Adverse Pregnancy Outcomes and Cardiovascular Disease Risk: Unique Opportunities for Cardiovascular Disease Prevention in Women: A Scientific Statement From the American Heart Association.

The purpose of the review is to summarize the unique cardiovascular disease (CVD) risk factors encountered during pregnancy and to provide the reader with a framework for acquiring a comprehensive obstetric history during the cardiovascular (CV) assessment of women. Individuals with a history of pregnancies complicated by hypertensive disorders of pregnancy (HDP), gestational diabetes (GDM), preterm delivery, low birth weight, and fetal growth restriction during pregnancy are at a higher risk of developing short- and long-term CV complications compared to those without adverse pregnancy outcomes (APOs). Women with a history of APOs can be at increased risk of CVD even after achieving normoglycemia and normal blood pressure control postpartum. Risk assessment and stratification in women must account for these APOs as recommended by the 2019 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the primary prevention of CVD. Early recognition, monitoring, and treatment of APOs are key to limiting CVD complications late in maternal life. Recognition of APOs as female-specific cardiovascular risk factors is critical for risk stratification for women and birthing persons. Further research is needed to understand the complex interplay between genetics, environmental, behavioral, and maternal vascular health, and the association between APOs and CVD risk.

Despite the efforts of investigators, public health andprivate caregivers, voluntary health organizations,and policymakers, heart disease continues to be the leading cause of death in women, both in the United States and throughout most of the world.1,2 A number of issues contribute to these disappointing statistics. Many women lack the basic awareness that cardiovascular disease is the leading cause of death among women. The American Heart Association’s (AHA) 2004 survey of women’s attitudes and knowledge showed that, when asked what they thought was the leading cause of death among women, 50 % of women answered this question incorrect-ly.3 Even more important, only 13 % of women personalized this information and answered that their own personal great-est health threat was heart disease. Although this level has increased from 7 % since the initial survey 6 years ago, it is still far too low. Furthermore, because coronary disease

Many studies,1,2 but not all, have shown that low bone density is associated with increased cardiovascular disease (CVD) risk. Vitamin D deficiency is common in the elderly and is associated with osteoporosis; however, the association of endogenous 25-OH vitamin D (25-OH D) levels with CVD events is controversial.3,4 CVD rates are higher during winter seasons and at increased geographic latitudes where average serum vitamin D levels are lowest.5 Low 25-OH D levels have been found in stroke6 and heart failure patients.7 Moreover, 25-OH D deficiency is associated with hypertension, obesity,8 glucose intolerance,8 and the metabolic syndrome,9 which may be responsible, at least in part, for its association with increased CVD risk. Article p 846 Although vitamin D supplementation improves bone strength, elevated serum vitamin D levels may be associated with lower levels of vascular calcification. In subjects at moderately high risk for coronary heart disease, endogenous serum vitamin D levels were inversely correlated with the extent of coronary artery calcification as determined by cardiac computed tomography.10 Vitamin D also has intriguing antiinflammatory properties11 that have potential therapeutic benefit in several autoimmune diseases and allograft rejection. In 2 small clinical trials,12,13 vitamin D supplementation lowered C-reactive protein levels. Additionally, 1,25(OH)2D induces relaxation of vascular smooth muscle cells …

Preeclampsia: Exposing Future Cardiovascular Risk in Mothers and Their Children

Cardiovascular disease is the leading cause of mortality in women. Beyond conventional cardiovascular risk factors, women additionally face sex-specific cardiovascular disease risk factors, which include a history of adverse pregnancy outcomes. Adverse pregnancy outcomes include the hypertensive disorders of pregnancy, gestational diabetes mellitus, preterm delivery, and small-for-gestational age delivery. Here, we review sex differences in cardiovascular disease with an emphasis on pregnancy-associated risk factors and discuss implications for the prevention and treatment of cardiovascular disease in women. Adverse pregnancy outcomes, especially the hypertensive disorders of pregnancy, have been linked to diverse cardiovascular conditions, accelerated cardiovascular aging, and multimorbidity. Chronic hypertension appears to be a key mediator of accelerated cardiovascular disease risk in women with hypertensive disorders of pregnancy. Recent genetic analyses suggest a shared genetic predisposition between adverse cardiometabolic traits and development of hypertension in pregnancy. Mechanisms linking gestational diabetes, preterm delivery, small-for-gestational age delivery, and infertility to cardiovascular disease are less well understood. The mechanisms linking adverse pregnancy outcomes to future cardiovascular disease remain incompletely understood. Further research is needed to better understand this relationship and the implications of adverse pregnancy outcomes for cardiovascular disease prevention.

