Serum levels of anti heat shock protein 70 antibodies in patients with stable and unstable angina pectoris

BACKGROUND: The heat shock protein (HSP) family comprises approximately 24 proteins displaying a high degree of sequence homology between different species. The induction of self-HSP immune reactivity is thought to be involved in the pathogenesis of several diseases. Antibodies to HSP60/65 have been demonstrated in the sera of patients with coronary artery disease. Moreover, the target antigens of the antibodies HSP60 and HSP70 are both expressed in smooth muscle cells and macrophages within atherosclerotic lesions. In this retrospective, case control study, we investigated whether patients with established atherosclerosis, with either stable or unstable angina have high levels of antibodies to HSP70. METHODS AND RESULTS: Patients with stable angina (n = 40) were from the outpatient clinic whereas patients with unstable angina (n = 91) were recruited upon admission and prior to performance of coronary angiography. Control patients (n = 18) were healthy subjects with no evidence of coronary artery disease. Serum levels of anti-HSP70 antibodies were assayed by ELISA. Patients with stable and unstable angina exhibited lower serum levels of antibodies to HSP70 (0.202+/-0.113 and 0.201+/-0.115, respectively) in comparison to control subjects (0.364+/-0.199, P = 0.0001 for both comparisons). Serum levels of antibodies to HSP70 did not differ significantly between patients with stable and unstable angina. No differences in serum levels of antibodies to HSP70 were evident between baseline and follow up in the patients with unstable angina. CONCLUSIONS: Patients with coronary atherosclerosis possess lower levels of anti-HSP70 antibody levels. Further research is required to explore whether higher levels of anti-HSP70 antibodies have a predictive value in coronary atherosclerosis.     

Role of interleukin-17 and interleukin-17-induced cytokines interleukin-6 and interleukin-8 in unstable coronary artery disease

BACKGROUND: Atherosclerosis is a chronic inflammatory disease and interleukins are considered to play a key role in the chronic vascular inflammatory response that is typical of atherosclerosis. The serum levels of several of these cytokines have been found to positively correlate with coronary arterial disease and its sequelae. AIM: The aim of our study was to evaluate the levels of a comparatively new cytokine IL-17, in patients with stable and unstable coronary artery disease in order to assess whether unstable coronary artery disease patients had higher IL-17 levels. MATERIALS AND METHODS: We analyzed the concentrations of IL-17, IL-6, IL-8 and IL-10 using enzyme-linked immunosorbent assay and heat-sensitive C-reactive protein using latex particle-enhanced immunoturbidimetry in 58 consecutive unselected patients divided into three groups: stable angina (n=14), unstable angina (n=24) and acute myocardial infarction (n=20). We further compared them with 20 healthy controls. These 58 patients were also angiographically studied and divided into two groups: simple lesion (n=22) and complex lesion (n=36), on the basis of the coronary plaque morphology. RESULTS: Our results show increased concentrations of the proinflammatory cytokines IL-17, IL-6, IL-8 and heat-sensitive C-reactive protein, and decreased concentration of IL-10 in plasma of unstable angina and acute myocardial infarction patients. Plasma concentration of IL-17 was also positively correlated with plasma concentrations of IL-6 and heat-sensitive C-reactive protein. Our findings further showed that IL-17 values were higher in patients having angiographically visible complex types of lesions but no difference was observed between complex and simple lesion morphology patients. CONCLUSION: In conclusion, these findings point towards a role of inflammation in the form of increased activity of IL-17, IL-6 and IL-8 in patients of unstable angina and acute myocardial infarction and thus suggest that IL-17-driven inflammation may play a role in the promotion of clinical instability in patients with coronary artery disease.     

阿托伐他汀对急性冠脉综合征患者血清中白介素18、基质金属蛋白酶2的影响

目的 探讨阿托伐他汀对急性冠脉综合征(ACS)患者血清白介素18(IL-18)、基质金属蛋白酶2(MMP2)的影响.方法 ACS组86例,稳定性心绞痛组(SAP) 40例,冠状动脉造影正常者40例为对照组,按随机原则,将ACS患者划分为阿托伐他汀组和普通治疗组,每组各43例.酶联免疫吸附法(ELISA)测定样本血清IL-18、MMP2水平,比较各组血清IL-18、MMP2水平的变化.结果 ACS组患者血清IL-18、MMP2水平显著高于SAP组和对照组(P＜0.05).阿托伐他汀组治疗前后及普通治疗组治疗前后比较,血清IL-18、MMP2水平均明显下降(P＜0.05).结论 阿托伐他汀可降低ACS患者血清IL-18、MMP2水平,抑制冠状动脉粥样斑块炎症反应和基质成分的降解,促进粥样硬化斑块的稳定性,降低ACS的发生率.     

