Hemorrhagic varices around the pancreatojejunostomy site due to left-sided portal hypertension after pancreaticoduodenectomy: A case report.

Pancreaticoduodenectomy (PD) with combined portal vein resection sometimes causes left-sided portal hypertension, which can be a problem. An appropriate treatment strategy for hemorrhagic ectopic varices due to left-sided portal hypertension after PD has not yet been determined. We report a case of repeated variceal rupture around the pancreatojejunostomy site. A 65-year-old woman with a history of PD for pancreatic head cancer was admitted with a chief complaint of bloody stools. She was diagnosed with pancreatojejunostomy variceal rupture, and an endoscopic cyanoacrylate injection was performed. As rebleeding occurred 2 weeks after the first treatment, endoscopic cyanoacrylate injection was repeated, and hemostasis was achieved. Additionally, she had esophageal, colonic, and gastrojejunostomy varices, and the future risk of these variceal ruptures was considered very high. Hence, a splenectomy was performed to prevent rebleeding or other variceal ruptures. Endoscopic cyanoacrylate injection is a useful treatment for hemorrhagic varices around the pancreatojejunostomy site. It is also necessary to understand portal vein hemodynamics and provide appropriate additional treatment in cases of recurrent variceal rupture due to left-sided portal hypertension after PD.

The Construction and Meaning of Race Within Hypertension Guidelines: A Systematic Scoping Review.

BACKGROUND: Professional society guidelines are evidence-based recommendations intended to promote standardized care and improve health outcomes. Amid increased recognition of the role racism plays in shaping inequitable healthcare delivery, many researchers and practitioners have critiqued existing guidelines, particularly those that include race-based recommendations. Critiques highlight how racism influences the evidence that guidelines are based on and its interpretation. However, few have used a systematic methodology to examine race-based recommendations. This review examines hypertension guidelines, a condition affecting nearly half of all adults in the United States (US), to understand how guidelines reference and develop recommendations related to race. METHODS: A systematic scoping review of all professional guidelines on the management of essential hypertension published between 1977 and 2022 to examine the use and meaning of race categories. RESULTS: Of the 37 guidelines that met the inclusion criteria, we identified a total of 990 mentions of race categories. Black and African/African American were the predominant race categories referred to in guidelines (n = 409). Guideline authors used race in five key domains: describing the prevalence or etiology of hypertension; characterizing prior hypertension studies; describing hypertension interventions; social risk and social determinants of health; the complexity of race. Guideline authors largely used race categories as biological rather than social constructions. None of the guidelines discussed racism and the role it plays in perpetuating hypertension inequities. DISCUSSION: Hypertension guidelines largely refer to race as a distinct and natural category rather than confront the longstanding history of racism within and beyond the medical system. Normalizing race as a biological rather than social construct fails to address racism as a key determinant driving inequities in cardiovascular health. These changes are necessary to produce meaningful structural solutions that advance equity in hypertension education, research, and care delivery.

Treatment patterns and factors associated with adherence in pulmonary arterial hypertension.

OBJECTIVE: Improving understanding of actual pulmonary hypertension (PH) treatment adherence patterns is crucial to properly treating these patients. We aimed to primarily assess adherence to treatments used for pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH) specific therapies, identify potential factors related to it and secondly describe its treatment patterns. METHODS: A 6-month observational cross-sectional study in a tertiary care hospital was conducted. Patients with PH-targeted therapy who picked it up in the ambulatory hospital pharmacy and who had been on treatment with the same drug for at least 1 year were included. Adherence was assessed as: 1) Proportion of days covered (PDC); and 2) Simplified Medication Adherence Questionnaire (SMAQ). PDC ≥80% was considered adherent. Statistical analyses were performed to evaluate the study outcomes. Logistic regressions were estimated to identify the association between baseline characteristics and factors associated with adherence. P < 0.05 indicated statistical significance. RESULTS: A total of 63 patients with 127 different treatments were included, 71.4% were females with a mean age (SD) of 59 (15) years. PAH was the most common diagnosis (74.6%). Double therapy was used in 39.7% of patients, being the combination of Macitentan + Tadalafil and Ambrisentan + Tadalafil the most prescribed. Endothelin receptor antagonists were the most used treatment (40.2%). Adherence according to PDC was 93.7%, showing no great differences depending on the targeted drug used, and according to SMAQ 61.9%. The agreement degree of both methods was slight (65.1%; Kappa 0.12). Only female sex (OR: 0.23, 95% CI: 0.06-0.90; p = 0.035) was associated with worse adherence in the SMAQ method but not in the PDC. Adverse events were reported by a 55.6% of participants and the perception of effective treatment was high (95.2%). CONCLUSIONS: Adherence to PH therapy differs depending on the assessment method; PDC showed greater adherence rate than SMAQ. According to SMAQ, female sex may have a negative impact on adherence in this cohort, but PDC revealed no factors influencing it. No notable differences in adherence between treatment types were found and generally patients felt the treatments were effective in controlling their disease.

