阿托伐他汀对不稳定型心绞痛患者IL-18和超敏CRP的影响

目的探讨阿托伐他汀对不稳定型心绞痛（UAP）患者白细胞介素18（IL-18）和超敏C反应蛋白（hs-CRP）的影响及其量效关系。方法UAP患者60例,按数字表法随机分为:阿托伐他汀20 mg组30例,每天口服阿托伐他汀20 mg,共4周;40 mg组30例,每天口服阿托伐他汀40 mg,共4周;分别于治疗前和治疗后测定血清IL-18和hs-CRP水平,比较治疗前和治疗后血清IL-18和hs-CRP的变化。另设30例健康体检者为对照组。结果①UAP组患者IL-18和hs-CRP水平显著高于对照组（P<0.01）;②两种剂量阿托伐他汀治疗后患者血清IL-18和hs-CRP水平显著降低（P<0.01）;③治疗后阿托伐他汀40 mg组比20 mg组hs-CRP和IL-18水平下降更显著（P<0.01）。结论UAP患者体内存在炎症反应,阿托伐他汀具有抗炎作用,大剂量使用抗炎效果更好,应早期大剂量应用。     

阿托伐他汀对不稳定型心绞痛患者C-反应蛋白的影响

目的探讨阿托伐他汀对不稳定型心绞痛(UA)患者C-反应蛋白(CRP)和血脂的影响。方法选择76例UA患者,随机分成两组,治疗组给予常规治疗加阿托伐他汀每晚10mg口服,对照组给予常规治疗,持续8周。然后比较两组患者治疗前、后CRP和血脂水平的变化。结果经用药后治疗组血清CRP水平及血脂水平较对照组降低明显,与对照组相比差异有统计学意义(P<0.05)。结论阿托伐他汀可降低UA患者血清CRP及血脂水平。     

阿托伐他汀对不稳定型心绞痛患者C-反应蛋白及细胞粘附分子的影响

目的 研究阿托伐他汀对不稳定型心绞痛(UA)患者C—反应蛋白(CRP)及可溶性细胞粘附分子(sICAM—l、sVCAM—1)的影响。方法 EUSA法测定32例不稳定型心绞痛患者、25例稳定型心绞痛(SA)患者和20名对照组的血清CRP、sICAM—l及sVCAM—l浓度，对UA患者予以阿托伐他汀10mg口服，1次／d，疗程8～10周，观察治疗前后CRP、sICAM—l及sVCAM—l的变化。结果 (1)UA组患者CRP、sICAM—l及sVCAM—l水平高于SA组(P＜0．05)和对照组(P＜0．01)，而后两组间比较差异无显著性(P＞0．05)。(2)治疗后，不稳定型心绞痛患者血清CRP、sICAM—lt和sVCAM—l水平显著降低(P＜0．05)。结论 在不稳定型心绞痛患者体内存在着炎性反应，可能与其冠脉病变的不稳定性有关，阿托伐他汀具有抗炎、稳定斑块等作用。     

C反应蛋白对不稳定型心绞痛患者预后的评价作用

目的探讨血清C反应蛋白(CRP)水平对不稳定型心绞痛(UAP)患者预后的评价作用。方法观察UAP58例,稳定型心绞痛69例作为对照组,两组均在住院后24h内采集静脉血,测血清CRP水平,出院后随访6个月,两组进行对比分析。结果UAP组CRP明显高于对照组,且UAP组在随访过程中发生急性心肌梗死(AMI)、心脏性死亡及其它心脏事件者CRP均高于对照组。除心脏性死亡外,均有统计学差异。结论CRP在UAP患者中均有不同程度增高,且发生AMI、心脏性死亡及其它心脏事件者的CRP更进一步增高。提示CRP对UAP患者的预后有一定的预测价值。     

Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability

BACKGROUND: In a group of patients admitted for unstable angina, we investigated whether C-reactive protein (CRP) plasma levels remain elevated at discharge and whether persistent elevation is associated with recurrence of instability. METHODS AND RESULTS: We measured plasma levels of CRP, serum amyloid A protein (SAA), fibrinogen, total cholesterol, and Helicobacter pylori and Chlamydia pneumoniae antibody titers in 53 patients admitted to our coronary care unit for Braunwald class IIIB unstable angina. Blood samples were taken on admission, at discharge, and after 3 months. Patients were followed for 1 year. At discharge, CRP was elevated (>3 mg/L) in 49% of patients; of these, 42% had elevated levels on admission and at 3 months. Only 15% of patients with discharge levels of CRP <3 mg/L but 69% of those with elevated CRP (P<0.001) were readmitted because of recurrence of instability or new myocardial infarction. New phases of instability occurred in 13% of patients in the lower tertile of CRP (/=8.7 mg/L, P<0.001). The prognostic value of SAA was similar to that of CRP; that of fibrinogen was not significant. Chlamydia pneumoniae but not Helicobacter pylori antibody titers significantly correlated with CRP plasma levels. CONCLUSIONS: In unstable angina, CRP may remain elevated for at >/=3 months after the waning of symptoms and is associated with recurrent instability. Elevation of acute-phase reactants in unstable angina could represent a hallmark of subclinical persistent instability or of susceptibility to recurrent instability and, at least in some patients, could be related to chronic Chlamydia pneumoniae infection.     

阿托伐他汀对不稳定型心绞痛患者高敏C反应蛋白的影响

目的研究不同剂量的阿托伐他汀对不稳定型心绞痛患者血清高敏C反应蛋白水平的影响。方法选取我院不稳定型心绞痛患者51例,随机分为小剂量组28例和大剂量组23例,分别给予阿托伐他汀10mg或40mg,每日1次。共用药30日,治疗前后分别测定患者血脂水平和血清高敏C反应蛋白水平。结果阿托伐他汀用药30日后,两组血脂水平和血清高敏C反应蛋白水平均明显降低,低剂量组从(17±6)μg/L降至(8.3±2.7)μg/L;高剂量组从(18±7)μg/L降至(8±3)μg/L。两组下降程度比较,差异有统计学意义。结论早期应用阿托伐他汀治疗不稳定型心绞痛,可减少斑块基质成分的降解和炎症反应,具有稳定斑块作用,使用大剂量阿托伐他汀的获益更多。     

Tissue factor and tissue factor pathway inhibitor levels in unstable angina patients during short-term low-molecular-weight heparin administration

High tissue factor (TF), tissue factor pathway inhibitor (TFPI) levels and a hypercoagulability state have been documented in unstable angina patients. We evaluated whether short-term enoxaparin administration (100 IU/kg b.i.d. for 3 d) reduces the high TF levels and the hypercoagulability state, and whether it influences the fibrinolytic system in 20 unstable angina patients. On d 3, we observed a significant reduction in TF levels both 1 h and 4 h after the morning injection (-25.6% and -21.7%; P < 0.001 respectively) in comparison with the base-line levels. Both 1 and 4 h after the morning injection on the d 3, TFPI levels significantly (P < 0.001) increased (+96.4%, +96.9% respectively) with respect to the base-line values. After enoxaparin administration, at all observation times, thrombin-antithrombin complexes and prothrombin fragment F1 + 2 levels were significantly (P < 0.001) lower with respect to base-line levels. We observed a slight but significant increase in tissue plasminogen activator antigen levels in preinjection samples, as well as 1 h and 4 h after enoxaparin administration, in comparison with the base-line values. This study provides evidence that low-molecular-weight heparin (LMWH) administration, in addition to a reduction of hypercoagulability and a mild fibrinolytic activation, is associated with decreased TF levels, so indicating a novel mechanism of interference of LMWH with the haemostatic system.     

