Mild Blood Pressure Elevation Research Articles

POS-525 INTEREST OF MANNITOL IN INTRACRANIAL HYPERTENSION DURING HEMODIALYSIS IN A PATIENT WITH ACUTE BRAIN INJURY: A CASE REPORT

Hemodialysis (HD) Patients with acute brain injury are at increased risk of dialysis disequilibrium syndrome (DDS). This is due to the added risk of increased intracranial pressure (ICP) during or following dialysis. We present here a case of severe intracranial hypertension due to post traumatic subdural hematoma in a long-term HD patient, improved by continuous mannitol infusions during HD sessions. A 37-year-old Caucasian woman, in HD during five years, had a car accident in january 2021 with initial loss of consciousness, vomiting, severe headache and a Glasgow score of 14/15. Cerebral CT showed frontal hemorrhagic contusions, a right temporal subdural hematoma, subarachnoid hemorrhage, a non-displaced fracture of the sagittal/frontal bones and severe cerebral edema (figure 1). The patient was transferred to the neurosurgical department for medical management and monitoring. No emergency surgery was needed. On day 4, during her first hemodialysis session post brain injury, the patient presented neurological deterioration, severe headache and vomiting. Her blood pressure was of 143/63, heart rate recorded at 76 and oxygen saturation was stable at 100%. On suspicion of cerebral edema, the session was stopped. CT revealed exacerbation of cerebral edema, with no change in lesions or hemorrhage. Similar problems were encountered on the following session. We tried a test dose of Mannitol 20%: 50ml over 5minutes after start of hemodialysis. Neurologic signs disappeared and the patient was stable. Slow Continous mannitol infusion at a dose of 0,2g/kg body weight was undergone during 3-hours HD session with blood pressure and heart rate monitoring. No complications and no clinical significant changes were observed, except a mild elevation of blood pressure(174/95) controlled by mannitol infusion rate reduction. On day 8, the patient received slower dose of Mannitol 20% : 0,2g/kg body weight over 3.5hours of hemodialysis with 50ml infused over 20min and the remaining 60ml over 3 hours. Repeated blood tests showed no hypernatremia. From day 10 and onwards, the patient was able to tolerate hemodialysis with similar settings. On day 20, a further CT scan showed improvement in cerebral edema and temporal hematoma. we began administrating smaller doses of Mannitol ( 0,1g/kg body weight). On day 28, Mannitol was discontinued, as neurological functions were stable and control cerebral CT showed almost total resorption of the hemmorage and a marked edema reduction (figure 2). This case highlights the inherent risks associated with hemodialysis in patients with acute brain injury. The patient in question was likely predisposed to DDS due to cerebral edema after traumatic subdural hemmorage. In high-risk patients, we suggest the infusion of hypertonic solutions such as mannitol during dialysis. It seems to be well tolerated and may allow correction of ICP and optimisation of hemodialysis sessions. However, the risk of hypertensive crisis and hypernatremia should be considered.

The Role of Perivascular Adipose Tissue in Early Changes in Arterial Function during High-Fat Diet and Its Combination with High-Fructose Intake in Rats

The aim of the current study was to evaluate the influence of a high-fat diet and its combination with high-fructose intake on young normotensive rats, with focus on the modulatory effect of perivascular adipose tissue (PVAT) on the reactivity of isolated arteries. Six-week-old Wistar–Kyoto rats were treated for 8 weeks with a control diet (10% fat), a high-fat diet (HFD; 45% fat), or a combination of the HFD with a 10% solution of fructose. Contractile and relaxant responses of isolated rat arteries, with preserved and removed PVAT for selected vasoactive stimuli, were recorded isometrically by a force displacement transducer. The results demonstrated that, in young rats, eight weeks of the HFD might lead to body fat accumulation and early excitation of the cardiovascular sympathetic nervous system, as shown by increased heart rate and enhanced arterial contractile responses induced by endogenous noradrenaline released from perivascular sympathetic nerves. The addition of high-fructose intake deteriorated this state by impairment of arterial relaxation and resulted in mild elevation of systolic blood pressure; however, the increase in arterial neurogenic contractions was not detected. The diet-induced alterations in isolated arteries were observed only in the presence of PVAT, indicating that this structure is important in initiation of early vascular changes during the development of metabolic syndrome.

