Antiatherogenic effects of high-density lipoprotein (HDL) cholesterol during the perimenopause

HDL Forum Editor Professor Philip Barter comments on findings suggesting that the antiatherogenic effects of high-density lipoprotein (HDL) cholesterol may decrease around the age of menopause. These results from the Los Angeles Atherosclerosis Study were published on-line in Atherosclerosis.

Fan AZ, Dwyer JH. Sex differences in the relation of HDL cholesterol to progression of carotid intima-media thickness: The Los Angeles Atherosclerosis Study. Atherosclerosis 2007; 195:e191-6.

It has long been recognized that the risk of cardiovascular disease in women increases at around the time of menopause. There have been many theories as to why this occurs, but the true explanation is still not known. Hormonal influences have been suggested, although the failure of hormone replacement therapy to reduce cardiovascular events in post-menopausal women suggests that such an explanation may be too simplistic. The recently reported results of the Los Angeles Atherosclerosis Study raise another possibility by suggesting that changes in the function of HDLs at around the time of menopause may be a contributing factor.

In this study, researchers studied the progression of carotid intima-media thickness (IMT), a well validated indicator of subclinical atherosclerosis, in 232 women aged 45-60 years over three examinations at 1.5 yearly intervals. None of the women had a history of cardiovascular disease or stroke at baseline. About 72% had undergone menopause; 47% were taking hormone replacement therapy, 76% were either on or had previously used oral contraceptives and 35% had undergone hysterectomy.

At the commencement of the study, carotid IMT was inversely associated with serum HDL cholesterol levels, consistent with the results of many previous studies. Unexpectedly, the concentration of HDL cholesterol was a direct and highly significant (p=0.0007) predictor of annual carotid IMT progression over the duration of the study. Women whose HDL cholesterol level was < 1.37 mmol/L had slower IMT progression than women with higher HDL cholesterol levels, raising the possibility that the protective effects of HDL may have been lost during the perimenopausal period.