DEBRA L. BYNUM, MD

Hypertension in the Elderly

Outline

Defining Systolic HypertensionRisks of SH in older personsPreventing stroke, CHF, CV events,

dementiaReview of major trialsChoice of treatmentPulse PressureSpecific 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 EuropeSystolic 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 TrialSCOPESHEPProgressHYVET-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 patientsFollow up: 44 monthsSignificant decline in strokesNo 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 upPerindopril and indapamide if toleratedOnly 48% in each group had HTNCognitive decline: 9% treatment group,

11% placebo group (p=.01)Stroke and cognitive decline decreased by

45%

HYVET-COG

Over 3000 patients2.2 year follow upNo 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 HTNOver 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.