Serum tumour necrosis factor-alpha,interleukin-2 and interleukin-10 activation in stable angina and acute coronary syndromes

BACKGROUND: Dynamic instability of coronary atherosclerotic plaque results in the development of both unstable angina and myocardial infarction. The aim of the study was to investigate the dynamics of serum concentrations of tumour necrosis factor (TNF)alpha, interleukin (IL)-10, and IL-2 in patients with myocardial infarction (MI) and unstable angina (UA) as compared to stable angina (SA) patients and healthy volunteers. METHODS: A total of 189 patients with coronary artery disease (CAD) were studied: 100 patients with SA (class II/III according to CCS), 57 patients with UA (Braunwald class IIIB; determinations at 6, 24, and 48 h after chest pain), and 32 patients with MI (determinations at admission, on the 7th and 30th days after MI). Twenty healthy volunteers acted as controls. RESULTS: Serum TNFalpha levels were elevated in all CAD groups (SA: 17.3+/-4; UA: 18.7+/-4; MI: 22.0+/-3 pg/ml; p<0.001) in comparison to the controls (8.3+/-1.4 pg/ml). However, the highest values were characteristic of MI patients, especially values obtained at admission (p<0.01 versus SA and UA). Mean serum concentrations of IL-2 were significantly higher in patients with MI and UA (89.6+/-40; 87.0+/-24 pg/ml, respectively; p<0.01) when compared to SA and the control group (58.3+/-49; and 51.5+/-39, respectively). Serum IL-10 levels were also higher in MI and UA patients. Levels of IL-2 and IL-10 measured following chest pain in unstable patients, as well as their consecutive determinations in MI patients did not show any change dynamics, that is, they were persistently elevated. CONCLUSIONS: When compared to stable CAD and healthy subjects, acute coronary syndromes are associated with long-term increase of serum concentrations of pro- and anti-inflammatory cytokines. It seems likely that sudden CAD progression leading to acute coronary syndromes is triggered/accompanied by prolonged immune activation.     

Elevated plasma levels of interleukin-2 and soluble IL-2 receptor in ischemic heart disease

BACKGROUND: T-lymphocytes are present in significant numbers in the atherosclerotic plaque, but their role in the progression and pathogenesis of coronary syndromes remains poorly understood. HYPOTHESIS: We sought to determine the relationship between T-lymphocyte activation and ischemic heart disease by measuring plasma levels of cytokines related to T-lymphocyte function in patients with stable and unstable angina. METHODS: Plasma levels of interleukin-2 (IL-2) and soluble IL-2 receptor (sIL-2R) were measured in 105 patients: 66 with stable angina, 24 with unstable angina, and 15 healthy controls. Patients who presented to the cardiac catheterization laboratory with unstable or stable anginal syndromes for coronary angiography or percutaneous coronary intervention enrolled in the study. RESULTS: Mean levels of IL-2 were significantly higher in patients with stable angina than in those with unstable angina. The differences between stable angina and control groups, or between unstable angina and control groups, were not statistically significant. Mean levels of slL-2R were significantly higher in patients with stable angina than in either patients with unstable angina or control patients. CONCLUSIONS: Levels of IL-2 and sIL-2 receptor are significantly elevated in patients with stable angina, but not in patients with unstable angina. The contribution of T-lymphocytes to the development of both stable and unstable angina requires further investigation.     

Inflammatory markers and coronary interventions: a potentially useful follow-up modality after stenting.

