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.     

Moderate alcohol consumption and lower levels of inflammatory markers in US men and women

OBJECTIVE: Moderate alcohol consumption is associated with substantially lower risk of cardiovascular disease (CVD). We assessed the relationship between alcohol intake and inflammatory markers to partially explain this beneficial effect. METHODS AND RESULTS: From two large prospective studies, we sampled 959 healthy male and 473 healthy female health professionals with reported alcohol intake. Markers of inflammation were soluble tumor necrosis factor-alpha receptors 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein (CRP), and interleukin-6 (IL-6). We found significant inverse linear trends for sTNF-R1 (p-trend<0.001 men; 0.03 women) and sTNF-R2 (p-trend=0.002 men; 0.08 women) with increasing alcohol intake. Compared to non-drinkers, men who consumed on average 1-2 drinks/day had 26% lower CRP (-0.66 mg/L, p=0.13), and 36% lower IL-6 (-1.12 pg/ml, p=0.02) levels. Among women, a similar though stronger association was observed at half drink per day. Compared to non-drinkers, both men and women who consumed 1-2 drinks/drinking day had significantly lower sTNF-R1 (-9% in men, -6% in women) and sTNF-R2 (-7% in men, -6% in women) levels as well as lower CRP (-10% in men, -32% in women) and IL-6 (-45% in men, -27% in women) levels. CONCLUSIONS: Alcohol in moderation is associated with lower levels of inflammatory markers and may lower risk of CVD through these mechanisms.     

C-reactive protein, interleukin-6, secretory phospholipase A2 group IIA and intercellular adhesion molecule-1 in the prediction of late outcome events after acute coronary syndromes

OBJECTIVE: We investigated whether levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A(2) group IIA (sPLA(2)-IIA) and intercellular adhesion molecule-1 (ICAM-I) predict late outcomes in patients with acute coronary syndromes (ACS). DESIGN: Prospective longitudinal study. CRP (mg L(-1)), IL-6 (pg mL(-1)), sPLA(2)-IIA (ng mL(-1)) and ICAM-1 (ng mL(-1)) were measured at days 1 (n = 757) and 4 (n = 533) after hospital admission for ACS. Their relations to mortality and rehospitalization for myocardial infarction (MI) and congestive heart failure (CHF) were determined. SETTING: Coronary Care Unit at Sahlgrenska University Hospital, Gothenburg, Sweden. SUBJECTS: Patients with ACS alive at day 30; median follow-up 75 months. RESULTS: Survival was related to day 1 levels of all markers. After adjustment for confounders, CRP, IL-6 and ICAM-1, but not sPLA(2)-IIA, independently predicted mortality and rehospitalization for CHF. For CRP, the hazard ratio (HR) was 1.3 for mortality (95% confidence interval (CI): 1.1-1.5, P = 0.003) and 1.4 for CHF (95% CI: 1.1-1.9, P = 0.006). For IL-6, HR was 1.3 for mortality (95% CI: 1.1-1.6, P < 0.001) and 1.4 for CHF (95% CI: 1.1-1.8, P = 0.02). For ICAM-1, HR was 1.2 for mortality (95% CI: 1.0-1.4, P = 0.04) and 1.3 for CHF (95% CI: 1.0-1.7, P = 0.03). No marker predicted MI. Marker levels on day 4 provided no additional predictive value. CONCLUSIONS: In patients with ACS, CRP, IL-6, sPLA(2)-IIA and ICAM-1 are associated with long-term mortality and CHF, but not reinfarction. CRP, IL-6 and ICAM-1 provide prognostic information beyond that obtained by clinical variables.     

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.     

Prolonged application of clopidogrel reduces inflammation after percutaneous coronary intervention in the porcine model

