Regional Differences in the US in Outcomes with Preeclampsia.

This study explores preeclampsia outcomes across US regions and examines regional differences in specific preeclampsia-associated pregnancy complications and disease management. Patient-reported measures were obtained from The Preeclampsia Registry, an open-access database composed of women with at least one pregnancy diagnosed with a hypertensive disorder of pregnancy. Pregnancies and associated outcomes were stratified by US region (Northeast, Midwest, South and West). Among 2,667 pregnancies of which 92% were in White women, maximum systolic blood pressure at any time in pregnancy was highest among women in the South and Midwest (p=0.039). Furthermore, more women in the South received pre-pregnancy antihypertensives (p=0.026) and antenatal steroids (p=0.025) and delivered at an earlier gestational age (p=0.014) compared to women in other regions. Pregnancy complications such as elevated liver enzymes were higher in women in the South (p=0.019), and women in the South and West had additional end-organ damage such as renal complications (p<0.001) and hemolysis (p=0.008) as compared to women in other regions. Further investigation is needed to assess whether healthcare access or policy could be contributing to these regional discrepancies.

Rheumatoid arthritis and cardiovascular complications during delivery: a United States inpatient analysis.

BACKGROUND AND AIMS: Persons with rheumatoid arthritis (RA) have an increased risk of obstetric-associated complications, as well as long-term cardiovascular (CV) risk. Hence, the aim was to evaluate the association of RA with acute CV complications during delivery admissions. METHODS: Data from the National Inpatient Sample (2004-2019) were queried utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and a diagnosis of RA. RESULTS: A total of 12 789 722 delivery hospitalizations were identified, of which 0.1% were among persons with RA (n = 11 979). Individuals with RA, vs. those without, were older (median 31 vs. 28 years, P < .01) and had a higher prevalence of chronic hypertension, chronic diabetes, gestational diabetes mellitus, obesity, and dyslipidaemia (P < .01). After adjustment for age, race/ethnicity, comorbidities, insurance, and income, RA remained an independent risk factor for peripartum CV complications including preeclampsia [adjusted odds ratio (aOR) 1.37 (95% confidence interval 1.27-1.47)], peripartum cardiomyopathy [aOR 2.10 (1.11-3.99)], and arrhythmias [aOR 2.00 (1.68-2.38)] compared with no RA. Likewise, the risk of acute kidney injury and venous thromboembolism was higher with RA. An overall increasing trend of obesity, gestational diabetes mellitus, and acute CV complications was also observed among individuals with RA from 2004-2019. For resource utilization, length of stay and cost of hospitalization were higher for deliveries among persons with RA. CONCLUSIONS: Pregnant persons with RA had higher risk of preeclampsia, peripartum cardiomyopathy, arrhythmias, acute kidney injury, and venous thromboembolism during delivery hospitalizations. Furthermore, cardiometabolic risk factors among pregnant individuals with RA rose over this 15-year period.

Preconception Counseling for a Patient With a Mechanical Tricuspid Valve.

A 37-year-old woman with mechanical tricuspid valve thrombosis presented for preconception consultation. Multimodality imaging confirmed a malfunctioning bileaflet mechanical tricuspid valve with both leaflets fixed and open. This case highlights the key discussions held by the multidisciplinary pregnancy heart team.

Heart Team Approach for Cardiogenic Shock Management in Pregnancy Complicated by Mechanical Mitral Valve Thrombosis.

A 27-year-old pregnant woman at 24 weeks of gestation was admitted with cardiogenic shock due to mechanical mitral valve thrombosis. Following discussion with the heart team, thrombolysis was achieved with tissue plasminogen activator therapy followed by heparin infusion. Ultimately, the patient required mitral valve replacement for persistently elevated gradients.

Assisted reproductive technology: what are the cardiovascular risks for women?

