Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
MODULE 3 CHAPTER 2A HYPERTENSION IN EXTREMES OF AGE Hypertension in extremes of age • 1.Hypertension in young • 2.Hypertension in elderly 1.HYPERTENSION IN YOUNG What is young age ? < 45 years Prevalence of HT according to age and race Prevalence of HT among children between 8 and 17 years Blood Pressure Grades (adults) BP Classification SBP mmHg DBP mmHg Normal <120 and <80 Prehypertension 120–139 or 80–89 Stage 1 Hypertension 140–159 or 90–99 Stage 2 Hypertension >160 or >100 Table 1 Classification of hypertension in youth McCrindlle, B. W. (2010) Assessment and management of hypertension in children and adolescents Nat. Rev. Cardiol. doi:10.1038/nrcardio.2009.231 Incidence of primary & secondary HT by age AGE RANGE ETIOLOGY < 1 year secondary HT : 99 % primary HT : 1 % 1- 12 years secondary HT : 70 – 85 % primary HT : 15 – 30 % 13 – 18 years primary HT : 85 % - 95 % secondary HT : 5 – 15% > 18 years primary HT : 95 % secondary HT : 5 % Prevalent causes of HT by age Age group Main causes neonates Renal artery / vein thrombosis, congenital renal anomalies, coarctation of aorta < 1 year Coarctation of aorta, renovascular / renal parenchymal disease 1- 6 years Renal parenchymal, renovascular disease, coarctation of aorta 7-12 years Renal parenchymal, renovascular disease, primary hypertension 13- 18 years Primary hypertension, medication or substance abuse, renal parenchymal disease Clinical approach of a young hypertensive : 4 goals • Detection and confirmation of hypertension • Detection of target organ damage • Identification of other risk factors for cardiovascular disease • Detection of secondary causes of hypertension Detection of hypertension • All children > 3 years should have their BP checked • Check BP for children < 3 years : - congenital heart disease - hematuria, proteinuria, recurrent UTI - family h/o congenital renal disease - evidence of raised intracranial pressure - solid organ/ bone marrow transplant - treatment with drugs known to raise BP - presence of any systemic illness known to raise BP Confirm high blood pressure • At least 2 readings, 5 minutes apart; preferably over 2 visits • Confirm elevated reading in contralateral arm • Rule out pseudo hypertension • All children with BP > 90th percentile by oscillometric method should be confirmed by auscultatory method Target organ damage : LVH in ECG Target organ damage : LVH in echo look for target organ damage • Microalbuminuria : urine albumin to urine creatinine ratio of 30 -300 µg/mg • Estimated GFR < 60 ml/min • Ultrasound evidence of arterial wall thickening or atherosclerotic plaque Identification of co morbidities • Diabetes : hypertensives are 2.5 times more likely to develop diabetes within next 5 years • Obesity : > 2/3rd of young hypertensives are either overweight or obese • Dyslipidemia • Smoking, tobacco use • Stress Risk factors for secondary hypertension : when to look for other causes? • Poor response to therapy (resistant HT) • Worsening of control in previously stable hypertensive patient • Stage 3 hypertension (SBP > 180 or DBP>110) • Onset of HT : age < 20 yrs or > 50 yrs • Significant target organ damage • Absence of family history of hypertension • Findings / history / lab point to a secondary cause Rule out pseudoresistance Improper BP measurement Excess sodium intake Inadequate diuretic therapy Medication • Inadequate doses •Drug actions and interactions: Nonsteroidal antiinflammatory drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives • Over-the-counter (OTC) drugs and herbal supplements Excess alcohol intake Identifiable causes of HTN JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314 Secondary hypertension A : Apnea, aldosteronism B : Bruits, bad kidneys (renal parenchymal disease) C : catecholamines, coarctation, cushings D : drugs, diet E : erythropoietin, endocrine disorders Screening history • Day time fatigue, sleepiness, snoring : OSA • Polyuria, nocturia, cramps, muscle weakness : aldosteronism • Multiple vascular risk factors, history of flash pulmonary edema, unexplained renal insufficiency : renal artery stenosis • Nocturia, hematuria, peripheral edema : renal parenchymal disease Screening history • Early onset HT, leg fatigue : aortic coarctation • Proximal weakness, weight gain, diabetes : cushings disease • Paroxysmal headache, palpitations, sweating : pheochromocytoma • History of drug intake, diet pattern • Lethargy, recent weight gain, change in voice : hypothyroidism • Heat intolerance, weight loss, palpitations : hyperthyroidism Screening physical examination • • • • • • • • Large neck size Muscle weakness Abdominal bruit Edema, signs of renal failure Disparity in arm BP, reduced or delayed leg pulses Truncal obesity, striae Sweaty palms, pallor, tachycardia Signs of endocrine disorder Routine screening laboratory tests for hypertension : all patients • Complete blood count • Blood chemistries (sodium, potassium, creatinine, fasting glucose) • Fasting lipid profile • Urine analysis • 12 lead electrocardiogram Laboratory work up for 20 HT DIAGNOSIS Renal parenchymal disease Renovascular disease Primary aldosteronism Sleep apnea SCREENING CONFIRMATION Urine analysis, BUN, USG, renal biopsy creatinine, eGFR Duplex renal USG MR angio, renal angiogram Serum potassium, CT scan of adrenals plasma aldosterone/renin ratio Sleep study with Polysomnography oxygen saturation Laboratory work up DIAGNOSIS Cushings syndrome Phaeochromocytoma SCREENING Plasma, urine cortisol Spot urine metanephrine CONFIRMATION Dexamethasone suppression test Urine/plasma catecholamines, CT abdomen Coarctation of aorta chest x ray Thyroid disorder Acromegaly TSH levels Growth hormone level CT angiography, angiography T3,T4 levels "The Goal is to Get to Goal!” Hypertension < 140/90 mmHg -PLUSDiabetes or Renal Disease < 130/80 mmHg Lifestyle Modification Modification Weight reduction Approximate SBP Reduction (range) 5-20 mmHg/ 10 kg weight loss Adopt DASH eating plan 8-14 mmHg Dietary sodium reduction 2-8 mmHg Physical activity 4-9 mmHg Moderation of alcohol consumption 2-4 mmHg JNC 7 Express. JAMA. 2003 Sep 10; 290(10):1314 Impact of a 5 mmHg Reduction Overall Reduction Stroke 14% Coronary Heart Disease 9% All Cause Mortality 7% Hypertension 2003;289:2560-2572. Essential hypertension in young Drug of choice in the absence of any compelling Indication : ARB’s or β blockers initiate with ARB’s (A) or β blockers (B) ↓ add CCB (C) or diuretics (D) ↓ add C or D accordingly ↓ resistant hypertension ↓ aldosterone receptor antagonists/α blockers/ clonidine Renal parenchymal disease • Most common secondary cause • Common causes : glomerulonephritis, diabetic nephropathy • Increased salt & fluid retention predominantly contribute to resistant HT • Treat underlying cause • 1st choice : ACE-I/ARB + loop diuretic • Goal of < 130/80 achieved only in < 15% Renovascular disease Case selection for revascularization • Surgical treatment of RAS does not always correct HT • RAS may not contribute to HT in all patients • Ideal case : - renal FFR < 0.8 - resistive index (controversial) • Success (> 90%) : if fall in BNP is by > 30% Renovascular disease • Fibromuscular dysplasia - < 10% of renal artery stenosis - common in young females - affects the distal part of the renal artery - treatment : ACE-I/ARB + loop diuretic Angioplasty Renovascular disease • Atherosclerotic disease : - 90 % of renal artery stenosis - ostioproximal part of artery involved - treatment : 2 or more drugs are often required : angioplasty + stenting in pts with - resistant HT, recurrent flash pulmonary edema, B/L RAS, U/L