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Date of release: 01 February, 2010

Changes in cardiovascular risk parameters during the menopause transition


Two new studies have addressed once again the issue of worsening of the cardiovascular risk profile in midlife, while focusing on the menopause transition and the role of menopause itself vis-à-vis aging as determinants of this physiological process. The first study investigated the SWAN cohort (Study of Women’s Health Across the Nation), a longitudinal, multi-site, community-based study of 3302 initially premenopausal and early perimenopausal women [1]. Those healthy women had an annual examination, during which biochemical tests were performed to assess cardiovascular risk factors. Two longitudinal models for each risk factor were employed: (1) a linear model that assumes a constant slope across the following three time periods: more than 12 months before the final menstrual period (FMP), within 12 months before and after the FMP, and more than 12 months after the FMP; (2) a piecewise linear model that allows the slope to differ across the three segments. It was found that low density lipoprotein cholesterol and apolipoprotein B demonstrated an increase within 1 year around the time of the FMP, consistent with menopause-induced changes. However, changes in levels of other risk factors – glucose, insulin, triglycerides, lipoprotein(a), factor VIIc, systolic blood pressure, plasminogen activator inhibitor-1 – were attributed to aging rather than menopause. Diastolic blood pressure and levels of tissue plasminogen activator antigen, fibrinogen and C-reactive protein did not change during the follow-up period. All these alterations were similar among the various ethnic groups.


 


The second study addressed the alleged effects of estrogen deficiency on blood flow and the rate of development of atherosclerotic plaque [2]. This was a cross-sectional study that included 120 early menopausal women (age range 42–55 years, <3 years in menopause) and 24 age-matched premenopausal women. Brachial artery flow-mediated dilation (FMD) and common carotid intima-media thickness (IMT) were studied. Estrogen receptor (ER)-α and ER-β polymorphisms were studied. FMD was significantly lower in early menopausal women compared with controls (5.43 ± 2.53 vs. 8.74 ± 3.17%, p < 0.001), whereas IMT did not differ between groups (p > 0.8). Severity of hot flushes was the most important independent predictor for FMD (p < 0.001) in menopausal women. Women with moderate/severe/very severe hot flushes had impaired FMD in contrast to women with no/mild hot flushes or controls. Women with no/mild hot flushes did not differ compared with controls. Age and systolic blood pressure were the main determinants of IMT (both p = 0.004). ER polymorphisms were not associated with vascular parameters.

Comment

Menopause has been considered a risk factor for coronary artery disease (CAD) simply because the graph of incidence of CAD becomes steeper after the menopause, placing postmenopausal women at a higher risk for CAD compared with premenopausal women of similar age groups. However, it has long been debated whether menopause per se (actually estrogen deficiency) or chronological age, or both are involved in this process. The following facts are well evidenced: that the CAD risk profile changes in midlife; that estrogen deficiency is associated with various metabolic alterations which are very much like the ‘metabolic syndrome’; that estrogen replacement may revert some of these ill changes; that aging is a powerful risk factor for cardiovascular disease in women. The 8th Workshop of the International Menopause Society held in Pisa in February 2009 was dedicated to these issues and the Proceedings were recently published in Supplement 1 of Climacteric (October 2009). The abundance of data makes the whole subject very complex, and the results of the SWAN study now put it in a sort of a better order by dividing the risk parameters into those changing as a result of either menopause or aging, and those which demonstrated no change during the peri- and early menopause [1]. While such information is interesting, I think it is practically not so important. The message is in the ‘big picture’: midlife is a turning point for women in regard to cardiovascular risk; thus measures should be taken to identify the risk as early as possible, to educate patients how to implement proper lifestyle behaviors, and to recommend on drug therapy when needed. The study by Bechlioulis and colleagues [2] showed clearly that the seeds of atherosclerotic disease are already there at the time of the menopause transition. Women in the early stages of menopause had endothelial dysfunction, an early marker for cardiovascular disease, but still did not demonstrate a change in plaque size, as the carotid intima-media thickness was comparable to that in the premenopausal controls. Interestingly enough, the arterial blood flow changes appeared only in women who suffered hot flushes, which is in accordance with previous data indicating that vasomotor symptoms may mark a higher cardiovascular risk [3].

Comentario

Amos Pines
Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel

    References

  1. Matthews KA, Crawford SL, Chae CU, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition? J Am Coll Cardiol 2009;54:2366-73. Published December 15, 2009.
    http://www.ncbi.nlm.nih.gov/pubmed/20082925

  2. Bechlioulis A, Kalantaridou SN, Naka KK, et al. Endothelial function, but not carotid intima-media thickness, is affected early in menopause and is associated with severity of hot flushes. J Clin Endocrinol Metab 2010 Jan 15. Epub ahead of print.
    http://www.ncbi.nlm.nih.gov/pubmed/20080857

  3. Gambacciani M, Pepe A. Vasomotor symptoms and cardiovascular risk. Climacteric 2009;12(Suppl 1):32-5.
    http://www.ncbi.nlm.nih.gov/pubmed/19811238