Katherine Elena Economy

Background: Hypertension is a leading modifiable cardiovascular risk factor prominently influenced by health-related social needs (HRSN). Whether detailed information on HRSN can improve identification of hypertension among minoritized women is unknown. Methods: Black and Latina women aged 18-65 years completed the Centers for Medicare and Medicaid Services Accountable Health Communities Screening Tool, assessing 13 HRSN domains. Hypertension was ascertained by a validated EHR-based algorithm or self-report of hypertension. Logistic regression tested associations of HRSN with hypertension. LASSO regression with 10-fold cross-validation was used to derive a poly-social risk score in the training set (random 70%) and tested in the validation set (30%) against a sociodemographic model (age, race, income, education). Results: Among 1302 participants (mean [SD] age 40.1 [11.3] years, 70.4% Black, 44.3% Latina), higher cumulative burden of HRSN was associated with increased odds of hypertension (adjusted odds ratio [aOR] for each additional domain of HRSN: 1.07 [95% CI 1.01-1.14], P=0.02). Food insecurity (aOR 2.30 [1.37-3.87], P= 0.002), lapse in utilities (aOR 1.44 [1.04-1.96], P=0.02), poor concentration (aOR 1.57 [1.13-2.17], P=0.007), and social isolation (aOR 1.77 [1.14-2.73], P=0.01) were associated with hypertension. In the validation set, the poly-social risk score did not improve discrimination for hypertension vs. the sociodemographic model (AUC 0.76 [95% CI 0.71-0.81] vs. AUC 0.80 [0.75-0.85]). Conclusions: In this cross-sectional analysis of Black and Latina women, greater cumulative social disadvantage was associated with hypertension. While inclusion of HRSN did not improve hypertension prediction beyond conventional sociodemographic indices, findings may inform targeted interventions among minorities at cardiometabolic risk.

BACKGROUND: Cardiac and vascular complications are the leading causes of maternal mortality and morbidity, but the contemporary burden of and secular trends in pregnancy-related cardiovascular complications are not well-characterized. We developed a multi-institutional electronic health record–based pregnancy cohort with rigorously defined cardiovascular outcomes to examine trends in prevalence of maternal cardiovascular comorbidities and cardiovascular disease (CVD) and incidence of pregnancy-related cardiovascular complications. METHODS: We identified pregnancy encounters that occurred between 2001 and 2019 from a primary care electronic health record cohort using International Classification of Diseases and Current Procedural Terminology codes. We used regular expressions to recover estimated gestational age from unstructured notes and used gestational age to define the pregnancy episode for each individual pregnancy. Leveraging this cohort, we quantified and examined trends in the prevalence of maternal cardiovascular comorbidities and CVD and incidence of cardiovascular complications in pregnancies over the course of 19 years of follow-up. We also compared clinical factors for pregnancies with and those without cardiovascular complications. RESULTS: Our pregnancy cohort comprised 56 833 pregnancies among 38 996 individuals (mean age at start of pregnancy, 32±5 years). Regular expressions recovered gestational age for 75% of pregnancies, with good correlation between gestational age ascertained by regular expressions versus manual review (Pearson r =0.9). Among 56 833 pregnancies, overall prevalence of maternal CVD was 4% (age-adjusted 8%) and increased over 19 years (age-adjusted prevalence 1% in 2001 and 7% in 2019; P P P <0.001 for all). CONCLUSIONS: In a large-scale electronic health record–based pregnancy cohort, both the prevalence of maternal cardiovascular comorbidities and CVD as well as the incidence of pregnancy-related cardiovascular complications within 1 year postpartum increased over the course of 2 decades. Our findings demonstrate an alarming rise in pregnancy-related cardiovascular complications in a contemporary real-world setting and highlight pregnancy as a crucial life opportunity for cardiovascular health optimization.

We identified 347 pregnancies in patients with β-thalassemia minor. Hemoglobin was <9 g/dL in 31% during third trimester and 7.6% at delivery. Postpartum hemorrhage occurred in 8.9%. Forty-six percent of IV iron administration was to iron-replete patients.

