Weight Change and Change of Total Cholesterol and High~DensityLipoprotein Cholesterol Results of the MONICA

Augsburg Cohort Study

Ernst Eberle, MD, DiplMath, Ulrich Keil, MD, PhD

Angela Doering, MD, DiplMath,

Data from the MONICA

(Monitoring

Trends and Determinants

and

in Cardiovascular

Disease)

Augsburg cohort were used to study the effect of weight change on changes in serum levels of total and high-density-lipoprotein cholesterol. Weight gain was associated with rising levels of total cholesterol and fulling levels of high-density-lipoprotein cholesterol in both sexes, more so in men than in women. Moreover, these relationships weakened with advancing age in women, but not in men. The results support the view that weight loss may more favorably affect lipid levels in men than in women, particularly at older ages. Ann Epidemiol 199 I ; 1487-492. KEY WORDS:

Cohort analysis; cholesterol, body weight

INTRODUCTION

Weight change has been correlated with changing lipid levels in a number of observational (l-6) and intervention studies (7, 8). In general, associations were more pronounced in men than in women ( l-3). The effect of age on these relationships has rarely been addressed, however. We therefore were interested in confirming earlier results on changing weight and total cholesterol (TC) and high-density-lipoprotein (HDL) cholesterol (HDL-C) 1eve 1s m a representative German population. We also evaluated these associations as a function of age.

METHODS

The World Health Organization (WHO) MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) project (9, 10) is designed to analyze trends in cardiovascular mortality, morbidity, and case fatality over 10 years in defined populations. This requires the continuous monitoring of cardiovascular diseases through coronary event and stroke registers and the periodic assessment of cardiovascular risk factors through population surveys. Overall, 39 centers in Europe, North America, Asia, Australia, and New Zealand contribute to a joint data pool. This report is confined to results from the MONICA center Augsburg (1 l), which comprises a South German population of about 500,000. In 1984 to 1985 and after a 3-year follow-up in 1987 to 1988, information on cardiovascular risk factors was collected from an age-sex stratified random sample of residents, aged 25 to 64 years. Of From the GSF-Forschungszentrum fiir Umwelr und Gesundheit (GSF), Institute of Epidemiology, Neuherberg (E.E., A.D., U.K.), and Department of Social Medicine and Epidemiology, Ruhr Universitit, Bochum (U.K.), Federal Republic of Germany. Address reprint requests to: Ulrich Keil, MD, GSF, institute D-8042 Neuherberg, FRG. Received November 16, 1990; revised February 19, 1991. 0 1991 Elsevier Science Publishing Co.,

Inc.

of Epidemiology,

Ingolstaedter

Landstr.

