Abstract 66: Increased Circulating Inflammatory Endothelial Cells (IEC) in African-American vs. Caucasians with Essential Hypertension

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Alfonso Eirin ◽  
Sandra M Herrmann ◽  
Monika L Gloviczki ◽  
Xiangyang Zhu ◽  
Hui Tang ◽  
...  

Introduction: Morbidity and mortality attributable to hypertension are higher in African American (AAEH) compared to Caucasian essential hypertensive (EH) patients, possibly related to a differential effect on vascular injury and repair. While circulating endothelial progenitor cells (EPC) preserve endothelial integrity IEC detach from sites of injury and represent markers of vascular damage. We hypothesized that plasma levels of IEC and inflammatory markers would be higher in AAEH compared to EH patients. METHODS: Inferior vena cava levels of CD34+/KDR+ (EPC) and VAP-1+ (IEC) cells were measured by FACS in EH and AAEH under fixed sodium intake (150 mEq/d) and blockade of the renin-angiotensin-system, and compared to systemic levels in normotensive control subjects (n=19 each). Systemic levels of inflammatory cytokines and EPC homing factors were measured by Luminex. Results: Blood pressure, serum creatinine, lipids, antihypertensive medications, and EPC levels did not differ between EH and AAEH patients. Circulating IEC were higher in AAEH, and inversely correlated with EPC levels (Figure). Systemic levels of inflammatory cytokines and EPC homing factors were higher in AAEH compared to EH patients (Table), and correlated directly with IEC. Conclusion: Despite preserved kidney function and controlled BP, circulating inflammatory markers were elevated in AAEH and correlated with increased IEC and decreased EPC levels. Increased release of cytokines and IEC in AAEH may impair EPC reparative capacity and predispose to hypertensive vascular injury. This process may aggravate vascular damage and accelerate hypertension-related morbidity/mortality rates in AAEH.

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1437.2-1438
Author(s):  
T. Kvlividze ◽  
V. Polyakov ◽  
В. Zavodovsky ◽  
Y. Polyakova ◽  
L. Seewordova ◽  
...  

Background:Interest in highly specialized tissue cytokines contributed to the discovery of new biologically active molecules. Nesfatin-1 (NF) - discovered in 2006 as an anorexigenic factor. NF-1 is believed to be involved in the regulation of energy homeostasis by regulating appetite and water intake. The role of NF-1 in the pathogenesis of inflammatory diseases is poorly understood. Recently, studies have found a relationship between an increased level of NF-1 and inflammatory markers in various pathologies.Objectives:Study of the level of nesfatin-1 in the blood serum of healthy people, determination of the correlation between the level of NF-1 with the severity of clinical symptoms and classic markers of inflammation in patients with RA.Methods:120 persons were examined: 90 patients with RA and 30 healthy people. All patients underwent a complete clinical and laboratory examination. Plasma NF-1 levels were determined using commercial test systems (RaiBiotech, cat # EIA-NESF) according to the manufacturer’s instructions. Patients with various forms of RA were comparable in age to the group of healthy individuals. Statistical processing of clinical examination data was carried out using the “STATISTICA 10.0 for Windows” software package. Quantitative data were processed statistically using the parametric Student’s t-test, qualitative data using the non-parametric chi-square test. The significance of differences between groups was determined using analysis of variance. The results were considered statistically significant at p <0.05.Results:The average level of NF-1 in blood serum in healthy individuals was 31.79 ± 3.21 ng / ml (M ± σ). The level of normal NF-1 values in healthy individuals, defined as M ± 2σ, ranged from 25.3 to 37.83 ng / ml. There was no significant difference in the levels of circulating NF-1 and BMI in healthy individuals and patients with RA (p> 0.05). The inverse relationship of a lower level of NF-1 with an increase in BMI was not significant.Group 1 (66 patients with RA) with increased serum NF-1 levels (> 37.83 ng / ml), and group 2 (44 patients) with normal values (<37.83 ng / ml). A high level of NF-1 was characteristic for patients with high activity according to DAS28, RF seropositive, ACCP-positive, with extra-articular manifestations, who had been ill for 10 years or more. A reliable relationship between the level of NF-1 in the blood serum and laboratory parameters of RA activity - ESR, CRP, was shown, and secondary synovitis was more common. Our data show a direct correlation between the NF-1 level of the pro-inflammatory markers of RA.Conclusion:The positive correlation between the level of NF-1 and classical markers of inflammation, such as CRP and ESR, confirms the involvement of NF-1 in the pathophysiology of inflammation in RA. This is also evidenced by the correlation of a high level of NF-1 in the blood serum with a more severe clinical picture of RA. It is known that NF-1 can promote the release of pro-inflammatory cytokines such as interleukin-8 (IL-8), interleukin-6 (IL-6), and macrophage inflammatory protein-1a (MIP-1a) in the chondrocytes of RA patients.It is necessary to further study the role of NF-1 in the pathogenesis of systemic inflammatory reactions and the possibility of targeting pro-inflammatory cytokines, the possibility of regulating the level of NF-1 by drugs.References:[1]Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R. Kvlividze T.Z., Zavodovsky B.V., Akhverdyan Yu.R., Polyakova Yu.V., Sivordova L.E., Yakovlev A.T., Zborovskaya I.A. Serum nesfatin -1 as a marker of systemic inflammation in rheumatoid arthritis. Klinicheskaya Laboratornaya Diagnostika (Russian Clinical Laboratory Diagnostics). 2019; 64 (1): 53-56 (in Russ.).Disclosure of Interests:None declared


