阿司匹林在心血管病患者中的抵抗现象

目的 :调查冠心病患者发生阿司匹林抵抗 （AR）的发生率和流行病学特征 ,并探讨其相关因素。方法 :病情稳定的冠心病患者 2 0 9例 ,每日服用阿司匹林 10 0 mg,连服 7d,服用最后一剂后 2 4h内抽取空腹静脉血 ,分别用二磷酸腺苷 （ADP）、花生四烯酸 （AA）诱导血小板凝集试验 （PAg T） ,检测血小板聚集率。结果 :患者中 AR发生率为3 .8% ,阿司匹林半敏感 （ASR）者占 2 5.8% ,且 AR或 ASR患者中的女性比率较阿司匹林敏感者 （AS）高 （P <0 .0 5） ,而 AS者中吸烟者较 AR或 ASR者多 （P<0 .0 1）。结论 :阿司匹林用于抗血小板治疗及预防动脉硬化事件的冠心病患者可产生 AR,预测 AR及抗血栓治疗个体化 ,将有利于抗血栓治疗     

阿司匹林抵抗研究进展

阿司匹林自上世纪 70年代起作为抗血小板药物而广泛应用于心脑血管疾病的二级预防。最近 ,抗血栓试验协作组的研究表明 ,应用抗血小板药物后 ,在动脉血栓疾病高危人群中 ,所有严重心血管事件联合终点都得到减少 〔1〕。其机制是通过灭活血小板环氧酶 1来抑制血栓烷素的生物合成来发挥作用。然而在有症状动脉血栓患者中 ,阿司匹林仍不能阻止至少 75 %的严重血管事件发生〔1〕。因此近年来学者提出了“阿司匹林抵抗”(aspirinresistance ,AR)这一概念。1　AR的定义1 1　 临床AR　临床AR是指阿司匹林的临床应用不能保护患者减少或避免缺血…     

阿司匹林抵抗现象的研究

阿司匹林是一种有着百年历史的临床药物,在心血管系统疾病,尤其是缺血性心脏病治疗中被广泛应用,但近年来发现有部分患者存在阿司匹林抵抗(AR)现象,本文就对这一现象作一综述。1 AR的定义阿司匹林在血栓性心血管疾病的1、2级预防中具有重要作用〔1〕。然而有部分患者虽然应用阿     

阿司匹林抵抗的现状及展望

阿司匹林（ASR）作为抗血小板药物广泛用于心脑血管病的二级预防及高危患者的一级预防,是心脑血管病预防和治疗的关键用药。大规模临床试验荟萃（meta）分析证实,ASR可减少高危患者心肌梗死、心源性猝死及脑卒中的危险性23％。但临床工作者发现,在规律服用治疗剂量ASR的情况下,仍有心脑血管事件的发生,故提出了阿司匹林抵抗（aspirin resistance AR）的概念。     

阿司匹林抵抗

1概述阿司匹林问世已有一百余年,开始主要用于止痛、退热、抗炎及抗风湿治疗。上世纪70年代发现,阿司匹林通过不可逆抑制环氧化酶-1的活性,发挥抗血小板聚集的作用。大量临床试验显示,阿司匹林在高危患者发生心肌梗死、缺血性脑血管病的一级预防中是一种有效的抗血小板药物。有研究表明,与安慰剂组比较,服用阿司匹林的中年男性在5年随访期间首次心肌梗死的发生率下降44%[1]。阿司匹林对于心肌梗死和缺血性血管事件的二级预防也证实有效,一个包括65项研究的荟萃分析表明,应用阿司匹林治疗的高危患者血管事件发生率下降23%[2]。每天口服75～32…     

阿司匹林心血管病一级预防新证据

本文详细介绍了阿司匹林在心血管疾病一级预防的新证据：高血压最佳治疗研究（HOT）的肾功能异常亚组分析和澳大利亚Fremantle糖尿病研究,并对美国3个学会的声明进行评述,认为这些最新的证据进一步证实了阿司匹林的一级预防效益。     

