AUTHOR=Styles Jennifer N. , Converse Reagan R. , Griffin Shannon M. , Wade Timothy J. , Klein Elizabeth , Nylander-French Leena A. , Stewart Jill R. , Sams Elizabeth , Hudgens Edward , Egorov Andrey I. 

TITLE=Human Cytomegalovirus Infections Are Associated With Elevated Biomarkers of Vascular Injury

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2020.00334

DOI=10.3389/fcimb.2020.00334

ISSN=2235-2988

ABSTRACT=<p><bold>Background:</bold> Human cytomegalovirus (HCMV) infects ~50% of adults in the United States. HCMV infections may cause vascular inflammation leading to cardiovascular disease, but the existing evidence is inconsistent.</p><p><bold>Objective:</bold> We investigated demographic predictors of HCMV infection and explored associations between HCMV infection status, the intensity of anti-HCMV Immunoglobulin G (IgG) antibody response, and biomarkers of inflammation and endothelial function which are known predictors of cardiovascular disease.</p><p><bold>Methods:</bold> We conducted a cross-sectional study of 694 adults residing in the Raleigh-Durham-Chapel Hill, NC metropolitan area. Serum samples were tested for IgG antibody response to HCMV, and for biomarkers of vascular injury including soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Associations between HCMV and biomarker levels were analyzed using two approaches with HCMV serostatus modeled as a binary variable and as an ordinal variable with five categories comprised of seronegative individuals and quartiles of anti-HCMV antibody responses in seropositive individuals.</p><p><bold>Results:</bold> HCMV seroprevalence in the study population was 56%. Increased body mass index, increased age, female gender, racial/ethnic minority status, and current smoking were significantly associated with HCMV seropositivity in a multivariate regression analysis. HCMV seropositivity was also associated with 9% (95% confidence interval 4–15%) and 20% (0.3–44%) increases in median levels of sICAM-1 and CRP, respectively, after adjusting for covariates. The association between HCMV seropositivity and median levels of sVCAM-1 and SAA were positive but not statistically significant. Significant positive associations were observed between the intensity of anti-HCMV IgG responses and levels of sICAM-1 and sVCAM-1 (<italic>p</italic>-values 0.0008 and 0.04 for linear trend, respectively). To our knowledge, this is the first epidemiological study to show a relationship between anti-HCMV IgG responses and vascular injury biomarkers sICAM-1 and sVCAM-1 in the general population.</p><p><bold>Conclusion:</bold> HCMV infections are associated with vascular injury and inflammation biomarkers in adult residents of North Carolina.</p>