Hypertension in the Elderly DEBRA L. BYNUM, MD Outline Defining Systolic Hypertension Risks of SH in older persons Preventing stroke, CHF,
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Transcript Hypertension in the Elderly DEBRA L. BYNUM, MD Outline Defining Systolic Hypertension Risks of SH in older persons Preventing stroke, CHF,
Hypertension in the Elderly
DEBRA L. BYNUM, MD
Outline
Defining Systolic Hypertension
Risks of SH in older persons
Preventing stroke, CHF, CV events,
dementia
Review of major trials
Choice of treatment
Pulse Pressure
Specific treatment groups:
Stage 1 SH
“Oldest old” : those over age 80
The History…
Systolic Hypertension in the Elderly so
common that once considered normal part of
aging
Previously : “Isolated Systolic Hypertension”
1980: JNC on HTN defined ISH as SBP >160
with DBP <90
Classification: JNC 7
Classification
SBP
DBP
Normal
<120
And <80
PreHypertension 120-139
Or 80-89
Stage 1 HTN
140-159
Or 90-99
Stage 2 HTN
>160
Or >100
Systolic Hypertension
Defined as SBP > 140 with DBP <90
No longer referred to as “Isolated”
How Common is Systolic Hypertension?
Prevalence: Framingham Data
Prevalence of HTN increases with age
SH accounts for 75% of HTN in those over 65
Over ½ of people over age 60 and ¾ of those over
the age of 70
PreHypertension
People over age 65: 26% four year risk of
HTN if BP 120-129/80-84
Those over age 65 with BP 130-139/85-89:
50% four year risk of HTN
Patients with BP 130-139/85-89 have twice
the risk of CVD events compared to those
with normal BP
Why the emphasis on the Systolic number?
Importance of SBP
Continued increase in SBP with age
Level/decrease in DBP with age (after 50-60)
Systolic Hypertension most common cause of HTN in
patients over age 50
After age 50, SBP is much more important risk factor
for CV events than DBP
SBP more often poorly controlled than DBP
SBP
Increase in SBP with age likely due to changes in
arterial stiffness
Framingham data from 1976 and meta-analysis of
60 observational studies: SH major risk factor for
stroke
Initial concern that SBP lowering would lead to
increased stroke in patients over age 80 NOT
SHOWN
Systolic Hypertension
JNC 7 clear in report: SH in patients over the age
of 60 much more important than DBP
SH assoicated with increased risk of CAD, LVH,
renal insufficiency, stroke, and CV mortality
Pulse Pressure (difference between SBP and DBP)
predictor of increased CV risk (likely marker of
“stiff “ arteries)
SH more closely associated with CV risk than DBP
in older patients (even in older patients with
diastolic hypertension)
Systolic Hypertension: summary
SH more common in older patients
SH more closely correlated with CV and
stroke events
Pulse Pressure also associated with increased
risk of CV events, likely marker of arterial
disease
Risks…
Epidemiological Studies:
Framingham and Physician’s Health Study: Stage I
SH: increased risk of CVD, CAD, and Stroke
Large RCTs: demonstrate significant benefits
of treating older patients with SH
DATA
SHEP trial : 1991
5000 patients, SBP 160-190, DBP <90, mean age 72
Chlorthalidone (thiazide) vs placebo
Second agents: atenolol, reserpine
Primary endpoint: stroke
Significant decrease in 5 year incidence of all strokes
(8% vs 5%, ARR 3%)
DATA : SHEP trial
Reduction in Heart Failure
2.3% vs 4.4 %
ARR 2%
NNT 48
DATA: SHEP…
32 % Relative Risk Reduction and 5% Absolute
Reduction in total combined CV events (secondary
outcome)
NNT: need to treat 18 people over 5 years to
prevent 1 major cardiovascular or cerebrovascular
event
?underestimation: goal BP only reached in 70%
treatment group; 44% placebo group also treated
(intention to treat analysis)
Benefits of Treatment: Additional Trials
Systolic Hypertension in Europe
Systolic Hypertension in China
All demonstrated decreased risk of stroke
and combined CV events in older patients
treated for SH
None powered to demonstrate difference in
all cause or cardiovascular mortality
Effect of treating SH on risk of Stroke
SHEP data: both hemorrhagic and ischemic
strokes decreased
Immediate effect on bleeds seen
2 years needed to see full effect of reduction
in ischemic stroke
Summary: Prevention of Cardiovascular
Endpoints
All trials demonstrated decreased stroke
(ischemic and hemorrhagic)
Decreased CHF
Reduction in combined CV events (26%
relative risk reduction in one meta-analysis)
Will treating hypertension prevent dementia?
