Effects of persistent platelet reactivity despite aspirin therapy on cardiac troponin I and creatine kinase-MB levels after elective percutaneous coronary interventions

BACKGROUND: Creatinine kinase-MB (CK-MB) and cardiac troponin I (cTnI) elevations are highly specific for myonecrosis after percutaneous coronary intervention (PCI). Aspirin is used to prevent thrombotic complications. Several studies have shown that some individuals exhibit a reduced or completely missing antiplatelet response to aspirin. The aim of this study is to investigate the effects of platelet reactivity despite aspirin therapy on CK-MB and cTnI levels after elective percutaneous coronary interventions despite 600 mg loading dose of clopidogrel. METHODS: One hundred fourteen (mean age 61.2+/-9.3 years, 78.1% male) patients receiving 300 mg daily enteric coated aspirin for at least 7 days with documented coronary artery disease were included in the study. Platelet reactivity despite aspirin was measured by platelet function analyzer (PFA)-100 collagen/epinephrine cartridge. Blood samples for CK-MB and cTnI were obtained before and at 6, 24, and 36 h after the PCI. Persistent platelet reactivity was defined when collagen/epinephrine closure time<165 s. RESULTS: A total of 87 (76.4%) patients were noted to have normal platelet reactivity (Group A), and 27 (23.6%) had persistent platelet reactivity (Group B). The elevations of CK-MB and cTnI levels were statistically significant within the groups (both P<0.001). However, there were no significant differences in the CK-MB and cTnI levels of the groups at baseline and after PCI for all studied hours. CONCLUSION: Persistent platelet reactivity was not associated with increased risk of CK-MB, cTnI elevations in low-to-intermediate risk PCI patients.     

稳定型心绞痛患者对阿司匹林的反应性

目的: 探讨在冠心病患者中,阿司匹林的个体差异及相关因素。方法: 稳定型心绞痛患者100例,服拜阿司匹林100 mg/d,7 d后测定血栓素B2（TXB2）、6-酮-前列腺素F1α（6-keto-PGF1α）、D-二聚体（D-D）、纤维蛋白原（FIB）、同型半胱氨酸（HCY）及C反应蛋白（CRP）水平,同时使用血栓弹力仪测定血小板的反应性,并根据反应性不同将患者分为四分位组（高反应性组和低反应性组）,观察两组患者的临床特征。结果: 血小板反应性呈正态分布;高反应性的患者中女性（52% vs.28%,P<0.05）及糖尿病患者（64% vs.32%,P<0.05）的比例较高;血栓前状态标记物中TXB2［(102±17)ng/L vs.(74±17)ng/L,P<0.05］及CRP［(7.7±1.6)mg/L vs.(4.3±1.2)mg/L,P<0.05］在血小板高反应性的患者中高于低反应性组。结论: 冠心病患者血小板反应性存在个体差异。     

High-dose statin and COX-2 inhibitor therapy rapidly decreases C-reactive protein level in patients with unstable angina

BACKGROUND AND AIM: Elevated levels of C-reactive protein (CRP) are associated with an increased risk of coronary events. The levels of CRP and other inflammatory markers are significantly elevated in patients with unstable angina. We hypothesised that a high-dose statin therapy alone or with cyclooxygenase-2 (COX-2) inhibitors, administered before coronary diagnostic or invasive procedures, can attenuate CRP elevation after the procedure and, consequently, more effectively reduce the rate of coronary events. METHODS: All patients with unstable angina in class III and IIB according to Braunwald classification were considered for inclusion in the present study. Finally, 60 patients with elevated CRP level (>3 mg/l) were randomised to three groups of pharmacological treatment before coronary angiography and subsequent angioplasty. Patients from group A received placebo, patients from group B - 80 mg of atorvastatin, and patients from group C - 80 mg of atorvastatin and 25 mg of rofecoxib. The levels of CRP were measured at baseline, after 3 days of therapy and 48 hours after invasive coronary procedure. RESULTS: The mean baseline CRP level in group A was 5.67+/-2.82 mg/l, in group B - 4.7+/-1.32 mg/l, and in group C - 6.78+/-2.56 mg/l (NS). After three days of pharmacological treatment, the mean CRP level was 5.82+/-2.69 mg/l in group A (NS compared with baseline) and was significantly reduced in group B to 2.5+/-1.37 mg/l and in group C to 3.01+/-1.57 mg/l (p<0.0013 compared with group A). Measurements performed 48 hours after the procedure revealed a marked CRP level increase in group A (up to 24.54+/-5.48 mg/l) and a much lower increase in groups B and C (up to 3.02+/-2.0 mg/l and 7.31+/-2.96 mg/l, respectively). CONCLUSIONS: High-dose statin therapy alone or in combination with COX-2 inhibitor, administered before invasive coronary procedure in patients with unstable angina, rapidly lowers CRP levels. This therapy also reduces a marked CRP elevation typically occurring after invasive coronary intervention. Attenuation of inflammatory reaction may be crucial for the reduction of coronary events following invasive coronary interventions.     

