Brief Report: Vascular Dysfunction and Monocyte Activation Among Women With HIV

Abstract

Objective: Women with HIV (WHIV) on antiretroviral therapy (ART) face an increased risk of cardiovascular disease (CVD) in the context of heightened systemic immune activation. Aortic stiffness, a measure of vascular dysfunction and a robust predictor of CVD outcomes, is highly influenced by immune activation. We compared aortic stiffness among women with and without HIV and examined interrelationships between aortic stiffness and key indices of systemic immune activation.

Methods: Twenty WHIV on ART and 14 women without HIV group-matched on age and body mass index (BMI) were prospectively recruited and underwent cardiovascular magnetic resonance imaging, as well as metabolic and immune phenotyping.

Results: Age and BMI did not differ significantly across groups (age: 52 ± 4 vs. 53 ± 6 years; BMI: 32 ± 7 vs. 32 ± 7 kg/m). Aortic pulse wave velocity (aPWV) was higher among WHIV (8.6 ± 1.3 vs. 6.5 ± 1.3 m/s, P < 0.0001), reflecting increased aortic stiffness. Among the whole group and among WHIV, aPWV related to sCD163 levels (whole group: R = 0.65, P < 0.0001; WHIV: R = 0.73, P = 0.0003) and to myocardial fibrosis (extracellular volume; whole group: R = 0.54, P = 0.001; WHIV: R = 0.47, P = 0.04). Both HIV status and sCD163 levels independently predicted aPWV, controlling for age, BMI, cigarette smoking status, and systolic blood pressure (HIV status: β-estimate = 0.69, 95% CI [0.1 to 1.3], P = 0.02; sCD163: β-estimate = 0.002, 95% CI [0.0006 to 0.004], P = 0.01). Among WHIV, sCD163 levels independently predicted aPWV, controlling for duration of HIV, CD4 count, and HIV viral load (sCD163: β-estimate = 0.004, 95% CI [0.002 to 0.005], P = 0.0005).

Conclusions: Asymptomatic WHIV on ART have increased aortic stiffness as compared to matched control subjects. Among WHIV, aPWV related to heightened monocyte activation (sCD163) and to downstream CVD pathology (myocardial fibrosis). CLINICALTRIALS.

Gov registration: NCT02874703.

Figures

FIGURE 1.

Assessment of aortic arch pulse wave velocity: (A) Image of the thoracic aorta (oblique parasagittal/candy cane view). The solid white line, which is perpendicular to the ascending aorta (1) and divides the proximal descending aorta (2), represents the acquisition planes for the pulse wave velocity assessment on cardiovascular MRI. B, Aortic flow-versus-time curves: aPWV is determined from the time delay of the representative aortic flow-versus-time curves recorded at the ascending aorta (location 1 (blue) in A and red velocity-time curve in B) and the descending aorta (location 2 (red) in A and blue velocity-time curve in B) using a cross-correlation method on the systolic upstroke part of the flow curves. Pulse wave velocity is defined as Δx/Δt, where Δx is the aortic path length along a midline in the vessel lumen (dashed white line in A), and Δt is the transit time (distance between systolic upstroke of ascending and descending aorta flow curves shown in B).

FIGURE 2.

aPWV and monocyte activation. A, aPWV among women with versus without HIV. aPWV was significantly higher among WHIV versus women without HIV. [Data are graphically shown as median (interquartile range).] B, Relationship between aPWV and systemic monocyte activation among WHIV. Among WHIV, aPWV related directly to a marker of systemic monocyte activation, soluble CD163.