【高血压英文课件】-Hypertension-and-The-Heart

Hypertension and The Heart Hypertension and The Heart Vasilios Papademetriou,MDProfessor of Medicine(Cardiology)Georgetown UniversityDirector Hypertension and Cardiovascular ResearchVAMC Washington DC Hypertension and The Heart VaFDRs Final Picture(April 11,1945)FDRs Final Picture(April 11,2FDRs BP as recorded April 1944 at Bethesda Naval Hospital FDRs BP as recorded April 1943【高血压英文课件】-Hypertension-and-The-Heart4【高血压英文课件】-Hypertension-and-The-Heart5CumulativeIncidence(%)CumulativeIncidence(%)Cumulative Incidence of Heart Failure by Baseline Hypertension StatusTime(y)Stage 12520151050246810121416Stage 2+Men aged 60-69 yNormotensive2468101214Men aged 70-79 yStage 2+Stage 1Normotensive403020100Levy D et al.JAMA.1996;275:1557-1562.2520151050246810121416Stage 2+Stage 1Women aged 60-69 yNormotensiveStage 1NormotensiveStage 2+4030201002468101214Women aged 70-79 yCumulativeCumulativeCumulative6Population-attributable risk defined as:(100 x prevalence x hazard ratio 1)/(prevalence x hazard ratio 1+1)Population-Attributable Risks for Development of CHFCHF,chronic heart failure;AP,angina pectoris;DM,diabetes mellitus;LVH,left ventricular hypertrophy;CHF,chronic heart failure;AP,angina pectoris;DM,diabetes mellitus;LVH,left ventricular hypertrophy;VHD,valvular heart disease;HTN,hypertension;VHD,valvular heart disease;HTN,hypertension;MI,myocardial infarction.MI,myocardial infarction.Levy D et al.JAMA.1996;275:1557-1562.AP5%DM6%LVH4%VHD7%MI34%HTN 39%MenWomenHTN 59%DM12%LVH5%VHD8%AP5%MI12%Population-attributable risk d7Effects of Hypertension on The Heartl lLeft Ventricular HypertrophyLeft Ventricular Hypertrophyl lVascular Disease:Vascular Disease:-Atherosclerosis -Atherosclerosis -Arteriosclerosis -ArteriosclerosisEffects of Hypertension on The8 8【高血压英文课件】-Hypertension-and-The-Heart【高血压英文课件】-Hypertension-and-The-Heart10【高血压英文课件】-Hypertension-and-The-Heart11【高血压英文课件】-Hypertension-and-The-HeartPrevalence of Systolic and Diastolic Dysfunction by AgeRedfield MM et al.JAMA.2003;289:194-202.%of Population01020304050EF50%EF75ALL60Prevalence of Systolic and DiaLeft Ventricular HypertrophyIndependent Predictor of:l lMyocardial infarctionMyocardial infarctionl lStrokeStrokel lHeart FailureHeart Failurel lTotal MortalityTotal Mortalityl lSudden DeathSudden DeathLeft Ventricular HypertrophyIn1515【高血压英文课件】-Hypertension-and-The-Heart16【高血压英文课件】-Hypertension-and-The-Heart17*Other antihypertensives excluding ACEIs,AII antagonists,beta-blockers.Dahlf B et al Am J Hypertens 1997;10:705713.LIFE:Design DosingDay 14Day 7Day1Mth1Mth2Mth 4Mth6Yr1Yr1.5Yr2Yr2.5Yr3Yr3.5Yr4Yr5Titration to target blood pressure:140/90 mmHgPlaceboLosartan 50 mg Atenolol 50 mgLosartan 50 mg+HCTZ 12.5 mgLosartan 100 mg+HCTZ 12.5 mgLosartan 100 mg+HCTZ 12.5-25 mg+others*Atenolol 50 mg+HCTZ 12.5 mgAtenolol 100 mg+HCTZ 12.5 mgAtenolol 100 mg+HCTZ 12.5-25 mg+others*Other antihypertensives excluLIFE:Blood Pressure Results Follow-up061218243036424854Study Month406080100120140160180SystolicDiastolicMean ArterialmmHgAtenololLosartanAtenolol 145.4 mmHgLosartan 144.1 mmHgAtenolol 80.9 mmHgLosartan 81.3 mmHgB Dahlof et