STEMI患者残余血小板聚集率与趋化因子CCL2的相关性

目的 观察和分析急性ST抬高型心肌梗死(STEMI）患者服用氯吡格雷后4~6 h的残余血小板聚集率（RPA）和血浆中趋化因子CCL2表达之间的关系。方法 入选STEMI患者107例。入院时均给予氯吡格雷600 mg，阿司匹林300 mg，在服用药物后4~6 h抽取静脉血，用光比浊法(TPA)检测ADP诱导的RPA,ELISA检测血浆中CCL2浓度。依据RPA检测结果分为2组:RPA≥59%为残余血小板高反应组（高反应组，n=51），RPA<59%为残余血小板正常反应组（正常反应组,n=56）。详细收集两组患者临床数据和血液生化检测资料。结果 两组间在年龄、性别、吸烟史、高血压病、糖尿病、空腹血糖（FPG）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）和脑钠尿肽（BNP）等方面均无明显的统计学差异。STEMI患者RPA与血浆CCL2浓度之间存在线性关系(r=0.427,P<0.01)。高反应组患者血浆CCL2浓度为（243±80）ng/L，正常反应组患者血浆CCL2浓度为（171±44）ng/L，两组间存在显著的统计学差异（P<0.01）。高反应组中肌钙蛋白T（TnT）、肌酸激酶同工酶（CK-MB）显著高于正常组〔(3.1±2.3) U/L vs.(2.3±1.4) U/L;(198±16) μg/L vs.(151±13) μg/L，均P<0.05〕。结论 STEMI患者残余血小板聚集率与趋化因子CCL2有相关性。     

Platelet aggregation and P-selectin levels during exercise treadmill test in patients with ischaemic heart disease

INTRODUCTION: Coronary artery disease (CAD) is associated with higher platelet activation sometimes despite aspirin use. There are conflicting data concerning platelet activation course during physical exercise in patients on aspirin with CAD. AIM: To assess platelet activation pattern during physical exercise in patients with CAD. METHODS: The study included 35 patients (20 men, 15 women) aged 64.7+/-10 years with CAD (CCS II) on aspirin treatment (75 mg daily) and a control group of 10 healthy subjects adjusted for age and gender. Treadmill testing was performed using the Bruce protocol. Platelet aggregation was measured with optical aggregation with the agonists ADP (10 microM), collagen (2 microg/ml) and arachidonic acid (0.5 mg/ml) before and at peak exercise; P-selectin platelet and soluble expression (basal and after stimulation with thrombin) was assessed with cytofluorometry before, at peak exercise and 1 hour after. RESULTS: There were no differences in collagen and ADP aggregation between patients and the control group. There was a significant increase of ADP aggregation at peak exercise in the control group (p <0.05). There was a positive correlation between platelet aggregation before exercise and at peak exercise with ADP (r=+0.86) and with collagen (r=+0.61). There was no difference in soluble P-selectin concentration between patients and the control group. Platelet P-selectin expression without stimulation with thrombin 1 hour after exercise was significantly higher in patients than in the control group (p <0.05). CONCLUSIONS: 1. Physical exercise does not intensify platelet aggregation in patients with CAD on 75 mg aspirin daily. 2. Despite taking aspirin, platelet activation measured with the expression of platelet P-selectin increases and there is further intensification during exercise testing. 3. The concentration of soluble P-selectin in patients with CAD does not reflect the expression of platelet P-selectin.     

