hypertension_ improving treatment and control - heart disease ...课件

1,Improving Blood Pressure Treatment in the Community: Implications of the JNC7 Recommendations and ALLHAT Results Nathan D. Wong, PhD, FACC Professor and Director Heart Disease Prevention Program University of California, Irvine,2,Peripheral vascular disease, Morbidity Disability,Renal disease,CAD,CHF LVH,Stroke,Hypertension,National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186-208.,Hypertension: A Significant CV and Renal Disease Risk Factor,3,Nearly 1 in 3 adults (31%) in the US has hypertension,Fields LE et al. Hypertension. 2004;44:398-404.,Hypertension: How Big Is the Problem?,At Least 65 Million Americans Require Treatment for Hypertension,4,Risk of Cardiovascular Events by Hypertensive Status,36-Year Follow-up in Patients Aged 35-64 Years,9.5,3.3,2.4,5.0,2.0,3.5,2.1,45.4,21.3,12.4,6.2,9.9,7.3,13.9,6.3,22.7,0,10,20,30,40,50,Normotensive,Hypertensive,Coronary Disease,Stroke,Peripheral Arterial Disease,Cardiac Failure,Biennial Age-Adjusted Rate per 1,000,Reprinted with permission from Kannel WB. JAMA. 1996;275:1571-1576.,5,SBP-Associated Risks: MRFIT,Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.,SBP versus DBP in Risk of CHD Mortality,Diastolic BP (mm Hg),Systolic BP (mm Hg),CHD Death Rate,100+,9099,8089,7579,7074,70,120,120139,140159,160+,48.3,20.6,10.3,11.8,8.8,8.5,9.2,23.8,16.9,13.9,12.8,12.6,11.8,31.0,25.5,24.6,25.3,25.2,24.9,37.4,34.7,43.8,38.1,80.6,40,40-49,50-59,60-69,70-79,80+,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 (%),7,Disease Relative Risk Kidney failure (ESRD) 2.8 Stroke 2.7 Heart failure 1.5 Peripheral vascular disease 1.8 Myocardial infarction* =1.6 Coronary artery disease 1.5,ESRD = end-stage renal disease; SBP 165 mm Hg. *Men only. Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part 1):587-594; Klag MJ et al. N Engl J Med. 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger. 1996;158:3779-3783; Neaton JD et al. Arch Intern Med. 1992;152:56-64.,Elevated SBP Alone Is Associated With Increased Risk of Cardiovascular and Renal Disease,8,9,Prevalence, Awareness, Treatment, and Control of Hypertension in US Adults 2003-2004 (Ong et al., Hypertension 2007; 49: 69-75),10,Prevalence (%) of HTN in US Adults, by Disease Status (Wong et al, Arch Intern Med 2007, in press),*P0.01 when compared to No-Disease Group,*,*,*,*,*,*,*,Mean age (y): 53.5 59.3 54.8 60.5 76.1 65.9 68.2 69.3 67.2,*,11,Treatment (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press),*P0.05, *P0.01 when compared to No-Disease group Treatment is in persons with HTN,*,*,*,*,12,Control (all treated) (%) of HTN in US Adults, by Disease Status (Wong et al., Arch Intern Med 2007, in press),*P0.05*P0.01 when compared to No-Disease Group Control is in persons with HTN defined as BP 140/90 If DM and CKD is based on BP130/80 control is *35.3% and *23.2%, respectively. If MetS is based on BP130/85 control is *46.7%,*,*,*,*,13,Minimum BP distance from goal of 140/90 in parenthesis, even with DM & CKD *p0.05 *p0.01 compared to no disease,Mean BP and Distance to Goal Among HTN Pts Not at Goal (Wong et al., Arch Intern Med 2007, in press),14,Blood Pressure Classification,15,4-Year Progression To Hypertension: The Framingham Heart Study,(120/80 mm Hg),(130/85 mm Hg),(130-139/85-89 mm Hg),Vasan, et al. Lancet 2001;358:1682-86,Participants age 36 and older,HOT Study: Significant Benefit From Intensive Treatment in the Diabetic Subgroup,Hansson L et al. Lancet. 