Treatment Of The Elderly: Is There Anything New?

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Treatment Of The Elderly Is There Anything New?

• Joel Handler, MD

Clinical Hypertension Leader Care Management
Institute Kaiser Permanente
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Prevalence of High BP in Americans Aged 20 Years
and Older by Age and Gender (NHANES IV 1999-2000)
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Does elderly hypertension have specific
characteristics?
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Characteristics of Hypertension in the
Elderly Increased Systolic blood pressure
and pulse pressure Left ventricular mass and
wall thickness Arterial stiffness
Calculated total peripheral resistance Decreased
Cardiac output and heart rate Renal
blood flow, plasma renin activity, and
angiotensin II levels Arterial compliance
and blood volume Diastolic blood
pressure Black H. JCH 2003 512
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Mean Systolic and Diastolic BP by Age and
Race/Ethnicity for Men and Women (US Population
³Age 18 Years, NHANES III)
Pulse pressure
Pulse pressure
Men, Age (y)
Women, Age (y)
Burt VI, et al. Hypertension. 199525305-313.
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Age 60
Age 61-75
Age gt75
Control to SBP goal, DBP goal, or both by age
group among 1189 treated subjects with
hypertension. Open columns represent subjects 60
years old (n295) gray bars, subjects 61 to
75 years old (n533) filled columns, subjects
gt75 years old (n361).
Lloyd-James et al. Hypertens 2000 36594-599
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Arterial Wall Compliance and Pulse Pressure Wave
Elastic Vessel
Stiff Vessel
Systole
Diastole
Systole
Diastole
Stroke Volume
Aorta
Resistance Arterioles
Pressure (Flow)
Young Artery
Arteriosclerotic Artery
Bentley Dw, Izzo JL. J Am Geriatr Soc. 1982
30352-359.
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Postural change in systolic blood pressure (mm Hg)
Relationship between basal supine systolic blood
pressure and postural change in systolic blood
pressure for aggregate data from older subjects.
Clin Sci 198569337-341
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If the standing blood pressure is consistently
much lower than the sitting blood pressure, the
standing blood pressure should be used to titrate
drug dosages during treatment. National High
Blood Pressure Education Program Working Group
Report on Hypertension in the Elderly.
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Cerebral Blood flow Percent of Control
Strandgaard et al. Lanset 1987 2658-661
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What are the measurement issues?
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2-year Incidence of Cardiovascular End Points
Staessen et al. JAMA 1999 282544
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Number of Strokes per 100 Patient Years
Fagard et al. Circulation 2000 1021139-1144
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Adjusted estimated relative risk for
cardiovascular disease by diastolic blood
pressure (DBP) goal cutoff categories.
Relative Risk 95
Confidence Interval p (trend) lt.001
Relative Risk
DBP cutoff, mm Hg
Somes GW et al. Arch Intern Med 1999 2004-2009
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200
180
160
140
K1
A sharp thump
K2
120
A blowing or whooshing sound
K3
100
A softer thump
K4
80
A softer blowing sound
60
40
20
0
K5
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Oslers Maneuver

• Palpable sclerotic radial artery above systolic
  level pseudohypertension?
• Prevalence 7.2 in 3387 SHEP patients
• More frequent self report of stroke
• Significant intra-observer variability
• Intra-arterial BP variability

