RESUMO
Importance: Following a hypertensive disorder of pregnancy, hypertension can worsen in the postpartum period following hospital discharge. Risk factors for hypertension exacerbation and associated outcomes have not been well characterized. Objective: We sought to identify risk factors and characterize outcomes for individuals requiring initiation of anti-hypertensive medication following hospital discharge postpartum through our hospital system's remote blood pressure management program. Design: We performed a cohort study of individuals delivered between 9/2019-6/2021 and enrolled in our remote blood pressure monitoring program, which utilizes standardized protocols for anti-hypertensive medication initiation postpartum. Setting: Postpartum unit at a referral hospital. Participants: Population-based sample of individuals with a hypertensive disorder of pregnancy (HDP, preeclampsia or gestational hypertension) and no pre-pregnancy hypertension. Exposure: Anti-hypertensive medication initiation timing: no anti-hypertensive medications, initiation prior to hospital discharge postpartum, and initiation after hospital discharge postpartum. Main outcomes: Postpartum readmission and emergency room visits. Results: Of 2,705 individuals in our cohort, 1,458 (54%) required no anti-hypertensive medications postpartum, 637 individuals (24%) were discharged on anti-hypertensive medications, and 610 (23%) required initiation of anti-hypertensive agents after discharge. Utilizing an inpatient threshold of ≥ 150/100 mmHg in line with current obstetric guidelines for medication initiation postpartum fails to identify 385 (63%) of individuals who required medication initiation after discharge. These individuals had higher home blood pressures, increased odds of Emergency Room visits [aOR 2.22 (95%CI 1.65-2.98)] and hospital readmissions postpartum [aOR 5.73 (95%CI 3.72-8.82)] compared with individuals discharged on no medications. Conclusions and Relevance: Over 20% of individuals with hypertensive disorders of pregnancy required initiation of anti-hypertensive medications after hospital discharge. Current blood pressure guidelines for medication initiation fail to identify the majority of these individuals during delivery hospitalization. These data support the critical role of remote blood pressure monitoring programs and highlight the need for improved tools for risk strati cation and liberalization of thresholds for medication initiation postpartum.
RESUMO
Pattern recognition receptors for fungi include dectin-1 and mannose receptor, and these mediate phagocytosis, as well as production of cytokines, reactive oxygen species, and the lipid mediator leukotriene B(4) (LTB(4)). The influence of G protein-coupled receptor ligands such as LTB(4) on fungal pattern recognition receptor expression is unknown. In this study, we investigated the role of LTB(4) signaling in dectin-1 expression and responsiveness in macrophages. Genetic and pharmacologic approaches showed that LTB(4) production and signaling through its high-affinity G protein-coupled receptor leukotriene B(4) receptor 1 (BLT1) direct dectin-1-dependent binding, ingestion, and cytokine production both in vitro and in vivo. Impaired responses to fungal glucans correlated with lower dectin-1 expression in macrophages from leukotriene (LT)- and BLT1-deficent mice than their wild-type counterparts. LTB(4) increased the expression of the transcription factor responsible for dectin-1 expression, PU.1, and PU.1 small interfering RNA abolished LTB(4)-enhanced dectin-1 expression. GM-CSF controls PU.1 expression, and this cytokine was decreased in LT-deficient macrophages. Addition of GM-CSF to LT-deficient cells restored expression of dectin-1 and PU.1, as well as dectin-1 responsiveness. In addition, LTB(4) effects on dectin-1, PU.1, and cytokine production were blunted in GM-CSF(-/-) macrophages. Our results identify LTB(4)-BLT1 signaling as an unrecognized controller of dectin-1 transcription via GM-CSF and PU.1 that is required for fungi-protective host responses.