OBJECTIVE: We determined the effect of prolonged treatment with clopidogrel on C-reactive protein (CRP) concentrations and blood thrombogenicity after percutaneous transluminal coronary angioplasty followed by intracoronary brachytherapy in the porcine model. ANIMAL MODEL: All 48 pigs received antiplatelet therapy, including aspirin (325 mg, daily) and clopidogrel (300 mg, loading dose) 1 day before PCI, followed by a daily dose of clopidogrel (75 mg/day) in addition to aspirin. During PCI, one of two balloon-injured arteries was randomly assigned to receive immediate radiation treatment. Animals were sacrificed after 24 h, 1 month, and 3 months post-PCI. The pigs, which were sacrificed 3 months post-PCI, were divided into two groups. The first group received clopidogrel in addition to aspirin for 3 months, and the second group received clopidogrel in addition to aspirin for only 1 month after PCI and then aspirin alone. METHODS: Blood was taken from all pigs before intervention, immediately after intervention, and before sacrifice. Serum CRP was measured by enzyme-linked immunosorbent assay. To analyze the procoagulant effects of PCI on blood thrombogenicity, a one-stage clotting assay was performed. RESULTS: Clopidogrel treatment for 3 months reduced CRP levels more than did clopidogrel therapy for 1 month only at 3 months post-PCI (27.9+/-3.9 vs. 56.6+/-11.3 microg/ml; P=.019). Baseline CRP levels were found to be 50.4+/-4.8 microg/ml. Plasma clotting was not affected by prolonged clopidogrel therapy (322.8+/-59.3 s vs. 295.2+/-52.5 s; P=ns). CONCLUSIONS: Prolonged treatment with clopidogrel reduced CRP levels post-PCI.     

CRP, interleukin-6, secretory phospholipase A2 group IIA, and intercellular adhesion molecule-1 during the early phase of acute coronary syndromes and long-term follow-up

OBJECTIVES: The objectives of this study were to examine the time course of the inflammatory response in acute coronary syndromes (ACS) and to assess the markers of inflammation and their relation to disease severity. METHODS: We prospectively studied 134 patients with ACS who survived for at least 30 months. The patients were divided into four groups: acute myocardial infarction (MI) with (n=54) or without (n=46) ST-segment elevation and unstable angina with (n=14) or without (n=20) increased risk. Plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6), secretory phospholipase A2 group IIA (sPLA2-IIA), and intercellular adhesion molecule-1 (ICAM-1) were measured on days 1 and 4 and after 3 and 30 months. RESULTS: The highest levels of CRP and sPLA2-IIA were seen on day 4 but for IL-6 on day 1. These three markers, but not ICAM-1, were significantly related to disease severity, CKMB, and ejection fraction. Patients in Killip class II-IV had higher levels than those in Killip class I. The individual acute-phase responses correlated with marker levels at 3 and 30 months. ICAM-1 correlated with the development of congestive heart failure. CONCLUSIONS: In ACS there seems to be an individual predisposition to inflammatory response. Plasma IL-6 is the first marker to rise, while sPLA2-IIA and CRP peak later. All three markers, especially CRP, may discriminate between MI and non-MI. ICAM-1 seems to reflect other aspects of the inflammatory processes than the other markers. The results emphasize the complexity of the inflammatory response in ACS and stress the need for further studies involving multiple markers.     

Apolipoprotein E genotype and circulating interleukin-10 levels in patients with stable and unstable coronary artery disease.

OBJECTIVES: This study was designed to assess the relation between apolipoprotein E (apoE) genotype and serum interleukin (IL)-10 levels in patients with acute coronary syndrome (ACS) and chronic stable angina (CSA). BACKGROUND: Genetic variations in the apoE gene affect the risk for coronary artery disease (i.e., carriers of the e4 allele have an increased risk). Increased levels of C-reactive protein (CRP), an inflammatory marker, correlate with an increased risk of acute coronary events, whereas increased IL-10 concentrations have an atheroprotective role. Studies have reported a negative association between the apoE e4 allele and CRP levels. METHODS: Apolipoprotein E genotypes were assessed in 166 consecutive ACS patients (119 men, mean age 68 years, interquartile range [IQR] 60 to 74 years) and 70 CSA patients (54 men, mean age 65 years, IQR 62 to 68 years). Serum IL-10 and CRP were assessed at study entry. RESULTS: Analysis of covariance showed that genetic variation in the apoE gene locus significantly influences serum IL-10 levels in both ACS (p = 0.009) and CSA patients (p = 0.013). Among ACS patients, IL-10 levels were lower in E3/E4 carriers compared with E3/E3 carriers (p = 0.01) and marginally lower compared with E2/E3 carriers (p = 0.065). Among CSA patients, IL-10 levels were lower in E3/E4 carriers compared with E2/E3 carriers (p = 0.004) and marginally lower compared with E3/E3 carriers (p = 0.086). CONCLUSIONS: The IL-10 concentrations differ in ACS and in CSA patients with different apoE genotypes. The e4 allele was associated with a trend toward lower IL-10 serum levels. Our results may provide an explanation of findings in previous studies that cardiovascular risk is higher in e4 carriers despite the presence of low CRP levels.     

