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1、高血压合并肾损害的处理,初少莉 上海交大医学院 附属瑞金医院 上海市高血压研究所、高血压科,概述 高血压伴CKD的处理,内 容,高血压与主要器官间的关系,CKD主要原因之一,高血压,50%-75%CKD,美国CKD患病率 (AJKD 2004),人群（10万）,National kidney foundation K/DOQI guideline Am J Kidney Dis. 2004:Suppt.1-234,30,40,76,53,59,15,GFR(ml/min),15-29,30-59,60-89,90,中国CKD流行病学资料,1余学清等,中华肾脏病杂志,2007,23(3)147-
2、151 2张路霞等,中华肾脏病杂志,2006,22(2)69-71 3张路霞等,中华肾脏病杂志,2007,23(3)152-155,CKD在不同人群中的患病率(%),Early detection and intervention of CKD and associated factors in Beijing,15.9,20.7,9.3,Incident Rates by Primary Diagnosis,US Renal Data System.USRDS 2000 Annual Data Report.Bethesda,MD:National Institutes of Health;
3、2000.,校正的风险比 （所有原因死亡 心血管事件 任何原因住院的）,* 校正年龄,收入,教育,肾透析,冠心病,慢性心衰,缺血性卒中,TIA,PAD,DM,HT,DL,肿瘤,痴呆,慢性肝病,慢性肺病,蛋白尿,住院 Go AS et al.N Engl J Med .2004;351:1296-1305,高血压增加心血管病与肾脏病的危险,Am J Hypertens 2000,13:3S-10S Hypertension 1995,25:587-594 N Engl J.Med. 1996,334:13-18,控制血压 保护肾脏,减少有效肾单位,增加肾小球 内压,肾硬化与纤维化,肾小球肥厚,高
4、血压,Wang H.Y in APCC,高血压伴CKD患者增加心血管危险的可能机制,同型半胱酸增加 交感活性增加 血浆非对称性二甲基精氨酸（asymmetric dimethylarginine , ADMA) 浓度增高 血管钙化的危险性增加,Updatared from Zoccali C.Kidney Int.2006;70:26-33,概述 高血压伴CKD的处理,内 容,CKD的处理 以抗高血压治疗为主的综合干预,非药物治疗: 改善生活方式及专科的营养治疗 药物治疗: 抗高血压药物治疗 降压目标 降压药物的选择 联合治疗 多重危险因素的控制（调脂、抗血小板等）,CKD患者均应进行抗高血压
5、治疗,降压 降低心血管病的危险(不论是否有高血压) 延缓肾脏病进展(不论是否有高血压),National kidney foundation K/DOQI guideline Am J Kidney Dis. 2004:Suppt.1-234,降压目标： CKD为心血管病的极高危因素，治疗要兼顾延缓肾功能不全进展及降低心血管病危险： 1、严格控制血压 (1g/日可更低) 2、降低蛋白尿，使其尽可能恢复正常,抗高血压药物的选择与应用,选择的原则： 遵循指南 坚持个化治疗 首选药物: （兼有降压、降蛋白尿、延缓GFR降低）,各主要权威指南,ESC/ESH(2007) ACEI or ARB ADA
6、 (2004) ACEI or ABR NKF:DOQI-BP(2004) ACEI or ABR KDQI-CKD(2002) ACEI or ABR JNC7（2003） ACEI or ABR CHINA(2005) ACEI or ARB CANADIAN (2002) ACEI or ABR WHO/ISH(1999) ACEI,（兼有降压、降蛋白尿、延缓GFR降低）,对CKD患者治疗 ACEI vs ARB 孰优孰劣？,Head-to-head trials Hypertension 0 Diabetes type 1 0 type 2 0 with nephropathy 0 P
7、ost MI (heart failure) OPTIMAAL, VALIANT Chronic Heart Failure ELITE II Pervention of disease progression 0 High CV risk Ontarget,Hypertension with CKD 0,ONTARGET The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial WWW.NEJM.ORG ON MARCH 31,2008 N ENGL J MED, 2008;358
8、:1547-1559,ONTARGET,Questions: 1. Is telmisartan “non-inferior” to ramipril ? 2. Is the combination superior to ramipril ? Outcome: Primary: CV death, MI, stroke, CHF hosp Key secondary: CV death, MI, stroke (HOPE trial outcome) Design: Single blind run-in (n=29,019) Randomized, double blind, double
9、 dummy study conducted in 733 centers in 40 countries (n=25,620) 56 months follow-up with 99.8% outcome ascertainment,Change in BP (mmHg),Time to Primary Outcome,ONTARGET,Primary Outcome & HOPE Primary Outcome,Time to Permanent Discontinuation of Study Medication,ONTARGET,Reasons for Permanently Sto
