1. Hypertension and The Older Patient
Debra L. Bynum, MD
Assistant Professor
Division of Geriatric Medicine
University of North Carolina

2. 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

3. 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

4. Definition
Systolic Hypertension (“isolated” having falsely benign connotation)
JNC defines as SBP >140 with DBP <90
Stage I SH: SBP
7th report from JNC: SH in patients over 60 much more important than diastolic HTN and treatment should focus on control of SBP

5. 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

6. 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)

7. 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

8. 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

9. Risks…The DATA SHEP trial: 1991
5000 patients, SBP , 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%)

10. 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)

11. 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

12. 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

13. 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

14. 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!

15. 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

16. How To Treat…

17. Lifestyle Modifications
DASH (Dietary Approaches to Stop Hypertension)
Effective in decreasing SBP
?increased Na responsiveness in older patients
Small, subgroup analysis
TONE trial

18. 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”

19. 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…

20. 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

21. 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, 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

22. 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

23. 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

24. 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

25. 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!

26. 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%)

27. 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…

28. 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…

29. Controversial Groups to Treat…
Stage I (SBP )
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

30. 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