Association of Macrophage Inflammation Biomarkers With Progression of Subclinical Carotid Artery Atherosclerosis in HIV-Infected Women and Men

Abstract

(See the editorial commentary by Feinstein and Lloyd-Jones on pages 1343-5.)Background. Monocytes and monocyte-derived macrophages promote atherosclerosis through increased inflammation and vascular remodeling. This may be especially true in chronic human immunodeficiency virus (HIV) infection.Methods. We examined 778 women (74% HIV + ) in the Women's Interagency HIV Study and 503 men (65% HIV + ) in the Multicenter AIDS Cohort Study who underwent repeated B-mode carotid artery ultrasound imaging in 2004-2013. We assessed baseline associations of the serum macrophage inflammation markers soluble (s)CD163, sCD14, galectin-3 (Gal-3), and Gal-3 binding protein (Gal-3BP) with carotid plaque formation (focal intima-media thickness >1.5 mm) over 7 years.Results. Marker levels were higher in HIV + persons versus HIV -persons. Presence of focal plaque increased over time: from 8% to 15% in women, and 24% to 34% in men. After adjustment for demographic, behavioral, and cardiometabolic factors, and CRP and interleukin-6, each standard deviation increase in sCD14 was associated with increased plaque formation (risk ratio [RR] 1.24, 95% confidence interval [CI] 1.07-1.43). This pattern was consistentby sex. sCD163 was associated with plaque formation in virally suppressed HIV + men (RR 1.52, 95% CI 1.04-2.22); Gal-3BP and Gal-3 were not associated with increased plaque.Conclusions. sCD14 and sCD163 may play important roles in atherogenesis among HIV + persons.

Subclinical cardiovascular disease in HIV controller and long‐term nonprogressor populations

“…This study supports previous work demonstrating elevated concentrations of inflammatory biomarkers among HIV controllers and LTNPs compared to HIV‐uninfected individuals . Levels of monocyte activation markers sCD163 and sCD14 have been associated with subclinical atherosclerosis in the MACS, WIHS and other cohorts . Despite elevated concentrations of sCD163 and sCD14 in HIV controllers and LTNPs compared to HIV‐uninfected individuals, we found similar prevalences of carotid and coronary subclinical atherosclerosis.…”

“…Inflammatory biomarker concentrations were collected for an ancillary study among 1281 individuals from MACS and WIHS who had serial carotid ultrasound scans . Characteristics of this cohort have been previously described . Biomarkers were chosen based on their established association with CVD risk .…”

“…Characteristics of this cohort have been previously described . Biomarkers were chosen based on their established association with CVD risk . Concentrations of soluble CD163 (sCD163), soluble CD14 (sCD14), interleukin‐6 (IL‐6), galectin‐3 (Gal‐3) and galectin‐3 binding protein (Gal‐3BP) were measured using ELISA in stored frozen sera collected at the core study visit closest to the vascular study visit.…”

Cardiovascular disease risk among women living with HIV in North America and Europe

“…Several physiology studies performed in all-male or predominantly male (>90% male) cohorts have revealed relationships between systemic markers of monocyte activation (sCD163, sCD14) and surrogates of atherosclerotic cardiovascular disease (ASCVD) risk including subclinical carotid artery atherosclerosis(21), aortic inflammation(22) (23), subclinical coronary atherosclerotic plaque(24) (25) (26), and pathologically remodeled coronary atherosclerotic plaque(27) (28). Separate physiology studies among WLHIV have confirmed parallel relationships between systemic immune activation markers and ASCVD risk surrogates, including subclinical carotid atherosclerosis(29) (30) (31) and the percent of non-calcified coronary atherosclerotic plaque(32). Cells of monocyte/macrophage lineage may also engender myocardial edema and fibrosis, presaging diastolic dysfunction and heart failure with preserved ejection fraction(33) (34).…”

Human immunodeficiency virus and liver disease: A comprehensive update

“…The extent to which these processes are synergistic and the mechanisms are largely unknown; however, it is possible they explain some of the extrahepatic manifestations of liver disease (and these viral infections). For example, cardiovascular disease incidence appears to be increased with HIV and HCV infection as well as nonalcoholic fatty liver disease (NAFLD), and macrophage activation has been linked to coronary and carotid artery inflammation . Clearly more work is needed to disentangle these associations and particularly to guide approaches to reducing the residual risk of inflammation that appears to be present in persons on long‐term ART.…”