Periprocedural levels of various inflammatory markers have been correlated with prognosis in patients undergoing percutaneous coronary interventions. However, long-term variations of interleukin-1 receptor antagonist (IL-1Ra) or C-reactive protein (CRP) during follow-up after coronary interventions were not previously investigated. The aim of our study was to perform serial evaluations of these markers before and after coronary stenting and to correlate them with clinical status. Plasma levels of IL-1Ra and CRP were measured at baseline and 3 and 6 months after the procedure in 31 patients with symptomatic coronary artery disease undergoing stent implantation, who had no evidence of myocardial ischemia at 6-month follow-up. While at 3 months there were no significant variations of baseline values, 6 months after the procedure a significant decrease from baseline was observed both in IL-1Ra and CRP levels (median -24 pg/ml, P = 0.048, and -0.13 mg/dl, P = 0.017, respectively). Six-month reduction in both IL-1Ra and CRP levels was significant in patients with unstable angina (n = 18; IL-1Ra: from 175 to 119 pg/ml, P = 0.001; CRP: from 0.52 to 0.18 mg/dl, P = 0.002) and nonsignificant in those with stable angina (n = 13) on admission (IL-1Ra: from 123 to 158 pg/ml, P = 0.22; CRP: from 0.19 to 0.10 mg/dl, P = 0.44). In conclusion, a significant reduction of IL-1Ra and CRP levels is observed 6 months after stent implantation in patients with preprocedural unstable angina who remain free of ischemia. This decrease suggests a stabilization of the inflammatory process and may be associated with a favorable prognosis after coronary interventions.     

Circulating Levels of IL-1β, a Prothrombotic Cytokine,are Elevated in Unstable Angina Versus Stable Angina

Background: Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. However, of the known proinflammatory cytokines, only elevated plasma levels of interleukin-6 have been linked to unstable angina. We sought to examine the plasma levels of other major proinflammatory cytokines in similar clinical settings and to determine the extent of the relationship between inflammation and unstable coronary syndromes by measuring the levels of various proinflammatory cytokines in patients with stable and unstable angina.Methods: We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in 97 patients: 67 with stable angina, 24 with unstable angina, and 15 healthy controls.Results: Mean levels of IL-1 were significantly higher in patients with unstable angina as compared to patients with stable angina (p = .009). Levels of IL-6 were significantly higher than control patients for both stable angina and unstable angina patients (p = .031 and .006, respectively). No significant differences were found in the levels of TNF-.Conclusions: Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina, and that the profile of circulating plasma levels of proinflammatory cytokines differs in unstable angina from that in stable angina.Abbreviated Abstract. Multiple studies support a role for inflammation in the pathogenesis of coronary atherosclerosis and unstable cardiac syndromes. We measured plasma levels of interleukin-1 beta (IL-1), tumor necrosis factor alpha (TNF-), and interleukin 6 (IL-6) in patients with stable and unstable coronary syndromes. Levels of IL-1 and IL-6 were found to be elevated in patients with unstable coronary syndromes. No significant differences were found in the levels of TNF-. Our results suggest that both IL-1 and IL-6 contribute to the pathogenesis of unstable angina.     

Cytokines in patients with ischaemic heart disease or myocardial infarction

BACKGROUND: Cytokines are responsible for the modulation of immunological and inflammatory processes as well as proliferative responses and apoptosis. It has been recently suggested that such cytokines as interleukin 6 (IL-6), soluble interleukin 6 receptor (sIL-6R) and anti-inflammatory cytokines such as interleukin 10 (IL-10) may play a significant role in the pathogenesis of acute coronary syndromes. AIM: To assess serum concentration of IL-6, sIL-6R and IL-10 in patients with ischaemic heart disease or acute myocardial infarction (AMI). METHODS: The study group consisted of 74 patients (25 females, 49 males, aged 40-69 years) divided into three groups; group I - 18 patients with AMI (up to 12 hours from the onset of symptoms), group II - 31 patients with unstable angina and group III - 25 patients with stable angina. The control group consisted of 20 healthy subjects. RESULTS: The IL-6 and sIL-6R serum levels were significantly higher in patients from groups I and II compared with patients from group III and controls, whereas the IL-10 serum concentration was similar in all studied groups. In patients with acute coronary syndromes serum concentrations of examined cytokines were positively correlated with acute inflammatory phase parameters and classical risk factors such as body mass index, blood pressure and lipid levels. CONCLUSIONS: IL-6 and sIL-6R are markers of acute coronary syndromes and may be used for the identification of high-risk patients with unstable angina or AMI.     