Studies of salt and stress sensitivity on arterial pressure in renin-b deficient mice

Excessive sodium intake is known to increase the risk for hypertension, heart disease, and stroke. Individuals who are more susceptible to the effects of high salt are at higher risk for cardiovascular diseases even independent of their blood pressure status. Local activation of the renin-angiotensin system (RAS) in the brain, among other mechanisms, has been hypothesized to play a key role in contributing to salt balance. We have previously shown that deletion of the alternative renin isoform termed renin-b disinhibits the classical renin-a encoding preprorenin in the brain resulting in elevated brain RAS activity. Thus, we hypothesized that renin-b deficiency results in higher susceptibility to salt-induced elevation in blood pressure. Telemetry implanted Ren-bNull and wildtype littermate mice were first offered a low salt diet for a week and subsequently a high salt diet for another week. A high salt diet induced a mild blood pressure elevation in both Ren-bNull and wildtype mice, but mice lacking renin-b did not exhibit an exaggerated pressor response. When renin-b deficient mice were exposed to a high salt diet for a longer duration (4 weeks), there was a trend for increased myocardial enlargement in Ren-bNull mice when compared with control mice, but this did not reach statistical significance. Multiple studies have also demonstrated the association of environmental stress with hypertension. Activation of the RAS in the rostral ventrolateral medulla and the hypothalamus is required for stress-induced hypertension. Thus, we next questioned whether the lack of renin-b would result in exacerbated response to an acute restraint-stress. Wildtype and Ren-bNull mice equally exhibited elevated blood pressure in response to restraint-stress, which was similar in mice fed either a low or high salt diet. These studies suggest that mechanisms unrelated to salt and acute stress alter the cardiovascular phenotype in mice lacking renin-b.

Highlights of the December issue.

Highlights of the December issue.

Is there an association between calcium level and preeclampsia in pregnant women? A systemic review

Background: Pregnancy-induced hypertension is a diagnosis used to describe a wide spectrum of patients who may have only mild elevations in blood pressure or severe hypertension with various organ dysfunctions. Preeclampsia is a form of pregnancy-induced hypertension which is defined as the new onset of hypertension and proteinuria after 20 weeks of gestation in a previously normotensive woman. Preeclampsia has been identified as the leading reason for maternal admission to the intensive care unit in the puerperal period. Trends of pregnancy-induced hypertension in low- and middle-income countries were increasing. The WHO recommend calcium supplementation as part of the antenatal care for the prevention of preeclampsia in pregnant women, particularly among those population where calcium intake low and at higher risk of developing hypertension.
 Methods: The data were searched electronically From Pub Med, Google Scholar, Cochrane database reviews and Google. Case-control, retrospective and prospective cohort and clinical trial and papers published in the English language was included. Out of 460 pieces of literature searched electronically, only 23 pieces of literature were used in this study. The other 435 references were not reviewed based on exclusion criteria. In this review 14 case-control studies, 2 cross-sectional studies, 1 longitudinal study, 2 clinical trials, and 4 reviews were included.
 Results: The age of the study participant’s ranges from 18-41, all study participant’s gestational age was greater than 12 wk. All studies used a diagnostic criteria for preeclampsia based on the following criteria: Blood pressure (BP) more than 140/90 and proteinuria >300 mg/do in 24 hr or 1+ in dipstick urine sample Low levels of calcium have a significant association to preeclampsia as indicated in most studies.
 Conclusion: Most studies explored that calcium level was low among preeclampsia women. Inconsistencies of recruitment (for example some researcher recruit at 20 weeks of gestational age others in 28 weeks of gestational age) of participant's leads to inconclusive and biased findings in this review. For future researcher should focus on pathophysiology calcium and hypertension. And also it is better the country should give special attention to improve the dietary calcium intake of pregnant women. In the future scientists should better assess calcium level through multiple methods like dietary, clinical and biochemical method and also the impact of calcium on neonatal and maternal should be assessed

Changes in Blood Pressure and Urine Albumin-Creatinine Ratio in a Randomized Clinical Trial Comparing Aflibercept, Bevacizumab, and Ranibizumab for Diabetic Macular Edema.

