Rudi WestendorpDept. of Gerontology and Geriatrics

• proper medical care for older people reflects in a continuous increase of life expectancy

• what to expect of cholesterol lowering ?

• how to treat hypertension in the elderly ?

agenda…..

development of life expectancy at birth

Science 2002;296:1029

life expectancy 1600-2000

Science 2002;296:1029

UN estimate 1980

UN estimate 1990

UN estimate 2000

the champions

Science 2002;296:1029

GDP driving life expectancy

calendar timecalendar timecalendar timecalendar time

mortality decline at all ages

japan

0

5

10

15

20

1950 1960 1970 1980 1990 2000

kalenderperiodest

erfte

per

jaar

(%)

calendar time

males

females

mor

talit

y (%

per

yea

r)

0

1

2

3

4

1950 1960 1970 1980 1990 2000

males

females

0

1

2

3

4

5

1950 1960 1970 1980 1990 2000

males

females

newborns age 60-64 age 80-84

differences in 1st world countries

OECD Health data 2004

stagnation of life expectancy

10

12

14

16

18

20

22

24

1950 1960 1970 1980 1990 2000 2010

calender time

life

exp

ecta

ncy

at

age

65

Netherlands Japan US

10

12

14

16

18

20

22

24

1950 1960 1970 1980 1990 2000 2010

calender time

femalesfemales malesmales

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mor

talit

y (1

980=

100%

)

1980-1984

1990-1994

1995-1999

2000-2004

Data source: http://www.mortality.org

period mortality in Japan

all causes (males and females)all causes (males and females)

period mortality in the US

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mor

talit

y (1

980=

100%

)

1980-1984

1990-1994

1995-1999

2000-2004

all causes (males and females)all causes (males and females)

Data source: http://www.mortality.org

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mor

talit

y (1

980=

100%

)

1980-1984

1990-1994

1995-1999

2000-2004

period mortality in the Netherlands

all causes (males and females)all causes (males and females)

Data source: http://www.mortality.org

guidelines

57 year; angina pectoris57 year; angina pectoris

Data source: Central Bureau of Statistics

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mo

rta

lity

(19

82

=1

00

%)

1982

2002

2006

period mortality in the Netherlands

ischaemic heart disease (males)ischaemic heart disease (males)

how are you doing ?

10

12

14

16

18

20

22

24

1950 1960 1970 1980 1990 2000 2010

calendar time

life

exp

ecta

ncy

at

age

65

Australia Japan New Zealand

femalesfemales

10

12

14

16

18

20

22

24

1950 1960 1970 1980 1990 2000 2010

calendar time

malesmales

period mortality in Australia

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mor

talit

y (1

980=

100%

)

1980-1984

1990-1994

1995-1999

2000-2004

all causes (males and females)all causes (males and females)

Data source: http://www.mortality.org

period mortality in New Zealand

0

20

40

60

80

100

120

40 50 60 70 80 90 100

age (years)

mor

talit

y (1

980=

100%

)

1980-1984

1990-1994

1995-1999

2000-2004

all causes (males and females)all causes (males and females)

Data source: http://www.mortality.org

• proper medical care for older people reflects in a continuous increase of life expectancy

• what to expect of cholesterol lowering ?

• how to treat hypertension in the elderly ?

agenda…..

85 86 87 88 89 90 years

observational studies

risk and LDL cholesterol

85 86 87 88 89

0.0

0.1

0.2

0.3

0.4

0.5

intermediate

high

low

p log rank = 0.16

LDL

age (years)