INTRODUCTION: Infertility affects 15% of women of reproductive age in the United States. The use of assisted reproductive technology (ART) has been rising globally, as well as a growing recognition of reproductive factors that increase risk for cardiovascular disease (CVD). AREAS COVERED: Women with infertility who use ART are more likely to have established CVD risk factors, such as obesity, dyslipidemia, hypertension, and diabetes. They are also more likely to experience adverse pregnancy outcomes, which are associated with both peripartum and long-term cardiovascular complications. ART may lead to increased cardiometabolic demands due to ovarian stimulation, pregnancy itself, and higher rates of multifetal gestation. Preeclampsia risk appears greater with frozen rather than fresh embryo transfers. EXPERT OPINION: The use of ART and its association with long term CVD has not been well-studied. Future prospective and mechanistic studies investigating the association of ART and CVD risk may help determine causality. Nevertheless, CVD risk screening is critical pre-pregnancy and during pregnancy to reduce pregnancy complications that elevate future CVD risk. This also offers a window of opportunity to connect patients to longitudinal care for early management of cardiometabolic risk profile and initiation of preventive lifestyle and pharmacotherapy interventions tailored toward patient-specific risk factors.

Female-specific risk factors of parity and menopause age and risk of carotid plaque: the multi-ethnic study of atherosclerosis.

BACKGROUND: Female-specific factors of grand multiparity (≥5 births) and early menopause age are associated with an increased risk of cardiovascular disease (CVD). However, mechanisms are incompletely understood. Carotid plaque is a marker of subclinical atherosclerosis and associated with increased CVD risk. We evaluated the association of female-specific factors with plaque burden. METHODS: We included 2,313 postmenopausal women in the Multi-Ethnic Study of Atherosclerosis, free of clinical CVD, whose parity and menopause age were ascertained by questionnaires and carotid plaque measured by ultrasound at baseline and 10 years later. Parity was categorized as nulliparity (reference), 1-2, 3-4 and ≥5 live births. Menopause age was categorized as <45, 45-49, 50-54 (reference) and ≥55 years. Multivariable regression was performed to evaluate the association of parity and menopause age with carotid plaque presence (yes/no) and extent [carotid plaque score (CPS)]. RESULTS: The mean age was 64±9 years; 52.3% had prevalent carotid plaque at baseline. Compared to nulliparity, grand multiparity was significantly associated with prevalent carotid plaque after adjustment for CVD risk factors (prevalence ratio 1.17 (95% CI 1.03-1.35)) and progression of CPS over 10 years [percent difference 13% (95% CI 3-23)]. There was not any significant association of menopause age with carotid plaque presence or progression in fully-adjusted models. CONCLUSION: In a multiethnic cohort, grand multiparity was independently associated with carotid plaque presence and progression. Early menopause, a known risk factor for CVD, was not captured by carotid plaque in this study. These findings may have implications for refining CVD risk assessment in women.

Sex-specific differences in cardiovascular risk factors and implications for cardiovascular disease prevention in women.

Cardiovascular disease (CVD) is the leading cause of mortality for women globally. Sex differences exist in the relative risks conferred by traditional CVD risk factors, including diabetes, hypertension, obesity, and smoking. Additionally, there are female-specific risk factors, including age of menarche and menopause, polycystic ovary syndrome, infertility and the use of assisted reproductive technology, spontaneous pregnancy loss, parity, and adverse pregnancy outcomes, as well as female-predominant conditions such as autoimmune diseases, migraines, and depression, that enhance women's cardiovascular risk across the lifespan. Along with measurement of traditional risk factors, these female-specific factors should also be ascertained as a part of cardiovascular risk assessment to allow for a more comprehensive overview of the risk for developing cardiometabolic disorders and CVD. When present, these factors can identify women at elevated cardiovascular risk, who may benefit from more intensive preventive interventions, including lifestyle changes and/or pharmacotherapy such as statins. This review describes sex differences in traditional risk factors and female-specific/female-predominant risk factors for CVD and examines the role of coronary artery calcium scores and certain biomarkers that can help further risk stratify patients and guide preventive recommendations.

