Treatment of Hypertension in the Elderly: A Major Challenge

1
Treatment of Hypertension in the Elderly A Major
Challenge

• Thomas G Pickering MD, D Phil
• Behavioral Cardiovascular Health and Hypertension
  Program
• Columbia Presbyterian Hospital

2
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

3
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

4
Continuous Relation Between Blood Pressure And
Risk Of CVD
Stroke CHD
4
4
2
2
Relative Risk
1
1
0.5
0.5
0.25
0.25
76
105
98
91
84
105
98
91
84
76
Usual Diastolic Pressure (mm Hg)
MacMahon et al. Lancet. 1990335765.
5
Change Of Blood Pressure With Age (NHANES - Black
Women)
Blood Pressure (mm Hg)
Age
6
Stiffer Arteries Increase Pulse Wave Velocity And
Pulse Pressure
Average Blood Pressure Waveform
Average Blood Pressure Waveform
Shoulder
Notch
Notch
Time (sec)
Time (sec)
52-year-Old Normal Pressure Wave
81-year-Old Early Pulse Wave Reflection
7
Pulse Pressure Predicts Risk Best In Older
HypertensivesA Meta-Analysis
EWPHE (N840) Syst-Eur (N4695) Syst-China
(N2394)
Diastolic Pressure (mm Hg)
2-Year Risk Of End Point
Systolic Blood Pressure (mm Hg)
Blacher et al. Arch Intern Med. 2000160.
8
Ambulatory BP and Cardiovascular Disease in the
Elderly with Systolic Hypertension The Syst-Eur
Study (N 808)
Placebo
Active treatment
Cardiovascular disease (per 1000 patient - year)
Staessen et al. JAMA 1999 282 539-46.
9
Consequences of Treating White Coat Hypertension
(Syst-Eur study)(Fagard et al, Circ 2000 102
1139)
Placebo
Active
Change of Clinic SBP mmHg
White coat HTN
Mild HTN
Moderate HTN
10
Consequences of Treating White Coat Hypertension
(Syst-Eur study)(Fagard et al, Circ 2000 102
1139)
Placebo
Active
Change of Daytime SBP mmHg
White coat HTN
Mild HTN
Moderate HTN
11
Consequences of Treating White Coat Hypertension
(Syst-Eur study)(Fagard et al, Circ 2000 102
1139)
Rate of strokes per1000 pt-years
Plt0.03
PNS
PNS
White coat HTN
Mild HTN
Moderate HTN
12
http//www.hcfa.gov/coverage/8b3-ff.htm
13
The White Coat Effect in the Real World(Little
et al, BMJ 2002 325 254)

• 173 hypertensive patients in 3 general practices
  in the UK
• Clinic (MD and RN), self-monitoring, and ABPM
• White coat effect estimated as difference
  between other measures of BP and daytime BP-
• Physician 19/11 mmHg
• Nurse 1 5/8 mmHg
• Nurse 2 5/6 mmHg
• Self-monitoring in clinic 10/13 mmHg
• Self-monitoring at home 5/6 mmHg

14
JNC 7 Self-Measurement of BP

• Provides information on
• Response to antihypertensive therapy
• Improving adherence with therapy
• Evaluating white-coat HTN
• Home measurement of gt135/85 mmHg is generally
  considered to be hypertensive.
• Home measurement devices should be checked
  regularly.

15
Analysis of The Influence of the Morning Surge of
BP on Stroke Incidence (Kario, Pickering et al)
16
Analysis of The Influence of the Morning Surge of
BP on Stroke Incidence (Kario,
Pickering et al)

• Cox regression analysis for clinical stroke
  events
• Covariates RR P value
• Age (10 yrs) 1.80 (1.21-2.69) 0.004
• Male gender 1.42 (0.76-2.67) 0.266
• BMI 0.98 (0.90-1.07) 0.663
• 24 hr SBP 1.37 (1.16-1.63 0.003
• SCI 4.40 (1.95-10.1) 0.001
• Morning BP surge 1.29 (1.10-1.51) 0.001
• Nocturnal BP fall 0.88 (0.73-1.06) 0.167
• Lowest sleep BP 1.05 (0.65-1.71) 0.837
• per 10 mmHg

17
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

18

JNC 7 New Features and Key Messages

• For persons over age 50, SBP is a more important
  than DBP as CVD risk factor.
• Starting at 115/75 mmHg, CVD risk doubles with
  each increment of
• 20/10 mmHg throughout the BP range.
• Persons who are normotensive at age 55 have a 90
  lifetime risk for developing HTN.
• Those with SBP 120139 mmHg or DBP 8089 mmHg
  should be considered prehypertensive who require
  health-promoting lifestyle modifications to
  prevent CVD.

