New-onset Hypertension Research Articles

Neurofilament light chain is elevated in patients with newly diagnosed idiopathic intracranial hypertension: A prospective study.

Idiopathic intracranial hypertension is a secondary headache disorder potentially causing visual loss. Neurofilament light chain is a candidate, prognostic biomarker, but further studies of neuronal biomarkers are needed. Our objective was to investigate neurofilament light chain in cerebrospinal fluid (cNfL) and plasma (pNfL), amyloid-beta 42 (Aβ-42), total-tau and phosphorylated-tau in cerebrospinal fluid in new-onset idiopathic intracranial hypertension. Prospective case-control study including new-onset idiopathic intracranial hypertension and age, sex and BMI matched controls. Biomarkers were compared between patients and controls and related to papilledema, visual fields and opening pressure. We included 37 patients and 35 controls. Patients had higher age-adjusted cNfL (1.4 vs. 0.6 pg/mL, p-adjusted < 0.001), pNfL (0.5 vs. 0.3 pg/mL, p-adjusted < 0.001) and total-tau/Aβ-42 (0.12 vs. 0.11, p-adjusted = 0.039). Significant, positive linear correlations were found between cNfL, pNfL, total-tau/Aβ-42 and opening pressure. Patients with severe papilledema had elevated cNfL compared to mild-moderate papilledema (median cNfL: 4.3 pg/mL (3.7) versus 1.0 pg/mL (1.4), p-adjusted = 0.009). cNFL was inversely associated with perimetric mean deviation (r = -0.47, p-adjusted < 0.001). cNfL, pNfL and total-tau/Aβ-42 were elevated in new-onset idiopathic intracranial hypertension. cNfL was associated with severity of papilledema and visual field defects at diagnosis. This indicates early axonal damage. Neurofilament light chain is a candidate biomarker for disease severity.

Progesterone Supplementation Improves the Maternal Syndrome of Superimposed Preeclampsia in the Dahl Salt Sensitive Rats

Introduction: Preeclampsia (PE) is characterized by new onset of hypertension after 20 weeks of gestation. It affects 5-7% of all pregnancies in the U.S., and is associated with reduced fetal weight, inflammation and hypertension (HTN). Importantly, 30% of HTN disorders in pregnancy are caused by chronic HTN that is present prior to pregnancy which increases the risk of superimposed PE (SIPE). The mechanisms responsible for the pathogenesis of PE and SIPE are unclear and currently the only treatment is early delivery of the fetus. Progesterone is important for the establishment and maintenance of pregnancy. We have previously shown that progesterone supplementation with 17-hydroxyprogesterone caproate (17-OHPC) improves inflammation, fetal weight and blood pressure in the preclinical RUPP rat model of PE, however the mechanism for this in SIPE is still unknown. Hypothesis: This study was designed to test the hypothesis that 17-OHPC reduces inflammation while improving maternal blood pressure in the preclinical pregnant Dahl Salt Sensitive (DS) rat model of SIPE. Methods: 17-OHPC (3.32mg/kg) or vehicle (Saline) was administrated intraperitoneally on gestation day (GD) 15 to normal pregnant (NP) Sprague-Dawley (SD) and pregnant Dahl Salt Sensitive (DS) rats. On GD 18, Uterine Artery Resistance Index (UARI) was measured by Vevo Doppler Ultrasound and carotid catheters were inserted. On GD 19, mean arterial blood pressure (MAP) and samples were collected. All data are expressed as mean ± standard error means (SEM). Results: MAP was 105±5 mmHg in SD+ Saline rats (n=7) and 105±4 mmHg in SD+17-OHPC rats (n=4), 137±3 mmHg in DS + Saline rats (p&lt;0.05, n=11), which improved to 125±4 mmHg in DS+17-OHPC rats (p&lt;0.05, n=7). Pup and Placenta weights were 2.1± 0.1 g, 0.6 ± 0.1 g in SD + saline rats and significantly reduced to 1.4±0.1 g, 0.5±0.1 g in DS+ Saline rats (p&lt;0.05). Neither placental weight nor pup weight was affected by 17-OHPC. UARI was 0.5 ±0.1 in SD+ Saline rats (n=6) and 0.5 ±0.1 in in SD+17-OHPC (n=4), 0.7±0.1 in DS+Saline rats (n=6, p&lt;0.05), which reduced to 0.5±0.1 in DS+17-OHPC (n=7, p&lt;0.05). TNF-alpha levels were 3.0±1.0 pg/mL in SD+ Saline rats, 11.0±1.2 in DS + Saline rats, which reduced to 4.1±1.6 in DS+17-OHPC (n=4, p&lt;0.05). Importantly, circulating and placental CD4+ T cells were 9.3±3.7 % Gate and 6.4± 1.6 % Gate in SD+ Saline rats (n=4), 38.9 ±2.9 % Gate and 33.1±4.3 % Gate in DS + Saline rats (n=6), which significantly reduced to 26.3 ± 0.1 % Gate and 3.4±1.2 % Gate in DS + 17-OHPC. Conclusion: Collectively, our findings demonstrate that 17-OHPC reduces inflammation and hypertension in the Dahl Salt Sensitive rat model of SIPE. Supported by NIH P20GM121334. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