1047-2797/91/$03.50

1,

488

Eberle et al. CHANGE OF WEIGHT AND CHOLESTEROL

AEP Vol. 1, No. 6 November 1992: 487-492

the 4022 participants

in the baseline examination (first MONICA survey from 1984 to 1985), 3753 took part in the follow-up examination (MONICA Augsburg cohort study). This cohort study is not part of the WHO MONICA core design. Age, sex, and average number of cigarettes smoked per day were assessed by questionnaire. Each subject was asked how much beer, wine, and spirits he or she drank on the previous workday and over the previous weekend. From this, the average number of grams of alcohol consumed per day was derived using the following conversions: 1 L of beer = 40 g of alcohol, 1 L of wine = 100 g of alcohol, and 1 shot of spirits (.02 L) = 6.2 g of alcohol. Height and weight were measured, with shoes and heavy clothing removed, and the body mass index (BMI) was calculated as weight divided by height squared (kg/m2). Nonfasting samples of venous blood were drawn while subjects were seated. Blood was allowed to clot and was refrigerated thereafter. The obtained serum was analyzed within 3 days. TC determinations were done by an enzymatic method (CHOD-PAP method, Fa. Boehringer, Mannheim). HDL-C levels were determined after precipitation of apoprotein B-containing lipoproteins with phosphotungstate/Mg2+. External quality control was performed by the Lipid Standardization Center of the WHO. Excluded from analyses were those individuals for whom BMI, TC, or HDL-C values were missing (54 1 of 3 753). Th e number of subjects taking drugs known to alter lipid levels was too small in most age strata to warrant further stratification. This is why individuals who were using gonadal hormones, cholesterol-lowering drugs, or antihypertensive agents were not included in this investigation (764 of 32 12). Results were derived from the remaining 2448 individuals, 1381 men and 1067 women. Change variables were defined as follow-up value minus baseline value. Multiple regressions of TC change and HDL-C change on BMI change, change in smoking status, and change in alcohol consumption were run in each age-sex stratum. The initial value of the independent variable (minus its mean value) was also included in each model to control for the regression to the mean effect. Reported significance levels relate to P values 4 .05. Adjusted means were derived from the regression model under consideration ( 12). They were for mean baseline lipid levels, no change in smoking status and alcohol consumption, and selected values of BMI change. RESULTS Table 1 presents baseline characteristics by sex and age. TC and BMI values increased with age in both sexes. TC levels were higher in men than in women with the exception of the oldest age group, whereas female HDL-C levels exceeded male levels in each age group. Use of alcohol and cigarettes was higher in men than in women across all ages. The corresponding changes are listed in Table 2. Over this 3-year period, TC levels increased markedly in men under age 45, while changes were less pronounced in older men. In women, increments were largest in the age group 45 to 54 years. HDL-C levels slightly decreased in both sexes and most age groups. BMI change was positive and generally greater in women than in men. Alcohol consumption and cigarette use tended to decrease in both sexes. In each of the multiple regression models considered, the initial lipid value (minus variable.

its mean

value)

The relationship

sion to the mean

(data

was more

closely

was consistently not presented).

related inverse,

to lipid change than any other indicating the presence of regres-

489

Eberle et al.

AEP Vol. 1, No. 6

November 1991: 487-492

CHANGE

TABLE

1 Baseline characteristics (mean ? stan&rJ Augsburg cohort 1984-1987 (n = 2448)

n

Men 25-34 35-44 45-54 55-64 Women 25-34 35-44 45-54 55-64

1381 368 373 350 290 1067 177 330 309 251

y y y y y y y y

In general, coefficients BMI

change

advancing over.

BMI

(kg/m’)

2 2 + 2

5.04 5.49 6.05 6.78

2 .7Y -+ .YO 2 1.07 2 1.15

1.10 1.10 1.13 1.10

I’ values

change.

25.3 26.7 27.4 27.5

+ 2 2 k

1.3 3.4 3. I 3.1

32.7 38.3 3Y.6 38.4

+ + k 2

31.2 35.1 31.4 56.5

8.2 7.8 6.6 5.5

t+ -t k

11.6 13.6 11.6 10.0

1.58 1.6Y 1.67 1.63

k 2 -c +-

.3H .42 .43 .3Y

22.Y 24.7 26.4 27.5

t2 -c 2

3.i 3.7 4.0 4.S

12.4 13.2 Y.2 9.5

+ 17.6 + 16.6 -f_ 1Y.7 k 13.1

4.5 2.2 1.8 1.4

t2 + -’

8.4 6.1 5.6 5.6

coefficients

Table

Although noting

the

that

was significantly

1 to 5% of individuals

These

Comparable

(and

changes

corresponded

or 9 kg, respectively, adjusted

mean

to weight

for a person

TC and HDL-C

who

Tables

to .53 mmol/L

in men and .04 mmol/L

corresponding

HDL-C

changes

HDL-C of at least

TC changes

to .44 mmol/L

in women

(see Table

by sex and age: MONICA

the

ranged

-. 14 mmol/L

in women

3

of at least 6 kg

5 and 6 contain

were between

and .08 mmol/L

2 Changes (mean k standard deviation) 1984-1987 (n = 2448)

with

BMI by at least

increases

BMI changes.

