Developing physical frailty specifications for investigation of frailty pathways in older people

Different frailty definitions are suitable for different purposes. When investigating its key multidimensional predictors and effects, narrower definitions of frailty that exclude these elements may be more desirable. For this purpose, candidate physical frailty specifications are constructed and then evaluated on their construct and concurrent validity. For 4638 participants aged 65 to 89 years from wave 2 (2004) of the English Longitudinal Study of Ageing, confirmatory factor analysis is performed to create physical frailty specifications with four indicators (slowness, weakness, exhaustion, and weight loss) and with three indicators (slowness, weakness, and either exhaustion or weight loss). Using derived factor scores, their convergent, discriminant, and concurrent validity are compared. For specifications with four indicators and with three indicators including exhaustion, slowness contributes dominantly to the physical frailty factor. However, with three indicators including weight loss, weakness contributes most. Where represented, weight loss only contributes minimally. Higher factor scores are significantly associated with chronic diseases, functional impairment, and poor self-rated health, although less so for the third specification. Factor scores for the first two specifications have low correlation with psychological and social frailty while those for the third have negligible correlation. Factor scores increase with higher Frailty Index although again less so for the third specification. Minor differences are seen across gender. On account of their convergent, discriminatory, and concurrent validity, physical frailty specifications with four indicators and with three indicators including exhaustion hold promise for use in investigation of frailty pathways involving multidimensional predictors and effects

Multidimensional predictors of physical frailty in older people: identifying how and for whom they exert their effects

Physical frailty in older people is an escalating health and social challenge. We investigate its physical, psychological, and social predictors, including how and for whom these conditions exert their effects. For 4,638 respondents aged 65 to 89 years from wave 2 of the English Longitudinal Study of Ageing, we examine prediction of future physical frailty by physical, psychological, and social conditions using latent growth curve analysis with multiple indicators. In addition, we explore their indirect effects through disease and physiologic decline, and repeat these analyses after stratification by gender, age group, and selected conditions which are possible moderators. We find that chronic disease, allostatic load, low physical activity, depressive symptoms, cognitive impairment, and poor social support all predict future physical frailty. Furthermore, chronic disease and allostatic load mediate the effects of low physical activity, depressive symptoms, and cognitive impairment on future physical frailty. Finally, although poor social integration is not a predictor of future physical frailty, this condition moderates the indirect effect of poor social support through chronic disease by rendering it stronger. By virtue of their roles as predictor, mediator, or moderator on pathways to physical frailty, chronic disease, allostatic load, low physical activity, cognitive impairment, depressive symptoms, poor social support, and poor social integration are potentially modifiable target conditions for population-level health and social interventions to reduce future physical frailty in older people

Pathways from physical frailty to activity limitation in older people: identifying moderators and mediators in the English longitudinal study of ageing

Physical frailty increases the risk of future activity limitation, which in turn, compromises independent living of older people and limits their healthspan. Thus, we seek to identify moderators and mediators of the effect of physical frailty on activity limitation change in older people, including gender- and age-specific effects. In a longitudinal study using data from waves 2, 4, and 6 of the English Longitudinal Study of Ageing, unique physical frailty factor scores of 4,638 respondents aged 65 to 89 years are obtained from confirmatory factor analysis of physical frailty, which is specified by three indicators, namely slowness, weakness, and exhaustion. Using a series of autoregressive cross-lagged models, we estimate the effect of physical frailty factor score on activity limitation change, including its moderation by social conditions, and indirect effects through physical and psychological conditions. We find that the effect of physical frailty on activity limitation change is significantly stronger with older age, while it has significant indirect effects through low physical activity, depressive symptoms, and cognitive impairment. In turn, indirect effects of physical frailty through low physical activity and cognitive impairment are stronger with older age. Sensitivity analyses suggest that these effects vary in their robustness to unmeasured confounding. We conclude that low physical activity, depressive symptoms, and cognitive impairment are potentially modifiable mediators on pathways from physical frailty to activity limitation in older people, including those who are very old. This evidence offers support for population-level interventions that target these conditions, to mitigate the effect of physical frailty on activity limitation, and thereby enhance healthspan