急性冠脉综合征早期辛伐他汀治疗对血脂和炎症反应标记物的影响

目的　观察急性冠脉综合征 (ACS)早期辛伐他汀治疗对血脂和炎症反应标记物的影响及差异 ,探讨他汀类药物在ACS早期治疗中的作用。　方法　ACS住院患者 12 3例 ,入院后测定血浆甘油三酯 (TG)、总胆固醇(TC)、低密度脂蛋白胆固醇 (LDL C)、高密度脂蛋白胆固醇 (HDL C)、白细胞介素 6 (IL 6 )和C反应蛋白 (CRP)水平 ,然后随机分为辛伐他汀治疗组和非辛伐他汀治疗组。出院时重复测定上述指标。同期测定 15例慢性稳定性心绞痛 (CAP)患者和 15名健康者作对照比较。　结果　 1 ACS患者血浆TC、LDL C、IL 6、CRP显著高于健康者 (P <0 0 1) ,血浆LDL C、IL 6显著高于CAP患者 (P <0 0 1)。 2 出院与入院时比较 ,辛伐他汀组和非辛伐他汀组血浆IL 6、CRP显著降低 (P <0 0 1) ,出院时辛伐他汀组血浆IL 6、CRP也显著低于非辛伐他汀组 (P <0 0 1)。 3 据入院时血浆IL 6、CRP水平 ,把ACS患者分别分为IL 6、CRP高值组和低值组 ,出院与入院时比较 ,高值组和低值组血浆IL 6、CRP均显著降低 (P<0 0 1,P<0 0 1) ,但只有高值组 ,出院时辛伐他汀治疗者血浆IL 6、CRP显著低于非辛伐他汀治疗者 (P <0 0 1,P <0 0 5 )。　结论　ACS患者早期辛伐他汀治疗有明显抗炎症作用。     

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.     

辛伐他汀对急性冠脉综合征患者血清C-反应蛋白的影响

目的观察急性冠脉综合征(ACS)患者早期应用辛伐他汀治疗对血脂和炎症反应标记物的影响及差异,探讨他汀类药物在ACS早期治疗中的作用。方法 ACS住院患者113例,入院后测定血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、白介素-6(IL-6)和C反应蛋白 (CRP)水平,然后随机分为辛伐他汀治疗组和对照组。出院时重复测定上述指标。同期测定30例健康者作对照比较。结果治疗组治疗后CRP、IL-6比治疗前明显下降,差异有显著性意义(P<0．05)。结论 ACS患者早期应用辛伐他汀治疗有明显的抗感染作用。     

Peripheral levels of matrix metalloproteinase-9, interleukin-6, and C-reactive protein are elevated in patients with acute coronary syndromes: correlations with serum troponin I

BACKGROUND: Acute coronary syndromes (ACS) are characterized by activation of systemic and local inflammatory mediators. The interrelation between these soluble inflammatory markers and their association with markers of myocardial necrosis have not been extensively studied. HYPOTHESIS: The study was undertaken to evaluate the association of the systemic levels of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1), with C-reactive protein (CRP), interleukin-6 (IL-6), and serum troponin-I in patients admitted with ACS. METHODS: Analysis of serum concentrations of the above inflammatory markers was performed in 53 patients with unstable angina (UA) and in 15 with non-ST-segment elevation myocardial infarction (NSTEMI) within 48 h of admission, and 34 patients with stable coronary artery disease. RESULTS: Compared with patients with stable angina, those with ACS had elevated admission levels of MMP-9 (p = 0.04), CRP (p < 0.001), and IL-6 (p = 0.001), but not TIMP-1 (p = 0.55). Compared with patients with UA, those with NSTEMI also had higher levels of IL-6 (p < 0.001), CRP (p = 0.002), and MMP-9 (p = 0.05). CONCLUSIONS: In patients with ACS, the admission levels of inflammatory mediators, including MMP-9, CRP, and IL-6 are significantly elevated, specifically in association with serum troponin I. Systemic and local markers of inflammatory activity may be directly associated with myocardial injury.     

