Treatment Of The Elderly: Is There Anything New?

Joel Handler, MD

Clinical Hypertension Leader

Care Management Institute

Kaiser Permanente

Prevalence of High BP in Americans Aged 20 Years and Older by Age and Gender (NHANES IV: 1999-2000)

Does elderly hypertension have specific characteristics?

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; 5:12

18-29 30-39 40-49 50-59 60-69 70-79 80+0

70

80

110

130

150

18-29 30-39 40-49 50-59 60-69 70-79 80+0

70

80

110

130

150

0

70

80

110

130

150

0

70

80

110

130

150D

BP

(mm

Hg

)S

BP

(mm

Hg

)D

BP

(mm

Hg

)S

BP

(mm

Hg

)

DB

P(m

m H

g)

SB

P(m

m H

g)

DB

P(m

m H

g)

SB

P(m

m H

g)

Men, Age (y) Women, Age (y)

Non-Hispanic BlackNon-Hispanic WhiteMexican American

Pulse pressure Pulse pressure

Mean Systolic and Diastolic BP by Age and Race/Ethnicity for Men and Women (US Population ³Age 18 Years, NHANES III)

Burt VI, et al. Hypertension. 1995;25:305-313.

Control to SBP goal, DBP goal, or both by age group among 1189 treated subjects with hypertension. Open columns represent subjects ≤60 years old (n=295); gray bars, subjects 61 to 75 years old (n=533); filled columns, subjects >75 years old (n=361).

100

80

60

40

20

0

Lloyd-James et al. Hypertens 2000; 36:594-599.

p<0.003

p<0.001

SBP Goal DBP Goal SBP & DBP Goal

p<0.001

Age ≤60 Age 61-75 Age >75

Lloyd-James et al. Hypertens 2000; 36:594-599

Bentley Dw, Izzo JL. J Am Geriatr Soc. 1982; 30:352-359.

Stroke Volume

Aorta

Resistance Arterioles

Pressure (Flow)

Young Artery

Systole Diastole

Elastic Vessel

Arteriosclerotic Artery

Stiff Vessel

Systole Diastole

Arterial Wall Compliance and Pulse Pressure Wave

Systolic Pressure

Diastolic Pressure (P3)

Time

PulsePressure

Systolic Pressure

Diastolic Pressure (P3)

Time

PulsePressure P2

Augmentation Pressure

A representative central arterial waveform with pulse pressure indicated.

Systolic Pressure (P1)

Diastolic Pressure (P3)

P2

Time

PulsePressure

Augmentation Pressure

A representative central arterial waveform with pulse pressure indicated.

50

40

30

20

10

0

-10

-20

-30

-40

-50

Basal supine systolicblood pressure (mm Hg)

Clin Sci 1985;69:337-341

Relationship between basal supine systolic blood pressure and posturalchange in systolic blood pressure for aggregate data from older subjects.

Pos

tura

l cha

nge

in s

ysto

licbl

ood

pre

ssu

re (

mm

Hg)

Clin Sci 1985;69:337-341

“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.

Cer

ebra

l Blo

od f

low

P

erce

nt

of C

ontr

ol

Autoregulation of cerebral blood flood

mmHg

Mean Arterial Blood Pressure

Cerebral Blood flowPercent of Control

Normotensive Patients

Treated Hypertensive Paitents

Hypertensive Patients

100

50

050 100 150 200

Strandgaard et al. Lanset 1987; 2:658-661

What are the measurement issues?

Nighttime24-hourDaytimeConventional

Systolic Blood Pressure, mm Hg

0.20

0.18

0.12

0.08

0.04

0.00

11090 130 150 170 190 210 210

Systolic blood pressure on conventional, 24-hour, daytime, and nighttime measurement at entry as predictors of the 2-year incidence of cardiovascular end points in the placebo group

Staessen et al. JAMA 1999; 282:544

2-y

ea

r In

cid

en

ce o

f C

ard

iova

scu

lar

En

d P

oin

ts

Staessen et al. JAMA 1999; 282:544

Num

ber

of

Str

okes

pe

r 10

0 P

atie

nt

Yea

rs

Fagard et al. Circulation 2000; 102:1139-1144

P=0.16

(2)

