Association between inflammatory-related disease burden and frailty: Results from the Women's Health and Aging Studies (WHAS) I and II

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Abstract

Frailty is associated with a pro-inflammatory state, which has been characterized by elevated levels of systemic inflammatory biomarkers, but has not been related to the number of co-existing chronic diseases associated with inflammation. We sought to determine the extent to which a higher number of inflammatory-related diseases is associated with frailty and to identify the most common disease patterns associated with being frail in older adults. We performed binomial regression analyses to assess whether a higher count of inflammatory-related diseases increases the probability of frailty using data from the WHAS I and II, companion cohorts composed of 70–79-year-old community-dwelling older women in Baltimore, Maryland (n = 620). An increase of one inflammatory-related disease was associated log-linearly with frailty (Prevalence Ratio (PR) = 2.28, 95% Confidence Interval (CI) = 1.81–2.87). After adjusting for age, race, education, and smoking status, the probability of frailty remained significant (PR = 1.97, 95%CI = 1.52–2.55). In the frail population, chronic kidney disease (CKD) and depressive symptoms (Prevalence = 22.9%, 95%CI = 14.2–34.8%); CVD and depressive symptoms (21.7%, 95%CI = 13.2–33.5%); CKD and anemia (18.7%, 95%CI = 11.1–29.7%); cardiovascular disease (CVD), CKD, and pulmonary disease (10.7%, 95%CI = 5.2–21.0%); CKD, anemia, and depressive symptoms (8.7%, 95%CI = 3.9–18.2%); and CVD, anemia, pulmonary disease, and depressive symptoms (5.0%, 95%CI = 1.6–14.4%) were among the most frequent disease combinations. Their prevalence percentages were significantly higher in the frail versus non-frail women. A higher inflammatory-related disease count, perhaps reflecting a greater pro-inflammatory burden, increases the likelihood of frailty. Shared mechanisms among specific disease combinations may further contribute to this risk.

Introduction

Frailty is an important syndrome of advancing age that is recognized as a risk factor for falls, disability, hospitalization, and death in older adults (Fried et al., 2001, Fried L.P. et al., 2004). It is hypothesized to result from a complex interplay of biochemical and multi-systemic changes that may result in decreased physiologic reserves in older adults (Fried et al., 2005). Previous observational studies have found an association between frailty and elevated levels of pro-inflammatory mediators, such as interleukin-6 (IL-6) and C-reactive protein (CRP) (Walston et al., 2002, Leng et al., 2007), implicating a chronic, pro-inflammatory state in the pathogenesis of frailty as well as many age-related chronic diseases that are also independently associated with frailty. These diseases include CKD, CVD, anemia, and diabetes mellitus (DM) (Fried et al., 2001, Newman et al., 2001, Shlipak et al., 2004, Chaves et al., 2005, Barzilay et al., 2007, Wilhelm-Leen et al., 2009).

An association between frailty and a pro-inflammatory state has been described in terms of elevated levels of systemic inflammatory markers, but has not been related to the number of chronic diseases with an inflammatory etiology, which are present in older adults. In this cross-sectional study, we sought to determine whether a higher count of inflammatory-related diseases is associated with a greater likelihood of being frail and to identify the specific disease patterns, based upon the total number of prevalent inflammatory-related diseases, which are most frequently associated with being frail in older adults. Results from this study would provide the basis for investigating shared disease mechanisms which may illuminate potential targets of treatment to prevent or delay frailty.

Section snippets

Study population

Data from the WHAS I and II, complementary longitudinal cohort studies of community-dwelling older women in Baltimore, MD were merged for this cross-sectional study. WHAS I, which consisted of 1002 women aged ≥65, represented the one-third most disabled women in Baltimore; WHAS II, composed of 436 women aged 70–79, was recruited from among the two-thirds least disabled in the community.

The two study cohorts were sampled using the Health Care Financing Administration's Medicare eligibility lists

Characteristics of study population

Table 1 presents the major baseline characteristics of the study population; 11.3% (n = 67) were frail, whereas 88.7% (n = 553) were non-frail. A higher percentage of the frail, older women were black, received less education, had lower cognitive function, and had more inflammatory-related diseases than compared to the non-frail, older women (all p-values <0.05). Of the frail population, 42.8% (n = 28) had ≥3 inflammatory-related diseases, compared to 15.3% (n = 81) in the non-frail population. Age (p

Discussion

This population-based study of older women highlights the new finding that the probability of frailty increased in a dose–response fashion as the number of chronic diseases that are associated with inflammation increased, accounting for age, race, education, and smoking. Many of the most frequent inflammatory-related disease combinations in frail older adults were also considerably less prevalent in non-frail older adults. Altogether, these results suggest not only that a higher

Conclusions

We demonstrated that the likelihood of frailty increases in a dose–response fashion as the chronic inflammatory-related disease count increases. Shared mechanisms among specific disease combinations may further contribute to this risk and facilitate the progression of frailty. Longitudinal ascertainment of chronic inflammatory-related diseases with respect to incident frailty in older adults will help establish a temporal relationship between a higher total disease count and the risk of

Conflict of interest statement

None.

Acknowledgements

This work was supported by the National Institute on Aging (grant numbers N01 AG12112, R01 AG11703, R37 AG19905, and T32 AG00247 to SSC); the National Institutes of Health-National Center for Research Resources (grant number UL1 RR 025005); the John A. Hartford Foundation Center of Excellence in Geriatric Medicine at Yale University (grant number 2007-0009 to SSC); the Robert Wood Johnson Foundation Amos Medical Faculty Development Program to COW; and the Johns Hopkins Claude D. Pepper Older

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