【高血压英文精品课件】get to goal, achieve control

PROFESSOR Dr.ALAA ETMAN MD NATIONAL HEART INSTITUTE Get to Goal, Achieve Control WHO World Health Report 2004 CV diseases Cancer Infectious and parasitic diseases Other non-infectious diseases Injuries Respiratory diseases Respiratory infections Maternal and perinatal conditions Nutritional deficiencies Cardiovascular diseases leading causes of global mortality Prevalence of Hypertension Proportion of Patients Treated/Not Treated for Hypertension in Europe* Wolf-Maier et al. Hypertension 2004;43:1017 Patients (%) EnglandSwedenGermanySpainItaly *Age adjusted; patients aged 3564 years Hypertension = 140/90mmHg threshold Prevalence of Hypertension Increases with Age Brown. BMJ 2006;332:8336 2039405960 Prevalence of Hypertension (%) Age (years) Estimated non-institutionalized US adults, 19992002 Adapted from Centers for Disease Control and Prevention Stroke 360:190313 Cardiovascular Mortality Risk Doubles with Each 20/10 mmHg Increment in Systolic/Diastolic BP* *Individuals aged 4069 years 4X risk 8X risk 2X risk 1X risk BP Reduction of 2 mmHg Decreases the Risk of CV Events by 710% Meta-analysis of 61 prospective, observational studies 1 million adults 12.7 million person-years 2 mmHg 2 mmHg decrease in decrease in mean SBPmean SBP 10% reduction in risk 10% reduction in risk of stroke mortalityof stroke mortality 7% reduction in risk 7% reduction in risk of ischaemic heart of ischaemic heart disease mortalitydisease mortality Lewington et al. Lancet 2002;360:190313 Hypertension in Egypt Hypertension is a major health problem in Egypt with a prevalence rate of 26.3% among the adult population ( 25 years)1. Only 8% of hypertensive Egyptians have their blood pressure controlled1. 1- Ibrahim MM, Rizk H, Apple LJ, et al. For the NHP investigation team. Hypertension, prevalence, awareness, treatment and control in Egypt. Results from the Egyptian National hypertension Project (NHP). Hypertension 1995; 26:880. More Than 80% Of hypertensive Patients have additional Co-morbidities Controlling SBP Is the Main Problem Adapted from Lloyd-Jones DM, et al. Hypertension. 2000;36:594599. DBP, mmHg SBP, mmHg 20601001201408040 67% did not reach SBP goal 4% 13% 29% 54% 80 100 120 140 160 180 200 220 90 140 Not at SBP or DBP goal At SBP and DBP goal IM thickness Lacunar infarcts Microalbuminuria MI, Angina Stroke Congestive Cardiac Failure Renal Failure Periferal Artery Disease Non-fatal recurrent events CRF Dialysis Dementia Treatment of Cardiovascular Risk Factors Genes Life style Death Life Style Changes Treatment of Silent Lesions To Interrupt Vascular Disease Progression Treatment of Clinical Events Natural History of Cardiovascular Disease Angiotensin II Plays a Central Role in Organ Damage A II Atherosclerosis* Vasoconstriction Vascular hypertrophy LV hypertrophy Fibrosis Remodeling Apoptosis Stroke DEATH GFR Proteinuria Aldosterone release Glomerular sclerosis Renal failure Hypertension Heart failure MI AT1 Receptor *preclinical data LV = left ventricular; MI = myocardial infarction; GFR = glomerular filtration rate Adapted from Willenheimer R et al Eur Heart J 1999;20(14):997-1008; Dahlf B J Hum Hypertens 1995;9(suppl 5):S37-S44; Daugherty A et al J Clin Invest 2000;105(11):1605-1612; Fyhrquist F et al J Hum Hypertens 1995;9(suppl 5):S19-S24; Booz GW, Baker KM Heart Fail Rev 1998;3:125-130; Beers MH, Berkow R, eds. The Merck Manual. 