Psychosocial Stressors as a Determinant of Maternal Cardiovascular Health During Pregnancy.

Maternal psychosocial stress may be a risk factor for poor cardiovascular health (CVH) during pregnancy. We aimed to identify classes of psychosocial stressors in pregnant women and to evaluate their cross-sectional association with CVH. We performed a secondary analysis of women from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b) cohort (2010 to 2013). Latent class analysis was used to identify distinct classes of exposure to psychosocial stressors based on psychological (stress, anxiety, resilience, depression) and sociocultural indicators (social support, economic stress, discrimination). Optimal and suboptimal CVH was defined based on the presence of 0 to 1 and ≥2 risk factors (hypertension, diabetes mellitus, smoking, obesity, inadequate physical activity), respectively based on the American Heart Association Life's Essential 8. We used logistic regression to evaluate the association between psychosocial classes and CVH. We included 8,491 women and identified 5 classes reflective of gradations of psychosocial stress. In unadjusted models, women in the most disadvantaged psychosocial stressor class were approximately 3 times more likely to have suboptimal CVH than those in the most advantaged class (odds ratio 2.98, 95% confidence interval: 2.54 to 3.51). Adjusting for demographics minimally attenuated the risk (adjusted odds ratio 2.09, 95% confidence interval: 1.76 to 2.48). We observed variation across psychosocial stressor landscapes in women in the nuMoM2b cohort. Women in the most disadvantaged psychosocial class had a greater risk of suboptimal CVH which was only partially explained by differences in demographic characteristics. In conclusion, our findings highlight the association of maternal psychosocial stressors with CVH during pregnancy.

Prevalence and Correlates of Elevated NT-proBNP in Pregnant Women in the General U.S. Population.

BACKGROUND: Physiologic changes in N-terminal pro-B-type natriuretic peptide (NT-proBNP) across trimesters of pregnancy have not been well studied. OBJECTIVES: The authors aimed to measure NT-proBNP in adult women, by pregnancy status and trimester, in a nationally representative sample from the National Health and Nutrition Examination Survey 1999 to 2004. METHODS: We conducted a cross-sectional analysis of 2,134 women (546 pregnant) aged 20 to 40 years without a history of cardiovascular disease. RESULTS: Among pregnant women in the first trimester, the prevalence of elevated NT-proBNP (>125 pg/mL) was 20.0% (SE, 6.6%) compared to 2.4% (SE, 0.8%) among women in the third trimester and 8.0% among nonpregnant women. After adjustment for demographics and cardiovascular risk factors, NT-proBNP was 44% higher (absolute difference 26.4 [95% CI: 11.2-41.6] pg/mL) in the first trimester of pregnancy compared to nonpregnant women. Among pregnant women only, adjusted NT-proBNP was 46% lower (absolute difference -22.2 [95% CI: -36.9 to -7.5] pg/mL) in women in the third trimester compared to women in the first trimester. NT-proBNP was inversely associated with body mass index and with systolic blood pressure. CONCLUSIONS: Women in the first trimester of pregnancy had significantly higher NT-proBNP than those in the third trimester and compared to similarly aged nonpregnant women. The dynamic nature of NT-proBNP should be taken into consideration when ordering NT-proBNP lab tests in pregnant women.

Mode of delivery among women with maternal cardiac disease.

OBJECTIVE: To determine if maternal cardiac disease affects delivery mode and to investigate maternal morbidity. STUDY DESIGN: Retrospective cohort study performed using electronic medical record data. Primary outcome was mode of delivery; secondary outcomes included indication for cesarean delivery, and rates of severe maternal morbidity. RESULTS: Among 14,160 deliveries meeting inclusion criteria, 218 (1.5%) had maternal cardiac disease. Cesarean delivery was more common in women with maternal cardiac disease (adjusted odds ratio 1.63 [95% confidence interval 1.18-2.25]). Patients delivered by cesarean delivery in the setting of maternal cardiac disease had significantly higher rates of severe maternal morbidity, with a 24.38-fold higher adjusted odds of severe maternal morbidity (95% confidence interval: 10.56-54.3). CONCLUSION: While maternal cardiac disease was associated with increased risk of cesarean delivery, most were for obstetric indications. Additionally, cesarean delivery in the setting of maternal cardiac disease is associated with high rates of severe maternal morbidity.