(0)

(6) (6)

(12)

(3)

P=0.03

MiSHNonSH MoSH

P=0.8640

20

0

DBP Cutoff, mm Hg

80 75 70 65 60 55 50 45 40 35 30 25

10

9

8

7

6

5

4

3

2

1

0

Somes GW et al. Arch Intern Med 1999; 2004-2009

Re

lativ

e R

isk

Adjusted estimated relative risk for cardiovascular disease by diastolic blood pressure (DBP) goal cutoff categories.

Relative Risk 95% Confidence Interval

p (trend) <.001

DBP cutoff, mm Hg

Somes GW et al. Arch Intern Med 1999; 2004-2009

200

140

160

120

180

20

40

60

80

100

0

A softer blowing sound

A sharp thump

A softer thump

A blowing or whooshing sound

K1

K2

K3

K4

K5

Osler’s 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

Do lifestyle measures really work for elderly hypertension?

ModificationApproximate 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

2–4 mmHg

Lifestyle ModificationsLifestyle Modifications

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.

42

0

-2-4

-6

-8-10

-12

-14

-16-18

-20 20-30 31-40 41-50

AGE [yrs]

Weinberger M. Hypertens 1991; 18:69

51-60 >60

Cha

nge

in M

ean

Art

eria

l Blo

od P

ress

ure

Weinberger M. Hypertens 1991; 18:69

Effect of 30 minute walk 3 days a weekAge 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

100

90

80

70

60

50

40

30

20

10

0

0 6

85.7%

71.4%

58.1%

52.1%50.0%

43.6%

16.3%

23.9%29.0%

32.0%

39.5%

70.1%

12 18 24 30

Time after Withdrawal, mo

Hazard Ratios Relative to Usual Care Sodium Reduction and Weight Loss: 0.47 (95% CI, 0.35-0.64), P<.001 Sodium Reduction: 0.60 (95% CI, 0.45-0.80), P<.001

Weight Loss: 0.64 (95% CI, 0.49-0.85, P=.002

Sodium Reduction and Weight Loss (n=147 )Sodium Reduction (n=144)Weight Loss (n=147)Usual Care (n=147)

TONE Study. JAMA 1998;279:844

Fre

e E

nd o

f P

oint

, %

Time after Withdrawal, mo

TONE Study. JAMA 1998;279:844

What is the effect of drug therapy related to age? Are the

recommendations different?

5 Year NNTs (Number Necessary to Treat)

Age <60 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; 272:1932-1938

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)

Prisant, Moser M. Arch Int Med 2000; 160:284

Major Clinical Trials Showing Benefit of Treating Isolated Systolic Hypertension

SHEP Syst-Eur Syst-China(n=4736) (n=4695) (n=2394)

Baseline 160-219/ 160-219/ 160-219/

SBP/DBP (mm Hg) <90 <95 <95

BP reduction: 27/9 23/7 20/5

SBP/DBP (mm Hg)

Drug therapy Chlorthalidone Nitrendipine NitrendipineAtenolol Enalapril Captopril

HCTZ HCTZ

Outcomes (%)

Stroke 33 42 38

CAD 27 30 27

CHF 55 29 —

All CVR disease 32 31 25

Journal of Clinical Hypertension Vol II, No. 5, page 336, September/October 2000.

SHEP stroke subset analysis

Ischemic Hemorrhagic Lacunar Atherosclerotic Embolicn = 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; 29:1333-1340

Comparative Drug Studies: Elderly Hypertension

NIC-E : Nicardipine = thiazide

SHELL : Lacidipine = thiazide

STOP-2 : CCB, ACEI = thiazide, BB

So, why aren’t we doing a better job?

