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Physiological Dysregulation, Frailty, and Impacts on Adverse Health and Functional Outcomes

ABSTRACT: Background: Multi-system physiological dysregulation (PD) may represent a biological endo-phenotype of clinical frailty. We investigated the co-occurrence of PD with physical frailty and its contributions to the known impact of frailty on adverse health outcomes. Methods: Data of 2,725 participants from the Singapore Longitudinal Aging Studies (SLAS-2), included baseline measures of physical frailty and PD derived from Mahalanobis distance (Dm) value of 23 blood biomarkers. We analyzed their concurrent association and their impacts on 9-year mortality, MMSE cognition, GDS depression, number of medications, disability, and hospitalization at baseline and follow up (mean 4.5 years). Results: Global PD (Log10Dm, mean = 1.24, SD = 0.24) was significantly but weakly associated with pre-frailty-and-frailty. Controlling for age, sex and education, pre-frailty-and-frailty (HR = 2.12, 95% CI = 1.51–3.00) and PD (HR = 3.88, 95% CI = 2.15–6.98) predicted mortality. Together in the same model, mortality HR associated with pre-frailty-and-frailty (HR = 1.83, 95% CI = 1.22–2.73) and PD (HR = 3.06, 95% CI = 1.60–5.85) were reduced after additionally adding global PD to the prediction model. The predictive accuracy for mortality were both approximately the same (PD: AUC = 0.62, frailty: AUC = 0.64), but AUC was significantly increased to 0.68 when combined (p < 0.001). Taken into account in the same model, frailty remained significantly associated with all health and functional outcomes, and PD was significantly associated with only MMSE, disability and medications used. In secondary analyses, there were mixed associations of system-specific PDs with frailty and different adverse outcomes. Conclusions: Co-existing PD and physical frailty independently predict mortality and functional and health outcomes, with increased predictive accuracy when combined. PD appears to be a valid representation of a biological endo-phenotype of frailty, and the potential utility of such subclinical measures of frailty could be further studied.

SUBMITTER: Lu Y

PROVIDER: S-EPMC8569246 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundDiabetes mellitus (DM) correlates with accelerated aging and earlier appearance of geriatric phenotypes, including frailty. However, whether pre-frailty or frailty predicts greater healthcare utilization in diabetes patients is unclear.MethodsFrom the Longitudinal Cohort of Diabetes Patients in Taiwan (n = 840,000) between 2004 and 2010, we identified 560,795 patients with incident type 2 DM, categorized into patients without frailty, or with 1, 2 (pre-frail) and ≥ 3 frailty components, based on FRAIL scale (Fatigue, Resistance, Ambulation, Illness, and body weight Loss). We examined their long-term mortality, cardiovascular risk, all-cause hospitalization, and intensive care unit (ICU) admission.ResultsAmong all participants (56.4 ± 13.8 year-old, 46.1% female, and 84.8% community-dwelling), 77.8% (n = 436,521), 19.2% (n = 107,757), 2.7% (n = 15,101), and 0.3% (n = 1416) patients did not have or had 1, 2 (pre-frail), and ≥ 3 frailty components (frail), respectively, with Fatigue and Illness being the most common components. After 3.14 years of follow-up, 7.8% patients died, whereas 36.6% and 9.1% experienced hospitalization and ICU stay, respectively. Cox proportional hazard modeling discovered that patients with 1, 2 (pre-frail), and ≥ 3 frailty components (frail) had an increased risk of mortality (for 1, 2, and ≥ 3 components, hazard ratio [HR] 1.05, 1.13, and 1.25; 95% confidence interval [CI] 1.02-1.07, 1.08-1.17, and 1.15-1.36, respectively), cardiovascular events (HR 1.05, 1.15, and 1.13; 95% CI 1.02-1.07, 1.1-1.2, and 1.01-1.25, respectively), hospitalization (HR 1.06, 1.16, and 1.25; 95% CI 1.05-1.07, 1.14-1.19, and 1.18-1.33, respectively), and ICU admission (HR 1.05, 1.13, and 1.17; 95% CI 1.03-1.07, 1.08-1.14, and 1.06-1.28, respectively) compared to non-frail ones. Approximately 6-7% risk elevation in mortality and healthcare utilization was noted for every frailty component increase.ConclusionPre-frailty and frailty increased the risk of mortality and cardiovascular events, and entailed greater healthcare utilization in patients with type 2 DM.