17th ed. Whitehouse Station, NJ: Merck Research Laboratories, 1999:1682-1704; Anderson S Exp Nephrol 1996;4(suppl 1):34-40; Fogo AB Am J Kidney Dis 2000;35(2):179-188. “Controlling blood pressure with medication is unquestionably one of the most cost-effective methods of reducing premature CV morbidity and mortality” Elliott. J Clin Hypertens 2003;5(Suppl. 2):313 Associated risk factors Blood Pressure and Cardiovascular Risk: ESHESC Guidelines Other RF, OD or disease BP (mmHg) Normal SBP 120129 or DBP 8084 High normal SBP 130139 or DBP 8589 Grade 1 SBP 140159 or DBP 9099 Grade 2 SBP 160179 or DBP 100 109 Grade 3 SBP 180 or DBP 110 No other RF Average riskAverage risk Low added risk Moderate added risk High added risk 12 RF Low added risk Low added risk Moderate added risk Moderate added risk Very high added risk 3 RF, MS, OD or diabetes Moderate added risk High added risk High added risk High added risk Very high added risk Established CV or renal disease Very high added risk Very high added risk Very high added risk Very high added risk Very high added risk MS = metabolic syndrome OD = subclinical organ damage RF = risk factors Reproduced from the Task Force of ESHESC. J Hypertens 2007;25:110587; Copyright 2007, with permission from Lippincott Williams and Wilkins Factors influencing prognosis in hypertension. Subclinical organ damage 2007 Guidelines for the management of arterial hypertension Electrocardiographic LVH Sokolow-Lyon 38 mm Cornell 2440 mm x ms Echocardiographic LVH (Left ventricular mass index): 125 g/m2 (males) 110 g/m2 (females) Carotid wall thickening (IMT 0.9 mm) or plaque Carotid-femoral pulse wave velocity 12 m/s Ankle / brachial blood pressure index 0.9 Mancia G, et al. J Hypertens. 2007;25:1105-87 LVH: Left ventricular hypertrophy IMT: Intima media thickness ESH/ESC 112:1651-1662; Chobanian AV, et al. JAMA. 2003;289:2560-2572. Physician-Related Barriers to Effective Antihypertensive Treatment Unfamiliarity with current treatment guidelines Blood pressure thresholds Isolated systolic hypertension Threshold for diabetic patients Use of monotherapy to treat patients with difficult-to-control blood pressure Belief that in-office blood pressure tends to be higher than at-home blood pressure Lack of time at office visits Therapeutic inertia Overestimation of adherence to guidelines Disagreement with guidelines Isolated systolic hypertension Concern about the relationship between diastolic blood pressure and myocardial infarction (i.e., the J curve) Reluctance to treat a seemingly “asymptomatic condition” Wang TJ, Vasan RS. Circulation. 2005;112:1651-1662; Chobanian AV, et al. JAMA. 2003;289:2560-2572; Okonofua EC, et al. Hypertension. 2006;47:345-351. Recommended Lifestyle Modifications and Their Individual Effects on Blood Pressure Chobanian AV, et al. JAMA. 2003;289:2560-2572; Blumenthal JA, et al. Arch Intern Med. 2000;160:1947-1958. Modifications*Recommendation Approximate SBP Reduction Reduce weight Maintain normal body weight (BMI of 18.524.9 kg/m2) 320 mm Hg Adopt DASH diet Rich in fruit, vegetables, and low-fat dairy; reduced saturated and total fat content 814 mm Hg Reduce dietary sodium 30 min/day most days of the week 49 mm Hg Moderate alcohol consumption Men: 2 drinks/day Women: 1 drink/day 24 mm Hg *Combining 2 or more of these modifications may or may not have an additive effect on blood pressure reduction. SBP = systolic blood pressure; BMI = body mass index; DASH = Dietary Approaches to Stop Hypertension Causes of Essential Hypertension Age Excess Sodium Consumption Overweight Excess Alcohol Consumption Physical Inactivity Elevated Systolic and/or Diastolic Blood Pressure Family History Stress Pathophysiology of Hypertension Sever P. J Cardiovasc Pharmacol . 