Seropositivity and Higher Immunoglobulin G Antibody Levels Against Cytomegalovirus Are Associated With Mortality in the Population-Based European Prospective Investigation of Cancer–Norfolk Cohort

Abstract

The relationship between cytomegalovirus (CMV) infection and mortality among immunocompetent individuals is uncertain. We aimed to examine whether seropositivity for CMV and the level of CMV immunoglobulin G (IgG) antibody are associated with all-cause and cause-specific mortality. We used data from a random sample of 13 090 participants aged 40-79 years at recruitment in 1993-1997 to the European Prospective Investigation of Cancer-Norfolk population-based cohort study. We measured baseline IgG antibody levels against CMV. Death certificates were obtained for all participants who died before 31 March 2011. Codes for the underlying cause of death were used to investigate cause-specific mortality. A total of 2514 deaths occurred during a mean follow-up of 14.3 years (SD, 3.3 years). Compared to seronegative participants (age- and sex-adjusted mortality rate, 12.4 [95% confidence interval {CI}, 11.3-13.2] per 1000 person-years at risk), rates increased across thirds of IgG antibody levels (score test of trend P < .0001). CMV seropositivity (prevalence 59%) was associated with increased all-cause mortality (age- and sex-adjusted hazard ratio [HR], 1.16 [95% CI, 1.07-1.26]), similarly in men and women (P for interaction = .52). The association persisted after additionally adjusting for measures of socioeconomic status and possible confounders. Cause-specific analyses suggested that increased mortality from cardiovascular disease (HR, 1.06 [95% CI, .91-1.24]), cancer (HR, 1.13 [95% CI, .98-1.31]), and other causes (HR, 1.23 [95% CI, 1.04-1.47) all appeared to contribute to the overall associations. Seropositivity and higher IgG antibody levels against CMV are associated with increased mortality and after adjustment for a range of potential confounders in the general population.