PurposeTo compare blood pressure and urine albumin-creatinine ratio over time for participants receiving aflibercept, bevacizumab, or ranibizumab.MethodsPreplanned secondary analyses from a randomized trial comparing aflibercept, bevacizumab, and ranibizumab for diabetic macular edema (DME). The Diabetic Retinopathy Clinical Research Network (DRCR.net) enrolled 660 participants with DME and visual acuity 20/32 or worse in at least one eye. Eyes received intravitreous injections of 2.0 mg aflibercept, 1.25 mg bevacizumab, or 0.3 mg ranibizumab based on a structured retreatment protocol over 2 years. Main outcome measures were (1) a change in blood pressure at 2 years, and (2) a change in urine albumin-creatinine ratio (UACR) at 1 year.ResultsAt baseline, 95 participants (14%) had normal blood pressure, 220 (33%) had borderline blood pressure elevation, 206 (31%) had mild blood pressure elevation, and 139 (21%) had moderate blood pressure elevation. Average change in mean arterial pressure from baseline to 2 years was −1.2 ± 15, −1.8 ± 13.5, −2.6 ± 14.4 mm Hg in the aflibercept, bevacizumab, and ranibizumab groups, respectively (global P = 0.69). At baseline 247 participants (38%) had no albuminuria (<30 mg/g), 195 (30%) had microalbuminuria (30–300 mg/g), and 212 (32%) had macroalbuminuria (>300 mg/g). Changes in UACR category were not different among treatment groups at the 52-week visit (global P = 0.29).ConclusionsThere do not appear to be treatment group differences for changes in blood pressure or UACR as a reflection of kidney function in patients with DME treated with aflibercept, bevacizumab, or ranibizumab.

Associations of Blood Pressure with Functional and Cognitive Changes in Patients with Alzheimer's Disease

Background: Midlife hypertension followed by late life hypotension resulting from neurodegeneration increases amyloidogenesis and tauopathy. Methods: Consecutive outpatients with late-onset Alzheimer's disease (AD) at various stages and their respective caregivers were assessed for score variations in 1 year of tests assessing caregiver burden, functionality and cognition according to blood pressure (BP) variations and APOE haplotypes, while also taking into account differential effects of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, β-blockers, calcium channel blockers, diuretics, or no antihypertensive medication on score changes. The diagnosis and treatment of arterial hypertension followed the JNC 7 report. Results: Variations in systolic BP (-11.76 ± 17.1 mm Hg), diastolic BP (-4.92 ± 10.3 mm Hg) and pulse pressure (-6.84 ± 12.6 mm Hg) were significant after 1 year (n = 191; ρ < 0.01). For APOE4+ carriers, rises in systolic or diastolic BP improved Clinical Dementia Rating Scale Sum of Boxes scores (ρ < 0.04), with marginally significant improvements in Mini-Mental State Examination scores resulting from risen systolic (ρ = 0.069) or diastolic BP (ρ = 0.079), and in basic independence only regarding risen diastolic BP (ρ = 0.055). APOE4- carriers resisted any functional or cognitive effects of BP variations. No differences were found regarding any antihypertensive class for variations in BP or any test scores, regardless of APOE haplotypes. Conclusions: Targeting mild BP elevations brings better functional and cognitive results for APOE4+ carriers with AD.

Hypertension in an Adolescent Secondary to Performance-Enhancement Supplement Use.

Objective: To describe the effects of performance-enhancing supplements and caffeine on the blood pressure (BP) of an adolescent male. Case Summary: An adolescent male presented to his primary care provider for a preseason athletic physical. On physical exam, his BP was 162/90, exceeding the 99th percentile for his age. It had been elevated during the previous 2 yearly physicals. He was referred to the Pediatric Preventive Cardiology Clinic for follow-up. Illegal substance use and renal trauma were ruled out. During the evaluation, the patient acknowledged using energy drinks and performance-enhancing supplements, the majority of which were caffeine-based. His intention was to continue the use of supplements, so lisinopril was initiated. On follow-up, however, the patient reported supplement discontinuation, intermittent medication adherence, and lower home-based BP readings. He was subsequently lost to follow-up. An objective causality assessment revealed that the adverse drug event was probable. Discussion: When working with adolescent patients, it is particularly important to conduct an in-depth interview reflecting lifestyle choices. Use of performance-enhancing supplements and caffeine for adolescent athletes has been well reported in the literature. Adolescent use of supplements may be driven by misguided beliefs and lack of knowledge about potentially detrimental health effects, such as altered heart rate and elevated BP. Little evidence-based research is available to provide treatment guidance for clinicians regarding potential effects. Conclusions: A thorough patient history, including specific questions probing for any recent or chronic use of nutritional supplements, including energy drinks, will help identify substances that may contribute to BP variations. Even mild BP elevations in adolescents should lead clinicians to further investigate supplement use and include specific questions on any product use within the past 24 hours, several days, or longer. Adolescents may not consider the potential for adverse health effects when ingesting performance-enhancing supplements or energy drinks.