1998;351:1755-1762.,0,5,10,15,20,25,90,85,80,Major cardiovascular events/1,000 patient-years,p=0.005 for trend,mm Hg,Target Diastolic Blood Pressure,17,Benefits of Lowering BP,Average Percent Reduction Stroke incidence 3540% Myocardial infarction 2025% Heart failure 50%,TROPHY Study ACC 2006: Even lowering BP in those with pre-HTN appears to reduce incidence of new HTN by up to 60%,18,19,Preventable CHD Events from Control of Hypertension in US Adults (Wong et al., Am Heart J 2003; 145: 888-95),PAR% = population attributable risk (proportion of CHD events preventable), NNT = number needed to treat to prevent 1 CHD event ; 0.01 comparing men and women for PAR%,20,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).,21,Baseline Characteristics and Follow-up,22,Doxazosin Arm Terminated Early,Futility of finding a significant difference for primary CHD outcome Statistically significant 20 percent higher rate of major secondary endpoint, combined CVD outcomes (80% higher rate of heart failure),Hypertension. 2003;42:239-246.,23,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).,Compared to chlorthalidone: DBP significantly lower in the amlodipine group (1 mm Hg), similar in the lisinopril group.,24,Cumulative Event Rates for the Primary Outcome (Fatal CHD or Nonfatal MI) by ALLHAT Treatment Group,Chlorthalidone Amlodipine Lisinopril,25,Subgroup Comparisons,Results were consistent across age, race, gender, and baseline diabetes subgroups, except: Stroke Black L/C RR (95% CI) = 1.40 (1.17 1.68) Non-Black L/C RR (95% CI) = 1.00 (0.85 1.17) Combined CVD Black L/C RR (95% CI) = 1.19 (1.09 1.30) Non-Black L/C RR (95% CI) = 1.06 (1.00 1.13),26,Nonfatal MI + CHD Death Subgroup Comparisons RR (95% CI),27,Prospective Studies Collaboration, Lancet 2002;360:1903-13,Predicted Cause-specific Mortality for 2 mm Hg lower SBP,CHD -4 to -7% Stroke -4 to -10% Heart failure -5 to -7% Higher numbers for younger hypertensives,28,Summary of Outcomes Relative Risks and 95% CI,29,Fasting Glucose Results,* p.05 compared to chlorthalidone,30,Outcome results were similar in diabetic and nondiabetic participants For both diabetic and nondiabetic participants, there were significant advantages for the diuretic arm,ALLHAT Results by Baseline Diabetic Status,31,Effect of 2-Year Changes in Fasting Glucose on ALLHAT Endpoints (Cox Regressions Beginning at 2 Years),32,Diuretics, Potassium, and Glucose,Based on 40+ years evidence, potassium depletion is a major factor relating thiazide treatment and abnormal glucose. Both reduced insulin release and decreased insulin sensitivity have been demonstrated. More attention than is often given to preventing or reversing hypokalemia is warranted, especially in patients at risk of diabetes. Reference: Wilcox CS. Seminars in Nephrology, 1999;19:557-68.,33,Large Hypertension Trials Comparing Two or More Regimens: CVD or CV Mortality,Trial n BP Outcomes CAPPP 10,985 +3/+1 captopril not superior to D/BB NORDIL 10,881 +3/0 diltiazem not superior to D/BB CONVINCE 16,602 0/+1 verapamil not superior to D/BB STOP-2 6,628 0/-1 isradipine/felodipine & 0/0 ACEIs not superior to D/BB INSIGHT 6,592 0/0 nifed GITS not superior to diuretic LIFE 9,193 +1/0 losartan superior to atenolol ANBP-2 6,083 +1/0 ACEIs not superior to diuretics ALLHAT 42,418 -3/-1 chlorthalidone superior to doxazosin, -1/+1,-2/ 0 amlodipine (HF only), lisinopril INVEST 22,576 0/ 0 verapamil (+trandolapril) equivalent to atenolol (+HCTZ) VALUE 15,313 +2/+2 valsartan not superior to amlodipine,34,35,36,Large, controlled trials have shown similar mortality or morbidity reductions with: Bendrofluazide (MRC) Chlorthalidone (SHEP, HDFP) Hydrochlorothiazide (VA, Oslo, Australian) Indapamide (PATS, PROGRESS) HCTZ/amiloride (MRC-O, STOP-H) HCTZ/triamterene (EWPHE),Conclusion Independent trial findings support the view that all thiazide diuretics are beneficial,37,angiotensin-converting enzyme inhibitors (ACEI); angiotensin receptor blocker (ARB); myocardial infarction (MI); cardiovascular (CV); heart failure (HF); left ventricular hypertrophy (LVH). Yusuf S et al. N Engl J Med. 2000;342:145-153; The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429-1435; The SOLVD Investigators. N Engl J Med. 1991;325:293-302; Granger CB et al. Lancet. 