JAHA Go Red for Women Spotlight 2023

February is Go Red for Women month, a time to increase public awareness of the impact of cardiovascular disease (CVD) among women. It is also a time to feature the robust literature regarding differences between men and women in the epidemiology, outcomes, and risk factors for CVD. In this issue of the Journal of the American Heart Association (JAHA), we feature a compendium of articles highlighting important findings that help provide a more nuanced understanding of sex‐related differences and sex‐specific (female) risk factors for CVD.

In some cases, sex‐related differences are disparities that are systematic, socially produced, and modifiable. ¹ For example, the subjective nature of decision‐making is at risk for bias. Breathett and colleagues studied the allocation process of advanced heart failure therapies and found that women were more likely to receive these therapies when teams making allocation decisions had better group dynamics and higher quality decision‐making processes. ² Further work is needed to promote high‐quality group decision‐making to address sex‐related disparities.

Lee and colleagues evaluated sex differences in receiving oral anticoagulation prescriptions among patients with nonvalvular atrial fibrillation in Scotland. They found that women were less likely to receive anticoagulation therapy than men, which was attributable to differences in treatment with vitamin K antagonists. ³ The reasons for this difference in treatment are unclear but may be because of biologic differences in achieving a stable therapeutic level. Yet, among women who were not treated, there was a greater increase in mortality and major adverse cardiac events without a difference in bleeding. Fortunately, Lee and colleagues found that with the introduction of direct oral anticoagulants, the disparities in treatment decreased over time.

Sex‐related differences among those with aortic disease are evaluated in 2 articles in this spotlight. Chang et al. found that women with aortic dissection had higher mortality than men, primarily among those managed medically. ⁴ It has been demonstrated that women with type B aortic dissection are more likely to be managed conservatively, whereas men are more likely to receive the intervention. ⁵ Although several clinical factors may account for the differences in management between men and women, sex‐related biases and a lack of knowledge about the prevalence and pathophysiology of aortic diseases in women may also lead to disparities in diagnosis and management. ⁶ Additionally, Yousef and colleagues evaluated a cohort of patients undergoing thoracic endovascular aortic repair and found similar in‐hospital mortality among men and women and that women had lower 30‐day readmission. ⁷ This is reassuring in the context of worse outcomes for women for many other cardiovascular procedures. However, women were much more likely to have aortic aneurysms, and men were more likely to have type B aortic dissections. These studies add to our knowledge of sex‐based differences in aortic pathophysiology and management and outcomes of aortic disease.

Several studies in this spotlight highlight female‐predominant or female‐specific risk factors. Brink and colleagues found that anthropometric obesity measures were more significant predictors of deep venous thrombosis and pulmonary embolism among women than men. ⁸ Abe and colleagues report increased rates of hospitalization for ST‐segment–elevation myocardial infarction among women under 45 years of age and identified an increased prevalence of female‐predominant risk factors such as autoimmune and rheumatic diseases as well as female‐specific risk factors such as adverse pregnancy outcomes. ⁹ Further exploring sex‐specific biological pathways, Xiao and colleagues evaluated the association between genetic risk of adverse cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) and female health conditions (endometrial cancer, polycystic ovarian disease, gestational diabetes). ¹⁰ Using polygenic scores, they found that polygenic susceptibility to cardiometabolic traits is associated with an increased risk of certain female‐specific health conditions.

We also feature several articles that highlight the importance of female‐specific reproductive factors. Kim et al. provide an overview of the contributions of the CARDIA (Coronary Artery Risk Development in Young Adults) study. ¹¹ Although not designed from the onset to be a Women's Health study, as of 2021, there have been >500 articles from CARDIA on this topic. This review features 77 of these articles that provide critical insight into the reproductive milestones, from menarche to menopause, that shape CVD risk. It also foreshadows the future contributions the CARDIA study is well positioned to provide on reproductive and chronological aging. To complement this review, other articles in this stoplight help better understand the impact of reproductive factors on CVD risk. Beginning with menarche, Chen et al. provide additional support that age of menarche is protective against hypertension in the CMEC (China Multi‐ethnic Cohort) and that adiposity (eg, waist circumference and body mass index) partly mediated this relation, especially among premenopausal women. ¹²

