1. Hypertension in the Elderly
Debra L. Bynum, MD

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
Specific treatment groups:
Stage 1 SH
“Oldest old” : those over age 80

3. 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

4. Classification: JNC 7 Classification SBP DBP Normal <120 And <80
PreHypertension
Or 80-89
Stage 1 HTN
Or 90-99
Stage 2 HTN
>160
Or >100

5. Systolic Hypertension
Defined as SBP > 140 with DBP <90
No longer referred to as “Isolated”

6. How Common is Systolic Hypertension?

7. 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

8. PreHypertension
People over age 65: 26% four year risk of HTN if BP /80-84
Those over age 65 with BP /85-89: 50% four year risk of HTN
Patients with BP /85-89 have twice the risk of CVD events compared to those with normal BP

9. Why the emphasis on the Systolic number?

10. 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

11. 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

12. 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)

13. 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

14. 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

15. DATA
SHEP trial : 1991
5000 patients, SBP , 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%)

16. DATA : SHEP trial Reduction in Heart Failure 2.3% vs 4.4 % ARR 2%
NNT 48

17. 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)

18. 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

19. 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

20. 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)

21. Will treating hypertension prevent dementia?

22. 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

23. Next Question:
Are patients treated for hypertension less likely to develop cognitive impairment or dementia?

24. Prospective Cohort Studies
Honolulu-Asia Aging Study
3 year Utah study of 3000 patients
Swedish study of nearly 2000 patients (average age 82) 1992
African American cohort (1900 patients) 2002

25. 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

26. Final Question:
Will treatment of hypertension reduce the risk of developing cognitive impairment or dementia?

27. RCTs looking at hypertension and dementia
Syst-Eur Trial
SCOPE
SHEP
Progress
HYVET-COG

28. 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

29. 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 ( /90-99)

30. 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

31. 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%

32. 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)

33. 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

34. How to Treat…

35. Lifestyle Modifications
DASH (Dietary Approaches to Stop Hypertension)
Effective in decreasing SBP
?increased Na responsiveness in older patients

36. 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

37. Lifestyle Changes: summary
Evidence that weight loss and Na restriction can be effective for mild SH in older patients

38. 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

39. Which agent? Calcium channel blockers?
SHELL (SH in Elderly: Lacidipine Long Term Study)
CCB and thiazide equal

40. 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

41. 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

42. 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

43. 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

44. Specific Groups Stage 1 HTN Over 85 age group
Previously “controversial” treatment groups

45. 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

46. 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…

47. 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

48. 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

49. 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

50. 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

51. 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

52. 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.