RAS in a single functioning kidney, worsening renal parameters Primary aldosteronism • Screening is recommended in the following situations : 1) unprovoked unexplainable hypokalemia 2) hypokalemia induced by diuretics, but resistant to correction 3) unexplained resistant hypertension 4) family h/o aldosteronism 5) adrenal mass in CT or MRI Primary aldosteronism • Adrenal adenoma - surgical excision is the treatment of choice - corrects HT in 60% of patient • Adrenal hyperplasia - aldosterone antagonist - surgical correction restores normal blood pressure in only 16% of patients Work up for aldosteronism Figure 8. Putative pathophysiological mechanisms involved in the interactions between obesity, OSA, and hypertension. Wolk R et al. Hypertension 2003;42:1067-1074 Copyright © American Heart Association Real and theoretical links connecting obesity to hypertension. Goodfriend T L , Calhoun D A Hypertension 2004;43:518524 Copyright © American Heart Association Obstructive sleep apnoea • Weight loss • Continuous positive airway pressure • ACE-I are the drug of choice • Aldosterone antagonists have a specific role • To look for pulmonary hypertension Cushings syndrome • HT is present in 70-90% of patients • CV risk is substantially higher because of associated co morbidities • Treatment - selective excision of the pituitary adenoma ; 70% cure rate - ectopic ACTH secretion : treatment of neoplasm - non surgical patients : metyrapone, ketoconazole Pheochromocytoma • α blockers : mainstay of treatment - phenoxybenzamine - prazosin • β blockers : useful in patients without elevated adrenaline • Resistant cases : add ACE-I, CCB • Avoid diuretics • Definitive treatment : surgery to remove the tumour • Pre-op preparation for 7-14 days : to control BP, deplete catecholamine stores and expand blood volume • Most cases are free of HT by 5 -7 years Coarctation of aorta: indications for treatment • SBP difference between upper and lower limb greater than 20 mmHg at rest • Significant hypertension or blood pressure response to exercise (more than 2 SD greater than mean) • LV dysfunction Coarctation of aorta : choice of treatment Native Co-A Recurrent Co-A Less than 1 yr 1 – 10 yrs (35 kg) >35 kg children and adults surgery Insufficient data Stenting Angioplasty Angioplasty Stenting Careful follow up for residual hypertension is essential 2.HYPERTENSION IN ELDERLY (>65Y) Prevalence of HBP in different parts of India City Men (%) Women (%) Jaipur Urban (1995) 30 33 Jaipur Urban (2002) 36 37 Mumbai Urban(1999) 44 45 Mumbai (Executives) 27 28 Thiruvananthapuram Urban (2000) 31 36 Haryana (Rural 1999) 5 5 Chennai (Urban 2007) 23.2 17.1 Hypertension , Pre hypertension in India Hypertension in the Elderly Ten Things You Need to Know: 1. 2. 3. 4. 5. There is a dramatic increase in HTN prevalence with aging; by age 70 yrs, the majority of people have HTN In older adults, HTN is characterized by an elevated SBP with normal or low DBP, due to age-associated stiffening of large arteries. HTN is a potent risk factor for CVD in the elderly. Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients 60-79 yrs old with antiHTN drug therapy though the effect on all-cause mortality has been modest. Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly. Ten Things You Need to Know 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of HTN and as adjunctive therapy in those with HTN. 7. Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons 65-79 yrs and a threshold SBP of 150 mm Hg in people age ≥80 yrs is reasonable. 8. Diuretics, ACEI, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts: choice is dictated by efficacy, tolerability, comorbidities, and cost. 9. Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated. 10. The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatmentrelated side effects. JNC VII Guidelines: Measurement of Blood Pressure Method In-office Brief Description Two readings, 5 minutes apart, sitting in chair Confirm elevated reading in contralateral arm Ambulatory BP monitoring Indicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep indicates increased CVD risk Self-measurement Provides information on response to Rx. May help improve adherence to Rx and evaluate “white-coat” HTN BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension, Rx=Treatment Source: Chobanian AV et al. JAMA 2003;289:2560-2572 OSLER’S MANEUVER DIAGNOSIS • The Osler's sign of pseudohypertension is an artificially and falsely elevated blood pressure reading obtained through sphygmomanometry due to arteriosclerotic, calcified blood vessels which do not physiologically compress with pressure. • Because they do not compress with pressure normally, the blood pressure reading is higher than it truly ought to be. • It can indicate pseudohypertension. It is also known as "Osler's maneuver". • The sign is named for William Osler. Hypertension in the Elderly 1.There is a dramatic increase in the prevalence of hypertension with aging; by age 70 years, the majority of people have hypertension. High Blood Pressure*: Prevalence Increases with Age Hypertension* Prevalence (%) National Health and Nutrition Examination Survey (NHANES) III 80 66% 72% 51% 60 38% 40 18% 20 3% 9% 0 18-29 30-39 40-49 50-59 Age 60-69 70-79 80+ *Hypertension defined as blood pressure >140/90 mmHg or treatment Source: JNC-VI. Arch Intern Med 1997;157:2413-2446 High Blood Pressure*: Prevalence Increases with Age Percent of Population National Health and Nutrition Examination Survey (NHANES) 90.0 80.0 70.0 60.0 50.0 40.0 30.0 20.0 10.0 0.0 20-34 35-44 45-54 Men 55-64 65-74 75+ Women *High blood pressure defined as blood pressure 140/90 mmHg or treatment Source: NHANES: 1999-2004, Source: NCHS and NHLBI High Blood Pressure*: Prevalence in U.S. Adults Prevalence of Hypertension* National Health and Nutrition Examination Survey (NHANES) 45 1988-1994 1999-2000 40 35 30 25 20 15 10 5 0 All M F Non-Hispanic Black M F Non-Hispanic White M F MexicanAmerican F=Female, M=Male *High blood pressure defined as blood pressure >140/90 mmHg or treatment Source: Fields LE et al. Hypertension 2004;44:398-404 High Blood Pressure: Lifetime Risk* Starting at Age 55-65 Years Framingham Heart Study Risk of hypertension (%) 100 80 Men Women 60 40 20 0 0 2 4 6 8 10 12 14 16 18 20 Years *Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg Source: Vasan RS, et al. JAMA 2002; 287:1003-1010 Change in Blood Pressure Levels in the United States Over Time National Health and Nutrition Examination Survey (NHANES) 100% 90% 70% 60% 50% Stage 2 40% Stage 1 Prehypertension 30% normotensive 20% 10% 0% 19 71 -1 97 5 19 76 -1 98 0 19 88 -1 99 4 19 99 -2 00 4 Blood pressure age-adjusted percentage 80% Source: Ford, E. S. et al. Figure 2b, Circulation 2009;120:1181-1188. Reprinted with permission. Mean Blood Pressure According to Age, Sex and Ethnic Group in U.S. Adults Chobanian N Engl J Med. 2007;357:789-96 SYSTOLIC HYPERTENSION-INDIA ISH CURES 52 MOHAN ET AL JAPI 2007 Hypertension in the Elderly 2. In older adults, hypertension is characterized by an elevated systolic blood pressure (BP) with normal or low diastolic BP, due to ageassociated stiffening of the large arteries. Joint Influences of SBP and Pulse Pressure on Coronary Heart Disease Adapted from Franklin Circulation 1999;100:354-60 Pathophysiology of Hypertension in the Elderly • Multiple changes occur in arterial media with aging, including reduced elastin content with increases in non-distensible collagen and calcium (e.g. arterial stiffening). • Age-associated arterial stiffening results in a gradual increase in systolic BP and a decrease in diastolic