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1、高血压病伴糖尿病的处理高血压病伴糖尿病的处理中国医科大学一院心内科中国医科大学一院心内科 齐国先齐国先 重庆重庆 2008 12 13多重危险因素的共同控制多重危险因素的共同控制Steno-2 Study 2003, 2008RCT of 160 T2DM pts with microalbuminuria强化干预 vs 常规干预 SBP: 130 mm Hg Total cholesterol 175 mg% HbA1c: 6.5%Initial FU:7.8yExtended FU:13.3yNEJM 2003; 348:383 NEJM 2008; 358:580STENO-2 STUD
2、Y: 危险因素的控制危险因素的控制Intensive GroupConventional GroupSystolic BP 15 mm Hg (146 131) 3 mm Hg (149 146)LDL-C 50 mg% (133 83) 11 mg% (137 126)HbA1c 0.5% (8.4 7.9) 0.2% (8.8 9.0)NEJM 2008; 358:580STENO-2 STUDY: 强化治疗的效果强化治疗的效果% Reduction in Complications With Intensive Rx at 13.3yTotal Mortality 40% (50% vs
3、 30%)Cardiovascular events 59% (65% vs 30%)Proliferative retinopathy 55% -Nephropathy 56% - NEJM 2008; 358:580HYPERTENSION AND DIABETES: PARTNERS IN CRIME!共同土壤学说: “Metabolic Syndrome”HTN vs No HTNDM vs No DM2.4x in DM2.0x in HTNNEJM 2000; 342:905 Diabetes Care 2005; 28:310高血压的发病率 IN DIABETES% with B
4、P 140/90All U.S. adults30%Diabetic U.S. adults60% Type 1 DM - Normoalbuminuria30% - Microalbuminuria40% - Macroalbuminuria80% Type 2 DM - At Dx50% - Microalbuminuria80% - Macroalbuminuria95%NEJM 2000; 342:905 Diabetes Care 2005; 28:310 Am J Kid Dis 2007; 49 (Suppl 2):S74J Cardiometab Syndr 2006; 1:9
5、5(86% 130/80)高血压增加糖尿病病人的并发症Relative Risk of ComplicationsDiabetes vs No Diabetes: CVD2.0 4.0 ESRD7.0Diabetes BP vs Diabetes CHD3.0 Stroke4.0 Retinopathy2.0 Nephropathy2.0 Neuropathy1.6 Mortality2.075% die from CVDJAMA 2004; 292:2495 Kid Internat 2000; 59:703 NEJM 2005; 352:341关注焦点“ SYSTOLIC BP”Stron
6、ger predictor of risk than diastolic BP:Cardiovascular diseaseRenal dysfunction65% of DM hypertensives have isolated systolic hypertensionSystolic hypertension more difficult to controlDiabetes Care 1994; 17:1247Lancet 2002; 360:1903Hypertension 2003; 42:1206糖尿病伴高血压病的控制达标现状% With BP 130/80NHANES, 20
7、03-200435%VA, 2001-200223%Community 1 care, 2002-200431-35%Academic medicine, 200233%GEMINI RCT, 200468%Arch Int Med 2007; 167:2394JAMA 2004; 292:2227Ann Fam Med 2006; 4:23J Gen Intern Med 2006; 21:1050控制不理想的原因何在？疾病本身的原因疾病本身的原因 Most DM pts need 3-4 drugs to control BPActivation of RAA systemVolume o
8、verload, especially if CKDSleep apnea from associated obesityVascular damageJ Hypertens 2005; 23:2305Hypertension 2000; 35:1038 Am J Hypertens 2004; 17:915J Cardiometab Syn 2007; 2:114控制不理想的原因何在？用药依从性低用药依从性低 Cost adherence 62%/30% Inadequate pt education BP 7/3 mm Hg Side effects refills 25% Complex
9、 regimens SBP 6 mm Hg - QD dosing Fixed-dose combo pills adherence 10-20%Arch Int Med 2006; 166:332, 1836Am J Therap 2005; 12:605J Gen Intern Med 2008; 23:588 Ann Intern Med 2006; 145:165 Int J Clin Prac 2006; 51:441改善的策略 IN DM-HTN CONTROL Educate patients: goal BP, etc Control cost Dose QD, fixed-c
10、ombo pills Address side effects ADHERENCE! Decrease clinician therapeutic 惰性惰性 - Q 1mo FU, Rx until BP goal BP: 1st reading higher 3 readings, 1 min apart “Alerting response” Discard 1st, average last 2Hypertension 2005; 45:142 J Hypertens 2005; 23:697 Can J Card 2007; 23:529 非诊室 BP MEASUREMENTRecom
11、mended for all HTN pts by AHA, 2008Best predictor of CVD eventsDetects “white coat” and “masked” HTN非诊室非诊室 BP goals 诊室诊室 BP goal Equivalent Goal BPOffice BP 130/80 Home BP 125/7524-h ABPM study:Daytime awake BP 125/75Full 24-h BP 120/70AHA Hypertension Primer, 2008; p.343血压类型 IN DMDAYTIMEOUT-OF-OFFI
