Cytomegalovirus antibody levels, inflammation, and mortality among elderly Latinos over 9 years of follow-up

Abstract

This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60-101 years) in California followed in 1998-2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.

Figure 1.

Kaplan-Meier survival curves for all-cause mortality by cytomegalovirus immunoglobulin G antibody titers for 1,468 subjects in the Sacramento Area Latino Study on Aging (California) from 1998 to 2008. Cytomegalovirus is divided into quartiles 1, 2, and 3 versus quartile 4. Panel A: unadjusted relation; panel B: adjusted for gender (male/female), age (above/below the mean), education (less than high school/high school or more), and comorbidities (none/one or more). Panel B shows survival for males older than 69 years of age with less than a high school education and one or more baseline comorbidities. Stratified log-rank test statistics were 17.6 (P < 0.001) for panel A and 17.04 (P < 0.001) for panel B.

Figure 2.

Kaplan-Meier survival curves for cardiovascular disease mortality by cytomegalovirus immunoglobulin G antibody titers for 1,468 subjects in the Sacramento Area Latino Study on Aging (California) from 1998 to 2008. Cytomegalovirus is divided into quartiles 1, 2, and 3 versus quartile 4. Panel A: unadjusted relation; panel B: adjusted for gender (male/female), age (above/below the mean), education (less than high school/high school or more), and comorbidities (none/one or more). Panel B shows survival for males older than 69 years of age with less than a high school education and one or more baseline comorbidities. Stratified log-rank test statistics were 7.08 (P < 0.01) for panel A and 7.05 (P < 0.01) for panel B.