| BackgroundCoronary heart disease (CHD) claims numerous lives in both developing and developed countries. The prevalence of coronary heart disease is also increasing. The role of percutaneous coronary intervention (PCI) in the treatment of patients with CHD has developed rapidly. Despite the successful reduction in restenosis rates, there is new controversy concerning the optimal management of incidental, nontarget lesions identified during percutaneous coronary intervention (PCI). Therefore, the prevention of non-culprit lesion progress becomes extremely important after the initial PCI. Recent evidence suggests inflammation is an important pathogenic factor in atherosclerosis and coronary heart disease. Inflammatory factors are involved in various stages of atherogenesis. Some biomarkers in cardiovascular disease emerged in induction of progression of inflammation. Thus, inflammatory markers may be predict or estimate development of cardiovascular events. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a recently described and potentially useful plasma inflammatory marker correlated with coronary heart disease. Several clinical studies investigated that Lp-PLA2 activity correlated with development of cardiovascular events, and may be characterized as independent novel predictors of cardiovascular risk comparison to traditional risk factors. Interleukin-8 (IL-8) is characterized as novel inflammatory factor and is secreted by some cellules involved in atherogenesis. Studies reported that levels of serum IL-8 can predict independently the development of cardiovascular events. However, there are few studies referring to associations of Lp-PLA2 activity and interleukin-8 with nonculprit lesions after initial PCI in patients with coronary heart disease. Therefore, we carried out the present study and tried to find satisfying answers to the above problem.Objectives The purpose of the present study was1. To investigate possible mechanisms for the pathogenesis of progression of nonculprit lesions after initial percutaneous coronary intervention (PCI) in patients with CHD.2. To elucidate the association of serum Lp-PLA2 activity and IL-8 levels with progression of nonculprit lesions after initial percutaneous coronary intervention in CHD patients.MethodsOur study comprised 123 patients (36 females,62.7±8.3 yr of age) with coronary heart disease (CHD) treated with initial PCI from Octomber 2007 to March 2009 in Affiliated Hospital of Medical College, Qingdao University. All participants were carried out secondary coronary angiography at the mean one-year angiographic follow-up. CHD patients were further divided into two subgroups according to the progression of nonculprit lesions after initial PCI. The progressor group consisted of 19 patients while the nonprogressor group consisted of 104 patients. All subjects completed a questionnaire on present condition, family and medical histories of cardiovascular risk factors and complications. Height, weight, body mass index (BMI), waist circumference, hip circumference and blood pressure (BP) were measured. Furthermore, fasting blood sample was collected from each subjects after PCI 12-20 hours fast to determine the triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), creatinine (Cr), blood urea nitrogen (BUN), fibrinogen (FIB), fasting blood glucose (FBG), uric acid (UA) and hypersensitivity C-reactive protein (hs-CRP). Lp-PLA2 activity was measured through hydrolysis with enzyme substrate color method. Interleukin-8 (IL-8) levels were determined by double antibody sandwich enzyme-linked immunosorbent assay (ELISA) method. Furthermore, some predictors of progression of nonculprit lesions were investigated and the relationships between the cardiovascular risk factors and serum Lp-PLA2 activity, IL-8 were analyzed respectively.ResultsThe current study comprised 123 patients with coronary heart disease who underwent percutaneous coronary interventions (PCI) and followed up mean one year. We found that 19 patients (15.4%) had progression of nonculprit lesions after initial PCI, of which 10 patients (8.13%) had clinical symptoms undergoing secondary PCI.(1) Clinical characteristics of all groups:Compared with nonprogressor group, the total cholesterol (TC) were significantly higher in the progressor group (4.47±1.02 mmol/L vs.3.59±0.57 mmol/L, P<0.05). However, there were no significant differences in age, gender, SBP, DBP, BMI, TQ HDL-C, LDL-C, creatinine, BUN, fibrinogen, FBG, UA, lactate dehydrogenase (LDH), Creatine Kinase-MB (CK-MB), ejection fraction, LVMI, percentage of smoking and drinking between nonprogressor group and progressor group (P all>0.05).(2) The mean levels of Lp-PLA2 activity, IL-8 and hs-CRP were significantly higher in progressor group than those in nonprogressor group(P all<0.01).(3) The coronary lesions was more serious in progressor group when compared with that in nonprogressor group, and the proportion of multi-vessel disease was higher in progressor group (P<0.05)(4) The independent association of Lp-PLA2 activity with cardiovascular risk factors in overall study population was confirmed by linear correlation analyses. The Lp-PLA2 activity significantly correlated positively with age, diastolic blood pressure, body mass index and triglyceride(r=0.658, P=0.044; r=0.800, P=0.025; r=0.951, P=0.009; r=0.845, P=0.020). However, Lp-PLA2 activity was unrelated to gender, LDL-C, HDL-C, fibrinogen, creatinine, urea nitrogen, and hs-CRP.