AT1-AA Induced Placental Ischemia Contributes to Hypertension in Female Offspring

Objective: Preeclampsia (PE), new-onset hypertension during the third trimester of pregnancy alongside other organ dysfunction, is associated with chronic inflammation and fetal growth restriction. Agonistic autoantibodies against the angiotensin II type 1 receptor (AT1-AA) are produced in PE women and induce a PE-like phenotype when infused into pregnant rats. AT1-AA is still present in maternal circulation up to eight years postpartum. We have shown that AT1-AA exposure during pregnancy contributes to impairment of cerebral blood flow in the postpartum period. Moreover, PE offspring are at higher risk for cardiovascular disease and hypertension but AT1-AA’s role in this elevated risk is unknown. The objective of this study was to determine if AT1-AA contributes to the risk for hypertension in PE offspring. Therefore, we hypothesized that AT1-AA infusion during pregnancy would cause offspring to have low birth weight and hypertension in adulthood. Methods: We infused AT1-AA (1:40) starting on gestational day (GD) 14 and allowed the dams to give birth on GD21. Birth weight was measured within 12 hours. Offspring were aged to 4 months. At that time, one male and female per litter were randomly selected to undergo carotid catheterization. The following day mean arterial pressure (MAP) was measured and blood and tissues were collected. Immune cells were measured by flow cytometry. Sex hormones were measured by mass spectroscopy. AT1-AA was measured by cardiomyocyte bioassay. Renal endothelin was measured by ELISA and RT-PCR. A two-way ANOVA was used for statistical analysis. Results: AT1-AA male and female offspring (6.1±0.1g, n=19, p&lt;0.05; 5.8±0.1g, n=19, p&lt;0.05) were larger at birth than NP male and female offspring (5.8±0.1g, n=11; 5.5±0.1g, n=11). Female AT1-AA offspring had elevated MAP (124±2 mmHg, n=14, p&lt;0.05) compared to NP female offspring (110±5 mmHg, n=8) while male AT1-AA offspring had similar MAP to male NP offspring. Circulating cytolytic NK cells trended higher in female AT1-AA offspring (2.73±0.37 % gated, n=9, p=0.0949) compared to female NP offspring (1.66±0.31 % gated, n=6). Female AT1-AA offspring also had elevated progesterone (41.3±6.0 pg/μL, n=8, p=0.0556) compared to female NP offspring (26.9±4.9 pg/μL, n=7). Renal PPET expression was increased in female AT1-AA offspring (2.6±0.69 fold increase, n=4, p&lt;0.05) compared to female NP offspring. Renal endothelin-1 was increased in female AT1-AA offspring (1.02±0.23 pg/mg, n=7, p=0.062) compared to female NP offspring (0.59±0.06 pg/mg, n=6). Male and female AT1-AA offspring had increased circulating AT1-AA (9.5±2.2 ΔBPM, n=6, p&lt;0.0001; 7.9±0.9 ΔBPM, n=8, p&lt;0.001) compared to male and female NP offspring (-0.4±.4 ΔBPM, n=7; -0.8±0.4 ΔBPM, n=4). Conclusion: These data demonstrate that AT1-AA infusion during pregnancy can predispose female offspring to have elevated blood pressure in adulthood. This study was supported by NIH grants RO1HD067541 (BL), F31HD110230 (NC), P20GM121334 (BL, LMA), HL151407 (DCC) and American heart association (AHA) early career award 19CDA34670055 (LMA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Imrecoxib: Advances in Pharmacology and Therapeutics.

