Module 3 chapter 2a. Module 3 chapter 2a Hypertension in extremes of age.

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: /nrcardio

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 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 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

Younger the patient, greater is the likelihood for a secondary cause
Higher the blood pressure elevation, greater is the likelihood for 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 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 SCREENING CONFIRMATION Renal parenchymal disease Urine analysis, BUN, creatinine, eGFR USG, renal biopsy Renovascular disease Duplex renal USG MR angio, renal angiogram Primary aldosteronism Serum potassium, plasma aldosterone/renin ratio CT scan of adrenals Sleep apnea Sleep study with oxygen saturation Polysomnography

Laboratory work up DIAGNOSIS CONFIRMATION Cushings syndrome
SCREENING CONFIRMATION Cushings syndrome Plasma, urine cortisol Dexamethasone suppression test Phaeochromo-cytoma Spot urine metanephrine Urine/plasma catecholamines, CT abdomen Coarctation of aorta chest x ray CT angiography, angiography Thyroid disorder Acromegaly TSH levels Growth hormone level T3,T4 levels

Treatment of secondary hypertension

"The Goal is to Get to Goal!”
Hypertension -PLUS- Diabetes or Renal Disease < 140/90 mmHg < 130/80 mmHg

Lifestyle Modification
Approximate SBP Reduction (range) Weight reduction 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 Weight reduction + DASH is equivalent to 1-2 antihypertensives JNC 7 Express. JAMA 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:

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. Figure 8. Putative pathophysiological mechanisms involved in the interactions between obesity, OSA, and hypertension. Wolk R et al. Hypertension 2003;42: Copyright © American Heart Association

Real and theoretical links connecting obesity to hypertension.
Real and theoretical links connecting obesity to hypertension. From left to right, the arrows indicate the effect of excess fat on the upper airway to cause obstructive sleep apnea, with consequent stimulation of sympathetic impulses that cause renin release and vasoconstriction; a poorly understood effect of excess fat on the kidney to cause sodium retention; production of angiotensinogen by adipocytes; and production of nonesterified fatty acids by adipocytes leading to generation of putative adrenal stimuli. Fatty acid release is stimulated by the sympathetic discharge that follows apnea. Aldosterone secretion is postulated to be increased by the activated renin–angiotensin cascade and by oxidized derivatives of fatty acids. Hypertension and vascular pathology is viewed as a result of direct sympathetic stimulation, sodium retention, and the direct and indirect effects of angiotensin and aldosterone, all increased by obesity to levels inappropriately high for a given subject’s fluid volume status. Goodfriend T L , Calhoun D A Hypertension 2004;43: 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
Less than 1 yr 1 – 10 yrs (35 kg) >35 kg children and adults Native Co-A surgery Insufficient data Stenting Recurrent Co-A Angioplasty 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 Haryana (Rural 1999) 5 Chennai (Urban 2007) 23.2 17.1

Hypertension , Pre hypertension in India

Hypertension in the Elderly
Ten Things You Need to Know: 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 yrs old with anti-HTN 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. 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 yrs and a threshold SBP of 150 mm Hg in people age ≥80 yrs is reasonable. 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. Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated. The high prevalence of both CV and non-CV comorbidities among the elderly dictates need for great vigilance to avoid treatment-related side effects.

Measurement of Blood Pressure
JNC VII Guidelines: Measurement of Blood Pressure Provides information on response to Rx. May help improve adherence to Rx and evaluate “white-coat” HTN Self-measurement Indicated for evaluation of “white-coat” HTN. Absence of 10–20% BP decrease during sleep indicates increased CVD risk Ambulatory BP monitoring Two readings, 5 minutes apart, sitting in chair Confirm elevated reading in contralateral arm In-office Brief Description Method JNC VII classification of hypertension is based on a mean of two appropriately performed readings as described above on two separate office visits. Blood pressure is classified as normal (<120/80 mm Hg), pre-hypertension ( /80-89 mm Hg), stage 1 hypertension ( /90-99 mm Hg), or stage 2 hypertension (>160/100 mm Hg). BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension, Rx=Treatment Source: Chobanian AV et al. JAMA 2003;289: 59

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.