阿司匹林在心血管病一级预防的地位

阿司匹林作为急性心肌梗死和冠心病二级预防的基础药物已得到广泛认可,然而近年来关于阿司匹林对心血管疾病的一级预防依然存在争议。阿司匹林可降低心脑血管事件的发生率,但同时又可增加出血事件。如何将其合理地运用在心血管疾病一级预防中使更多的患者获益是临床工作者的一大难题。越来越多的大规模临床研究表明阿司匹林作为心血管疾病一级预防药物的关键在于把握危险分层,进一步评价患者的状况,规范使用阿司匹林将会有效地减少心血管疾病的风险。与此同时国外许多指南及我国专家的共识均能指导医生在心血管疾病一级预防中规范地运用阿司匹林。     

阿司匹林抵抗

研究表明在接受阿司匹林治疗的心血管疾病患者中有5％～45％存在阿司匹林抵抗，由于全球有大量的患者依赖阿司匹林的抗血小板治疗，所以关于阿司匹林抵抗的研究已经引起广泛关注。本文综述阿司匹林抵抗的可能机制。     

老年心血管病合并高同型半胱氨酸血症患者阿司匹林抵抗发生率及危险因素调查

目的探讨老年心血管病患者合并高同型半胱氨酸血症(Hhcy)的阿司匹林抵抗(AR)的发生率及危险因素。方法共纳入370例老年心血管病患者,其中Hhcy患者216例(Hhcy组),非Hhcy患者154例(对照组),均接受常规阿司匹林治疗(≥75mg)>1个月。阿司匹林的疗效评价采用光比浊法检测血小板聚集率,AR定义为花生四烯酸诱导的血小板聚集率≥20%。结果 Hhcy组AR发生率显著高于对照组(16.7%vs 7.8%,P=0.012);与对照组比较,Hhcy组同型半胱氨酸和肌酐水平显著升高(P<0.05,P<0.01)。logistic回归分析显示,Hhcy是发生AR的独立危险因素(OR=2.406,95%CI:1.201~4.820,P=0.013)。结论老年心血管病患者合并Hhcy的AR发生率明显增加,Hhcy是老年心血管病患者发生AR的重要危险因素。     

阿司匹林在心血管病一级预防中的新证据新指南

<正>有效降低人群心血管病发病率和病死率,主要依靠一级预防。阿司匹林在心血管病一级预防中的地位,尚存争议。近年,国内外相关指南更新,再次肯定阿司匹林在心血管病一级预防的作用,同时还有许多问题,待进一步明确。1阿司匹林对心血管病一级预防的获益阿司匹林在一级预防中的研究,包括9项随机临床对照试验。在6项较早期的研究中,英国男性医师试验、美国男性医师健康研究和血栓预防研究,均为男性患者;高血压最适治疗研究和阿司匹林一级预防计划,则包含男性和女性患者。女性健康研究仅为女性患者。新近发表的一系列研究,为阿司匹林对心血管病一级预防,提供了更多的证据。     

High prevalence of aspirin resistance in elderly patients with cardiovascular disease and metabolic syndrome

Objective Metabolic syndrome is known to be a prothrombotic state. We undertook this study to examine a hypothesis that aspirin resistance may be associated with metabolic syndrome, and to assess other potential determinants of aspirin resistance in patients with cardiovascular disease (CVD). Methods A total of 469 elderly patients with CVD were recruited. One hundred and seventy-two patients with metabolic syndrome and 297 without metabolic syndrome (control group) received daily aspirin therapy (≥ 75 mg) over one month. Platelet aggregation was measured by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)- and ≥ 70% adenosine diphosphate (ADP) ADP-induced aggregation according to LTA. Aspirin semi-responders were defined as meeting one (but not both) of these criteria. Results By LTA, 38 of 469 (8.1%) patients were aspirin resistant. The prevalence of aspirin resistance was higher in the metabolic syndrome group compared with the control group [11.6 % vs. 6.6%, odds ratio (OR) = 2.039; 95% confidence interval (CI) = 1.047–3.973]. In the multivariate logistic regression analysis, metabolic syndrome (OR = 4.951, 95% CI = 1.440–17.019, P = 0.011) was a significant risk factor for aspirin resistance. Conclusions A significant number of patients with CVD and metabolic syndrome are resistant to aspirin therapy. This might further increase the risk of cardiovascular morbidity and mortality in these patients.     

