inflammation and so early on plasma ET, APN detected at different time points, understanding for clinical RS, the development of the mechanism provides a theoretical basis. TZDs, RSG plays a preventive role in patients with T2DM of RS after PCI through increasing plasma APN and decreasing plasma ET levels. RSG may increase plasma APN levels, decreased plasma ET levels with the postoperative administration effects appear gradually over time, but worth looking forward to a long-term effects of the application.
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