cum

ula

tive

mo

rtal

ity

for

card

iova

scu

lar

dis

ease

Arch Intern Med 2003; 163:1549

-1

-0,5

0

0,5

1

1,5

40 50 60 70 80

age in years

% c

han

ge

in m

ort

alit

y p

er 0

.026

mm

ol/

L

rise

in

ch

ole

ster

ol

*

*** NS

NS

Adapted from: R.A. Kronmal et al in Arch Intern Med 1993

Framingham study

LDL cholesterol, coronary heart disease and age

0.1

1

10

100

20 30 40 50 60 70 80

mean age at total cholesterol measurement

risk

of n

on-fa

tal o

r fat

al C

VD

From van Vliet et al. Exp Gerontol 2008

cholesterol, coronary heart disease and age

risk and HDL cholesterol

Arch Intern Med 2003; 163:1549

85 86 87 88 89

0.0

0.1

0.2

0.3

0.4

0.5

low

intermediate

high

p log rank = 0.006

HDL

age (years)

cum

ula

tive

mo

rtal

ity

for

card

iova

scu

lar

dis

ease

0.1

1

10

40 50 60 70 80 90

mean age at HDL measurement

risk

of n

on-fa

tal a

nd fa

tal C

VD

From van Vliet et al. Exp Gerontol 2008

HDL cholesterol, coronary heart disease and age

joined forces

LeidenLeidenCorkCork GlasgowGlasgow

Primary Endpoint:CHD Death, Nonfatal MI, Fatal or Nonfatal Stroke

· Total cholesterol 4–9 mmol/L· 50% at high risk of vascular disease· 50% with vascular disease· Good cognitive function

Double-blind, randomized placebo-controlled trial in: 5804 men (48%) and women (52%; 70-82 years)

Average Follow-up:3.2 years

Pravastatin 40 mg qd(N=2891)

Placebo(N=2913)

statins in old age

PROSPER study. Lancet 2002

PROSPER study. Lancet 2002

pravastatin and vascular risk

00

55

1010

1515

2020

00 11 22 33

PlaceboEvents = 473/2913 (16.2%)

PravastatinEvents = 408/2891 (14.1%)

15% RRR(P = 0.014)

% W

ith E

vent

NNT=48

Years

0.97

0.85

1.11

0.76

pravastatin betterpravastatin better placebo betterplacebo better1.01.00.750.750.50.5 1.51.51.251.25

vascular diseasevascular disease

coronary eventscoronary events

non-vascular non-vascular diseasedisease

mortalitymortality

PROSPER study. Lancet 2002

fatal events

0.1

1

10

60 65 70 75 80

mean age at statin use

risk

of c

ogni

tive

impa

irmen

t

Longitudinal studies

Cross-sectional studies

From van Vliet et al. Exp Gerontol 2008

statin use, cognitive impairment and age

-1.6

-1.2

-0.8

-0.4

0

0 12 24 36

-1

0

1

2

3

0 12 24 36

-0.4

-0.3

-0.2

-0.1

0

0 12 24 36

From: J Sheperd et al in Lancet 2002

pravastatin and cognitive function

pravastatinpravastatinplaceboplacebo

monthsmonths

monthsmonthsstroop test (attention)stroop test (attention)stroop test (attention)stroop test (attention)

LDT (executive function)LDT (executive function) WLT (memory)WLT (memory)ch

ange

(num

bers

)ch

ange

(num

bers

)ch

ange

(sec

onds

)ch

ange

(sec

onds

)

chan

ge (w

ords

)ch

ange

(wor

ds)

• proper medical care for older people reflects in a continuous increase of life expectancy

• what to expect of cholesterol lowering ?

• how to treat hypertension in the elderly ?

agenda…..

Psaty et al. JAMA 1997Psaty et al. JAMA 1997

metanalysis of antihypertensive trialsin middle age

systolische bloodpressure

85 86 87 88 89 90 91 92

age (years)

0,0

0,2

0,4

0,6

0,8

cum

ulat

ive m

orta

lity (a

ll cau

ses)

< 140 mmHg>= 140 mmHg <160 mmHg >= 160 mmHg

systolic blood pressure

log rank p<0.001

blood pressure and survival

J Hypertension. 2006;24:287

blood pressure and survival

J Hypertension. 2006;24:287

diastolic blood pressure

85 86 87 88 89 90 91 92

age (years)

