The association between the reproductive health of young women and cardiovascular disease across the lifespan

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Okoth, Kelvin ORCID: https://orcid.org/0000-0002-2745-4083 (2023). The association between the reproductive health of young women and cardiovascular disease across the lifespan. University of Birmingham. Ph.D.

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Abstract

Background: In women, cardiovascular disease (CVD) is the leading cause of death, accounting for one-third of all deaths worldwide. Traditionally, CVD has been perceived as a male-dominated condition, with reproductive-age group women perceived to be protected from CVD. Recent analyses of age-and sex-specific data from high-income countries have revealed that the observed ongoing decline in CVD mortality was sustained in older adults (> 55 years) but had slowed in young adults (< 55 years). The rate of decline was slowest in young women. Contemporary data describing CVD trends among young adults from the United Kingdom (UK) are scarce. Several lines of evidence suggest that reproductive factors (adverse pregnancy outcomes and fertility-related endocrine factors) in young women may serve as markers of their cardiometabolic health throughout the lifespan (young adulthood, midlife, and old age). The breadth, level, and quality of evidence on the relationship between reproductive factors and CVD is unclear. Also, awareness of these reproductive factors as factors that enhance CVD is low among healthcare providers and women themselves.

Aim: The aim of this thesis was to examine the association between female reproductive factors and cardiovascular disease across the lifespan.

Methods: A series of annual cohort and cross-sectional studies (1998-2017) were constructed to estimate incidence rates and prevalence among 16-50-year-old men and women (Objective 1). An umbrella review (tertiary level review of existing systematic reviews and meta-analyses) was conducted to consolidate higher-level evidence on the association between female reproductive factors and CVD (Objective 2). Cochrane, Medline and Embase were searched for relevant systematic reviews and meta-analyses from inception until 31st August 2019. Three separate retrospective matched cohort studies were conducted using UK primary care data. Cox proportional hazard models were fitted to estimate adjusted hazard ratio’s (aHR) and corresponding 95% confidence interval (95% CI) for CVD in women with (i) endometriosis (Objective 3), (ii) pelvic inflammatory disease (Objective 4), (iii) menstrual cycle characteristics including irregular and frequent or infrequent cycles (Objective 5) versus a matched comparator group.

Results: Overall, from 1998 to 2017, the incidence and prevalence of ischaemic heart disease (IHD) and angina decreased, while coronary revascularisation, stroke/transient ischaemic attack (TIA), and heart failure (HF) increased in both sexes. (P for trend <0.05 for all except MI incidence and prevalence in men, revascularisation incidence in men, and stroke/TIA incidence in women). The umbrella review analysis included a total of 32 reviews evaluating multiple reproductive factors. The average period of follow-up was 7 to 10 years. All reviews were rated moderate in quality except three. In summary, the effect sizes for CVD ranged from 1.01 to 4-fold. The effect sizes were greatest (2-fold) for stillbirth, gestational diabetes, pre-term birth, current use of oral contraceptives (combined oral contraceptives or progesterone only pill), pre-eclampsia and recurrent pre-eclampsia. The effect size for HF was 4-fold in pre-eclampsia. The aHR for composite CVD were: 1.24 (95% CI 1.13–1.37) for endometriosis; 1.10 (95% CI 0.93-1.30) for pelvic inflammatory disease; 1.08 (95% CI 1.00-1.19) for irregular menstrual cycles; and 1.24 (1.02-1.52) for frequent or infrequent menstrual cycles.

Conclusion: Overall, among young adults in the UK, the incidence and prevalence (1998-2017) of IHD and angina exhibited a downward trend while stroke/TIA, HF, and revascularisation, exhibited an upward trend. MI incidence increased in women but remained stable in men. From menarche to menopause, female reproductive factors were associated with CVD throughout the lifespan. Physicians addressing health indicators should consider the adverse impact of female reproductive factors on CVD. Policymakers should consider including female reproductive risk factors in clinical guidelines as part of CVD risk evaluation.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):