Gender equity and cardiovascular disease: hypertensive disorders of pregnancy as an under-recognized cardiovascular risk factor

This editorial refers to ‘Adverse pregnancy outcomes and risk of atrial fibrillation: findings from the HUNT study’, by H. Morooka et al. https://doi.org/10.1093/eurjpc/zwaf233. Equity, a basic tenet of public health and global health, is under threat. Health research, including gender equality, is no exception. For example, the Women’s Health Initiative, the US’s largest and longest running study of women’s health, which is estimated to have prevented 126 000 cases of breast cancer and 76 000 cases of cardiovascular disease (CVD), was due to be scrapped. Fortunately, on 24 April 2025, the US government announced that it would continue funding the study.1 These geopolitical issues are pertinent because women face numerous inequalities in CVD, from epidemiology to trials and diagnostics to drugs. Successive calls to action, including a specific Lancet Commission on women and CVD,2,3 have attempted to raise awareness of the gaps in both prevention and treatment of CVD, with limited success to-date. In this regard, atrial fibrillation (AF) has been highlighted as a priority for research and care, affecting at least 29·4 (95% UI 22·4–37·3) million women globally, and associated with increased risk of stroke, heart failure, myocardial infarction, and other CVDs. Moreover, lifetime risk of AF for women is 20–25% at age 40 years.3 Therefore, opportunities to improve prevention and management of AF need to be identified. Moreover, AF is associated with higher absolute all-cause mortality risk in women than men.4 Research regarding sex-specific differences and inequalities in AF is therefore crucial. Pregnancy may offer several potential avenues for further research, treatment, and prevention of AF in women, including age at pregnancy. The Women’s Health Initiative showed that rates of ischaemic stroke (3.8% vs. 2.4%), haemorrhagic stroke (1.0% vs. 0.5%), and CVD death (3.9% vs. 2.3%) were significantly higher among women with pregnancy in advanced age (≥40 years), compared with pregnancy in normal age. After adjustment for age, race/ethnicity, heart failure, systolic blood pressure, AF, alcohol use, and cigarette smoking, women with pregnancy in advanced age were more likely to experience haemorrhagic stroke, but not ischaemic stroke, myocardial infarction, and cardiovascular death.5 In other words, AF is one of the factors that explain higher rates of stroke and CVD death in women with pregnancy in advanced age. However, consideration of more proximal factors is needed to better prevent stroke and its risk factors, such as AF. Prior research suggests an association between hypertensive disorders of pregnancy (HDP) and risk of AF, but the mediator of this association is unclear. The impact of adverse pregnancy outcomes, including preterm birth and small/large-for-gestational age (SGA/LGA) offspring, on later risk of AF is unknown. In this issue of European Journal of Preventive Cardiology, Morooka and colleagues conducted a prospective analysis study for 15 104 parous women with 34 674 births. The authors used data from an ongoing, population-based cohort study (HUNT study), based in Trøndelag county, Norway, and linked these data with hospital-derived data on AF and birth data from the Medical Birth Registry of Norway.6 Atrial fibrillation was common: 2.0% of women developed AF. Adverse pregnancy outcomes were even more common: 8.8% had HDP and 9.5%, 18.9%, and 18.0% of women had a history of preterm birth, SGA, and LGA offspring, respectively. Obesity (40.4% vs. 24.4%), diabetes mellitus (18.9% vs. 2.6%), hyperthyroidism (6.9% vs. 2.8%), and hypertension (47.4% vs. 21.6%) were more prevalent in women with AF than those without AF, after age-standardization. The authors describe three main findings. First, a history of HDP was associated with a doubling of risk of AF among women aged 45–65 years, compared to women with normotensive pregnancies. Second, for women over 45 years, a history of LGA offspring was associated with a 37% increased AF risk, compared to women with a history of appropriate-for-gestational-age offspring. Third, after pregnancy, body mass index (BMI) might explain about 40% of the associations between HDP and LGA with AF. This research has several advantages over