Pregnancy- the ultimate cardiovascular stress test.

Pregnancy is characterised by physiological adaptations and hormonal and metabolic changes 10 , which ensure adequate uteroplacental blood flow for the developing foetus 11 . Oestradiol increases nitric oxide and vasodilatory prostaglandin synthesis, which lead to a decrease in peripheral vascular resistance (PVR). This results in a compensatory increase in stroke volume and cardiac output 12 . These changes are most marked in the first trimester and are associated with a decrease in blood pressure (BP) and increase in heart rate 11 , 13 . Additionally, left ventricular wall thickness, mass and end diastolic volume increase throughout pregnancy 11 , 14 . During labour, cardiac output increases even further. Uterine contractions cause an auto-transfusion of up to 500 mL of blood back into the maternal circulation. Moreover, pain further elevates heart rate and blood pressure. Post delivery, inferior vena cava obstruction from the foetus is relieved and cardiac output increases 14 . Cardiac output returns to baseline around 2 weeks postpartum. While these changes are well tolerated in healthy women, women with underlying cardiac disease may struggle to adapt. Moreover, in those with pregnancy complications such as preeclampsia, these changes may persist.

Pregnancy provides a unique window into a woman’s cardiovascular health. The profound haemodynamic and hormonal changes of pregnancy, while well tolerated by most, can unmask undiagnosed or subclinical cardiac disease, effectively acting as a natural “stress test.” Adverse pregnancy outcomes including hypertensive disorders of pregnancy, gestational diabetes, and preterm birth are now recognised as early indicators of increased long-term cardiovascular risk. Despite growing awareness, structured pathways for cardiovascular risk assessment, prevention, and long-term follow-up after adverse pregnancy outcomes remain limited. Establishing evidence-based models of care is essential to close this gap. Future research should prioritise optimal screening strategies, early intervention, and targeted management of subclinical cardiovascular disease in this high-risk population to prevent progression to symptomatic disease. Additionally, there is a critical need to include women of reproductive age in well-designed clinical trials and large observational datasets.

Cardiovascular disease (CVD) remains the leading cause of death in women globally 1 . Despite this, women remain under-diagnosed and under-treated 2 . Importantly, much of the existing evidence for CVD management is derived from studies involving postmenopausal women, limiting its applicability to women of childbearing age. This gap is particularly significant in the context of pregnancy and the postpartum period, where unique physiological changes and risk factors influence cardiovascular health. Underrepresentation or exclusion from cardiovascular clinical trials limits understanding of the contribution of sex to CVD, and consequently the development of sex‑specific strategies and evidence‑based strategies for CVD prevention and management in this population 3 . In a recent systematic review, women accounted for only 41% of all participants in CVD trials with particularly low representation in studies assessing coronary artery disease, arrhythmias, acute coronary syndrome and heart failure 4 . Only 30.6% trials in this review involved patients aged between 19 and 55 years. Even when included, women often contribute proportionately less to treatment effect estimates and the overall evidence base 5 . Historically, pregnant women have been excluded from CVD trials largely due to ethical and safety concerns, particularly teratogenicity risk 6 . Although data from the Registry of Pregnancy and Cardiac Disease indicates that approximately 32% of pregnant women with CVD use cardiac medications, research involving pregnant and lactating women remains scarce 7 . Together, these factors have contributed to a relative lack of evidence to inform optimal care and improve outcomes in women over their lifespan. Recently, sex and gender specific CVD risk factors have become increasingly recognised 8 . Pregnancy, in particular, has been described as the ‘ultimate CVD stress test’ 9 , offering a unique opportunity to identify women with underlying CVD and those at risk of CVD. This review sought to explore the complex interactions between pregnancy and CVD and its implications for improving early risk identification and prevention across the life course in women.