5). The

cohort

with

decreases

their

losses or weight

mmol/L

TABLE

positive

at age 45 years and

showed

(see Table

in men and - .07 mm&L

of

weakened

associated

increased

from -.22 .10 mmol/L

for

4).

stratum

for these

those

coefficients

was consistently

negatively)

is 175 cm tall.

changes

than

of BMI change significance

(Table

of individuals

smaller

the regression

relationship

in each age-sex

numbers

were

3 displays

the impact

in men of all ages but not in women

About

Cigarette use (c&/d)

.17 .40 .18 .40

and failed to reach statistical

BMI change

Alcohol use (g/d)

+ t k k

variables.

it is worth

hy sex and age: MONICA

1.32 1.30 1.33 1.36

for BMI change

change

age in women

2 BMI units. units.

HDL-C

(mmol/L)

for TC

Also,

change

TC

of other

across all analyses,

deviation)

(mmol/L) 5.54 6.06 6.26 6.30

AND CHOLESTEROL

OF WEIGHT

and 6).

Augshurg

Change in n

Met3 25-34 35-44 45-54 55-64 WlXT1en 25-34 35-44 45-54 55-64

TC (mmol/L)

HDL-C (mmol/L)

(kg/m’)

BMI

Alcohol

use

(g/d)

Cigarette use (cigid)

1381 y y y y

368 373 350 290 1067

.27 .20 .08 .lO

+ + + +

.72 .80 .72 .7Y

.oo p.02 .OO -.03

t _f k 2

.2Y .80 .25 .28

.i .3 .2 .2

r ++ t

1.2 1.2 1.2 1.2

-1.3 -4.7 -3.0 -6.3

-’ r t t

28.9 30.1 27.7 29.0

-.8 p.5 -.5 -.7

+ + + f

7.8 6.6 6.0 4.5

y y y y

177 330 309 251

.25 .20 .30 .14

? f + ”

.60 .63 .6Y .73

.Ol -.Oj -.Ol -.05

2 2 + f

.28 .28 .33 .26

.7 .5 .4 .2

+ + f +

1.4 1.6 1.5 1.6

-.8 -1.8 -2.3 -1.4

t _f + t

16.8 14.6 19.8 14.8

p.4 .3 .l -.3

k + t f

4.4 3.5 2.4 3.6

490

Eberle et al. CMANGE OF WEIGHT AND CHOLESTEROL

AEP Vol. 1, No. 6 November 1991: 487-492

TABLE 3 Regression of TC change on BMI change“ by sex and age: MONICA cohort 198441987 (n = 2448) Men Coefficient 25-34 35-44 45-54 55-64 ’

y y y y

Augsburg

Women p value

.08 .ll .12 .15

Coefficient

.0037

p value

.08 .06 .04 .04

.0006 .OOOl .OOOl

.0135 .0055

.1404 .I344

Controlhng forhas&w TC. change in cigarette use, and change m alcohol c~msurnptmn

TABLE 4 Regression of HDL-C change on BMI change” by sex and age: MONICA Augsburg cohort 1984-1987 (n = 2448) Men

Women

Coefficient

p value

25-34 y

-.04

35-44 45-54 55-64

-.03 -.03 -.04

.0015 .OllO .0034 .0014

y y y

y Controlling

for baseline

HDLC,

change

m cigarette

use.

-.03 -.Ol -.Ol .oo

and

change

m alcohol

TABLE 5 Adjusted” mean TC changes by sex, BMI change, cohort 1984-1987 (n = 2448)

.0584

.1487 .3637

.7038

consumptim

and age: MONICA

BMI change for men

25-34 y

p value

Coefficient

Augsburg

BMI change for women

-2

0

3

-2

0

3

35-44

y

.06 -.05

.23 .17

.47 .so

.04 .06

.20 .18

.44 .36

45-54 55-64

y y

-.18 -.22

.06 .08

.42 .53

.21 .06

.29 .14

.41 .26

* Model contams haseltne TC, change in cigarette use. and change m alcohol consumption. The means are for mean value of baseline TC and no changes m cigarette use and alcohol consumption.