2003;362:772-776; Dahlof B et al. Lancet. 2002;359:995-1003; Cohn JN et al. N Eng J Med. 2001;345:1667-1675.,HOPE,CONSENSUS,Placebo (n=4652) Ramipril (n=4645),Placebo (n=126) Enalapril (n=127),LIFE,Atenolol (n=4588) Losartan (n=4605),CHARM-Added,MI, stroke, or CV death in high-risk patients,Total mortality in severe HF,Death, MI, or stroke in patients aged 5580 years with hypertension and LVH,Relative Risk Reduction, %,CV death or HF hospitalization in patients with chronic HF,Placebo (n=1272) Candesartan (n=1276),ACEIs,SOLVD,Placebo (n=1284) Enalapril (n=1285),Mortality in chronic HF,Val-Heft,Valsartan (n=2511) Placebo (n=2499),All cause mortality and morbidity in patients with HF,ACEIs and ARBs Reduce Cardiovascular Morbidity and Mortality,ARBs,40,30,20,10,0,38,Implications for Your Practice and Your Patients,The blood pressure goal for most patients with hypertension is 140/90 mm Hg. Initial drug therapy for most should be either thiazide-type diuretic alone or combined with other drug classes. Most patients with uncontrolled Stage 1 or Stage 2 hypertension should experience better blood pressure control and better long term CVD risk when the medication regimen includes a thiazide-type diuretic.,39,Algorithm for Treatment of Hypertension,Not at Goal Blood Pressure (140/90 mmHg) (130/80 mmHg for those with diabetes or chronic kidney disease),Initial Drug Choices,Lifestyle Modifications,40,AHA Scientific Statement Recommendations: General CVD Prevention, High CAD Risk, Stable and Unstable Angina, NSTEMI, STEMI, LVD (Circulation 2007; 115: 2761-2788),41,AHA 2007 Statement Recommendations,A target BP of =10% 10-year risk from FRS,42,Compelling Indications for Individual Drug Classes,43,Rahuel J et al. J Struct Biol. 1991;107:227-236.,Angiotensinogen,Aliskiren binds to a pocket in the renin molecule, blocking angiotensinogen from being cleaved by renin,Renin Inhibition With Aliskiren Binding of Angiotensinogen Prevented,44,(Pro)Renin Receptor Actions: Binding of (Pro)Renin Increased renin catalytic activity Activates VSMC ERK1/2,Aliskiren Suppresses the Entire SystemTargets the Point of Activation,Renin,Ang II,Angiotensinogen,ARBs,AT1 receptor,Ang I,Target cell,renin-angiotensin-aldosterone system (RAAS); vascular smooth muscle cells (VSMC); extracellular singal-regulated kinases (ERK 1/2); angiotensin (Ang); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme inhibitor (ACEI); angiotensin receptor blockers (ARB); type 1 angiotensin II receptor (AT1) .,Aliskiren,45,Lifestyle Modifications,Most patients will experience better control if they modify diet and exercise. Physician advice sometimes works and should always be given along with a follow-up visit appointment to monitor both blood pressure and lifestyle change efforts. Most of us do not do lifestyle counseling beyond simple advice and admonishment the time factor is a problem. Nevertheless, lifestyle modification is at the top of the JNC7 algorithm.,46,47,Lifestyle Modification,48,The Japanese Diet and Lifestyle,49,Keys to Physician Influence in Lifestyle Modification,Advice giving and follow-up monitoring are a minimum (many pts are not adequately titrated to goal BP) Some evidence that brief behavioral counseling aimed at matching messages to patient readiness to change and eliciting the patients own motivation to change can move the patient along a continuum of change,50,Physician Influence in Lifestyle Modification- What to Do PICM,Permission: Ask the patient for permission to talk about lifestyle