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. 2020 Oct 7:371:m3502.
doi: 10.1136/bmj.m3502.

Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review

Kelvin Okoth  1 , Joht Singh Chandan  1 , Tom Marshall  1 , Shakila Thangaratinam  1   2 , G Neil Thomas  1 , Krishnarajah Nirantharakumar  3   4   5 , Nicola J Adderley  1
Affiliations

Association between the reproductive health of young women and cardiovascular disease in later life: umbrella review

Kelvin Okoth et al. BMJ. .

Erratum in

Abstract

Objective: To consolidate evidence from systematic reviews and meta-analyses investigating the association between reproductive factors in women of reproductive age and their subsequent risk of cardiovascular disease.

Design: Umbrella review.

Data sources: Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31 August 2019.

Review methods: Two independent reviewers undertook screening, data extraction, and quality appraisal. The population was women of reproductive age. Exposures were fertility related factors and adverse pregnancy outcomes. Outcome was cardiovascular diseases in women, including ischaemic heart disease, heart failure, peripheral arterial disease, and stroke.

Results: 32 reviews were included, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three reviews were of moderate quality. A narrative evidence synthesis with forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: twofold for pre-eclampsia, stillbirth, and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes, and premature ovarian insufficiency; and less than 1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. A longer length of breastfeeding was associated with a reduced risk of cardiovascular disease. The associations for ischaemic heart disease were twofold or greater for pre-eclampsia, recurrent pre-eclampsia, gestational diabetes, and preterm birth; 1.5-1.9-fold for current use of combined oral contraceptives (oestrogen and progesterone), recurrent miscarriage, premature ovarian insufficiency, and early menopause; and less than 1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms. For stroke outcomes, the associations were twofold or more for current use of any oral contraceptive (combined oral contraceptives or progesterone only pill), pre-eclampsia, and recurrent pre-eclampsia; 1.5-1.9-fold for current use of combined oral contraceptives, gestational diabetes, and preterm birth; and less than 1.5-fold for polycystic ovary syndrome. The association for heart failure was fourfold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current use of progesterone only contraceptives, use of non-oral hormonal contraceptive agents, or fertility treatment.

Conclusions: From menarche to menopause, reproductive factors were associated with cardiovascular disease in women. In this review, presenting absolute numbers on the scale of the problem was not feasible; however, if these associations are causal, they could account for a large proportion of unexplained risk of cardiovascular disease in women, and the risk might be modifiable. Identifying reproductive risk factors at an early stage in the life of women might facilitate the initiation of strategies to modify potential risks. Policy makers should consider incorporating reproductive risk factors as part of the assessment of cardiovascular risk in clinical guidelines.

Systematic review registration: PROSPERO CRD42019120076.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work; KN reports funding from AstraZeneca and fees from Sanofi, MSD, and Boehringer Ingelheim outside the submitted work.

Figures

Fig 1
Fig 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram
Fig 2
Fig 2
Forest plot showing studies investigating the association between miscarriage and risk of stroke. Note, weights are from random effects analysis
Fig 3
Fig 3
Forest plot showing studies investigating the association between gestational diabetes and risk of stroke. Note, weights are from random effects analysis
Fig 4
Fig 4
Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of composite cardiovascular disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes
Fig 5
Fig 5
Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of ischaemic heart disease. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes
Fig 6
Fig 6
Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of stroke. Circles indicate non-fatal outcomes, open diamonds fatal outcomes, and filled diamonds combined fatal and non-fatal outcomes. *Ischaemic stroke. †Haemorrhagic stroke
Fig 7
Fig 7
Forest plot showing results of meta-analyses from reviews that investigated the association between various reproductive factors and risk of heart failure. Circles indicate non-fatal outcomes
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