Transcript Document

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