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Do lifestyle measures really work for elderly
hypertension?
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Lifestyle Modifications
Modification Approximate SBP Reduction (range)
Weight Reduction 5-10 mmHg/10kg
Adopt DASH eating plan 8-14 mmHg
Dietary sodium reduction 2-8 mmHg
Physical activity 4-9 mmHg
Moderation of alcohol consumption 24 mmHg
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Change in Mean Arterial Blood Pressure
Bar graph shows change in mean arterial blood
pressure used to define salt responsivity as a
function of age in normotensive open bars and
hypertensive color bars subjects.
Weinberger M. Hypertens 1991 1869
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Effect of 30 minute walk 3 days a week Age 70 -
79 Systolic Diastolic Exercise Group
Baseline 156 10 mm Hg 86 8 mm Hg 3
months 151 15 mm Hg 80 6 mm Hg Control
Group Baseline 153 7 mm Hg 85 8 mm
Hg 3 months 156 10 mm Hg 85 6 mm
Hg Conone et al. Med Scl in Sports and
Exercise. 1991
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Free End of Point,
Time after Withdrawal, mo
TONE Study. JAMA 1998279844
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What is the effect of drug therapy related to
age? Are the recommendations different?
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5 Year NNTs (Number Necessary to Treat) Age
lt60 Age 60 12 trials, n 33,000 13 trials, n
16,564 Stroke NNT 168 Stroke NNT 43 CHD event
NNT 184 CHD event NNT 61 Stroke, CHD NNT n.
a. Stroke, CHD NNT 18 CV mortality NNT 205
CV mortality NNT 52 Mulrow et al. JAMA
1994 2721932-1938
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Trials Examining Treatment of Hypertension in the
Elderly EWPHE MRC-Elderly SHEP STOP-H Syst-China
Syst-Eur (N 840) (N 4396) (N 4736) (N
1627) (N 2394) (N 4695) Stroke reduction,
-36 -25 -33 -47 -38 -42 CAD change,
-20 -19 -27 -13 6 -26 CHF reduction, -22 Not
stated -55 -51 -58 -27 of Patients
receiving 35 52 (b-blocker) 44 67 11-26 26-36
combination drug therapy 38 (diuretic) Pris
ant, Moser M. Arch Int Med 2000 160284
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Major Clinical Trials Showing Benefit of Treating
Isolated Systolic Hypertension SHEP Syst-Eur Sys
t-China (n4736) (n4695) (n2394) Baseline 160-
219/ 160-219/ 160-219/ SBP/DBP (mm Hg)
lt90 lt95 lt95 BP reduction 27/9 23/7 20/5 SBP/DBP
(mm Hg) Drug therapy Chlorthalidone Nitrendipine
Nitrendipine Atenolol Enalapril Captopril HCTZ
HCTZ Outcomes () Stroke 33 42 38 CAD 27 30 27 C
HF 55 29 All CVR disease 32 31 25 Journal of
Clinical Hypertension Vol II, No. 5, page 336,
September/October 2000.
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SHEP stroke subset analysis Ischemic Hemorrhagic
Lacunar Atherosclerotic Embolic n 217 n 28 n
66 n 26 n 25 0.63 0.47 0.53
0.99 0.55 (0.??-0.83) (0.21-1.04) (0.32-0.88)
(0.46-2.31) (0.24-1.25)
Davis BR et al. Stroke 1998 291333-1340
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Comparative Drug Studies Elderly
Hypertension NIC-E Nicardipine
thiazide SHELL Lacidipine thiazide
STOP-2 CCB, ACEI thiazide, BB
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So, why arent we doing a better job?
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Independent Predictors of Using Antihypertensives
Medications in 2000 Variable Adjusted OR (95
CI) of Using Antihypertensives Comorbid
conditions Asthma/COPD 0.43 (0.40-0.47)
Depression 0.50 (0.45-0.55) GI
disorders 0.59 (0.54-0.64) Osteoarthritis 0.63
(0.59-0.67) Cardiovascular conditions
Coronary artery disease 1.31 (1.23-1.40)
Cerebrovascular disease 1.03 (.97-1.10)
Congestive heart failure 1.05 (0.99-1.11)
Diabetes 1.16 (1.10-1.22) Wang PS et al.
Hypertension 2005 46273-279
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HDFP 5 Year Incidence ADRs
Age ADRs/100/5 Years
30 39 34.1
40 49 36.8
50 59 38.0
60 69 29.1
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Barriers to Optimal Control of Hypertension Inacc
urate measurement of blood pressure (BP) Focusing
on diastolic BP rather than systolic BP
goal Failure to consider absolute global
risk Failure to advocate lifestyle
modifications Failure to use polypharmacy Failure
to use effective drug combinations Failure to
titrate doses upward Fear of reaching excessively
low diastolic BP The patient with truly resistant
hypertension Behavioral barriers Franklin S.
JCH 2006 8524
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Prevalence of Renal Arterial Lesions in
Normotensive and Hypertensive Patients Age, Normo
tensive Hypertensive Years Normal Lesion Normal Le
sion 31-40 7 3 6 10 41-50 26
8 14 22 51-60 99 35 28 50 60 69 56 15 48 Eyle
r WR, Clark MD, Garman JE, et al. Radiology
1962 78879-892.
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What is the systolic blood pressure goal?
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Blood Pressure in SHEP and Syst-Eur (mm
Hg) SHEP Syst-Eur Entry 160-219/lt90 160-219/lt95
Goal (SBP) lt160 20 ? lt150 20
? Baseline 170/77 174/86 Achieved
Rx 143/68 151/79 Achieved Placebo 155/72 161/84
Difference Rx-Placebo 12/4 10/5 Journal of
Clinical Hypertension, Vol II, No. 5, page 336.
March/April 2000.
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Ischemic Heart Disease Mortality Rate in Each
Decade of Age
SBP
DBP
Age at risk
256
256
80-89 y
128
128
70-79 y
64
64
60-69 y
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IHDmortality (floating absolute risk and 95 CI)
50-59 y
16
16
40-49 y
8
8
4
4
2
2
1
1
120
140
160
180
70
80
90
110
100
Usual SBP (mm Hg)
Usual DBP (mm Hg)
IHD, ischemic heart disease. Prospective Studies
Collaboration. Lancet. 20023601903-1913.
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What have we learned from ALLHAT?
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Cumulative Event Rates for the Primary Outcome
(Fatal CHD or Nonfatal MI) by ALLHAT Treatment
Group
RR (95 CI) p value
A/C 0.98 (0.90-1.07) 0.65
L/C 0.99 (0.91-1.08) 0.81
Chlorthalidone Amlodipine Lisinopril
Number at Risk