0,0

0,2

0,4

0,6

0,8

<70 mmHg>= 90 mmHg>=70 mmHg <90 mmHg

log rank p<0.001

cum

ulat

ive m

orta

lity (a

ll cau

ses)

imminent heart failure

P<0.05P<0.05

mean systolic blood pressure (mmHg)

200180160140120

Stro

ke V

olum

e In

dex

(ml/m

in/m

2)

60

50

40

30

20

10

P<0.05P<0.05

Van bemmel et al. J Hypertension 2008

reflex tachycardia

20 30 40 50

Stroke Volume Index (ml/m2)

40

50

60

70

80

90

100

110

hear

t rat

e (b

eats

/min

)

P<0.001P<0.001

Van bemmel et al. J Hypertension 2008

systolic function is conserved (HFPEF)

P<0.05P<0.05

mean systolic blood pressure (mmHg)220200180160140120

Left

Vent

ricul

ar E

ject

ion

Frac

tion

(%)

90

80

70

60

50

40

30

Van bemmel et al. J Hypertension 2008

-1,38

-1,63

-1,21 -1,26

-2

-1,5

-1

-0,5

0

0,5

Categories of diastolic blood pressure

Cre

atin

ine

clea

ran

ce (

ml/

min

)

reference

P=0.01 P=0.03

P=0.32

≤ 70 70-79 80-89 ≥ 90 mmHg

n=135 n=219 n=148 n=48

bloodpressure and renal function

J Am Soc Nephrol. 2006;17:2561

HYpertension in theVery Elderly Trial

Hyvet. NEJM 2008;358:1887

HYpertension in theVery Elderly Trial

Hyvet. NEJM 2008;358:1887

1,00,0 0,2 0,4 0,6 0,8 1,2 1,4 1,6 1,8 2,0

Control betterTreatment better

Total mortality

Cardiovascular deaths

Major coronary events

Heart failure

Major cardiovascular events

RR 1.14; p 0.05

RR 1.11; p 0.42

RR 0.77; p 0.03

RR 0.85; p 0.45

RR 0.56; p 0.01

Treatment better Control better

Stroke RR 0.67; p 0.01

metanalysis of antihypertensive trials

Lancet 1999;353:993-6.

in old age

blood pressure in old age

organ damage

organ function

+_

140 / 90blood pressure (mmHg)

CBF

blood pressure (mmHg)

60 200

autoregulation of cerebral blood flow

HYVET cognition

Hyvet. Lancet Neurol NEJM 2008;7:683

cum

ulat

ive p

ropo

rtion

with

dem

entia

(%)

cum

ulat

ive p

ropo

rtion

with

dem

entia

(%)

follow-up (years)follow-up (years)

imaging of flow

scanplane

basilar artery

internal carotid arteries

vertebral arteries

coronal view sagittal view

J Magn Reson Imaging 2002;16:1

perfusion of the brain

0

100

200

300

400

500

600

700

800

900

1000

Young withoptimal cognition

Old withoptimal cognition

To

tal

Cer

ebra

l B

loo

d F

low

(m

l/m

in)

Old withdementia

J Magn Reson Imaging 2002;16:1

blood pressure and cognition later in life

betterworse betterworse

ERGO studyERGO study

age 65-74age 65-74

ERGO studyERGO study

age 75-84age 75-84

Leiden 85+ studyLeiden 85+ study

age 85age 85

unpublished

HYpertension in theVery Elderly Trial

Hyvet. NEJM 2008;358:1887

conclusions• a gain in average life expectancy lower than 2-3 a gain in average life expectancy lower than 2-3 year per decade suggests ‘old age’ problems year per decade suggests ‘old age’ problems

• cholesterol lowering in old age is good for the heart cholesterol lowering in old age is good for the heart but not for the brainbut not for the brain

• treatment of hypertension in the elderly needs treatment of hypertension in the elderly needs subtletysubtlety