Vaccines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 436
Author(s):  
Ali A. Rabaan ◽  
Shamsah H. Al-Ahmed ◽  
Javed Muhammad ◽  
Amjad Khan ◽  
Anupam A Sule ◽  
...  

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a severe pandemic of the current century. The vicious tentacles of the disease have been disseminated worldwide with unknown complications and repercussions. Advanced COVID-19 syndrome is characterized by the uncontrolled and elevated release of pro-inflammatory cytokines and suppressed immunity, leading to the cytokine storm. The uncontrolled and dysregulated secretion of inflammatory and pro-inflammatory cytokines is positively associated with the severity of the viral infection and mortality rate. The secretion of various pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6 leads to a hyperinflammatory response by recruiting macrophages, T and B cells in the lung alveolar cells. Moreover, it has been hypothesized that immune cells such as macrophages recruit inflammatory monocytes in the alveolar cells and allow the production of large amounts of cytokines in the alveoli, leading to a hyperinflammatory response in severely ill patients with COVID-19. This cascade of events may lead to multiple organ failure, acute respiratory distress, or pneumonia. Although the disease has a higher survival rate than other chronic diseases, the incidence of complications in the geriatric population are considerably high, with more systemic complications. This review sheds light on the pivotal roles played by various inflammatory markers in COVID-19-related complications. Different molecular pathways, such as the activation of JAK and JAK/STAT signaling are crucial in the progression of cytokine storm; hence, various mechanisms, immunological pathways, and functions of cytokines and other inflammatory markers have been discussed. A thorough understanding of cytokines’ molecular pathways and their activation procedures will add more insight into understanding immunopathology and designing appropriate drugs, therapies, and control measures to counter COVID-19. Recently, anti-inflammatory drugs and several antiviral drugs have been reported as effective therapeutic drug candidates to control hypercytokinemia or cytokine storm. Hence, the present review also discussed prospective anti-inflammatory and relevant immunomodulatory drugs currently in various trial phases and their possible implications.


Author(s):  
Kathryn Foti ◽  
Randi E. Foraker ◽  
Pamela Martyn-Nemeth ◽  
Cheryl A.M. Anderson ◽  
Nancy R. Cook ◽  
...  

