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.