Abstract
Objectives: 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 of systematic reviews and meta-analyses of observational studies.
Data sources: Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31st August 2019.
Elligibility criteria: 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: We included 32 reviews, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three were of moderate quality. A narrative evidence synthesis aided by forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: 2-fold for pre-eclampsia, stillbirth and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes and premature ovarian insufficiency; and <1.5-fold for early menarche, polycystic ovary syndrome, among ever parous women and early menopause. A longer duration of breastfeeding was associated with reduced cardiovascular disease risk. The associations for ischaemic heart disease were ≥2-fold for pre-eclampsia, re-current pre-eclampsia, gestational diabetes and preterm birth; 1.5-1.9-fold for current combined oral contraceptive (oestrogen and progesterone) use, recurrent miscarriage, premature ovarian insufficiency and early menopause; <1.5-fold for any current oral contraceptive pill use (combined oral contraceptive or progesterone-only), miscarriage, polycystic ovary syndrome and menopausal symptoms. For stroke outcomes, the associations were ≥2-fold for any current oral contraceptive pill use, pre-eclampsia and recurrent pre-eclampsia; 1.5-1.9-fold in current combined oral contraceptive use, gestational diabetes and preterm birth; and <1.5-fold in polycystic ovary syndrome. The association for heart failure was 4-fold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current progesterone only pill use, non-oral hormonal contraceptive use or fertility therapy.
Conclusion: From menarche to menopause, reproductive factors are associated with cardiovascular disease in women. It is not feasible in this review to present absolute numbers on the scale of the problem; however, if these associations are causal they may account for a substantial proportion of unexplained cardiovascular disease risk in women, risk which may be modifiable.Identification of reproductive risk factors at an early stage in the life course of women may facilitate the initiation of potential risk modification strategies. Policy makers should consider incorporating reproductive risk factors as part of cardiovascular risk assessment in clinical guidelines.
Systematic review registration: PROSPERO CRD42019120076
Design: Umbrella review of systematic reviews and meta-analyses of observational studies.
Data sources: Medline, Embase, and Cochrane databases for systematic reviews and meta-analyses from inception until 31st August 2019.
Elligibility criteria: 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: We included 32 reviews, evaluating multiple risk factors over an average follow-up period of 7-10 years. All except three were of moderate quality. A narrative evidence synthesis aided by forest plots and tabular presentations was performed. Associations for composite cardiovascular disease were: 2-fold for pre-eclampsia, stillbirth and preterm birth; 1.5-1.9-fold for gestational hypertension, placental abruption, gestational diabetes and premature ovarian insufficiency; and <1.5-fold for early menarche, polycystic ovary syndrome, among ever parous women and early menopause. A longer duration of breastfeeding was associated with reduced cardiovascular disease risk. The associations for ischaemic heart disease were ≥2-fold for pre-eclampsia, re-current pre-eclampsia, gestational diabetes and preterm birth; 1.5-1.9-fold for current combined oral contraceptive (oestrogen and progesterone) use, recurrent miscarriage, premature ovarian insufficiency and early menopause; <1.5-fold for any current oral contraceptive pill use (combined oral contraceptive or progesterone-only), miscarriage, polycystic ovary syndrome and menopausal symptoms. For stroke outcomes, the associations were ≥2-fold for any current oral contraceptive pill use, pre-eclampsia and recurrent pre-eclampsia; 1.5-1.9-fold in current combined oral contraceptive use, gestational diabetes and preterm birth; and <1.5-fold in polycystic ovary syndrome. The association for heart failure was 4-fold for pre-eclampsia. No association was found between cardiovascular disease outcomes and current progesterone only pill use, non-oral hormonal contraceptive use or fertility therapy.
Conclusion: From menarche to menopause, reproductive factors are associated with cardiovascular disease in women. It is not feasible in this review to present absolute numbers on the scale of the problem; however, if these associations are causal they may account for a substantial proportion of unexplained cardiovascular disease risk in women, risk which may be modifiable.Identification of reproductive risk factors at an early stage in the life course of women may facilitate the initiation of potential risk modification strategies. Policy makers should consider incorporating reproductive risk factors as part of cardiovascular risk assessment in clinical guidelines.
Systematic review registration: PROSPERO CRD42019120076
| Original language | English |
|---|---|
| Article number | m3502 |
| Pages (from-to) | 1-21 |
| Number of pages | 21 |
| Journal | BMJ |
| Volume | 371 |
| Early online date | 7 Oct 2020 |
| DOIs | |
| Publication status | E-pub ahead of print - 7 Oct 2020 |