急性冠状动脉综合征患者白细胞介素-10及白细胞介素-6表达

目的:通过与C反应蛋白(CRP)检测对比,探讨抗炎因子白细胞介素(IL)-10、促炎因子IL-6与急性冠状动脉综合征(ACS)的关系。方法:冠心病患者78例,其中ACS患者40例(ACS组),稳定型心绞痛(SAP组)患者38例,33例胸痛综合征(CPS组)患者作为对照。所有患者均行冠状动脉造影检查。采用ELISA法检测血浆IL-6、IL-10水平,采用免疫比浊法测定CRP值。结果:与SAP组及CPS组相比,ACS组血浆IL-10水平明显降低,IL-6、CRP水平明显升高,差异有统计学意义;SAP组IL-10水平低于CPS组,IL-6、CRP水平高于CPS组,差异无统计学意义;血浆IL-10水平与IL-6及CRP水平呈负相关,IL-6水平与CRP水平正相关。结论:血浆IL-10水平降低和IL-6、CRP值升高对患者ACS的发生有预测价值。抗炎因子和促炎因子水平的失衡是导致斑块不稳定、急性冠状动脉事件发生的重要因素。     

Pre-procedural plasma levels of C-reactive protein and interleukin-6 do not predict late coronary angiographic restenosis after elective stenting.

AIMS: Inflammatory markers may serve as an important prognostic predictor in patients with coronary heart diseases. In patients undergoing coronary interventions, it has been shown that baseline C-reactive protein (CRP) could predict late clinical restenosis. Only a few small studies have examined the possible relationship with angiographic restenosis. In patients with stable angina pectoris,we examined whether baseline CRP and IL-6 predict late coronary angiographic restenosis after stenting. METHODS AND RESULTS: Pre-procedural plasma levels of CRP and IL-6 were measured in 216 patients with stable angina pectoris undergoing elective coronary stenting. Angiographic follow-up was performed in all patients at 6 months. Baseline CRP levels were 6.15 +/- 0.78 mg/L versus 5.24 +/- 1.17 mg/L in the patent and restenosis groups, respectively (P=0.64). IL-6 levels were 0.46 +/- 0.03 ng/L versus 0.40 +/- 0.07 ng/L in the patent and restenosis groups, respectively (P=0.50). CRP levels were obtained again at the time of angiographic follow-up and were found to be similar in both groups (2.89 +/- 0.29 mg/L versus 2.61 +/- 0.63 mg/L, P=0.72). Moreover, in a sub-group of 43 patients, serial blood samples were obtained at several time points after the procedure up to 6 months. Both CRP and IL-6 plasma levels increased significantly in response to the procedure. CRP levels peaked at 3 days (11.27 +/- 1.53 mg/L versus 4.26 +/- 0.72 mg/L at baseline, P<0.0001). IL-6 levels reached maximum values after 24 h (1.08 +/- 0.14 ng/L versus 0.53 +/- 0.08 ng/L at baseline, P<0.0001). However, in this sub-group of patients, neither peak CRP nor IL-6 levels were found to predict late angiographic restenosis. CONCLUSIONS: Coronary stenting is associated with transient increases in both CRP and IL-6 levels. However, pre-procedural CRP and IL-6 levels do not predict late coronary angiographic restenosis.     

不同剂量阿司匹林对急性冠状动脉综合征炎性标志物和预后的影响

目的 观察不同剂量阿司匹林对急性冠状动脉综合征(ACS)患者炎性标志物和临床预后的影响.方法 将ACS患者随机分为不同剂苗阿司匹林治疗组(A组100 mg/d、B组500 mg/d和C组1000 mg/d)治疗和随访1年,检测各时段炎性标志物水平,并记录有关临床事件.结果 共入选312例,A组106例,B组104例,C组102例.所有入选者基线超敏C反应蛋白(hsCRP)、IL-6、TNFα均显著高于正常参考值,应用不同剂量阿司匹林治疗1、6、12个月后,炎性标志物均下降,治疗前后各指标比较差异均有统计学意义,但各组间比较差异无统计学意义.3组急性冠状动脉事件发生率差异无统计学意义,B、C组发生胃肠道不适症状者较A组增加.结论 ACS患者血清炎性标志物升高,应用阿司匹林治疗后炎性标志物水平显著下降,但大剂量阿司匹林(500～1000 mg)未见炎性标志物水平进一步下降和再发心脏事件减少,而胃肠道不良反应有所增加.     