Implementation of prevention policies has often been impeded or delayed due to the lack of randomized controlled trials (RCTs) with hard clinical outcomes (eg, incident disease, mortality). Despite the prominent role of RCTs in health care, it may not always be feasible to conduct RCTs of public health interventions with hard outcomes due to logistical and ethical considerations. RCTs may also lack external validity and have limited generalizability. Currently, there is insufficient guidance for policymakers charged with establishing evidence-based policy to determine whether an RCT with hard outcomes is needed before policy recommendations. In this context, the purpose of this article is to assess, in a case study, the feasibility of conducting an RCT of the oft-cited issue of sodium reduction on cardiovascular outcomes and then propose a framework for decision-making, which includes an assessment of the feasibility of conducting an RCT with hard clinical outcomes when such trials are unavailable. We designed and assessed the feasibility of potential individual- and cluster-randomized trials of sodium reduction on cardiovascular outcomes. Based on our assumptions, a trial using any of the designs considered would require tens of thousands of participants and cost hundreds of millions of dollars, which is prohibitively expensive. Our estimates may be conservative given several key challenges, such as the unknown costs of sustaining a long-term difference in sodium intake, the effect of differential cotreatment with antihypertensive medications, and long lag time to clinical outcomes. Thus, it would be extraordinarily difficult to conduct such a trial, and despite the high costs, would still be at substantial risk for a spuriously null result. A robust framework, such as the one we developed, should be used to guide policymakers when establishing evidence-based public health interventions in the absence of trials with hard clinical outcomes.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Lisa M Lewis

Background : Medication adherence (ADH) is key to decreasing hypertension (HTN)-related morbidity and mortality in older African-American (AA) adults. However, older AA adults have poorer ADH to prescribed antihypertensive medications when compared to their younger and Caucasian-American counterparts. Patient beliefs and cultural concepts about their medications influence their medication ADH. An important cultural concept in this regards is spirituality, which is a significant resource in the AA community. Thus, the purpose of this qualitative study was to explore the role of spirituality in ADH to antihypertensive medications for older AA adults. Methods: Older AA adults who were members of a Program of All Inclusive Care for the Elderly (PACE) and who were (a) diagnosed with HTN; (b) prescribed at least one antihypertensive medication; (c) self-identified as African-American or Black; and (d) self-identified as spiritual completed one in-depth individual face-to-face in this qualitative descriptive study informed by grounded theory. Demographic data were also collected. Results : Twenty-one PACE members completed the study. All of the participants were female. The mean age of participants was 73 years with most completing high school (67%). The mean HTN diagnosis was16.7 years and mean number of prescriptions for antihypertensives was 3.3. Participants indicated that their spirituality was used in a collaborative process with formal health care to manage their ADH to antihypertensive medications. This process was identified as Partnering with God to Manage My Medications. Partnering with God to Manage My Medications indicated that the PACE members acknowledged personal responsibility for adhering to their antihypertensive medication regimen but used their spirituality as a resource for making decisions to remain adherent; coping with medication side effects; and increasing their self-efficacy to deal with barriers to ADH . Conclusions : Spirituality played a positive role in medication adherence for the PACE members. Incorporating individual beliefs, such as spirituality, into patient treatment for HTN may capitalize on their inner resources for medication ADH and demonstrates culturally appropriate care.


2018 ◽  
Vol 50 (10) ◽  
pp. 904-912 ◽  
Author(s):  
Fatima Trebak ◽  
Wencheng Li ◽  
Yumei Feng