Serum profiles of matrix metalloproteinases and their tissue inhibitor in patients with acute coronary syndromes. The effects of short-term atorvastatin administration

There is increasing evidence that abnormal cytokine expression and increased metalloproteinase activity are implicated in the pathophysiology of acute coronary syndromes. This study investigates the serum profiles of representative metalloproteinases (MMP-1, -2, -9) and their tissue inhibitor (TIMP-1) in patients with myocardial infarction (MI) and unstable angina (UA) in relation to circulating proinflammatory cytokine (TNF-alpha and IL-6) activity. Furthermore, we examined the effects of a 30-day treatment with atorvastatin on serum levels of these inflammatory factors. Serum concentrations of MMP-1, -2, -9, TIMP-1, IL-6 and TNF-alpha were measured (enzyme-linked immunosorbent assay (ELISA) method) in 23 acute myocardial infarction patients and 20 unstable angina patients on 0 day, 1st, 3rd, 7th and 30th day after admission. Sixteen normal volunteers were used as healthy controls. Additionally, 12 patients of myocardial infarction group and 11 patients of unstable angina group were treated with atorvastatin (20 mg/day) for 30 days in a randomized design. In patients with myocardial infarction and unstable angina, serum levels of MMP-2, -9, TIMP-1, TNF-alpha and IL-6 were significantly higher than those of healthy controls in all time frames (p<0.05). In the group of unstable angina patients, we observed a statistically significant reduction in the levels of MMP-9, TIMP-1 and IL-6 after the 30-day atorvastatin administration. Our results suggest that serum MMPs, TIMP-1 and proinflammatory cytokines play an important role in the pathophysiology of the acute coronary syndromes. The reduction of these factors by short-term atorvastatin administration may provide a new insight into the pleiotropic effects of statins on unstable coronary artery disease.     

血管内超声评价斑块稳定性及其与血清高敏C反应蛋白和白细胞介素6的关系

目的 应用血管内超声技术探讨不稳定型心绞痛患者不稳定性斑块与血清高敏C反应蛋白和白细胞介素6的关系.方法 38例拟诊为冠心病患者行血管内超声检查,其中8例患者经血管内超声检查未发现冠状动脉有明显狭窄病变为对照组;30例经血管内超声检查发现冠状动脉有明显狭窄病变为冠心病组,其中不稳定型心绞痛18例,稳定型心绞痛组12例.检测所有患者血清高敏C反应蛋白和白细胞介素6水平.结果 38例患者均有不同程度的内膜增厚;8例对照组无动脉粥样硬化斑块;30例冠心病患者有不同类型的动脉粥样硬化斑块.不稳定型心绞痛患者血清高敏C反应蛋白和白细胞介素6水平显著高于稳定型心绞痛组和对照组;不稳定性斑块组高敏C反应蛋白和白细胞介素6水平高于稳定性斑块组.结论 不稳定型心绞痛患者血清高敏C反应蛋白和白细胞介素6水平明显增高,提示高敏C反应蛋白和白细胞介素6水平升高与动脉粥样硬化斑块不稳定性有关.     

Relationship between interleukin-18 levels and characterization of atherosclerotic plaque and percutaneous coronary intervention

Background lnterleuldn-18(IL- 18) plays a key role in the development,progression and outcome of coronary artery disease and its complications.However,its variability relation to the characterization of atherosclerotic plaque and percutaneous coronary intervention are still unknown.Methods Fifty four patients with coronary artery disease [22 patients with stable angina (SA) and 32 patients with acute coronary syndrome (ACS)] were enrolled in this study.All patients underwent percutaneous coronary intervention (PCI).The stability of the plaques at the criminal vessels was assessed with analogical IVUS.Serum IL-18 levels were measured at the time points of 5 rain before PCI,and Oh,6h,24h and lmonth after PCI in all patients.Results ACS group consisted mainly of lipidic unstable plaques while SA group of fibrous stable plaques.Moreover,compared with those in SA group,eccentricity index (EI) and remodeling index (RI) were significantly higher in ACS group.Positive remodeling was seen in ACS group while negative or no remodeling in SA group.Further,serum IL-18 levels were significantly elevated in patients with ACS than those in SA group before PCI,increased at Oh,6h,24h after PCI (P＜0.05)and were not significant different at 1 month after PCI from those before PCI.Conclusions There is significant difference in the composition and structural characteristics of atherosclerotic plaques between ACS and UA groups.PCI triggersd and enhances the inflammatory response in a short time.Serum levels of IL- 18 are the predictors of progression of unstable plaque in atherosclerosis.Post-operative complications of PCI might be reduced by inhibiting IL- 18.(J Geriatr Cardiol 2008;5:21-24)     