BP. • Flow-mediated arterial dilation, primarily mediated by endothelium-derived nitric oxide, declines markedly with aging. • Neurohormonal profile of older hypertensive adults characterized by increased plasma norepinephrine, low renin, and low aldosterone levels. • Many so-called “normal aging changes” in arterial structure and function are blunted/absent in populations not chronically exposed to high sodium/high calorie diets, low physical activity levels, and high rates of obesity. Conceptual Framework for CV Adaptations to Arterial Stiffening Occurring with Aging CBF indicates coronary blood flow; DBP, diastolic blood pressure; EF, ejection fraction; LA, left atrial; LV, left ventricular; SBP, systolic blood pressure; ↑, increased; and ↓, decreased. Hypertension in the Elderly 3. Hypertension is a potent risk factor for cardiovascular (CV) disease in the elderly. Coronary Heart Disease Rates by SBP and Age Adapted from Lewington et al. Lancet. 2002; 360:1903-1913 180 mm Hg 160 mm Hg 256 140 mm Hg 128 120 mm Hg 64 32 Coronary Heart Disease Mortality 16 8 4 2 1 40-49 50-59 60-69 Age 70-79 80-89 Hypertension as a Risk Factor in the Elderly • In older adults, hypertension (HTN) is the most prevalent modifiable CV risk factor: antecedent HTN is estimated in: – – – – – ~70% of patients with incident myocardial infarctions ~77% of patients with incident strokes ~74% with chronic heart failure ~90% with acute aortic syndrome 30% to 40% with atrial fibrillation • HTN is also a major risk factor for conditions directly influencing CV risk in the elderly: – Diabetes – Metabolic syndrome – Chronic kidney disease • The number of deaths attributable to HTN in the U.S. rose 56% between 1995 and 2005, largely reflecting the increasing number of older Americans and high prevalence of HTN in the elderly. Hypertension in the Elderly 4. Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients 60-79 years old with antihypertensive drug therapy though the effect on all-cause mortality has been modest. In HYVET, antihypertensive therapy reduced all-cause mortality in people ≥80 years old by 21%. • Randomized Hypertension in the Very Elderly Trial (HYVET) In 3,845 patients ≥80 years old with SBP ≥160 mm Hg, at 1.8year follow-up, those randomized to indapamide vs placebo had: – 30% nonsignificant decrease in fatal/nonfatal stroke – 39% significant decrease in fatal stroke – 21% significant decrease in all-cause mortality – 23% insignificant decrease in CV death – 64% significant decrease in heart failure HYVET: Treatment of hypertension in patients 80 years of age or older. N Engl J Med. 2008;358:1887-98. Hypertension in the Elderly 5. Although increases in the treatment and control of BP in older hypertensive adults have occurred over the past 2 decades, BP control rates remain suboptimal in the elderly. Extent of Awareness, Treatment and Control of High Blood Pressure by Age NHANES: 2005-2006 Frequency of Untreated Hypertension According to Subtype and Age Chobanian N Engl J Med. 2007;357:789-96 Hypertension in the Elderly 6. Non-pharmacologic lifestyle measures should be encouraged in older adults, both to retard development of hypertension and as adjunctive therapy in those with hypertension. Non-Pharmacologic Lifestyle Measures Shown Beneficial in Elderly Hypertensive • Regular physical Subjects activity • • • • Sodium restriction Weight control Smoking cessation Avoidance of excessive alcohol intake Hypertension in the Elderly 7. Although the specific BP at which antihypertensive therapy should be initiated in the elderly is unclear, a threshold of 140/90 mm Hg in persons 65-79 years and a threshold systolic BP of 150 mm Hg in people age 80 years and older is reasonable. Risk of Adverse Outcomes Among DenardoPatients et al. Am J Med 123:719-726, 2010and BP Elderly CAD by Age BP