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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