fromhypertensiontoheartfailure课件

Hypertension and The Heart,Vasilios Papademetriou, MD Professor of Medicine (Cardiology) Georgetown University Director Hypertension and Cardiovascular Research VAMC Washington DC,FDRs Final Picture (April 11, 1945),FDRs BP as recorded April 1944 at Bethesda Naval Hospital,CV Complications of Untreated Hypertension (N=500),2,0,5,10,15,20,25,30,35,40,45,50,18,12,8,16,50,Renal Failure,Stroke,Enceph,MI,Angina,CHF,MI, myocardial infarction; CHF, chronic heart failure. Perera GA J. Chron Dis. 1955;1:33-42.,Event rate (%),LVH, left ventricular hypertrophy; MI, myocardial infarction; CHF, chronic heart failure. Vasan RS and Levy D. Arch Intern Med. 1996;156:1789-1796.,Progression From Hypertension to Heart Failure,Hypertension,Smoking Dyslipidemia Diabetes,Obesity Diabetes,MI,LVH,CHF,Normal LV Structure and Function,LV Remodeling,Subclinical LV Dysfunction,Overt Heart Failure,Cumulative Incidence (%),Cumulative Incidence (%),Cumulative Incidence of Heart Failure by Baseline Hypertension Status,Time (y),Stage 1,25,20,15,10,5,0,2,4,6,8,10,12,14,16,Stage 2+,Men aged 60-69 y,Normotensive,Levy D et al. JAMA. 1996;275:1557-1562.,25,20,15,10,5,0,2,4,6,8,10,12,14,16,Stage 2+,Stage 1,Women aged 60-69 y,Normotensive,Stage 1,Normotensive,Stage 2+,40,30,20,10,0,2,4,6,8,10,12,14,Women aged 70-79 y,Population-attributable risk defined as: (100 x prevalence x hazard ratio 1)/(prevalence x hazard ratio 1 + 1),Population-Attributable Risks for Development of CHF,CHF, chronic heart failure; AP, angina pectoris; DM, diabetes mellitus; LVH, left ventricular hypertrophy; VHD, valvular heart disease; HTN, hypertension; MI, myocardial infarction. Levy D et al. JAMA. 1996;275:1557-1562.,AP 5%,DM 6%,LVH 4%,VHD 7%,MI 34%,HTN 39%,Men,Women,HTN 59%,DM 12%,LVH 5%,VHD 8%,AP 5%,MI 12%,Effects of Hypertension on The Heart,Left Ventricular Hypertrophy Vascular Disease: -Atherosclerosis -Arteriosclerosis,Prevalence of Systolic and Diastolic Dysfunction by Age,Redfield MM et al. JAMA. 2003;289:194-202.,% of Population,0,10,20,30,40,50,EF50%,EF40%,Diastolic Dysfunction,Systolic Dysfunction,Mild,Moderate,Severe,60,SYSTOLIC AND DIASTOLIC HEART FAILURE,LOW EF HIGH LV MASS MYOCYTE HYPERTOPHY INTERSTITIAL FIBROSIS ABNORM CALC HANDLING REDUCED CONTRACTILITY SLOWED RELAXATION DEPLETED PREL0AD RESERVE LARGE VOLUMES,NORMAL EF HIGH LV MASS MYOCYTE HYPERTROPHY INTERSTITIAL FIBROSIS ABNORM CALC HANDLING REDUCED CONTRACTILITY SLOWED RELAXATION DEPLETED PRELOAD RESERVE SMALL VOLUMES,KONSTAM MA; J OF CARDIAC FAILURE, 2003 VOL 9, No 1; 1-3.,Left Ventricular Hypertrophy,Independent Predictor of: Myocardial infarction Stroke Heart Failure Total Mortality Sudden Death,*Other antihypertensives excluding ACEIs, AII antagonists, beta-blockers. Dahlf B et al Am J Hypertens 1997;10:705713.,LIFE: Design Dosing,Day 14,Day 7,Day 1,Mth 1,Mth 2,Mth 4,Mth 6,Yr 1,Yr 1.5,Yr 2,Yr 2.5,Yr 3,Yr 3.5,Yr 4,Yr 5,Titration to target blood pressure: 140 / 90 mmHg,Placebo,Losartan 