替格瑞洛对ACS患者PCI后QTd及hs-CRP、sCD40L的影响

目的：探讨替格瑞洛对急性冠脉综合征（ACS）患者在经皮冠状动脉支架植入术（PCI）后QT离散度（QTd）以及对炎性因子hs-CRP、sCD40L的影响;方法：抽取本院2017年1月至2017年12月接受PCI治疗的ACS患者69例,随机分为对照组34例（口服氯吡格雷）、试验组35例（口服替格瑞洛）,两组均使用阿司匹林行双联抗血小板聚集（DAPT）治疗1年。测量两组治疗前及术后24h、1月、1年QTd值以及静脉血hs-CRP、sCD40L值。术后6个月随访恶性心律失常的发生情况;结果：术后24h、1月、1年,试验组QTd值及hs-CRP、sCD40L水平均低于对照组（P<0.05）。术后6个月内,试验组恶性心律失常发生率（22.9%）小于对照组（47.1%）（P<0.05）。结论 ACS患者PCI围术期应用替格瑞洛能显著缩短QTd,降低炎性因子hs-CRP、sCD40L水平,降低恶性心律失常发生率,显著改善预后。     

Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory activity in patients with coronary artery disease--a randomized placebo-controlled study

The balance between different immunological stimuli is essential in the progression and stabilization of atherosclerotic plaques. Immune regulation has been suggested as potential target for the treatment of atherosclerotic disease. We sought to determine whether treatment with pentoxifylline, a phosphodiesterase inhibitor with immunomodulating properties, could reduce the pro-inflammatory response observed in patients with acute coronary syndromes (ACS) and increase anti-inflammatory activity. In a double-blind, prospective, placebo-controlled study, 64 patients with ACS were randomized to receive pentoxifylline 400mg TID or placebo for 6 months. Analysis of the pro-inflammatory markers, C-reactive protein (CRP), interleukin (IL)-6, IL-12, interferon-gamma and tumor necrosis factor (TNF)-alpha and the anti-inflammatory cytokines, transforming growth factor (TGF)-beta1 and IL-10 were done at baseline, 1 and 6 months. Pentoxifylline treatment significantly reduced the adjusted levels of CRP and TNF-alpha compared to placebo after 6 months (P=0.04 and P<0.01, respectively). IL-12 increase was significantly less pronounced with pentoxifylline (P=0.04). The levels of the anti-inflammatory cytokine, IL-10, also declined significantly less in the pentoxifylline group compared to placebo (P<0.01) with a trend towards a higher increase of TGF-beta1 in the former group (P=0.16). Pentoxifylline reduces pro-inflammatory and increases anti-inflammatory response in patients with ACS and may have beneficial clinical effects on cardiovascular events.     

Dietary alpha-linolenic acid decreases C-reactive protein,serum amyloid A and interleukin-6 in dyslipidaemic patients

BACKGROUND: Inflammation plays an important role in the pathogenesis of coronary artery disease. We examined whether dietary supplementation with alpha-linolenic acid (ALA, 18:3n-3) affects the levels of inflammatory markers in dyslipidaemic patients. METHODS: We recruited 76 male dyslipidaemic patients (mean age=51+/-8 years) following a typical Greek diet. They were randomly assigned either to 15 ml of linseed oil (rich in ALA) per day (n=50) or to 15 ml of safflower oil (rich in linoleic acid (LA, 18:2n-6)) per day (n=26). The ratio of n-6:n-3 in linseed oil supplemented group was 1.3:1 and in safflower oil supplemented group 13.2:1. Dietary intervention lasted for 3 months. Blood lipids and C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) levels were determined prior and after intervention. CRP and SAA were measured by nephelometry and IL-6 by immunoassay. RESULTS: Dietary supplementation with ALA decreased significantly CRP, SAA and IL-6 levels. The median decrease of CRP was 38% (1.24 vs. 0.93 mg/l, P=0.0008), of SAA 23.1% (3.24 vs. 2.39 mg/l, P=0.0001) and of IL-6 10.5% (2.18 vs. 1.7 pg/ml, P=0.01). The decrease of inflammatory markers was independent of lipid changes. Dietary supplementation with LA did not affect significantly CRP, SAA and IL-6 concentrations but decreased cholesterol levels. CONCLUSIONS: Dietary supplementation with ALA for 3 months decreases significantly CRP, SAA and IL-6 levels in dyslipidaemic patients. This anti-inflammatory effect may provide a possible additional mechanism for the beneficial effect of plant n-3 polyunsaturated fatty acids in primary and secondary prevention of coronary artery disease.     

Hormone therapy, C-reactive protein, and progression of atherosclerosis: data from the Estrogen Replacement on Progression of Coronary Artery Atherosclerosis (ERA) trial

Objective

To compare the effects of estrogen and estrogen plus progestin on levels of C-reactive protein (CRP) and interleukin-6 (IL-6), and to examine the relationship between these changes and progression of angiographically defined coronary disease.

