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Total cholesterol andmortality risk
in the oldest old
A Weverling, GJ Blauw, AM Lagaay, DL Knook, E Meinders, RGJ Westendorp
Leiden, NL
Lancet 1997;350:1119-23
1
Leiden Study 85+
• All inhabitants aged 85 years & over
• Prospective population cohort
• Follow-up: 10 years (1987-1996)
• Specific mortality data
Lancet 1997;350:1119-23
2
Main CV risk factorsCollected during house visits
• Medical history (risk factors)• Smoking
• Diabetes
• Hypertension
• CV diseases
• Physical examination• Arterial blood pressure
• Blood tests• Total Cholesterol
Lancet 1997;350:1119-23
4
Methods: Analyses
• Risk facors• Cholesterol: three groups:
high = ≥ 6.5 mmol/L = > 260 mild = 5 - 6.4 mmol/L = 200-259 low = < 5 mmol/L = < 200
• Kaplan Meier curves • Cox, time-to-event analyse• Adjustment for age, sex, & risk factors
Lancet 1997;350:1119-23
5
Results
1258 Persons 85+
221 death during inclusion period 60 refusal977 Informed consent
253 No blood sample
724 Participants with blood sample
Lancet 1997;350:1119-23
6
Subjects(no)
Mortality risk
Unadjusted Adjusted age and sex
Adjusted age, sex and
≥ 6.5 mmol/L 171 0.56 (0.45-0.69) 0.62 (0.49-0.77) 0.64 (0.50-0.82)5.0- 6.4 mmol/L 350 0.72 (0.60-0.86) 0.78 (0.65-0.94) 0.81 (0.66-1.01) < 5.0 mmol/L 203 1.00 1.00 1.00
10 - year mortality risks adjusted for various determinants
Total cholesterol
risk factors
Lancet 1997;350:1119-23
8
All cause mortality
0 2 4 6 8 100
0.2
0.4
0.6
0.8
1E
stim
ated
Mor
talit
y P
roba
bilit
y
Years of follow-up
< 5 mM; < 2005.0-6.4 mM; 200-259
≥ 6.5 mM ; > 260
Lancet 1997;350:1119-23
9
COMPARISON OF TOTAL CHOLESTEROL LEVELS IN 137 SUBJECTSWHO WERE SAMPLED AT BASELINE AND AFTER 5-YEARS FOLLOW-UP
Baseline Repeated measurement after 5-years follow-up
Total cholesterol level≥ 6.5mmol/L
5.0-6.4mmol/L
< 5.0mmol/L
All
Total cholesterol level≥ 6.5 mmol/L 21 14 5 40 (29%)
5.0-6.4 mmol/L 8 41 18 67 (49%) < 5.0 mmol/L 1 5 24 30 (22%) All 60 (44%) 47 (34%)137 (100%)
Lancet 1997;350:1119-23
10
5 -YEAR MORTALITY RISKS FOR THREE GROUPS OF PARTICIPANTS
Total cholesterol level Mortality risk
Measured in 1987(n=724)
Measured in 1991(n=137)
Stable cholesterol levelsin 1987 and 1991
(n=86)
≥ 6.5 mmol/L 0.55 (0.42-0.73) 0.42 (0.23-0.78) 0.50 (0.22-1.16)5.0-6.4 mmol/L 0.69 (0.56-0.86) 0.57 (0.35-0.95) 0.65 (0.32-1.33)< 5.0 mmol/L 1.00 1.00 1.00
Lancet 1997;350:1119-23
11
Cardiovascular mortality
0 2 4 6 8 100
0.2
0.4
0.6
0.8
1E
stim
ated
Mor
talit
y P
roba
bilit
y
Years of follow-up
< 5 mM; < 2005.0-6.4 mM; 200-259
≥ 6.5 mmol/L; > 260
Lancet 1997;350:1119-23
12
Infectious mortality
0 2 4 6 8 100
0.1
0.2
0.3
0.4
0.5E
stim
ated
Mor
talit
y P
roba
bilit
y
< 5 mm ; < 2005-6.4 mM; 200-259≥ 6.5 mM ; > 260
Years of follow-up
Lancet 1997;350:1119-23
13
Persons 85 + : conclusions
• High mortality risk (90% at 10 yrs)• CVD stays the first cause of mortality• total chol. is not a risk factor for CV death• high total chol. increased survival
+ 1 mM chol = - 15 % in mortality (RR 0.85 ; 0.79-0.91)
• low total chol. increased risk of death due to infection or cancer
Question : roles of LDL-C & HDL-C ?Lancet 1997;350:1119-23
14
HDL- or LDL-cholesterol : which one is the risk factor
of CAD and Stroke at old age?
AWE Weverling-Rijnsburger, IJAM Jonkers, E van Exel,
J Gussekloo, RGJ Westendorp
Arch Intern Med 2003;163:1549-55
15
Methode
• Leiden 85, tweede cohort• start september 1997• 4 jaar follow-up• alle inwoners van Leiden op 85ste
verjaardag
Arch Intern Med 2003;163:1549-54
16
Deelnemers
705 85 jarigen
14 overleden 92 weigeren deelname
599 deelnemers
38 géén bloedmonster
561 deelnemers met cholesterolwaarden
Arch Intern Med 2003;163:1549-54
17
Resultaten
• Mediane follow-up 2.6 jaar
• 152/561 (27%) overleden gedurende f/up 67 cardiovasculair 28 infectieziekte 25 maligniteit 32 overige
Arch Intern Med 2003;163:1549-54
18
Bij mensen van 85 jaar is
• ⇑ totaal chol géén risico HVZ sterfte
• ⇑ LDL-chol géén risico HVZ sterfte
• ⇓ HDL-chol blijft risico HVZ sterfte
Arch Intern Med 2003;163:1549-54
23
Dus bij de oudste ouderen
hangt de mortaliteit vanhart- en vaatziekten samen
met een laag HDL-cholesterol
(en niet met een hoog LDL-cholesterol)
Arterioscler Thromb Vasc Biol 2000;20:744-50
24
• preventie therapie zou overwogen moeten worden–hoog risico op HVZ–voorspellende waarde van het HDL-C
• gunstige effect van statine therapie blijft onduidelijk …
25