TABLE 6 Adjusted0 mean HDL-C changes by sex, BMI change, Augsburg cohort 1984- 1987 (n = 2448)

BMI change for women

BMI change for men -2 25-34 y 35-44 y 45-54 y 55-64 y a Model value

.lO .06 .07 .06 contains

of hasehne

baseline HDL-C

no

0

3

.02 .oo .Ol -.02

-.lO -.09 -.08 -.14

-2 .08 .oo .Ol -.04

0

3

.02 -.02 -.Ol -.04

-.07 -.05 -.04 -.04

change in cigarette use, and change in alcohol consumption. The means arc for mean changes in cigarette use and alcohol consumption.

HDL-C, and

and age: MONICA

491

Eberle et al. CHANGE OF WEIGHT AND CHOLESTEROL

AEP Vol. 1, No. 6 November J99 J : 487-492

DISCUSSION The present

study is the first to relate

levels

in a German

about

menopause

in HDL-C

showed

in both

apparent These

findings

Change

initial

13), the association

The impact TC change, HDL-C

above

only

statistical

gain was

age groups.

in participants

predictor

of changing

with other

observational

and negative

of the

to no BMI change,

lipid levels studies

for HDL-C

( 1,

change.

up to .lO mmol/L

increased

of BMI).

For these

amounted

on lipid levels in women significant

people

in

the BMI

to .30 mmol/L

power

study subjects

coefficient

for TC

than

in the youngest similar

explanation

and the variation

to assess. For

held for women

was weaker

and was numerically is an unlikely

is more difficult

association

age 34 the association

significance

of female

Weight

in younger

seen

at

(1).

and HDL-C

loss (2 units

the regression

Lack of statistical

numbers

changes

period

and women

was little change

period.

marked

for TC change

and statistically

However,

marginal men.

of BMI change

change,

while there

for HDL-C.

a positive

years old.

weight

as compared

and to .08 mmol/L

with

in TC and HDL-C

age range

in this 3-year

In accordance

as .22 mmol/L

substantial

effect on lipid levels,

of TC,

to be the most powerful

was positive

as much

with

in agreement

lipid levels).

to changes

but more

study over an 8-year

in BMI proved

individuals

elevations

of all ages,

are therefore

TC decreased

changes

in the 25 to 34.year

the greatest

and women

offspring

in men (barring

weight

Men

sexes and most age groups

in men

Framingham

3-5,

population.

below 45

in men.

age group

to coefficients

found

of this outcome,

of changes

As to reached

given

in that

were grossly comparable

across age groups. Sex differences been

reported

in the association

in other

observational

data (1, 2, 4). Short-term effect of weight in women

weight-loss

Incomplete

control

a change

than

weight

able

for our cohort

change

change

and change

in a manner

programs

In addition,

for TC and small for HDL-C for confounding

in dietary

habits

variables

study

subjects.)

the effect of BMI change

may play a role in these

(MRFIT) data (7) indicated an effect independent of diet, however.

no detailed

The

Multiple

of weight

dietary Risk

with changing

loss more favorably

information

was avail-

this topic

would

cholesterol

be useful for a better

Intervention

loss on cholesterol

in women.

understanding

In

lipid levels

Factor

lipid levels at all ages. The present

alters lipid levels in men than

results.

in changing

We therefore decline confounding, as the only explanation suggest that attention be given to the question of whether weight associated

with the present of a sex differential

in most age groups.

may be more important

per se. (Unfortunately,

in lipid levels have

consistent

also offer evidence

on lipid levels (14, 15).

change

is age-dependent

particular,

of weight studies

level

Trial that

was

of our findings and change in women is

data indicate Further

of the effect

that weight

information of weight

on

loss on

levels.

