Brachial Artery Echogenicity and Grayscale Texture Changes in HIV-Infected Individuals Receiving Low-Dose Methotrexate

Abstract

Objective We evaluated the biological effects of low-dose methotrexate (LDMTX) on 3 novel brachial artery grayscale ultrasound measures that may indicate subclinical arterial injury. Approach and Results Exploratory analysis from a clinical trial of people with HIV infection at increased cardiovascular disease risk who were randomly assigned to LDMTX (target dose 15 mg/week) or placebo. Brachial artery ultrasound grayscale median, gray level difference statistic texture contrast (GLDS-CON), and gray level texture entropy were measured at baseline and after 24 weeks of intervention. Findings from the intention-to-treat (N=148) and adequately dosed (N=118) populations were consistent, so the adequately dosed population results are presented. Participants were a median (Q1, Q3) age of 54 (50, 60) years. After 24 weeks, the LDMTX intervention was associated with a 25.4% (−18.1, 58.6; p=0.007) increase in GLDS-CON compared to 1.3% (−29.1, 44.7; p=0.97) with placebo (p=0.05) and a 0.10 u (−0.06, 0.23; p=0.026) increase in entropy compared to 0.02 u (−0.11, 0.14; p=0.54) with placebo (p=0.14). At week 24, changes in CD4+ T-cells correlated inversely with changes in GLDS-CON (ρ= −0.20, p=0.031), and entropy (ρ= −0.21, p=0.023). Changes in D-dimer levels, but no other inflammatory biomarkers, also correlated inversely with changes in GLDS-CON (ρ= −0.23, p=0.014) and entropy (ρ= −0.26, p=0.005). Conclusions Brachial artery GLDS-CON and entropy increased after 24 weeks of LDMTX, though the latter was not significantly different from placebo. Grayscale changes were associated with decreases in CD4+ T-cell and D-dimer concentrations and may indicate favorable arterial structure changes.

HIV infection and coronary heart disease: mechanisms and management

“…By contrast, in another study published in 2018, low dose methotrexate significantly lowered the CD8 + T cell count but had no effect on inflammatory markers or endothelial function 105 . However, low dose methotrexate did favourably affect specialized ultra sonography indices in the brachial artery 106 . These preliminary studies with inflammatory biomarkers as surrogate end points will hopefully lead to clinical trials on anti inflammatory treatments with cardiovascular events as end points in the population living with HIV.…”

Lipid Abnormalities in Persons Living With HIV Infection

“…Similarly, in a multicentre study, our group reported no effect of low-dose methotrexate on inflammatory markers or endothelial function 80 but methotrexate did favourably affect coronary artery echogenicity, a surrogate marker of plaque composition. 81 These preliminary studies with inflammatory biomarkers as surrogate end points will hopefully lead to larger trials of anti-inflammatory treatments with CV events as end points among individuals living with HIV.…”

Changes in carotid artery structure with smoking cessation

“…9,10,[27][28][29] We hypothesize that as BMI increases, tissue composition and arterial wall structure are altered due to inflammatory cell infiltration, which alters the echogenicity and texture features seen on an ultrasound image. 9,10,21,28,30 Ultrasound grayscale features differ based on scatterer sizes in phantoms, thus confirming that ultrasound grayscale images are representative of the medium that the sound wave is traversing. 21,30 Thus, as tissue composition and structure of the arterial wall are altered either by weight gain and changes in overall health (i.e.…”

“…35 In our studies of brachial artery grayscale, changes with exercise and an anti-inflammatory intervention were detected within 6 months of therapy. 30…”