Relation of heart rate variability to serum levels of C-reactive protein in patients with unstable angina pectoris

Heart rate variability (HRV) and systemic markers of inflammation have prognostic value in patients with unstable angina pectoris (UAP). However, it is unknown whether any relation exists between HRV parameters and indexes of inflammation in this clinical context. We assessed HRV on 24-hour electrocardiographic Holter recordings, performed within 24 hours of admission, and measured C-reactive protein (CRP) serum levels by a high-sensitivity assay on admission, in 531 patients with UAP (65+/-10 years of age; 347 men) who were enrolled in the prospective multicenter study Stratificazione Prognostica dell'Angina Instabile (SPAI). A significant inverse correlation was found between CRP levels and all HRV parameters, with the highest r coefficient shown with SD of all RR intervals (r= -0.23; p<0.001) in the time domain and with very low-frequency amplitude (r= -0.22; p<0.001) in the frequency domain. When patients were categorized into 4 groups according to CRP quartile levels, statistically significant lower HRV values were observed in the upper CRP quartile. On separate multiple regression analyses, including the most important clinical and laboratory variables, SD of all RR intervals and very low-frequency amplitude were the most significant predictors of increasing CRP levels (p<0.001 for the 2 comparisons). In contrast, in models with SD of all RR intervals and very low-frequency amplitude as dependent variables, CRP was a strong predictor of impaired cardiac autonomic function (p<0.001 for the 2 comparisons). Thus, our data show that, in patients with UAP, high levels of serum CRP levels are significantly associated with decreased HRV, suggesting a possible pathophysiologic link between cardiac autonomic dysfunction and inflammatory activity.     

氟伐他汀对不稳定型心绞痛患者CRP、TNF-α和cTnI的影响

目的：研究氟伐他汀对不稳定型心绞痛患者血清G反应蛋白（CRP）、肿瘤坏死因子-α（TNF-α）和肌钙蛋白I（cTnI）的影响.方法：选择2002年7月至2004年4月住院的60例不稳定型心绞痛患者,随机分为两组.氟伐他汀组（31例）在常规药物治疗基础上加用氟伐他汀40mg/d、对照组（29例）用常规药物治疗.分别于治疗前、治疗后2周采集静脉血,测定血清CRP、TNF-α和cTnI浓度.结果：治疗后,对照组及氟伐他汀组血清CRP、TNFα和cTnI浓度较治疗前均明显降低,且氟伐他汀组血清TNF-α、CRP和cTnI浓度明显低于同期对照组. 结论：氟伐他汀可明显降低不稳定型心绞痛患者血清CRP、TNF-α和cTnI浓度.     

Canonical pathway of nuclear factor kappa B activation selectively regulates proinflammatory and prothrombotic responses in human atherosclerosis

Nuclear factor kappa B (NF-kappa B) activation has been observed in human atherosclerotic plaques and is enhanced in unstable coronary plaques, but whether such activation has a protective or pathophysiological role remains to be determined. We addressed this question by developing a short-term culture system of cells isolated from human atherosclerotic tissue, allowing efficient gene transfer to directly investigate signaling pathways in human atherosclerosis. We found that NF-kappa B is activated in these cells and that this activity involves p65, p50, and c-Rel but not p52 or RelB. This NF-kappa B activation can be blocked by overexpression of I kappa B alpha or dominant-negative I kappa B kinase (IKK)-2 but not dominant-negative IKK-1 or NF-kappa B-inducing kinase, resulting in selective inhibition of inflammatory cytokines (tumor necrosis factor alpha, IL-6, and IL-8), tissue factor, and matrix metalloproteinases without affecting the antiinflammatory cytokine IL-10 or tissue inhibitor of matrix metalloproteinases. Our results demonstrate that the canonical pathway of NF-kappa B activation that involves p65, p50, c-Rel, and IKK-2 is activated in human atherosclerosis and results in selective up-regulation of major proinflammatory and prothrombotic mediators of the disease.     

瑞舒伐他汀对不同血脂、C反应蛋白水平的不稳定型心绞痛患者颈动脉粥样硬化斑块的影响

目的探讨瑞舒伐他汀对不同血脂、C反应蛋白（CRP）水平的不稳定型心绞痛（UAP）患者颈动脉粥样硬化斑块的影响。方法：测定60例UAP患者低密度脂蛋白胆固醇（LDL-C）、超敏CRP（hsCRP）水平,并以LDL-C和hsCRP中位数水平为基础将受试者分为4组,所有入选患者口服瑞舒伐他汀10 mg／d,治疗12个月,分别于治疗前及治疗后3、6、9和12个月时测定三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、LDL-C、hsCRP水平,以及颈动脉中层厚度（IMT）,并计算颈动脉斑块积分。结果：经瑞舒伐他治疗9个月,高LDL-C,高hsCRP组颈动脉斑块积分较治疗前下降（P〈0-05）,治疗12个月时下降更为显著（P〈0-01）;并且,高LDL-C低hsCRP组颈动脉斑块积分下降程度不如低LDL-C高hsCRP组明显;而低LDL-C低hsCRP组颈动脉斑块积分与治疗前相比无统计学意义。结论：hsCRP的检测可以作为是否进行他汀类药物治疗的参考指标,尤其是对于那些LDL-C降至正常水平的患者。     