19

JNC 7 New Features and Key Messages

• For persons over age 50, SBP is a more important
  than DBP as CVD risk factor.
• Starting at 115/75 mmHg, CVD risk doubles with
  each increment of
• 20/10 mmHg throughout the BP range.
• Persons who are normotensive at age 55 have a 90
  lifetime risk for developing HTN.
• Those with SBP 120139 mmHg or DBP 8089 mmHg
  should be considered prehypertensive who require
  health-promoting lifestyle modifications to
  prevent CVD.

20
JNC 7 New Features and Key Messages (Continued)

• Thiazide-type diuretics should be initial drug
  therapy for most, either alone or combined with
  other drug classes.
• Certain high-risk conditions are compelling
  indications for other drug classes.
• Most patients will require two or more
  antihypertensive drugs to achieve goal BP.
• If BP is gt20/10 mmHg above goal, initiate therapy
  with two agents, one usually should be a
  thiazide-type diuretic.

21
JNC 7 New Features and Key Messages (Continued)

• Thiazide-type diuretics should be initial drug
  therapy for most, either alone or combined with
  other drug classes.
• Certain high-risk conditions are compelling
  indications for other drug classes.
• Most patients will require two or more
  antihypertensive drugs to achieve goal BP.
• If BP is gt20/10 mmHg above goal, initiate therapy
  with two agents, one usually should be a
  thiazide-type diuretic.

22
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

23
BP Control Rates
Trends in awareness, treatment, and control of
high blood pressure in adults ages 1874
Sources Unpublished data for 19992000
computed by M. Wolz, National Heart, Lung, and
Blood Institute JNC 6.
24
Characteristics of Patients with Uncontrolled
Hypertension in the US NHANES (Hyman et al,
NEJM 2001 345 479)

• Predictors of Uncontrolled Hypertension
• HTN Undiagnosed HTN Diagnosed
• Factor Rel Risk Attrib Risk Rel
  Risk Attrib Risk
• Age gt65 7.69 0.46
  2.08 0.32
• Male sex 1.58 0.22
  1.30 0.12
• Black race 1.45 0.05
  - -
• MD visits 1.40 0.09
  1.89 0.08

25
How far should BP be lowered in the elderly?

• Trial Starting BP Final BP
• HOT 170 140-144
• EWPHE 183 149
• SHEP 170 144
• Syst-Eur 174 151

Conclude No evidence to support lowering BP
tolt140 mmHg
26
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

27
Trends in Antihypertensive Drug Use(Kaplan 2003)
Diuretics
No. of prescriptions (millions)
CCBs
Beta blockers
ARBs
ACEI
Alpha blockers
Year
28
Limited Efficacy of Monotherapy in Treating
Hypertension (Materson NEJM 1993 328 914)
Patients Responding
29
Major Outcomes in High Risk Hypertensive Patients
Randomized to Angiotensin-Converting Enzyme
Inhibitor or Calcium Channel Blocker vs Diuretic

• The Antihypertensive and Lipid-Lowering Treatment
  to Prevent Heart Attack Trial (ALLHAT)

The ALLHAT Collaborative Research Group Sponsored
by the National Heart, Lung, and Blood Institute
(NHLBI)
JAMA. 20022882981-2997
30
BP Results by Treatment Group
31
Cumulative Event Rates for the Primary Outcome
(Fatal CHD or Nonfatal MI) by ALLHAT Treatment
Group
Chlorthalidone Amlodipine Lisinopril
32
Cumulative Event Rates for Stroke by ALLHAT
Treatment Group
Chlorthalidone Amlodipine Lisinopril
33
Overall Conclusions
Because of the superiority of thiazide-type
diuretics in preventing one or more major forms
of CVD and their lower cost, they should be the
drugs of choice for first-step antihypertensive
drug therapy.
34
ANBP2 Australian Trial of ACEI vs Diuretics in
the Elderly (Wing et al
NEJM, 2003 348 583)