Background: Women with a history of adverse pregnancy outcomes (APOs) are at increased risk of developing cardiovascular disease (CVD). Whether maintaining higher cardiovascular health is associated with a lower risk of CVD in this population is not known. Aims: To evaluate the association between Life’s Essential 8 (LE8) and incident CVD in women with a history of APOs. Methods: We included 2,263 participants with a prior diagnosis of APOs (including hypertensive disorders of pregnancy, gestational diabetes, placental abruption, small for gestational age, or preterm birth) and 107,260 parous participants without a history of APOs from the UK Biobank, all of whom were free of CVD at baseline. LE8 was calculated at baseline (range 0-100). Multivariable-adjusted Cox models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) between LE8 score and incident total and subtypes of CVD. We also examined the interaction between LE8 score and incident CVD among individuals with and without a history of APOs. Results: Over a mean 13.5 years of follow-up, 197 incident CVD events were documented in women with a history of APOs. Compared to women in the bottom tertile of LE8 score (<67), those in the top tertile (>76) had a lower incidence of total CVD, HR (95% CI) of 0.43 (0.29, 0.65), CHD [0.31 (0.17, 0.56)] and AF [0.46 (0.23, 0.91)]. We observed a significant interaction between history of APOs, LE8 score, and incident CVD ( Table 1 ). Women with a history of APO who maintained high LE8 score were at similar risk as those without APO with a high LE8 score, 0.95 (0.63-1.43), whereas there was an excess risk observed for those with an intermediate (HR with vs. without APO: 1.73 vs 1.25) and low LE8 scores (HR with vs. without APO: 2.48 vs 1.81). Conclusion: Among women with a history of APOs, better cardiovascular health as assessed using the LE8 score was associated with a significantly lower incidence of incident CVD. Additionally, women with a history of APOs who maintained high LE8 scores had similar risk of CVD as women without a history of APOs.

Adverse pregnancy outcomes (APOs) and low socioeconomic status (SES) are both associated with an increased long-term risk of atherosclerotic cardiovascular disease (ASCVD). In this analysis, we evaluated whether the association between a history of APO and ASCVD risk varies across different SES groups. We conducted this analysis using data from the UK Biobank, a large prospective cohort including participants aged 40 years to 69 years recruited between 2006 and 2010, with ongoing follow-up. APOs included hypertensive disorders of pregnancy, gestational diabetes mellitus, low birth weight (<2.5 kg), and stillbirth. At enrollment, SES was assessed using the following indicators: household income, education, employment, and Townsend Deprivation Score. The hazard ratio (HR) for new-onset ASCVD was analyzed according to history of APO and SES categories. Among 146,064 women, those with a history of APO had a higher risk of new-onset ASCVD and overall lower SES-including lower income, less education, higher unemployment, and greater deprivation-compared with those without APO (p<0.001). The increased ASCVD risk associated with APO history was significant only in the low SES group (adjusted HR, 1.26; 95% confidence interval [CI], 1.16 to 1.36), but not in the high SES group (adjusted HR, 1.07; 95% CI, 0.74 to 1.55, p=not significant). We found that women with low SES were more vulnerable to the adverse effects of APO history, resulting in a greater increase in ASCVD risk. This study highlights the need for SES-tailored preventive policies to reduce long-term cardiovascular disease in women with a history of APO.

In recent years, high-quality evidence has been accumulating that pregnancy complications are linked to a range of chronic diseases in later life. Pregnancy is regarded as a metabolic "stress test" which may unmask women's underlying risk of future cardiovascular disease (CVD) or chronic kidney disease (CKD). However, the potential for this information to be used in long-term cardio-renal risk reduction has not been fully realised. Women who have a history of hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, intra-uterine growth restriction, or pregnancy loss are at higher risk of CVD, cerebrovascular disease, and premature mortality relative to those whose pregnancies were uncomplicated.