First Question: Is Hypertension a Risk Factor for
Dementia?
Longitudinal studies (15-20 year followup)
demonstrate association between midlife
hypertension and later cognitive
impairment/dementia
• 20 year followup study, Hypertentsion 1998
• 15 year study: blood pressure and dementia, Lancet 1996
Next Question:
Are patients treated for hypertension less likely to
develop cognitive impairment or dementia?
Prospective Cohort Studies
Honolulu-Asia Aging Study 1965-1996
3 year Utah study of 3000 patients
Swedish study of nearly 2000 patients (average age
82) 1992
African American cohort (1900 patients) 2002
Prospective studies
Patients on antihypertensive treatment have lower
risk of developing cognitive
impairment/dementia/cerebral atrophy
Problems
Confounding with no placebo group
Reliance on self report of treatment and adherence
Final Question:
Will treatment of hypertension reduce the risk of
developing cognitive impairment or dementia?
RCTs looking at hypertension and dementia
Syst-Eur Trial
SCOPE
SHEP
Progress
HYVET-COG
Syst-Eur Trial
2400 patients with ISH, average age 70
3.9 year followup
Long term treatment of HTN: reduced risk of
dementia from 7.4 to 3.3 cases/1000 patient years
Decrease in vascular and alzheimer type dementias
Trial stopped early because of stroke risk reduction
SCOPE: Study of Cognition and Prognosis in the
Elderly
Nearly 5000 patients
Follow up: 44 months
Significant decline in strokes
No difference in dementia
Short follow up
84% “controls” were treated (2003)
Inclusion criteria: mild hypertension (160-179/90-99)
SHEP: systolic hypertension in the elderly
program
JAMA 1991
5000 patients, 4.5 year follow up
1.6 % treatment patients vs 1.9% placebo patients
developed dementia (no sig difference)
44% in placebo group were treated b/c of BP
High rate of drop out for cognitive assessment
PROGRESS: Perindopril Protection against recurrent
stroke study
6100 patients, average age 64, hx of stroke or TIA
3.9 year follow up
Perindopril and indapamide if tolerated
Only 48% in each group had HTN
Cognitive decline: 9% treatment group, 11%
placebo group (p=.01)
Stroke and cognitive decline decreased by 45%
HYVET-COG
Over 3000 patients
2.2 year follow up
No significant difference in dementia (total 263 new
cases of dementia)
Problems
Short follow up (trial stopped)
Patients over 80 started on treatment (not looking at
treatment from 60-70)
Summary : Dementia and Systolic Hypertension
Observational studies suggest less risk of
cognitive decline in older patients treated for
SH
Risk of confounding: more frail patients may be less
likely to be treated…
May be that treatment in MIDDLE AGE/young older
age is most important
RCTs mixed, but may need longer followup,
more patients
How to Treat…
Lifestyle Modifications
DASH (Dietary Approaches to Stop
Hypertension)
Effective in decreasing SBP
?increased Na responsiveness in older patients
Lifestyle: TONE trial
Older patients with SH, BP < 145/85 on 1 med
Medication stopped
4 groups: Na restriction, weight reduction, both Na
restriction and weight reduction, usual care
Outcome: remaining free of HTN or need to restart
medication or CV event
25% in usual care group remained “free”
38% in Na restriction, 40% in weight reduction,
and 44% in combined treatment did well
Lifestyle Changes: summary
Evidence that weight loss and Na restriction
can be effective for mild SH in older patients
Which agent is best?
