Frailty and risk of metabolic dysfunction-associated steatotic liver disease and other chronic liver diseases.

BACKGROUND & AIMS: Frailty is associated with multiple morbidities. However, its effect on chronic liver diseases remains largely unexplored. This study evaluated the association of frailty with the risk of incident metabolic dysfunction-associated steatotic liver disease (MASLD), cirrhosis, liver cancer, and liver-related mortality. METHODS: A total of 339,298 participants without prior liver diseases from the UK Biobank were included. Baseline frailty was assessed by using physical frailty and the frailty index, categorizing participants as nonfrail, prefrail, or frail. The primary outcome was MASLD, with secondary outcomes, including cirrhosis, liver cancer, and liver-related mortality, confirmed through hospital admission records and death registries. RESULTS: During a median follow-up of 11.6 years, 4,667 MASLD, 1,636 cirrhosis, 257 liver cancer, and 646 liver-related mortality cases were identified. After multivariable adjustment, the risk of MASLD was found to be higher in participants with prefrailty (physical frailty: HR = 1.66, 95% CI = 1.40-1.97; frailty index: HR = 2.01, 95% CI = 1.67-2.42) and frailty (physical frailty: HR = 3.32, 95% CI = 2.54-4.34; frailty index: HR = 4.54, 95% CI = 3.65-5.66) than in those with nonfrailty. Similar results were also observed for cirrhosis, liver cancer, and liver-related mortality. Additionally, the frail groups had a higher risk of MASLD, which was defined as magnetic resonance imaging-derived liver proton density fat fraction > 5%, than the nonfrail group (physical frailty: OR = 1.64, 95% CI = 1.32-2.04; frailty index: OR = 1.48, 95% CI = 1.30-1.68). CONCLUSIONS: Frailty was associated with an increased risk of chronic liver diseases. Public health strategies should target reducing chronic liver disease risk in frail individuals. IMPACT AND IMPLICATIONS: While frailty is common and associated with a poor prognosis in people with MASLD and advanced chronic liver diseases, its impact on the subsequent risk of these outcomes remains largely unexplored. Our study showed that frailty was associated with the increased risks of MASLD, cirrhosis, liver cancer, and liver-related mortality. This finding suggests that assessing frailty may help identify a high-risk population vulnerable to developing chronic liver diseases. Implementing strategies that target frailty could have major public health benefits for liver-related disease prevention.

Impact of healthy lifestyle on the incidence and progression trajectory of mental disorders: A prospective study in the UK Biobank.

BACKGROUND: Healthier lifestyle decreased the risk of mental disorders (MDs) such as depression and anxiety. However, research on the effects of a comprehensive healthy lifestyle on their progression is lacking. METHODS: 385,704 individuals without baseline MDs from the UK Biobank cohort were included. A composite healthy lifestyle score was computed by assessing alcohol intake, smoking status, television viewing time, physical activity, sleep duration, fruit and vegetable intake, oily fish intake, red meat intake, and processed meat intake. Follow-up utilized hospital and death register records. Multistate model was used to examine the role of healthy lifestyle on the progression of specific MDs, while a piecewise Cox regression model was utilized to assess the influence of healthy lifestyle across various phases of disease progression. RESULTS: Higher lifestyle score reduced risks of transitions from baseline to anxiety and depression, as well as from anxiety and depression to comorbidity, with corresponding hazard ratios (HR) and 95 % confidence intervals (CI) of 0.94 (0.93, 0.95), 0.90 (0.89, 0.91), 0.94 (0.91, 0.98), and 0.95 (0.92, 0.98), respectively. Healthier lifestyle decreased the risk of transitioning from anxiety to comorbidity within 2 years post-diagnosis, with HR 0.93 (0.88, 0.98). Higher lifestyle scores at 2-4 years and 4-6 years post-depression onset were associated with reduced risk of comorbidity, with HR 0.93 (0.87, 0.99) and 0.92 (0.86, 0.99), respectively. LIMITATION: The generalizability to other ethnic groups is limited. CONCLUSION: This study observed a protective role of holistic healthy lifestyle in the trajectory of MDs and contributed to identifying critical progression windows.

Associations of blood biomarkers with arterial stiffness in patients with diabetes mellitus: A population-based study.

BACKGROUND: Arterial stiffness contributes to additional cardiovascular risks in diabetic patients by triggering the loss of vascular and myocardial compliance and promoting endothelial dysfunction. Thus, prevention of arterial stiffness is a public health priority, and the identification of potential biomarkers may provide benefits for early prevention. This study investigates the relationships between serum laboratory tests and pulse wave velocity (PWV) tests. We also investigated the associations between PWV and all-cause mortality. METHODS: We examined a panel of 33 blood biomarkers among diabetic populations in the Atherosclerosis Risk in Communities Study. The carotid-femoral (cfPWV) and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The aortic-femoral arterial stiffness gradient (afSG) was calculated as faPWV divided by cfPWV. Biomarker levels were log-transformed and correlated with PWV. Cox proportional hazard models were employed for survival analysis. RESULTS: Among 1079 diabetic patients, biomarkers including high-density lipoprotein cholesterol, glycated hemoglobin, high-sensitivity troponin T, cystatin C, creatinine, and albuminuria were significantly correlated with afSG (R = 0.078, -0.193, -0.155, -0.153, -0.116, and -0.137, respectively) and cfPWV (R = -0.068, 0.175, 0.128, 0.066, 0.202, and 0.062, respectively). Compared with the lowest tertile of afSG, the risk of all-cause mortality was lower in the highest tertile (hazard ratio 0.543; 95% confidence interval 0.328-0.900). CONCLUSION: Certain biomarkers related to blood glucose monitoring, myocardial injury, and renal function significantly correlated with PWV, suggesting that these putative risk factors are likely to be important atherosclerosis mechanisms in diabetic patients. AfSG may be an independent predictor of mortality among diabetic populations.

The independent and joint association of accelerometer-measured physical activity and sedentary time with dementia: a cohort study in the UK Biobank.

BACKGROUND: Research on the association of physical activity and sedentary time with dementia is accumulating, though elusive, and the interaction effects of the two remain unclear. We analysed the joint associations of accelerometer-measured physical activity and sedentary time with risk of incident dementia (all-cause dementia, Alzheimer's disease and vascular dementia). METHODS: A total of 90,320 individuals from the UK Biobank were included. Accelerometer-measured total volume of physical activity (TPA) and sedentary time were measured at baseline and dichotomised by median (low TPA [< 27 milli-gravity (milli-g)], high TPA [≥ 27 milli-g]; low sedentary time [< 10.7 h/day], high sedentary time [≥ 10.7 h/day]). Cox proportional hazards models were used to evaluate the joint associations with incident dementia on both additive and multiplicative scales. RESULTS: During a median follow-up of 6.9 years, 501 cases of all-cause dementia were identified. Higher TPA was associated with a lower risk of all-cause dementia, Alzheimer's disease and vascular dementia; the multivariate adjusted hazard ratios (HRs) (95% CI) per 10 milli-g increase were 0.63 (0.55-0.71), 0.74 (0.60-0.90) and 0.69 (0.51-0.93), respectively. Sedentary time was only found to be linked to all-cause dementia, and the HR for high sedentary time was 1.03 (1.01-1.06) compared with that for low sedentary time. No additive and multiplicative relationship of TPA and sedentary time to incident dementia was found (all P values > 0.05). CONCLUSION: Higher TPA level was related to a lower risk of incident dementia irrespective of sedentary time, which highlighted the implication of promoting physical activity participation to counteract the potential detrimental effect of sedentary time on dementia.