REFERENCES 1. trends

Anderson

in

Framingham

lipoprotein

KM, Wilson PWF, Garrison cholesterol

measurements

offspring study, Atherosclerosis.

RJ, Castelli WP. Longitudinal in

a general

population

and secular sample.

The

1987;68:59-66.

2. Ashley FW, Kannel WB. Relation of weight change to change in atherogenic The Framingham study, J Chronic Dis. 1974;27:103-14.

traits:

492

Eberle et al. CHANGE OF WEIGHT AND CHOLESTEROL

3. nant

Berm

MAM,

of changes 4.

Criqui

JD. Change years:

5. Framingham 6.

tion

HB,

Noppa

H. Body weight

7.

Caggiulla

AW,

(MRFIT)

IV. Intervention

8.

Glueck

Christiakis

CJ, Gordon in total

The Lipid Research

in relation disease,

MJ, Turner

cholesterol

heart

correlates

disease

after six

of risk factor

risk factors

DJ, Nelson

to incidence

of ischemic

Am J Epidemiol.

in the

lipids,

Prev Med.

JJ, Davis CE, Tyroler lipoprotein

Primary

Prevention

disease

Risk Factor

Intervcn-

Dietary

and other

in hypercholesterolemic

Trial,

and

1981;10:443-75. HA.

cholesterol

heart

1980;111:693-704.

M, et al. The Multiple

on blood

Coronary

MR, Holdbrook

liproprotein

WI’. Life-style

of coronary

G, Farrand

and low density

Clinics

determiin young

1987;125:812-31.

heart

Trial

as a major cholesterol

1983;118:52-9.

study

change

for ischemic

E, Klauher

and low density

RJ, Castelli

eight-year

Am J Epidemiol.

in risk factors

lates of changes

in high

ED, Garrison

An

lipoprotein

1989;130:1109-22.

Am J Epidemiol.

Eaker

in body fatness

density

DD, Barrett-Connor

of change

adults:

offspring,

MB. Increase

and high

Am J Epidemiol.

study,

Hubert

Katan

cholesterol

Frankville

and correlates

in young

change

total

period, MH,

A prospective

change

De Vries JHM,

in serum

men over a lo-year

AEP Vol. I, No. 6 November 1991: 487-492

Am J Clin Nutr.

corrcmen:

1986;44:489-

500. 9. Health

World

10.

WHO

MONICA 11.

Organization:

MONICA

Project

(monitoring

collaboration, Keil U, Stieber

Augsburg.

MONICA

Manual.

Version

1.1.

Geneva:

World

1986.

project

international area

Health

Organization,

Results

Principal

trends J Clin

Investigators. determinants

Epidemiol.

J, Doering from

and

the

The

World

Health

in cardiovascular

Organization

disease):

A major

1988;41:105-14.

A, et al. The cardiovascular survey

first MONICA

risk factor

1984185,

Acta

profile Med

in the study

Stand

Suppl.

1988;728:119-28. L. A comparison

12.

Wilkosky

TC,

Chambless

measures,

J Chronic

Dis.

1985;38:849-56.

13. disease

Borkan risk:

Epidemiol. 14. cholesterol

GA,

Patterns

Sparrow

D, Wisniewski

of risk factor

change

C,

of direct Vokonas

associated

with

adjustment

I’S

Body

long-term

of epidemiologic

weight weight

and

coronary

change,

Am J

1986;124:410-9. Brownell levels

KD,

Stunkard

in obese

men

J. Differential and

women

changes during

in plasma

weight

high-density

reduction,

Arch

lipoproteinIntern

Med.

1981;141:1142-6. 15.

Zimmermann

obesity

on plasma

sition,

Arteriosclerosis.

J, Kaufmann

lipoprotein

NA,

Fainaru

and apolipoprotein

1984;4: 115-23.

M, et al. Effect of weight

levels and on high density

loss in moderate

lipoprotein

compo-