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
National Health and Nutrition Examination Survey (NHANES) III 72% 66% 51% 38% Hypertension* Prevalence (%) 18% 9% The National Health and Nutritional Examination Survey (NHANES) III was a large U.S. survey designed to estimate the prevalence of selected diseases and risk factors. The NHANES III sample was selected from 81 counties between 1988 and The prevalence of hypertension in a representative sample from NHANES III demonstrates that approximately 25% of the U.S. adult population has hypertension and its prevalence increases steadily with advancing age. 3% 18-29 30-39 40-49 50-59 60-69 70-79 80+ Age *Hypertension defined as blood pressure >140/90 mmHg or treatment Source: JNC-VI. Arch Intern Med 1997;157: 62

National Health and Nutrition Examination Survey (NHANES)
High Blood Pressure*: Prevalence Increases with Age National Health and Nutrition Examination Survey (NHANES) 0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0 90.0 20-34 35-44 45-54 55-64 65-74 75+ Percent of Population Men Women The prevalence of hypertension increases with advancing age in men and women alike. Prior to age 55, hypertension is more prevalent in men. After age 55, hypertension is more prevalent in women. *High blood pressure defined as blood pressure 140/90 mmHg or treatment Source: NHANES: , Source: NCHS and NHLBI

High Blood Pressure*: Prevalence in U.S. Adults
National Health and Nutrition Examination Survey (NHANES) 45 40 35 30 25 Prevalence of Hypertension* 20 15 10 This slide shows the NHANES hypertension data by sex, race, and ethnicity. Comparison of data from 1988 to 1994 with that from 1999 to 2000 demonstrates that the rate of hypertension increased during this period. Increases were seen in all subpopulations studied: non-Hispanic black men and women, non-Hispanic white men and women, and Mexican-American men and women. The only group in which the increase was significant was non-Hispanic white women. Overall: The incidence of hypertension is increasing in the U.S. 5 Mexican- American Non-Hispanic White Non-Hispanic Black F M All F=Female, M=Male *High blood pressure defined as blood pressure >140/90 mmHg or treatment Source: Fields LE et al. Hypertension 2004;44: 64

Lifetime Risk* Starting at Age 55-65 Years
High Blood Pressure: Lifetime Risk* Starting at Age Years Framingham Heart Study Men Women Risk of hypertension (%) A total of 1,298 participants from the Framingham Heart Study that were between 55 and 65 years of age and free of hypertension at baseline ( ) were included in the study cohort. Data from long-term follow-up indicates that the lifetime risk of developing hypertension is about 90 percent. The residual life-time risk for developing hypertension (depicted above) was estimated for participants who reached the age of 65 free of hypertension. Years *Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg Source: Vasan RS, et al. JAMA 2002; 287:

Change in Blood Pressure Levels in the United States Over Time
National Health and Nutrition Examination Survey (NHANES) Blood pressure age-adjusted percentage The prevalence of favorable blood pressure status (using only systolic and diastolic blood pressures) for 4 NHANES periods is shown here. The age-adjusted estimates for the 4 time periods were 21.6%, 28.8%, 48.9%, and 43.7%, respectively. Source: Ford, E. S. et al. Figure 2b, Circulation 2009;120: Reprinted with permission.

Mean Blood Pressure According to Age, Sex and Ethnic Group in U. S
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

2. In older adults, hypertension is characterized by an elevated systolic blood pressure (BP) with normal or low diastolic BP, due to age-associated 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.

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: 120 mm Hg 140 mm Hg 160 mm Hg 180 mm Hg 256 128 Coronary Heart Disease Mortality 64 32 16 8 For every 20 mm Hg systolic or 10 mm Hg diastolic increase in BP, there is a doubling of mortality from both ischemic heart disease and stroke. Data from observational studies involving more than 1million individuals have indicated that death from both ischemic heart disease and stroke increases progressively and log linearly from BP levels as low as 115 mm Hg systolic and 75 mm Hg diastolic upward. The increased risks are present in all age groups ranging from 40 to 89 years old. 4 2 1 50-59 60-69 70-79 80-89 40-49 Age

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.

4. Numerous randomized trials have shown substantial reductions in CV outcomes in cohorts of patients years old with anti-hypertensive 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 1.8-year 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:

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

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 Subjects
Regular physical activity Sodium restriction Weight control Smoking cessation Avoidance of excessive alcohol intake

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 years and a threshold systolic BP of 150 mm Hg in people age 80 years and older is reasonable.

Risk of Adverse Outcomes Among Elderly CAD Patients by Age and BP
Denardo et al. Am J Med 123: , 2010 BP nadirs indicate BP’s with lowest hazard ratio at each age.

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.