10、pping Study Medications,Save money ?,Prefer tolerability ?,ARB,ACEI,Telmisartan is as effective as ramipril, with a slightly better tolerability.,高血压只有30%单药能够达标 高血压伴CKD时增加额外的降压难度 （难治性高血压多，目标血压 130/80mmHg）,联合降压治疗,利尿剂,受体阻滞剂,AT1-受体阻滞剂,a受体阻滞剂,钙离子拮抗剂,ACEI,ESH/ESC2007: 降压联合治疗方案,ACEI与ARB联合治疗 (伴CKD),Benefit
11、 Clear role in CHF (CHARM-added, Val-HeFT ) Clear role in non-diabetic nephropathy (COOPERATE) Unclear role in diabetic nephropathy (CALM II ) Small effect in HT 2007ASH in Chicago,Effect on proteinuria,ACEI+ARB vs ACEI alone 30% reduction (95%CI 23-37%) ACEI+ARB vs ARB alone 39% reduction (95%CI 31
12、-48%) (Eight trial reported data on proteinuria, albuminuria, or ACR),Doulton TW,et al. Hypertension.2005;45:880-886,Time to Primary Outcome （ARB与ACEI联合）,ONTARGET,Tel + Ram,Ram alone,Reasons for Permanently Stopping Study Medications,ONTARGET,结 论 （Tel plus Ram vs. Ram）,1. Tel与Ram联合较Ram单用，并未更大程 度降低主次
13、要终点，提示联合并不优于单用； 2. 联合较单用ACEI增加不良事件,ONTARGET,（期待对于CKD患者的亚组分析结果）,不同联合方案的比较,联合CCB vs 联合利尿药,迄今，无针对CKD的联合治疗方案头对头临床试验,HOT研究 肾脏病患者亚组数据分析证实非洛地平 降压达标效果好,血压 治疗前 随访 6 24 终点 低 SBP (mmHg) 170 15 142 15 141 14 141 15 高 17217 144 16 141 17 141 17 低 DBP (mmHg) 105 4 84 7 83 7 83 7 高 106 4 85 8 82 8 82 9,血清肌 酐水平,Hyp
14、ertension Unit. J Am Soc Nephrol 2001; 12: 218-25,HOT研究 肾脏病患者亚组数据分析证实非洛地平 对肾功能无不良影响,Hypertension Unit. J Am Soc Nephrol 2001; 12: 218-25,Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension,Targeted Population for Recruitment into the ACCOMPLISH St
15、udy,Men or women age 55 years SBP 160 mmHg or currently on antihypertensive therapy Evidence of cardiovascular or renal disease or target organ damage,DSMB Oct 17 2007,Pre-specified efficacy boundary was crossed with 60% of the expected trial information Executive Committee accepted the recommendati
16、on Last patient last visit was Jan 24, 2008 Total of 1176 unique patients with events 95.3% of primary events are adjudicated,Systolic Blood Pressure Over Time,mm Hg,Month,5731 5387 5206 4999 4804 4285 2520 1045 5709 5377 5154 4980 4831 4286 2594 1075,Patients,*Mean values are taken at 30 months F/U
17、 visit,129.3 mmHg,130mmHg,Difference of 0.7 mmHg p0.05*,DBP: 71.1,DBP: 72.8,差1.7mmHg,37.2,37.9,ACCOMPLISH: Exceptional Control Rates with Initial Combination Therapy,ACEI / HCTZ N=5733,Control rate (%),CCB / ACEI N=5713,10,20,30,40,50,60,70,80,90,P0.001 at 30 months follow-up,Control defined as 140/
18、90 mmHg,Kaplan Meier for Primary Endpoint,Cumulative event rate,HR (95% CI): 0.80 (0.72, 0.90),Time to 1st CV morbidity/mortality (days),p = 0,650,526,.0,0,0,2,INTERIM RESULTS Mar 08,提 示,联合治疗可获得非常好的血压控制； 2. 初始 ACEI / CCB优于ACEI/DD的联合治疗，这对以DD作为降压基础治疗的观点提出挑战,Initial combinations of Medications,diuretics,ACEI or ARB,CCB,利尿治疗的利弊, 利尿药,抑肾脏钠（镁）重吸收,低镁血症,低钠血症,心排,低钾血症,体位性 低血压,肾血流,PRA,GRF,糖耐量异常, 高尿酸血症或痛风（排泄减少、吸收增加）,其它,血容量, 限制利尿药的剂量，也限制利尿药的降压作用,其它机制,高血压伴CKD的处理 （小 结）,应以降压为主的综合治疗 降压需达标（130/80mmHg) 首选降压药物：ACEI或ARB（靶剂量） 大多数患者需要联合治疗 RASi ARB还需验证（伴CKD） RASi CCB潜在优势 RASiDD（顽固、容量增加时优先） 个体化治疗尤为重要,谢 谢,谢 谢,上海瑞金医院,