Immune Mechanisms in Hypertension

Low grade inflammation may have a key role in the pathogenesis of hypertension and cardiovascular disease. Several studies showed that both innate and adaptive immune systems may be involved, being T cells the most important players. Particularly, the balance between Th1 effector lymphocytes and Treg lymphocytes may be crucial for blood pressure elevation and related organ damage development. In the presence of a mild elevation of blood pressure, neo-antigens are produced. Activated Th1 cells may then contribute to the persistent elevation of blood pressure by affecting vasculature, kidney and perivascular fat. On the other hand, Tregs represent a lymphocyte subpopulation with an anti-inflammatory role, being their activity crucial for the maintenance of cardiovascular homeostasis. Indeed, Tregs were demonstrated to be able to protect from blood pressure elevation and from the development of organ damage, including micro and macrovascular alterations, in different animal models of genetic or experimental hypertension. In the vasculature, inflammation leads to vascular remodeling through cytokine activity, smooth muscle cell proliferation and oxidative stress. It is also known that a consistent part of ischemia-reperfusion-induced acute kidney injury is mediated by inflammatory infiltration and that Treg cell infusion have a protective role. Also the central nervous system has an important role in the maintenance of cardiovascular homeostasis. In conclusion, hypertension development involves chronic inflammatory process. Knowledge of cellular and molecular players in the progression of hypertension has dramatically improved in the last decade, by assessing the central role of innate and adaptive immunity cells and proinflammatory cytokines driving the development of target organ damage. The new concept of role of immunity, especially implicating T lymphocytes, will eventually allow discovery of new therapeutic targets that may improve outcomes in hypertension and cardiovascular or renal disease in humans and uncover an entirely novel approach in the treatment of hypertension and vascular disease.

Accelerated hypertension after venlafaxine usage.

Venlafaxine is the first antidepressant that acts via inhibiting serotonin and noradrenaline reuptake. Hypertension is observed in doses exceeding 300 mg/day and is the most feared complication. We report a patient with accelerated hypertension after venlafaxine use observed at a dose of 150 mg/day. A 23-year-old patient with symptoms of insomnia, depression, anhedonia, fatigue admitted our clinic. Venlafaxine at a dose of 75 mg/day was initiated after he was diagnosed with major depressive disorder. After 5 months, venlafaxine dose was uptitrated to 150 mg/day due to inadequate response to drug. After using venlafaxine for ten months at the dose of 150 mg/day, he admitted our clinic with headache and epistaxis. He was hospitalized after his blood pressure was measured as 210/170 mmHg. No secondary causes for hypertension were found, and venlafaxine treatment was considered possible etiologic factor. After stopping venlafaxine treatment, his blood pressure was reverted back to normal limits. While mild elevation of blood pressure could be observed after venlafaxine treatment, this case shows that accelerated hypertension with a diastolic blood pressure rise above 120 mmHg could be observed at relatively low doses of venlafaxine. Close monitoring of blood pressure is necessary after initiation of treatment, as accelerated hypertension could cause endorgan damage with potentially catastrophic results.

Acute transient freezing of gait in a patient with posterior reversible encephalopathy syndrome

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a transient clinical and neuroradiologic syndrome caused by cerebral vasogenic edema. Various reversible neurologic symptoms were shown in patients with PRES. Freezing of gait (FOG) is mainly observed in neurodegenerative diseases.Case presentationWe report a 43-year-old man, with undergoing hemodialysis therapy for chronic renal failure, had mild elevation of blood pressure. His consciousness level suddenly deteriorated, and brain MRI demonstrated hyperintense lesions in the bilateral basal ganglia on fluid-attenuated inversion recovery images, diffusion-weighted images, and apparent diffusion coefficient maps. After improvement of disturbance of consciousness, he showed FOG accompanied by bradykinesia and postural instability. His FOG spontaneously improved concurrently with alleviation of basal ganglionic lesions on follow-up MRI.ConclusionsIt is suggested that vasogenic edema on bilateral basal ganglia associated with PRES can cause acute transient FOG.

VXM01, an oral T-cell vaccine targeting the tumor vasculature: Results from a randomized, controlled, first-in-man study in pancreatic cancer patients.