Increased sodium appetite is a physiological response to sodium deficiency; however, it has also been implicated in disease conditions such as congestive heart failure, kidney failure, and salt-sensitive hypertension. The central nervous system is the major regulator of sodium appetite and intake behavior; however, the neural mechanisms underlying this behavior remain incompletely understood. Here, we investigated the involvement of the (pro)renin receptor (PRR), a component of the brain renin-angiotensin system, in the regulation of sodium intake in a neuron-specific PRR knockout (PRRKO) mouse model generated previously in our laboratory. Sodium intake following deoxycorticosterone (DOCA) stimulation was tested by assessing the preference of mice for 0.9% saline or regular water in single-animal metabolic cages. Blood pressure was monitored in conscious, freely moving mice by a telemetry system. We found that saline intake and total fluid intake were significantly reduced in PRRKO mice following DOCA treatment compared with that in wild-type (WT) mice, whereas regular water intake was similar between the genotypes. Sodium preference and total sodium intake were significantly reduced in PRRKO mice compared with WT mice. PRRKO mice also excreted less urine and urinary sodium compared with WT mice following DOCA treatment, whereas potassium excretion was similar between the two groups. Finally, we found that the sodium balance, calculated by subtracting urinary sodium excretion from sodium intake, was greater in WT mice than in PRRKO mice. Collectively, these findings suggest that the neuronal PRR plays a regulatory role in DOCA-induced sodium intake.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Saima Husain ◽  
Mari K Nishizaka ◽  
Eduardo Pimenta ◽  
Krishna K Gaddam ◽  
Suzanne Oparil ◽  
...  

Primary aldosteronism (PA) is a common cause of resistant hypertension with a prevalence of approximately 20%. Spironolactone is the drug of choice for the medical management of patients with PA. Blacks have been reported to have low-renin HTN and respond better to diuretics and calcium channel blockers. Racial differences in response to spironolactone in patients with resistant hypertension have not been previously described. Consecutive subjects referred to the University of Alabama at Birmingham hypertension clinic for resistant hypertension had been evaluated with a plasma aldosterone concentration (PAC), plasma renin activity (PRA), and a 24-hr urine collection for aldosterone, sodium, and potassium during the patient’s usual diet. The BP response to spironolactone was compared retrospectively in patients. For clinical reasons, subjects had been treated with a median dose of 25 mg of spironolactone and the BP response at 6 weeks, 3 and 6 months was compared retrospectively. A total of 117 patients with resistant hypertension were included in the analysis, including 59 white and 58 black subjects. Both groups had a similar number of antihypertensive medications at baseline. PAC, PRA, U-aldo and serum potassium levels were also similar. BP reduction at 6-weeks, 3- and 6-months after treatment with spironolactone was similar in black and white subjects. At 3 months, the mean reduction in systolic BP was −19.5±19.0 and −23.2±20.0 for blacks and whites, respectively (p= 0.321). These data indicate that African American and white subjects with resistant hypertension respond equally well to spironolactone.


2021 ◽  
pp. 000313482110385
Author(s):  
David P Stonko ◽  
Faris K. Azar ◽  
Richard D. Betzold ◽  
Jonathan J. Morrison ◽  
Ryan B. Fransman ◽  
...  

Introduction Injuries to the inferior vena cava (IVC), while uncommon, have a high mortality despite modern advances. The goal of this study is to describe the diagnosis and management in the largest available prospective data set of vascular injuries across anatomic levels of IVC injury. Methods The American Association for the Surgery of Trauma PROspective Observational Vascular Injury Treatment (PROOVIT) registry was queried from November 2013 to January 2019. Demographics, diagnostic modalities, injury patterns, and management strategies were recorded and analyzed. Comparisons between anatomic levels were made using non-parametric Wilcoxon rank-sum statistics. Results 140 patients from 19 institutions were identified; median age was 30 years old (IQR 23-41), 75% were male, and 62% had penetrating mechanism. The suprarenal IVC group was associated with blunt mechanism (53% vs 32%, P = .02), had lower admission systolic blood pressure, pH, Glasgow Coma Scale (GCS), and higher ISS and thorax and abdomen AIS than the infrarenal injury group. Injuries were managed with open repair (70%) and ligation (30% overall; infrarenal 37% vs suprarenal 13%, P = .01). Endovascular therapy was used in 2% of cases. Overall mortality was 42% (infrarenal 33% vs suprarenal 66%, P<.001). Among survivors, there was no difference in first 24-hour PRBC transfusion requirement, or hospital or ICU length of stay. Conclusions Current PROOVIT registry data demonstrate continued use of ligation extending to the suprarenal IVC, limited adoption of endovascular management, and no dramatic increase in overall survival compared to previously published studies. Survival is likely related to IVC injury location and total injury burden.


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