Download geriatric htn 2009

Hypertension in the Elderly Its Different
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From in the Young
Physiology
HYVET Trial Results
Managing the Elderly Hypertensive
Mrs M M- 84 yo F with BPs from
184/85 – 107/58
Hx of Sjogrens syncope and CVA
Prevalence of High BP in Americans Aged 20 Years and Older by Age and
Gender (NHANES IV: 1999-2000)
Benefits of Lowering BP in all
patients
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20–25%
Heart failure
50%
35% reduction in stroke rate
Ave Age 73
SHEP Study; JAMA 265:3255; 1991
Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and
Women (US Population ³Age 18 Years, NHANES III)
150
130
110
Non-Hispanic Black
Non-Hispanic White
Mexican American
SBP
(mm Hg)
SBP
(mm Hg)
150
110
DBP
(mm Hg)
80
70
70
0
150
150
SBP
(mm Hg)
0
130
110
130
110
Pulse pressure
80
Pulse pressure
80
DBP
(mm Hg)
SBP
(mm Hg)
DBP
(mm Hg)
80
DBP
(mm Hg)
130
70
0
18-29 30-39 40-49 50-59 60-69 70-79
Men, Age (y)
Burt VI, et al. Hypertension. 1995;25:305-313.
80+
70
0
18-29 30-39 40-49 50-59 60-69 70-79
Women, Age (y)
80+
Aging: Vascular Changes
• Increased thickness
of intima and media.
• Matrix
– collagen deposition
– increased fibronectin
– crosslinking
(Advanced
Glycosylation
Endproducts)
Net result is increased vascular stiffness.
Arterial Wall Compliance and Pulse Pressure Wave
Elastic Vessel
Systole Diastole
Stiff Vessel
Systole Diastole
Stroke Volume
Aorta
Resistance
Arterioles
Pressure (Flow)
Young Artery
Bentley Dw, Izzo JL. J Am Geriatr Soc. 1982; 30:352-359.
Arteriosclerotic Artery
Consequences of decreased
vascular compliance
•
•
•
•
•
Relative increase in systolic pressure.
Increase in pulse pressure (SBP – DBP)
Decreased baroreceptor sensitivity?
Increased impedance of flow
Increased afterload for the LV to overcome
Consequences of Decreased
Baroreceptor Sensitivity
• Increased BP variability
• Impaired BP homeostasis
– Hypertension
– Postural (orthostatic) hypotension
– Post-prandial hypotension
• Increase in sympathetic nervous system
activity
Salt Sensitivity of Blood
Pressure
• Definition: Mean arterial blood pressure
on high vs. low Na+ diet
– > 5 mm Hg increase => Sodium Sensitive
– < 5 mm Hg increase => Sodium Resistant
• Two thirds of older hypertensives are
sodium sensitive.
Dengel et al., Am J Physiol 274:E403, 1998
Characteristics of Hypertension in the
Elderly
Increased
Systolic blood pressure and pulse pressure
Left ventricular mass and wall thickness
Arterial stiffness
Calculated total peripheral resistance
Decreased
Cardiac output and heart rate
Renal blood flow, plasma renin activity, and angiotensin II levels
Arterial compliance and blood volume
Diastolic blood pressure
Black H. JCH 2003; 5:12
Cerebral Blood flow
Percent of Control
Normotensive Patients
Treated Hypertensive Paitents
100
50
Cerebral Blood flow
Percent of Control
Hypertensive Patients
0
50
100
150
200
Mean Arterial Blood Pressure
Autoregulation of cerebral blood flood
Strandgaard et al. Lancet 1987; 2:658-661
mm Hg
Blood Pressure & The Very
Elderly (aged 80 or more)
• Epidemiologic population studies suggest better survival
with higher levels of blood pressure
• Worse survival reported in hypertensives with SBP levels
below 140 mmHg (Oates et al. 2007)
• Clinical trials recruited too few.