Project description:BackgroundEarly recognition of older people at risk of undesirable clinical outcomes is vital in preventing future disabling conditions. Here, we report the prognostic performance of an electronic frailty index (eFI) in comparison with traditional tools among nonfrail and prefrail community-dwelling older adults. The study is to investigate the predictive utility of a deficit-accumulation eFI in community elders without overt frailty.MethodsParticipants aged 65-80 years with a Clinical Frailty Scale of 1-3 points were recruited and followed for 2 years. The eFI score and Fried's frailty scale were determined by using a semiautomated platform of self-reported questionnaires and objective measurements which yielded cumulative deficits and physical phenotypes from 80 items of risk variables. Kaplan-Meier method and Cox proportional hazards regression were used to analyze the severity of frailty in relation to adverse outcomes of falls, emergency room (ER) visits and hospitalizations during 2 years' follow-up.ResultsA total of 427 older adults were evaluated and dichotomized by the median FI score. Two hundred and sixty (60.9%) and 167 (39.1%) elders were stratified into the low- (eFI ≤ 0.075) and the high-risk (eFI > 0.075) groups, respectively. During the follow-up, 77 (47.0%) individuals developed adverse events in the high-risk group, compared with 79 (30.5%) in the low-risk group (x2, p = 0.0006). In multivariable models adjusted for age and sex, the increased risk of all three events combined in the high- vs. low-risk group remained significant (adjusted hazard ratio (aHR) = 3.08, 95% confidence interval (CI): 1.87-5.07). For individual adverse event, the aHRs were 2.20 (CI: 1.44-3.36) for falls; 1.67 (CI: 1.03-2.70) for ER visits; and 2.84 (CI: 1.73-4.67) for hospitalizations. Compared with the traditional tools, the eFI stratification (high- vs. low-risk) showed better predictive performance than either CFS rating (managing well vs. fit to very fit; not discriminative in hospitalizations) or Fried's scale (prefrail to frail vs. nonfrail; not discriminative in ER visits).ConclusionThe eFI system is a useful frailty tool which effectively predicts the risk of adverse healthcare outcomes in nonfrail and/or prefrail older adults over a period of 2 years.

Project description:Background Intrinsic capacity (IC) and frailty are complementary in advancing disability prevention through maintaining functionality. Objectives We examined the relationship between IC and frailty status at baseline and 1-year, and evaluated if IC decline predicts frailty onset among robust older adults. The secondary objectives investigated associations between IC, physical fitness and health-related outcomes. Design Prospective cohort study. Setting Community-based assessments. Participants Older adults aged>55 years, who were independent in ambulation (walking aids permitted). Measurements 5 domains of IC were assessed at baseline: locomotion (Short Physical Performance Battery, 6-minute walk test), vitality (nutritional status, muscle mass), sensory (self-reported hearing and vision), cognition (self-reported memory, age- and education adjusted cognitive performance), psychological (Geriatric Depression Scale-15, self-reported anxiety/depression). Composite IC (0–10) was calculated, with higher scores representing greater IC. Frailty status was based on modified Fried criteria, with frailty progression defined as incremental Fried score at 1-year. Results 809 participants (67.6+6.8 years) had complete data for all 5 IC domains. 489 (60.4%) participants were robust but only 213 (26.3%) had no decline in any IC domain. Pre-frail and frail participants were more likely to exhibit decline in all 5 IC domains (p<0.05), with decremental composite IC [9 (8–9), 8 (6–9), 5.5 (4–7.5), p<0.001] across robust, prefrail and frail. IC was significantly associated with fitness performance, independent of age and gender. Higher composite IC reduced risk for frailty progression (OR=0.62, 95% CI 0.48–0.80), and reduced frailty onset among robust older adults (OR=0.53, 95% CI 0.37–0.77), independent of age, comorbidities and social vulnerability. Participants with higher IC were less likely to experience health deterioration (OR=0.70, 95% CI 0.58–0.83), falls (OR=0.76, 95% CI 0.65–0.90) and functional decline (OR=0.64, 95% CI 0.50–0.83) at 1-year. Conclusion Declining IC may present before frailty becomes clinically manifest, increasing risk for poor outcomes. Monitoring of IC domains potentially facilitates personalized interventions to avoid progressive frailty. Electronic Supplementary Material Supplementary material is available for this article at 10.14283/jfa.2022.28 and is accessible for authorized users.

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Physiological Dysregulation, Frailty, and Impacts on Adverse Health and Functional Outcomes

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