普伐他汀、阿托伐他汀对心绞痛患者C反应蛋白及血脂的影响

目的:探讨普伐他汀、阿托伐他汀对不稳定型心绞痛(UA)患者C反应蛋白和血脂的影响。方法:106例不稳定型心绞痛患者被随机分为普伐他汀组(53例)及阿托伐他汀组(53例),测定治疗前,治疗8周后C反应蛋白和血脂的变化。结果:两组治疗前后C反应蛋白(CRP)和血脂均有显著下降(P<0.05),且阿托伐他汀组较普伐他汀组血脂下降更显著(P<0.05)。结论:普伐他汀、阿托伐他汀均可降低UA患者CRP及血脂水平,同剂量阿托伐他汀较普伐他汀降脂效果更显著,其抗炎作用不依赖降脂作用。     

Enhanced plasma levels of oxidized low-density lipoprotein increase circulating nuclear factor-kappa B activation in patients with unstable angina

OBJECTIVES: The purpose of this study was to investigate the effect of circulating levels of oxidized low-density lipoprotein (ox-LDL) on nuclear factor-kappa B (NF-kB) activation in peripheral blood mononuclear cells (PBMC) of patients with unstable angina (UA) or stable angina (SA) and control subjects. BACKGROUND: Nuclear factor-kB might be involved in atherosclerosis, as is suggested by the presence of activated NF-kB in human atherosclerotic lesions. METHODS: Levels of plasma ox-LDL and circulating NF-kB in PBMC (and in separated lymphocytes and monocytes) were measured in 27 control subjects and 29 SA and 27 UA patients. In in vitro studies, the effect of ox-LDL and of the sera derived from a subgroup of UA patients and control subjects on monocytic NF-kB activation was also evaluated. RESULTS: The UA and SA patients had higher levels of circulating ox-LDL and NF-kB in PBMC than control subjects (p < 0.001). The increase in circulating NF-kB was mainly due to the activation of monocytes. In the in vitro studies, ox-LDL dose-dependently increased the activation of NF-kB in monocytes, but not in lymphocytes derived from healthy volunteers. This increase was related to the expression of lectin-like ox-LDL receptor-1 on monocytes. The incubation of monocytes with the sera derived from the UA patients induced a significant increase in NF-kB activation compared with the sera derived from the control subjects. CONCLUSIONS: The data suggest that the activation of NF-kB in monocytes of UA patients is, at least in part, induced by circulating molecules such as ox-LDL, which has been found to be particularly elevated in UA patients.     

替米沙坦对老年高血压不稳定性心绞痛患者脂联素及C反应蛋白的影响

目的探讨过氧化物酶体增殖物活化受体γ(PPARγ)激动剂替米沙坦对伴有高血压的老年不稳定性心绞痛患者血清脂联素及C反应蛋白的影响。方法用随机方法(分层抽样法)将120例伴有高血压的老年不稳定性心绞痛患者分为替米沙坦组(60例)和培垛普利组(60例),分别用酶联免疫吸附法及酶标多克隆抗体夹心法测定患者在治疗前和治疗后6个月的血清脂联素、高敏C反应蛋白(hs-CRP)浓度,并观察血糖、胰岛素敏感性指数(ISI)及血脂水平的改变。结果用培垛普利及替米沙坦治疗6个月后,平均血压显著下降〔(126±16)至(104±11)mmHg及(125±14)至(103±12)mmHg,均为P<0.05〕,血清脂联素浓度及ISI明显升高〔(5.8±2.7)至(6.3±2.5)mg/L,(5.9±2.9)至(8.4±3.1)mg/L及0.0075±0.0015至0.0088±0.0019,0.0069±0.0013至0.0137±0.0037,P<0.05及P<0.01〕,而hs-CRP明显下降〔(0.79±0.13)至(0.54±0.09)mg/L及(0.80±0.12)至(0.38±0.06)mg/L,P<0.05及P<0.01)〕,尤以替米沙坦组较甚。替米沙坦组治疗6个月后,心血管事件发生率显著下降(P<0.01)。结论与培垛普利相比,替米沙坦能够明显升高伴有高血压的老年不稳定性心绞痛患者血清脂联素浓度及显著降低其血浆hs-CRP水平和心血管事件发生率。     