Comparison of platelet activation in unstable and stable angina pectoris and correlation with coronary angiographic findings

We sought to investigate the relation between platelet activation and the angiographic evidence of ruptured plaque in patients presenting with unstable and stable angina pectoris. We prospectively enrolled 25 consecutive patients (5 women and 20 men, mean age 62 +/- 3 years), 17 with unstable angina and 8 with stable angina. Systemic venous blood samples were collected within 4 to 6 hours of admission for flow cytometry analysis. Activation-dependent epitope CD63 and glycoprotein IIb/IIIa on the platelet membrane were assayed. Fibrinogen levels were also measured. All patients with unstable angina underwent cardiac catheterization and had angiographic evidence of ruptured plaque. Of the patients with stable angina, 5 underwent coronary angiography with smooth noncomplex lesions and 3 had negative technetium-99m sestamibi stress tests. Patients with unstable angina were characterized by 39% higher levels of fibrinogen than patients with stable angina (423 +/- 304 vs 304 +/- 51 mg/dl, p = 0.004). The percentage of platelets positive for the activation-dependent epitope CD63 was 5 times higher in patients with unstable than stable angina (14.6 +/- 5.6% vs 2.75 +/- 1.6%, p = 0.0026). They also had a 15% higher expression of their glycoprotein IIb/IIIa (517 +/- 79 vs 449 +/- 50 mean fluorescence intensity, p = 0.038). Thus, this study establishes a direct relation between the morphology of ruptured plaque and platelet activation in patients with unstable angina. This may allow for further risk stratification. Patients with unstable complex lesions had a fivefold higher expression of the platelet activation epitope CD63 than patients with stable angina. Furthermore, they had 15% more glycoprotein IIb/IIIa aggregation sites expressed on their platelet membrane, thus indicating an intense thrombogenic potential.     

Serum neopterin and complex stenosis morphology in patients with unstable angina

OBJECTIVES: We sought to assess the relation between serum neopterin concentration and complex coronary artery stenosis in patients with unstable angina. BACKGROUND: Monocyte activation is associated with acute atheromatous plaque disruption and acute coronary syndromes. Angiographically demonstrated complex coronary stenosis is often an expression of plaque disruption. Increased serum concentration of neopterin, a pterydine derivative secreted by macrophages after stimulation by interferon-gamma, has been observed in patients with acute coronary syndromes as compared with control subjects and patients with stable angina pectoris. METHODS: We studied 50 patients with unstable angina (32 men) who underwent coronary angiography after hospital admission. All coronary stenoses with > or =30% diameter reduction were assessed and classified as "complex" (irregular or scalloped borders, ulceration or filling defects suggesting thrombi) or "smooth" (absence of complex features). Serum neopterin levels were assessed within 24 h of hospital admission using a commercially available immunoassay (enzyme-linked immunosorbent assay kit, IBL, Hamburg, Germany). RESULTS: Thirty-nine patients were classified in Braunwald class IIIb, four in class IIb and seven in class Ib. The number of complex lesions per patient was 2.6+/-1.8 (mean +/- SD). The mean neopterin concentration was 7.76+/-3.62 nmol/liter. A significant correlation was observed between neopterin serum concentration and the presence of complex coronary stenoses (r = 0.35, p = 0.015). Multiple regression analysis showed that serum neopterin (p < 0.0001) was independently associated with the number of complex lesions. Other variables associated with complex lesions were the number of vessels with > or =75% stenosis (p < 0.0001), plasma creatinine (p = 0.003), triglycerides (p = 0.014) and a history of unstable angina (p = 0.032). CONCLUSIONS: Serum neopterin concentration is associated with the presence of angiographically demonstrated complex lesions in patients with unstable angina and may represent a marker of coronary disease activity.     