Thromboxane-dependent CD40 ligand release in type 2 diabetes mellitus.

OBJECTIVES: The goals of this study were to characterize the platelet contribution to soluble CD40 ligand (sCD40L), to correlate its formation with the extent of oxidative stress and platelet activation, and to investigate the effects of improved metabolic control and low-dose aspirin on these processes. BACKGROUND: Inflammation, oxidative stress, and platelet activation are involved in the pathogenesis of type 2 diabetes (T2DM) and its complications. The CD40-CD40L interactions result in inflammatory and pro-thrombotic responses. METHODS: Urinary 8-iso-prostaglandin (PG)F2alpha and 11-dehydro-thromboxane (TX)B2, in vivo markers of oxidative stress and platelet activation, respectively, plasma CD40L, and C-reactive protein (CRP) were measured in 114 T2DM patients and 114 control patients. A randomized, parallel group, 17-day study of aspirin (30, 100, or 325 mg/day) was performed in 18 T2DM patients. A similar study was performed in six healthy volunteers (aspirin, 100 mg/day). Twenty poorly controlled T2DM patients were studied before and after improved metabolic control. RESULTS: Compared with control patients, diabetic patients showed significantly higher levels of 8-iso-PGF2alpha, 11-dehydro-TXB2, sCD40L, and CRP. On multiple regression analysis, 11-dehydro-TXB2 and 8-iso-PGF2alpha excretion rates predicted sCD40L levels. Soluble CD40L linearly correlated with 11-dehydro-TXB2 (rho = 0.67, p < 0.0001), and both were reduced after one week of aspirin (p < 0.0026), with slow recovery over 10 days after aspirin withdrawal. Improved metabolic control was associated with a reduction in sCD40L, 8-iso-PGF2alpha, and 11-dehydro-TXB2. CONCLUSIONS: This study provides several lines of evidence for the dependence of sCD40L release on TXA(2)-dependent platelet activation in T2DM and provides novel mechanistic insight into the amplification loops of persistent platelet activation in this setting.     

Increased platelet reactivity in unstable angina patients is not related to C-reactive protein levels

Platelets are a major component of thrombi, and coronary thrombosis plays a key role in the pathogenesis of unstable angina (UA). Whether platelet aggregability is increased in UA patients however, is not known. Furthermore, no study has investigated the relationship between platelet reactivity and inflammation in UA patients In this study, venous blood samples were collected at admission in coronary care unit in 37 patients with unstable angina (Braunwald class IIIB) and in 37 sex- and age-matched patients with chronic stable angina (CSA). Patients taking thienopyridine or anticoagulant drugs were excluded from the study, as also were excluded patients with a history of acute myocardial infarction in the previous 12 months. Platelet aggregability was measured on flowing blood as time to occlude a ring coated with collagen-adenosine diphosphate (ADP), using the platelet function analyzer (PFA-100) system. By this method, the time to occlusion (closure time) is taken as a measure of platelet adhesion/aggregability, with shorter times indicating greater platelet reactivity.There were 23 men and 14 women in both groups, and age was 67.7 +/- 8 and 67.5 +/- 8 years in UA and SA, respectively (P = 0.93). Closure time was significantly reduced in UA patients (78.8 +/- 14 s), compared to SA patients (93.3 +/- 19 s, P < 0.001). Among UA patients, serum C-reactive protein (CRP) levels had a median value of 5.1 mg/l (bottom and top quartile levels, 1.50-7.95). There was no significant correlation between closure time and CRP levels (r = 0.22, P = 0.29). Our data show that, in patients with unstable angina there is an increase of platelet reactivity in response to ADP/collagen stimulation, which is not related to inflammation.     

