Associations of age, adiposity, alcohol intake, menstrual status, and estrogen therapy with high-density lipoprotein subclasses.

Abstract

We used nondenaturing polyacrylamide gradient gel electrophoresis to examine the associations of age, adiposity, alcohol intake, and exogenous estrogen with high-density lipoprotein (HDL) subclasses in 427 members of 51 principally Mormon kindreds. The absorbency of protein stain was used as an index of mass concentrations at intervals of 0.01 nm within five HDL subclasses: HDLj,. (7.2 to 7.8 nm), HDL, b (7.8 to 8.2 nm), HDL,, (8.2 to 8.8 nm), HDL 2a (8.8 to 9.7 nm), and HDL 2b (9.7 to 12 nm). Age and alcohol intake were obtained from questionnaires, and body mass index was computed from clinic measurements as weight (kg)/height (m) 2. The results suggest that HDL,,, concentrations were higher after menopause than before. Adult men (>18 years old) had significantly higher HDL^ and HDL, b and significantly lower HDL 2b and HDL?* levels than younger boys. Compared with the women, adult men had higher levels of HDI^. and HDL, b and lower levels of HDL 2b , HDL 2a , and larger-diameter HDL Ja particles. There were no significant differences between the HDL profiles of women and younger boys, suggesting that the divergence in HDL occurs during puberty. Eighty-eight percent of the increase in HDL associated with estrogen replacement in postmenopausal women occurred within HDL,,, and HDL 2a . Reported alcohol intake in adult men correlated with two HDL regions: one within the HDL 2b region and a second within the HDL,,^, region, whereas in women the positive correlation between alcohol and HDL levels was within the HDL 2b region only. In both men and premenopausal adult women, increasing levels of body mass index were associated with higher levels of HDL^ and lower levels of HDL 2b . Statistical adjustment for HDL cholesterol levels eliminated the significant relations of alcohol with HDL subclasses in both men and women. The adjustment did not eliminate the significant relations of age and body mass index to HDL^ and HDL;,,,. Thus, gradient gel electrophoresis of HDL subclasses appears to identify important physiological relations that are independent of HDL cholesterol levels. (Arterioscler Thromb. 1993;13:1654-1661 KEY WORDS • gradient gel electrophoresis • HDL • age • menopause • menstrual • puberty • alcohol • adiposity • HDL 2 • HDL 3 • apolipoprotein A-I • estrogen C oronary heart disease (CHD) risk increases with age and adiposity and is reduced in association with alcohol intake and postmenopause estrogen use.14 These relations may be attributable in part to changes in high-density lipoproteins (HDLs).4 -5 Plasma concentrations of HDL cholesterol and apolipoprotein (apo) A-I, one of the principal HDL proteins, are inversely associated with CHD risk, 6 aging, 5 and adiposity 7 and positively associated with alcohol consumption 8 and postmenopause estrogen use. 9HDLs include multiple distinct subclasses of particles that have different mobilities on nondenaturing polyacrylamide gradient gels. The different mobilities reflect the impeded migration of larger HDL through the gel. Gradient gel electrophoresis 10 has...

Variations in high-density lipoprotein subclasses during the menstrual cycle

“…This is consistent with our previous observation that postmenopausal estrogen replacement primarily increases HDL 2a [11]. Estrogen and progesterone are elevated during the luteal phase.…”

“…Persons were excluded from this analysis if they reported drinking, smoking, using birth control pills, or taking drugs known to affect plasma HDL. We have previously reported that there were 89 premenopausal women who had regular menstrual periods in this sample [11]. The day of the cycle was determined from the following questionnaire item: "Do you have regular cycles or periods?…”

“…Prior studies have demonstrated that these subclasses show specific relationships to shared environment or inheritance [10], aging [11], sexual maturation [11], adiposity [11], alcohol intake [11], exercise [12,13], and other lipoproteins [14]. Variations in these subclasses during the menstrual cycle have not been previously described.…”

Sex and Age Differences in Lipoprotein Subclasses Measured by Nuclear Magnetic Resonance Spectroscopy: The Framingham Study

“…Whereas women had larger HDL particles than men, we found that this sex differential narrowed by ϳ50% with increasing age. Age-related changes in HDL subclasses have been reported by other investigators, with concentrations of HDL 3b increasing after menopause (38 ) and concentrations of small HDL increasing during puberty among boys (39 ). There is also some evidence that HDLcholesterol concentrations are more strongly (inversely) associated with CHD risk among women than men (40 ), and this may, in part, be attributable to the larger mean HDL particle size of women.…”

Low-Calorie Diet-Induced Reduction in Serum HDL Cholesterol Is Ameliorated in Obese Women with the -3826 G Allele in the Uncoupling Protein-1 Gene

“…Low circulating HDL-C levels are regarded as a major atherosclerotic risk factor (Gordon et al 1977;Gordon et al 1989;Kitamura et al 1994) via the interplay of environmental, nutritional, and genetic factors (Williams et al 1993(Williams et al , 1995Watts 2001). In the present study, circulating HDL-C levels were reduced to a significantly less extent by a LCD in subjects with the G allele than those without the G allele, although weight loss and nutrient intake levels did not differ between genotypes.…”