al.Lancet 2002;359:995-1003LIFE:Blood Pressure Results Intention-to-TreatLIFE:Fatal/Nonfatal StrokeLosartanAtenololAdjusted Risk Reduction 249%,p=0001Unadjusted Risk Reduction 258%,p=0.0006Proportion of patients with first event(%)0 1 2 3 4 5 6 7 8B Dahlof et al.Lancet 2002;359:995-1003 0 6 12 18 24 30364248546066Study MonthIntention-to-TreatLIFE:Fatal/LIFE:Fatal/Nonfatal Myocardial InfarctionIntention-to-Treat 0 1 2 3 4 5 6 7 8Proportion of patients with first event(%)AtenololLosartanAdjusted Risk Reduction-73%,p=049Unadjusted Risk Reduction-50%,p=063B Dahlof et al.Lancet 2002;359:995-1003 0 6 12 18 24 30364248546066Study MonthLIFE:Fatal/Nonfatal Myocardia00.511.52Total MortalityHosp for APHosp for HFRevascularization23LIFE:Other Classified EndpointsFavors LosartanFavors AtenololHazard Ratio(95%CI)00.511.52Total MortalityHosp fLVH Prevalence at Baseline and Annual Follow-Up in LIFELVH Prevalence at Baseline and24HR=0.58,95%CI 0.38-0.86P-0.008Hazard ratios represent risk reduction associated with absence versus presence of LVHHR=0.58,95%CI 0.38-0.86Haz25HR=0.34,95%CI 0.17-0.71P-0.004Hazard ratios represent risk reduction associated with absence versus presence of LVHHR=0.34,95%CI 0.17-0.71Hazar26HR=0.48,95%CI 0.24-0.930.031Hazard ratios represent risk reduction associated with absence versus presence of LVHHR=0.48,95%CI 0.24-0.93Hazar27HR=0.36,95%CI 0.23-0.53P0.001Hazard ratios represent risk reduction associated with absence versus presence of LVHHR=0.36,95%CI 0.23-0.53Hazar28LIFE Echo Substudy:Change in LVMIChange from Baseline to Year in LIFE*p=0.021,adjusted for baseline LVMI and baseline&in-treatment BPChange(g/m2)Devereux RB et al.Am J Hypertens 2002;15:15A LIFE Echo Substudy:Change in【高血压英文课件】-Hypertension-and-The-Heart30Regression of Hypertensive LVH:Results of 2000 Meta-AnalysisSchmieder et al:J Am Coll Cardiol 2001;37:261-262AP0.05P40%ACE inhibitor treated/not treatedPrimary outcome for Overall Programme:All-cause deathPrimary outcome for each trial:CV death or CHF hospitalisationCHARM AddedCHARMPreservedCHA33CHARM-Preserved Primary and secondary outcomesCV death,CHF hosp.333 366-CV death170170-CHF hosp.241276CV death,CHF hosp,365399 MI CV death,CHF hosp,388429 MI,stroke CV death,CHF hosp,460497 MI,stroke,revasc candesartan betterHazard ratioplacebo better0.81.01.2p-value0.9180.0720.1180.1260.0780.123Covariateadjustedp-value0.6350.0470.0510.0510.0370.13Candesartan Placebo0.890.990.850.900.880.91CHARM-Preserved Primary and sEffects of Hypertension on The HeartLeft Ventricular HypertrophyVascular Disease:-Atherosclerosis -ArteriosclerosisEffects of Hypertension on The ATHERO-ARTERIO-SCLEROSIS SCLEROSIS (Increased vascular stiffness Decreased vascular compliance)Focal,OcclusiveInflammatoryEndothelial dysfunctionRelated to LDL cholesterol oxidation“Inside-out”Sensitive to A II and other substancesDiffuse,DilatoryFibrotic(elastin breakdown,collagen increase)Adventitial and medial hypertrophyRelated to age and BP“Outside-in”Sensitive to A II and other substances ATHERO-ARTERIO-S353636Integrated Perspective on CV Risk Factors and Vascular DiseaseCVDiseaseRoss.Ross.N Engl J MedN Engl J