3090 Background: VXM01 is an orally available, bacterially transmitted DNA vaccine targeting VEGFR-2. Pre-clinically, VXM01 showed anti-tumor activity in multiple tumor types. This first-in-human study was designed to evaluate the safety and tolerability of VXM01. Secondary endpoints included VEGFR-2 specific T-cell responses, tumor perfusion changes, and related biomarkers. Methods: A randomized, double-blinded, placebo-controlled, dose-escalation study was conducted in 45 patients with advanced pancreatic cancer. VXM01 or placebo was given on days 1, 3, 5, and 7. Doses were escalated from 10(6) CFU to 10(10) CFU over 5 dose groups, each including 6 VXM01 and 3 placebo patients. VEGFR-2 specific T-cell activity was monitored by ELISpot and T(reg) specificity assays before, during and after the vaccination course. Tumor perfusion was assessed by DCE-MRI on days 0 and 38. Biomarkers included CA19-9, VEGF-A and collagen IV. Results: Patients were enrolled from 12/2011 to 10/2012. Most commonly observed AEs were leukopenia, abdominal pain, and diarrhea, which were all equally distributed between treatment and placebo group. While a mild elevation in average blood pressure was observed in the VXM01 group over the placebo group, the hypertension adverse event rate did not differ between both groups. No DLTs were observed. VEGFR-2 specific effector T-cell response was increased in 57% of evaluable VXM01 treated patients, during and after the vaccination course. In 25% of the VXM01 group, the T-cell response score post-vaccination was higher than maximum placebo levels. In contrast, VEGFR-2 specific T(reg) responses were overall reduced in vaccinated patients. DCE-MRI data indicated a &gt;33% drop in K(trans)/tumor perfusion in 35% of evaluable VXM01 treated patients vs. 10% in the placebo group. Mean changes were -4% (VXM01) and +15% (placebo). Reduced tumor perfusion correlated with VEGFR-2 specific T-cell responses and biomarker responses. Conclusions: VXM01 appeared safe and was well tolerated without DLTs across 5 tested dose levels. The data suggest further that VXM01 induces and enhances a VEGFR-2 specific T-cell response and impacts tumor perfusion. Clinical trial information: ISRCTN68809279.

Demographic, Metabolic, and Blood Pressure Characteristics of Living Kidney Donors Spanning Five Decades

While cautious criteria for selection of living kidney donors are credited for favorable outcomes, recent practice changes may include acceptance of less than ideal donors. To characterize trends in donor acceptance, the Renal and Lung Living Donors Evaluation (RELIVE) Study evaluated 8,951 kidney donors who donated between 1963 and 2007 at three major U.S. transplant centers. Over the study interval, there was an increase in the percentage of donors >40 years old from 38% to 51%; donors >60 years varied between 1% and 4%. The proportion of donors with obesity increased from 8% to 26% and with glucose intolerance from 9% to 25%. The percentage of hypertensive donors was consistent (5-8%). Accepted donors ≥60 years old were more likely to have obesity, glucose intolerance, and/or hypertension compared to younger donors (p<0.0001). Our results demonstrate important trends in acceptance of older and more obese donors. The fraction of older donors accepted with glucose intolerance or hypertension remains small and for the majority includes mild elevations in glucose or blood pressure that were previously classified as within normal limits.

Intracranial bleeding following induction of anesthesia in a patient undergoing elective surgery for refractory epilepsy

Background:A patient with refractory epilepsy due to underlying mesial temporal sclerosis underwent general anesthesia for an elective anterior temporal lobectomy and amgydalo-hippocampectomy. He was a known hypertensive and his blood pressure was well controlled on medication.Case Description:Following induction of general anesthesia and subsequent opening of the craniotomy flap it was noted that the patient had a very swollen brain that herniated out of the dural defect. There was an underlying spontaneous intraparenchymal bleed encountered in the region of the left temporal lobe with associated subarachnoid hemorrhage within the sylvian fissure. The clot was evacuated and subsequently brain swelling reduced allowing us to proceed with the intended surgery. Despite the intracranial findings there was no overt abnormality in the hemodynamic status from the time of induction of anesthesia to the craniotomy opening excepting a mild nonsustained elevation of blood pressure at the outset.Conclusion:This case is of interest due to the fact that spontaneous intraparenchymal bleeding after induction of anesthesia has not been reported before in literature and should be considered in any patient in which brain swelling occurs in a setting of elective neurosurgery in which the primary lesion does not cause elevated intracranial pressure.

