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Cardiovascular disease is the leading cause of pregnancy mortality. Socioeconomic and racial disparities in pregnancy are well established. Despite this, little is known about the impact of social determinants of health in pregnant patients with heart disease. This study aims to determine whether pregnant patients with heart disease living in lower income neighborhoods and managed at cardio-obstetrics programs have higher rates of cardiac events or preterm deliveries compared with those living in higher income neighborhoods. This is a retrospective cohort study of 206 patients between 2010 and 2020 at a quaternary care hospital in Northern California. The exposure was household income level based on neighborhood defined by the US Census data. Patients in lower income neighborhoods (N = 103) were 45% Hispanic, 34% White, and 14% Asian versus upper income neighborhoods (N = 103), which were 48% White, 31% Asian, and 12% Hispanic (p p = 0.16), postpartum cardiac events (14% vs. 17%; p = 0.7), and preterm delivery (24% vs. 17%; p = 0.23). The rates of antepartum hospitalization were higher for lower income neighborhoods (42% vs 22%; p = 0.004). While there is no significant difference in cardiac events and preterm delivery rates between patients from low versus high income neighborhoods, patients from lower income neighborhoods have higher antepartum hospitalization rates. Earlier identification of clinical deterioration provided by a cardio-obstetrics team may contribute to increased hospitalizations, which might mitigate socioeconomic disparities in outcomes for these pregnant patients with heart disease.

Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance. Methods: We conducted a meta-analysis on genome-wide association studies of autosomal chromosomes in 22,997 individuals of primarily European ancestry across 12 cohorts to identify protein quantitative trait loci (pQTL) for 92 cardiometabolic associated plasma proteins. Results: We identified 503 (337 cis and 166 trans) conditionally independent pQTLs, including several novel variants not reported in the literature. We conducted a sex-stratified analysis and found that 118 (23.5%) of pQTLs demonstrated heterogeneity between sexes. The direction of effect was preserved but there were differences in effect size and significance. Additionally, we annotate trans-pQTLs with nearest genes and report plausible biological relationships. Using Mendelian randomization, we identified causal associations for 18 proteins across 19 phenotypes, of which 10 have additional genetic colocalization evidence. We highlight proteins associated with a constellation of cardiometabolic traits including angiopoietin-related protein 7 (ANGPTL7) and Semaphorin 3F (SEMA3F). Conclusion: Through large-scale analysis of protein quantitative trait loci, we provide a comprehensive overview of common variants associated with plasma proteins. We highlight possible biological relationships which may serve as a basis for further investigation into possible causal roles in cardiometabolic diseases.

Triple negative breast cancers (TNBC) pose exceptional challenges with fatal brain metastases as a clear and unmet need. Immune checkpoint inhibitors (ICIs) are promising therapeutic strategies, but most TNBC are resistant, or “cold” tumors, due to lack of tumor-resident immune engagement. No FDA-approved therapies exist which promote a “cold-to-hot” transition or induce the important biomarker PD-L1, often used for ICI clinical decision-making. Maximal ICI susceptibility, or a full “cold-to-hot” transition, requires reciprocal Wnt signaling inhibition and Jak/STAT/interferon signaling activation. We report a new compound combination (CHA1) that fits the above criteria. CHA1 is comprised of EGCG (epigallocatechin-3-gallate; green-tea compound) and decitabine (DNA-methyltransferase (DNMT1) inhibitor; 5’deaza-cytidine; FDA-approved for hematologic malignancies). We used immune-compromised and syngeneic TNBC pre-clinical models to investigate tumor-intrinsic and tumor-resident T-cell effects, respectively. All results required CHA1 (but not EGCG or decitabine alone) and utilized attainable human dose equivalences with manageable safety profiles. CHA1 triggered efficient Wnt signaling inhibition by elevating Wnt pathway inhibitors (HBP1 and SFRP1) and traversed the blood-brain barrier to reduce both tumor and brain metastatic growth. Transcriptomic and expression analyses revealed that CHA1 treatment effectuated a robust tumor-intrinsic JAK/STAT/IFN response 1) to induce PDL1 and 2) to induce antigen presentation and processing genes, including MHC-1, MHC-2 and numerous genes attributed to professional antigen-presenting cells; 3) to induce CD8+-T-cell infiltration and activation. Additionally, CHA1 pre-treatment improved anti-PDL1 efficacy in a syngeneic setting. Lastly, we derived a composite gene signature emblematic of CHA1 treatment and of a favorable clinical prognosis in-silico. Together, our work supports a model in which CHA1 influences epigenetics, Wnt and Jak/STAT/IFN signaling mechanisms—all to reprogram an epithelial-mesenchymal TNBC tumor to express antigen-presenting properties and to recruit and activate tumor-resident CD8+-T-cells. We discuss our findings in the context of cancer biology and immunity with implications for improving ICI susceptibility for TNBC.

Introduction: Cardiovascular disease is the leading cause of maternal mortality. The hemodynamic changes that occur during pregnancy make this a particularly vulnerable time for women with heart disease. Additionally, it is known that social determinants have an effect on certain outcomes in pregnancy, although research to quantify this effect is limited. We compared demographics and outcomes for women in upper- and lower-income brackets based on zip codes. Methods: We performed a retrospective cohort study of high-risk pregnant patients with cardiac diagnoses between November 2010 and June 2019. Patients were stratified into upper- and lower-income based on median household income in their zip code (2018 U.S. census). Results: We studied 191 pregnancies. Patients were stratified by zip code into lower ( Conclusions: Our study examined the relationship between median income per zip code and pregnancy outcomes, and demographics in women with heart disease. Our observations demonstrate a significant difference in maternal age, race, distribution of cardiac diagnoses, and antepartum hospitalizations. Despite all women being treated at the same facility, antepartum hospitalizations differed based on income bracket. Social determinants of health are important factors that impact outcomes in the cardiac-obstetric population and require further investigation.