Med.1999;340:115-126.1999;340:115-126.Oxidative Stress&InflammationOxidative Stress&InflammationEndothelial DysfunctionEndothelial DysfunctionRoss.Ross.N Engl J MedN Engl J Med.1999;340:115-126.1999;340:115-126.Integrated Perspective on CV R3939Stroke and IHD Mortality vs Usual Systolic BP by AgeIHD=ischemic heart diseaseIHD=ischemic heart diseaseProspective Studies Collaboration.Prospective Studies Collaboration.LancetLancet.2002;360:1903-1913.2002;360:1903-1913.MortalityMortality(Floating Absolute Risk and 95%CI)(Floating Absolute Risk and 95%CI)Usual Systolic BP(mm Hg)Usual Systolic BP(mm Hg)50-59 years50-59 years60-69 years60-69 years70-79 years70-79 years80-89 years80-89 yearsStrokeStrokeAge at risk:Age at risk:2562561281286464323216168 84 42 21 10 0120120140140160160180180IHDIHDUsual Systolic BP(mm Hg)Usual Systolic BP(mm Hg)50-59 years50-59 years60-69 years60-69 years70-79 years70-79 years80-89 years80-89 yearsAge at risk:Age at risk:40-49 years40-49 years2562561281286464323216168 84 42 21 10 0120120140140160160180180Stroke and IHD Mortality vs Us)AGING AND ARTERIAL STIFFNESS PATHOPHYSIOLOGY Young elastic vessels Old inelastic vesselsAdapted from Izzo JL.J Am Geriatr Soc.1981;29:520-524.SYSTOLEDIASTOLEDIASTOLESYSTOLESTROKEVOLUMERESISTANCEARTERIOLESAORTAPRESSURE(FLOW)STROKEVOLUMERESISTANCEARTERIOLESAORTAPRESSURE(FLOW)(Increased systolicDecreased diastolic)AGING AND ARTERIAL STIFFNES4018-29 30-39 40-49 50-59 60-69 70-7980+0708011013015018-29 30-39 40-49 50-59 60-69 70-7980+070801101301500708011013015007080110130150DBP(mm Hg)SBP(mm Hg)DBP(mm Hg)SBP(mm Hg)DBP(mm Hg)SBP(mm Hg)DBP(mm Hg)SBP(mm Hg)Men,Age(y)Women,Age(y)Non-Hispanic BlackNon-Hispanic BlackNon-Hispanic WhiteNon-Hispanic WhiteMexican AmericanMexican AmericanPulse pressurePulse pressurePulse pressurePulse pressureSBP&DBP by Age&Race/Ethnicity&Gender (US Population Age 18 Years,NHANES III)Burt VI,et al.Hypertension.1995;25:305-313.18-2930-3940-4950-5960-6970-79414040-4950-5960-6970-7980+Age(y)17%16%16%20%20%11%Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by AgeISH(SBP 140 mm Hg and DBP 90 mm Hg)SDH(SBP 140 mm Hg and DBP 90 mm Hg)IDH(SBP 140 mm Hg and DBP 90 mm Hg)020406080100Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age.Franklin et al.Hypertension 2001;37:869-874.Frequency of hypertensionsubtypes in all untreated hypertensives(%)4040-4950-5960-6970-7980+Age 424444Effect of Systolic BP and Diastolic BP on CHD Mortality:MRFIT Screenees(N=316,099)*Men aged 35 to 57 years followed up for a mean of 12 years.*Men aged 35 to 57 years followed up for a mean of 12 years.Adapted from:Neaton et al.Adapted from:Neaton et al.Arch Intern Med.Arch Intern Med.1992;152:56-64.1992;152:56-64.Death rateDeath rateper 10,000per 10,000person-yearsperson-yearsDiastolic BPDiastolic BP(mm Hg)(mm Hg)Systolic BPSystolic BP(mm Hg)(mm Hg)Effect of Systolic BP and DiasHypertension:A Major Risk Factor for CHFTime,decadesVasan RS,Levy D.Arch Intern Med.1996;156:1789-1796.DeathObesityDiabetesSmokingDyslipidemiaSystolic DysfunctionDiastolic DysfunctionSubclinicalLeft VentricularDysfunctionCHFOvert HeartFailureTime,monthsHypertensionLVHMILeft