Physical frailty, genetic predisposition, and incident arrhythmias.

Cross-sectional evidence suggests a possible link between frailty and atrial fibrillation (AF). It remains unclear whether frailty and incident arrhythmias are longitudinally associated. This study aimed to determine whether the frailty phenotype is longitudinally associated with incident arrhythmias, especially AF. In this prospective cohort of UK Biobank, individuals with arrhythmias at baseline, those without data for frailty phenotype, and no genetic data were excluded. Five domains of physical frailty, including weight loss, exhaustion, low physical activity, low grip strength, and slow gait speed, were assessed. A total of 142 single-nucleotide polymorphisms was used to calculate the polygenic risk score (PRS) for AF. Hospital inpatient records and death records were used to identify incident arrhythmias. This study included 464 154 middle-aged and older adults (mean age 56.4 ± 8.1 years, 54.7% female) without arrhythmia at baseline. During a median follow-up of 13.4 years (over 5.9 million person-years), 46 454 new-onset arrhythmias cases were recorded. In comparison with non-frailty, the multivariable-adjusted hazard ratios (HRs) of AF were 1.12 (95% CI: 1.09, 1.15, P < 0.0001) and 1.44 (95% CI: 1.36, 1.51, P < 0.0001) for participants with pre-frailty and frailty, respectively. Similar associations were observed for other arrhythmias. We found that slow gait speed presented the strongest risk factor in predicting all arrhythmias, including AF (HR 1.34, 95% CI: 1.30, 1.39), bradyarrhythmias (HR 1.30, 95% CI: 1.22, 1.37), conduction system diseases (HR 1.29, 95% CI: 1.22, 1.36), supraventricular arrhythmias (HR 1.32, 95% CI: 1.19, 1.47), and ventricular arrhythmias (HR 1.37, 95% CI: 1.25, 1.51), with all P values <0.0001. In addition to slow gait speed, weight loss (HR 1.13, 95% CI: 1.09, 1.16, P < 0.0001) and exhaustion (HR 1.11, 95% CI: 1.07, 1.14, P < 0.0001) were significantly associated with incident AF, whereas insignificant associations were observed for physical activity (HR 1.03, 95% CI: 0.996, 1.08, P = 0.099) and low grip strength (HR 1.00, 95% CI: 0.97, 1.03, P = 0.89). We observed a significant interaction between genetic predisposition and frailty on incident AF (P for interaction <0.0001), where those with frailty and the highest tertile of PRS had the highest risk of AF (HR 3.34, 95% CI: 3.08, 3.61, P < 0.0001) compared with those with non-frailty and the lowest tertile of PRS. Physical pre-frailty and frailty were significantly and independently associated with incident arrhythmias. Although direct causal inference still needs to be further validated, these results suggested the importance of assessing and managing frailty for arrhythmia prevention.

Zhang Y ，Liu M ，Li J ，Ruan L ，Wu X ，Zhang C ，Chen L ... -  《-》

Physical Frailty, Genetic Predisposition, and Incident Parkinson Disease.

Zheng Z ，Lv Y ，Rong S ，Sun T ，Chen L ... -  《-》

Diabetes status, genetic susceptibility, and incident arrhythmias: A prospective cohort study of 457,151 participants.

The association of diabetes onset age and duration with incident arrhythmias remains unclear. This study evaluates the association of diabetes onset age and duration with incident arrhythmias and assesses modifications by the genetic predisposition to atrial fibrillation (AF). We included 457,151 participants from the UK Biobank study. Multivariable Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) were used for the association between diabetes status, genetic predisposition, and risk of incident arrhythmias. The polygenic risk score (PRS) for AF comprised 142 single-nucleotide variants. Over 12 years of follow-up, we documented 23,518 AF, 9079 bradyarrhythmia, 9280 conduction system diseases, 3358 supraventricular arrhythmias, and 3095 ventricular arrhythmias. Compared with non-diabetes, the risks of AF increased by 19%, 25%, and 36% for those with diabetes durations <5, 5-9, and ≥10 years, respectively. After multivariate adjustment, with the increase in diabetes onset age, the HRs of outcomes were gradually attenuated. The multivariable-adjusted HRs (95% CI) of diabetes for AF were 1.46 (1.24-1.71) in early middle age (<55 years), 1.21 (1.12-1.30) in late middle age (55-64 years), and 1.15 (1.06-1.24) in the elderly population (≥65 years). A significant interaction between diabetes status and AF-PRS for incident AF was observed (P for interaction <0.001). The same trends were observed for the other arrhythmias. Diabetes was associated with higher risks of incident arrhythmias, and younger age at onset of diabetes was significantly associated with higher risk of subsequent arrhythmias.

Dai L ，Zuo Y ，Lv Y ，Zeng H ，Chen L ... -  《-》

Childhood maltreatment, genetic risk, and subsequent risk of arrhythmias: a prospective cohort study.

Chen Y ，Xue H ，Zhou J ，Shu X ，He Z ，Ai S ，Feng H ，Zhang J ，Liang YY ，Lv Y ，Zhou Y ... -  《European Journal of Psychotraumatology》

Frailty Predicts Incident Atrial Fibrillation in Women but Not in Men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

Frailty and atrial fibrillation (AF) are common aging problems and increasing globally. The association(s) between frailty and AF has been inconclusive. The purpose of this prospective population-based cohort was to investigate the associations between frailty and incident AF in older men and women. In total 839 participants, women (n = 458) and men (n = 381), aged 61-74 years from the Kuopio Ischaemic Heart Disease Risk Factor Study were included (March 1, 1998, to December 31, 2001). At the baseline, frailty prevalence was 49.3% (n = 414), and non-frailty 50.7% (n = 425) of the total population. Frailty was ascertained with the presence of 3-5 and prefrailty 1-2 of the following criteria: weight loss (highest 20% over 7 years), self-reported tiredness, weakness (measured by handgrip strength), slow walking speed (walking pace), and low physical activity (lowest 20%). AF events were obtained by record linkages from the national computerized hospitalization registry in Finland up to December 31, 2019. Multivariate Cox proportional hazard regression estimated the hazard ratio (HR) of incident events, adjusted for potential confounders. During the mean follow-up of 14.2 years, 288 AF cases (169 women; 119 men) occurred. After adjustment for possible confounders, the HRs (95% confidence intervals [CIs]) for AF was 1.46 (1.48-1.85) in the frail population, compared to the non-frail group. The association was observed only among older frail women (multivariable-adjusted HR 1.78, 95% CI [1.28-2.48]) (p for interaction = 0.04). No statistically significant associations were observed between frailty and future AF incident among men (multivariable-adjusted HRs 1.12, 95% CI (0.77-1.63)). In this population-based epidemiological cohort, the risk of developing AF was increased in women affected by frailty at baseline but not in men.

Tajik B ，Voutilainen A ，Lyytinen A ，Kauhanen J ，Lip GYH ，Tuomainen TP ，Isanejad M ... -  《-》