More efficient adaptation of cardiovascular response to repeated restraint in spontaneously hypertensive rats: the role of autonomic nervous system.

We hypothesized that sympathetic hyperactivity and parasympathetic insuficiency in spontaneously hypertensive rats (SHR) underlie their exaggerated cardiovascular response to acute stress and impaired adaptation to repeated restraint stress exposure compared to Wistar-Kyoto rats (WKY). Cardiovascular responses to single (120 min) or repeated (daily 120 min for 1 week) restraint were measured by radiotelemetry and autonomic balance was evaluated by power spectral analysis of systolic blood pressure variability (SBPV) and heart rate variability (HRV). Baroreflex sensitivity (BRS) was measured by the pharmacological Oxford technique. Stress-induced pressor response and vascular sympathetic activity (low-frequency component of SBPV) were enhanced in SHR subjected to single restraint compared to WKY, whereas stress-induced tachycardia was similar in both strains. SHR exhibited attenuated cardiac parasympathetic activity (high-frequency component of HRV) and blunted BRS compared to WKY. Repeated restraint did not affect the stress-induced increase in blood pressure. However, cardiovascular response during the post-stress recovery period of the 7th restraint was reduced in both strains. The repeatedly restrained SHR showed lower basal heart rate during the dark (active) phase and slightly decreased basal blood pressure during the light phase compared to stress-naive SHR. SHR subjected to repeated restraint also exhibited attenuated stress-induced tachycardia, augmented cardiac parasympathetic activity, attenuated vascular sympathetic activity and improved BRS during the last seventh restraint compared to single-stressed SHR. Thus, SHR exhibited enhanced cardiovascular and sympathetic responsiveness to novel stressor exposure (single restraint) compared to WKY. Unexpectedly, the adaptation of cardiovascular and autonomic responses to repeated restraint was more effective in SHR.

Haemodynamic contributors to pulmonary hypertension across the spectrum of adult congenital heart disease.

AIMS: Adult congenital heart disease (ACHD) includes multiple disease states that predispose to pulmonary hypertension (PH). Haemodynamically, PH depends on abnormalities in three components: pulmonary blood flow (Qp), pulmonary vascular resistance (PVR) and pulmonary venous pressure (PVP). We sought to evaluate the prevalence and prognostic impact of individual haemodynamic abnormalities in ACHD. METHODS AND RESULTS: Retrospective study of ACHD patients undergoing cardiac catheterization at Mayo Clinic between 1999 and 2022 who were followed for the combined endpoint of death/heart transplantation. Among 1005 patients, 37% had mean pulmonary artery pressure (mPAP) ≥25 mmHg with more systemic ventricular disease, cyanotic disease and shunt lesions, highest N-terminal pro-B-type natriuretic peptide and worse right heart remodelling/dysfunction. Among those with biventricular circulation, elevated PVP, PVR and mPAP were associated with prognosis, but not increased Qp >8 L/min. However, risk of death/transplant increased for PVR only at ≥3 Wood units (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.17-4.15; p < 0.0001) and for mPAP only at ≥25 mmHg (HR 3.15, 95% CI 2.17-4.58; p < 0.0001), not at current recommended lower cutpoints. Combined abnormalities in PVP and PVR were associated with worst outcome (HR 5.20, 95% CI 3.55-7.63; p < 0.0001) with intermediate risk with either abnormality (HR 2.11, 95% CI 1.46-3.04; p < 0.0001). Findings were consistent across type of biventricular ACHD. Only with the Fontan (univentricular) circulation was a lower mPAP threshold (20 mmHg) associated with adverse outcomes. CONCLUSIONS: Elevation of mPAP ≥25 mmHg in ACHD with a biventricular circulation is prognostically important regardless of disease phenotype, but milder PH of 21-25 mmHg is not associated with adverse outcome unless associated with Fontan circulation. Elevation in PVP >15 mmHg and PVR ≥3 Wood units were each individually associated with mortality with combined abnormalities associated with greatest risk. Categorizing PH in ACHD by haemodynamic mechanism (PVR, PVP or Qp) allows meaningful prognostication, and may allow more unified study of targeted therapies across heterogeneous disease states in ACHD.

