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

Author:

Chen Sijia12,Pawelec Graham34ORCID,Trompet Stella1,Goldeck David35,Mortensen Laust H6,Slagboom P Eline7,Christensen Kaare8ORCID,Gussekloo Jacobijn19,Kearney Patricia10,Buckley Brendan M11,Ford Ian12ORCID,Jukema J Wouter13,Westendorp Rudi G J11415,Maier Andrea B1617ORCID

Affiliation:

1. Department of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands

2. Department of Experimental Immunology, Academic Medical Center, Amsterdam, the Netherlands

3. Department of Immunology, University of Tübingen, Tübingen, Germany

4. Health Sciences North Research Institute, Sudbury, Ontario, Canada

5. Fairfax Centre, Kidlington, United Kingdom

6. Methods and Analysis, Statistics Denmark, Copenhagen, Denmark

7. Section of Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands

8. Danish Aging Research Center, University of Southern Denmark, Odense, Denmark

9. Department of Public Health and Primary Care, Leiden University Medical Centre, Leiden, the Netherlands

10. Department of Epidemiology and Public Health, University College Cork, Cork, Ireland

11. Department of Pharmacology and Therapeutics, University College Cork, Cork, Ireland

12. Robertson Center for Biostatistics, University of Glasgow, United Kingdom

13. Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands

14. Leyden Academy on Vitality and Ageing, Leiden, the Netherlands

15. Department of Public Health, University of Copenhagen, Copenhagen, Denmark

16. Department of Medicine and Aged Care, @AgeMelbourne, The Royal Melbourne Hospital, University of Melbourne, Melbourne, Australia

17. Department of Human Movement Sciences, @AgeAmsterdam, Amsterdam Movement Sciences, Vrije University, Amsterdam, the Netherlands

Abstract

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.

Funder

European Commission

SenterNovem

Centre for Medical Systems Biology

Netherlands Genomics Initiative

Netherlands Organization for Scientific Research

Ministry of Health, Welfare and Sports

National Institutes of Health

National Institute on Aging

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Immunology and Allergy

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