High prevalence of aspirin resistance in elderly patients with cardiovascular disease (CVD) and hyperhomocysteinaemia

Although aspirin resistance is well reported in CVD, little is known about aspirin response in elderly patients with hyperhomocysteinaemia. The aim of the present study was to explore the prevalence of aspirin resistance in elderly patients with CVD and hyperhomocysteinaemia. A total of 370 elderly patients with CVD were recruited. The study included 216 patients with hyperhomocysteinaemia and 154 patients with normohomocysteinaemia receiving daily aspirin therapy (≥75 mg) over 1 month. The effect of aspirin was assessed using by light transmission aggregometry (LTA). Aspirin resistance was defined as ≥20% arachidonic acid induced aggregation according to LTA. Aspirin resistance was defined in 48 (13.0%) of 370 patients. The prevalence of aspirin resistance was higher in hyperhomocysteinaemic patients than normohomocysteinaemic patients (16.7% vs. 7.8%, odds ratio (OR) = 2.367; 95% confidence interval (CI) = 1.188–4.715, p = 0.012). In the multivariate logistic regression analysis, hyperhomocysteinaemia (OR = 2.406, 95% CI = 1.201–4.820, p = 0.013) was a significant risk factor for aspirin resistance. A significant number of CVD patients with hyperhomocysteinemia are resistant to aspirin therapy. Hyperhomocysteinemia is a significant risk factor for aspirin resistance in elderly patients with CVD.     

Establishing a predictive model for aspirin resistance in elderly Chinese patients with chronic cardiovascular disease

Background Resistance to anti-platelet therapy is detrimental to patients. Our aim was to establish a predictive model for aspirin resistance to identify high-risk patients and to propose appropriate intervention. Methods Elderly patients (n = 1130) with stable chronic coronary heart disease who were taking aspirin (75 mg) for > 2 months were included. Details of their basic characteristics, laboratory test results, and medications were collected. Logistic regression analysis was performed to establish a predictive model for aspirin resistance. Risk score was finally established according to coefficient B and type of variables in logistic regression. The Hosmer–Lemeshow (HL) test and receiver operating characteristic curves were performed to respectively test the calibration and discrimination of the model. Results Seven risk factors were included in our risk score. They were serum creatinine (> 110 ?mol/L, score of 1); fasting blood glucose (> 7.0 mmol/L, score of 1); hyperlipidemia (score of 1); number of coronary arteries (2 branches, score of 2; ≥ 3 branches, score of 4); body mass index (20–25 kg/m², score of 2; > 25 kg/m², score of 4); percutaneous coronary intervention (score of 2); and smoking (score of 3). The HL test showed P ≥ 0.05 and area under the receiver operating characteristic curve ≥ 0.70. Conclusions We explored and quantified the risk factors for aspirin resistance. Our predictive model showed good calibration and discriminative power and therefore a good foundation for the further study of patients undergoing anti-platelet therapy.     

冠心病患者阿司匹林抵抗及其影响因素

目的探讨冠心病患者阿司匹林抵抗（Aspirin resistance,AR）现象及其影响因素。方法入选1 731例入院诊断为冠心病（急性冠状动脉综合征和稳定型心绞痛）的患者。采用血小板聚集仪分别测定花生四烯酸（AA）、腺苷二磷酸（二磷酸腺苷,ADP）诱导的血小板聚集率。AR定义为0.5 mmol/L花生四烯酸时血小板平均聚集率≥20%,用10μmol/L ADP时血小板平均聚集率≥70%。阿司匹林半抵抗（Aspirin semiresistance,ASR）即符合上述两个条件之一者。均不符合者为阿司匹林敏感（Aspirin sensitive,AS）。用统计学方法分析各组间各项临床特征差异及影响AR与ASR的危险因素。结果1 731例患者中AR的发生率3.58%（62/1 731）,ASR的发生率20.34%（352/1 731）。与AS相比,AR＋ASR中以女性、高龄、高脂血症患者较多,吸烟者较少。而且AS患者的血小板计数偏高,总胆固醇水平偏低。Logistic回归分析表明,女性[相对比值比（OR）=1.377,95%可信区间（CI）1.084～1.751,P=0.009〗、老年（OR=1.504,95%CI1.005～2.253,P=0.047）、总胆固醇（TCHO）（OR=1.249,95%CI1.114～1.401,P=0.000）升高是发生AR与ASR的危险因素。结论服用阿司匹林的冠心病患者中AR发生率为3.58%,ASR发生率为20.34%。发生AR与ASR危险因素有女性、高龄、高血脂。     