Fertility is another important milestone for reproductive health, as extensive research has documented associations between the timing and regularity of the menstrual cycle and early menopause with cardiovascular risk. However, infertility has been understudied, and research tends to focus on severe infertility corresponding to diagnoses of polycystic ovary syndrome and endometriosis. Farland et al. used data from the Nurses Health Study II to document that nonspecific infertility (ie, trying to conceive without success) was associated with an increased risk of coronary heart disease and that this relationship was most pronounced at younger ages and among those classified as overweight and/or obese. ¹³

Several articles in this spotlight focus on adverse pregnancy‐related outcomes. The United States is experiencing a maternal health crisis, with the highest mortality rate of any industrialized country and significant racial and ethnic inequities in maternal health. ¹⁴ CVD is the leading cause of maternal deaths, and Graves et al. provide a call to action to improve cardio‐obstetric care highlighting strategies in education, collaborative care models, and approaches to addressing inequities. ¹⁵ Management of hypertension during pregnancy is a critical tenet of cardio‐obstetric care, given substantial evidence that chronic hypertension is a risk factor for poor maternal, infant, and cardiometabolic outcomes. Lailler et al. corroborated these findings using data from the French National Health Data System to document that chronic hypertension before pregnancy was associated with maternal (eg, preeclampsia, venous thromboembolism) and infant outcomes (eg, preterm birth, infant death). ¹⁶ Among women with chronic hypertension, receiving antihypertensive medication was associated with a lower risk of obstetric hemorrhage, stroke, and acute coronary syndrome. An equally important hypertension disorder during pregnancy is preeclampsia. Efforts to minimize the impact of preeclampsia on adverse pregnancy outcomes and longer term cardiometabolic outcomes require more etiologic investigations. The identification of key biomarkers may help with this. Chen et al. provided evidence that third‐trimester maternal serum chemerin levels may be an important maternal biomarker for postpartum hypertension in women with preeclampsia. ¹⁷ Finally, Magnus et al. document breastfeeding as a protective factor to reduce adverse cardiometabolic outcomes among childbearing women. ¹⁸ Using data from the UK Avon Study Longitudinal Study of Parents and Children cohort, they found that breastfeeding 6 to 9 months was associated with improved cardiometabolic health, especially among women with hypertensive disorders during pregnancy. Taken together, these findings support guidelines recommending the initiation of pharmacological treatment and provide insight into potential targets for future interventions to address hypertensive disorders during pregnancy.

A common theme among the articles featured in this spotlight is the use of observational data, which despite extensive efforts, is fraught with bias and residual confounding. To address these limitations, an exciting study by Ardissino et al. used a Mendelian randomization framework to document the causal role of reproductive factors (age at first birth, number of live births, earlier menarche) with CVD outcomes (eg, higher arterial fibrillation, coronary heart disease, heart failure, and stroke). ¹⁹ They documented that modifiable CVD risk factors and social determinants of health (SDoH) partly mediate these associations. The inclusion of SDoH was novel, as more research is needed to understand the role that SDoH may play in cardiovascular health inequities. Meyerovitz et al. also acknowledge the need for more research that addresses SDoH as a fundamental cause of CVD health inequities. They investigated whether SDOH factors mediated racial inequities in hypertension control among women of childbearing age. ²⁰ Although associations persisted after adjustment for a broad range of SDoH factors, the authors note that future studies should incorporate key structural drivers (eg, structural racism) of CVD inequities. ²¹

In addition to highlighting and reflecting on the scientific contributions advancing our understanding of the epidemiology, risk factors for, and outcomes of CVD among women, we would like to acknowledge the extent to which women contribute to cardiovascular science. In their brief communication, Blumer and colleagues evaluated the contribution of women. ²² They found that from 2002 to 2020, there has been an increase in the proportion of women authors. Additionally, women in the senior author position were more likely to mentor women and diverse research teams. This is exciting. However, the proportion of women in the first or last author position remained the same over this time frame, and women comprised less than 25% of authors in cardiovascular subspecialties. Women in cardiovascular science have made great strides, and we have many to go. This spotlight highlights critical avenues for future investigation as we fight to reduce sex‐specific inequities in cardiovascular health.

Disclosures

None.