Low- vs high-dose aspirin. Effects on platelet function in hyperlipoproteinemic and normal subjects

Low-dose aspirin may be inadequate for inhibition of platelet function in hyperlipoproteinemics due to increased platelet reactivity. Platelet function was studied in 18 type II hyperlipoproteinemic and 12 normal subjects after at least ten days of treatment with placebo and with low-dose (0.45 mg/kg/day) and high-dose (900 mg/day) aspirin. In the normal and hyperlipoproteinemic subjects, low-dose aspirin produced near maximal (90%) inhibition of platelet thromboxane generation, significant prolongation of the bleeding time, and significant inhibition of platelet aggregation, similar in degree to the inhibition produced by high-dose aspirin. There was no significant difference between hyperlipoproteinemic and normal subjects in any of the platelet function measures before and after aspirin treatment. Thus, a daily 0.45-mg/kg aspirin dose (20 to 45 mg) effectively inhibited platelet function in type II hyperlipoproteinemics, who do not appear to have an increased dose requirement for aspirin.     

Platelet function measured by VerifyNow identifies generalized high platelet reactivity in aspirin treated patients

Selected aspirin treated patients may exhibit high platelet reactivity to agonists other than arachidonic acid. This study aimed to determine whether the VerifyNow identifies generalized high platelet reactivity supported by correlations with other established methods that stimulate platelets with various agonists. Stable outpatients with coronary artery disease (n = 110) were treated with aspirin in a two 3 x 3 Latin square design (81, 162 and 325 mg/day for 4 weeks each). VerifyNow (arachidonic acid (AA) cartridge); light transmittance aggregometry; thrombelastography; PFA-100; flow cytometry; PlateletWorks; and urinary 11- dehydro thromboxane levels were measured. Multianalyte profiling measured fibrinogen and von Willebrand factor (vWF). Patients with >or=550 ARU by VerifyNow had increased 5 mM AA-, 5 microM ADP-, and 2 microg/mL collagen-induced platelet aggregation compared to patients with <550 ARU (p 相似文献   

Medicare Coverage Policies: A Macro and Micro Analysis

Markers of inflammation, such as C-reactive protein (CRP) and fibrinogen, have been shown to be predictive of cardiovascular disease. In the Physicians Health Study, the magnitude of reduction in the risk of myocardial infarction with aspirin therapy was related to baseline CRP levels, raising the possibility that the protective effect of aspirin may be due to antiinflammatory properties in addition to its antiplatelet effect. We therefore investigated whether aspirin therapy lowers CRP levels. Because heavy physical exertion is a well-known trigger of myocardial infarction, we also investigated the effect of aspirin on CRP levels before and after strenuous exercise. Thirty-two healthy men, aged 29 ± 6 years, were enrolled in a randomized, double-blind, parallel study. Blood samples were obtained immediately before and after maximal treadmill exercise at baseline and following 7 days of aspirin therapy (81 or 325 mg). The levels of CRP, as measured by ELISA, increased by 13% following exercise (P < 0.0001). However, aspirin did not significantly alter CRP levels, either at rest (0.81 ± 0.13 mg/L before aspirin vs. 0.78 ± 0.13 mg/L on aspirin) or following exercise (0.92 ± 0.13 mg/L before aspirin vs. 0.86 ± 0.13 mg/L on aspirin), P = 0.73. When the resting and postexercise data were combined, the levels were 0.87 ± 0.13 mg/L before aspirin and 0.82 ± 0.13 mg/L on aspirin (a nonsignificant 6% reduction, P = 0.20). In conclusion, in healthy male subjects CRP levels were not significantly reduced by short-term aspirin therapy. Our data, taking together with other reports, suggest that aspirin may not affect the levels of inflammatory markers. However, further studies are needed with a longer duration of therapy, among subjects with coronary heart disease, and using additional markers of inflammation besides CRP to determine the long-term effects of aspirin use.     

