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1、Lp-PLA2 脂蛋白磷脂酶A2化学发光法测定,直揭动脉粥样斑块稳定性,南京诺尔曼生物技术有限公司,南京诺尔曼生物技术有限公司,1、公司简介2、LA-PLA2项目简介3、LA-PLA2临床应用简介,1、公司简介2、LA-PLA2项目简介3、LA-PLA2临床应用简介,不稳定的恶性斑块是血管中的定时炸弹！,lipid core,不稳定性动脉粥样硬化斑块,外膜,AMI与血管造影：68%对象狭窄程度50%,Erling Falk et al. Coronary plaque disruption. Circulation. 1995; 92:657-671,斑块的组成和稳定性是ACS的决定因素，而不
2、是其体积和相应的血管阻塞程度。 血管造影不能反应斑块的组成和稳定性。另外，更小的斑块似乎更有可能导致急性临床事件。,急性冠脉综合征患者LDL-C水平：72%患者130 mg/dL, 130 LDL-C (mg/dL), 130 LDL-C (mg/dL),Database was analyzed for CAD hospitalizations from 2000 to 2006 with documented lipid levels in the first 24 hours of admissionEven when only patients without prior histor
3、y of CHD, other atherosclerotic vascular disease, or diabetes were studied, 72.1% have admission LDL130 mg/dLLess than 25% of patients had an admission LDL 130 mg/dL,Sachdeva et al. Lipid levels in patients hospitalized with coronary artery disease: An analysis of 136905 hospitalizations in Get With
4、 The Guidelines. Am Heart J 2009; 157:111-7.e2,1. The Spin Stops Here: Inhibition of Lipoprotein Associated Phospholipase A2A Promising Target but a Negative Initial Trial?.American Association for Clinical Chemistry. 2009, 55(1):18-20.,2. Elkind MS, et al. High-Sensitivity C-Reactive Protein, Lipop
5、rotein-Associated Phospholipase A2, and Outcome After Ischemic Stroke. Arch Int Med. 2006;166:2073-2080,hsCRP与Lp-PLA2比较,早期性,敏感性,无创性,.,特异性,Lp-PLA2,国际权威指南一致推荐,“脂蛋白相关磷脂酶A2（Lp-PLA2)是血管内皮炎症的独立危险因子，也是目前检测血管内皮炎症的新指标。对心脑血管栓塞性疾病的预测、治疗和预后的判断具有重要意义。”,胡大一教授,张运教授,摘自2012中国脑卒中大会主题论坛报告,胡大一教授主持颁布Lp-PLA2临床应用专家建议,小结：不
6、稳定斑块是定时炸弹传统检查方法对斑块稳定性的直接监测不理想脂蛋白磷脂酶A2获得了国际指南和中国专家的认可,Lp-PLA2在动脉粥样斑块的硬化过程中起到很高的促进作用,Silva et al. Lipids in Health and Disease 2011, 10:170,Lp-PLA2的含量就能直接反映动脉粥样斑块的炎症程度,Lp-PLA2在动脉粥样斑块形成中的作用,血管腔,血管内膜,稳定斑块 vs 易损斑块,小型坏死脂质池,血栓,大型坏死脂质池,Stable PlaqueLow Lp-PLA2 content (reddish-brown staining)Thick fibrous c
7、ap / high collagen contentSmall lipid poolFew inflammatory cells,Corson MA et al, Am J Card Suppl 2008:101 (41F-50F),Ruptured PlaqueHigh Lp-PLA2 content (reddish-brown staining)Thin fibrous cap / low collagen contentLarge lipid poolMany inflammatory cells,1,2,American Association of Clinical Endocri