Methods

Baseline and follow-up (year 1 and year 3) plasma levels of IL-6 and CRP were measured in a subset of 232 patients from the Estrogen Replacement in Atherosclerosis (ERA) trial.

Results

Serial angiograms were also available at baseline and closeout. Estrogen alone increased CRP by 40% (P = .01) at 1 year and 38% P = .002) at closeout. Estrogen plus medroxyprogesterone acetate increased CRP by 44.7% P = .001) at 1 year and 54.7% P = .0001) at closeout as compared with baseline levels. There were no significant changes in IL-6 with either treatment. In women in the active treatment arm, change in CRP during the first year was not associated with progression of coronary disease P = .2).

Conclusions

Estrogen and estrogen plus medroxyprogesterone significantly raise CRP levels in women with established coronary disease. In contrast, IL-6 levels are not affected by estrogen or estrogen plus progestin. Estrogen-induced changes in CRP are not associated with progression of atherosclerosis.     

经皮冠状动脉腔内介入围术期应用高维持剂量氯吡格雷对炎症因子的影响

目的:探讨高维持剂量(150 mg/d)氯吡格雷是否能抑制动脉粥样硬化炎症反应。方法:经Grace评分分级的高危急性冠状动脉综合征(ACS)患者80例,经皮冠状动脉腔内介入术(PCI)后随机分为氯吡格雷75 mg/d组(n=40)与氯吡格雷150 mg/d组(n=40),30 d后均以75 mg/d维持治疗。分别检测PCI术前、30 d的高敏C反应蛋白(hs-CRP)、白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平。随访术后6个月的主要不良心脏事件(MACE)及出血事件的发生情况。结果:1.氯吡格雷150 mg/d组和75 mg/d组,术前hs-CRP、IL-6、TNF-α水平比较差异无统计学意义(P>0.05);2.2组PCI术后30 d血清hs-CRP、IL-6、TNF-α水平均较术前显著降低(P<0.01),且氯吡格雷150 mg/d组较75 mg/d组对上述炎症因子的抑制程度更明显(P<0.05);3.2组MACE发生情况差异有统计学意义(P<0.05),而出血事件发生率差异无统计学意义(P>0.05)。结论:PCI围术期应用高维持剂量氯吡格雷,可以进一步抑制高危ACS患者动脉炎症反应而不增加出血风险,有助于降低短期MACE发生率。     

Effect of cyclooxygenase-2 inhibition with rofecoxib on endothelial dysfunction and inflammatory markers in patients with coronary artery disease

OBJECTIVES: The aim of this study was to determine whether selective cyclooxygenase-2 (COX-2) inhibition with rofecoxib can modulate endothelial dysfunction and levels of circulating inflammatory markers in patients with established coronary artery disease (CAD). BACKGROUND: Expression of COX-2 is upregulated in atherosclerosis. Thus, it has been hypothesized that COX-2 may contribute to atherogenesis by producing eicosanoids, which mediate vascular inflammation and endothelial dysfunction. METHODS: In a randomized, double-blind, placebo-controlled, parallel-design trial, we studied the vascular effects of rofecoxib on brachial artery vasoreactivity and inflammatory markers in 60 patients with angiographically proven CAD who were taking concomitant low-dose aspirin. Patients were randomly assigned to receive either rofecoxib (25 mg/day; n = 30) or placebo (n = 30) for eight weeks. Brachial artery endothelium-dependent flow-mediated dilation (FMD), endothelium-independent nitroglycerin-mediated dilation (NMD), and inflammatory markers (i.e., high-sensitivity C-reactive protein [CRP], soluble intercellular adhesion molecule-1 [sICAM-1], and soluble interleukin-6 receptor [sIL-6r]) were measured at baseline and after eight-week follow-up. RESULTS: Baseline clinical characteristics were similar in the two groups. After eight weeks of treatment, FMD did not significantly change in either the rofecoxib or placebo group (4.0 +/- 3.0% to 4.0 +/- 3.8% vs. 2.7 +/- 2.7% to 3.1 +/- 2.7%, respectively; p = 0.6 by two-way analysis of variance). Similarly, NMD remained unchanged in both groups. Levels of CRP, sICAM-1, and sIL-6r were not significantly altered in either the rofecoxib or placebo group. CONCLUSIONS: The addition of selective COX-2 inhibition with rofecoxib did not appear to have any favorable or adverse effects on endothelial dysfunction or vascular inflammation in patients with CAD using concomitant low-dose aspirin.