• Meta-analysis (n=1670)
(Gueyffier et al. 1997)
– 36% reduction in the risk of stroke (BENEFIT)
– 14% (p=0.05) increase in total mortality (RISK)
• Hypertension in the Very Elderly Trial (HYVET) pilot results
(n=1273) similar to meta-analysis (Bulpitt et al. 2003)
The Trial:
International, multi-centre, randomised double-blind placebo controlled
Inclusion Criteria:
Aged 80 or more,
Systolic BP; 160 -199mmHg
+ diastolic BP; <110 mmHg,
Informed consent
Exclusion Criteria:
Standing SBP < 140mmHg
Stroke in last 6 months
Dementia
Need daily nursing care
CHF or Cr more than 1.7
Primary Endpoint:
All strokes (fatal and non-fatal)
+ Perindopril 4 mg
+ Perindopril 2 mg
Indapamide SR 1.5 mg
Target blood pressure
Placebo
150/80 mmHg
Placebo
+ Placebo
+ Placebo
M-2
M-1
M0
M3
M6
M9
M12
M18
M24
M60
4761 Entered into
Placebo Run-in
916 not randomised
Placebo
1912
Active
1933
• 3845 randomised; Western Europe (86) Eastern Europe
(2144), China (1526), Australasia (19), Tunisia (70)
• At end of trial; 1882 still in double blind, 17 vital status
not known, 220 in open follow-up
Baseline data
Placebo
(n= 1912)
Active
(n= 1933)
83.5
83.6
60.3%
60.7%
Sitting SBP (mmHg)
173.0
173.0
Sitting DBP (mmHg)
90.8
90.8
Orthostatic Hypotension‡
8.8%
7.9%
Isolated Systolic Hypertension
32.6%
32.3%
Age (years)
Female
Blood Pressure:
‡ Fall in SBP ≥ 20mmHg and/or fall in DBP ≥ 10mmHg
Baseline Data
(Previous Cardiovascular
History)
Placebo
(%)
Active
(%)
Cardiovascular disease
12.0
11.5
Known Hypertension
89.9
89.9
Anti-hypertensive treatment
65.1
64.2
Stroke
6.9
6.7
Myocardial Infarction
3.2
3.1
Heart Failure
2.9
2.9
Baseline data
(Cardiovascular Risk factors)
Placebo
Active
6.6%
6.4%
6.9%
6.8%
Total cholesterol (mmol/l)
5.3
5.3
HDL Cholesterol (mmol/l)
1.35
1.35
Serum Creatinine (μmol/l)
89.2
88.6
Uric acid (µmol/l)
279
280
Body Mass Index (kg/m2)
24.7
24.7
Current smoker
Diabetes
(Known DM/ DM treatment/glucose>11.1mmo/l)
Blood pressure separation
180
15 mmHg
170
160
Blood Pressure (mmHg)
150
140
Placebo
130
120
Indapamide SR +/perindopril
Median follow-up 1.8 years
I
110
100
6 mmHg
90
80
70
0
1
2
3
Follow-up (years)
4
5
All stroke
(30% reduction)
Placebo
P=0.055
Indapamide
SR
±perindopril
Placebo
IndapamideSR ±perindopril
Fatal Stroke
(39% reduction)
Placebo
P=0.046
Indapamide
SR
±perindopril
Placebo
IndapamideSR ±perindopril
Heart Failure
(64% reduction)
Placebo
P<0.0001
IndapamideSR
±perindopril
Placebo
IndapamideSR ±perindopril
Total Mortality
(21% reduction)
Placebo
P=0.019
Indapamide
SR
±perindopril
Placebo
IndapamideSR ±perindopril
Summary at median
1.8 Yrs
HR
95% CI
NNT
All Stroke
0.70
(0.49, 1.01) NS
Stroke Death
0.61
(0.38, 0.99) 241
All cause
mortality
0.79
(0.65, 0.95) 82
NCV/Unknown
death
0.81
(0.62, 1.06) NS
CV Death
0.77
(0.60, 1.01) NS
Cardiac Death
0.71
(0.42, 1.19) NS
Heart Failure
0.36
(0.22, 0.58) 106
CV events
0.66
(0.53, 0.82) 60
0.1
0.2
0.5
0
2
Conclusions
• Antihypertensive treatment based on indapamide
(SR) 1.5mg (± perindopril) reduced stroke mortality
and total mortality in a very elderly cohort.
• NNT (2 years) = 94 for stroke and 40 for mortality
• Large and significant benefit in reduction of heart
failure events and for combined endpoint of
cardiovascular events
• Benefits seen early
• Treatment regime employed was safe
5 Year NNTs for younger and older
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•
•
•
•
•
Age <60
12 trials, n = 33,000
Stroke NNT = 168
CHD event NNT = 184
Stroke & CHD NNT = NA
CV mortality NNT = 205
Age ≥60
13 trials, n = 16,564
Stroke NNT = 43
CHD event NNT = 61
Stroke & CHD NNT = 18
CV mortality NNT = 52
• Mulrow et al. JAMA 1994; 272:1932-1938
J curve of all cause Mortality found
in several studies
• The risk for the primary
outcome, all-cause death,
and MI, but not stroke,
progressively increased
with low diastolic blood
pressure. Excessive
reduction in diastolic
pressure should be
avoided in patients with
CAD who are being
treated for hypertension.
• INVEST Trial Secondary
analysis
AIM 144:884 (2006)
Treatment Recs for the Elderly with
HTN
• Don’t have to have goal lower than 150/80
– DBP lower than 65 are possibly undesirable
• Diuretics are generally preferred
– Effective, have best data in reducing complications
• Don’t overuse diuretics
– Keep the dose low
– Combo Rx is usually necessary and desirable
• Keep an eye for orthostatic symptoms and if
present back off on Rx – Check standing BPs
• Lifestyle changes can be effective
– Low Salt diet, aerobic exercise and weight loss
“If the standing blood pressure
is consistently much lower than
the sitting blood pressure,
the standing blood pressure
should be used to titrate drug
dosages during treatment.”
National High Blood Pressure Education
Program Working Group Report on
Hypertension in the Elderly.
References
• Beckett NS et al, “Treatment of HTN in Patients 80 Yrs of age or
Older”(HYVET) NEJM 358:1887-98 2008
• Psaty, Bruce, et al Health Outcomes Associated With Various
Antihypertensive Therapies Used as First-Line Agents: A Network
Meta-analysis. JAMA 289:2534-44
• Oates DJ et al “Blood Pressure and Survival in the Oldest Old” J Am
Geriatr Soc 55:383-388, 2007
• SHEP Coop Research Group, SHEP Trial JAMA 265:3255; 1991
• Messerli, Franz H. MD; Mancia, et al; “Dogma Disputed: Can
Aggressively Lowering Blood Pressure in Hypertensive Patients with
Coronary Artery Disease Be Dangerous? AIM: 144:884 (2006)
• Chobanian, A “Isolated Systolic HTN in the Elderly” Clinical Practice
NEJM: 357:789-96 2007