VentricularRemodelingHypertension:A Major Risk Fac454500.511.522.533.5ActivePlacebo1.63.5p.001Development of CHFActive 112 of 6,914Placebo 240 of 6,92355%risk reductionMoser,Herbert JACC 1996;27:1214-2800.511.522.533.5ActivePlacebo1-60-50-40-30-20-100Coops&WarrenderEWPHESHEPSTOPHypertension-35-53-54-51Risk Reduction of Heart Failurein Elderly HypertensivesRiskreduction(%)-60-50-40-30-20-100Coops&EWPH47HEART FAILUREFROM HYPERTENSION TO HEART FAILURE IN SHEPKostis et al,JAMA 1997about 85%about 15%HEART FAILUREFROM HYPERTENSIONFatal and Nonfatal HospitalizedHeart FailureSHEP Study by Age GroupKostis et al.JAMA.1997.%Follow-Up(y)Age 60-69 yAge 70-79 yAge 80+yFatal and Nonfatal Hospitalize4949Treatment of Hypertension and CVD Outcomes Placebo Controlled Trials17 randomized,placebo-controlled trials(48,000 subjects)14 diuretic and 3 beta blocker based trials.All differences are statistically significant.CVD,cardiovascular disease;CHD,coronary heart disease.Herbert PR et al.Arch Intern Med.1993;153:578-581.Moser M,Herbert PR.J Am Coll Cardiol.1996;27:1214-1218.-16-21-38-52-60-50-40-30-20-100HeartfailureFatal/nonfatalstrokesCVD deathsFatal/nonfatalCHD eventsRiskreduction(%)Treatment of Hypertension and 50There is no question that treatment of Hypertension will prevent CV ComplicationsDoes it Matter How We Do it?There is no question that treaACE/CCB Trials vs Beta-Blockers/DiureticsMajor cardiovascular events included stroke,myocardial infarction,heart failure,or death from any cardiovascular cause Adapted from Blood Pressure Lowering Treatment Trialists Collaboration.Lancet 2000;356:1956-1964.ACE/CCB Trials vs Beta-BlockerCONVINCEHazard Ratios for Subgroups SOC Diuretic 181165SOC -Blocker 183200USA 204212Canada 93 86Western Europe 39 35Other 28 32COER-v SOCNo.of Events0.40.60.81.01.21.41.61.8Hazard Ratio(COER-verapamil/SOC)Favors Favors COER-v Favors Favors SOC -BlockerJAMA.2003.CONVINCEHazard Ratios for Sub5353CONVINCECVD-Related 2 EndpointsEventEventCOER-vCOER-vSOCSOCHRHRP P value value1 1 or CVD Hosp or CVD Hosp7937937757751.051.050.310.31CVD HospitalizationCVD Hospitalization Angina Angina2022021901901.091.090.390.39 Revascularization Revascularization1631631661661.011.010.910.91 CHF CHF1261261001001.301.300.050.05 TIA TIA 89 891051050.870.870.330.33 Renal Insufficiency Renal Insufficiency 27 27 34 340.810.810.430.43 Acc HTN Acc HTN 22 22 18 181.261.260.370.37(No.of events)JAMA.2003.CONVINCECVD-Related 2 Endpoi5454Randomized Designof ALLHATHigh-risk hypertensive patientsConsent/Randomize(42,418)AmlodipineChlorthalidoneDoxazosinLisinoprilEligible for lipid-loweringNot eligible for lipid-loweringConsent/Randomize(10,355)Pravastatin Usual careFollow for CHD and other outcomes until death or end of study(up to 8 yr).ALLHATRandomized Designof ALLHATHig55Years to CHD Event01234567Cumulative CHD Event Rate0.04.08.12.16.2Cumulative Event Rates for the Primary Outcome(Fatal CHD or Nonfatal MI)by ALLHAT Treatment Group RR(95%CI)p valueA/C0.98(0.90-1.07)0.65L/C0.99(0.91-1.08)0.81ALLHATChlorthalidoneAmlodipineLisinoprilYears to CHD Event01234567Cumu56CumulativeEventRateYears of follow-updoxazosinchlorthalidoneHeart