1998;31(suppl 2):S1-S4. Sever P. J Cardiovasc Pharmacol . 1998;31(suppl 2):S1-S4. Hypertension Syndrome! Its More Than Just Blood Pressure Decreased Arterial Compliance Endothelial Dysfunction Abnormal Glucose Metabolism Neurohormonal Dysfunction Renal-Function Changes Blood-Clotting Mechanism Changes Obesity Abnormal Insulin Metabolism LV Hypertrophy and Dysfunction Accelerated Atherogenesis Abnormal Lipid Metabolism Hypertension Kannel WB. JAMA. 1996;275:1571-1576. Weber MA et al. J Hum Hypertens. 1991;5:417-423. Dzau VJ et al. J Cardiovasc Pharmacol. 1993;21(suppl 1):S1-S5. Blood Pressure Regulation Short Term Regulation of Blood Pressure: Pressure Natriuresis Arterial pressure is a signal for regulation of NaCl excretion. Arterial pressure NaCl reabsorbed in the proximal tubule more NaCl to Macula Densa Tuboglomerular Feedback (TGF) autoregulation RBF, GFR ECFV: Extracellular fluid volume, a function of Na+ reabsorption ; RBF: Renal blood flow; PT: Proximal tubule; GFR: Glomerular filtration rate; TGF: tubuloglomerular feedback In addition, there is an accompanying increase in urine Na+, volume output: pressure natriuresis/diuresis. Pressure natriuresis can normalize BP by decreasing the effective circulating volume this response connects BP and ECFV. Predicted Long-Term Effects of a Hypertensive Stimulus Renal function curve Predicted long-term effects of a hypertensive stimulus, caused by increased total peripheral resistance (normal renal-pressure natriuresis mechanism). Blood pressure is initially elevated (from point A to point B), but hypertension cannot be sustained because sodium excretion exceeds intake, thereby reducing extracellular fluid volume until blood pressure returns to normal and intake and output of sodium are balanced. Hall et al. Kidney Int Suppl, Volume 49 Supplement 55.June 1996.S-35-S-41 The Renin Angiotensin Aldosterone System (RAAS) Hanon S., et al. J Renin Angiotensin Aldosterone Syst 2000;1:147150; Chen R., et al. Hypertension 2003;42:542547; Hurairah H., et al. Int J Clin Pract 2004;58:173183; Steckelings U.M., et al. Peptides 2005;26:14011409 ACE Inhibition S., et al. J Renin Angiotensin Aldosterone Syst150; Chen R., et al. Hypertension 2003;42:542547; Hurairah H., et al. Int J Clin Pract 200H2000;1:147anon 4;58:173183; Steckelings U.M., et al. Peptides 2005;26:14011409 Bradykinin/NO Inactive fragments Vasodilation Tissue protection ACE Inhibitor Angiotensin I Angiotensin II Chymase tPA Cathepsin AT1 RECEPTOR Vasoconstriction Sodium retention SNS activation Inflammation Growth-promoting effects Aldosterone Apoptosis Angiotensin II escape AT2 RECEPTOR Vasodilation Natriuresis Tissue regeneration Inhibition of inappropriate cell growth Differentiation Anti-inflammation Apoptosis Selective AT1 Receptor Blockade (ARB) Bradykinin/NO Inactive fragments ACE Angiotensin I Angiotensin II Chymase tPA Cathepsin ARB Bradykinin? NO? AT1 RECEPTOR Vasoconstriction Sodium retention SNS activation Inflammation Growth-promoting effects Aldosterone Apoptosis AT2 RECEPTOR Vasodilation Natriuresis Tissue regeneration Inhibition of