8、nologists (AACE) Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis Endocrine Practice (2012),AACE Lp-PLA2临床指南 2012,Lp-PLA2 has been identified as a strong and independ predictor of CVD events and stroke in patients with and without manifest CAD, as well as in patients with
9、low LDL-C. Current best evidence indicates that an Lp-PLA2 level less than 200 ng/mL is normal, 200 and 223 ng/mL is intermediate, and 223 ng/mL is high. Lp-PLA2 appears to act synergistically with CRP (described above) such that when both are elevated, risk is substantial. However, while CRP is a m
10、arker of general inflammation, Lp-PLA2 appears to specifically indicate vascular inflammation and is not influenced by obesity.”,Lp-PLA2的临床指导意义,风险预测预后评估治疗指导,无症状高危人群心血管风险预测,25 prospective epidemiologic studies have investigated the association of Lp-PLA2 with future CAD events .10 of 11 studies have
11、shown a statistically significant association between elevated Lp-PLA2 and primary coronary or cardiovascular events.12 of 13 have shown a statistically significant association with recurrent coronary or cardiovascular events.Elevated Lp-PLA2 is consistently associated with a doubling of risk for CA
12、D (top quantile vs bottom quantile).,Corson MA et al, Review of the evidence for the clinical utility of Lp-PLA2 as a cardiovascular risk marker. Am J Card Suppl 2008:101 (41F-50F),预测稳定性冠心病患者心血管事件复发风险,3766 名稳定性CAD 患者检测Lp-PLA2 水平，并对患者不良心血管事件随访4.8 年（中值）；不良事件包括：死亡、心肌梗死（MI）、冠脉重建术、不稳定性心绞痛(UA)住院及中风。,不同LP-
13、PLA2水平，在随访期间不良心血管事件的发生率,Marc S. Sabatine, David A. Morrow, Michelle ODonoghue, ,et al.Prognostic Utility of Lipoprotein-Associated Phospholipase A2 for Cardiovascular Outcomes in Patients With Stable Coronary Artery Disease. Journal of The American Heart Association, 2007;27:2463-2469,不良心血管事件的发生率,P
14、= 0.03,Lp-PLA2水平与缺血性脑卒中发生率呈正相关性,调整传统危险因子和hsCRP后，位于Lp-PLA2活性最高四分位数者与最低四分位数者相比,发生缺血性脑卒中的风险显著增加,随机抽取1822例,平均随访6.4年，有 110例缺血性脑卒中。,传统危险因子：年龄、性别、体重指 数、收缩压、LDL、HDL、糖尿病、 胆固醇、白细胞计数、吸烟、饮酒,Hok-Hay S. Oei et al. Circulation 2005, 111：570-575.,预测首次卒中发生的风险,Lp-PLA2的临床指导意义,风险预测预后评估治疗指导,心肌梗死预后,Gerber Y, et al. Lp-PL
15、A2 and an prognosis after myocardial infarction in the community. Arterioscler Thromb Vasc Biol. 2006, 26(11):2517-22.,Olmsted County, Minn, residents who experienced an MI between 2003 and 2005 were identified and followed.271 patients. During the first year of follow-up, 42 deaths occurred.Further