Prevalence of and risk factors for aspirin resistance in elderly patients with coronary artery disease

Objective To assess the prevalence of and related risk factors for aspirin resistance in elderly patients with coronary artery disease (CAD). Methods Two hundred and forty-six elderly patients (75.9 ± 7.4 years) with CAD who received daily aspirin therapy (≥ 75 mg) over one month were recruited. The effect of aspirin was assessed using light transmission aggregometry (LTA) and thrombelastography platelet mapping assay (TEG). Aspirin resistance was defined as ≥ 20% arachidonic acid (AA)-induced aggregation and ≥ 70% adenosine diphosphate (ADP)-induced aggregation in the LTA assay. An aspirin semi-responder was defined as meeting one (but not both) of the criteria described above. Based on the results of TEG, aspirin resistance was defined as ≥ 50% aggregation induced by AA. Results As determined by LTA, 23 (9.3%) of the elderly CAD patients were resistant to aspirin therapy; 91 (37.0%) were semi-responders. As determined by TEG, 61 patients (24.8%) were aspirin resistant. Of the 61 patients who were aspirin resistant by TEG, 19 were aspirin resistant according to LTA results. Twenty-four of 91 semi-responders by LTA were aspirin resistant by TEG. Multivariate logistic regression analysis revealed that elevated fasting serum glucose level (Odds ratio: 1.517; 95% CI: 1.176–1.957; P = 0.001) was a significant risk factor for aspirin resistance as determined by TEG. Conclusions A significant number of elderly patients with CAD are resistant to aspirin therapy. Fasting blood glucose level is closely associated with aspirin resistance in elderly CAD patients.     

Low-dose aspirin increases aspirin resistance in patients with coronary artery disease

PURPOSE: We sought to investigate the association of aspirin dose and aspirin resistance in stable coronary artery disease patients measured by a point-of-care assay. METHODS: We studied 468 consecutive stable coronary artery disease patients in a referral cardiac center who were taking aspirin 80 to 325 mg daily for > or =4 weeks. The VerifyNow Aspirin (Ultegra RPFA-ASA, Accumetrics Inc, San Diego, Calif) was used to determine aspirin responsiveness. An aspirin reaction unit (ARU) > or =550 indicates the absence of aspirin-induced platelet dysfunction, based on correlation with epinephrine-induced light transmission aggregometry. Demographic and clinical data were collected to analyze the predictors of aspirin resistance. RESULTS: Aspirin resistance was noted in 128 (27.4%) patients. Univariate predictors of aspirin resistance include elderly (P = 0.002), women (P <0.001), anemia (P <0.001), renal insufficiency (P = 0.009) and aspirin dose < or =100 mg (P = 0.004). Multivariate analysis revealed hemoglobin (odds ratio [OR] 0.6; 95% confidence interval [CI] 0.51 to 0.69; P <0.001) and aspirin dose < or =100 mg (OR 2.23; 95% CI 1.12 to 4.44; P = 0.022) to be independent predictors of aspirin resistance. Daily aspirin dose < or = 100 mg was associated with increased prevalence of aspirin resistance compared with 150 mg and 300 mg daily (30.2% vs 16.7% vs 0%, P = 0.0062). CONCLUSION: A 100 mg or less daily dose of aspirin, which may have lower side effects, is associated with a higher incidence of aspirin resistance in patients with coronary artery disease. Prospective randomized studies are warranted to elucidate the optimal aspirin dosage for preventing ischemic complications of atherothrombotic disease.     

