Atherosclerosis 151 2000 559 – 566
Regulation of plasma low density lipoprotein levels in postmenopausal women
Anna Karjalainen
a
, Jorma Heikkinen
b
, Markku J. Savolainen
a
, Ann-Christine Ba¨ckstro¨m
c
, Y. Antero Kesa¨niemi
a,
a
Department of Internal Medicine and Biocenter Oulu, Uni6ersity of Oulu, Kajaanintie
50
, FIN-
90220
Oulu, Finland
b
Oulu Deaconess Institute, Oulu, Finland
c
Orion Corporation Orion Pharma, Espoo, Finland Received 23 March 1999; received in revised form 23 September 1999; accepted 13 October 1999
Abstract
To study the regulation of plasma low density lipoprotein LDL cholesterol in postmenopausal women n = 79, fasting plasma lipids and lipoproteins, the fractional catabolic rate FCR and production rate for LDL apolipoprotein B apo B, cholesterol
absorption, apolipoprotein E phenotype and polymorphisms of the apo B and 7a-hydroxylase genes were determined. The level of LDL cholesterol was related to FCR r = − 0.757, P B 0.001 and the production r = 0.531, P B 0.001 of LDL apo B and
body mass index r = 0.265, P B 0.05. In contrast, cholesterol absorption efficiency, apolipoprotein E phenotype, EcoRI and XbaI polymorphisms of the apo B gene and the polymorphism of 7a-hydroxylase gene were found to have no significance for the
regulation of LDL cholesterol concentration in these postmenopausal women. © 2000 Elsevier Science Ireland Ltd. All rights reserved.
Keywords
:
Lipoproteins; Apolipoprotein B; Cholesterol absorption; Menopause www.elsevier.comlocateatherosclerosis
1. Introduction
Cardiovascular diseases are less common in fertile women than in men of the same age. After the
menopause, however, the difference between men and women gradually levels off in about 10 years [1], and
cardiovascular diseases also become a leading cause of morbidity and mortality in women.
Hypercholesterolemia, especially a high concentra- tion of plasma low density lipoprotein LDL choles-
terol, is a well-known risk factor for atherosclerosis [2]. After the menopause, plasma total and LDL choles-
terol in women tend to increase to the levels usually seen in men, while HDL cholesterol decreases [3].
The menopausal hormonal changes, particularly es- trogen deficiency, may contribute to the development
of atherogenic lipid changes. This assumption is sup- ported by the favourable metabolic effects observed
during hormone replacement therapy HRT [4,5] and the lower incidence of cardiovascular diseases in
women on HRT [1,6]. However, the latter finding has not been observed in all the studies [7].
In addition to age and gender, obesity, dietary fac- tors, smoking, alcohol consumption and physical activ-
ity, are known to affect cholesterol metabolism. In several studies genetic factors, e.g. apolipoprotein apo
E polymorphism [8,9], are also shown to regulate serum cholesterol levels. However, most of the studies
on
the regulatory
mechanisms of
cholesterol metabolism have been carried out in men and the
mechanisms resulting in increased LDL cholesterol af- ter the menopause are poorly understood. Therefore,
the aim of the present study was to elucidate the regulatory mechanisms of LDL metabolism in post-
menopausal women. Specifically the following ques- tions were raised: first, what are the major factors
associated with plasma LDL levels in postmenopausal females? and second, by what mechanisms are the
plasma LDL levels regulated?
Corresponding author. Tel.: + 358-8-3154100; fax: + 358-8- 3155423.
E-mail address
:
antero.kesaniemioulu.fi Y.A. Kesa¨niemi 0021-915000 - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved.
PII: S 0 0 2 1 - 9 1 5 0 9 9 0 0 4 3 0 - X
2. Subjects and methods