Aspirin adherence, aspirin dosage, and C-reactive protein in the first 3 months after acute coronary syndrome

Persistent elevation of inflammatory markers such as C-reactive protein (CRP) has been associated with an increased risk of recurrent cardiac events after acute coronary syndromes (ACS). Conflicting evidence is available regarding whether aspirin can reduce CRP after ACS. We investigated whether the dosage and adherence to aspirin was associated with the CRP level 3 months after ACS. Adherence to aspirin was monitored for 3 months in a cohort of 105 patients enrolled within 1 week of an ACS using an electronic chip stored in the pill bottle cap. The CRP level was measured at baseline and 3 months. Logistic regression analysis was used to test whether poor adherence to aspirin and a lower aspirin dosage were associated with increased CRP levels, controlling for age, ACS type, disease co-morbidity, baseline CRP level, use of clopidogrel and statins, depressive symptoms, smoking, and adherence to other medications. Aspirin adherence was inversely correlated with the CRP level at 3 months (Spearman's r = -0.36, p < 0.001). In the adjusted model, every 10% decrease in aspirin adherence was associated with a 1.7 increased risk (95% confidence interval 1.2 to 2.4) of a CRP level of ≥ 3.0 mg/L at 3 months. Low-dose aspirin was associated with a 7.1 increased risk (95% confidence interval 1.5 to 33.3) of a CRP level of ≥ 3.0 mg/L. The Charlson co-morbidity index, depressive symptoms, and baseline CRP level were also predictive of a CRP level of ≥ 3.0 mg/L at 3 months. The association between aspirin adherence and CRP level was not attenuated by controlling for other risk-reducing behaviors. In conclusion, a strong association was found between aspirin adherence and the CRP level after an ACS.     

Aspirin modifies nitric oxide synthase activity in platelets: effects of acute versus chronic aspirin treatment

OBJECTIVE: We examined the effects of aspirin on basal and beta-adrenoceptor (beta-AR)-mediated nitric oxide synthase (NOS) activity in normal platelets. METHODS: NOS activity was determined from the conversion of L-[3H]arginine to L-[3H]citrulline, both basally and following beta-AR stimulation, in platelets from healthy human subjects following both short- and long-term aspirin administration. RESULTS: Basal L-[3H]citrulline increased following aspirin 800 mg administered intravenously in vivo, from 0.31+/-0.12 to 0.76+/-0.14 pmol/10(8) platelets (P<0.01). Isoproterenol at 1 micromol/l increased platelet NOS activity before but not following intravenous aspirin. After short-term in vitro treatment with aspirin 10 micromol/l, 400 micromol/l or 4 mmol/l, basal platelet L-[3H]citrulline increased similarly, an effect not seen with indomethacin 100 micromol/l or ibuprofen 10 micromol/l. Platelet NOS activity was not increased by albuterol 1 micromol/l, in the presence of indomethacin, ibuprofen or aspirin in vitro. By contrast, oral aspirin 75 mg daily for 14 days did not affect basal platelet NOS activity, but abolished beta-adrenergic NOS activation. CONCLUSIONS: Aspirin activates basal platelet NOS acutely, but not chronically, through a mechanism independent of cyclooxygenase (COX) inhibition. By contrast, both short- and long-term aspirin treatment inhibit platelet beta-adrenergic NOS activation by a COX-dependent mechanism. This indicates that aspirin exerts divergent effects on basal and beta-AR-stimulated platelet NOS activity, which are likely to be of clinical relevance.     

