Association Between the Reproductive Health of Young Women and Cardiovascular Disease in Later Life: Umbrella Review

Okoth, Kelvin; Chandan, Joht Singh; Marshall, Tom; Thangaratinam, Shakila; Thomas, G; Nirantharakumar, Krishnarajah; Adderley, Nicola J

doi:10.1097/01.aoa.0000766020.37448.96

Cited by 17 publications

(27 citation statements)

References 125 publications

(188 reference statements)

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“…Use of oral contraceptive pills is associated with stroke in young women; one recent systematic review and meta-analysis demonstrated an odds ratio (OR) of 2.47 for use of any type of oral contraceptive, although when broken down by formulation, combined oral contraceptives remained significant while progesterone-only pills were not associated with increased risk. 46…”

Section: Risk Factors For Strokementioning

confidence: 99%

The Impact of Sex and Gender on Stroke

Rexrode

Madsen

et al. 2022

Circulation Research

275

143

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Women face a disproportionate burden of stroke mortality and disability. Biologic sex and sociocultural gender both contribute to differences in stroke risk factors, assessment, treatment, and outcomes. There are substantial differences in the strength of association of stroke risk factors, as well as female-specific risk factors. Moreover, there are differences in presentation, response to treatment, and stroke outcomes in women. This review outlines current knowledge of impact of sex and gender on stroke, as well as delineates research gaps and areas for future inquiry.

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Section: Risk Factors For Strokementioning

confidence: 99%

The Impact of Sex and Gender on Stroke

Rexrode

Madsen

et al. 2022

Circulation Research

275

143

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“…A recent meta-analysis found that PCOS was associated with a 30% higher risk of overall CVD (odds ratio [OR], 1.30 [95% CI, 1.09–1.56]), including both coronary heart disease (CHD; OR, 1.44 [95% CI, 1.13–1.84]) and stroke (OR, 1.36 [95% CI, 1.09–1.70]). 35 A recent Danish registry found 19% increased risk of incident CVD (adjusted HR, 1.19 [95% CI, 1.07–1.33]) for women with PCOS, but this association was not seen in women after age 50 years. 36 Women with PCOS are also ≈3-fold more likely to develop APOs, including gestational diabetes mellitus (GDM) and preeclampsia, which in turn predict increased CVD risk.…”

Section: Polycystic Ovary Syndrome and Cvd Riskmentioning

confidence: 99%

“…Similar associations have been observed for subclinical atherosclerosis and clinical CVD events. 35 In the SWAN (Study of Women’s Health Across the Nation) Heart Study, women who did not breastfeed had elevated risks of aortic calcification (adjusted OR, 3.85 [95% CI, 1.47–10.00]) and CAC (adjusted OR, 2.78 [95% CI, 1.05–7.14]) compared to women who breastfed each child for ≥3 months, even after adjustment for demographic and lifestyle factors. 123 In the Nurses’ Health Study, women with ≥2 years of cumulative breastfeeding versus no breastfeeding had 23% (95% CI, 6%–38%) lower adjusted risk of CHD events.…”

Section: Breastfeeding and Cvd Risk Reductionmentioning

confidence: 99%

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women

O’Kelly

Michos

Shufelt

et al. 2022

Circulation Research

157

121

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Beyond conventional risk factors for cardiovascular disease, women face an additional burden of sex-specific risk factors. Key stages of a woman’s reproductive history may influence or reveal short- and long-term cardiometabolic and cardiovascular trajectories. Early and late menarche, polycystic ovary syndrome, infertility, adverse pregnancy outcomes (eg, hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, and intrauterine growth restriction), and absence of breastfeeding are all associated with increased future cardiovascular disease risk. The menopause transition additionally represents a period of accelerated cardiovascular disease risk, with timing (eg, premature menopause), mechanism, and symptoms of menopause, as well as treatment of menopause symptoms, each contributing to this risk. Differences in conventional cardiovascular disease risk factors appear to explain some, but not all, of the observed associations between reproductive history and later-life cardiovascular disease; further research is needed to elucidate hormonal effects and unique sex-specific disease mechanisms. A history of reproductive risk factors represents an opportunity for comprehensive risk factor screening, refinement of cardiovascular disease risk assessment, and implementation of primordial and primary prevention to optimize long-term cardiometabolic health in women.

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“…Preeclampsia pregnancies increase the likelihood of adverse pregnancy events, notably fetal growth restriction (FGR), and also increase the risk of cardiovascular diseases for both mother and offspring post-pregnancy. 4–7 Therefore, preeclampsia is currently recognized as a significant contributor to overall cardiovascular disease burden. 8 Preeclampsia is characterized by a prohypertensive milieu including endothelial dysfunction, 9,10 immune dysfunction, 11–13 and altered renin-angiotensin aldosterone system activation.…”

mentioning

confidence: 99%

Midgestation Leptin Infusion Induces Characteristics of Clinical Preeclampsia in Mice, Which Is Ablated by Endothelial Mineralocorticoid Receptor Deletion

et al. 2022

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Background: Patients with preeclampsia demonstrate increases in placental leptin production in midgestation, and an associated increase in late gestation plasma leptin levels. The consequences of mid-late gestation increases in leptin production in pregnancy is unknown. Our previous work indicates that leptin infusion induces endothelial dysfunction in nonpregnant female mice via leptin-mediated aldosterone production and endothelial mineralocorticoid receptor (ECMR) activation, which is ablated by ECMR deletion. Therefore, we hypothesized that leptin infusion in mid-gestation of pregnancy induces endothelial dysfunction and hypertension, hallmarks of clinical preeclampsia, which are prevented by ECMR deletion. Methods: Leptin was infused via miniosmotic pump (0.9 mg/kg per day) into timed-pregnant ECMR-intact (WT) and littermate-mice with ECMR deletion (KO) on gestation day (GD)11-18. Results: Leptin infusion decreased fetal weight and placental efficiency in WT mice compared with WT+vehicle. Radiotelemetry recording demonstrated that blood pressure increased in leptin-infused WT mice during infusion. Leptin infusion reduced endothelial-dependent relaxation responses to acetylcholine (ACh) in both resistance (second-order mesenteric) and conduit (aorta) vessels in WT pregnant mice. Leptin infusion increased placental ET-1 (endothelin-1) production evidenced by increased PPET-1 (preproendothelin-1) and ECE-1 (endothelin-converting enzyme-1) expressions in WT mice. Adrenal aldosterone synthase ( CYP11B2 ) and angiotensin II type 1 receptor b ( AT1Rb ) expression increased with leptin infusion in pregnant WT mice. KO pregnant mice demonstrated protection from leptin-induced reductions in pup weight, placental efficiency, increased BP, and endothelial dysfunction. Conclusions: Collectively, these data indicate that leptin infusion in midgestation induces endothelial dysfunction, hypertension, and fetal growth restriction in pregnant mice, which is ablated by ECMR deletion.

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Association Between the Reproductive Health of Young Women and Cardiovascular Disease in Later Life: Umbrella Review

Cited by 17 publications

References 125 publications

The Impact of Sex and Gender on Stroke

The Impact of Sex and Gender on Stroke

Pregnancy and Reproductive Risk Factors for Cardiovascular Disease in Women

Midgestation Leptin Infusion Induces Characteristics of Clinical Preeclampsia in Mice, Which Is Ablated by Endothelial Mineralocorticoid Receptor Deletion

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