• Subjects were 6083 hypertensives aged 65-84 , BP
  gt160/90 mmHg
• Randomized to ACEI (Enalapril) or Diuretic
  (HCTZ)
• Significant 11 (just) reduction in combined CV
  events for ACEI group (17 in men, 0 in women)
• Blood Pressures were identical for the two
  groups throughout the study

35
Comparison of ALLHAT and ANBP2

• Study Conclusions
• ALLHAT- Diuretics Better than ACEI
• ANBP2- ACEI better than Diuretics
• Can they be reconciled?
• Other studies show that ACEI prevent heart
  failure
• Higher incidence of heart failure in ALLHAT ACEI
  group occurred early, and may have been due to
  diuretic withdrawal
• Higher incidence of stroke in ALLHAT ACEI group
  may have been due to higher BP
• Higher percentage of blacks in ALLHAT- blacks
  did better with stroke, coronary endpoints, and
  heart failure In D than in ACEI group

36
PROGRESS PATS Effects of Diuretics and ACEI
on Recurrent Stroke (Messerli et al, Arch Int Med
163 2557, 2003)
PROGRESS PATS PROGRESS
Perindopril
Indapamide Both
Reduction of SBP or stroke
37
LIFE Reduction of stroke but not MI with
Losartan in Isolated Systolic Hypertension(Kjelds
en et al JAMA 2002 288 1491)
38
Effects of Diuretics and Beta Blockers on
Cardiovascular Mortality (JNC VI)
Drug Dose No. RR (95 CI)
Diuretics High 11 0.78
(0.62-0.97) Diuretics Low 4 0.76
(0.65-0.89) Beta blockers 4 0.89
(0.76-1.05)
0.4 0.7 1.0
RR (95 CI)
Treatment Treatment Better Worse
39
Prevention of Dementia with Calcium Channel
Blocker Treatment in ISH- Syst-Eur (Forette et
al, Arch Int Med 2002 162 2046)
40
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

41
Hypertension in the Very Old(Bulpitt J Hum Hyp
1994 8603)
Four Reasons why Hypertension may be Different
in the Elderly

• They are survivors
• Many have taken years to become hypertensive
• Some have atheromatous renal artery stenosis
• Diastolic pressure falls in the elderly

42
BP and Survival in the Very Old(Mattila et al,
BMJ 1988296 887)
561 Finns aged 84-102 (mean 88)
Systolic Pressure mmHg
5 year survival
Diastolic Pressure mmHg
43
Hypertension in the Very Elderly Trial (HYVET)

• 2100 hypertensives aged gt80 randomised to No
  treatment, ACEI, or diuretic
• 5 year F/U
• Endpoint is a 40 reduction in stroke

44
HYVET Results of Pilot Study
(Bulpitt et al, J Hypertens 2003 21 2409)

• 1283 hypertensive patients aged gt80 randomized
  to Diuretic, ACEI, or no treatment
• Target BP lt150/80 follow-up 13 months
• Results
• Total mortality no effect
• CV mortality no effect
• Stroke events Diuretics RR 0.313, plt0.01
• ACEI RR 0.629, p 0.21

45
Treating older adults Updates and Practical
Approaches

• Risks associated with high BP
• JNC 7 Guidelines
• Goals of treatment
• Choice of drugs
• Hypertension in the very old
• Non-drug treatment

46
JNC 7 Lifestyle Modification
47
Lifestyle Modification PREMIER(JAMA 2003 289
2083)
Baseline 3 mo
6 mo
48
Conclusions Hypertension in the Elderly

• An increasing problem with the ageing of the US
  population
• Related to increased stiffness of arteries
• Importance of white coat HTN, and out-of-office
  monitoring
• Diuretics drugs of choice, with addition of
  others- emphasis on combination Rx
• BP control is more important than drugs used
• Include lifestyle modifications
• Benefits of treatment in very old (gt85) are
  unproven, but diuretics may be protective