Rofecoxib, a COX-2 inhibitor, lowers C-reactive protein and interleukin-6 levels in patients with acute coronary syndromes

BACKGROUND: Patients with acute coronary syndromes (ACS) have high levels of inflammatory mediators such as C-reactive protein (CRP) and interleukin (IL)-6. AIM: To evaluate whether patients with ACS treated with rofecoxib, a COX-2 inhibitor, will have reduced CRP, IL-6, and soluble tumor necrotic factor receptor-1 (sTNF-R1) levels and improved endothelial function. METHODS AND RESULTS: Thirty-four patients hospitalized with ACS were randomized to receive rofecoxib, 25 mg/d plus aspirin 100 mg/d, or placebo plus aspirin, 100 mg/d, for a period of 3 months. Blood samples for CRP, IL-6, and sTNF-R1 levels were drawn prior to randomization, and after 1 month and 3 months. CRP levels in the rofecoxib group (n = 18) were significantly lower both at 1 month and 3 months compared to the baseline levels (p < 0.02). IL-6 levels were significantly lower at 1 month (p < 0.02) in the rofecoxib group, but not at 3 months. There was no change in endothelial function or sTNF-R1 levels. CONCLUSION: Patients recovering from ACS had lower levels of CRP and IL-6 at 1 month and lower CRP levels at 3 months when treated with rofecoxib plus aspirin. Suppression of inflammatory processes may lead to retardation of coronary atherosclerosis and coronary events.     

Assessment of biochemical aspirin resistance at rest and immediately after exercise testing.

Some aspirin-treated patients experience thromboembolic events, a phenomenon termed 'aspirin resistance', which may be clinical or biochemical by definition. Physical exercise is known to enhance platelet secretion and aggregability. To evaluate the presence of biochemical aspirin resistance at rest and immediately after exercise in individuals with stable coronary artery disease or coronary artery disease risk factors. We prospectively enrolled 101 patients who had received 100 or 300 mg/day enteric-coated aspirin for at least 7 days. Biochemical aspirin resistance (defined as normal collagen-epinephrine closure time < 165 s) was studied using the standardized platelet function analyzer. Of the 101 patients, 63 were aspirin sensitive both at rest and immediately after exercise, 18 exhibited biochemical aspirin resistance both at rest and after exercise, and 20 were aspirin sensitive at rest but exhibited biochemical aspirin resistance immediately after exercise. The results of exercise testing were similar in all three groups (each P > 0.05). Our results indicate that in almost 20% of the patients, aspirin did not seem to protect against exercise-induced platelet activation, despite the presence of aspirin sensitivity at rest. We did not, however, determine the extent to which the biochemical aspirin resistance noted in our study applied to clinical events.     

Prothrombotic Response to Coronary Angioplasty in Patients with Unstable Angina and Raised C-Reactive Protein

Background: To better understand the mechanisms linking C reactive protein (CRP) to the risk of coronary thrombosis, we investigated the relation between inflammatory state and hemostatic response to coronary angioplasty in patients with either stable or unstable angina. Methods: Plasma levels of von Willebrand factor (vWF) antigen, vWF collagen binding activity, vWF-cleaving-protease, CRP, and whole-blood platelet reactivity were measured before and 24 h after angioplasty in 18 patients with recent unstable angina and in 17 with stable angina. Each group was divided according to preprocedural CRP levels: 3 mg/l (in 9 unstable and 9 stable patients) or <3 mg/l (in 9 unstable and 8 stable patients). Results: Baseline hemostatic parameters did not differ significantly among the four subgroups of patients. After angioplasty, virtually all patients with unstable angina and raised preprocedural CRP showed increased vWF antigen (P = 0.01), vWF collagen-binding (P = 0.001), CRP (P = 0.008), and platelet reactivity (P = 0.0007) compared to baseline, whereas no significant change of these variables was seen within the other three sets of patients. In the overall population, the changes in vWF antigen and vWF-collagen-binding induced by angioplasty correlated with those in CRP levels (r = 0.47, P = 0.004 and r = 0.44, P = 0.008). Baseline levels of vWF cleaving protease and modifications of this enzyme with angioplasty did not differ significantly among subgroups. Conclusions: Our data suggest that high preprocedural levels of CRP predict a significant vWF rise after angioplasty in patients with unstable angina. The rise in vWF is associated with that in CRP and with enhanced platelet reactivity. Such changes may contribute to the worse prognosis of unstable patients with raised indices of inflammation.     