Chlorthalidone

15,255

14,477

13,820

13,102

11,362

6,340

2,956

209

Amlodipine

9,048

8,576

8,218

7,843

6,824

3,870

1,878

215

Lisinopril

9,054

8,535

8,123

7,711

6,662

3,832

1,770

195


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Nonfatal MI CHD Death Subgroup Comparisons
RR (95 CI)
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Cumulative Event Rates for Heart Failure by
ALLHAT Treatment Group
RR (95 CI) p value
A/C 1.38 (1.25-1.52) lt.001
L/C 1.19 (1.07-1.31) lt.001
Chlorthalidone Amlodipine Lisinopril
Number at risk

Chlor

15,255

14,528

13,898

13,224

11,511

6,369

3,016

384

Amlo

9,048

8,535

8,185

7,801

6,785

3,775

1,780

210

Lisin

9,054

8,496

8,096

7,689

6,698

3,789

1,837

313


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Heart Failure Subgroup Comparisons RR (95 CI)
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Thiazide Myths

• Sulfa cross reactivity
• Gout
• Renal stones

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Thiazide Related Gout

• Thiazide related hyperuricemia is dose related
• HDFP Trial 15 episodes of gout over 5 years in
  3693 patients treated with chlorthalidone
  25-100mg (equivalent to 50-200 mg HCTZ)
• Low dose thiazide (HCTZ 12.5-25 mg) is not
  contraindicated in gout

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Thiazide Myths Exposed

• Significant cross reactivity with sulfa
  antibiotics has not been demonstrated sulfa
  allergic patients have the same mildly increased
  reactivity to penicillin and thiazide (NEJM
  20033491628-35) thiazide can be administered
  to patients with sulfa allergy
• Thiazide is first line treatment for calcium
  kidney stones due to idiopathic hypercalciuria
  and also treats idiopathic calcium lithiasis
  avoid thiazide with hyperparathyroidism (raises
  serum Ca)

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Treatment Recommendations for the Elderly in JNC 7

• Recommendations are no different according to age
  for
• BP classification
• BP goals
• Lifestyle interventions
• Selection of medications