Hypertension and The Older Patient

Debra L. Bynum, MD

Assistant Professor

Division of Geriatric Medicine

University of North Carolina

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 as Risk Marker Controversial treatment groups

– Stage I SH– “Oldest old” those over 85

The History

Systolic Hypertension in the Elderly so common once thought to be almost normal part of aging

Previously known “Isolated Systolic Hypertension”

1980 JNC on HTN defined ISH as SBP> 160 with DBP <90

Definition

Systolic Hypertension (“isolated” having falsely benign connotation)

JNC defines as SBP >140 with DBP <90– Stage I SH: SBP 140-159– 7th report from JNC: SH in patients over 60 much more

important than diastolic HTN and treatment should focus on control of SBP

Prevalence

HTN seen in over 60% of those over age 65

Elevations of SBP with decreases in DBP common with age due to diminished arterial compliance (increased Pulse Pressure)

SH accounts for 65-75% HTN in those over 65

The Importance Of SH

SH associated with increased risks of CAD, LVH, renal insufficiency, stroke and cardiovascular mortality

SH and pulse pressure more closely associated with CV risk than diastolic BP in older patients (even in older patients with diastolic HTN)

The Problem

Still underestimated importance

Fear of treating older patients may interfere with appropriate management

Older patients have most visits to clinics and hospitals but lowest rates of adequate BP control

Up to 75% of older patients being treated for HTN are undertreated

Risks…

Epidemiological studies:– Framingham: Stage I SH: increased risk CVD (RR

1.47), CAD (RR 1.44), stroke (RR 1.42) and CHF (RR 1.6)

– Physicians’ Health Study: similar risks

Several Large RCTs demonstrate significant benefits of treating older patients with SH

Risks…The 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– 5 year incidence stroke: 8.2 % with placebo, 5.2%

treatment (ARR 3%)

SHEP…

32% Relative Risk Reduction and 5% Absolute Reduction in total CV events

NNT: need to treat 18 people over 5 years to prevent 1 major cardiovascular or cerebrovascular event

Underestimation: goal BP reached in only 70% in treatment group; 44% of placebo group 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 systolic hypertension

None powered to demonstrate difference in all cause or cardiovascular mortality

Summary: Prevention of Cardiovascular endpoints…

All trials demonstrated decreased cerebrovascular events, mainly stroke

Trials demonstrate reduction of combined cardiovascular events with 26% relative risk reduction per meta-analysis

The Link with Dementia: SYST-EUR Trial

Does treatment of older patients with SH decrease incidence of vascular disease?

CCB nitrendipine +/- enalapril +/- HCTZ

2 year f/u (stopped early): significant decrease in strokes

SYST-EUR: additional information…

After termination, patients followed 2 years

Continued difference in BP between original placebo group and initial treatment group (SBP/DBP 7/3 lower) at 4 years

Original treatment group had persistent decreased risk of dementia

– 7.4 vs 3.3 cases/1000 patient-years– Decreased both vascular and alzheimer type dementia!

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…

5 RCTs look at dementia and SH

All show significant decrease risk of stroke

Most demonstrate decrease risk of cognitive decline with treatment

How To Treat…

Lifestyle Modifications

DASH (Dietary Approaches to Stop Hypertension)

– Effective in decreasing SBP– ?increased Na responsiveness in older patients– Small, subgroup analysis

TONE trial

TONE trial

Older patients with SH, BP< 145/85 on 1 med Medication stopped

4 groups: Na restriction, Weight reduction, both Na restriction/wt reduction, usual care

Outcome: remaining free of HTN, medication restart or CV outcome

25 % in usual care group remained “free”

38% in Na restriction, almost 40% in weight reduction and 44% of those in Na restriction/weight reduction remained “free”

Lifestyle changes: summary

Evidence that weight loss and Na restriction can be effective for mild SH in older patients

Some literature suggests that this population may be less amenable to such lifestyle changes…

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 yrs Most pronounced effect seen in those over age 65

Ca Channel Blockers– SHELL (SH in Elderly: Lacidipine Long Term Study)– CCB and thiazide similar effectiveness

Which agent?

Beta Blockers may not be first line…

– LIFE study (25 events/1000 patient years in those on losartan vs 35 events/1000 pt yrs on atenolol)

– Meta-analysis of 10 trials, 16000 older patients with SH Diuretic better than B blocker in preventing combined endpoint Beta blockers and diuretics decreased risk of stroke, BUT Beta blockers were not effective at preventing CAD, CV

mortality or all cause mortality

Beta blockers

Indicated in patients with prior MI/ACS

2002 prospective study of patients with prior MI and HTN treated with beta blockers, ACE I, diuretic, Ca Channel blockers, or alpha blocker

Incidence of new coronary events lowest in those on beta blockers and ACE I

Which agent?

ALLHAT…

– RCT of 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

Treatment

Triad: Age, HTN and DM

More aggressive treatment of CV risk factors– Dyslipidemia– HTN– Smoking reduction

Age as the new “CV” equivalent

Treatment goal: reduction of CV events

Summary: Which Antihypertensive?

First Line: Thiazide type diuretics

Second line agents: ACE inhibitors or ARB agents

Long acting calcium channel blockers

Beta blockers in those with CAD or other indications

Not alpha blockers or ca channel blockers in those with prior MI/ ACS

Need to individualize treatment!

Quality of Life

Studies demonstrate no significant impact with treatment

ACE inhibitors/ARBs have better profile

CCBs well tolerated

Sexual dysfunction most commonly reported with thiazides

Nonselective Beta blockers reported to have some subjective negative effects on cognition and mood

Higher risk of Postural hypotension (30%)

The Pulse Pressure: Risk Factor or Marker?

Wide pulse pressure (over 50) may be better marker for cerebrovascular disease and CHF than mean or DBP in older patients

?Causal or Marker for bad outcomes

Likely due to poor arterial compliance…

The Pulse Pressure…

Trials: those who had CV event on treatment were more likely to have lower DBP and higher pulse pressure (DBP < 68 and PP >50)

Concern: Is “overtreatment” risky?

BUT: the risk of events in patients with lower DBP on treatment was still less than that in the placebo group!

AND: Lower DBP and Higher PP likely more of a MARKER for bad outcomes…

Controversial Groups to Treat…

Stage I (SBP 140-159)– Observational data supports that this group is still at higher

risk of bad things…– Not clear that treatment reduces bad outcomes…– Consideration of other RFs (DM, CAD)

Oldest Old (over age 85)– Possibly higher risk of side effects, BUT– Group at highest ABSOLUTE RISK of CV event– Evidence suggests that patients in this age group actually

had GREATER absolute benefit with reduction in outcomes compared to younger groups

SUMMARY

SH is not benign and carries increased risk of stroke, CHF, and CV events

SH and pulse pressure more important risk factors for CVA and CVD in this group

Even “mild” SH carries increased risk SH is a risk factor for all cause dementia Treatment of SH is well tolerated and associated with

reduction in stroke, CHF, CV events, dementia Patients over 85 have greatest risk of CVA and CV

disease and stand to gain most Lower DBP and higher PP with treatment likely marker

and not cause of higher risk Thiazide diuretics = first line Other agents: ACEI, ARBs, CCBs