Long-term risk factors of recurrent stroke, myocardial infarction and death in patients leaving hospital with a diagnosis of ischemic stroke or TIA.

Objectives. The prevalence of patients with prior stroke is increasing globally. Accordingly, there is a need for up-to-date evidence of patient-related prognostic factors for stroke recurrence, post stroke myocardial infarction (MI) and death based on long-term follow-up of stroke survivors. For this purpose, the RIALTO study was established in 2004. Design. A prospective cohort study in which patients diagnosed with ischemic stroke (IS) or transient ischemic attack (TIA) in three Copenhagen hospitals were included. Data were collected from medical records and by structured interview. Data on first stroke recurrence, first MI and all-cause death were extracted from the Danish National Patient Registry and the Danish Civil Registration System. Results. We included 1215 patients discharged after IS or TIA who were followed up by register data from April 2004 to end of 2018 giving a median follow-up of 3.5-6.9 years depending on the outcome. At the end of follow-up 406 (33%) patients had been admitted with a recurrent stroke, 100 (8%) had a MI and 822 (68%) had died. Long-term prognostic predictors included body mass index, diabetes, antihypertensive and lipid lowering treatment, smoking, a sedentary lifestyle as well as poor self-rated health and psychosocial problems. Conclusions. Long-term risk of recurrent stroke and MI remain high in patients discharged with IS or TIA despite substantial improvements in tertiary preventive care in recent decades. Continued attention to the patient risk profile among patients surviving the early phase of stroke, including comorbidities, lifestyle, and psychosocial challenges, is warranted.

Electrocardiographic abnormalities and NT-proBNP levels at long-term follow-up of patients with dyspnea after pulmonary embolism.

OBJECTIVES: Electrocardiogram (ECG) and measurement of plasma brain natriuretic peptides (BNP) are established markers of right ventricular dysfunction (RVD) in the setting of acute pulmonary embolism (PE) but their value at long-term follow-up is largely unknown. The purpose of this prospective study was to determine the prevalence of ECG abnormalities, describe levels of N-terminal proBNP (NT-proBNP), and establish their association with dyspnea at long-term follow-up after PE. DESIGN: All Swedish patients diagnosed with acute PE in 2005 (n = 5793) were identified through the Swedish National Patient Registry. Surviving patients in 2007 (n = 3510) were invited to participate. Of these, 2105 subjects responded to a questionnaire about dyspnea and comorbidities. Subjects with dyspnea or risk factors for development of chronic thromboembolic pulmonary hypertension were included in the study in a secondary step, which involved collection of blood samples and ECG registration. RESULTS: Altogether 49.3% had a completely normal ECG. The remaining participants had a variety of abnormalities, 7.2% had atrial fibrillation/flutter (AF). ECG with any sign of RVD was found in 7.2% of subjects. Right bundle branch block was the most common RVD sign with a prevalence of 6.4%. An abnormal ECG was associated with dyspnea. AF was associated with dyspnea, whereas ECG signs of RVD were not. 61.2% of subjects had NT-proBNP levels above clinical cut-off (>125 ng/L). The degree of dyspnea did not associate independently with NT-proBNP levels. CONCLUSIONS: We conclude that the value of ECG and NT-proBNP in long term follow-up after PE lies mostly in differential diagnostics.