Compelling Indications for Drug Classes
JNC VII Guidelines: Compelling Indications for Drug Classes Clinical-Trial Basis Compelling Indication ALLHAT, HOPE, ANBP2, LIFE, CONVINCE High CAD Risk ACC/AHA Post-MI Guidelines, BHAT, SAVE, Capricorn, EPHESUS Post-MI MERIT-HF, COPERNICUS, CIBIS, SOLVD, AIRE, TRACE, Val-HeFT, RALES Initial Therapy Options Diuretic, BB, ACE-I, CCB BB, ACE-I, Aldo ANT Diuretic, BB, ACE-I, ARB, Aldo ANT Heart Failure Diabetes Mellitus Diuretic, BB, ACE-I, ARB, CCB NKF-ADA Guideline, UKPDS, ALLHAT Chronic Kidney Disease Compelling indications refer to treatments that have demonstrated efficacy for a particular patient population in large randomized controlled trials. 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: 86

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

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

Half life of most antihypertensive drugs is increased 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
(mean SBP achieved) (Mean SBP achieved)

GUIDELINES II - API API

Blood Pressure Lowering Therapy Evidence: Primary Prevention
Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study 9,193 high-risk hypertensive* patients with LVH randomized to losartan (100 mg) or atenolol (100 mg) for 5 years An ARB provides greater efficacy in patients with LVH 16 12 Atenolol Proportion with CV death, MI, or stroke (%) 8 Losartan 4 13% RRR, P=0.021 In the LIFE trial, treatment with once daily losartan (compared to atenolol) in adults with essential hypertension and electrocardiographic evidence of left ventricular hypertrophy resulted in a significant decrease in the primary composite endpoint of death, MI, or stroke without a significant blood pressure difference between the two arms. This difference was driven predominantly by a statistically significant decrease in stroke, with no statistically significant difference in death from cardiovascular disease and myocardial infarction. There were also fewer new cases of diabetes mellitus in the losartan arm. Overall: In the LIFE trial, an ARB was more effective than a beta blocker in reducing CV risk in hypertensive patients with evidence of LVH. 6 12 18 24 30 36 42 48 54 60 66 Study Month ARB=Angiotensin receptor blocker, CV=Cardiovascular, DBP=Diastolic blood pressure, LVH=Left ventricular hypertrophy, MI=Myocardial infarction, SBP=Systolic blood pressure *Defined by SBP= mmHg or DBP= mmHg Source: Dahlöf B et al. Lancet 2002;359: Adapted with permission. 93

Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) 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 Both BP lowering regimens provide similar efficacy 6 Atenolol-based regimen 4 Nonfatal MI and fatal CHD (%) Amlodipine-based regimen 2 RRR = 10%, P = The goal of the ASCOT-BPLA study was to compare two antihypertensive regimens, one the combination of a diuretic and beta-blocker and the other the combination of a calcium channel blocker and ACE inhibitor, in patients with hypertension and at least 3 additional cardiovascular risk factors. The primary end point (by an intention to treat analysis) was the incidence of non-fatal myocardial infarction (including silent myocardial infarction) and fatal coronary heart disease. The study was stopped prematurely after 5.5 years of median follow-up. There was no statistically significant difference between the two treatment regimens with respect to the primary end point, nor the incidence of fatal and non-fatal stroke, total cardiovascular events and procedures, and all-cause mortality. Among patients receiving the calcium channel blocker and ACE inhibitor regimen, however, there was a lower incidence of diabetes mellitus. 1 2 3 4 5 6 Time since randomization (years) BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarction Source: Dahlöf B et al. Figure 3, Lancet 2005;366: Adapted with permission. 94

Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA) Amlodipine-based rate/1000 patient years Atenolol-based rate/1000 patient years Amlodipine-based better Atenolol-based better <0.05 <0.01 <0.0001 0.001 <0.001 NS Secondary endpoints Nonfatal MI + fatal CHD Total coronary endpoint Total CV events/procedures All-cause mortality CV mortality Fatal/nonfatal stroke Fatal/nonfatal HF P In the ASCOT-BPLA study, the amlodopine-based regimen did appear more efficacious in lowering several secondary endpoints including nonfatal MI plus fatal CHD (silent myocardial infarctions were excluded in this analysis), total coronary endpoints, total CV events and procedures, all-cause mortality, cardiovascular mortality, and fatal and nonfatal stroke. There was no difference in fatal and nonfatal heart failure. 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: Reprinted with permission.

