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Risk Factors for Intestinal Barrier Impairment in Patients With Essential Hypertension.

ABSTRACT: Background: Previous studies have indicated an association between hypertension and intestinal barrier dysfunction in mice models. The present study aims to investigate the association between hypertension and intestinal barrier impairment in humans and identify the novel potential risk factors for hypertension. Methods: Medical data from consecutive inpatients were retrospectively pooled from patient records. We compared intestinal barrier serum markers [diamine oxidase (DAO), lipopolysaccharide (LPS), and _D-lactate] between those patients with and without hypertension. Moreover, the associations between intestinal barrier markers and cardiovascular risk, hypertension history, blood pressure control, hypertensive complications, and antihypertensive medication history were also analyzed. Results: Overall, 106 hypertensive and 251 normotensive subjects were included. Patients with hypertension had a higher level of DAO (28.30 vs. 18.73%, P = 0.044) and LPS (22.64 vs. 11.16%, P = 0.005). In hypertensive patients, multivariate logistic regression analyses showed that long hypertension history (?20 years), poor control of diastolic blood pressure, cardiac and renal complications, and use of multiple antihypertensive medications were risk factors for elevated DAO, while the use of multiple antihypertensive medications was a risk factor for elevated _D-lactate (P < 0.05). Conclusions: Hypertension is associated with impairment of intestinal barrier, especially in patients with long duration, poor blood pressure control, cardiac and renal complications, and use of multiple antihypertensive medications. The current study indicates that intestinal barrier dysfunction might be a potential predictor of hypertension.

SUBMITTER: Li C

PROVIDER: S-EPMC7873557 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Risk Factors for Intestinal Barrier Impairment in Patients With Essential Hypertension.

Li Cao C Xiao Ping P Lin Da D Zhong Hao-Jie HJ Zhang Ran R Zhao Zhi-Gang ZG He Xing-Xiang XX

Frontiers in medicine 20210127

<b>Background:</b> Previous studies have indicated an association between hypertension and intestinal barrier dysfunction in mice models. The present study aims to investigate the association between hypertension and intestinal barrier impairment in humans and identify the novel potential risk factors for hypertension. <b>Methods:</b> Medical data from consecutive inpatients were retrospectively pooled from patient records. We compared intestinal barrier serum markers [diamine oxidase (DAO), lip ...[more]

PMID: 33585498

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Project description:Impaired intestinal barrier plays an important role in the pathogenesis of hypertension primarily through promoting the development of chronic low-grade inflammation. Baicalin is the major flavonoid component of Scutellaria baicalensis Georgi, a medicinal plant commonly used for the treatment of inflammatory intestinal disorders and hypertension in traditional Chinese medicine. However, it remains to be elucidated whether baicalin alleviates hypertension-associated intestinal barrier impairment. The current study thus investigated the effects of baicalin on the intestinal barrier integrity, the intestinal expression of genes encoding proinflammatory factors and tight junction proteins, the serum levels of the inflammatory markers, the amount of fecal short-chain fatty acids (SCFAs) and the abundance of SCFAs-producing bacteria in the spontaneously hypertensive rats (SHRs). The results showed that baicalin alleviated the pathological lesions in the ilium and the proximal colon in the SHRs. Baicalin treatment resulted in decreased ileal and colonic expression of proinflammatory genes in the SHRs. In addition, baicalin treatment attenuated hypertension-associated intestinal hyperpermeability and decreased the serum levels of inflammatory indicators such as high-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, and IL-6 in the SHRs. The protective effect of baicalin on the intestinal integrity was also supported by well-preserved intestinal ultrastructure and increased intestinal expression of genes encoding tight junction proteins such as zonula occludens-1 (ZO-1), cingulin, and occludin in the SHRs. Lastly, baicalin treatment increased the amount of fecal SCFAs and the abundance of SCFAs-producing bacteria in the SHRs. In conclusion, the work here provides for the first time the morphological, biochemical, and molecular evidence supporting the protective effects of baicalin on the intestinal integrity in the SHRs, which may help better understand the therapeutic effects of S. baicalensis Georgi in the treatment of hypertension.