FailureC:15,268D:9,06713,644 7,8455,5313,0892,4271,351 9,541 5,457 Rel risk 2.04z=10.95,p=651.33 (1.18,1.49)Age=651.20 (1.06,1.35)Age 651.23 (1.01,1.50)Total1.20 (1.09,1.34)Heart Failure Subgroup Compa5959BP Results by Treatment GroupCompared to chlorthalidone:SBP significantly higher in the amlodipine group(1 mm Hg)and the lisinopril group(2 mm Hg).ALLHAT1301351401451500123456YearsBP(mmHg)ChlorthalidoneAmlodipineLisinoprilCompared to chlorthalidone:DBP significantly lower in the amlodipine group(1 mm Hg).70758085900123456YearsBP(mmHg)BP Results by Treatment GroupC60606161FavorsFavorsFirst ListedFirst ListedFavorsFavorsSecond ListedSecond Listed0.51.02.0BP-Lowering Treatment TrialistsComparisons of Comparisons of different active treatmentsdifferent active treatmentsLancetLancet.In press.In press.Relative Risk RR(95%CI)RR(95%CI)BP DifferenceBP Difference(mm Hg)(mm Hg)CA vs D/BB CA vs D/BB 1.33(1.21,1.47)1.33(1.21,1.47)1/01/0 0.93(0.86,1.01)0.93(0.86,1.01)CA vs D/BB CA vs D/BB1/01/0 1.01(0.94,1.08)1.01(0.94,1.08)CA vs D/BB CA vs D/BB1/01/0 ACE vs CA ACE vs CA 0.82(0.73,0.92)0.82(0.73,0.92)1/11/1 1.12(1.01,1.25)1.12(1.01,1.25)ACE vs CA ACE vs CA1/11/1 0.96(0.88,1.05)0.96(0.88,1.05)ACE vs CA ACE vs CA1/11/1StrokeStrokeCoronary Heart DiseaseCoronary Heart DiseaseHeart FailureHeart Failure 1.09(1.00,1.18)1.09(1.00,1.18)ACE vs D/BB ACE vs D/BB2/02/0 0.98(0.91,1.05)0.98(0.91,1.05)ACE vs D/BB ACE vs D/BB2/02/0 1.07(0.96,1.19)1.07(0.96,1.19)ACE vs D/BB ACE vs D/BB2/02/0FavorsFirst ListedFavorsSeco6464BP-Lowering Treatment TrialistsStrokeStrokeSystolic Blood Pressure Systolic Blood Pressure Difference Between Randomised Difference Between Randomised Groups(mm Hg)Groups(mm Hg)Relative Risk of StrokeRelative Risk of Stroke0.250.250.500.500.750.751.001.001.251.251.501.50-10-10-8-8-6-6-4-4-2-20 02 24 4Systolic Blood Pressure Systolic Blood Pressure Difference Between Randomised Difference Between Randomised Groups(mm Hg)Groups(mm Hg)Relative Risk of CHDRelative Risk of CHD0.250.250.500.500.750.751.001.001.251.251.501.50-10-10-8-8-6-6-4-4-2-20 02 24 4CHDCHDLancetLancet.In press.In press.BP-Lowering Treatment TrialistHypertension:A Major Risk Factor for CHFTime,decadesVasan RS,Levy D.Arch Intern Med.1996;156:1789-1796.DeathObesityDiabetesSmokingDyslipidemiaSystolic DysfunctionDiastolic DysfunctionSubclinicalLeft VentricularDysfunctionCHFOvert HeartFailureTime,monthsHypertensionLVHMILeft VentricularRemodelingHypertension:A Major Risk Fac6565Prevention of Cardiac Complications of Hypertensionl lIts the Blood Pressure stupid Its the Blood Pressure stupid l lTreat Blood Pressure to GoalTreat Blood Pressure to Goall lSystolic BP Reduction is Probably more Systolic BP Reduction is Probably more importantimportantl lDiuretic Trerapy is as good as anyDiuretic Trerapy is as good as anyl lCalcium Channel Blockers/Alfa Blockers Calcium Channel Blockers/Alfa Blockers seem to be less effective in preventing seem to be less effective in preventing Heart FailureHeart FailurePrevention of Cardiac Complica6666WORKING HARD,Right Tools?WORKING HARD,Right Tools?Lancet 3/01Lancet 3/01Science 3/01Science 3/01Lancet 3/01Science 3/01