Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: Results from the Cardiovascular Health Study

Background: The biological basis of frailty has been difficult to establish owing to the lack of a standard definition, its complexity, and its frequent coexistence with illness. Objective: To establish the biological correlates of frailty in the presence and absence of concurrent cardiovascular disease and diabetes mellitus. Methods: Participants were 4735 community-dwelling adults 65 years and older. Frail, intermediate, and nonfrail subjects were identified by a validated screening tool and exclusion criteria. Bivariate relationships between frailty level and physiological measures were evaluated by Pearson χ ² tests for categorical variables and analysis of variance F tests for continuous variables. Multinomial logistic regression was performed to evaluate multivariable relationships between frailty status and physiological measures. Results: Of 4735 Cardiovascular Health Study participants, 299 (6.3%) were identified as frail, 2147 (45.3%) as intermediate, and 2289 (48.3%) as not frail. Frail vs nonfrail participants had increased mean ± SD levels of C-reactive protein (5.5 ± 9.8 vs 2.7 ± 4.0 mg/L), factor VIII (13790 ± 4480 vs 11860 ± 3460 mg/dL), and, in a smaller subset, D dimer (647 ± 1033 vs 224 ± 258 ng/mL) (P ≤ 001 for all, χ ² test for trend). These differences persisted when individuals with cardiovascular disease and diabetes were excluded and after adjustment for age, sex, and race. Conclusions: These findings support the hypothesis that there is a specific physiological basis to the geriatric syndrome of frailty that is characterized in part by increased inflammation and elevated markers of blood clotting and that these physiological differences persist when those with diabetes and cardiovascular disease are excluded.