The selected pro- and anti-inflammatory cytokines in the patients with coronary heart disease: preliminary communication

Recent findings suggest that inflammation and cytokines regulation may play a role in the pathogenesis of atherosclerosis and coronary heart disease. The aim of this study was to assess serum concentrations of selected pro- (TNF alpha) and antiinflammatory (IL-10) cytokines in patients with coronary heart disease. We studied 29 patients with coronary heart disease: 14 with stable angina (group I) and 15 with unstable angina (group II). The control group (group K) consisted of 10 healthy subjects. Patients with inflammatory diseases, previous myocardial infarction (last 6 months) and with ECG abnormalities, that would invalidate ST-segment analysis, were excluded from examined groups. We evaluated: clinical state of patients and results of some diagnostic examinations (lipids, ECG, echocardiography, coronary angiography, concomitant diseases). In each patients serum levels of TNF alpha and IL-10 were measured according to the special protocol by ELISA. The mean serum concentrations of TNF alpha and IL-10 were significantly higher in group I (respectively: 18.75 +/- 11.7 pg/ml, 89.0 +/- 114.9 pg/ml) and II (14.21 +/- 5.9 pg/ml, 49.38 +/- 72.9 pg/ml) in comparison to the healthy subjects (9.41 +/- 1.7 pg/ml, 9.69 +/- 4.5 pg/ml). We found positive correlations between mean TNF alpha and IL-10 concentrations in group II (48 hours after last symptom) and between mean TNF alpha concentration and LVM (left ventricular mass), LVMI (left ventricular mass index) in group I. The concentrations of TNF alpha and IL-10 did not correlate with other clinical parameters. The results of our study suggest that serum concentrations of pro- (TNF alpha) and antiinflammatory (IL-10) cytokines may be increased in patients with stable and unstable angina. These increased concentrations do not reflect the clinical state of patients.     

Systemic inflammation in unstable angina is the result of myocardial necrosis

OBJECTIVES: We investigated whether the source of the acute phase response in unstable angina (UA) lay within the culprit coronary plaque or distal myocardium. BACKGROUND: An inflammatory response is an important component of the acute coronary syndromes. However, its origin and mechanism remain unclear. METHODS: In 94 stable patients undergoing coronary angiography, the relationship between systemic levels of tumor necrosis factor (TNF)-alpha, interleukin-6 (IL-6) and C-reactive protein (CRP) and extent of atherosclerosis was studied. The temporal relationship between these markers and troponin T (TnT) was determined in 91 patients with UA. Cytokine levels were measured in the aortic root and coronary sinus of 36 unstable patients. RESULTS: There was no relationship found between stable coronary atherosclerosis and inflammatory marker levels. Compared with this group, admission levels of IL-6 (3.6 +/- 0.3 ng/ml vs. 10.7 +/- 1.7 ng/ml, p < 0.05) and CRP (2.3 +/- 0.1 mg/l vs. 4.6 +/- 0.6 mg/l, p < 0.05) were elevated in patients with UA. In this group, IL-6 and CRP remained elevated in those who subsequently experienced major adverse cardiac events. This inflammatory response occurred in parallel to the appearance of TnT. Both TNF-alpha (19.2 +/- 3.4 ng/ml vs. 17.1 +/- 3.3 ng/ml, p < 0.001) and IL-6 (10.3 +/- 1.4 ng/ml vs. 7.7 +/- 1.1 ng/ml, p < 0.01) were elevated in the coronary sinus compared with aortic root in patients with UA. This was principally observed in those who were TnT positive. There was no cytokine gradient across the culprit plaque. CONCLUSIONS: There is an intracardiac inflammatory response in UA that appears to be the result of low-grade myocardial necrosis. The ruptured plaque does not appear to contribute to the acute phase response.     

Increased levels of monocyte-related cytokines in patients with unstable angina

Inflammatory cytokines play important roles in coronary artery disease. We investigated the clinical significance of monocyte-related cytokine expression in patients with angina pectoris. We studied 26 patients with stable effort angina and 20 patients with unstable angina in whom stenotic lesions of the coronary arteries were confirmed by selective coronary angiography. Plasma levels of interleukin-6 (IL-6), macrophage colony stimulating factor (MCSF), and monocyte chemoattractant protein-1 (MCP-1) were measured. Plasma levels of IL-6, MCSF, and MCP-1 in patients with unstable angina were significantly higher than those in patients with stable angina or control subjects. Patients with unstable angina were further divided into sub-groups according to their clinical classification; Levels of IL-6, MCSF, and MCP-1 in patients, who had anginal attacks at rest within the 48 h prior to admission (Braunwald class IIIB) were significantly higher than those in patients, who did not have attacks at rest (class IB). Five unstable patients, who were refractory to medical therapy and were referred for emergency coronary revascularization showed marked elevation of plasma MCSF and MCP-1 levels. In conclusion, plasma levels of monocyte-related cytokines were elevated in unstable angina. These increases were marked in patients with unstable angina with recent ischemic attack at rest, suggesting that activation of monocytes is involved in vulnerability of underlying atheromatous plaque.     