Imrecoxib, a cyclooxygenase-2 (COX-2) selective non-steroidal anti-inflammatory drug (NSAID), was discovered via the balanced inhibition strategy of COX-1/COX-2. It is indicated for the relief of painful symptoms of osteoarthritis. There have been some pharmacological and therapeutic advances since the approval of imrecoxib in 2011. However, an update review in this aspect is not yet available. Relevant literature until January 2024 was identified by search of PubMed, Web of science, Embase and CNKI. From the perspective of efficacy, imrecoxib provides relief of osteoarthritis symptoms, and potential off-label use for treatment of idiopathic pulmonary fibrosis, perioperative pain, hand-foot syndrome, axial spondyloarthritis, COVID-19, cartilage injury, and malignancies such as lung and colon cancer. From a safety point of view, imrecoxib showed adverse effects common to NSAIDs; however, it has lower incidence of new-onset hypertension than other types of selective COX-2 inhibitors, less gastrointestinal toxicities than non-selective NSAIDs, weaker risk of drug interaction than celecoxib, and more suitable for elderly patients due to balanced inhibition of COX-1/COX-2. From a pharmacoeconomic perspective, imrecoxib is more cost-effective than celecoxib and diclofenac for osteoarthritis patients. With the deepening of the disease pathophysiology study of osteoarthritis, new therapeutic schemes and pharmacological mechanisms are constantly discovered. In the field of osteoarthritis treatment, mechanisms other than the analgesic and anti-inflammatory effects of COX-2 inhibitors are also being explored. Taken together, imrecoxib is a moderate selective COX-2 inhibitor with some advantages, and there would be more clinical applications and research opportunities in the future.

THE ASSOCIATION BETWEEN HYPERTENSION SUBTYPES DEFINED BY HOME BLOOD PRESSURE IN HYPERTENSIVE PATIENTS AND INCIDENCE OF HYPERTENSION MEDIATED ORGAN DAMAGE

Objective: To investigate the association between different hypertension subtypes, based on home blood pressure measurements, and new-onset hypertension mediated organ damage (HMOD). Design and method: A retrospective cohort study was conducted from January 2019 to March 2023. Patients, who aged at least 18 years and did not have HMOD, were categorized into normotension, isolated diastolic hypertension (IDH), isolated systolic hypertension (ISH), and combined systolic-diastolic hypertension (SDH) based on the average 7-consecutive-day home blood pressure. The primary outcome was a composite of the first following events of HMOD, including ischemic heart disease, heart failure, stroke, chronic kidney disease, new-onset proteinuria, and death. The secondary outcomes consisted of each HMOD and change of estimated glomerular filtration rate (eGFR). Results: The total of 2,351 patients were screened and the 1,314 patients were finally enrolled. The median follow-up period was 24.10 ± 12.54 months. Most of them were women (65.91%) and did not have diabetes mellitus (81.66%). The overall baseline eGFR was 87.75 ± 15.57 ml/min/1.73m2. The average home systolic and diastolic blood pressure were 121.76 ± 7.49/ 73.37 ± 7.10 mmHg in normotensive group, 127.84 ± 5.02/ 88.20 ± 3.48 mmHg in IDH group, 140.60 ± 6.14/ 74.79 ± 7.17 mmHg in ISH group, and 143.45 ± 9.09/ 91.74 ± 5.67 mmHg in SDH group. Multivariable Cox proportional analysis demonstrated that patients with IDH, ISH, and SDH had a similar risk of the composite primary outcome compared to normotensive individuals (adjusted HR of 1.12, 95% CI (0.52 to 2.45), p-value = 0.770 in IDH; adjusted HR of 1.25, 95% CI (0.74 to 2.10), p-value = 0.406 in ISH; adjusted HR of 0.81, 95% CI (0.34 to 1.91), p-value = 0.633 in SDH). However, ISH was significantly associated with an increased risk of slope of eGFR decline (mean change was -2.48 ml/min/1.73m2/year, 95% CI (-3.71 to -1.25), p-value &lt; 0.001). No significant associations were observed for the other secondary endpoints. Conclusions: Although hypertension subtypes defined by home blood pressure might not increase the incidence of composite HMOD, patients with ISH had significantly higher rate of annual renal function loss.

Computational model captures cardiac growth in hypertensive pregnancies and in the postpartum period.