C-reactive protein response induced by fungal infections

Serial determinations of C-reactive protein (CRP) were performed by single radial immunodiffusion in four groups of patients with fungal disease in order to determine its use as an aid to diagnosis. Elevated values (17-284 mg/l) of CRP were seen in 13 patients with fungal septicaemia before and/or within a few days after the first positive blood culture. C-reactive protein was not elevated in two patients with transient fungaemia. In 76 per cent (25/33) of deep-seated fungal infections in patients with malignant disorders of the blood CRP increased to 104-380 mg/l. In the remainder values of 36-92 mg/l were seen. In 37 per cent (19/51) of episodes of acute uncomplicated fungal stomatitis in patients with malignant disorders of the blood CRP rose to 110-320 mg/l. C-reactive protein was not found to be raised from the normal value (less than or equal to 6 mg/l) in 6 per cent of the episodes; in the rest, values below 100 mg/l were seen. CRP in 23 patients with acute fungal stomatitis but who were not immunocompromised remained normal. Thus, with regard to its ability to induce high (greater than 100 mg/l) CRP values, deep-seated fungal disease would seem to resemble bacterial rather than viral infection.     

Markers of inflammation and platelet aggregation in patients with non ST elevation acute coronary syndrome treated with atorvastatin or pravastatin

AIM: To find out whether early use of atorvastatin and pravastatin in patients with non-ST elevation acute coronary syndrome is associated with rapid changes of platelet aggregation and plasma levels of markers of inflammation. MATERIAL AND METHODS: Ninety patients (<24h from pain onset, age 64+/-10 years) treated with aspirin and heparin were randomized to open atorvastatin 10 mg/day (n=30), atorvastatin 40 mg/day (n=29) or pravastatin 40 mg/day (n=31). Spontaneous and ADP induced platelet aggregation (light transmission), plasma levels of interleukin 6 (IL-6) and C-reactive protein (CRP) (immunoassay) were assessed at baseline, on days 7 and 14. RESULTS: Baseline clinical characteristics, platelet aggregation parameters, CRP and IL-6 levels were similar in all groups. In all groups levels of total and low-density lipoprotein (LDL) cholesterol (CH) were lowered by days 7 (p<0.01) and 14 (p<0.01 vs. baseline and for both atorvastatin groups vs. day 7). Spontaneous platelet aggregation decreased by 15% from baseline, p<0.01, on day 14 in patients receiving atorvastatin 40 and was unchanged in other groups. Changes of ADP induced platelet aggregation, IL-6 and CRP levels were not significant in all groups. However combination of 2 atorvastatin groups (n=59) revealed decrease of CRP by 18% from baseline on day 14 (from 6.94+/-0.97 to 4.76+/-0.76 mg/l, p=0.028). No correlations were found between changes of LDL CH and those of other parameters. CONCLUSION: In otherwise conventionally treated patients with non-ST elevation acute coronary syndrome early use of atorvastatin was associated with rapid (in 14 days) decrease of CRP level. Higher dose of atorvastatin (40 mg/day) induced favorable changes of spontaneous platelet aggregation. There were no significant changes of parameters studied in pravastatin treated patients.     

Effects of low-dose aspirin on serum C-reactive protein and thromboxane B2 concentrations: a placebo-controlled study using a highly sensitive C-reactive protein assay.

OBJECTIVES

We performed a placebo-controlled study to evaluate the effect of low-dose aspirin on serum C-reactive protein (CRP) levels.

BACKGROUND

Elevated circulating concentrations of CRP, an inflammatory marker, increase the risk of thrombotic cardiovascular diseases such as myocardial infarction (MI). Moreover, low-dose aspirin therapy has been reported to be more effective in preventing MI in men with higher CRP levels than it is in those with lower levels, raising the possibility that aspirin prevents thrombosis by reducing vascular inflammation. The effect of low-dose aspirin therapy on serum CRP levels in men has been addressed recently, but the results of the two studies conflict.

