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)

Normal <120 and <80

Prehypertension 120–139 or 80–89

Stage 1 Hypertension 140–159 or 90–99

Stage 2 Hypertension >160 or >100

BP Classification SBP mmHg DBP mmHg

Table 1 Classification of hypertension in youth

McCrindlle, B. W. (2010) Assessment and management of hypertension in children and adolescentsNat. 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

• 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. 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 SCREENING CONFIRMATIONRenal 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 SCREENING CONFIRMATIONCushings syndrome Plasma, urine

cortisolDexamethasone suppression test

Phaeochromo-cytoma

Spot urine metanephrine

Urine/plasma catecholamines, CT abdomen

Coarctation of aorta chest x ray CT angiography, angiography

Thyroid disorderAcromegaly

TSH levelsGrowth 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 ModificationModification 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

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 compellingIndication : 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;43:518-524

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 Angioplasty Stenting

Careful follow up for residual hypertension is essential

2.HYPERTENSION IN ELDERLY (>65Y)

Prevalence of HBP in different parts of IndiaCity 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. There is a dramatic increase in HTN prevalence with aging; by age 70 yrs, the majority of people have HTN

2. In older adults, HTN is characterized by an elevated SBP with normal or low DBP, due to age-associated stiffening of large arteries.

3. HTN is a potent risk factor for CVD in the elderly.4. Numerous randomized trials have shown substantial reductions

in CV outcomes in cohorts of patients 60-79 yrs old with anti-HTN drug therapy though the effect on all-cause mortality has been modest.

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.

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 treatment-related side effects.

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

BP=Blood pressure, CVD=Cardiovascular disease, HTN=Hypertension, Rx=Treatment

Source: Chobanian AV et al. JAMA 2003;289:2560-2572

JNC VII Guidelines: Measurement of Blood Pressure

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.

0

20

40

60

80

Hyp

ert

en

sion

* Pre

vale

nce

(%

)

18-29

National Health and Nutrition Examination Survey (NHANES) III

30-39 40-49 50-59 60-69 70-79 80+

Age

3%9%

18%

Source: JNC-VI. Arch Intern Med 1997;157:2413-2446

51%

66%72%

38%

*Hypertension defined as blood pressure >140/90 mmHg or treatment

High Blood Pressure*: Prevalence Increases with Age

Source: NHANES: 1999-2004, Source: NCHS and NHLBI

0.010.020.030.040.050.060.070.080.090.0

20-34 35-44 45-54 55-64 65-74 75+

P

erc

ent

of

Popula

tion

Men Women

National Health and Nutrition Examination Survey (NHANES)

*High blood pressure defined as blood pressure 140/90 mmHg or treatment

High Blood Pressure*: Prevalence Increases with Age

Source: Fields LE et al. Hypertension 2004;44:398-404

All

0

Pre

vale

nce

of

Hypert

en

sion*

45

30

20

1510

25

40

5

35

Mexican-American

Non-Hispanic White

Non-Hispanic Black

FM FM FM

1999-20001988-1994

F=Female, M=Male

*High blood pressure defined as blood pressure >140/90 mmHg or treatment

National Health and Nutrition Examination Survey (NHANES)

High Blood Pressure*: Prevalence in U.S. Adults

0

20

40

60

80

100

0 2 4 6 8 10 12 14 16 18 20

Ris

k of

hypert

ensi

on (

%)

*Residual lifetime risk of developing hypertension among people with blood pressure <140/90 mmHg

Years

Men Women

Source: Vasan RS, et al. JAMA 2002; 287:1003-1010

Framingham Heart Study

High Blood Pressure: Lifetime Risk* Starting at Age 55-65 Years

Source: Ford, E. S. et al. Figure 2b, Circulation 2009;120:1181-1188. Reprinted with permission.

National Health and Nutrition Examination Survey (NHANES)

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Stage 2

Stage 1

Prehypertensionnormotensive

Bloo

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Change in Blood Pressure Levels in the United States Over Time

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

CURES 52 MOHAN ET AL JAPI 2007

ISH

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 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.

Hypertension in the Elderly

Coronary Heart Disease Rates by SBP and AgeAdapted from Lewington et al. Lancet. 2002; 360:1903-1913

120 mm Hg

140 mm Hg

160 mm Hg

180 mm Hg

Coronary Heart Disease Mortality

256

128

64

32

16

8

4

2

40-49

Age50-59 60-69 70-79 80-89

1

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 60-79 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%.

Hypertension in the Elderly

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;358:1887-98.

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.

Hypertension 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.

Hypertension in the Elderly

Non-Pharmacologic Lifestyle Measures Shown Beneficial in Elderly Hypertensive Subjects

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

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.

Hypertension in the Elderly

Risk of Adverse Outcomes Among Elderly CAD Patients by Age and BP

Denardo et al. Am J Med 123:719-726, 2010

BP nadirs indicate BP’s with lowest hazard ratio at each age.

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.

Hypertension in the Elderly

Clinical-Trial BasisCompelling 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

Recurrent Stroke Prevention

PROGRESSDiuretic, ACE-I

NKF-ADA Guideline,UKPDS, ALLHAT

NKF Guidelines, Captopril Trial, RENAAL, IDNT, REIN,

AASK

Diuretic, BB, ACE-I,ARB, CCB

ACE-I, ARB

Diabetes Mellitus

Chronic Kidney Disease

Source: Chobanian AV et al. JAMA 2003;289:2560-2572

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

JNC VII Guidelines: Compelling Indications for Drug Classes

Antihypertensive Treatment-RelatedSide 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

9. Initiation of antihypertensive drugs in the elderly should generally be at the lowest dose with gradual increments as tolerated.