Approximately one-third of women in the U.S. experience an adverse pregnancy outcome (APO), which are recognized as sex-specific cardiovascular disease (CVD) risk factors. We examine if APOs confer additional CVD risk beyond that of traditional CVD risk factors. Women, age 40-79, with a pregnancy history and no pre-existing CVD were identified in the electronic health record of one health system (n = 2306). APOs included any APO, hypertensive disease of pregnancy (HDP), and gestational diabetes (GDM). Hazard ratios of time to CVD event were estimated from survival models using Cox proportional hazard regression. Discrimination, calibration, and net reclassification of re-estimated CVD risk prediction models including APOs were examined. There was no significant association between any APO, HDP, or GDM and time to CVD outcome in survival models (95% confidence intervals all include 1). Including any APO, HDP, GDM in the CVD risk prediction model did not significantly improve discrimination and there were no clinically relevant changes in net reclassification of cases and non-cases. The strongest predictor of time to CVD event in the survival models was Black race, with hazard ratios ranging from 1.59 to 1.62, statistically significant for all three models. Women with APOs did not have an additional risk of CVD, controlling for traditional risk factors in the PCE and this sex-specific factor did not improve risk prediction. Black race was consistently a strong predictor of CVD even with data limitations. Further study of APOs can help determine how to best use this information for CVD prevention in women.

Cardiovascular risk management following gestational diabetes and hypertensive disorders of pregnancy: a narrative review.

Introduction: Lifetime risk for cardiovascular disease (CVD) is higher in women who experience adverse pregnancy outcomes (APOs) including pre-eclampsia, preterm birth, gestational hypertension, and gestational diabetes. APOs are risk-enhancing factors for atherosclerotic cardiovascular disease (ASCVD) in contemporary cholesterol guidelines. Hypothesis: History of APOs impacts consideration for lipid therapy in a significant proportion of women with borderline to intermediate CVD risk . Methods: A single center retrospective chart review of new patients who presented to the University of Florida Women’s Heart Health Clinic between July 2017 - July 2019 was performed. New female patients were routinely screened for pregnancy history with an obstetrics questionnaire, and cardiovascular history and lipid profiles were collected where available. Patients were stratified by age and calculated 10-yr risk of a cardiovascular event using the ACC/AHA Pooled Cohort Equation. APO history within age and risk categories in addition to pregnancy history documentation in electronic health records were then assessed. Results: Of the 182 new patients who presented to the University of Florida Women’s Heart Health Clinic between July 2017 - July 2019, average age was 49 years old and 71.3% were Caucasian. 25% of the study population had history of APO, and of patients with history of APO, only 55% had documented lipid profiles, 46% had pregnancy history documented in the obstetrics section of the electronic health record, and 17% had pregnancy history documented in their past medical history section. For patients aged 40-75 y/o with borderline-intermediate 10-yr CV event risk, risk-enhancing factors influenced consideration of potential statin therapy, with 20% of patients in the intermediate risk group having history of APO. Conclusions: Pregnancy history impacts potential statin therapy in a significant percentage of women aged 40-75 y/o with borderline-intermediate 10-yr ASCVD risk. However, APOs are often under-recognized and poorly documented as non-traditional CVD risk factors in women. Efforts to improve recognition of APOs in clinical practice should be promoted to improve CVD risk reduction efforts, particularly in young women.

Worse ischemic symptoms and cardiac function in women with suspected ischemia with no obstructive coronary artery disease and adverse pregnancy outcomes history

Introduction: Hypertensive disorders of pregnancy (HDP) are risk factors for cardiovascular disease (CVD). However, associations between subclinical blood pressure (BP) elevations in pregnancy and CVD risk are unknown. Aims: To identify BP patterns during pregnancy among individuals without HDP and determine their association with long-term CVD risk and hypertension (HTN) 2-7 years after delivery. Methods: We included nulliparous individuals from the prospective, multicenter nuMoM2b Study Heart Health Study (nuMoM2b-HHS) who had &gt; 1 BP from each trimester, and excluded those with chronic HTN or HDP. We modeled patterns using group-based trajectory analysis of the mid-BP (average of systolic and diastolic BP) during pregnancy. We selected the final number of groups based on the Bayesian Information Criteria. At 2-7 years after delivery, 30-year predicted CVD risk was estimated using the Framingham risk score; incident HTN was defined as BP &gt; 130/80. Generalized linear models estimated associations between mid-BP trajectory group and CVD risk, adjusting for sociodemographics, adverse pregnancy outcomes, and first-trimester mid-BP. Results: Of 3309 participants, mean age was 27.1 (SD 5.5) years. Five mid-BP groups were identified ( FIGURE ). Incident HTN at mean follow-up of 3.7 years after delivery was 4.2% in low-stable, 11.1% moderate-stable, 21.4% moderate-decreasing, 21.8% moderate increasing, and 44.2% in elevated-stable groups. Compared with the moderate-stable group, adjusted 30-year predicted CVD risk was significantly higher by 0.8% (0.4, 1.1), 1.6% (0.9, 2.3) and 2.6% (2.1, 3.1) in the moderate-decreasing, moderate-increasing and elevated-stable groups, respectively. Conclusions: Among people not meeting HDP criteria, but with elevated mid-BP during pregnancy, nearly half had HTN within 5 years after delivery, and long-term CVD risk was higher. Mid-BP elevations during pregnancy may inform long-term CVD risk even in the absence of HDP.