inappropriate cell growth Differentiation Anti-inflammation Apoptosis Hanon S., et al. J Renin Angiotensin Aldosterone Syst 2000;1:147150; Chen R., et al. Hypertension 2003;42:542547; Hurairah H., et al. Int J Clin Pract 2004;58:173183; Steckelings U.M., et al. Peptides 2005;26:14011409 Rationale for Dual RAAS Blockade with ACEI 1:147150; Chen R., et al. Hypertension 2003;42:542547; Hurairah H., et al. Int J Clin Pract 2004;58:173183; Steckelings U.M., et al. Peptides 2005;26:14011409 Consider: BP level before treatment Absence or presence of TOD and risk factors Choose between If goal BP not achieved If goal BP not achieved 23-drug combination at full doses ESH/ESC Algorithm for the Treatment of Hypertension TOD = target organ damage Marked BP elevation High/very high CV risk Lower BP target Mild BP elevation Low/moderate CV risk Conventional BP target Task Force of ESH/ESC. J Hypertens 2007;25:110587 2-drug combination at low dose Single agent at low dose Previous combination at full dose Add a third drug at low dose Full-dose monotherapy 2-3 drug combination at full dose Previous agent at full dose Switch to different agent at low dose Advantages of Multiple-mechanism Therapy: Efficacy Components with a different mechanism of action interact on complementary pathways of BP control1 Each component can potentially neutralize counter- regulatory mechanisms, e.g. Diuretics reduce plasma volume, which in turn stimulates the renin angiotensin system (RAS) and thus increases BP; addition of a RAS blocker attenuates this effect1,2 Multiple-mechanism therapy may result in BP reductions that are additive2 1Sica. Drugs 2002;62:44362 2Quan et al. Am J Cardiovasc Drugs 2006;6:10313 Multiple-mechanism therapy results in a greater BP reduction than seen with its single-mechanism components1,2 Advantages of Multiple-mechanism Therapy: Safety/Tolerability Components of multiple-mechanism therapy can be given at lower dosages to achieve BP goal than those required as monotherapy therefore better tolerated1,2 Compound-specific adverse events can be attenuated, e.g.,1,2 RAS blockers may attenuate the edema that is caused by CCBs 1Sica. Drugs 2002;62:44362 2Quan et al. Am J Cardiovasc Drugs 2006;6:10313 Multiple-mechanism therapy may have an improved tolerability profile compared with its single-mechanism components1,2 *Lower doses generally used in fixed-dose combinations + = potential advantage Advantages of Fixed Versus Free Combinations of Two Antihypertensive Drugs FixedFree Simplicity of treatment+ Compliance+ Efficacy+ Tolerability+* Price+ Flexibility+ Better Compliance with Antihypertensive Drugs Leads to a Lower Risk of Hospitalization Level of compliance (%) All-cause hospitalization risk (%) *p90 and 90 mmHg and 20%): Double-blind, randomized study vs. placebo and enalapril 20 mg Primary outcome: 31% in CV events vs. placebo 41% hospitalization for angina 27% coronary revascularization ASCOT-BPLA/CAFE3,4 19,257 HTN patients: Multicenter, randomized, prospective study vs. atenolol Primary outcome: 10% in non-fatal MI 366:895906; 2Julius et al. Lancet 2004;363:202231 Exforge Clinical data Page 70 Amlodipine/Valsartan: BP Reductions Across All Grades of Hypertension - (Exzellent Trial1) DBP (mmHg) 17 18 29 n = n = 18001800 n = n = 22932293 n = n = 890890 1Schrader J et al. PS38 Late Breaking Abstracts Session. ESH/ISH Congress, 14 June 2008. -19 -32 -49 Page 71 Amlodipine/Valsartan