nadirs indicate BP’s with lowest hazard ratio at each age. Hypertension in the Elderly 8. Diuretics, ACE-inhibitors, angiotensin receptor blockers, calcium antagonists, and beta blockers have all shown benefit on CV outcomes in randomized trials among elderly cohorts. The choice of specific agents is dictated by efficacy, tolerability, presence of specific comorbidities, and cost. JNC VII Guidelines: Compelling Indications for Drug Classes Compelling Indication Initial Therapy Options Clinical-Trial Basis Heart Failure Diuretic, BB, ACE-I, ARB, Aldo ANT MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES Post-MI BB, ACE-I, Aldo ANT ACC/AHA Post-MI Guidelines, BHAT, SAVE, Capricorn, EPHESUS High CAD Risk Diuretic, BB, ACE-I, CCB ALLHAT, HOPE, ANBP2, LIFE, CONVINCE Diabetes Mellitus Diuretic, BB, ACE-I, ARB, CCB NKF-ADA Guideline, UKPDS, ALLHAT Chronic Kidney Disease ACE-I, ARB NKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN, AASK Recurrent Stroke Prevention Diuretic, ACE-I PROGRESS ACE-I=Angiotensin converting enzyme inhibitor, Aldo ANT=Aldosterone antagonist, ARB=Angiotensin receptor blocker, BB=b-blocker, CAD=Coronary artery disease, CCB=Calcium channel blocker, MI=Myocardial infarction Source: Chobanian AV et al. JAMA 2003;289:2560-2572 Antihypertensive Treatment-Related Side Effects The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects such as: – Electrolyte disturbances – Renal dysfunction – Excessive orthostatic BP decline Hypertension in the Elderly 9. Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated. Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug Pharmacokinetics Absorption and distribution of antihypertensive drugs are unpredictable in the elderly Physiologic Changes with Aging: Potential to Influence Antihypertensive Drug Pharmacokinetics Continued Half life of most antihypertensive drugs is increased in the elderly Percent of Elderly People in Outcomes Trials Taking ≥Two Antihypertensive Medications ACCOMPLISH (131 mmHg) Trial Name/SBP Achieved CONVINCE (136 mmHg) INVEST (136 mmHg) ALLHAT (138 mmHg) HYVET (138 mmHg) Australian HTN (142 mmHg) LIFE (143 mmHg) SHEP (146 mmHg) STONE (147 mmHg) STOP-2 (151 mmHg) EWPHE (151 mmHg) Syst-Eur (151 mmHg) MRC-Elderly (153 mmHg) Syst-China (not reported) (mean SBP achieved) (Mean SBP achieved) 0 10 20 30 40 50 60 70 80 90 100 Percent (%) 0 GUIDELINES II - API API Blood Pressure Lowering Therapy Evidence: Primary Prevention Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study Proportion with CV death, MI, or stroke (%) 9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 years 16 12 Atenolol Losartan 8 4 13% RRR, P=0.021 0 0 6 12 18 24 30 36 42 48 54 60 66 Study Month An ARB provides greater efficacy in patients with LVH ARB=Angiotensin receptor blocker, CV=Cardiovascular, DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by SBP=160-200 mmHg or DBP=95-115 mmHg Source: Dahlöf B et al. Lancet 2002;359:995-1003. Adapted with permission. Blood Pressure Lowering Therapy Evidence: Primary Prevention Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) Nonfatal MI and fatal CHD (%) 19,342 high-risk hypertensive patients with 3 additional CV risk factors randomized to amlodipine (10 mg) & perindopril (8 mg) or atenolol (100 mg) & bendroflumethiazide (2.5 mg) for 5.5 years 6 Atenolol-based regimen 4 Amlodipine-based regimen 2 RRR = 10%, P = 0.1052 0 0 1 2 3 4 5 6 Time since randomization (years) Both BP lowering regimens provide similar efficacy BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarction Source: Dahlöf B et al. Figure 3, Lancet 2005;366:895-906. Adapted with permission. Blood Pressure Lowering Therapy Evidence: Primary Prevention Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) Secondary endpoints Nonfatal MI + fatal CHD Total coronary endpoint Total CV