High-Sensitivity Troponin T and I Among Pregnant Women in the US-The National Health and Nutrition Examination Survey, 1999-2004.

This cross-sectional study investigates the expected physiologic concentrations of high-sensitivity cardiac troponin in normal pregnancy.

The role of proprotein convertase subtillisin/kexin type 9 in placental salvage and lipid metabolism in women with preeclampsia.

INTRODUCTION: Preeclampsia is associated with decreased maternal low-density lipoprotein cholesterol (LDL-c), which is essential for fetal growth. The underlying mechanisms for decreased LDL-c in preeclampsia remain unknown. Proprotein convertase subtillisin/kexin type 9 (PCSK9) regulates serum LDL-c via LDL receptor (LDL-R) degradation. We describe the possible role of PCSK9 in lipid metabolism in all compartments of the parturient (maternal blood, placental tissue, and fetal blood) in pregnancies with and without preeclampsia. METHODS: This is an observational study examining PCSK9 levels in maternal sera, umbilical cord blood, and PCSK9 protein content in placental tissue in three different locations (maternal placental interface, fetal placental interface, and umbilical cord) in women with and without preeclampsia at >23 weeks gestation. RESULTS: 68 parturients with preeclampsia and 55 without preeclampsia were enrolled. Maternal serum LDL-c (116.6 ± 48.9 mg/dL vs 146.1 ± 47.1 mg/dL, p = 0.0045) and PCSK9 (83 [61.8127.6] ng/mL vs 105.3 [83.5142.9] ng/mL, p = 0.011) were also reduced in the preeclamptics versus controls. There were no differences in PCSK9 protein content between preeclamptics and controls at comparative placental interfaces. However, PCSK9 protein content increased between the preeclampsia maternal placental interface (1.87 ± 0.62) and the preeclampsia umbilical cord (2.67 ± 1.08, p = 0.0243). DISCUSSION: PCSK9 levels are lower in maternal sera in preeclampsia when compared to controls. Placental PCSK9 protein content in preeclampsia increases from the maternal interface to the umbilical cord; however, this is not seen in controls. This suggests a potential compensatory mechanism for PCSK9 which allows for higher circulating fetal LDL-c levels in preeclampsia.

Performance of glycated albumin as a biomarker of hyperglycemia in pregnancy: Results from the National Health and Nutrition Examination Survey 1999-2004.

AIM: We sought to evaluate the performance of glycated albumin (GA) as a measure of hyperglycemia in pregnant women. METHODS: We used data from 555 pregnant women aged 20-40 years who participated in NHANES 1999-2004 and did not report a pre-pregnancy diagnosis of diabetes. We used Pearson's correlations and evaluated the area under the curve (AUC) for GA to detect elevated concentrations of random glucose, HbA1c, or fasting glucose (subset). We compared results to 1607 nonpregnant women aged 20-40 without diabetes. RESULTS: In pregnant women, 1.9 % had HbA1c ≥ 39 mmol/mol (≥5.7 %), 9.1 % had random glucose ≥ 5.3 mmol/L (≥95 mg/dL), and 10.7 % had fasting glucose ≥ 5.3 mmol/L. In pregnancy, GA was poorly correlated with HbA1c (r = 0.08) and random glucose (r = 0.17). BMI was positively associated with HbA1c (r = 0.33) and random glucose (r = 0.25) but was inversely associated with GA (r = -0.27). GA had poor discrimination for detecting hyperglycemia in pregnant women, defined as HbA1c ≥ 39 mmol/mol (AUC = 0.634) or random glucose ≥ 5.3 mmol/L (AUC = 0.628). Similar patterns were observed among nonpregnant women. CONCLUSIONS: GA is not a sensitive test to screen for hyperglycemia in pregnancy. GA was inversely associated with adiposity in pregnant women without diabetes. Pregnancy-related weight gain may complicate interpretation of repeated GA measurements.