Heart growth in the pregnant patient helps maintain cardiovascular function while supporting the growing fetus. However, in some cases, the cardiovascular demand of pregnancy can trigger life-threatening conditions, including hypertensive disorders of pregnancy and peripartum cardiomyopathy. The mechanisms that control heart growth throughout pregnancy are unclear, and treating these diseases remains elusive. We previously developed a computational model that accounts for hormonal and hemodynamic interactions throughout pregnancy and demonstrated its ability to capture realistic cardiac growth in normal rat pregnancy. In this study, we evaluated whether this model could capture heart growth beyond normal pregnancy. After further validation of our normal pregnancy predictions, we tested our model predictions of three rat studies of hypertensive pregnancies. We next simulated the postpartum period and examined the impact of lactation on cardiac growth in rats. We demonstrate that our multiscale model can capture cardiac growth associated with new-onset hypertension during pregnancy and lactation status in the postpartum period. We conclude by elaborating on the potential clinical utility of our model in the future.NEW & NOTEWORTHY Our multiscale model predicts appropriate heart growth beyond normal pregnancy, including elevated heart weights in rats with induced hypertension during pregnancy and in lactating mice and decreased heart weight in nonlactating mice. Our model captures distinct mechanisms that result in similar organ-level growth, highlighting its potential to distinguish healthy from diseased pregnancy-induced growth.

Habitual coffee consumption and office, home, and ambulatory blood pressure: results of a 10-year prospective study.

Heterogeneous are the results of the published studies aimed at determining the long-term effects of habitual coffee consumption on blood pressure (BP). Specifically, no data are available on the longitudinal association between habitual coffee consumption and office, home and 24 h BP profile and variability. In 1408 subjects recruited in the Pressioni Arteriose Monitorate E Loro Associazioni (PAMELA) study, followed for a 10 year follow-up period and classified as coffee consumers and nonconsumers (self-reporting), we prospectically investigated the association between habitual coffee consumption and office, home and 24-h ambulatory BP; 24-h BP variability; and development of a new hypertensive state. Data were also analysed according to gender. When data were adjusted for confounders habitual coffee nonconsumers and consumers displayed similar long-term BP changes during the follow-up in office, home, and ambulatory BP. No difference was found between heavy and moderate coffee consumers. Furthermore, also new-onset hypertension and patterns of BP variability were superimposable in coffee nonconsumers and consumers, independently on confounders including gender, number, and characteristics of the antihypertensive drug treatment. The present study, which is the first longitudinal investigation never performed examining in a prospective fashion the long-term (10 year) effects of coffee consumption on office, home, and ambulatory BP, provides conclusive evidence that habitual coffee consumption is associated with neutral effects on in-office and out-of-office BP values and related variabilities. This is the also the case for the new-onset hypertensive state.

Hypertension, Cardiovascular Risk Factors, and Uterine Fibroid Diagnosis in Midlife

Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.

The soluble (pro)renin receptor promotes a preeclampsia-like phenotype both in vitro and in vivo

Preeclampsia is classified as new-onset hypertension coupled with gross endothelial dysfunction. Placental (pro)renin receptor ((P)RR) and plasma soluble (P)RR (s(P)RR) are elevated in patients with preeclampsia. Thus, we aimed to interrogate the role (P)RR may play in the pathogenesis of preeclampsia. Human uterine microvascular endothelial cells (HUtMECs, n = 4) were cultured with either; vehicle (PBS), 25–100 nM recombinant s(P)RR, or 10 ng/ml TNF-a (positive control) for 24 h. Conditioned media and cells were assessed for endothelial dysfunction markers via qPCR, ELISA, and immunoblot. Angiogenic capacity was assessed through tube formation and adhesion assays. Additionally, pregnant rats were injected with an adenovirus overexpressing s(P)RR from mid-pregnancy (day 8.5), until term (n = 6–7 dams/treatment). Maternal and fetal tissues were assessed. HUtMECs treated with recombinant s(P)RR displayed increased expression of endothelial dysfunction makers including vascular cell adhesion molecule-1, intracellular adhesion molecule-1, and endothelin-1 mRNA expression (P = 0.003, P = 0.001, P = 0.009, respectively), along with elevated endothelin-1 protein secretion (P < 0.001) compared with controls. Recombinant s(P)RR impaired angiogenic capacity decreasing the number of branches, total branch length, and mesh area (P < 0.001, P = 0.004, and P = 0.009, respectively), while also increasing vascular adhesion (P = 0.032). +ADV rats exhibited increased systolic (P = 0.001), diastolic (P = 0.010), and mean arterial pressures (P = 0.012), compared with -ADV pregnancies. Renal arteries from +ADV-treated rats had decreased sensitivity to acetylcholine-induced relaxation (P = 0.030), compared with -ADV pregnancies. Our data show that treatment with s(P)RR caused hypertension and growth restriction in vivo and caused marked endothelial dysfunction in vitro. These findings demonstrate the significant adverse actions of s(P)RR on vascular dysfunction that is characteristic of the preeclamptic phenotype.

Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study.

Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.

Reducing severe maternal morbidity for birthing persons with severe hypertension through a statewide quality improvement initiative

BackgroundHypertensive disorders of pregnancy are a leading preventable cause of severe maternal morbidity and maternal mortality worldwide. ObjectiveTo assess the improvement in hospital care processes and patient outcomes associated with hypertensive disorders of pregnancy after introduction of a statewide Severe Maternal Hypertension quality improvement initiative. Study DesignA prospective cohort design comparing outcomes before and after introduction of the Illinois Perinatal Quality Collaborative statewide hypertension quality improvement initiative among 108 hospitals across Illinois. Participating hospitals recorded data for all cases of new-onset severe hypertension (>160 systolic or >110 diastolic) during pregnancy through 6 weeks postpartum from May 2016 to December 2017. Introduction of the statewide quality improvement initiative included implementation of severe maternal hypertension protocols, standardized patient education and discharge planning, rapid access to medications and standardized treatment order sets, and provider and nurse education. The main outcome measure was the reduction of severe maternal morbidity for pregnant/postpartum patients with severe hypertension. Key process measures include time-to-treatment of severe hypertension, frequency of provider/nurse debriefs, appropriate patient education, and early postpartum follow up. ResultsData were reported for 8,073 cases of severe maternal hypertension. The frequency of patients with new-onset severe hypertension treated within 60 minutes increased from 41% baseline to 87% (p<0.001) at the end of the initiative. The initiative was associated with increased proportion of patients receiving preeclampsia education at discharge (41% to 89%, p<0.001), scheduling follow-up appointments within 10 days of discharge (68% to 83%, p<0.001), and having a care team debrief after severe hypertension was diagnosed (17% to 59%, p<0.001). Conversely, severe maternal morbidity was reduced from 11.5% baseline to 8.4% (p<0.002) at the end of the study period. Illinois hospitals were able to achieve time-to-treatment goal regardless of hospital characteristics including geography, birth volume, and patient mix. ConclusionsIntroduction of a statewide quality improvement effort was associated with improved time-to-treatment of severe hypertension, as well as increased frequency of provider/nurse debriefs, appropriate patient education, and early postpartum follow up scheduled at discharge, and reduced severe maternal morbidity.

БЕРЕМЕННОСТЬ, ПОЧКИ, АРТЕРИАЛЬНАЯ ГИПЕРТЕНЗИЯ

Preeclampsia, often presenting as new-onset hypertension and proteinuria in the third trimester of pregnancy, can rapidly progress to serious complications and therefore presents a unique challenge, simultaneously affecting both mother and fetus, sometimes putting their well-being at odds with each other. This condition may require fairly high competencies not only from obstetricians-gynecologists, but also from doctors of other specialties, including internists and general practitioners, cardiologists, nephrologists, laboratory and functional diagnostics doctors. This literature review was prepared with the aim of summarizing and briefly presenting modern ideas about theoretical and practical issues about the relationship between pregnancy, kidney function, and blood pressure that are important for these specialists.

The role of T cell stimulated agonistic autoantibodies to the angiotensin II type I receptor (AT1-AA) in mediating multiorgan dysfunction in IL-17 induced hypertension during pregnancy.