16、 adjustment for traditional risk factors, LDL-C, Killip class, EF, hs-CRP, reperfusion or revascularization, resulted in an increase in the association.HRs for mortality in the Middle and Upper Lp-PLA2 tertiles were 2.93 and 7.61.,467 名首次发生缺血性中风患者排除年龄、性别、种族和民族、冠心病史、糖尿病、高血压、高血脂症、房颤、吸烟以及hs-CRP 影响；,Lp-
17、PLA2 浓度最高四分位患者相较于浓度最低四分位患者，中风复发的风险增大（校正风险率，2.08；95%CI，1.04-4.18），中风复发、心梗、血管性死亡并发事件发生的风险增大（校正风险率，1.86；95%CI，1.01-3.42）；,Mitchell S. V. Elkind, Wanling Tai, Kristen Coates, ,et al. High-Sensitivity C-Reactive Protein, Lipoprotein-Associated Phospholipase A2, and Outcome After Ischemic Stroke. Arch Int
18、ern Med. 2006;166:2073-2080,Lp-PLA2 浓度高提示卒中复发风险增大,正常情况下，脑卒中和心梗后，Lp-PLA2的含量和活性水平急剧降低;如卒中后Lp-PLA2水平仍高，预示卒中复发和心血管事件风险增加。,Mitchell S.V. Elkind,Vladimir Leon, Yeseon P. Moon,et al. High-Sensitivity C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 Stability Before and After Stroke and Myocar
19、dial Infarction. Journal of The American Heart Association, 2009 ; 40 : 3233-3237.,Lp-PLA2的临床指导意义,风险预测预后评估治疗指导,选择急性脑梗死患者86例， 随机分为2组：阿托伐他汀常规剂量组43例：20mg/天，大剂量组43例：40mg/天， 分别于治疗前及治疗14天后测量患者血浆Lp-PLA2 水平。43例健康体检者为对照组，不予阿托伐他汀治疗。 ACI患者血浆Lp-PLA2较治疗前均有明显下降（P 0.01），对两组治疗后的Lp-PLA2水平进行比较， 大剂量治疗组Lp-PLA2下降较常规剂量更明
20、显（P=0.036）,他汀类药物强化治疗的依据,陈军,等.不同剂量阿托伐他汀对急性脑梗死患者血浆Lp-PLA2水平的影响.临床医学工程 2011;18(7):982,Michael H et al. Consensus panel recommendation for incorporating Lp-PLA2 testing into CAD risk assessment guidelines. The American Journal of Cardiology . 2008, 101 (12A) :51F-57F.,血脂达标标准改变,ATP III 心血管疾病危险因素：1.抽烟2.高血
21、压3.低的高密度脂蛋白胆固醇（男性40mg/dL，女性50mg/dL ）4.家族性的心血管病史（CAD）5.年龄（男性45岁，女性55岁）,冠心病等危症：动脉粥样硬化的其他临床表现形式糖尿病两个以上风险因素+hs-CRP2mg/L慢性肾病踝臂指数0.9颈动脉狭窄程度50%,心血管疾病极高风险（已确诊为心血管疾病并同时存在以下四个因素）：多个主要危险因素（尤其是糖尿病）控制不佳的高危因素（特别是长期抽烟）代谢综合症的多重危险因素急性冠脉综合征,Lp-PLA2升高200ng/ml，可以采取的措施第一，应提高目前治疗手段的管理级别，强化治疗目标或者调整方案。第二，有众多临床证据表明他汀类药物可以降低
22、Lp-PLA2水平。这也许正是其可以减小甚至逆转AS斑块的药理机制之一。因此可以根据病人情况使用足量足疗程他汀类药物治疗，或者强化降脂治疗方案。第三，Lp-PLA2是心血管疾病治疗新靶点。国际制药巨头正在研发针对血管炎症的特异性治疗药物。,1、公司简介2、LA-PLA2项目简介3、LA-PLA2临床应用简介,中国专家建议：1、无症状危险人群筛查，尤其是动脉粥样硬化性心血管疾病中等危险人群，Lp-PLA2是独立危险因素。2、已接受他汀治疗且胆固醇水平控制较好的患者，检测Lp-PLA2可提高心脑血管事件风险预测价值。3、发生急性血栓事件的患者，包括ACS和缺血性卒中，检测Lp-PLA2有助于近期和远期风险评估。,一年一次 体检,入院即刻检测治疗后，1-6月一次,未来心脑血管疾病风险,不良预后及复发风险,评估药物疗效,Lp-PLA2的临床价值总结,诺尔曼磷脂酶A2的检测方式,一、检测场所：本院检验科生化室二、检测方式：直接输入该项目名称的首字字母，即： “脂蛋白”的字母：ZDB-脂蛋白磷脂酶A2三、收费标准：364元/人份四、医保情况： 医保 90%报销五、门诊诊和病房均可使用六、血标本不受任何限制，空腹、餐后均可,研发决定未来 专注决定成功,