Thiazide diuretics: first line in large trials
ACE inhibitors:
LIFE (Losartan Intervention for Endpoint Reduction)
Losartan vs beta blocker:
Losartan decreased risk CV events
HOPE (Heart Outcomes Prevention Evaluation)
Patients with DM, over 55, CVD risk
Ramipril 10/day decreased morbidity/mortality at 5
years
Most pronounced effect seen in those over age 65
Which agent?
Calcium channel blockers?
SHELL (SH in Elderly: Lacidipine Long Term Study)
CCB and thiazide equal
Which agent?
ALLHAT
RCT 45,000 patients
Thiazide vs amlodipine, lisinopril, or doxazosin
(doxazosin arm stopped due to increase risk CHF)
Overall NO difference
Trend for thiazide treated patients to have less risk of
stroke and CHF
Which agent?
Blood Pressure Lowering Treatment Trialists’ Collaboration:
Meta-analysis of RCTs looking at different regimens for HTN
BMJ 4/2008
31 trials, over 190,000 patients
1. NO difference between age groups with benefit of
treatment; benefits seen in ALL age groups
2. NO differences between classes of drugs
Treatment
Uncontrolled hypertension most often due to
difficult to control systolic pressure
Systolic hypertension usually requires more
than one drug
Balance with risk for orthostatic
hypotension: need to follow with standing
blood pressures
Which Agent: Summary
Overall similar
Thiazides considered first line
?concern for beta blockers unless other indication
Some evidence to avoid alpha blockers unless other
indication for use
Need to individualize treatment
Most often will require more than one drug for SH
Specific Groups
Stage 1 HTN
Over 85 age group
Previously “controversial” treatment groups
Stage 1 HTN
Prehypertension and stage 1 HTN clearly
associated with increased risk of cerebrovascular
events, CHF and CV events, and even dementia
Consider other risk factors (DM, CAD, and AGE)
Recommendations from JNC:
Treat Stage 1 HTN
Lifestyle modifications for Prehypertension,
added pharmacologic treatment if other vascular
risk factors present
Over 80: concerns
Observational data that very old patients with
lower BPs have higher mortality
JAGS 2007: retrospective cohort study of VA
patients over age 80 found lower 5 year survival in
patients with lower BPs
Risk of confounding…
HYVET: Hypertension in the Very Elderly Trial
RCT of nearly 4000 patients from Europe, China, Australia,
Tunisia
Age over 80
SBP > 160
Indapamide vs placebo
ACE inhibitor (perindopril) or placebo added as second agent
when needed
Primary endpoint: stroke
HYVET…
Mean age : 83
Mean standing BP: 173/90
Target SBP = 150
12% had hx of CV disease
1.8 year follow up
Treatment group: 15/6 lower BP
HYVET: results
Endpoint
Treatment (rate per
1000 patient-year/#
events)
Placebo
Stroke
12.4 (51)
17.7 (69)
Death from stroke
6.5 (27)
10.7 (42)
Mortality
47.2 (196)
59.6 (235)
Death from CV cause
23.9 (99)
30.7 (121)
Any MI
2.2 (9)
3.1 (12) p=.45
Any heart failure
5.3 (22)
14.8 (57)
Any CV event
33.7 (138)
50.6 (193)
Any CV event:
Death from CV cause,
stroke, MI, CHF
HYVET: results
30% decrease in rate of fatal or nonfatal stroke
39% decrease in rate of death from stroke
21 % decrease in all cause mortality
23% decrease in CV death
64% decrease in heart failure
Fewer adverse events in treatment group
HYVET: Other points
Target SBP of <150
Only 50% treatment group reached target BP
Followed standing BP to keep over 140
7.9% in treatment group vs 8.8% in placebo
group had orthostatic hypotension
Summary
SH is not benign
SH is a risk factor for all cause dementia
Treatment is associated with decreased CHF and stroke, and
? Dementia
Over 80: Benefits seen with modest tx goal (SBP 150)
Follow standing BPs to avoid orthostatic hypotension
First Line: thiazides, then calcium channel blockers or ACE
inhibitors; Beta blockers only if indication other than HTN.