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; 46:273-279

HDFP 5 Year Incidence ADR’s

Age ADR’s/100/5 Years

30 – 39 34.1

40 – 49 36.8

50 – 59 38.0

60 – 69 29.1

Barriers to Optimal Control of Hypertension

Inaccurate 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; 8:524

Prevalence of Renal Arterial Lesions in Normotensive and Hypertensive Patients

Age, Normotensive HypertensiveYears Normal Lesion Normal Lesion

31-40 7 3 6 10

41-50 26 8 14 22

51-60 99 35 28 50

60+ 69 56 15 48

Eyler WR, Clark MD, Garman JE, et al. Radiology 1962; 78:879-892.

What is the systolic blood pressure goal?

Blood Pressure in SHEP and Syst-Eur (mm Hg)

SHEP Syst-Eur

Entry 160-219/<90 160-219/<95

Goal (SBP) <160 + ≥20 <150 + ≥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.

IHDmortality(floating

absolute risk and 95% CI)

Usual SBP (mm Hg)

IHD, ischemic heart disease.Prospective Studies Collaboration. Lancet. 2002;360:1903-1913.

Ischemic Heart Disease Mortality Rate in Each Decade of Age

120 140 160 180

256

128

64

32

16

8

4

2

1

SBP

40-49 y

Age at risk:

70-79 y

60-69 y

50-59 y

80-89 y

Usual DBP (mm Hg)70 80 90 110100

256

128

64

32

16

8

4

2

1

DBP

What have we learned from ALLHAT?

Years to CHD Event0 1 2 3 4 5 6 7

Cumulative CHD Event Rate

0

.04

.08

.12

.16

.2

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

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

ALLHAT

ChlorthalidoneAmlodipineLisinopril

Nonfatal MI + CHD Death – Subgroup Comparisons – RR (95% CI)ALLHAT

Amlodipine Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 0.97 (0.86, 1.09)

Diabetic 0.99 (0.87, 1.13)

Non-Black 0.97 (0.87, 1.08)

Black 1.01 (0.86, 1.18)

Women 0.99 (0.85, 1.15)

Men 0.98 (0.87, 1.09)

Age>=65 0.97 (0.88, 1.08)

Age <65 0.99 (0.85, 1.16)

Total 0.98 (0.90, 1.07)

Lisinopril Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 0.99 (0.88, 1.11)

Diabetic 1.00 (0.87, 1.14)

Non-Black 0.94 (0.85, 1.05)

Black 1.10 (0.94, 1.28)

Women 1.06 (0.92, 1.23)

Men 0.94 (0.85, 1.05)

Age >= 65 1.01 (0.91, 1.12)

Age < 65 0.95 (0.81, 1.12)

Total 0.99 (0.91, 1.08)

Cumulative CHF Rate

Years to HF0 1 2 3 4 5 6 7

0

.03

.06

.09

.12

.15

Cumulative Event Rates for Heart Failure by ALLHAT Treatment Group

RR (95% CI) p value

A/C 1.38 (1.25-1.52) <.001

L/C 1.19 (1.07-1.31) <.001

ALLHAT

ChlorthalidoneAmlodipineLisinopril

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

Heart Failure – Subgroup Comparisons – RR (95% CI)ALLHAT

Amlodipine Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 1.33 (1.16, 1.52)

Diabetic 1.42 (1.23, 1.64)

Non-Black 1.33 (1.18, 1.51)

Black 1.47 (1.24, 1.74)

Women 1.33 (1.14, 1.55)

Men 1.41 (1.24, 1.61)

Age >= 65 1.33 (1.18, 1.49)

Age < 65 1.51 (1.25, 1.82)

Total 1.38 (1.25, 1.52)

Lisinopril Better Chlorthalidone Better

0.50 1 2

Non-Diabetic 1.20 (1.04, 1.38)

Diabetic 1.22 (1.05, 1.42)

Non-Black 1.15 (1.01, 1.30)

Black 1.32 (1.11, 1.58)

Women 1.23 (1.05, 1.43)

Men 1.19 (1.03, 1.36)

Age >= 65 1.20 (1.06, 1.35)

Age < 65 1.23 (1.01, 1.50)

Total 1.20 (1.09, 1.34)

Thiazide Myths

• Sulfa cross reactivity

• Gout

• Renal stones

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

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 2003;349:1628-35); 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)

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