高血压代谢危险因素控制面临的困惑与启示_祝之明.ppt

高血压代谢危险因素控制面临的困惑与启示,祝之明 第三军医大学全军高血压代谢病中心 重庆大坪医院高血压内分泌科 重庆市高血压研究所,Dyslipidemia,Abdominal Obesity,Diabetes,Uric acid,Renal lesion,Endothelium damage,Hypertensive Syndrome - Constellations of Cardiometabolic Risk Factors,Hypertension 80%,高血压,危险因素,CVD事件,Abdominal obesity Waist circumference 102cm (M), 88cm (W) Dyslipidaemia TC5.0 mmol/l (原为6.1) or LDL-C 3.0 mmol/l (原为4.0) or HDL-C:M 1.7 mmol/l (150 mg/dL) IFG & IGT Fasting plasma glucose 5.6-6.9 mmol/L(102-125 mg/dL) Abnormal glucose tolerance test,ESC/ESH 2007高血压指南,Metabolic syndrome the cluster of three out of 5 risk factors among abdominal obesity, altered fasting plasma glucose, BP130/85mmHg, low HDL-cholesterol and high TG (as defined above) Diabetes Mellitus Fasting plasma 7.0 mmol/l (126 mg/dL) on repeated measurements, or Postload plasma glucose 11.0 mmol/l (198 mg/dL),（J Hypertens 2007, 25：1105）,ESC/ESH 2007关注高血压伴发的代谢异常,（J Hypertens 2007, 25：1105）,如何评估高血压的代谢危险性,Diabetes Vasc Dis Res 2008;5:914,心血管代谢危险性评估,1. Framingham score (USA) Age, Sex, SBP, TC, Smoking, HDL-c 2. The UKPDS risk engine (UK) Age, Sex, SBP, Smoking, TC/HDL-c, HbA1c 3. PROCAM score (Germany) Age, LDL-c, TC, smoking, HDL-c, SBP, FH of MI,DM, TG 4. ICVD (China) Age, Sex, SBP, BMI, TC, Smoking, DM,危险分层： ESC/ESH,靶器官损害的评价,干预高血压相关的代谢危险因素能显著降低心脑血管事件吗？,Lower blood pressure Yes (30%-60%) Lower lipids Yes (17%-43%) Lower body weight Paradox Lower glucose Uncertain,BMI and WC vs fat parameters,肥胖与心血管危险存在U形关系,Gu DF, et al.JAMA. 2006;295:776-783,肥胖与心衰 Paradox prognosis: excess body weight have a paradoxical protective role ?,Enchaiah S, et al. N Engl J Med 2002; 347:305-13.,DIAMOND study group Gustafsson1 F,Eur Heart J,2005, 26:5864,肥胖与AMI,Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study Yusuf S, et al. Lancet 2005; 366: 1640,Nicoletti I, et al. Inter J Cardiol, 2006,107 :395399,Paradox prognosis: excess body weight have a paradoxical protective role ?,生活方式改变的局限,BMI不能反映内脏脂肪的实际变化,腹型肥胖的类型与代谢综合征的关系,MS 43%,MS 78%,MS 89%,中华医学杂志 2008,Proposed mechanisms by which visceral obesity, as the most dangerous form of obesity, could be linked to the athero-thrombotic-inflammatory abnormalities of insulin resistance.,ATVB, 2008,微血管并发症,心肌梗死,HbA1c,37%,14%,强化降糖与减少CVD事件面临的困惑,糖尿病相关的死亡,21%,1%,Stratton IM, et al. BMJ 2000; 321:405412.,糖尿病作为冠心病的等危症是有条件的 Diabetes and Coronary Risk Equivalency,糖尿病不合并其他危险因素，其心血管危险不高，也即单纯高血糖 至少在短期对心血管危害不大。糖尿病合并其他危险因素，其心血 管危险性明显增加，可视为冠心病等危症。 Grandy SM, Diabetes Care, 2006,理论假说,降压和调脂的临床试验证实：血压和血脂水平控制得越严格，获得的益处更大。 合理假设:强化血糖控制有益于减少CVD事件,控制血糖至一定范围显著减少心脑血管事件,ACCORD, ADVANCE, VADT 强化血糖控制无益处 在ACCORD试验结果公布之前一个月，Eur Heart J连续刊登了2篇降糖治疗增加心血管事件的临床研究，编辑部予以评论。,DIGAMI 2 trial The impact of glucose lowering treatment on long-term prognosis in patients with type 2 diabetes and myocardial infarction: a report from the DIGAMI 2 trial,1996 DIGAMI 1 研究显示予胰岛素治疗显著减少糖尿病的急性心肌梗塞死亡率 Circulation 1999;99:26262632. 2005 DIGAMI 2 探讨降糖治疗对糖尿病心肌梗塞的影响 入选1181例2型糖尿病，平均年龄68岁，67%为男性，平均随访2.1年 37% 口服降糖药，58%用胰岛素,European Heart Journal (2008),与口服降糖药相比，胰岛素与全因死亡和心血管死亡无关，但可增加非致死心梗或脑卒中 (HR:1.95, 95% CI:1.352.82; P=0.0004),Euro Heart Survey on Diabetes and the Heart Glucose lowering treatment in patients with coronary artery disease is prognostically important not only in established but also in newly detected diabetes mellitus: a report from the Euro Heart Survey on Diabetes and the Heart,本研究比较了目前的降糖治疗对冠心病己合并糖尿病和新发糖尿病的作用。 从110个中心，入选4676例冠心病患者，其中1425例既往有糖尿病，452例为新发糖尿病。探讨不同的降糖治疗对心血管事件(死亡、心梗、卒中)的影响。,European Heart Journal (2008),与口服降糖药相比，对合并糖尿病的冠心病，胰岛素治疗增加1年心血管死亡风险2.23 (95% CI 1.244.03; P =0.006)，但对新发糖尿病患者，与未降糖治疗相比，降糖治疗则明显减少其心血管事件,最近的血糖控制试验带来的困惑,Jessup M, et al. NEJM, 2003,348:2007-18. Blaschke F, et al. ATVB, 2006,26:28-40 VanGaal LF, et al. Lancet, 2005,365:1389-97,多靶点药物,降压药物的选择,降压药物的选择,Effect of Inhibition of the RAS on Development of Type 2 Diabetes Mellitus (Meta-Analysis of Randomized Trials),Am J Cardiol 2007;99:1006 1012,Irbesartan for the treatment of hypertension in patients with the metabolic syndrome: A sub analysis of the Treat to Target post authorization survey. Prospective observational, two armed study in 14,200 patients Cardiovascular Diabetology 2007, 6:12,降糖药对心血管事件的影响,European Heart Journal (2008),不同降糖药组合对LDL-C和血压影响不同,Bolen S Ann Intern Med. 2007,客观评价-blocker在糖尿病治疗中的作用,予100 mg/d阿替洛尔能防止低血糖诱发的QTc延长和QTd离散Diabetes, 2003 虽然予beta受体阻断剂可能增加糖脂代谢紊乱和胰岛素抵抗，但可显著降低糖尿病合并心衰的死亡率。 对降糖治疗中出现的低血糖诱发的致死性心律失常的防治，也是其他药物难以取代的。,Fonarow GC. An Approach to Heart Failure and Diabetes Mellitus Am J Cardiol 2005;96suppl:47E52E),Changes in Serum Potassium MediateThiazide-Induced Diabetes,Hypertension. 2008;52:1022-1029,Thiazide-induced diabetes occurs (42%) early after initiating treatment and appears to be