Impaired physiological adaptation in pregnancy has been found to unmask or predispose to underlying cardiovascular risk 46 (Fig. 1 ). This risk is compounded in those who are socioeconomically disadvantaged with reduced access to care, low income levels and inadequate social supports 47 . Fig. 1 Complex interplay between pregnancy and CVD. Pregnancy complications are associated with long-term CVD. Pregnancy complications are associated with long-term CVD. Preeclampsia (PE) is defined as onset of hypertension after 20-weeks’ gestation associated with proteinuria, maternal organ and/or uteroplacental dysfunction 48 . PE has been attributed to abnormal physiological adaptation to pregnancy and endothelial dysfunction 49 , 50 . It is now recognised that PE is associated with a significant increase in long-term CVD with a 4-fold increase in heart failure (HF) and 2-fold increase in coronary artery disease 48 . Even in asymptomatic women with a history of PE, evidence of subclinical atherosclerosis has been observed during pregnancy which persists postpartum 51 . In the long-term, women with prior PE have a 2-fold increased risk of developing coronary plaque, with greater volumes of non-calcified plaque, largely driven by increased fibrous and fibrous fatty plaque volumes 52 . Similarly, PE is associated with altered cardiac structure in the antenatal period with higher left ventricular mass, higher relative wall thickness and evidence of diastolic dysfunction. These changes are thought to persist postpartum, increasing risk of clinical heart failure 53 . A history of hypertensive disorder of pregnancy (including preeclampsia and gestational hypertension) has also been found to confer a higher incidence of aortic stenosis and mitral regurgitation 54 . Gestational diabetes (GDM) is a well-known risk factor for future development of type 2 diabetes (T2DM) as well as CVD independent of T2DM 55 . Moreover, preterm birth, intrauterine growth restriction (IUGR), stillbirth, miscarriage, low birth weight and placental abruption have also been found to increase CVD risk 23 , 56 , 57 . Increasing evidence suggests that PE and GDM reflect underlying metabolic disturbances, including insulin resistance, which may unmask a predisposition to future cardiometabolic disease. Insulin resistance typically increases in late pregnancy as part of normal physiology, but may be exaggerated in these conditions, and has been proposed as an early marker of future metabolic syndrome and CVD 58 . Assisted reproductive technologies (ARTs) are associated with an increased risk of short-term CVD, particularly during the treatment cycle and throughout pregnancy 59 – 61 . This is thought to be due to hormonal changes, ovarian hyperstimulation causing a prothrombotic state and endothelial dysfunction. Furthermore, conditions which predispose to infertility such as polycystic ovary syndrome (PCOS) and endometriosis, are also known to increase CVD risk 62 , 63 . It remains unclear whether these associations exist due to shared pathophysiological mechanisms or whether pregnancy complications, including PE and GDM, lead to oxidative damage to the maternal cardiovascular system which persists long-term and predisposes to later-life CVD 64 . On one hand, factors such as obesity, metabolic abnormalities, insulin resistance, inflammation and endothelial dysfunction predispose women to both pregnancy complications and CVD. On the other hand, studies have identified an increase in inflammatory cytokines and antiangiogenic proteins such as soluble fms-like tyrosine kinase (sFlt-1) within the placenta and serum of preeclamptic women 65 , 66 . Inflammation, oxidative stress and microvascular dysfunction persist postpartum and have been thought to predispose to later life CVD 67 , 68 . Despite the mechanistic uncertainty, these associations present an opportunity for clinicians to identify and prevent CVD in this high-risk population. Despite the well-established association between pregnancy complications and long-term cardiovascular outcomes, uniform recommendations on postpartum follow up are lacking. International guidelines currently differ with respect to timing and frequency of monitoring (Table 1 ). Engagement of women in the postpartum period is limited by multiple barriers, including lack of knowledge among women and health professionals about the association between pregnancy complications and future cardiovascular disease. This is compounded by the practical challenges of the postpartum period, including time constraints, fatigue, and limited access or ability to attend primary care services 69 . Early follow up postpartum in dedicated Women’s Health clinics are likely to be most beneficial in this high-risk group 70 . These clinics would involve regular risk factor screening, education regarding long-term CVD risk, as well as, tailored