FDC: BP Reductions for Patients with Diabetes (Exzellent Trial1) n = n = 639639 n = n = 795795 n = n = 295295 1Schrader J et al. PS38 Late Breaking Abstracts Session. ESH/ISH Congress, 14 June 2008. -19 -32 -48 DBP (mmHg) 11 15 18 syst.BP reduction (mmHg) Amlodipine/Valsartan: Powerful SBP Drops of Over 40 mmHg in Patients with Baseline MSSBP 180 mmHg LSM Change in MSSBP from baseline (mmHg) LSM Change in MSSBP from baseline (mmHg) p=0.1 20 10 0 Amlodipine/Valsartan 10/160 mg Amlodipine 10 mg p=0.0018 40 30 N=55 31.7 N=46 40.1 LSM=least square mean MSSBP=mean sitting systolic blood pressure EX-EFFeCTS1 Patients with Stage 2 Hypertension 20 10 0 N=42 Amlodipine/Valsartan 10/160320 mg Amlodipine 10 mg 43.5 40 30 50 37.2 N=38 EX-STAND2 Black Patients with Stage 2 Hypertension 1.Destro et al. J Am Soc Hypertens 2008;2:294302 2.Flack et al. J Hum Hypertens 2009 (E-pub ahead of print). Amlodipine/Valsartan: Up to 9 Out of 10 Patients Reach BP Goal 140/90 mmHg Amlodipine/Valsartan 5/160 mgAmlodipine/Valsartan 10/160 mg Diabetic patients with BP 130/80 mmHg at Week 8 were 47.0% and 49.2% for 5/160 mg and 10/160 mg doses, respectively Patients (%) Data shown are at Week 8 No hydrochlorothiazide add-on was permitted until after Week 8 Randomized, double-blind, multinational, parallel-group, 16-week study n=440n=369n=71n=449n=375n=74 80.0 Adapted from Allemann et al. J Clin Hypertens 2008;10:18594 Amlodipine/Valsartan: Additional BP Drops in Non- responders to Ramipril/Felodipine 30.7 mmHg 14.3 mmHg 15.4 mmHg p0.00017.0 mmHg p0.0001 Week0510 N=133 After Amlo/Val 10/160 After Ram 5 + Fel 5 Open, sequential, non- responder, 10-week study After Amlo/Val 10/160 After Ram 5 + Fel 5 Week0510 Trenkwalder et al. J Hypertens 2007;25(Suppl. 2):S228 (abstract P24.261) Page 75 *p0.01 vs. amlodipine Fogari et al. J Hum Hypertens 2007;21:220-4 EXFORGE Significantly Reduces Fluid Retention Vs Amlodipine Monotherapy 25 20 15 10 5 0 Ankle-foot volume increase (%) Amlodipine 10 mg EXFORGE 10/160 mg n=80 70% difference Amlodipine/Valsartan: Powerful SBP Drops of 43 mmHg in Patients with a Baseline MSSBP 180 mmHg *p0.001; p0.002 vs. baseline Change from baseline in MSSBP at 6-week endpoint (mmHg) Endpoint BP (mean) 0 10 20 30 40 50 Amlodipine (510 mg) + valsartan (160 mg) 145.4 mmHg157.4 mmHg Lisinopril (1020 mg) + HCTZ (12.5 mg) n=15n=11 Change in MSDBP (mmHg)26.1*21.7* Poldermans et al. Clin Ther 2007;29:27989 Baseline mean sitting systolic BP (MSSBP): 188 mmHg Baseline mean sitting diastolic BP (MSDBP): 113 mmHg Randomized, double-blind, multicenter, active-controlled study Page 77 Blood Pressure and Cardiovascular Risk: ESHESC Guidelines Other RF, OD or disease BP (mmHg) Normal SBP 120129 or DBP 8084 High normal SBP 130139 or DBP 8589 Grade 1 SBP 140159 or DBP 9099 Grade 2 SBP 160179 or DBP 100109 Grade 3 SBP 180 or DBP 110 No other RFAverage riskAverage risk Low added risk Moderate added risk High added risk 12 RF Low added risk Low added risk Moderate added risk Moderate added risk Very high added risk 3 RF, MS, OD or diabetes Moderate added risk High added risk High added risk High added risk Very high added risk Established CV or renal disease Very high added risk Very high added risk Very high added risk Very high added risk Very high added risk MS = metabolic syndrome OD = subclinical organ damage RF = risk factors Reproduced from the Task Force of ESHESC. J Hypertens 2007;25:11058