(5) The independent association of IL-8 levels with cardiovascular risk factors in overall study population was confirmed by linear correlation analyses. Serum IL-8 significantly correlated positively with systolic blood pressure, diastolic blood pressure and LDL-C (r=0.666, P=0.045; r=0.993, P=0.000; r=0.660, P=0.047), and tended to be associated negatively with HDL-C (r=-0.621, P=0.053)(6) Stepwise multiple variable logistic regression analysis was conducted to determine the risk factors in age, sex, SBP, DBP, BMI, TG, HDL-C, LDL-C, Lp-PLA2 activity, IL-8, FIB, FBG, UA, LVMI, smoking and drinking for progression of coronary lesions, which showed Lp-PLA2 activity and IL-8 were independent risks, indicating Lp-PLA2 activity and IL-8 were independent predictors for the progression of nonculprit coronary lesions after initial percutaneous coronary intervention.Conclusions(1) Inflammation and plaque instability caused by the initial PCI may be the mechanisms of progression of nonculprit lesions after initial percutaneous coronary intervention (PCI) in patients with CHD.(2) The proportion of progression of nonculprit lesions after initial percutaneous coronary intervention at one year follow-up was 15.4%, in which 10 patients (8.13%) had clinical symptoms requiring to undergo secondary PCI.(3) Lp-PLA2 activity, IL-8, hs-CRP, multiple complex lesions and hypercholesterolemia may be related to the progression of nonculprit lesions after initial percutaneous coronary intervention.(4) Lp-PLA2 activity and IL-8 were independent predictors of progression of nonculprit lesions after initial percutaneous coronary intervention (PCI) in CHD patients. BackgroundAtherosclerosis is the underlying cause of cardiovascular disease (CHD). Evidences suggested that inflammation is an important pathogenic factor in atherosclerosis and coronary heart disease. Inflammatory factors are involved in various stages of atherogenesis. Some biomarkers in cardiovascular disease emerged in induction of progression of inflammation. Thus, inflammatory markers may be predict or estimate development of cardiovascular events. Lipoprotein-associated phospholipase A2 (LP-PLA2) is a recently described and potentially useful plasma inflammatory marker correlated with coronary heart disease. Several clinical studies investigated that Lp-PLA2 activity correlated with development of cardiovascular events, and may be characterized as independent novel predictors of cardiovascular risk comparison to traditional risk factors. Interleukin-8 (IL-8) is characterized as novel inflammatory factor and is secreted by some cellules involved in atherogenesis. Studies reported that levels of serum IL-8 can predict independently the development of cardiovascular events.3-hydroxy-3-methyl glutaric acid mono-coenzyme A (HMG-COA) reductase inhibitors (statins) are a class of safe and effective drug used to lower plasma lipids level. Statins are effective not only in terms of lowering lipids but also for correcting endothelial dysfunction of resistant arteries, attenuating collagen deposition, improving biological activity of endothelial nitric oxide synthase (eNOS), increasing nitric oxide (NO) biosynthesis, inhibit smooth muscle cell proliferation, reversal of vascular remodeling, inhibition of thrombosis, anti-inflammatory, anti-oxidation and stabilization of atherosclerotic atherosclerosis (AS) plaques. In this study, the atherosclerotic rabbit models established by high-fat feeding and balloon injury and treated with rosuvastatin. We observed the effect of rosuvastatin on the proliferation of rabbit carotid artery intima and expression of Lp-PLA2 and IL-8 in order to explore a new way of diagnosis and treatment of atherosclerosis.Objectives1. To observe whether there are vascular inflammation in rabbit atherosclerosis model;2. To study the mechanism which underlying the role of Lp-PLA2 and IL-8 in vascular inflammatory reaction;3. To clarify the effect of rosuvastatin on vascular inflammation.Methods30 New Zealand rabbits were randomly divided into three groups:normal control group (n=10), hyper-lipid diet control group (n=10) and rosuvastatin treatment group (n=10). Animals in normal control group received normal diet, the other two groups received arterial intimal injury of carotid with balloon after four weeks hyper-lipid diet feeding, then treated with hyper-lipid diet, hyper-lipid diet and rosuvastatin for six weeks, respectively.3 ml blood was drawn from the ear vein of all the rabbits after the carotid arterial intimal injury (at the end of the fourth week) and before sacrifice (at the end of the tenth week). Serum TC, TG, LDL-C, HDL-C, Lp-PLA2 and IL-8 levels were measured. At the end of the experiment, all rabbits were sacrificed, the carotid arteries were isolated and paraffin-embedded slices and