479: Late preterm neonatal morbidity in high-risk hypertensive versus normotensive women

479 Late preterm neonatal morbidity in high-risk hypertensive versus normotensive women Cynthia Gyamfi-Bannerman, Victoria Fratto, Cande Ananth Columbia University Medical Center, Dept of Obstetrics and Gynecology, New York, NY OBJECTIVE: Late preterm (LP, 34 0/7 to 36 6/7 weeks) neonatal morbidity is now well-described. We previously reported the associations of neonatal respiratory morbidity in relation to mild and severe elevations in blood pressure (BP) in low-risk women. We now hypothesized that elevated BP will be associated with increased risk of late preterm neonatal morbidity in women with history of chronic hypertension, preeclampsia (PEC), or insulin-dependent diabetes in the current pregnancy (the “high-risk” cohort). STUDY DESIGN: This is a secondary analysis of a Maternal-Fetal Medicine Units Network study of aspirin to prevent preeclampsia in highrisk women (defined above). Women that delivered non-anomalous singleton births at 34 weeks were divided into 3 groups: normotensive, mild PEC or gestational hypertension (GH), and severe PEC/GH. The primary outcomes included respiratory (respiratory distress syndrome (RDS) or intubation) and non-respiratory (bronchopulmonary dysplasia, intraventricular hemorrhage, retinopathy of prematurity, SGA 10%, NICU admission, perinatal death, pulmonary hypertension, seizures, and 5 min Apgar 5) morbidity. We also analyzed these associations within sub-groups of women with a history of chronic hypertension, preeclampsia, or insulin-dependent diabetes in the current pregnancy. Analyses were adjusted for a variety of confounding factors. RESULTS: Of the 1542 women that met the inclusion criteria, 18.9% (n 256) and 14.3% (n 184) were diagnosed with mild or severe hypertension respectively. When compared to normotensive women, LP delivery rates were higher in women with mild PEC/GH (31.3% versus 15.8%; P 0.001) and in women with severe PEC/GH (42.4% versus 15.8%; P 0.001). The associations of respiratory morbidity in relation to hypertension groups are shown in the Table. CONCLUSION: In this cohort of high-risk women, the increased risk of late preterm neonatal morbidity in women that develop severe PEC/GH is evident only among infants that have morbidity that are non-respiratory in etiology. 480 The risks of neonatal sepsis and respiratory morbidity in fetuses exposed to corticosteroids after preterm PROM Cynthia Gyamfi-Bannerman, Chia-Ling Nhan-Chang, Cande Ananth Columbia University Medical Center, Dept of Obstetrics and Gynecology, New York, NY OBJECTIVE: Controversy exists regarding administration of antenatal corticosteroids (ACS) among women with preterm premature rupture of membranes (PPROM) after 30-32 weeks gestation. Reasons cited include (i) increased risk of neonatal sepsis; and (ii) increased fetal stress after PPROM causing endogenous steroid production and negating possible benefit. We sought to assess the risk of neonatal sepsis and respiratory distress syndrome (RDS) in a cohort of women with PPROM from 30 0/7 to 36 6/7 weeks of gestation. STUDY DESIGN: This is a secondary analysis of a Maternal-Fetal Medicine Units Network multicenter, observational study regarding mode of delivery after prior uterine surgery. Women with singleton gestations delivering from 30 0/7 to 36 6/7 weeks exposed to ACS were compared to women delivering at the same gestational ages who were unexposed. Associations between steroid exposure and risks of neonatal sepsis and RDS were estimated through a propensity score (PS) analysis based on log-linear regression models. These models were weighted based on the inverse probability of treatment weight. RESULTS: We identified 1743 women with PPROM who met inclusion criteria; of those 48% (n 836) received ACS. The mean gestational age was, on average, 2 weeks lower in women exposed to ACS than those unexposed (32.5 versus 34.7 weeks, P 0.001). In the unadjusted analyses, the risks of both RDS and sepsis were 40% and 60% higher in the ACS-exposed than in the unexposed groups. However, when these risks were adjusted for confounders at baseline (age, nulliparity, race, single marital status) and gestational age at delivery through a PS-based analysis, prenatal exposure to corticosteroid exposure was no longer associated with increased risks of both RDS and sepsis. CONCLUSION: In a cohort of women with PPROM, ACS exposure was not associated with increased risks of respiratory morbidity or neonatal sepsis. The PS method safeguards against treatment (steroid) selection bias in this observational cohort study. Odds of neonatal morbidity by blood pressure group Risk of neonatal morbidity by BP group in high-risk women www.AJOG.org Doppler Assess, Fetus, Prematurity, U/S, Med-Surg-Diseases Poster Session III

