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

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.

Estrogen Receptors: Therapeutic Perspectives for the Treatment of Cardiac Dysfunction after Myocardial Infarction

“…Likewise, a prospective study demonstrated that women under 40 years old with premature ovarian insufficiency (POI) showed a 50–70% higher risk of death by ischemic heart disease when compared with those reaching menopause by 50 [ 109 , 110 , 111 ]. In addition, POI seems to predispose to electrocardiographic alterations [ 112 ] with reduced cardiac automaticity [ 108 ].…”

Trends in National Canadian Guideline Recommendations for the Screening and Diagnosis of Gestational Diabetes Mellitus over the Years: A Scoping Review

“…In Canada, as in much of the world, there has been debate concerning: (a) the appropriate timing and method for screening, specifically the utility of a 50 g glucose challenge test (GCT) prior to an oral glucose tolerance test (OGTT) with a higher glucose load (one step vs. two step approach); (b) what constitutes the most appropriate glucose load (e.g., 75 g vs. 100 g in glucose tolerance testing); (c) the specific glucose threshold values above which a test is considered abnormal at different time points following the glucose load; and (d) the number of abnormal values required to warrant a GDM diagnosis [ 3 ]. Although the hyperglycemia observed in GDM typically resolves post-partum, GDM history is a risk factor for incident diabetes mellitus [ 4 ], hypertension [ 5 ], and cardiovascular disease later in life [ 6 ]. The original definitions of GDM were conceived with a focus on the future risk of maternal diabetes mellitus [ 7 ].…”

“…(d) the number of abnormal values required to warrant a GDM diagnosis [3]. Although the hyperglycemia observed in GDM typically resolves post-partum, GDM history is a risk factor for incident diabetes mellitus [4], hypertension [5], and cardiovascular disease later in life [6]. The original definitions of GDM were conceived with a focus on the future risk of maternal diabetes mellitus [7].…”

Pregnancy Loss and Cardiovascular Disease: A Nationwide Cohort Study

“…Results from studies, examining the association between pregnancy loss, and later myocardial infarction and ischemic stroke have shown ambiguous results, [10,11,14] and meta-analyses have as a result concluded that there is not enough evidence to draw meaningful conclusions about the possible link, although prior stillbirth is increasingly accepted to be a risk factor for later cardiovascular disease. [9,36] To our knowledge, no studies have evaluated the outcome of venous thromboembolism, and further no studies have presented clinically meaningful absolute risk estimates. Adjustment of confounders varied among studies examining the risk of myocardial infarction and stroke after pregnancy loss.…”

“…The reproductive profile is easily assessable and possibly an important indicator for at-risk women. [9] A first step in evaluating the applicability of pregnancy history as a marker for later cardiovascular disease, is large scale investigations into the strength of association. This could facilitate development of new risk stratification schemes and early prevention strategies, such as lifestyle modifications and prophylactic medication, for women not identified by traditional risk factors.…”