Background:
Atherosclerosis is a chronic inflammatory disease involving both innate and adaptive immune responses, characterized by the accumulation of T lymphocytes throughout the atherosclerotic plaque. Therefore, we hypothesized that increased CD4+ memory cells and decreased CD4+ naïve cells would be associated with atherosclerosis. To date, no multi-ethnic population-based studies have examined this question.
Methods:
Peripheral blood memory and naive subpopulations were measured by flow cytometry and defined by the markers CD4+CD45RO+ and CD4+CD45RA+, respectively. Data were analyzed as a proportion of CD4+ cells. Associations were explored with demographic and cardiovascular disease-related variables, and markers of infection, inflammation and subclinical atherosclerosis in a random subset (n=914 participants, composed of European Americans (n=397), Chinese Americans (n=96), African Americans (n=187) and Hispanics (n=234); mean age 66 years) of the Multi-Ethnic Study of Atherosclerosis (MESA). Agatston score, a measure of coronary calcification, was evaluated by cardiac computed tomography (CT) scan; serologies representing past exposure to pathogens were measured in serum by immunoassays. CD4+ cell indices were measured at Exam 4 (2005-2007); cardiovascular disease variables were obtained at the nearest previous exam; some measures, such as serologies, were available only at baseline (2000-2002).
Results:
Mean levels of circulating naïve, but not memory, CD4+ T cells were higher in woman than men (30.0% and 26.3%, respectively; P<0.0001) and negatively associated with age (P<0.0001). European Americans (EAs) had higher levels of naïve cells compared with African Americans and Hispanics (30.7%, 26.0% and 25.0%, respectively) and lower levels of memory cells compared with the same groups (50.7%, 55.7% and 58.0%, respectively; P<0.05); Chinese Americans were similar to EAs. Adjusting for age, gender and race/ethnicity, CD4+ naïve cells were inversely associated with past exposure to cytomegalovirus (CMV), Hepatitis A and H. Pylori (P<0.001), while memory cells were positively associated with CMV and H. Pylori (P<0.01). Using standardized linear regression models, CD4+ naïve cells were inversely associated with BMI (β= -1.62 ± 0.48), the inflammatory markers C-reactive protein (CRP) (β= -1.21 ± 0.48) and IL-6 (β= -1.79 ± 0.48) and with a positive Agatston score (β= -1.53 ± 0.65) (P<0.05); memory cells were positively associated with these same variables, after adjusting for age, gender and ethnicity.
Conclusion:
Differences in CD4+ T lymphocytes, including increased populations of memory cells and decreased populations of naïve cells, are associated with atherosclerosis as estimated by Agatston scores. These findings suggest that excess immune activation, as reflected by these differences, may contribute to atherosclerotic calcification.
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