immunohistochermical staining of Lp-PLA2 and IL-8 were performed. Positive expression index of Lp-PLA2 and IL-8 were calculated with image analysis software.Results:(1) Before hyper-lipid diet feeding, there were no significant difference in the body weight and serum TC, TG, LDL-C and HDL-C among three groups.4 weeks for feeding, TC, TG and LDL-C were significantly elevated in hyper-lipid diet control group and rosuvastatin treatment group when compared with normal control group (P all<0.05).10 weeks for feeding, the serum TC, TG and LDL-C in hyper-lipid diet control group were higher compared with that of 4 weeks for feeding, while the serum TC, TG and LDL-C in rosuvastatin treatment group were decreased, and the serum HDL-C in rosuvastatin treatment group was increased (P<0.05)(2) Compared with normal control group, Lp-PLA2 and IL-8 level were significantly increased in hyper-lipid diet control group and rosuvastatin treatment group at the end of the fourth week (P all<0.05).10 weeks for feeding, Lp-PLA2 and IL-8 level were higher in hyper-lipid diet control group than that of 4 weeks for feeding, while Lp-PLA2 and IL-8 level were significantly decreased in rosuvastatin treatment group (P<0.05)。(3) The atherosclerotic lesions were not observed in normal control group. Compared with hyper-lipid diet control group, the intimal area, intimal/medial area ratio and luminal stenosis degree were lower significantly in rosuvastatin treatment group (P＜0.05). There is no statistical significance in medial area of carotid arteries among three groups (P>0.05)(4) There is no atherosclerotic lesions and positive expression of Lp-PLA2 and IL-8 in normal control group.In hyper-lipid diet control group, the intimal hyperplasia, atheromatous plaque and vascular stenosis were found and the expression of Lp-PLA2 and IL-8 were significantly increased (P＜0.05). Compared with hyper-lipid diet control group, the pathological changes were lighter and the expression of Lp-PLA2 and IL-8 were decreased in rosuvastatin treatment group (P<0.05) Conclusions:1. The vascular inflammation was showed in carotid arteries of rabbit atherosclerotic model.2. The body weight and serum TC, TG, LDL-C were increased, while HDL-C was decreased in rabbit atherosclerotic model.3. Lp-PLA2 and IL-8 level were elevated in atherosclerotic rabbit and the expression of Lp-PLA2 and IL-8 were increased in atherosclerotic plaque. All these abnormalities may be involved in the progression of atherosclerosis.4. Rosuvastatin may result in decreased total cholesterol, triglyceride, HDL-C as well as increased HDL-C significantly, which reveals that rosuvastatin has powerful activity of regulating lipid.5. Rosuvastatin can reduce Lp-PLA2 and IL-8 level, and decrease expression of Lp-PLA2 and IL-8 in atherosclerosis plaques. It demonstrates that rosuvastatin may inhibit or reverse atherosclerosis by reducing the inflammatory action and improving the atherosclerotic plaques stability. Background:In acute coronary syndromes, the relation of the level of high-sensitivity C-reactive protein (hs-CRP) to the progression of atherosclerosis remains unclear. Methods and Results:The study group comprised 123 patients with ACS who underwent percutaneous coronary interventions (PCI) and follow-up (mean interval,12 months) coronary angiography. Progression was defined as≥10% diameter reduction of a preexisting stenosis≥50%,≥30% diameter reduction of a stenosis<50%, development of a new stenosis≥30% in a previously normal segment, or progression of any stenosis to total occlusion. Progressors had higher hs-CRP levels on admission and at 48h after PCI, a higher level of total cholesterol and a higher rate of multiple complex lesions than nonprogressors. Multivariate analysis showed that admission hs-CRP elevation (hs-CRP level on admission≥0.166mg/dl, median value; odds ratio (OR) 2.92, p=0.010), post-PCI hs-CRP elevation (hs-CRP level 48h after PCI≥1.586mg/dl, median value; OR 2.67, p=0.022), and multiple complex lesions (OR 2.66, p=0.017) were independent predictors of progression of nonculprit lesions. Conclusions:Enhanced inflammatory response to PCI, as well as baseline inflammatory activity as reflected by hs-CRP level, may be involved in the progression of atherosclerosis in ACS Objective To evaluate the complications of priorβ-adrenergic blocker therapy to patients who have PCI(percutaneous coronary intervention) therapy. Methods We analyzed 210 consecutive patients undergoingβ-adrenergic blocker;of these patients 105 hadβ-adrenergic blocker therapy,105 had not. CK-MB,TnT(Troponin T,E(Epinephrine) and NE(Norepinephrine) were tested before PCI, and 6-8h,16-24h after PCI. Procedural complications, in hospital and 1-year outcomes were evaluated. Results 1)There were not significant difference between the two groups on CK-MB,E,NE.2) The complications were lower inβ-group than no-βgroup (arrhythmia7% vs 15%, slow flow3% vs2%, spasm2.5% vsl.1%, in hospital mortality 0.9% vs2.0%, one year mortality 2.0% vs2.8%). Conclusions Priorβ-adrenergic blocker therapy can reduce the incidence of complications.
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