Pregnancy, stress, sleep issues, physiology among women's unique cardiovascular concerns

Women face many female-specific risks for heart disease and stroke, including pregnancy, physical and emotional stress, sleep patterns and many physiological factors, according to multiple studies highlighted in this year’s Go Red for Women® special issue of the Journal of the American Heart Association, published online today.

“Although cardiovascular disease is the leading cause of death in men and women, women are less likely to be diagnosed and receive preventive care and aggressive treatment compared to men,” said Journal of the American Heart Association Editor-in-Chief Barry London, M.D., Ph.D., Ph.D., the Potter Lambert Chair in Internal Medicine, director of the division of cardiovascular medicine, director of the Abboud Cardiovascular Research Center, professor of cardiovascular medicine and professor of molecular physiology and biophysics at the University of Iowa’s Carver College of Medicine in Iowa City, Iowa. “Identifying and addressing the unique ways cardiovascular disease affects women is critical to improving outcomes and saving lives, and we’re pleased to highlight this very important and impactful research.”

Of note in this issue is a report from the American Heart Association’s Go Red for Women Strategically Focused Research Network. Launched in Spring 2016, this initiative funded five research centers to extensively study cardiovascular (CVD) risk in women:

• Columbia University Irving Medical Center in New York City - Sleep & CVD Risk in Women Across the Lifespan
• Johns Hopkins University School of Medicine in Baltimore - Role of Sex Hormones and Cyclic GMP-PKG in Cardiac and Metabolic Disorders in Patients with Heart Failure with preserved Ejection Fraction (HFpEF)
• Magee-Women’s Research Institute and Foundation in Pittsburgh - Women’s Cardiovascular Health and Microvascular Mechanisms: Novel Insights from Pregnancy
• New York University Langone Medical Center in New York City - The Women’s Heart Attack Research Program: Mechanisms of Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA), Platelet Activity and Stress
• University of California at San Diego - Sedentary Behavior & CVD Risk in Latina Women

This report highlights the findings of the centers, showing how insufficient sleep, sedentariness and pregnancy-related complications may increase CVD risk in women. It also details the presentation and factors associated with myocardial infarction with non-obstructive coronary arteries and heart failure with preserved ejection fraction in women. Additional collaborative studies assessed the relations among CVD risks and various lifestyle behaviors including nightly fasting duration, mindfulness and behavioral and physical risk factors. Other research focused on metabolomic profiling of heart failure with preserved ejection fraction in women.

Among the many findings:

• Researchers at Columbia University Irving Medical Center found that both poor sleep quality and risk of obstructive sleep apnea affected systolic and diastolic blood pressure. Women who reported adequate sleep duration (seven or more hours a night), good sleep quality, no insomnia or snoring, low risk for obstructive sleep apnea and a tendency for morning activities and morning alertness had better overall cardiovascular health. These associations were stronger among postmenopausal women and women from underrepresented racial and ethnic groups. Researchers also found that poor sleep may negatively impact cardiovascular health through consumption of a higher-energy and lower-quality diet. It may also influence psychosocial risk factors for CVD including depression, low social support and caregiving.
• Researchers at the University of California at San Diego were focused on understanding risk factors, intervention methods for and metabolic consequences of higher levels of sedentary behavior and sitting time among Latinas. In their analysis of data from 401 women of Mexican heritage women who participated in the Hispanic Community Health Study/ Study of Latinos Casitas Ancillary Study, participants were found to sit, on average, 5.65 hours per day. Women more most likely to spend their sedentary time in front of screens such as televisions or computers (3.15 hours per day), as compared to leisure time sitting (e.g., knitting, talking with friends - 1.77 hours per day) or transportation (1.02 hours per day). Through additional studies of interventions and the molecular consequences of sitting, researchers found the amount of time spent sitting can be reduced significantly by employing a behavior modification program and higher cumulative sitting time is associated with certain cardiometabolic risk biomarkers that can increase cardiovascular risk.

Many of the studies in the Association’s Strategically Focused Research Network have been published in scientific journals and presented at scientific meeting, and significant research continues. The findings generated by the initiative and the new investigators trained in multi-disciplinary research, will further promote awareness among the public and in the medical field about the female-specific factors that influence CVD.

Below are highlights of additional manuscripts focused on cardiovascular disease in women in this special issue of the Journal of the American Heart Association. The complete manuscripts can be here.

Early pregnancy atherogenic profile in a first pregnancy and hypertension risk 2-7 years after delivery – Janet Cotav, et al.

In the nuMoM2b-Heart Health Study, researchers evaluated whether cardiometabolic risk factors identified early in a first pregnancy were related to adverse pregnancy outcomes (APO) and/or gestational diabetes (GDM), as well as subsequent maternal hypertension 2-7 years after giving birth.

The multicenter cohort of 4,471 women were tracked for adverse pregnancy outcomes including hypertensive disorders of pregnancy, preterm delivery, low birthweight for gestational age and gestational diabetes and for their risk of hypertension (130/80 mmHg or antihypertensive use) 2-7 years after giving birth.

Among all participants, 24.6% of the women (1,102) experienced an adverse pregnancy outcome or gestational diabetes during a first birth. Women with at least one of these complications were, on average, more likely to be older than 35, to smoke, and to be of non-Hispanic Black race/ethnicity.