Project description:BackgroundCognitive impairment is prevalent in Chinese patients with hypertension; however, current evidence on prevalence and risk factors is required to be synthesized.ObjectivesThis systematic review and meta-analysis aimed to evaluate the prevalence and risk factors of cognitive impairment in Chinese patients with hypertension.MethodsTwo reviewers independently searched PubMed, Web of Science, Embase, The Cochrane Library, CNKI, CBM, the Wanfang database, and the VIP database from their inception to 7 June 2023. The gray literature and the reference lists of the included studies were also retrieved manually. Moreover, we also independently performed the eligibility screening, data extraction, and data synthesis. The primary outcome was the prevalence of cognitive impairment in Chinese patients with hypertension, and the secondary outcomes were the risk factors for cognitive impairment in patients with hypertension. R (version 4.0.3) was used for data synthesis.ResultsIn total, 82 studies involving 53,623 patients with hypertension were included in this meta-analysis. The pooled prevalence of cognitive impairment in patients with hypertension was 37.6% (95% CI: 33.2-42.2%). A total of 12 risk factors, including advanced age (r = -0.34, 95% CI: -0.45, -0.21), female sex (OR = 1.15, 95% CI: 1.01-1.32), BMI > 24 Kg/m2 (OR = 1.76, 95% CI: 1.04-3.00), lower educational level (OR = 2.01, 95% CI: 1.10-3.67), single status (OR = 1.63, 95% CI: 1.32-2.02), complications with diabetes (OR = 1.44, 95% CI: 1.14-1.80), coronary heart disease (OR = 1.49, 95% CI: 1.12-1.97), higher stage of hypertension [stage 3 vs. stage 1, OR = 3.08, 95% CI: 1.82-5.22; stage 2 vs. stage 1, OR = 1.83, 95% CI: 1.29-2.60], no regular physical activity (OR = 0.40, 95% CI: 0.21-0.77), higher levels of systolic blood pressure (r = -0.25, 95% CI: -0.42, -0.08), Hcy (r = -0.39, 95% CI: -0.63, -0.09), and IL-6 (r = -0.26, 95% CI: -0.48, -0.02) were detected.ConclusionCognitive impairment is prevalent in Chinese patients with hypertension, and the increased prevalence was associated with several demographic characteristics, complicated disease, no regular physical activity, worse hypertension status (higher stages and SBP), and high levels of biomarkers. Therefore, more attention should be paid to the early identification and treatment of patients with hypertension who are at high risk for cognitive impairment in clinical practice. In addition, relevant risk factors should be controlled to reduce the incidence of cognitive impairment.Systematic review registrationhttp://www.crd.york.ac.uk/PROSPERO, identifier [CRD42023410437].

Project description:BackgroundCognitive impairment in hemodialysis patients has been acknowledged over the last years and has been reported in up to 80% of patients. Older age, high prevalence of cardiovascular risk factors, such as stroke and transient ischemic attack, uremia, and multiple metabolic disturbances represent the most common factors for cognitive impairment in hemodialysis patients.MethodsWe conducted a prospective cohort study on 408 patients from 10 hemodialysis centers in the regional government district of Middle Hesse (Germany). Patients underwent a neuropsychological test battery consisting of five tests, in addition to a phonemic fluency test, to assess cognitive profile. The patients were classified as no cognitive impairment or mildly-, moderately- or severely-impaired cognitive function, depending on the degree of impairment and number of domains where the deficit was determined. We analyzed the cognitive profile and the change in performance over time in hemodialysis patients based on their cognitive status at baseline vs. 1-year follow-up.ResultsOf 479 eligible patients, 408 completed all tests at baseline. Only 25% (n = 102) of the patients had no cognitive impairment. Fourteen per cent (n = 57), 36.5% (n = 149), and 24.5% (n = 100) of patients showed mild, moderate, and severe impairment, respectively. In patients with cognitive impairment, all cognitive domains were affected, and impairment was significantly associated with depression and education. The most impaired cognitive performance was immediate memory recall, and the best performance was found in naming ability. No significant change was observed after 1-year follow up in any domain.ConclusionOur study shows that the prevalence of cognitive impairment in hemodialysis patients is high and that it is affected by the presence of depression. Furthermore, education has an effect on cognitive test results. As depression has a significant influence on cognitive impairment, its early identification is essential in order to initiate treatment at an early stage, hoping to positively influence cognitive performance.

Project description:Rationale: The dysfunctional gut-kidney axis forms a vicious circle, which eventually becomes a catalyst for the progression of chronic kidney disease (CKD) and occurrence of related complications. However, the pathogenic factors of CKD-associated intestinal dysfunction and its mechanism remain elusive.Methods: We first identified the protein-bound uremic toxin indoxyl sulfate (IS) as a possible contributor to intestinal barrier injury. Transepithelial electrical resistance, permeability assay and transmission electron microscopy were carried out to evaluate the damaging effect of IS on intestinal barrier in intestinal epithelial cells, IS-injected mice and CKD mice. In vitro and in vivo experiments were performed to investigate the role of IS in intestinal barrier injury and the underlying mechanism. Finally, CKD mice treated with AST-120 (an oral adsorbent for IS) and gene knockout mice were used to verify the mechanism and to explore possible interventions for IS-induced intestinal barrier injury.Results: Transepithelial electrical resistance and the expressions of tight junction-related genes were significantly suppressed by IS in intestinal epithelial cells. In vitro experiments demonstrated that IS inhibited the expression of dynamin-related protein 1 (DRP1) and mitophagic flux, whereas DRP1 overexpression attenuated IS-induced mitophagic inhibition and intestinal epithelial cell damage. Furthermore, IS suppressed DRP1 by upregulating the expression of interferon regulatory factor 1 (IRF1), and IRF1 could directly bind to the promoter region of DRP1. Additionally, the decreased expression of DRP1 and autophagosome-encapsulated mitochondria were observed in the intestinal tissues of CKD patients. Administration of AST-120 or genetic knockout of IRF1 attenuated IS-induced DRP1 reduction, mitophagic impairment and intestinal barrier injury in mice.Conclusions: These findings suggest that reducing IS accumulation or targeting the IRF1-DRP1 axis may be a promising therapeutic strategy for alleviating CKD-associated intestinal dysfunction.

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Risk Factors for Intestinal Barrier Impairment in Patients With Essential Hypertension.

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Risk Factors for Intestinal Barrier Impairment in Patients With Essential Hypertension.

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