METHODS

Effects of aspirin (81 mg every day or 325, 81 or 40 mg every-third-day given for 31 days) on serum CRP, using a highly-sensitive assay, and on serum platelet-cyclo-oxygenase (COX)-1-derived thromboxane (Tx) B₂ concentrations were studied simultaneously in 57 healthy volunteers (30 men and 27 women).

RESULTS

Trough platelet COX-1-derived serum Tx B₂ concentrations decreased by 100% with daily aspirin and by 90%, 84% and 78% with 325, 81 and 40 mg aspirin every-third-day (p < 0.001). However, there were no significant changes in serum CRP levels from baseline with daily low-dose aspirin therapy, with any of the every-third-day aspirin regimens or with placebo treatment.

CONCLUSIONS

Low doses of aspirin that markedly inhibit platelet COX-1 activity, as manifested by a profound decline in platelet-derived serum Tx B₂ concentrations, have no detectable effect on serum CRP levels in healthy men and women.     

Relationship of C-reactive protein to presence and severity of coronary atherosclerosis in patients with stable angina pectoris or a pathological exercise test

BACKGROUND: C-reactive protein (CRP) level is a sensitive marker of inflammation and a probable predictor of cardiovascular risk. The aim of this study was to assess the relationship between the presence and the extent of coronary atherosclerosis and CRP level in patients referred for coronary angiography for stable angina pectoris or a pathological exercise test. PATIENTS AND METHODS: A group of 200 patients were prospectively analyzed for the relationship between the presence and extent of coronary atherosclerosis and high-sensitivity CRP. Patients with stable angina pectoris or a pathological exercise test were included. RESULTS: For the whole group the CRP geometric mean was 2.92 mg/l and the median 3.0 mg/l. There was no difference between groups of patients with different extents of coronary lesions (P = 0.320, one-way analysis of variance). In patients without significant coronary disease the CRP geometric mean was 3.1 (2.28-4.21) mg/l with a variation coefficient of 118.4%; in patients with coronary artery disease the geometric mean was 2.83 (2.34-3.43) mg/l with a variation coefficient of 104.0%. The difference in CRP between both groups was not significant (P = 0.601). There was also no significant difference in CRP levels between groups of patients with and without a history of myocardial infarction (2.65 (2.08-3.36) mg/l and 3.18 (2.54-3.98) mg/l, P = 0.266) respectively. There was no correlation between the classification of angina pectoris and the logarithm of CRP level (P = 0.331). This relationship was not confirmed even in the group of patients with significant coronary artery disease (P = 0.693). CONCLUSIONS: CRP level is not related to the extent or the presence of coronary atherosclerosis assessed by coronary angiography, history of myocardial infarction or class of stable angina pectoris in patients referred for coronary angiography for stable angina pectoris or a pathological exercise test.     

Anti-inflammatory effects of simvastatin in subjects with hypercholesterolemia

AIMS: Beneficial effects of statins in preventing cardiovascular events may depend, at least in part, on their anti-inflammatory action. The aim of the study was to assess the influence of simvastatin and aspirin on serum levels of C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in hypercholesterolemic subjects. METHODS AND RESULTS: In 33 asymptomatic men with total cholesterol (TC) >6.5 mmol l(-1) and in 25 men with coronary heart disease and borderline-high cholesterol levels (between 5.2 and 6.5 mmol l(-1)) chronically treated with low-dose aspirin (75 mg/d), serum levels of CRP, TNF-alpha, IL-6, and IL-8 were determined before and after a 3-month simvastatin therapy (20-40 mg daily). In the former group, these markers of inflammation were also measured before and after a 2-week treatment with aspirin (300 mg/d), implemented prior to and in combination with simvastatin. A distinct reduction of CRP and TNF-alpha was found in both groups; IL-6 levels were decreased only in subjects with marked hypercholesterolemia. Aspirin had no effect on the anti-inflammatory action of simvastatin. CONCLUSIONS: In men with hypercholesterolemia simvastatin treatment lowers serum levels of CRP and proinflammatory cytokines. Low-dose aspirin does not add to the anti-inflammatory action of simvastatin.