Cardiovascular Complications During Delivery Admissions Associated With Assisted Reproductive Technology (from a National Inpatient Sample Analysis 2008 to 2019).

Women who conceive through assisted reproductive technology (ART) have a known increased risk of obstetric complications. However, whether ART is also associated with higher risk of developing cardiovascular complications during delivery admissions has not been well established. We used data from the National Inpatient Sample (2008 to 2019) and used the International Classification of Diseases codes to identify delivery hospitalizations and ART procedures. A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among women who conceived through ART (n = 108,542). Women with an ART history were older at the time of delivery (median 35 vs 28 years, p <0.01) and had a higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p <0.01). After adjustment for age, race/ethnicity, co-morbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum cardiovascular complications, including pre-eclampsia/eclampsia (adjusted odds ratio [aOR] 1.48, 95% confidence interval [CI] 1.45 to 1.51), heart failure (aOR 1.94, 95% CI 1.10 to 3.40), and cardiac arrhythmias (aOR 1.39, 95% CI 1.30 to 1.48), compared with natural conception. Likewise, the risk of acute kidney injury (aOR 2.57, 95% CI 2.25 to 2.92), ischemic stroke (aOR 1.73, 95% CI 1.24 to 2.43), hemorrhagic stroke (aOR 1.63, 95% CI 1.27 to 2.11), pulmonary edema (aOR 2.29, 95% CI 2.02 to 2.61), and venous thromboembolism (aOR 1.92, 95% CI 1.63 to 2.25) were higher with ART. However, odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs 2 days, p <0.01) and cost of hospitalization ($5,903 vs $3,922, p <0.01) were higher for deliveries among women with a history of ART. In conclusion, women who conceived with ART had higher risk of pre-eclampsia, heart failure, arrhythmias, stroke, and other complications during their delivery hospitalizations. This may, in part, contribute to their increased resource utilization seen.

Effect of Sex on Coronary Endothelial Dysfunction in People Living With HIV.

Background Impaired coronary endothelial function (CEF) predicts cardiovascular events and occurs in people living with HIV (PLWH). Women compared with men living with HIV have worse cardiovascular outcomes, but prior CEF studies included few women. The authors aimed to compare CEF in women with HIV versus without HIV, investigate sex differences in CEF and PCSK9 (proprotein convertase subtilisin/kexin type 9) (a proinflammatory biomarker), and evaluate whether increased serum levels of PCSK9 are associated with CEF in PLWH. Methods and Results Magnetic resonance imaging was performed to measure CEF (as percent change in coronary cross-sectional area and coronary blood flow during isometric handgrip exercise, an endothelial-dependent stressor) and serum PCSK9 levels were measured in 106 PLWH and 76 people without HIV. CEF was significantly reduced in women with versus without HIV (cross-sectional area change -0.5%±9.7 versus 9.5%±3.2, respectively). After adjustment for age, body mass index, and menopausal status, women with HIV still had reduced CEF (percentage of cross-sectional area: ß -8.3 [-13 to -3.6], P=0.001) compared with women without HIV. PCSK9 was elevated in women living with HIV versus without (306 ng/mL [200-412 ng/mL] versus 180 ng/mL [154-223 ng/mL], P<0.001), and no sex differences in either CEF or PCSK9 were detected in PLWH. Elevated PCSK9 was associated with impaired CEF in PLWH; however, no significant sex differences in the association were detected. Conclusions Among PLWH, coronary endothelial dysfunction is present in women and comparable to men. PCSK9 is higher in women with versus without HIV and a significant inverse relationship between PCSK9 and CEF was shown. Future studies should determine whether PLWH would benefit from interventions to improve endothelial function.