Preeclampsia (PE), new-onset hypertension during pregnancy accompanied by organ dysfunction, is associated with chronic inflammation including elevated IL-17, CD4+ T cells, B cells and natural killer (NK) cells. IL-17 can serve as a signal for either the adaptive or innate immune activation. We have previously shown that IL-17 contributes to increased blood pressure in association with elevated TH17 cells, NK cells and B cells secreting angiotensin II type 1 receptor agonistic autoantibodies (AT1-AA) during pregnancy. Moreover, we have shown an important role for CD4+T cells and AT1-AA in multiorgan dysfunction as measured by mitochondrial oxidative stress (mt ROS). However, we do not know the role of adaptive immune cells such as T cells or B cells secreting AT1-AA in mediating the PE phenotype in response to elevated IL-17. In order to answer this question, we infused IL-17 (150 pg/day i.p.) into either Sprague Dawley (SD) or athymic nude rats via mini-osmotic pump from gestational day (GD) 14-19 of pregnancy. On GD 19, blood pressure was determined and NK cells, mtROS and respiration and AT1-AA production from B cells were measured. Infusion of IL-17 increased blood pressure in the presence or absence of T cells. Mean arterial pressure (MAP) increased with IL-17 from 98±2mm Hg (n=12) to 114±2 (n=12) in SD rats and from 99±4mm Hg (n=7) versus 115±2mm Hg (n=7) in athymic nude rats. Similar trends were seen in NK cells and placental mt ROS. Knowing that IL-17 stimulates AT1-AA in SD pregnant rats, we included a group of SD and athymic nude pregnant rats infused with IL-17 and the AT1-AA inhibitor peptide ('n7AAc'). The inhibitor attenuated blood pressure (104.9±3.2, p=.0001) and normalized NK cells and mt function in SD pregnant rats. Importantly, the AT1-AA was not produced in pregnant nude IL-17 treated rats, nor did 'n7AAc' effect MAP, in nude athymic rats. These findings suggest two conclusions; one is that IL-17 causes hypertension and multiorgan dysfunction in the absence of T cells and AT1-AA, possibly through its activation of innate cells and secondly, in the presence of T cells, blockade of the AT1-AA attenuates the effect of IL-17. This study indicates the critical effects of elevated IL-17 during pregnancy and suggest treatment modalities to consider for PE women.

Lasix for the prevention of de novo postpartum hypertension: a randomized placebo-controlled trial (LAPP Trial)

Birthing people with de novo postpartum hypertensive disorders continue to be among the populations at highest risk for severe maternal morbidity. Randomized controlled trials demonstrate a benefit of oral loop diuretics in decreasing postpartum hypertensive morbidity in patients with an antenatal diagnosis of preeclampsia. It is not known whether this same therapy benefits patients at risk for new-onset postpartum hypertension. This study aimed to evaluate whether oral furosemide can reduce the risk for de novo postpartum hypertension among high-risk birthing people by reducing postdelivery blood pressure. From October 2021 to April 2022, we conducted a randomized triple-masked placebo-controlled clinical trial of individuals at high risk for de novo postpartum hypertension at a single university-based tertiary care medical center. A total of 82 postpartum patients with no antenatal diagnosis of chronic hypertension or a hypertensive disorder of pregnancy who were at high risk for the development of de novo postpartum hypertension based on a prespecified risk factor algorithm were enrolled after childbirth. The participants were randomly assigned in a 1:1 ratio to a 5-day course of 20-mg oral furosemide daily or identical-appearing placebo starting within 8 hours of delivery. Participants were followed for 6 weeks postpartum using Bluetooth-enabled remote blood pressure monitoring and electronic surveys. The primary outcome was mean arterial pressure averaged over the 24 hours before discharge or the 24 hours before antihypertensive therapy initiation. The study was powered to detect a 5 mm Hg difference in average mean arterial pressure (standard deviation, 6.4 mm Hg) with 90% power at an alpha of 0.05, requiring a sample size of 41 per group. Secondary outcomes included the rate of de novo postpartum hypertension, readmission data, other measures of hypertensive and maternal morbidity, breastfeeding data, and drug-related neonatal outcomes. The primary outcome was assessed in 80 of the 82 participants. Baseline characteristics were similar between the groups. There was no significant difference in average mean arterial pressure in the 24 hours before discharge (or antihypertensive initiation) in the furosemide group (88.9±7.4 mm Hg) compared with the placebo group (86.8±7.1 mm Hg; absolute difference, 2.1 mm Hg; 95% confidence interval,-1.2 to 5.3). Of the 79 participants for whom secondary outcomes were assessed, 10% (n=8) developed de novo postpartum hypertension and 9% (n=7) were initiated on antihypertensive therapy. Rates were not significantly different between the groups (P=.71 and P>.99, respectively). De novo postpartum hypertension is a common phenomenon among at-risk patients, warranting close monitoring for severe hypertension and other maternal morbidity. There is insufficient evidence to suggest that furosemide reduces average mean arterial pressure in the 24 hours before discharge from the delivery hospitalization (or antihypertensive medication initiation) compared with placebo.

The Association between the Diversity of Coenzyme Q10 Intake from Dietary Sources and the Risk of New-Onset Hypertension: A Nationwide Cohort Study.