Determinants of aspirin resistance in patients with type 2 diabetes

BackgroundCardiovascular disease is a leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Numerous patients with T2DM show resistance to aspirin treatment, which may explain the higher rate of major adverse cardiovascular events observed compared with non-diabetes patients, and it has recently been shown that aspirin resistance is mainly related to accelerated platelet turnover with persistent high platelet reactivity (HPR) 24 h after last aspirin intake. The mechanism behind HPR is unknown. The aim of this study was to investigate the precise rate and mechanisms associated with HPR in a population of T2DM patients treated with aspirin.MethodsIncluded were 116 consecutive stable T2DM patients who had attended our hospital for their yearly check-up. HPR was assessed 24 h after aspirin intake using light transmission aggregometry (LTA) with arachidonic acid (AA) and serum thromboxane B2 (TXB2) measurement. Its relationship with diabetes status, insulin resistance, inflammatory markers and coronary artery disease (CAD) severity, using calcium scores, were investigated.ResultsUsing LTA, HPR was found in 27 (23%) patients. There was no significant difference in mean age, gender ratio or cardiovascular risk factors in patients with or without HPR. HPR was significantly related to duration of diabetes and higher fasting glucose levels (but not consistently with HbA_1c), and strongly related to all markers of insulin resistance, especially waist circumference, HOMA-IR, QUICKI and leptin. There was no association between HPR and thrombopoietin or inflammatory markers (IL-6, IL-10, indoleamine 2,3-dioxygenase activity, TNF-α, C-reactive protein), whereas HPR was associated with more severe CAD. Similar results were found with TXB2.ConclusionOur results reveal that ‘aspirin resistance’ is frequently found in T2DM, and is strongly related to insulin resistance and severity of CAD, but weakly related to HbA_1c and not at all to inflammatory parameters. This may help to identify those T2DM patients who might benefit from alternative antiplatelet treatments such as twice-daily aspirin and thienopyridines.     

Prevalence of aspirin resistance in patients with type 2 diabetes

Abstract Aspirin resistance has been recognised to occur in patients with cardiovascular disease and is associated with poor clinical prognosis. The purpose of the present study was to evaluate the prevalence of aspirin resistance in 172 patients with diabetes mellitus type 2 (DM-2). Platelet function of 172 consecutive patients with type 2 diabetes on chronic aspirin therapy was evaluated. The effect of aspirin was assessed using the platelet function analyser (PFA-100) system, reporting platelet-dependent thrombus formation as the time required to close a small aperture in a biologically active membrane. Resistance to aspirin was defined as a normal collagen/epinephrine-induced closure time (82–165 s). Aspirin responders were defined when closure time was 300 s. Thirty-seven (21.5%) of the type 2 diabetic patients were found to be resistant to chronic aspirin therapy, 29 (16.9%) were semi-responders and 106 (61.6%) were responders. Univariate analysis revealed that aspirin non-responders were significantly younger (p<0.05) compared to aspirin responders. A significant number of type 2 diabetic patients are resistant to aspirin therapy. Aspirin resistance can be evaluated by point-of-care testing and should be recognised in diabetic patients that are treated for primary or secondary prevention.     

阿司匹林抵抗对冠状动脉介入术后病人的远期影响

目的了解冠状动脉支架术后冠心病患者阿司匹林抵抗（AR）的状况及其远期影响。方法选择经皮冠状动脉介入术（PCI）后不稳定性心绞痛患者118例,在体外应用ADP诱导的血小板最大聚集率≥70％和0．5％花生四烯酸诱导血小板最大聚集率≥20％者为AR患者,并设立复合终点,随访12个月以上。结果有26例被判断为AR,两组患者除性别以外在年龄、冠心病相关危险因素和药物治疗等方面比较差异无统计学意义（P〉0．05）。平均随访期（18．51±7．65）个月,13例发生了终点事件（11．02％）,AR患者中6例（23．08％）,非AR患者中7例（7．61％）,P=0．05;多因素分析提示AR仍是远期不良事件的独立预测因素（HR2．31;95％CI1．23—5．37;P〈0．05）。结论冠状动脉支架术后的冠心病患者中AR发生率22．03％,AR是发生远期不良事件的重要危险因素。