Cardiovascular disease (CVD) remains the leading cause of death in women. Although traditional risk factors increase later-life CVD, pregnancy-associated complications additionally influence future CVD risk in women. Recent guidelines for the prevention of CVD in women have added adverse pregnancy outcomes as major CVD risk factors. Studies have shown that women with a history of preeclampsia, gestational diabetes, preterm delivery, and delivery of a small-for-gestational-age infant have an increased risk of developing cardiometabolic risk factors and subsequent CVD. A history of multiple adverse pregnancy outcomes further increases this risk. It has been suggested that these pregnancy complications may unmask preexisting elevated CVD risk; however, whether the pathophysiologic changes underlying these conditions directly result in long-term cardiovascular damage is unclear. The purpose of this review was to highlight the associations between adverse pregnancy outcomes and future CVD, and to emphasize the importance of considering pregnancy history in assessing a woman's CVD risk. Targeted efforts to initiate screening and risk-reduction strategies in women with prior history of pregnancy complications, particularly lifestyle modification, may help decrease the burden of CVD in women.

Background: Adverse pregnancy outcomes (APOs) are increasingly recognized as risk indicators for future cardiovascular disease (CVD), yet their long-term implications across diverse populations remain insufficiently understood. Current guidelines lack comprehensive strategies for post-APO CVD screening. Objective: To assess the association between APOs and subsequent CVD and cardiovascular risk factors (CRF) in a racially and socioeconomically diverse cohort, and to identify demographic and socioeconomic risk factors for CVD/CRF among individuals with APOs. Methods: This retrospective cohort study included pregnant adult members of Kaiser Permanente Northern California who delivered between July 1, 2008, and June 30, 2013, with follow-up through December 31, 2023. Patients with APOs—defined as hypertensive disorders of pregnancy, gestational diabetes, preterm delivery, placental abruption, and/or small for gestational age—were matched 1:3 by age and delivery date to those without APOs. The primary outcome was incident CVD, including coronary artery disease, acute coronary syndrome, ischemic or hemorrhagic stroke, cardiomyopathy, and atrial fibrillation/flutter. The secondary outcome was CRF, defined as incident type 2 diabetes or hypertension. Adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) were estimated. Results: Among 41,502 participants, 12,612 (30.4%) experienced one or more APOs. Over a mean follow-up of 12.5 years, APO-exposed individuals had higher adjusted risk of CVD (aHR 1.39; 95% CI 1.08-1.79), CRF (aHR 1.53; 95% CI 1.41-1.66), and the composite outcome CVD/CRF (aHR 1.51; 95% CI 1.40-1.63). In the APO-exposed group, significant risk factors of CVD/CRF included advancing age (aHR 1.30 per 5 years; 95% CI 1.25-1.35), parity &gt;=3 (aHR 1.38; 95% CI 1.20-1.59) vs. nulliparity, Black (aHR 2.10; 95% CI 1.84-2.40) and Asian/Pacific Islander (aHR 1.97; 95% CI 1.79-2.16) compared to White, highest neighborhood deprivation index quintile (aHR 1.56; 95% CI 1.33-1.82) vs. lowest quintile, and pre-pregnancy BMI &gt;=40 kg/m2 (aHR 4.97; 95% CI 4.15-5.95) vs. BMI &lt;25. Conclusions: APOs are associated with long-term increased risk of CVD and CRF. This risk is influenced by demographic and socioeconomic factors, emphasizing the importance of integrating reproductive history and social determinants into cardiovascular risk stratification and screening efforts.