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      Unraveling the associations of age and menopause with cardiovascular risk factors in a large population-based study

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          Abstract

          Background

          Although the association between menopause and cardiovascular disease (CVD) risk has been studied extensively, the simultaneous role of chronological aging herein remains underexposed. This study aims to disentangle the relationships of menopausal status and chronological aging with CVD risk factors in the largest study population to date.

          Methods

          In this cross-sectional study, CVD risk factors were compared between women with a different menopausal status within the same yearly age strata. The study population comprised female participants of the baseline visit of the population-based LifeLines Cohort Study. A total of 63,466 women, aged between 18 and 65 years, was included. Of them, 39,379 women were considered to be premenopausal, 8669 were perimenopausal, 14,514 were naturally postmenopausal, and 904 were surgically postmenopausal.

          Results

          Compared to postmenopausal women aged 45 years, average total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c) were 0.5 and 0.4 mmol/L higher, respectively, in postmenopausal women aged 50. Systolic and diastolic blood pressure levels were 4 and 1 mmHg higher, respectively. At all ages between 46 and 55 years, and after adjustment for confounders, naturally postmenopausal women had 0.2 to 0.4 mmol/L higher TC and 0.1 to 0.3 mmol/L higher LDL-c levels compared to premenopausal women in the same age range. Systolic blood pressure levels were up to 4 mmHg lower in naturally post- compared to premenopausal women at all ages between 29 and 52 years. Body mass index levels were up to 3.2 kg/m 2 higher in women with surgical menopause compared to all other women between the ages 32 and 52 years. All aforementioned results were statistically significant.

          Conclusions

          Chronological age and menopausal status are both independently associated with CVD risk factors. Based on the comparatively smaller observed differences associated with menopausal status than with chronological aging, the significance of a more unfavorable lipid profile in a later reproductive stage may be less obvious than previously thought.

          Electronic supplementary material

          The online version of this article (doi:10.1186/s12916-016-0762-8) contains supplementary material, which is available to authorized users.

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          Most cited references39

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          Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or to the menopausal transition?

          This prospective study examined whether changes in traditional and novel coronary heart disease (CHD) risk factors are greater within a year of the final menstrual period (FMP), relative to changes that occur before or after that interval, in a multiethnic cohort. Understanding the influence of menopause on CHD risk remains elusive and has been evaluated primarily in Caucasian samples. SWAN (Study of Women's Health Across the Nation) is a prospective study of the menopausal transition in 3,302 minority (African American, Hispanic, Japanese, or Chinese) and Caucasian women. After 10 annual examinations, 1,054 women had achieved an FMP not due to surgery and without hormone therapy use before FMP. Measured CHD risk factors included lipids and lipoproteins, glucose, insulin, blood pressure, fibrinogen, and C-reactive protein. We assessed which of 2 models provided a better fit with the observed risk factor changes over time in relation to the FMP: a linear model, consistent with chronological aging, or a piecewise linear model, consistent with ovarian aging. Only total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B demonstrated substantial increases within the 1-year interval before and after the FMP, consistent with menopause-induced changes. This pattern was similar across ethnic groups. The other risk factors were consistent with a linear model, indicative of chronological aging. Women experience a unique increase in lipids at the time of the FMP. Monitoring lipids in perimenopausal women should enhance primary prevention of CHD.
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            Postmenopausal status and early menopause as independent risk factors for cardiovascular disease: a meta-analysis.

            Loss of ovarian function and subsequent deficiency of endogenous estrogens is suggested to enhance cardiovascular disease risk and related death after menopause. The aim was to obtain valid estimates of the cardiovascular disease risk associated with postmenopausal status and early menopause. A literature search of observational studies was performed using PubMed and EMBASE (1966 to May 1, 2004). Eighteen studies on postmenopausal status and age at menopause in relation to cardiovascular disease were selected. Six studies investigated menopausal status, nine studies investigated menopausal age, and three studied both. General variance-based methods were used to pool relative risk estimates and corresponding 95% confidence intervals. Stratification was performed for study design, type of menopause, outcome, and adjustment for age and smoking. The pooled relative risk estimate for postmenopausal versus premenopausal status and cardiovascular disease was 1.36 (95% CI, 1.15-1.60). In the stratified analysis, the pooled effect was 0.96 (95% CI, 0.77-1.21) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 2.62 (95% CI, 2.05-3.35). For early menopause and cardiovascular disease, with the menopausal age category containing 50 years as a reference, the pooled relative risk estimate was 1.25 (95% CI, 1.15-1.35). In the stratified analysis, the pooled effect was 1.38 (95% CI, 1.21-1.58) after controlling for age and smoking. The pooled effect of bilateral oophorectomy on cardiovascular disease was 4.55 (95% CI, 2.56-8.01). Overall, there was no convincing relationship between postmenopausal status and cardiovascular disease. However, there was a modest effect of early menopause on cardiovascular disease. The effect was more pronounced for women with an artificial menopause than for women with a natural menopause.
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              Changes in body composition in women over six years at midlife: ovarian and chronological aging.

              Understanding the menopause association with body weight is important because excess weight increases risk for stroke, incident cardiovascular disease, cardiovascular mortality, and all-cause mortality among the middle-aged. The objective of this study was to examine chronological age and ovarian age and consider how these could influence body size and composition in midlife women. The Study of Women's Health Across the Nation is a longitudinal, community-based study. This report uses data from the Michigan Study of Women's Health Across the Nation site. Participants were 543 premenopausal or early perimenopausal African-American and Caucasian women aged 42-52 yr at baseline examination. Waist circumference, fat mass and skeletal muscle mass, from bioelectrical impedance, were assessed in seven annual serial measures. Annual FSH values were assayed by ELISA. The final menstrual period was defined retrospectively after 12 months of amenorrhea. There was an absolute cumulative 6-yr increase in fat mass of 3.4 kg and a 6-yr decrease in skeletal muscle mass of approximately 0.23 kg. There was an absolute cumulative 6-yr increase of approximately 5.7 cm in waist circumference. The (log)FSH change was positively correlated with (log)(fat mass) change. Waist circumference increased over the time period, but 1 yr after final menstrual period, the rate of increase slowed. Fat mass continued to increase with no change in rate. Both time (chronological aging) and ovarian aging contributed to substantial changes in body composition (fat and skeletal muscle mass) and waist circumference. These changes have important ramifications for establishing a metabolic environment that can be healthy or unhealthy.
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                Author and article information

                Contributors
                a.c.dekat@umcutrecht.nl
                y.t.vanderschouw@umcutrecht.nl
                Journal
                BMC Med
                BMC Med
                BMC Medicine
                BioMed Central (London )
                1741-7015
                4 January 2017
                4 January 2017
                2017
                : 15
                : 2
                Affiliations
                [1 ]Department of Reproductive Medicine and Gynecology, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3508 GA The Netherlands
                [2 ]Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3508 GA The Netherlands
                Article
                762
                10.1186/s12916-016-0762-8
                5210309
                28049531
                ba3b5f78-2b92-45f7-bc7e-8d41664ad5e0
                © The Author(s). 2016

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 30 August 2016
                : 30 November 2016
                Categories
                Research Article
                Custom metadata
                © The Author(s) 2017

                Medicine
                menopause,cardiovascular risk,female aging
                Medicine
                menopause, cardiovascular risk, female aging

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