Associations of Cytomegalovirus Infection With All-Cause and Cardiovascular Mortality in Multiple Observational Cohort Studies of Older Adults

Sijia Chen, Graham Pawelec, Stella Trompet, David Goldeck, Laust H Mortensen, P Eline Slagboom, Kaare Christensen, Jacobijn Gussekloo, Patricia Kearney, Brendan M Buckley, Ian Ford, J Wouter Jukema, Rudi G J Westendorp, Andrea B Maier, Sijia Chen, Graham Pawelec, Stella Trompet, David Goldeck, Laust H Mortensen, P Eline Slagboom, Kaare Christensen, Jacobijn Gussekloo, Patricia Kearney, Brendan M Buckley, Ian Ford, J Wouter Jukema, Rudi G J Westendorp, Andrea B Maier

Abstract

Background: Whether latent cytomegalovirus (CMV) infection in older adults has any substantial health consequences is unclear. Here, we sought associations between CMV-seropositivity and IgG titer with all-cause and cardiovascular mortality in 5 longitudinal cohorts.

Methods: Leiden Longevity Study, Prospective Study of Pravastatin in the Elderly at Risk, Longitudinal Study of Aging Danish Twins, and Leiden 85-plus Study were assessed at median (2.8-11.4 years) follow-up . Cox regression and random effects meta-analysis were used to estimate mortality risk dependent on CMV serostatus and/or IgG antibody titer, in quartiles after adjusting for confounders.

Results: CMV-seropositivity was seen in 47%-79% of 10 122 white community-dwelling adults aged 59-93 years. Of these, 3519 had died on follow-up (579 from cardiovascular disease). CMV seropositivity was not associated with all-cause (hazard ratio [HR], 1.05; 95% confidence interval [CI], .97-1.14) or cardiovascular mortality (HR, 0.97; 95% CI, .83-1.13). Subjects in the highest CMV IgG quartile group had increased all-cause mortality relative to CMV-seronegatives (HR, 1.16; 95% CI, 1.04-1.29) but this association lost significance after adjustment for confounders (HR, 1.13; 95% CI, .99-1.29). The lack of increased mortality risk was confirmed in subanalyses.

Conclusions: CMV infection is not associated with all-cause or cardiovascular mortality in white community-dwelling older adults.

Trial registration: ClinicalTrials.gov NCT03070600.

Keywords: Herpesviridae; aged; cardiovascular; cytomegalovirus; immunoglobulin G; mortality; seroepidemiologic studies.

© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
Meta-analysis of all-cause mortality and CMV infection in 5 cohorts. A, Meta-analysis of the association between all-cause mortality risk and CMV seropositivity in comparison to CMV-seronegative individuals. B, Comparison of individuals in the highest antibody quartile (IgG4) to CMV-negative individuals. C, Comparison of individuals in the highest antibody quartile (IgG4) to ones in the lowest antibody quartile (IgG1). Abbreviations: CI, confidence interval; CMV, cytomegalovirus; F1, siblings of long-living participants; F2, offspring; IgG, immunoglobulin G; IV, inverse variance; LLS, Leiden Longevity Study; LSADT, Longitudinal Study of Ageing in Danish Twins; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; SE, standard error.
Figure 2.
Figure 2.
Meta-analysis of cardiovascular mortality and CMV infection in 5 cohorts. A, Meta-analysis of the association between cardiovascular mortality risk and CMV seropositivity in comparison to CMV-seronegative individuals. B, Comparison of individuals in the highest antibody quartile (IgG4) to CMV-negative individuals. C, Comparison of individuals in the highest antibody quartile (IgG4) to ones in the lowest antibody quartile (IgG1). Abbreviations: CI, confidence interval; CMV, cytomegalovirus; F1, siblings of long-living participants; F2, offspring; IgG, immunoglobulin G; IV, inverse variance; LLS, Leiden Longevity Study; LSADT, Longitudinal Study of Ageing in Danish Twins; PROSPER, Prospective Study of Pravastatin in the Elderly at Risk; SE, standard error.

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