Coenzyme Q10 (CoQ10) is a food active component with blood-pressure-improving properties. However, the association between the variety and quantity of different sources of dietary CoQ10 and new-onset hypertension remains uncertain. We aimed to investigate the associations between the diversity and quantity of CoQ10 intake from eight major food sources and new-onset hypertension risk. A total of 11,489 participants were included. Dietary intake was evaluated via three consecutive 24 h recalls and household food inventory. The diversity score of CoQ10 sources was calculated by the sum of food groups consumed in the ideal range. Cox proportional hazard models were used for evaluating their associations with hypertension. Model performance was assessed by ROC analyses and 200-times ten-fold cross-validation. The relationships between CoQ10 and hypertension were U-shaped for meat, egg, vegetable, and fruit sources, inverse J-shaped for fish, and nut sources, and L-shaped for dairy products sources (all p-values < 0.001). A higher diversity score was associated with lower hypertension risk (HR (95% CI): 0.66 (0.64, 0.69)). The mean areas under the ROC curves for 6, 12 and 18 years were 0.81, 0.80 and 0.78, respectively. There is a negative correlation between the diversity of CoQ10 with moderate intake from different sources and new-onset hypertension. One diversity score based on CoQ10 was developed.

Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring

BackgroundOffspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence.MethodsA subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors.ResultsMale offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex.ConclusionThe results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.

Systemic Bevacizumab for Recurrent Respiratory Papillomatosis: A Single Institution's Experience.

Medical therapies to limit disease recurrence are critically needed for recurrent respiratory papillomatosis (RRP). Systemic bevacizumab is emerging as an exciting adjuvant therapy toward this end, but uptake has been poor due to the lack of experience and awareness of best prescribing practices. The objective of this study was to describe a single tertiary care academic medical center's experience using systemic bevacizumab for the treatment of RRP. A retrospective review was performed to identify patients with RRP on systemic bevacizumab. Demographic and clinical characteristics, findings on imaging reports, and disease response at all anatomic subsites involved in papilloma were documented. Of the 17 RRP patients on systemic bevacizumab, 9 (52.9%) were male, and 12 (70.6%) were diagnosed with juvenile-onset RRP. The total lifetime number of surgeries was high, with more than half (n = 9; 52.9%) undergoing more than 50 surgeries. Following induction of systemic bevacizumab, a significant reduction in patients with laryngeal (n = 15; 94.1% vs. n = 7; 41.2%, p < 0.001) and tracheal (n = 11; 64.7% vs. n = 5; 29.4%, p = 0.04) RRP was noted. Surgical frequency was significantly lower following systemic bevacizumab (2.5 vs. 0.5 surgeries per year; p < 0.001). The most common complications were new-onset hypertension (n = 4; 23.5%) and proteinuria (n = 5; 29.4%). Systemic bevacizumab is effective in reducing the number of surgeries needed for RRP while exhibiting a relatively safe complication profile. Papillomas in the larynx and trachea are most responsive to systemic bevacizumab, while pulmonary RRP is most likely to exhibit a partial-to-stable response. 4 Laryngoscope, 134:3253-3259, 2024.

Abstract P326: Patient Predictors of Antihypertensive Medications Prescription Classes Revealed by the All of Us Research Project (AOURP) Registry

Hypertension (HTN) treatment guidelines recommend five general classes (ACEi, ARB, CCB, diuretics, beta-blockers) of medications with minimal guidance regarding specific classes for different types of patients. Understanding heterogeneity in HTN treatment and demographic and clinical traits of individuals receiving different medication classes may provide insights into outcome disparities and enable the development of more tailored treatment recommendations. Using EHR data from the national All of Us Research Project (AOURP) registry, we examined patient predictors of first-line HTN medication class usage. From the AOURP we selected: 1) patients aged 18+ and diagnosed with new-onset HTN between 2010 and 2021 which is determined by having no HTN medication prescription prior to diagnosis date; 2) patients not pregnant within a year before and after the HTN diagnosis. We restricted our analyses to individuals receiving routine care within the EHR database as defined by having at least one in-person visit in the year prior to the first HTN diagnosis and prescribed with a single class of HTN medications within a year of their HTN diagnosis. We performed multivariate regression analysis on the outcome of whether a certain class of first-line medication was prescribed another class. Our covariates include age, sex, race/ethnicity, comorbidities (diabetes, CVD, CKD), and household income. All reported odds ratios below have a p-value of less than 0.05. Among 5,521 AOURP participants, ACEi was the most prescribed class (29%), followed by CCB (23%), Diuretic (22%), Beta-blocker (17%), and ARB (9%). We found ACEi were more likely to prescribed for females (OR: 0.74) while diuretics were less likely to be prescribed for males (OR: 1.45). We found CCB (OR: 2.73) and diuretics (OR: 1.54) were more likely to be prescribed for Blacks than their White counterparts. We also found that ACEi (OR: 2.75) were more likely prescribed for diabetics. In terms of household income, we found that ARB (OR: 1.67) were prescribed more frequently for those in higher income brackets (&lt;$25,000 vs $100,000+) compared to other classes of medication. This corresponds to the fact that ARB are relatively newer and more expensive class of HTN medications. Our findings show that although there are levels of clinical equipoise in terms of prescribed medication classes among the general population, evidence-based guidance on personalized antihypertension treatments may be needed.