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* An amlodipine-based regimen provides greater benefit 0.16 0.14 0.12 0.10 0.08 0.06 0.04 0.02 0.00 Composite of CV death, MI, stroke, hospitalization for angina, sudden cardiac arrest, and coronary revascularization (%) Benazepril/HCTZ Benazepril/Amlodipine The ACCOMPLISH trial sought to evaluate the effect of two antihypertensive treatment regimens (one the combination of benazepril and HCTZ and the other the combination of benazepril and amlodipine) in high-risk hypertensive patients. The trial was stopped early (pre-specified stopping rule) because the blood pressure regimen of benazepril/amlodipine showed superiority to benazepril/HCTZ in reducing the primary endpoint of CV death, myocardial infarction, hospitalization for angina, sudden cardiac arrest, and coronary revascularization. For the secondary end point of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio for benazaepril/amlodipine was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. 20% RRR, HR=0.80, P=0.0002 Time to first cardiovascular event (days) *The study was prematurely stopped Source: Jamerson K et al. NEJM 2008;359:

Hypertension in the Very Elderly (HYVET) Trial 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 Blood pressure control in patients >80 years of age provides benefit Rate/1000 patient years (%) P=0.06 P=0.05 P=0.02 P<0.001 (Primary end point) The HYVET trial enrolled 3845 patients from Europe, China, Australasia, and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more. Patients were randomly assigned to receive either the diuretic indapamide (sustained release, 1.5 mg) or matching placebo. The angiotensin-converting–enzyme inhibitor perindopril (2 or 4 mg), or matching placebo, was added if necessary to achieve the target blood pressure of 150/80 mm Hg. The primary end point was fatal or nonfatal stroke. At 2 years, 25.8%, 23.9%, and 49.5% of patients in the active-treatment group were receiving indapamide alone, indapamide and perindopril (2 mg), and indapamide and perindopril (4 mg), respectively; 14.2%, 13.4%, and 71.8% of patients in the placebo group, respectively, were receiving the corresponding placebos. At 2 years, the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group. In an intention-to-treat analysis, active treatment was associated with a 30% reduction in the rate of fatal or nonfatal stroke (95% confidence interval [CI], –1 to 51; P=0.06), a 39% reduction in the rate of death from stroke (95% CI, 1 to 62; P=0.05), a 21% reduction in the rate of death from any cause (95% CI, 4 to 35; P=0.02), a 23% reduction in the rate of death from cardiovascular causes (95% CI, –1 to 40; P=0.06), and a 64% reduction in the rate of heart failure (95% CI, 42 to 78; P<0.001). Fewer serious adverse events were also reported in the active-treatment group (358, vs. 448 in the placebo group; P=0.001). CV=Cardiovascular, CVA=Stroke Source: Beckett NS et al. NEJM 2008;358:

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 Both a CAS and NCAS provide similar efficacy 6 12 18 24 36 48 54 42 60 30 Calcium antagonist strategy (CAS)* Non-calcium antagonist strategy (NCAS)* Incidence of death, MI, or stroke RR=0.98, P=0.57 The goal of the INVEST study was to compare morbidity and mortality in a randomized, open label, blinded end point study of patients with hypertension and coronary artery disease treated with a calcium antagonist strategy (CAS) or a non–calcium antagonist strategy (NCAS). The CAS consisted of sustained release verapamil and the NCAS consisted of atenolol. By the end of the study, approximately half of the patients in each group were also taking trandolapril and hydrochlorothiazide to achieve blood pressure goals according to JNC VI. Trandolapril was also recommended for patients with heart failure, diabetes, or renal impairment. The primary outcome was first occurrence of death (all cause), nonfatal myocardial infarction, or nonfatal stroke. At 24 months, there were no statistical differences between the treatment strategies and the primary outcome. A total of 72% of CAS and 71% of NCAS patients achieved a systolic blood pressure of less than 140 mm Hg and diastolic blood pressure of less than 90 mm Hg. Overall, the treatment strategy of verapamil-trandolapril was as clinically effective as the atenolol-hydrochlorothiazide strategy in hypertensive patients with coronary artery disease. Overall: In CAD patients with hypertension, multiple agents will likely be needed to control BP. Starting with a calcium channel blocker versus a beta blocker does not impact the composite event rate of death, MI and stroke. Months 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: 98

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 in the Elderly
Although the optimal BP treatment goal in the elderly has not been determined, a therapeutic target of <140/90 mm Hg in persons aged years and a SBP of mm Hg, if tolerated, in persons aged ≥80 years is reasonable.

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, 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

Module 3 chapter 2a. Module 3 chapter 2a Hypertension in extremes of age.

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Module 3 chapter 2a. Module 3 chapter 2a Hypertension in extremes of age.

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Presentation on theme: "Module 3 chapter 2a. Module 3 chapter 2a Hypertension in extremes of age."— Presentation transcript:

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