events/procedures All-cause mortality CV mortality Fatal/nonfatal stroke Fatal/nonfatal HF Amlodipine-based Atenolol-based rate/1000 rate/1000 patient years patient years 7.4 14.6 27.4 13.9 4.9 6.2 2.5 Amlodipinebased better Atenololbased better 8.5 16.8 32.8 15.5 6.5 8.1 3.0 P <0.05 <0.01 <0.0001 <0.05 0.001 <0.001 NS 0.50 0.70 1.00 1.45 2.00 An amlodopine-based regimen appears to reduce the rate of other CV events CHD=Coronary heart disease, CV=Cardiovascular, HF=Heart failure, MI=Myocardial infarction Source: Dahlöf B et al. Figure 4, Lancet 2005;366:895-906. Reprinted with permission. Blood Pressure Lowering Therapy Evidence: Primary Prevention Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) 11,506 high-risk hypertensive patients randomized to benazepril (40 mg) and amlodipine (10 mg) or benazepril (40 mg) and HCTZ (25 mg) for 36 months* Composite of CV death, MI, stroke, hospitalization for angina, sudden cardiac arrest, and coronary revascularization (%) 0.16 0.14 0.12 Benazepril/HCTZ 0.10 0.08 Benazepril/Amlodipine 0.06 0.04 0.02 20% RRR, HR=0.80, P=0.0002 0.00 0 200 400 600 800 1000 1200 1400 Time to first cardiovascular event (days) An amlodipine-based regimen provides greater benefit *The study was prematurely stopped Source: Jamerson K et al. NEJM 2008;359:2417-28. Blood Pressure Lowering Therapy Evidence: Primary Prevention Hypertension in the Very Elderly (HYVET) Trial Rate/1000 patient years (%) 3,845 patients >80 years with SBP >160 mm Hg randomized to treatment to indapamide (1.5 mg) and perindopril (2-4 mg if needed) vs. placebo for 2 years 70 P=0.02 60 P<0.001 50 40 30 P=0.06 20 Indapamide +/perindopril P<0.001 P=0.05 Placebo 10 0 Fatal or Nonfatal CVA* Death All cause Any heart from CVA mortality failure Any CV event (Primary end point) Blood pressure control in patients >80 years of age provides benefit CV=Cardiovascular, CVA=Stroke Source: Beckett NS et al. NEJM 2008;358:1887-98 Blood Pressure Lowering Therapy Evidence: Secondary Prevention International Verapamil-Trandolapril Study (INVEST) 22,576 patients with HTN and CAD randomized to a BP lowering strategy with verapamil SR (240 mg) or atenolol (50 mg) for 2.7 years Calcium antagonist strategy (CAS)* Non-calcium antagonist strategy (NCAS)* Incidence of death, MI, or stroke 25 20 15 10 5 RR=0.98, P=0.57 0 0 6 12 18 24 30 36 42 48 54 60 Months Both a CAS and NCAS provide similar efficacy BP=Blood pressure, HTN=Hypertension, MI=Myocardial infarction *Trandolapril (up to 4 mg) was added in those with diabetes mellitus, chronic kidney disease, or heart failure Source: Pepine CJ et al. JAMA 2003;290:2805-2816 Hypertension in the Elderly 10.The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects. Target Blood Pressure Goals Elderly in the Although the optimal BP treatment goal in the elderly has not been determined, a therapeutic target of <140/90 mm Hg in persons aged 65-79 years and a SBP of 140-145 mm Hg, if tolerated, in persons aged ≥80 years is reasonable. Hypertension in the Elderly • Summary and Conclusions – – – – – – – Very highly prevalent Major, treatable risk factor for CV disease Typically, SBP elevation with low DBP (“stiff arteries”) Many comorbidities make management challenging Life style modification useful, even with drug therapy Begin with low drug doses and titrate drugs slowly For those ≥80 years, 140-145 mm Hg is acceptable SBP goal HBP in elderly- takeaways • • • • • • • • • • 1.Confirm BP- Serial readings 2.Secondary causes – Renal Artery Stenosis 3.Postural BP 4.Pseudohypertension – osler’s maneuver 5.Systolic/ Diastolic / Combined/ increased PP 6.To rule out AR in increased PP 7.ISH – Diuretics 8.Increased PP – ACEI / Calcium Blockers (Small dose) 9.Low dose – gradual increase 10.Comorbidities/ Co existing drug / electrolyte problems END OF MODULE 3 CHAPTER 2A