previous studies. First, diagnoses of adverse pregnancy outcomes were available from a national birth registry and validated diagnoses of AF were also available. Second, the long follow-up period tracked women into older age when absolute risk of AF is greatest. Third, this represents one of the first studies to estimate the excess risk of AF in parous women and the proportion explained by adverse levels of modifiable cardiovascular risk factors (systolic and diastolic blood pressure, BMI, and diabetes). Fourth, the robust methods are an advance in terms of the use of mediation analysis, allowing estimation of the relative proportion of direct and indirect pathways that may affect development of AF. Direct effects are pathways independent of a modifiable AF risk factor, and the indirect effect is the pathway via modifiable AF risk factors. However, there are some limitations. First, adjustment for gestational diabetes, pre-pregnancy BMI, smoking, and alcohol intake was not possible, making confounding by these factors a potential issue. Second, the study population in Norway means that the generalizability of the findings to other countries, including low-middle income contexts, is difficult to judge. Third, the data are based on the HUNT study survey in 2006–8. There have been major advances in care of pregnancy, hypertension, AF and CVD in the last two decades and therefore, the applicability of the findings to the current era of clinical practice needs to be balanced with changes in practice. It is becoming clear that not all HDP is equal: i.e. the subtype of HDP matters. In a recent, population-based, retrospective, Canadian cohort study of 771 521 nulliparous women between 2002 and 2017, 8% of women were diagnosed with HDP, which is very similar to the study by Morooka and colleagues. The investigators suggested a dose–response relationship between HDP and risk of AF, with more severe HDP subtypes and pre-pregnancy chronic hypertension associated with a 1.5–2.2 times higher cause-specific rate of AF, and a 1.4–2.1 times higher cause-specific rate of mortality, compared with no hypertension in pregnancy.7 The CVD risk associated with HDP is far beyond AF. For example, in another Norwegian cohort study of 508 422 women, preeclampsia was associated with a doubled risk of heart failure (hazard ratio, HR 2.00, 95% CI 1.50–2.68, P < 0.001), especially those with one lifetime birth and those with recurrent preeclampsia.8 In fact, adverse pregnancy outcomes also influence the risk of CVD in offspring. For example, in the Helsinki Birth Cohort Study, which includes 13 345 people born as singletons in Helsinki in the years 1934–44, high maternal BMI (≥30 kg/m2) during pregnancy and maternal height were found to predict AF in offspring.9 In a Danish study of 2 491 340 individuals from 1977 to 2018 with a median follow-up time was 18.37 years, maternal HDP was associated with an increased risk of early-onset CVD (HR: 1.23; 95% CI 1.19–1.26; P < 0.001). Again, the risk varied by type of HDP, i.e. preeclampsia or eclampsia: HR 1.22 (95% CI 1.18–1.26; P < 0.001), gestational hypertension: 1.25 (95% CI 1.17–1.34; P < 0.001), and pre-gestational hypertension: 1.28 (95% CI 1.15–1.42; P < 0.001). The risk also varied by subtype of CVD, e.g. hypertensive disease (HR 2.11; 95% CI 1.96–2.27; P < 0.001) and myocardial infarction (HR 1.49; 95% CI 1.12–1.98; P = 0.007). Maternal history of CVD and diabetes further increased the risk of CVD in offspring.10 A history of HDP has far-reaching effects for women and their children. Improved surveillance of traditional and female-specific CVD risk factors, such as hypertension and diabetes, before and during pregnancy, and targeted prevention strategies to reduce the occurrence and burden of HDP should be a priority for health systems. The broader context is that HDP and risk of AF in women are areas of research and practice which need and deserve increased focus if we are to move towards the ideal of gender equity in prevention, diagnosis and treatment of CVD. Finally, the detailed study of the impact of pregnancy and its outcomes requires longitudinal study over generations, showing the value for research and care to health systems which have historically and currently prioritized linked electronic health records and related research. There are no new data associated with this article.