50 mg,Atenolol 50 mg,Losartan 50 mg + HCTZ 12.5 mg,Losartan 100 mg + HCTZ 12.5 mg,Losartan 100 mg + HCTZ 12.5-25 mg + others*,Atenolol 50 mg + HCTZ 12.5 mg,Atenolol 100 mg + HCTZ 12.5 mg,Atenolol 100 mg + HCTZ 12.5-25 mg + others*,LIFE: Blood Pressure Results Follow-up,Study Month,Systolic,Diastolic,Mean Arterial,mmHg,Atenolol 145.4 mmHg,Losartan 144.1 mmHg,Atenolol 80.9 mmHg,Losartan 81.3 mmHg,B Dahlof et al. Lancet 2002;359:995-1003,Intention-to-Treat,LIFE: Fatal/Nonfatal Stroke,B Dahlof et al. Lancet 2002;359:995-1003,Study Month,LIFE: Fatal/Nonfatal Myocardial Infarction,Intention-to-Treat,B Dahlof et al. Lancet 2002;359:995-1003,Study Month,LIFE: Cardiovascular Mortality,Intention-to-Treat,B Dahlof et al. Lancet 2002;359:995-1003,Study Month,0,0.5,1,1.5,2,Total Mortality,Hosp for AP,Hosp for HF,Revascularization,23,LIFE: Other Classified Endpoints,Favors Losartan,Favors Atenolol,Hazard Ratio (95% CI),LVH Prevalence at Baseline and Annual Follow-Up in LIFE,HR = 0.58, 95% CI 0.38-0.86 P-0.008,Hazard ratios represent risk reduction associated with absence versus presence of LVH,HR=0.34, 95% CI 0.17-0.71 P-0.004,Hazard ratios represent risk reduction associated with absence versus presence of LVH,HR=0.48, 95% CI 0.24-0.93 0.031,Hazard ratios represent risk reduction associated with absence versus presence of LVH,HR=0.36, 95% CI 0.23-0.53 P0.001,Hazard ratios represent risk reduction associated with absence versus presence of LVH,LIFE Echo Substudy: Change in LVMI,Change from Baseline to Year in LIFE,*,* p=0.021, adjusted for baseline LVMI and baseline & in-treatment BP,Change (g/m2),Devereux RB et al. Am J Hypertens 2002;15:15A,Regression of Hypertensive LVH: Results of 2000 Meta-Analysis,Schmieder et al: J Am Coll Cardiol 2001;37:261-262A,P0.05,P0.09 vs -blockers,LVM Regression (%),Diuretics,Beta- Blockers,ACE- Inhibitors,Ca+ Blockers,AII receptor Blockers,CHARM Added,CHARM Preserved,CHARM Programme,3 component trials comparing candesartan to placebo in patients with symptomatic heart failure,CHARM Alternative,n=2028 LVEF 40% ACE inhibitor intolerant,n=2548 LVEF 40% ACE inhibitor treated,n=3025 LVEF 40% ACE inhibitor treated/not treated,Primary outcome for Overall Programme: All-cause death,Primary outcome for each trial: CV death or CHF hospitalisation,CHARM-Preserved Primary and secondary outcomes,CV death, CHF hosp. 333 366 - CV death 170 170 - CHF hosp. 241 276 CV death, CHF hosp, 365 399 MI CV death,CHF hosp, 388 429 MI, stroke CV death,CHF hosp, 460 497 MI, stroke, revasc,candesartan better,Hazard ratio,placebo better,0.8,1.0,1.2,p-value,0.918,0.072,0.118,0.126,0.078,0.123,Covariate adjusted p-value,0.635,0.047,0.051,0.051,0.037,0.13,Candesartan,Placebo,0.89,0.99,0.85,0.90,0.88,0.91,Effects of Hypertension on The Heart,Left Ventricular Hypertrophy Vascular Disease: -Atherosclerosis -Arteriosclerosis,ATHERO- ARTERIO- SCLEROSIS SCLEROSIS (Increased vascular stiffness Decreased vascular compliance),Focal, Occlusive