Hypertension in the Elderly

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

(mean SBP achieved)

Percent (%)

Syst-China (not reported) MRC-Elderly (153 mmHg)

EWPHE (151 mmHg) Syst-Eur (151 mmHg)

STOP-2 (151 mmHg) STONE (147 mmHg)

SHEP (146 mmHg) LIFE (143 mmHg)

Australian HTN (142 mmHg) HYVET (138 mmHg)

ALLHAT (138 mmHg) INVEST (136 mmHg)

CONVINCE (136 mmHg)

100

0

90 80 70 60 50 40 30 20 10

ACCOMPLISH (131 mmHg)

0

Tria

l Nam

e/S

BP

Ach

ieve

d

(Mean SBP achieved)

GUIDELINES II - API

API

Losartan Intervention for Endpoint (LIFE) Reduction in Hypertension Study

Source: Dahlöf B et al. Lancet 2002;359:995-1003. Adapted with permission.

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

0 6 12 18 24 30 36 42 48 54 60 66

Study Month

4

8

12

16

0Pro

port

ion w

ith C

V

death

, M

I, o

r st

roke

(%

) Atenolol

13% RRR, P=0.021

Losartan

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

Blood Pressure Lowering Therapy Evidence: Primary Prevention

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

Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)

Nonfa

tal M

I and f

ata

l C

HD

(%

)

6

2

4

01 2 3 4 5 60

Time since randomization (years)

RRR = 10%, P = 0.1052

Atenolol-based regimen

Amlodipine-based regimen

Source: Dahlöf B et al. Figure 3, Lancet 2005;366:895-906. Adapted with permission.

BP=Blood pressure, CV=Cardiovascular, CHD=Coronary heart disease, MI=Myocardial infarction

Blood Pressure Lowering Therapy Evidence: Primary Prevention

Anglo-Scandinavian Cardiac Outcomes Trial—Blood Pressure Lowering Arm (ASCOT-BPLA)

Secondary endpointsNonfatal MI + fatal CHD 7.4 8.5Total coronary endpoint 14.6 16.8Total CV events/procedures 27.4 32.8 All-cause mortality 13.9 15.5 CV mortality 4.9 6.5 Fatal/nonfatal stroke 6.2 8.1 Fatal/nonfatal HF 2.5 3.0

Amlodipine-based rate/1000

patient years

<0.05<0.01

<0.0001

<0.05 0.001

<0.001 NS

P

Amlodipine-based better

Atenolol-based better

0.50 0.70 1.00 1.45 2.00

Atenolol-based

rate/1000patient years

Source: Dahlöf B et al. Figure 4, Lancet 2005;366:895-906. Reprinted with permission.

CHD=Coronary heart disease, CV=Cardiovascular, HF=Heart failure, MI=Myocardial infarction

An amlodopine-based regimen appears to reduce the rate of other CV events

Blood Pressure Lowering Therapy Evidence: Primary Prevention

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

Avoiding Cardiovascular Events Through Combination Therapy in Patients Living with Systolic Hypertension

(ACCOMPLISH)

Benazepril/HCTZ

Benazepril/Amlodipine

Com

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f C

V d

eath

, M

I, s

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, hosp

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or

angin

a, su

dden c

ard

iac

arr

est

, and c

oro

nary

re

vasc

ula

riza

tion (

%)

Time to first cardiovascular event (days)

20% RRR, HR=0.80, P=0.0002

Source: Jamerson K et al. NEJM 2008;359:2417-28.

0.16

0.14

0.12

0.10

0.08

0.06

0.04

0.02

0.00

0 200 400 600 800 1000 1200 1400

*The study was prematurely stopped

Blood Pressure Lowering Therapy Evidence: Primary Prevention

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

Hypertension in the Very Elderly (HYVET) Trial

Source: Beckett NS et al. NEJM 2008;358:1887-98

CV=Cardiovascular, CVA=Stroke

0

10

20

30

40

50

60

70

Fatal orNonfatal

CVA*

Deathfrom CVA

All causemortality

Any heartfailure

Any CVevent

Indapamide +/-perindoprilPlacebo

Rate

/100

0 pa

tient

yea

rs (%

)

P=0.06

P=0.05

P=0.02

P<0.001

P<0.001

(Primary end point)

Blood Pressure Lowering Therapy Evidence: Primary Prevention

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

0

5

10

15

20

25

0 6 12 18 24 36 48 5442 6030

International Verapamil-Trandolapril Study (INVEST)

Months

RR=0.98, P=0.57

Calcium antagonist strategy (CAS)*Non-calcium antagonist strategy (NCAS)*

Source: Pepine CJ et al. JAMA 2003;290:2805-2816

*Trandolapril (up to 4 mg) was added in those with diabetes mellitus, chronic kidney disease, or heart failure

Inci

dence

of

death

, M

I, o

r st

roke

BP=Blood pressure, HTN=Hypertension, MI=Myocardial infarction

Blood Pressure Lowering Therapy Evidence: Secondary Prevention

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.

Hypertension in the Elderly

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 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