Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Abstract

BackgroundStudies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.ResultsBlood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.ConclusionsPrior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated.

Physical Function Impairment of Older, HIV-Infected Adults Is Associated with Cytomegalovirus Immunoglobulin Response

“…12 Similarly, among 295 older (mean age 78 years), community dwelling men and women, both CMV seropositivity (77%) and higher CMV IgG titers were associated with increased relative risk of frailty. 11 In contrast, in a cohort of 567 men and women aged 80 years and older (74% CMV seropositive), CMV seropositivity was associated with a lower prevalence of frailty in adjusted analyses, and higher CMV IgG titers were not associated with frailty or physical function impairment, after adjustments for age, sex, and education. 29 These findings suggest that the relationship between CMV seropositivity and frailty or physical function impairment may differ by gender or by age, with a survival effect among the oldest populations.…”

The emergence of frailty and sarcopaenia in diabetes mellitus: description of inter-relationships and clinical importance

“…Recent research suggests that previous infection with cytomegalovirus in those with diabetes may be associated with the development of frailty presumably because of a possible effect on immunosenescence [42]. A recent paper from Indonesia suggests that the use of metformin may reduce the risk of frailty (on the basis of FI-40 criteria), which was speculated to result from beneficial effects on inflammatory markers, advanced glycosylation products and muscle function [43].…”

Known unknowns: how might the persistent herpesvirome shape immunity and aging?

“…In children, CMV seropositivity is associated with resistance to EBV infection in vitro [20], and young CMV+ adults show greater responses to seasonal influenza vaccination compared to uninfected counterparts [*21]. However, in the elderly, CMV has been associated with increased risk of cardiovascular disease (CVD) [16], Alzheimer’s disease (AD) [22], and frailty [23,24]. Although the age of acquisition of CMV is somewhat dependent on socioeconomic status and ethnicity (within the US), between 40–95% of people are CMV seropositive before age 40 [25], and therefore live with CMV for at least 25 years before they reach age 65.…”