High-Sensitivity Troponin T, NT-proBNP, and Cognitive Outcomes in SPRINT.

BACKGROUND: Hs-cTnT (cardiac troponin T measured with a highly sensitive assay) and NT-proBNP (N-terminal pro-B-type natriuretic peptide) may identify adults with hypertension who derive greater cognitive benefits from lower systolic blood pressure targets. METHODS: In the SPRINT (Systolic Blood Pressure Intervention Trial) MIND study, participants were categorized as having both hs-cTnT and NT-proBNP in the lower 2 tertiles (n=4226), one in the highest tertile (n=2379), and both in the highest tertile (n=1506). We assessed the effect of intensive versus standard treatment on the composite of mild cognitive impairment (MCI) or probable dementia (PD) across biomarker categories. RESULTS: Over a median follow-up of 5.1 years, 830 of 8111 participants (10.2%) developed MCI or PD. Participants in the highest biomarker category were at higher risk of MCI or PD compared with those in the lowest category (hazard ratio, 1.34 [95% CI, 1.00-1.56]). The effect of intensive treatment on reducing the risk of MCI or PD was greater among participants in the lowest biomarker category (hazard ratio, 0.64 [95% CI, 0.50-0.81]) than those in the intermediate (hazard ratio, 1.01 [95% CI, 0.80-1.28]) or highest categories (hazard ratio, 0.90 [95% CI, 0.72-1.13]; Pinteraction=0.02). The 5-year absolute risk differences in MCI or PD with intensive treatment were -2.9% (-4.4%, -1.3%), -0.2% (-3.0%, 2.6%), and -1.9% (-6.2%, 2.4%) in the lowest, intermediate, and highest biomarker categories, respectively. CONCLUSIONS: In SPRINT, the relative effect of intensive systolic blood pressure lowering on preventing cognitive impairment appears to be stronger among participants with lower compared with higher cardiac biomarker levels, though the absolute risk reductions were similar.

Milestones to optimize of transjugular intrahepatic portosystemic shunt technique as a method for the treatment of portal hypertension complications.

This editorial describes the milestones to optimize of transjugular intrahepatic portosystemic shunt (TIPS) technique, which have made it one of the main methods for the treatment of portal hypertension complications worldwide. Innovative ideas, subsequent experimental studies and preliminary experience of use in cirrhotic patients contributed to the introduction of TIPS into clinical practice. At the moment, the main achievement in optimize of TIPS technique is progress in the qualitative characteristics of stents. The transition from bare metal stents to extended polytetrafluoroethylene-covered stent grafts made it possible to significantly prevent shunt dysfunction. However, the question of its preferred diameter, which contributes to an optimal reduction of portal pressure without the risk of developing post-TIPS hepatic encephalopathy, remains relevant. Currently, hepatic encephalopathy is one of the most common complications of TIPS, significantly affecting its effectiveness and prognosis. Careful selection of patients based on cognitive indicators, nutritional status, assessment of liver function, etc., will reduce the incidence of post-TIPS hepatic encephalopathy and improve treatment results. Optimize of TIPS technique has significantly expanded the indications for its use and made it one of the main methods for the treatment of portal hypertension complications. At the same time, there are a number of limitations and unresolved issues that require further randomized controlled trials involving a large cohort of patients.

Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Comparison of routine office blood pressure measurement versus standardized attended manually activated oscillometric office blood pressure measurement in patients with chronic kidney disease.