12、CE BP125/75130/80OFFICE BPNORMOTENSION: Office BP 130/80 Day ABPM 125/75 Home BP 125/75WHITE-COAT HTN: Office BP 130/80 Day ABPM 125/75 Home BP 125/75MASKED HTN: Office BP 130/80 Day ABPM 125/75 Home BP 125/75 SUSTAINED HTN: Office BP 130/80 Day ABPM 135/85 Home BP 135/85评价 OF HYPERTENSION IN DM BP
13、q visit Proper techniqueBP = 120/129/70-79BP 130/80 on 2 visits 1 mo apartBP 120/70FU BP q visitConsider Out-of-office BP: Home BP 24 hr ABPMRisk Stratify for Rx 125/75 125/75危险分层-初始治疗Lower CVD riskInitial lifestyle RxHigher CVD riskInitial drug Rx Lifestyle RxDiabetes Care 2008; 31(Supple 1):S24Off
14、ice BP 130/80 on 2 visits 1 month apart or Home BP or daytime awake BP by 24-hr ABPM 125/75Higher Risk DM5: BP 140/90, or Albuminuria, or CVD or LVHLower Risk DM5: BP = 130-139/80-89 No TOD Pharmacologic Rx Lifestyle modification Lifestyle modification for 3 mo trialModified from:Diabetes Care 2007;
15、 29(Suppl):S4Can J Cardiol 2007; 23:529BP 130/80生活方式干预（资料很少） BP mm HgWeight loss/Kg1/1Low Na 60y) less effective CHF:CCBs less effective for prevention? ARBs, diuretics more effective?ACEI effectiveArch Intern Med 2005; 165:1410Ann Intern Med 2006 ; 144:272BBs vs OTHER ANTI-HTN AGENTSMeta-analyses:#
16、 RCTsHazard Ratio For StrokeLindholm, 2005131.16 (1.04-1.30)Bangalore, 2007121.15 (1.01-1.30)Khan, 2006: Age 60y71.18 (1.07-1.30) Age 60y50.99 (0.67-1.44) 15-18% stroke risk with BB - Especially in elderly 60y Equally(not more) protective for MI, deathAm J Card 2007; 100:1254J Am Coll Card 2007; 50:
17、563BBs FOR HTN: NEW GUIDELINESNot 1st - line Rx unless HF, post-MI, angina:AHA, 2007NICE/BHS, 2006CHEP, 2008 and ESC/ESH, 2007Carvedilol possibly favored over metoprolol:Greater in microalbuminuriaLesser in wt, TG, HbA1cCirculation 2007; 115:2761 Can J Card 2007; 23:529 Eur Heart J 2007; 28:1462Hype
18、rtension 2005; 46:1309 Kid Internat 2006; 70:1905LESS EFFECTIVE BP DRUGS: ALPHA-BLOCKERS (Doxazosin, Terazosin)ALLHAT: -blocker vs diuretic, 8749 DM patientsDoxazosin vs ChlorthalidoneFatal/non-fatal CHDNo differenceCombined CVD events 22% by diureticCHF 85% by diuretic Limit -blockers to 4th Step R
19、xJ Clin Hypertens 2004; 6:116PHARM-RX OF HTN IN DMBP 130/80Single drug Rx BP by 10/5 mm HgBegin low-dose 2-drug Rx if BP 150/902-drug Rx:ACE-I (ARB) Diuretic vs ACE-I (ARB) CCBMost DM pts require 3-drug RxStandard regimen:ACE-I (ARB) Diuretic CCBPHARM-RX OF HTN IN DMAdjust diuretic eGFRwww.kidney.or
20、g/professionals/kdoqi/gfr_calculator.cfmeGFR 30-50 ml/min/1.73m2 thiazideChlorthalidone, 25 mg/d preferred if need 3 drugseGFR 30-50 ml/min/1.73m2 loop diureticFurosemide or bumetamide bidTorsemide qdTitrate dose to 4-5 lb wt lossPHARM-RX OF HTN IN DIABETESAccurate Dx of HTN: BP 130/80 in office, an
21、d/or BP 125/75 out-of-office ACE-I or ARB Lifestyle s If BP 150/90: - ACE-I or ARB Diuretic (or CCB?)Add Diuretic Thiazide for most patients Loop diuretic if eGFR 50 (Cr 1.5 mg%) and K+ 4.5 Spironolactone or amiloride Monitor K+ carefullyAm J Kid Dis 2007; 49(Suppl 2):S74 Diabetes Care 2007; 30(Suppl 1):S4BP 130/80 after 1 moAdd DHP CCB (amlodipine or other) Stop Non-DHP CCB Add: - DHP CCB (amlodipine or other) - BB (esp., carvedilol)BP 130/80 after 1 moConsultationBP 130/80 after 1 mo
