total cholesterol and mortality risk in the oldest...

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

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BASELINE CHARACTERISTICS, year 1987

Lancet 1997;350:1119-23

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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

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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

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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

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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

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Methode

• Leiden 85, tweede cohort• start september 1997• 4 jaar follow-up• alle inwoners van Leiden op 85ste

verjaardag


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Deelnemers

705 85 jarigen

14 overleden 92 weigeren deelname

599 deelnemers

38 géén bloedmonster

561 deelnemers met cholesterolwaarden


17

Resultaten

• Mediane follow-up 2.6 jaar

• 152/561 (27%) overleden gedurende f/up 67 cardiovasculair 28 infectieziekte 25 maligniteit 32 overige


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19


20


High

21

Coronary artery

Stroke


High

22

Bij mensen van 85 jaar is

• ⇑ totaal chol géén risico HVZ sterfte

• ⇑ LDL-chol géén risico HVZ sterfte

• ⇓ HDL-chol blijft risico HVZ sterfte


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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

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• preventie therapie zou overwogen moeten worden–hoog risico op HVZ–voorspellende waarde van het HDL-C

• gunstige effect van statine therapie blijft onduidelijk …

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total cholesterol and mortality risk in the oldest...

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