Context: Erroneous blood pressure measurement could lead to improper treatment and hence progression of chronic kidney disease (CKD). In routine clinical practice, there is poor adherence to the various steps to be followed during blood pressure measurement. Automated oscillometric BP measurement is difficult to perform in routine clinical practice due to several practical limitations. Aims: To evaluate the quality of blood pressure measurement and to compare routine office blood pressure measurement with standardized attended manually activated oscillometric blood pressure measurement in patients with CKD attending the nephrology outpatient department (OPD) of a tertiary care referral center. Settings and Design: This cross-sectional study was conducted in patients aged more than 18 years with CKD stage 3-5ND, and previously diagnosed hypertension, in the nephrology OPD of a tertiary care referral center between July 2022 and September 2022. Methods and Material: The quality of blood pressure measurement was evaluated using a questionnaire. The study participants had their blood pressure checked by both methods-routine office blood pressure and standardized attended manually activated oscillometric blood pressure. Results: Standardized attended manually activated oscillometric blood pressure measurement yielded a significantly higher systolic blood pressure (SBP) compared to routine office blood pressure measurement (Mean SBP: 139.53 ± 29.1 vs 132.57 ± 23.59; P < 0.001). However, the diastolic blood pressure did not differ significantly between the two methods of measurement. Conclusions: Standardized attended manually activated oscillometric BP measurement yields a higher systolic BP compared to routine office BP measurement. Further studies are required to compare the standardized attended oscillometric BP measurement used in this study with unattended automated oscillometric BP measurement and ambulatory BP measurement.

Comparison of flow-mediated dilation (FMD) of the brachial artery in normotensive versus preeclamptic pregnant females.

Introduction: Flow-mediated dilation (FMD) of the brachial artery is an ultrasonography test that assesses the endothelial response to reactive hyperemia. The aim of this study was to assess the changes in FMD in preeclamptic pregnant patients and compare them with normotensive pregnant females. Methods: An analytical cross-sectional comparative study was conducted in the Department of Obstetrics and Gynaecology at King George's Medical University (KGMU) after obtaining ethical approval. A total of 110 normotensive and 100 preeclamptic patients were recruited for the study. Using a Toshiba Ultrasound Machine with a 7-12 MHz probe, the baseline diameter of the brachial artery D1 was measured. Afterward, the cuff of the sphygmomanometer was placed distally on the forearm and it was inflated up to ≥250 mm of Hg pressure and later slowly deflated. At 90th seconds after cuff deflation, the mean of three measurements of vessel caliber (D2) was obtained. The FMD% was obtained by the following equation: FMD (%) = [(D2 - D1)/D1] ×100, where D1 = basal diameter and D2 = post-occlusion diameter. All patients were followed till delivery for maternofetal outcome. Results: FMD% was significantly lower in the preeclampsia group, and it went on decreasing with increasing severity of preeclampsia. At the cutoff of 9.4 for FMD%, its sensitivity for the prediction of preeclampsia was 65.3%, specificity was 89.3%, positive predictive value (PPV) was 94%, and negative predictive value (NPV) was 50%. Discussion: FMD is a noninvasive test, and it gets decreased before clinical signs of preeclampsia, so it can be used as a predictor of preeclampsia.

Prevalence of hypertension, screening, awareness, and associated risk factors in teaching institution of Etawah District, Uttar Pradesh: A cross-section study.

Background: Hypertension is one of the leading causes of death worldwide, affecting over one billion people. It is responsible for roughly half of all heart disease and stroke-related deaths globally. Because hypertension does not cause any symptoms on its own, it is commonly referred to as "the silent killer." Objective: This study aimed to determine (1) the prevalence of hypertension and its associated risk factors and (2) the level of awareness of hypertension status among study participants. Material and Methods: A facility-based cross-sectional analytical study was conducted for 3 months during January-March 2023 at the teaching institution in Etawah District, Uttar Pradesh. It was conducted among 392 study participants who were ≥18 years old. Data were collected through a predesigned, pretested, semi-structured questionnaire, and anthropometric measurement was determined using standard guidelines. Results: The overall prevalence of hypertension screening was 69.4% (male: 33.8% and female: 66.2%), respectively. The majority of hypertensives were found in female participants. Tobacco and alcohol consumption, obesity, physical inactivity, stress and strain, and an unhealthy diet were also associated with hypertension. Among 392 study participants, only 67 (24.6%) were aware of their hypertension status. Conclusion: We conclude that hypertension has been described as an "Iceberg disease" as those who suffer are usually unaware and hence usually seek healthcare services at a very late stage. Preventive measures should be needed to improve hypertension screening, awareness, treatment, and control.

BMA-based Mendelian randomization identifies blood metabolites as causal candidates in pregnancy-induced hypertension.