Differential TNF production by monocyte subsets under physical stress: Blunted mobilization of proinflammatory monocytes in prehypertensive individuals

Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared nonclassical (CD14(+)CD16(++); HLA-DR(+)), intermediate (CD14(++)CD16(+); HLA-DR(++)), and classical (CD14(++)CD16(-); HLA-DR(+/-)) monocyte trafficking and their LPS-stimulated TNF production in response to a physical stressor (20-min treadmill exercise at 65-70% VO(2peak)) in participants with high prehypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor (AR) sensitivity, pre-exercise cells were also treated with isoproterenol (Iso). When cells were stimulated with LPS, the CD16 molecules were downregulated, and monocyte subsets were differentiated based on HLA-DR expression. Monocyte subpopulations (as % of total monocytes) and intracellular TNF production were evaluated by flow cytometry. TNF production in all subsets decreased post-exercise and with ex-vivo incubation with Iso, irrespective of BP (p<0.001), with nonclassical and intermediate monocytes being a major source of TNF production. Overall, % nonclassical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise (p<0.001). However, % increase in nonclassical monocytes under exercise-induced adrenergic activation was blunted in high PHT individuals (p<0.05), but not in individuals with mild PHT and NBP. These findings extend our previous reports by showing that the mobilization of proinflammatory monocytes under physical stress is attenuated with even mild BP elevation. This may be indicative of monocytic AR desensitization and/or greater adhesion of "proinflammatory" monocytes to the vascular endothelium in hypertension with potential clinical implications of vascular pathology.

47. Differing trafficking and TNF-alpha production by monocyte subsets under adrenergic activation: Blunted mobilization of “pro-inflammatory” monocytes in individuals with elevated blood pressure

Elevated blood pressure (BP) and infiltration of the vasculature by monocytes contribute to vascular pathology; but, monocyte migratory characteristics based on differing inflammatory potential under adrenergic activation remains unclear. We compared “non-classical” (CD16++CD14+), “intermediate” (CD16+CD14++), and “classical” (CD16-CD14++) monocyte trafficking and their LPS-stimulated TNF-alpha production in response to a physical stressor (20-min treadmill exercise at 65–70% VO2peak) in participants ( n = 77) with high pre-hypertension (PHT), mild PHT or normal BP (NBP). To determine adrenergic receptor sensitivity, pre-exercise cells were also treated with isoproterenol (Iso) before LPS stimulation. Monocyte subpopulations and intracellular TNF-alpha production were evaluated by flow cytometry. Epinephrine and norepinephrine levels were significantly elevated during exercise. Overall, % non-classical monocytes increased, % intermediate did not change, whereas % classical decreased post-exercise ( p < .001). However, the % increase in non-classical monocytes under adrenergic activation was blunted in PHT individuals ( p < .05). TNF-alpha production in all subsets decreased post-exercise and with in-vitro Iso treatment, irrespective of BP ( p < .001), with nonclassical and intermediate monocytes being a major source of TNF-alpha production. These findings extend our previous reports by showing that the mobilization of “pro-inflammatory” monocytes under sympathoadrenal activation is attenuated with even mild BP elevation. This may be indicative of monocytic adrenergic receptor desensitization and/or greater adhesion of “pro-inflammatory” monocytes to the vascular endothelium in hypertension with clinical implications of vascular pathology.

