Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors

Clayton, G. L., Soares, A. G., Kilpi, F., Fraser, A., Welsh, P. , Sattar, N. , Nelson, S. M. , Tilling, K. and Lawlor, D. A. (2022) Cardiovascular health in the menopause transition: a longitudinal study of up to 3892 women with up to four repeated measures of risk factors. BMC Medicine, 20, 299. (doi: 10.1186/s12916-022-02454-6) (PMID:35974322) (PMCID:PMC9382827)

Abstract

Background: Women experience adverse changes in cardiovascular health in mid-life; whether the menopausal transition influences these remains strongly debated. The aim of this study was to examine associations of reproductive age (time since final menstrual period (FMP)) with change in carotid intima media thickness (CIMT) and cardiovascular risk factors and determine the role of chronological and reproductive age. Methods: We used data from 1702 women from a pregnancy-based UK cohort who had up to four repeat cardiovascular health measures between mean age 51 (SD = 4.0) and 56 (SD = 3.6) years and experienced a natural menopause. Multilevel models were used to assess the relationship between cardiovascular measures and time since FMP (reproductive age), whilst adjusting for the underlying effects of chronological age and confounders (socioeconomic factors, body mass index, smoking, alcohol, parity, age at menarche). In addition, we looked at the relationship between cardiovascular measures by chronological age according to menopausal stages (pre-menopause, peri-menopause and post-menopause) using information from women who had and had not experienced menopause (N = 3892). Results: There was no strong evidence that reproductive age was associated with CIMT (difference in mean 0.8 μm/year, 95% CI − 0.4, 2.1), whereas there was a strong positive association of chronological age (7.6 μm/year, 95% CI 6.3, 8.9). Consistent with this, we found weaker linear associations of reproductive compared with chronological age for atherosclerotic risk factors, such as with systolic blood pressure (− 0.1 mmHg/year, 95% CI − 0.3, 0.1, and 0.4 mmHg/year, 95% CI 0.2, 0.5, respectively) and non-HDL-cholesterol (0.02 mmol/l/year, 95% CI 0.005, 0.03, and 0.06, 95% CI 0.04, 0.07, respectively). In contrast, associations with fat mass (0.06 kg/m2/year, 95% CI 0.03, 0.10, and 0 kg/m2/year, 95% CI − 0.04, 0.04, respectively) and C-reactive protein (0.01, 95% CI 0.001, 0.02, and 0.01, 95% CI − 0.001, 0.02 natural logged mg/l/year, respectively) were stronger for reproductive compared with chronological age. Both reproductive and chronological age were (weakly) positively associated with glucose (0.002, 95% CI 0.0001, 0.003, and 0.002, 95% CI 0.0001, 0.003 natural logged mmol/l/year, respectively). Conclusions: Our results suggest that going through the menopausal transition does not further increase women’s risk of atherosclerosis (measured by CIMT) beyond effects of ageing. Menopausal transition may, in additional to ageing, modestly increase adiposity and glucose levels and therefore a possible associated diabetes risk.

• Item Type: Articles
• Keywords: ALSPAC, cardiovascular, menopause, menopausal transition, reproductive age, time to final menstrual period, CIMT.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Nelson, Professor Scott and Sattar, Professor Naveed and Welsh, Professor Paul
• Authors: Clayton, G. L., Soares, A. G., Kilpi, F., Fraser, A., Welsh, P., Sattar, N., Nelson, S. M., Tilling, K., and Lawlor, D. A.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: BMC Medicine
• Publisher: BioMed Central
• ISSN: 1741-7015
• ISSN (Online): 1741-7015
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in BMC Medicine 20: 299
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
190524		The relationship of the menopausal transition to healthy aging and chronic disease risk	Naveed Sattar	Wellcome Trust (WELLCOTR)	092830/Z/10/Z	Institute of Cardiovascular & Medical Sciences
190835		The menopausal transition and healthy ageing and wellbeing	Scott Nelson	Medical Research Council (MRC)	G1001357/1	Med - Reproductive and Maternal Medicine