Reproductive health of young women linked to CVD in later life

The reproductive profile of women from menarche to menopause contributes to their future risk of cardiovascular disease (CVD), suggests a recent study.

“A large proportion of unexplained risk of CVD in women might be attributable to reproductive risk factors, but the exact magnitude of the effect is unclear,” the researchers said. “Identification of reproductive risk factors at an early stage in the life course of women might facilitate the initiation of strategies to modify potential risks.”

This umbrella review searched the databases of Medline, Embase, and Cochrane for systematic reviews and meta-analyses from inception until 31 August 2019. Screening, data extraction, and quality appraisal were carried out by two reviewers independently. A narrative synthesis with forest plots and tabular presentations was conducted.

Participants involved women of reproductive age, with exposures such as fertility-related factors and adverse pregnancy outcomes. CVDs, including ischaemic heart disease (IHD), heart failure (HF), peripheral arterial disease, and stroke, were the main outcomes.

Thirty-two reviews, which assessed multiple risk factors over a mean follow-up period of 7–10 years, met the eligibility criteria. All but three reviews were of moderate quality.

The associations with composite CVD risk 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 <1.5-fold for early menarche, polycystic ovary syndrome, ever parity, and early menopause. [BMJ 2020;371:m3502]

On the other hand, women who breastfeed longer had a much lower risk of CVD than those who don’t or had shorter duration of breastfeeding.

For IHD, the associations 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 <1.5-fold for miscarriage, polycystic ovary syndrome, and menopausal symptoms.

Associations for stroke outcomes 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 <1.5-fold for polycystic ovary syndrome.

For HF, the association was fourfold for pre-eclampsia. There was no association between CVD outcomes and current use of progesterone only contraceptives, use of nonoral hormonal contraceptive agents, or fertility treatment.

The findings on combined hormonal contraceptive agents and combined oral contraceptives were consistent with those on adverse effects of the use of hormonal contraceptive agents reported in current evidence-based guidelines. [https://www.fsrh.org/standards-and-guidance/documents/combined-hormonal-contraception/]

Evidence presented in this review also supported the consensus statement from the European Headache Federation, which reported that the risk of stroke was higher in women with migraine. [J Headache Pain 2017;18:108]

“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 CVD in women, and the risk might be modifiable,” the researchers said.

“Large prospective studies are needed to confirm the association between current use of combined oral contraceptives in patients with obesity and the risk of cardiovascular disease. Similarly, prospective studies with a longer duration of follow-up are needed to investigate the association between reproductive factors and the risk of heart failure,” they added.