Pregnancy-induced hypertension (PIH), a prominent determinant of maternal mortality and morbidity worldwide, is hindered by the absence of efficacious biomarkers for early diagnosis, contributing to suboptimal outcomes. Here, we explored potential causal relationships between blood metabolites and the risk of PIH using Mendelian randomization (MR). We employed a two-sample univariable MR approach to empirically estimate the causal relationships between 249 circulating metabolites and PIH. Inverse variance weighted, MR-egger, weight median, simple mode, and weighted mode methods were used for causal estimates. The exposure-to-outcome directionality was confirmed with the MR Steiger test. The Bayesian model averaging MR (MR-BMA) method was applied to detect the predominant causal metabolic traits with alignment for pleiotropy effects. In the primary analysis, analyzing 249 metabolites, we identified 25 causally linked to PIH, including 11 lipid-related traits and 6 associated with fatty acid (un)saturation. Importantly, MR-BMA analyses corroborated the total concentration of branched-chain amino acids(total-BCAA) to be the highest rank causal metabolite, followed by leucine (Leu), phospholipids to total lipids ratio in medium LDL (M-LDL-PL-pct), and Val (all P < 0.05). The directionality of causality predicted by univariable MR and MR-BMA for these metabolites remained consistent. This study highlights the causal connection between metabolites and PIH risk. It highlighted BCAAs as the strongest causal candidates warranting further investigation. Since PIH typically occurs in the second and third trimesters, extending these findings could inform earlier strategies to reduce its risk. Directed acyclic graph of the MR framework investigating the causal relationship between metabolites and PIH. MR: Mendelian randomization; GIVs: genetic instrument variables; SNPs: single-nucleotide polymorphism; IVW: inverse variance weighted; WM: weighted median; PIH: pregnancy-induced hypertension; SM: significant metabolite; MR-BMA: Bayesian model averaging MR.

Associations of E-proteinoid 3 receptor genetic polymorphisms with salt sensitivity, longitudinal blood pressure changes, and hypertension incidence in Chinese adults.

The E-proteinoid 3 receptor (PTGER3), a member of the prostaglandin E2 (PGE2) subtype receptor, belongs to the G-protein-coupled superfamily of receptors. Animal studies have demonstrated its involvement in salt sensitivity by regulating sodium reabsorption. This study aimed to investigate the association between genetic variants of PTGER3 and salt sensitivity, longitudinal blood pressure (BP) changes, and the incidence of hypertension in Chinese adults. A chronic salt intake intervention was conducted involving 514 adults from 124 families in the 2004 Baoji Salt-Sensitivity Study Cohort in northern China. These participants followed a 3-day regular baseline diet, followed by a 7-day low-salt diet (3.0 g/d) and a 7-day high-salt diet (18 g/d), and were subsequently followed for 14 years. The findings revealed a significant relationship between the single nucleotide polymorphism (SNP) rs17482751 of PTGER3 and diastolic blood pressure (DBP) response to high salt intervention. Additionally, SNPs rs11209733, rs3765894, and rs2268062 were significantly associated with longitudinal changes in systolic blood pressure (SBP), DBP, and mean arterial pressure (MAP) during the 14-year follow-up period. SNP rs6424414 was significantly associated with longitudinal changes in DBP over 14 years. Finally, SNP rs17482751 showed a significant correlation with the incidence of hypertension over 14 years. These results emphasize the significant role of PTGER3 gene polymorphism in salt sensitivity, longitudinal BP changes, and the development of hypertension in the Chinese population.

Myo-inositol trispyrophosphate prevents right ventricular failure and improves survival in monocrotaline-induced pulmonary hypertension in the rat.

