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