Interleukin-18: a strong predictor of the extent of coronary artery disease in patients with unstable angina

The aim of this study was to confirm that plasma interleukin (IL)-18 level is associated with the extent of coronary artery disease in unstable angina patients. Previous studies have shown that patients with unstable angina have significantly higher plasma IL-18 levels than healthy volunteers. However, the association between IL-18 and the extent of coronary artery atherosclerosis in patients with unstable angina remains unclear. Plasma concentrations of IL-18 and high-sensitivity C-reactive protein (hs-CRP) were measured in 166 consecutive patients admitted for coronary arteriography. One hundred and eighteen patients with unstable angina had coronary artery disease (coronary artery disease group; severity score: 2.32 ± 1.47; Gensini score: 31.3 ± 25.9), and 48 patients with coronary risk factors and without coronary artery lesions served as the risk control group. Plasma levels of IL-18 were higher in the coronary artery disease group than in the risk control group (P = 0.062). Additionally, plasma levels of IL-18 were significantly higher in 77 coronary artery disease patients with severity score ≥2 than in the risk control group (242.3 ± 110.6 vs 209.8 ± 120.3 pg/ml, P = 0.016). By univariate analysis, log-transformed plasma IL-18 concentration was positively correlated with coronary artery disease severity score (r = 0.244, P = 0.009). By multiple regression analyses, the association between coronary artery disease severity score and IL-18 remained significant (β = 0.733, P = 0.017) when controlling for age, diabetes mellitus and left ventricular ejection fraction. Additionally, coronary artery disease severity score was greater in the highest tertile (>246 pg/ml) of plasma IL-18 levels than in the middle (176–246 pg/ml) and the lowest (<176 pg/ml) tertiles (2.79 ± 1.52 vs 2.05 ± 1.08 vs 2.13 ± 1.66, P = 0.028). Of note, plasma hs-CRP level had no significant correlation with coronary artery severity. Plasma IL-18 level is associated with the extent of coronary artery disease in unstable angina patients, suggesting the link between IL-18 and coronary artery atherosclerosis in these patients.     

C-reactive protein and coronary artery disease

Evidence suggests that inflammation plays a key role in the pathogenesis of atherosclerosis. The chronic inflammatory process can develop to an acute clinical event by the induction of plaque rupture and therefore cause acute coronary syndromes. The aim of this study was to determine the serum levels of the circulating acute-phase reactant C-reactive protein (CRP), which is a sensitive indicator of inflammation, in patients with chronic stable coronary artery disease (CAD) and acute coronary syndromes (ACS). We studied 56 subjects: 1) 25 consecutive patients (18 men, 7 women; mean age, 68.5 +/- 14.3 years, range, 40-86) with unstable angina (UA) or acute myocardial infarction (AMI); 2) 31 consecutive patients (25 men, 6 women; mean age 64 +/- 12.7; range, 47-83, years) with signs and symptoms of clinically stable CAD. High-sensitivity-C-reactive protein (hs-CRP) levels were determined with a commercially available enzyme-linked immunoassay method. In patients with unstable angina and AMI before reperfusion therapy, CRP levels were not significantly different to those in patients with stable CAD (5.96 +/- 2.26 versus 4.35 +/- 2.6 mg/L; P = 0.12), but tended to be higher in patients with unstable angina and AMI. Baseline CRP levels in the subgroup of patients with AMI (6.49 +/- 2.28 mg/L) were significantly higher than levels in patients with stable CAD (4.35 +/- 2.6 mg/L; P = 0.02). CRP levels in patients with unstable angina and AMI were measured four times during a 72-hour period (0, 12, 24, and 72 hours). The lowest value was observed at baseline and differed significantly from values measured at any other time of the observation period (P < 0.001; 5.96 +/- 2.26; 9.5 +/- 9.04, 18.25 +/- 11.02; 20.25 +/- 10.61). CRP levels after 12, 24, and 72 hours were also significantly different to the initial values for patients with stable CAD (P < 0.01). There was no correlation between CRP and creatine kinase (CK), CK-MB isoenzyme, or troponin I positivity as markers for the extent of the myocardial injury during the observation period. Baseline levels of serum CRP tended to be higher in patients with unstable angina or AMI but were not significantly different from levels in patients with chronic stable CAD. In the subgroup of patients with AMI, baseline CRP levels were significantly higher than the levels in patients with stable CAD. CRP as a marker of inflammation is significantly increased in patients with AMI and unstable angina shortly after the onset of symptoms (after a period of 12 hours), supporting the hypothesis of an activation of inflammatory mechanisms in patients with an acute coronary syndrome or AMI.     