BACKGROUND AND PURPOSE: Pulmonary hypertension (PH) results from pulmonary vasculopathy, initially leading to a compensatory right ventricular (RV) hypertrophy, and eventually to RV failure. Hypoxia can trigger both pulmonary vasculopathy and RV failure. Therefore, we tested if myo-inositol trispyrophosphate (ITPP), which facilitates oxygen dissociation from haemoglobin, can relieve pulmonary vasculopathy and RV hypoxia, and eventually prevent RV failure and mortality in the rat model of monocrotaline-induced PH. EXPERIMENTAL APPROACH: Rats were injected with monocrotaline (PH) or saline (control) and received ITPP or placebo for 5 weeks. Serial echocardiograms were obtained to monitor the disease, pressure-volume loops were recorded and evaluated, myocardial pO2 was measured using a fluorescent probe, and histological and molecular analyses were conducted at the conclusion of the experiment. KEY RESULTS AND CONCLUSIONS: ITPP reduced PH-related mortality. It had no effect on progressive increase in pulmonary vascular resistance, yet significantly relieved intramyocardial RV hypoxia, which was associated with improvement of RV function and reduction of RV wall stress. ITPP also tended to prevent increased hypoxia inducible factor-1α expression in RV cardiac myocytes but did not affect RV capillary density. IMPLICATIONS: Our study suggests that strategies aimed at increasing oxygen delivery to hypoxic RV in PH could potentially be used as adjuncts to other therapies that target pulmonary vessels, thus increasing the ability of the RV to withstand increased afterload and reducing mortality. ITPP may be one such potential therapy.

Urine metabolic profile in rats with arterial hypertension of different genesis.

The diversity of pathogenetic mechanisms underlying arterial hypertension leads to the necessity to devise a personalized approach to the diagnosis and treatment of the disease. Metabolomics is one of the promising methods for personalized medicine, as it provides a comprehensive understanding of the physiological processes occurring in the body. The metabolome is a set of low-molecular substances available for detection in a sample and representing intermediate and final products of cell metabolism. Changes in the content and ratio of metabolites in the sample mark the corresponding pathogenetic mechanisms by highlighting them, which is especially important for such a multifactorial disease as arterial hypertension. To identify metabolomic markers for hypertensive conditions of different origins, three forms of arterial hypertension (AH) were studied: rats with hereditary AH (ISIAH rat strain); rats with AH induced by L-NAME administration (a model of endothelial dysfunction with impaired NO production); rats with AH caused by the administration of deoxycorticosterone in combination with salt loading (hormone-dependent form - DOCA-salt AH). WAG rats were used as normotensive controls. 24-hour urine samples were collected from all animals and analyzed by quantitative NMR spectroscopy for metabolic profiling. Then, potential metabolomic markers for the studied forms of hypertensive conditions were identified using multivariate statistics. Analysis of the data obtained showed that hereditary stress-induced arterial hypertension in ISIAH rats was characterized by a decrease in the following urine metabolites: nicotinamide and 1-methylnicotinamide (markers of inflammatory processes), N- acetylglutamate (nitric oxide cycle), isobutyrate and methyl acetoacetate (gut microbiota). Pharmacologically induced forms of hypertension (the L-NAME and DOCA+NaCl groups) do not share metabolomic markers with hereditary AH. They are differentiated by N,N-dimethylglycine (both groups), choline (the L-NAME group) and 1-methylnicotinamide (the group of rats with DOCA-salt hypertension).

Multiple forms of perceived job discrimination and hypertension risk among employed women: Findings from the Sister Study.

BACKGROUND: Hypertension has been linked to socially patterned stressors, including discrimination. Few studies have quantified the risk of hypertension associated with exposure to perceived job discrimination. METHODS: We used prospective cohort data from the Sister Study (enrollment from 2003-2009) to estimate self-reported incident hypertension associated with perceived job discrimination based on race, gender, age, sexual orientation, or health status. Job discrimination in the prior 5 years was assessed in 2008-2012, and incident doctor-diagnosed hypertension was ascertained in previously hypertension-free participants. RESULTS: Among the 16,770 eligible participants aged 37-78 years at the start of follow-up, 10.5% reported job discrimination in the past 5 years, and 19.2% (n = 3226) reported incident hypertension during a median follow-up of 9.7 years (interquartile range 8.2-11.0 years). Self-reported poor health or inclusion in minoritized groups based on race/ethnicity or sexual orientation were more frequent among those reporting job discrimination. In a Cox proportional hazards model adjusting for covariates, report of at least one type of job discrimination (compared to none) was associated with a 14% (hazard ratio = 1.14 [95% confidence: 1.02-1.27]) higher hypertension risk. Results from sensitivity analyses reinforced the findings. CONCLUSIONS: Results suggest that interventions addressing job discrimination could have workplace equity and health benefits.