BACKGROUND: Preeclampsia is a hypertensive disorder of pregnancy characterized by systemic endothelial dysfunction. The pathophysiology of preeclampsia remains incompletely understood. This study used human venous endothelial cell (EC) transcriptional profiling to investigate potential novel mechanisms underlying EC dysfunction in preeclampsia. METHODS: Venous ECs were isolated from postpartum patients with severe preeclampsia and those with normotensive pregnancy using a J wire–based technique in the antecubital vein followed by CD144 (vascular endothelial cadherin) magnetic bead isolation. Venous EC transcriptomes were compared between preeclamptic and normotensive individuals. Differentially expressed genes were carried forward for genetic validation using expression quantitative trait loci from the Genotype-Tissue Expression project as exposures for vascular-specific Mendelian randomization. Functional validation of the top candidate was performed in human umbilical vein ECs using gain- and loss-of-function genetic approaches. RESULTS: Seventeen individuals with preeclampsia and 7 normotensive controls were included. Pairwise analysis yielded 14 protein-coding genes nominally differentially expressed in participants with preeclampsia. Mendelian randomization revealed a significant association between higher genetically predicted METAP1 (methionyl aminopeptidase 1) expression in aortic and tibial arterial tissues and greater risk of preeclampsia. METAP1 overexpression in human umbilical vein ECs decreased angiogenesis, with a 66% decrease in tube formation ( P =7.9×10 ⁻³ ) and 72% decrease in cell proliferation ( P =2.9×10 ⁻² ). Furthermore, METAP1 overexpression decreased VEGFA expression and increased expression of multiple preeclampsia-related genes, for example, FLT1 , INHBA , and IL1B . Conversely, METAP1 knockdown produced opposite effects on tube formation, cell proliferation, and inflammation-related gene expression. CONCLUSIONS: In a cohort of early postpartum individuals, we observed greater METAP1 expression in venous ECs of women with preeclampsia versus normotensive delivery. Mendelian randomization supported a causal relationship between greater vascular METAP1 expression and higher preeclampsia risk, and functional experiments demonstrated antiangiogenic and proinflammatory effects of METAP1 in human ECs consistent with alterations observed in preeclampsia. Ex vivo EC transcriptomics can identify novel mechanisms underlying preeclampsia pathophysiology, with implications for prevention and treatment.

BACKGROUND: Preeclampsia is a pregnancy-specific hypertensive disorder associated with an imbalance in circulating proangiogenic and antiangiogenic proteins. Preclinical evidence implicates microvascular dysfunction as a potential mediator of preeclampsia-associated cardiovascular risk. METHODS: Women with singleton pregnancies complicated by severe antepartum-onset preeclampsia and a comparator group with normotensive deliveries underwent cardiac positron emission tomography within 4 weeks of delivery. A control group of premenopausal, nonpostpartum women was also included. Myocardial flow reserve, myocardial blood flow, and coronary vascular resistance were compared across groups. sFlt-1 (soluble fms-like tyrosine kinase receptor-1) and PlGF (placental growth factor) were measured at imaging. RESULTS: The primary cohort included 19 women with severe preeclampsia (imaged at a mean of 15.3 days postpartum), 5 with normotensive pregnancy (mean, 14.4 days postpartum), and 13 nonpostpartum female controls. Preeclampsia was associated with lower myocardial flow reserve (β, −0.67 [95% CI, −1.21 to −0.13]; P =0.016), lower stress myocardial blood flow (β, −0.68 [95% CI, −1.07 to −0.29] mL/min per g; P =0.001), and higher stress coronary vascular resistance (β, +12.4 [95% CI, 6.0 to 18.7] mm Hg/mL per min/g; P =0.001) versus nonpostpartum controls. Myocardial flow reserve and coronary vascular resistance after normotensive pregnancy were intermediate between preeclamptic and nonpostpartum groups. Following preeclampsia, myocardial flow reserve was positively associated with time following delivery ( P =0.008). The sFlt-1/PlGF ratio strongly correlated with rest myocardial blood flow ( r =0.71; P <0.001), independent of hemodynamics. CONCLUSIONS: In this exploratory cross-sectional study, we observed reduced coronary microvascular function in the early postpartum period following preeclampsia, suggesting that systemic microvascular dysfunction in preeclampsia involves coronary microcirculation. Further research is needed to establish interventions to mitigate the risk of preeclampsia-associated cardiovascular disease.