nutritional and exercise counselling 71 . The clinic team would ideally consist of obstetric medicine physicians, nurses, obstetricians, medical interpreters and indigenous liaison officers where required - to facilitate access for women of all cultural and socioeconomic backgrounds. Telehealth or digital clinics have been identified as effective and accessible interventions- ideal for time-poor mothers and those living in regional or remote areas 71 . Table 1 CVD monitoring post PE guidelines Guideline Country Year Population Recommendations for follow up 2025 European Society of Cardiology (ESC) Guidelines for the management of cardiovascular disease and pregnancy 19 Europe 2025 Women with adverse pregnancy outcomes including preeclampsia Longer duration of postpartum care including cardiovascular risk assessment and counselling on CVD risk prevention. British National Institute for Health and Care Excellent (NICE) guideline: Hypertension in pregnancy: diagnosis and management United Kingdom 2019, updated in 2023 Women who have had an hypertensive disorder of pregnancy including preeclampsia or gestational hypertension Advise women about increased risk of hypertension and CVD in later life. Advise women to discuss how to reduce their risk of CVD with their GP or specialist- including avoiding smoking, maintaining a healthy lifestyle and maintaining a healthy weight. Advise women who have had preeclampsia to achieve and keep a BMI within the healthy range before their next pregnancy. Dutch multidisciplinary guideline: Cardiovascular risk management after reproductive and pregnancy-related disorders 72 Netherlands 2016 Women with prior preeclampsia Structured cardiovascular follow up including cardiovascular risk assessment and optimisation of modifiable risk factors through lifestyle modification and management of traditional CVD risk factors. American College of Obstetricians and Gynaecologists (ACOG) Gestational Hypertension and Preeclampsia Practice Bulletin Summary 73 USA 2020 Women with preeclampsia or gestational hypertension (higher-risk individuals require earlier review) BP check and visit within 3-10 days of delivery for high-risk individuals. Comprehensive postpartum visit between 4–6 weeks after delivery. Later postpartum visits (2 weeks to 1 year postpartum) with focus on BP management, lifestyle optimisation, cardiovascular risk assessment and transition to primary care. SOMANZ Hypertension in Pregnancy Guideline 2023 74 Australia 2023 Women with hypertensive disorders of pregnancy Inform women about long-term risks and importance of postpartum follow up prior to discharge from hospital. Follow up with healthcare provider within 1 week of discharge from hospital to ensure stable BP. At 3–6 months postpartum, follow up review of BP, urine protein assessment, BMI and metabolic profile (fasting blood glucose, fasting cholesterol) should be considered. Weight management, lifestyle changes and smoking cessation should be discussed. Annual follow up of BP, urine protein, BMI and metabolic profile. The 2021 International Society for the Study of Hypertension in Pregnancy (ISSHP) classification, diagnosis and management recommendations for international practice 75 International 2021 Women with hypertensive disorders of pregnancy BP should be monitored at least once on days 3–7 postpartum. At 3 months postpartum, all women should be reviewed to ensure BP, urinalysis and any laboratory abnormalities have normalised. At 6 months postpartum, all women should be reviewed again, BP > 120/80 mmHg should lead to discussion of lifestyle change. Women should be counselled about heightened health risks for mother and offspring. Cardiovascular risk score should be calculated. Annual medical review is recommended for the first 5–10 years postpartum. Healthy lifestyle should be adopted including eating well, exercising, aiming for an ideal body weight, living smoke-free and aiming for a BP < 120/80 mmHg. Society of Obstetricians and Gynaecologists Canada Guideline: Hypertensive disorders of pregnancy: Diagnosis, Prediction, Prevention and Management 76 Canada 2014 BP should be measured at least once daily on days 3–7 postpartum. At 6 weeks postpartum, women should be counselled on future obstetric and cardiovascular health risks. Women should be counselled on evidence-based therapies to lower risk of HDP in future pregnancy including avoiding weight gain. Screening and treatment of cardiovascular risk factors should be individualised based on the woman’s cardiovascular risk and health behaviours should be considered as first line therapy. International guidelines differ with respect to timing and frequency of CVD monitoring post pregnancy complicated by PE. CVD monitoring post PE guidelines International guidelines differ with respect to timing and frequency of CVD monitoring post pregnancy complicated by PE.