Comparison of C-reactive protein and terminal complement complex in patients with unstable angina pectoris versus stable angina pectoris

Elevated C-reactive protein (CRP) can identify patients with coronary artery disease who are prone to future acute events. We investigated whether elevated CRP is related to the activation of the terminal complement cascade in 66 patients with unstable angina pectoris (UAP), in 45 patients with stable angina pectoris, and in 42 controls. CRP, additional acute phase reactants, the terminal complement complex (sC5b-9), leukocytes, and troponin T were measured. In 47 patients with UAP the CRP values were regarded as elevated (>0.3 mg/dl). In patients with UAP and elevated CRP, the plasma levels of sC5b-9 were markedly higher than in patients with UAP and lower CRP (245 +/- 14 vs 188 +/- 19 ng/ml, p <0.02) and in patients with stable angina pectoris with slightly (0.4 +/- 0.1 mg/dl) increased CRP (sC5b-9 173 +/- 21 vs 130 +/- 7 ng/ml [controls; p <0.05]). A further acute phase reaction was present only in patients with UAP and elevated CRP already on admission (p <0.01). sC5b-9 was not related to troponin release. Thus, elevated CRP levels are associated with activation of the plaque destabilizating terminal complement system in patients with UAP during the acute phase reaction. This may explain the prognostic value of CRP in acute coronary syndromes (ACS).     

Prognostic value of C-reactive protein and troponin T level in patients with unstable angina pectoris

OBJECTIVES: The prognosis of unstable angina pectoris may be more accurately predicted by the combination of C-reactive protein (CRP), which is a known inflammation marker, and troponin T (TnT), which is used for risk assessment for the prognosis of acute coronary syndrome. The present study investigated the correlations between pathophysiology and prognosis of severe unstable angina pectoris and CRP and TnT levels. METHODS: The correlation between CRP at admission and the prognosis was studied in 367 patients with severe unstable angina pectoris (Braunwald type II and III) who were admitted to our hospital between January 1998 and December 2000. The in-hospital and long-term prognosis was investigated in TnT-positive patients. In-hospital cardiac events were defined as death, myocardial infarction, heart failure and angina attacks during hospitalization. Long-term cardiac events were defined as death, myocardial infarction, heart failure and recurrence of angina. RESULTS: The incidence of in-hospital cardiac events in all patients was 30.2%. The CRP levels were higher in patients with cardiac events (0.97 +/- 2.67 vs 0.53 +/- 1.29 mg/d/, p = 0.057), but there was no significant difference between the two groups. The incidence of long-term cardiac events was 26.8%. The mean CRP level was significantly higher in patients with cardiac events than in patients without cardiac events (1.17 +/- 1.86 vs 0.43 +/- 1.14 mg/dl, p = 0.098). In TnT-positive patients (TnT > 0.1 ng/ml, 23% of all patients), the incidence of in-hospital cardiac events was 47.6% (p < 0.0001), significantly higher than that in all patients. TnT-positive patients with CRP levels of 0.5 mg/dl or higher (8% of all patients) had a markedly higher incidence of in-hospital cardiac events of 56.7% (p = 0.001) and long-term cardiac events of 46.7% (p = 0.01). CONCLUSIONS: CRP levels were useful in prediction of the long-term prognosis. TnT levels were useful in prediction of in-hospital prognosis. The present study suggested the possibility that the combined use of these biological markers could predict the prognosis of patients with unstable angina at early stage and more accurately.