Incidence of new-onset hypertension before, during, and after the COVID-19 pandemic: a 7-year longitudinal cohort study in a large population.

While the augmented incidence of diabetes after COVID-19 has been widely confirmed, controversial results are available on the risk of developing hypertension during the COVID-19 pandemic. We designed a longitudinal cohort study to analyze a closed cohort followed up over a 7-year period, i.e., 3years before and 3years during the COVID-19 pandemic, and during 2023, when the pandemic was declared to be over. We analyzed medical records of more than 200,000 adults obtained from a cooperative of primary physicians from January 1, 2017, to December 31, 2023. The main outcome was the new diagnosis of hypertension. We evaluated 202,163 individuals in the pre-pandemic years and 190,743 in the pandemic years, totaling 206,857 when including 2023 data. The incidence rate of new hypertension was 2.11 (95% C.I. 2.08-2.15) per 100 person-years in the years 2017-2019, increasing to 5.20 (95% C.I. 5.14-5.26) in the period 2020-2022 (RR = 2.46), and to 6.76 (95% C.I. 6.64-6.88) in 2023. The marked difference in trends between the first and the two successive observation periods was substantiated by the fitted regression lines of two Poisson models conducted on the monthly log-incidence of hypertension. We detected a significant increase in new-onset hypertension during the COVID-19 pandemic, which at the end of the observation period affected ~ 20% of the studied cohort, a percentage higher than the diagnosis of COVID-19 infection within the same time frame. This observation suggests that increased attention to hypertension screening should not be limited to individuals who are aware of having contracted the infection but should be extended to the entire population.

Adiposity indices and their higher predictive value for new-onset hypertension in metabolically healthy young women: findings from a population-based prospective cohort study

Background and aimsThe present study aimed to investigate the predictive ability of selected adiposity indices, such as body mass index (BMI), waist-to-hip ratio (WHR), waist circumference (WC), and waist-to-height ratio (WHtR), for new-onset hypertension in metabolically healthy Taiwanese adults. The study also sought to establish sex-specific cutoff points for these indices and to analyze the risk of new-onset hypertension, taking into account sex and age.MethodsThis prospective cohort study utilized the Taiwan Biobank database to examine metabolically healthy participants aged between 20 and 65 at baseline. Four adiposity indices, namely BMI, WHR, WC, and WHtR, were calculated and used to predict new-onset hypertension over 4 years. Receiver operating characteristics (ROCs) and areas under the curve (AUCs) were used to evaluate the effectiveness of the parameters in predicting new-onset hypertension over 4 years. Sex-specific cutoff points were identified and used to assess the risk of new-onset hypertension.ResultsThis study analyzed 13,375 participants over 4.28 years. The incidence of new-onset hypertension was 17.65%. The new-onset rate of hypertension was 34.39% in men and 65.61% in women. Adiposity indices effectively predict new-onset hypertension, with WHtR having the highest predictive value (i.e., AUC) for both sexes. The classification of participants into low and high categories for each adiposity index was based on sex-specific cutoff points, and the risk of new-onset hypertension was assessed according to sex and age. This study found that high adiposity indices predicted a significantly higher risk of new-onset hypertension in metabolically healthy adults. The risk was equal for both sexes. Young women had a higher risk of new-onset hypertension than middle-aged women when they were further categorized. All risk ratios of the indices in young women were over two-fold and significant.ConclusionAccording to the sex-specific cutoff point, high adiposity indices had a higher predictive value for new-onset hypertension in metabolically healthy Taiwanese young women.