Markers of microbial translocation predict hypertension in HIV‐infected individuals

Abstract

ObjectivesThe aim of the study was to test the hypothesis that microbial translocation, quantified by levels of lipopolysaccharide (LPS) and subsequent monocyte activation [soluble (sCD14)], is associated with hypertension in HIV-infected individuals. MethodsIn this exploratory substudy, 42 patients were recruited from a larger, longitudinal HIV-infected cohort study on blood pressure. LPS and sCD14 levels were measured retrospectively at the time of nadir CD4 cell count, selecting untreated HIV-infected patients with both advanced immunodeficiency and preserved immunocompetence at the time of nadir. Patients with later sustained hypertension (n = 16) or normotension (n = 26) throughout the study were identified. LPS was analysed using the Limulus Amebocyte Lysate colorimetric assay (Lonza, Walkersville, MD) and sCD14 using an enzyme-linked immunosorbent assay (ELISA). Nonparametric statistical tests were applied. ResultsIn the HIV-infected patients [median (interquartile range) age 42 (32-46) years; 79% male and 81% Caucasian], LPS and sCD14 levels were both negatively correlated with nadir CD4 cell count. Plasma levels of LPS (P < 0.001) and sCD14 (P = 0.024) were elevated in patients with later hypertension compared with patients with normotension. There was a stepwise increase in the number of patients with hypertension across tertiles of LPS (P = 0.001) and sCD14 (P = 0.007). Both LPS and sCD14 were independent predictors of elevated blood pressure after adjustment for age and gender. For each 10-unit increase in LPS (range 66-272 pg/ml), the increment in mean blood pressure in the first period of blood pressure recording was 0.86 (95% confidence interval 0.31-1.41) mmHg (P = 0.003). ConclusionsAs LPS and sCD14 were both independently associated with elevated blood pressure, microbial translocation may be linked to the development of hypertension.Keywords: HIV infection, hypertension, lipopolysaccharide, nadir CD4 cell count, soluble CD14. Accepted 5 December 2012 IntroductionNon-AIDS-related morbidities such as hypertension, cardiovascular disease (CVD), malignancy, and renal, liver and bone diseases have emerged as increasing clinical problems in HIV-infected patients [1]. In fact, non-AIDS-related mortality today exceeds AIDS-related mortality in populations with access to antiretroviral therapy (ART) [2]. A premature ageing process has been suggested to occur in HIV-infected individuals for which several contributing factors have been proposed, including viral replication, drug toxicity, lifestyle factors, and persistent immune Primary HIV infection is characterized by massive T-cell depletion in the gastrointestinal mucosa with subsequent enhanced translocation of bacterial products such as lipopolysaccharide (LPS) and flagellin from the intestinal lumen into the systemic circulation [3,4]. LPS is a potent inducer of immune response and inflammation through the innate immune system. Soluble CD14 (sCD14) is a marker of monocyte activation and is shed from monocytes upon LPS stimulation [5]. Microbial tr...

Microbial Translocation and Cardiometabolic Risk Factors in HIV Infection

“…106 Hence, it could be hypothesized that TLR4 stimulation and subsequent endothelial dysfunction might explain the close association between microbial translocation and hypertension previously reported. 90 In support of this hypothesis, strong and significant correlations were found between plasma LPS levels and asymmetric dimethylarginine (ADMA), a marker of nitric oxide-dependent endothelial dysfunction and its structural isomer symmetric dimethylarginine (SDMA), a novel biomarker of vascular and renal diseases. 107 Endothelial dysfunction can be directly assessed by flowmediated dilatation (FMD).…”

“…Indeed, plasma levels of both LPS and sCD14 at the time of nadir were elevated in HIVinfected compared to controls, predicted sustained hypertension, and were intercorrelated in subjects who developed hypertension several years later. 90 These data indicate that HIV-related factors including immunodeficiency and microbial translocation could be involved in the development of hypertension.…”

Clinical Implications of Circulating Microbiome in Cardiovascular Disease Patients

“…Circulating endotoxins also influence cardiac troponin T levels [100]. Circulating LPS and sCD14 were associated with hypertension in HIV-infected individuals [101]. Furthermore, HIV replication and antiretroviral therapy with elevated LPS levels were associated with atherosclerosis [102].…”

Documento de consenso sobre alteraciones metabólicas y riesgo cardiovascular en pacientes con infección por el virus de la inmunodeficiencia humana

“…La elevación de la TA en pacientes con VIH, debe tratarse siguiendo las mismas normas que se usan para la población general [43][44][45][46] . La decisión de iniciar tratamiento se basa en las cifras de TA y en el grado de RCV total 34,42 .…”

“…A la hora de decidir qué fármaco antihipertensivo emplear, deberemos considerar diversos factores relacionados con las vías metabólicas del TAR y de los distintos antihipertensivos, ya que existen potenciales interacciones farmacológicas o efectos tóxicos que limitan su uso 34,[43][44][45][46][47][48][49] . Las interacciones más esperadas ocurren entre ITINN e IP por sus interacciones con el grupo del CYP P450, siendo poco probables con raltegravir o maraviroc.…”