Herpesvirus Infections and Risk of Frailty and Mortality in Older Women: Women's Health and Aging Studies

Objectives: To examine the relationship between herpesvirus infections and mortality and incident frailty risks in community-dwelling older women. Design: Nested prospective cohort study. Setting: Women's Health and Aging Studies I and II. Participants: Community-dwelling older women aged 70 to 79 (n = 633). Measurements: Baseline serum antibody (immunoglobulin G) levels against four herpesviruses (herpes simplex virus types 1 (HSV-1) and 2 (HSV-2), varicella-zoster virus (VZV), 7 Epstein-Barr virus (EBV)), 3-year incident frailty rates, and 5-year mortality. Results: Women seropositive for HSV-1 and HSV-2, but not VZV and EBV, had higher risk of 3-year incident frailty (HSV-1: hazard ratio (HR) = 1.90, 95% confidence interval (CI) = 0.96–3.74; HSV-2: HR = 2.10, 95% CI = 1.05–4.37) and 5-year mortality (HR = 1.73, 95% CI = 0.93–3.20; HR = 1.80, 95% CI = 0.94–3.44, respectively) than seronegative women. Incremental increases in serum HSV-1 and HSV-2 antibody levels were associated with incrementally higher risks of incident frailty and mortality. After adjustment for potential confounders, only higher serum HSV-2 antibody level was independently predictive of higher risk of mortality in older women (for each unit increase in antibody index, HR = 1.47, 95% CI = 1.05–2.07). Conclusion: HSV-1 and HSV-2 antibody levels are not independently associated with risk of incident frailty in older women. Only HSV-2 antibody level is independently predictive of 5-year mortality risk, with each incremental increase in the antibody level adding further risk.