Inflammatory Endothelial dysfunction Related to LDL cholesterol oxidation “Inside-out” Sensitive to A II and other substances,Diffuse, Dilatory Fibrotic (elastin breakdown, collagen increase) Adventitial and medial hypertrophy Related to age and BP “Outside-in” Sensitive to A II and other substances,Integrated Perspective on CV Risk Factors and Vascular Disease,Smoking,Diabetes,Hypertension,Dyslipidemia,Oxidative Stress Inflammation Endothelial Dysfunction,Ross R, N Engl J Med 340 (1999) & Davies, Circulation 94 (1996),Hemorrhaged microvessels,Ruptured plaque (coronary artery),Plaque rupture,Unstable Plaque,Thinning of fibrous cap,BP and Risk of CHD Mortality,CHD, coronary heart disease. Multiple Risk Factor Intervention Trial (MRFIT); n=347,978 men without previous myocardial infarction. Neaton JD et al. In: Hypertension: Pathophysiology, Diagnosis, and Management. 1995:127-144.,Stroke and IHD Mortality vs Usual Systolic BP by Age,IHD=ischemic heart disease Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.,Mortality (Floating Absolute Risk and 95% CI),),AGING AND ARTERIAL STIFFNESS PATHOPHYSIOLOGY Young elastic vessels Old inelastic vessels,Adapted from Izzo JL. J Am Geriatr Soc. 1981;29:520-524.,SYSTOLE,DIASTOLE,DIASTOLE,SYSTOLE,STROKE VOLUME,RESISTANCE ARTERIOLES,AORTA,PRESSURE (FLOW),STROKE VOLUME,RESISTANCE ARTERIOLES,AORTA,PRESSURE (FLOW),(,Increased systolic,Decreased diastolic,Men, Age (y),Women, Age (y),Pulse pressure,Pulse pressure,SBP & DBP by Age & Race/Ethnicity &Gender (US Population Age 18 Years, NHANES III),Burt VI, et al. Hypertension. 1995;25:305-313.,40,40-49,50-59,60-69,70-79,80+,Age (y),17%,16%,16%,20%,20%,11%,Distribution of Hypertension Subtype in the untreated Hypertensive Population in NHANES III by Age,Numbers at top of bars represent the overall percentage distribution of untreated hypertension by age. Franklin et al. Hypertension 2001;37: 869-874.,Frequency of hypertension subtypes in all untreated hypertensives (%),Franklin SS, et al. Circ. 1999;100:354.,60,70,80,90,100,110,DBP (mm Hg),0.5,1,1.5,2,2.5,3,SBP 170 mm Hg (P = 0.01),SBP 150 mm Hg (P = 0.02),SBP 130 mm Hg (P = 0.06),SBP 110 mm Hg (P = 0.03),CHD hazard ratio,Relationship of SBP and DBP to risk for CHD:The Framingham Heart Study,Mean age = 61 years (range: 50-79), n = 1924,Adjusted for age, sex, and other risk factors P = probability for coefficients,Effect 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. Adapted from: Neaton et al. Arch Intern Med. 1992;152:56-64.,Death rate per 10,000 person-years,Diastolic BP (mm Hg),Systolic BP (mm Hg),Hypertension: A Major Risk Factor for CHF,Time, decades,Vasan RS, Levy D. Arch Intern Med. 1996;156:1789-1796.,Death,Systolic Dysfunction,Diastolic Dysfunction,Subclinical Left Ventricular Dysfunction,CHF,Overt Heart Failure,Time, months,Hypertension,LVH,MI,Left Ventricular Remodeling,0,0.5,1,1.5,2,2.5,3,3.5,Active,Placebo,1.6,3.5,p.001,Development of CHF,Active 112 of 6,914 Placebo 240 of 6,923 55% risk