冠心病患者动脉粥样硬化斑块特征与Th细胞漂移的关系

目的探讨急性冠状动脉综合征(ACS)患者和稳定型心绞痛(SA)患者外周血γ干扰素(INF-γ)、白细胞介素4(IL-4)、白细胞介素2(IL-2)及白细胞介素10(IL-10)水平与斑块形态特征的关系。方法 70例患者分为两组,其中ACS组37例,SA组33例,采用ELISA检测冠状动脉造影前外周血INF-γ、IL-4、IL-2及IL-10水平。根据冠状动脉造影斑块形态特征将冠状动脉斑块分为Ⅰ、Ⅱ及Ⅲ型,根据超声特点将颈动脉斑块分为易损性斑块和稳定性斑块,比较不同斑块类型者INF-γ、IL-4、IL-2及IL-10水平变化。结果 ACS患者INF-γ和IL-2水平高于SA患者(P<0.05),IL-4和IL-10水平无显著性差异。ACS患者冠状动脉斑块主要为Ⅱ型,颈动脉斑块主要为易损性斑块;SA患者冠状动脉斑块主要为Ⅰ和Ⅲ型,颈动脉斑块主要为稳定性斑块;不同斑块类型者INF-γ、IL-4、IL-2及IL-10水平不同,冠状动脉斑块Ⅱ型者INF-γ、IL-2水平较Ⅰ和Ⅲ型者显著性升高(P<0.05),而IL-4和IL-10水平无明显差异。颈动脉易损性斑块者INF-γ和IL-2水平较稳定性斑块者显著性升高(P<0.05),而IL-4和IL-10水平无明显差异。结论 Th细胞漂移和斑块特征与斑块的稳定性有关,对于冠状动脉事件有一定的预示作用。     

64层螺旋CT冠状动脉成像检测不稳定斑块的危险因素分析

目的 探讨64层螺旋CT冠状动脉成像(64SCTA)检测冠状动脉粥样斑块的价值,分析形成不稳定斑块的危险因素.方法 选择112例住院冠心病患者行64SCTA和导管法冠状动脉造影,均检测血清内皮素-1、基质金属蛋白酶-9(MMP-9)、白介素-6(IL-6)、肿瘤坏死因子-α和超敏C反应蛋白(hs-CRP).以冠状动脉造影为标准评价64SCTA检测冠状动脉斑块的作用;根据检测正确的粥样斑块CT值将患者分为软斑块组(51例)和非软斑块组(61例),比较两组各检测指标的差异,分析软斑块形成的危险因素. 结果 64SCTA检测冠状动脉斑块的灵敏度为87.4%,特异度为87.1%,阳性预测值82.2%,阴性预测值91.0%.软斑块组与非软斑块组比较,MMP-9、IL-6、hs-CRP、冠状动脉病变数及诊断、性别和糖尿病的构成比差异有统计学意义.Logistic回归分析显示,MMP-9>5.231 ng/L(P=0.0215,OR=2.33,95%CI 1.13～4.79)、hs-CRP>3.583 mg/L(P=0.0008,OR=4.32,95%CI 1.84～10.15)和不稳定心绞痛(P=0.0339,0R=4.33,95%CI 1.12～16.77)为软斑块形成的危险因素.结论 64SCTA检测冠状动脉斑块价值较高,是目前无创方法检测冠状动脉斑块最为可靠的手段之一.MMP-9、hs-CRP和不稳定心绞痛为不稳定斑块的独立危险因素.