Women with an APO or GDM were more likely to have an elevated cardiovascular risk profile in the first trimester: they were more likely to have obesity (34.2% vs. 19.5%); had a higher mean blood pressure (SBP 112.2 mm Hg vs. 108.4 mm Hg; DBP 69.2 mm Hg vs. 66.6 mm Hg); had higher mean concentrations of glucose (5.0 vs. 4.8 mmol/L); had a higher median level of insulin (77.6 pmol/L vs. 27 60.1 pmol/L); high triglycerides (1.4 mmol/L  vs. 1.3 mmol/L) and hsCRP, high sensitivity c-reactive protein, a marker for inflammation (5.6 nmol/L vs. 4.0 nmol/L); or had lower HDL-C or good cholesterol (1.8 mmol/L vs. 1.9 mmol/L).

A total of 32.8% of women with APOs or GDM had hypertension (blood pressure ≥130/80 mmHg or took blood pressure medication) within 2-7 years after delivery, compared to 18.1% of women with no APO or GDM. Compared to women with no complications, those who had an APO or GDM had higher rates of elevated blood pressure (7.6% vs. 6.3%) and stage 1 (19.9% vs. 13.3%) and stage 2 hypertension (12.9% vs. 4.8%). After accounting for confounders (age, race/ethnicity, insurance status and smoking), early pregnancy BMI, total cholesterol, HDL-C, LDL-C, glucose, insulin, hsCRP, triglycerides, blood pressure, diet quality and physical activity were all related to increased risk of hypertension 2-7 years after giving birth.

The researchers said because women typically have access to health care during pregnancy and postpartum, assessment of cardiometabolic health early in pregnancy may help to identify risk for APO and GDM and to identify opportunities to improve cardiovascular health later in life.

The Associations of Job Strain, Life Events and Social Strain with Coronary Heart Disease in the Women's Health Initiative Observational Study - Yvonne Michael, et al

Researchers analyzed long-term health data for 80,825 women in the Women’s Health Initiative Observational Study, who had a mean age of 63.4 years when they enrolled in the study, and they were followed for an average of 14.7 years. They aimed to determine the independent and synergistic effect of different stress domains, including work, stressful life events and social relationships, on women’s coronary heart disease (CHD) risk.

Job strain was determined by factoring job control (whether workers can exert influence over tasks) and job demand (the workload and intensity of the job). Stressful life events and social strain were assessed through self-reported questionnaires. Cox proportional hazard models were used to evaluate associations of each stressor with CHD separately and together.

A total of 3,841 women (4.8%) developed coronary heart disease during an average of 14.7 years of follow-up. After adjustment for age, other stressors, job tenure and socioeconomic factors, highly stressful life events were associated with a 12% increased risk of CHD, and high social strain was associated with a 9% increased risk of CHD. While job strain was not independently associated with CHD risk, researchers observed a statistically significant interaction between job strain and social strain. Women who had high social strain but low job control and low job demand had a 21% increased risk of CHD.

Researchers concluded that stressful life events and social strain were each associated with increased risk of CHD among women. For job strain, the increased CHD risk was confounded by socioeconomic factors. Exposure to job strain and social strain interacted synergistically, resulting in a higher risk of CHD than expected from exposure to either stressor alone.

This study is accompanied by an editorial, Pearls and Purple: The Dawn of a Modern Age - Melissa Tracy, et al.

Sexual Assault and Carotid Plaque among Midlife Women – Rebecca Thurston, et al.

Researchers in this study examined whether women who reported being the victim of sexual assault had higher carotid artery plaque build-up levels and if those levels continued to rise during midlife. Study participants included 160 non-smoking, CVD-free women ages 40-60 years, 28% of whom reported being the victim of sexual violence. The women were assessed twice between 2012 and 2020, and at both evaluations, they completed questionnaires, physical measures, blood tests and ultrasounds to measure plaque build-up in the carotid artery.

Compared to women who did not report a history of sexual assault, the women who were victims of sexual violence were four times more likely to have plaque build-up of more than 30% of the carotid artery at baseline and three times more likely to have that extent of plaque build-up at follow-up.

Researchers said their findings indicate sexual assault is associated with a higher level of carotid atherosclerosis, and the levels appear to increase over midlife. The associations were not explained by standard CVD risk factors, depression or symptoms of post-traumatic stress.

Other studies in this special issue include:

• Sex differences in the association of body composition and cardiovascular mortality - Preethi Srikanthan, et al.
• Maternal coronary heart disease, stroke and mortality within one, three, and five years of delivery among women with hypertensive disorders of pregnancy and pre-pregnancy hypertension – Angela Malek, et al.
• Gender issues in Italian catheterization laboratories: The GENDER-CATH Study - Chiara Bernelli, et al.
• Breast cancer promotes cardiac dysfunction through deregulation of cardiomyocyte calcium handling protein expression that is not reversed by exercise training - Carlos Negrao, et al.
• Long-term postpartum cardiac function among women with preeclampsia - Sajid Shahul, et al.
• Sex differences in heart failure with preserved ejection fraction - Shungo Hikoso, et al.
• Healthy lifestyle and clonal hematopoiesis of indeterminate potential - Results from the Women's Health Initiative - Bernhard Haring, et al.
• Gender differences in publication authorship during COVID-19: A bibliometric analysis of high impact cardiology journals - Nosheen Reza, et al.
• Developing an internally validated Veterans Affairs women’s cardiovascular disease risk score using Veterans Affairs national electronic health records - Haekyung Jeon-Slaughter, et al.
• The Women in cardiology Twitter network: An analysis of a global professional virtual community from 2016 to 2019 - Janet Han, et al.
• A paucity of female interventional cardiologists: What are the issues and how can we increase recruitment and retention of women? - Cindy Grines, et al.
• Sex differences in rupture risk and mortality in untreated patients with intact abdominal aortic aneurysms – Rebecka Hultgren, et al.