reduction,Moser, Herbert JACC 1996;27:1214-28,-60,-50,-40,-30,-20,-10,0,Coops & Warrender,EWPHE,SHEP,STOP Hypertension,-35,-53,-54,-51,Risk Reduction of Heart Failure in Elderly Hypertensives,Risk reduction (%),HEART FAILURE,FROM HYPERTENSION TO HEART FAILURE IN SHEP,Kostis et al, JAMA 1997,about 85%,about 15%,Fatal and Nonfatal Hospitalized Heart Failure SHEP Study by Age Group,Kostis et al. JAMA. 1997.,%,Follow-Up (y),Age 60-69 y,Age 70-79 y,Age 80+ y,Treatment of Hypertension and CVD Outcomes Placebo Controlled Trials,17 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,-10,0,Heart failure,Fatal/nonfatal strokes,CVD deaths,Fatal/nonfatal CHD events,Risk reduction (%),There is no question that treatment of Hypertension will prevent CV Complications,Does it Matter How We Do it ?,ACE/CCB Trials vs Beta-Blockers/Diuretics,Major 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.,CONVINCE Hazard Ratios for Subgroups,SOC Diuretic,181,165,SOC,-Blocker,183,200,USA,204,212,Canada,93,86,Western Europe,39,35,Other,28,32,COER-v,SOC,No. of Events,Favors COER-v Favors SOC ,-Blocker,JAMA. 2003.,CONVINCE CVD-Related 2 Endpoints,(No. of events),JAMA. 2003.,Randomized Design of ALLHAT,High-risk hypertensive patients,Consent / Randomize (42,418),Amlodipine Chlorthalidone Doxazosin Lisinopril,Eligible for lipid-lowering,Not eligible for lipid-lowering,Consent / Randomize (10,355),Pravastatin Usual care,Follow for CHD and other outcomes until death or end of study (up to 8 yr).,Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group,Chlorthalidone Amlodipine Lisinopril,Cumulative Event Rate,Years of follow-up,doxazosin,chlorthalidone,Heart Failure,C: 15,268 D: 9,067,13,644 7,845,5,531 3,089,2,427 1,351,9,541 5,457,JAMA. 2000;283:1967-1975.,SBP Results by Treatment Group,Months,BP (mmHg),Chlorthalidone,Doxazosin,Heart Failure Subgroup Comparisons RR (95% CI),Amlodipine Better Chlorthalidone Better,0.50,1,2,Non-Diabetic,1.33 (1.16, 1.52),Diabetic,1.42 (1.23, 1.64),Non-Black,1.33 (1.18, 1.51),Black,1.47 (1.24, 1.74),Women,1.33 (1.14, 1.55),Men,1.41 (1.24, 1.61),Age = 65,1.33 (1.18, 1.49),Age 65,1.51 (1.25, 1.82),Total,1.38 (1.25, 1.52),Lisinopril Better Chlorthalidone Better,0.50,1,2,Non-Diabetic,1.20 (1.04, 1.38),Diabetic,1.22 (1.05, 1.42),Non-Black,1.15 (1.01, 1.30),Black,1.32 (1.11, 1.58),Women,1.23 (1.05, 1.43),Men,1.19 (1.03, 1.36),Age = 65,1.20 (1.06, 1.35),Age 65,1.23 (1.01, 1.50),Total,1.20 (1.09, 1.34),BP Results by Treatment Group,Compared to chlorthalidone: SBP significantly higher in the amlodipine group (1 mm Hg) and the lisinopril group (2 mm Hg).,Years,BP (mmHg),Chlorthalidone,Amlodipine,Lisinopril,BP (mmHg),Favors First Listed,Favors Second Listed,0.5,1.0,2.0,BP-Lowering Treatment Trialists Comparisons of different active treatments,Lancet. In press.,Relative Risk,RR (95% CI),BP Difference (mm Hg),Stroke,Coronary Heart Disease,Heart Failure,0.5,1.0,2.0,BP-Lowering Treatment Trialists Comparisons of different active trea