INCREASED DIETARY PROTEIN INTAKE LOWERS BLOOD PRESSURE IN OVERWEIGHT SUBJECTS

Objective: Several intervention trials have shown that diet composition affects blood pressure (BP). In this study we focused on the effect of dietary protein content on BP. Design and Method: In this randomized double-blind parallel group study, 94 adult untreated overweight subjects with mildly elevated BP (BMI 25-35 kg/m2, BP > 130/85 and <160/100 mm Hg) were included. After a 2-week run-in period on a weight-maintaining standardized diet (15 en% protein (P), 30 en% fat (F) and 55 en% carbohydrate (C)), subjects were randomized to a high P or a high C diet for 4 weeks. On the high C diet 60 g of C of the run-in diet was replaced by 3x20 g of maltodextrin supplements, on the high P diet 60 g of C was replaced by 3x20 g of a protein supplement (mixture of 20% pea, 20% soy, 30% egg and 30% milk protein isolate). Supplements were matched for Na, P, K, Ca and Mg content and taken with each meal. Office and 24-h ambulatory blood pressures (ABP) were assessed at the end of the run-in and after 4 weeks supplement use. BP differences between groups after 4 weeks were analyzed by ANCOVA with BP at the end of the run-in as covariate. Results :At the end of run-in office BP (mean ± SE) was 142.6 ± 1.6/92.2 ± 0.9 mm Hg in the C and 143.3 ± 1.8/92.9 ± 1.0 mm Hg in the P group; daytime ambulatory BPs were 147.5 ± 1.8/91.0 ± 1.1 mm Hg and 147.2 ± 1.8/92.5 ± 1.2 mm Hg respectively. After 4 weeks, office SBP and DBP were lower in the P than in the C group (-4.9 mm Hg (95% CI -1.5, -8.2), p = 0.005 and - 2.7 mm Hg (95% CI -0.1, -5.4), p = 0.045) and daytime ambulatory SBP tended to be (-4.1 mm Hg (95% CI + 0.2, -8.3), p = 0.06). No significant between-group differences in daytime ambulatory DBP (-1.7 mm Hg (95% CI + 1.3, -4.8), p = 0.26) or night-time BP were found. Conclusions: An increase in dietary protein content, in exchange for dietary carbohydrates (glucose), in a weight-maintaining diet lowers blood pressure in overweight subjects with mild blood pressure elevation.

Alterations in capillary morphology are found in mild blood pressure elevation

Remodeling of small resistance arteries is an early sign of target organ damage in hypertension. Peripheral capillary morphology abnormalities in hypertension are not well studied. The study objective was to determine whether altered capillary morphology is associated with SBP, DBP, or both in individuals without and with mild blood pressure elevation (SBP = 130-160 mmHg). Another objective was to determine whether capillary morphology is associated with minimum forearm vascular resistance, a measure of altered resistance artery structure. Participants included 115 nonpregnant, nondiabetic individuals 23-55 years of age. A five-component morphology score (distribution, tone, configuration, hypertrophy, and extravasates) was developed to describe fingernail bed capillaries visualized using venous congestion in digital photomicrographs. Multiple linear regression models adjusted for age, sex, race, tobacco use, hyperglycemia, dyslipidemia, and renal function were used to analyze the relationship between SBP, DBP, and minimum forearm vascular resistance with the morphology score. The total morphology score was significantly associated with SBP and DBP as well as minimum forearm vascular resistance (P < 0.005 for all). Among the five individual morphology score components, hypertrophy was significantly associated with SBP and DBP (P = 0.002 and 0.001, respectively), whereas extravasates were significantly associated with SBP only (P = 0.002). A five-component capillary morphology score is associated with SBP, DBP, and altered resistance artery structure in individuals with and without mild blood pressure elevation. These observations suggest that target organ damage at the level of the microcirculation can be detected using capillary morphology.

Options and Decision-Making: Hypertensive Disorders of Pregnancy

Hypertension remains the most commonly encountered medical condition in pregnant women, complicating up to 15% of all pregnancies. It results in frequent hospital admissions, maternal morbidity and mortality and iatrogenic preterm birth with concomitant neonatal morbidity and mortality. Hypertensive disorders of pregnancy comprise a spectrum of severity ranging from a mild elevation of blood pressure to severe pre-eclampsia and hemolysis, elevated liver enzymes and low platelet syndrome that may result in transient or chronic multiorgan failure. As regular antenatal surveillance is the only manner by which to accurately identify those who are at risk, antenatal care schedules have been designed to detect hypertension and proteinuria. Early referral for specialist care for those who are at risk and those who develop hypertension is encouraged in the hope that this will translate into improved management of women with prophylactic, antihypertensive and anticonvulsant therapy. Advances in the understanding of the pathophysiology of the hypertensive disorders of pregnancy are likely to influence future research into both identifying those who are at risk and the role of interventions, and so lead to improved maternal and neonatal outcomes. This article highlights the pathophysiology of these conditions, the classification and identification of high-risk women, clinical manifestations and options for management.