Relationship between Renal Function, Fibrin Clot Properties and Lipoproteins in Anticoagulated Patients with Atrial Fibrillation

Background: Mechanisms by which chronic kidney disease (CKD) influences fibrin clot properties in atrial fibrillation (AF) remain ill-defined. We aimed to investigate the effects of AF and CKD on fibrin clot properties and lipoproteins, and determine the relationship between these factors. Methods: Prospective cross-sectional study of patients recruited from cardiology services in Liverpool between September 2019 and October 2021. Primary groups consisted of anticoagulated AF patients with and without CKD in a 1:1 ratio. Control group comprised anticoagulated patients without AF or CKD. Fibrin clot properties were analysed using turbidity and permeation assays. Detailed lipoprotein characteristics, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL and oxidised LDL, were measured. Results: Fifty-six anticoagulated patients were enrolled (median age 72.5; 34% female); 46 with AF (23 with CKD and 23 without CKD) and 10 controls. AF was associated with changes in three indices of fibrin clot properties using PTT (T(lag) 314 vs. 358 s, p = 0.047; Abs(peak) 0.153 vs. 0.111 units, p = 0.031; T(lysis50%) 884 vs. 280 s, p = 0.047) and thrombin reagents (T(lag) 170 vs. 132 s, p = 0.031; T(max) 590 vs. 462 s, p = 0.047; T(peak50%) 406 vs. 220 s, p = 0.005) while the concomitant presence of CKD led to changes in fibrin clot properties using kaolin (T(lag) 1072 vs. 1640 s, p = 0.003; T(max) 1458 vs. 1962 s, p = 0.005; T(peak50%) 1294 vs. 2046, p = 0.008) and PPP reagents (T(lag) 566 vs. 748 s, p = 0.044). Neither of these conditions were associated with changes in fibrin clot permeability. Deteriorating eGFR was significantly correlated to the speed of clot formation, and CKD was independently associated with unfavourable clot properties (T(lag) −778, p = 0.002; T(max) −867, p = 0.004; T(peak50%) −853, p = 0.004 with kaolin reagent). AF alone was not associated with changes in lipoprotein distribution while AF patients with CKD had lower total cholesterol, LDL-C and small dense LDL due to the presence of other risk factors. No significant relationship was observed between fibrin clot properties and lipoprotein distribution. Conclusions: There are important changes that occur in fibrin clot properties with AF and CKD that may account for the increased risk of thromboembolic complications. However, these changes in fibrin clot properties were not attributable to alterations in lipoprotein distribution

Social determinants of health and cardiovascular outcomes in patients with heart failure

BackgroundWe examined the associations between family income and educational attainment with incident atrial fibrillation (AF), myocardial infarction (MI), stroke and cardiovascular (CV) death among patients with newly-diagnosed heart failure (HF).MethodsIn a nationwide Danish registry of HF patients diagnosed between 2008 and 2018, we established a cohort for each outcome. When examining AF, MI and stroke, respectively, patients with a history of these outcomes at diagnosis of HF were excluded. We used cause-specific proportional hazard models to estimate hazard ratios for tertile groups of family income and three levels of educational attainment.ResultsAmong 27,947 AF-free patients, we found no association between income or education and incident AF. Among 27,309 MI-free patients, we found that lower income (hazard ratio 1.28 [95% CI 1.11-1.48] and 1.11 [0.96-1.28] for lower and medium vs. higher income) and education (1.23 [1.04-1.45] and 1.15 [0.97-1.36] for lower and medium vs. higher education) were associated with MI. Among 36,801 stroke-free patients, lower income was associated with stroke (1.38 [1.23-1.56] and 1.27 [1.12-1.44] for lower and medium vs. higher income) but not education. Lower income (1.56 [1.46-1.67] and 1.32 [1.23-1.42] for lower and medium vs. higher income) and education (1.20 [1.11-1.29] and 1.07 [0.99-1.15] for lower and medium vs. higher education) were associated with CV death.ConclusionsIn patients with newly-diagnosed HF, lower family income was associated with higher rates of acute MI, stroke and cardiovascular death. Lower educational attainment was associated with higher rates of acute MI and cardiovascular death. There was no evidence of associations between income and education with incident AF