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Background: We investigated the association between atrial fibrillation (AF) and dementia, and its subtypes (vascular‐VaD, Alzheimer, mixed and rare dementia), and identified predictors for dementia in AF patients. Methods: The analysis was based on 183,610 patients with new‐onset AF and 367,220 non‐AF controls in the United Kingdom between 1998 and 2016, identified in three prospectively collected, linked electronic health records sources. Time‐to‐event (dementia or subtypes) analyses were performed using Cox proportional hazards and weighted Cox. Sub‐analyses performed: including & censoring stroke and age (median used as cut‐off). Results: Over a median follow‐up of 2.67 years (IQR.65–6.02) for AF patients and 5.84 years for non‐AF patients (IQR 2.26–11.80), incidence of dementia in the AF cohort was 2.65 per 100 person‐years, compared to 2.02 in the non‐AF cohort. After adjustment, a significant association was observed between AF and all‐cause dementia (HR = 1.38, 95% CI: 1.31–1.45), driven by a strong association with VaD (HR = 1.55, 95% CI: 1.41–1.70). AF was also associated with mixed dementia (HR = 1.26, 95% CI: 1.01–1.56), but we could not confirm an association with Alzheimer (HR = 1.05, 95% CI:.94–1.16) and rare dementia forms (HR = 1.19, 95% CI:.90–1.56). Ischemic stroke (HR = 1.40, 95% CI: 1.26–1.56), subarachnoid haemorrhage (HR = 2.08, 95% CI: 1.47–2.96), intracerebral haemorrhage (HR = 1.95, 95% CI: 1.54–2.48) and diabetes (HR = 1.32, 95% CI: 1.24–1.41) were identified as the strongest predictors of dementia in AF patients. Conclusions: AF patients have an increased risk of dementia, independent of stroke, with highest risk of VaD. Management and prevention of the identified risk factors could be crucial to reduce the increasing burden of dementia. [ABSTRACT FROM AUTHOR]

Background and Aims Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. Methods Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes—the composite of heart failure, ischaemic stroke, or death—according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. Results The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A , 13.5%; TET2 , 6.6%; and ASXL1 , 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P <.001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10–1.74, P <.01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14–1.99, P =.004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05–2.60, P =.030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E / E ′, and a more severely enlarged left atrium than those without CHIP mutations (all P <.05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). Conclusions CHIP mutations, primarily DNMT3A or TET2 , are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes. [ABSTRACT FROM AUTHOR]

Aims: To explore the relationship between remnant cholesterol (RC) and the risk of premature mortality as well as life expectancy in the general population., Methods: We included a total of 428 804 participants from the UK Biobank for analyses. Equivalent population percentiles approach based on the low-density lipoprotein cholesterol cut-off points was performed to categorize participants into three RC groups: low (with a mean RC of 0.34 mmol/L), moderate (0.53 mmol/L), and high (1.02 mmol/L). We used multivariable Cox proportional hazards models to evaluate the relationship between RC groups and the risk of premature mortality (defined as death before age 75 years). Life table methods were used to estimate life expectancy by RC groups., Results: During a median follow-up of 12.1 years (Q1-Q3 11.0-13.0), there were 23 693 all-cause premature deaths documented, with an incidence of 4.83 events per 1000 person-years [95% confidence interval (CI): 4.77-4.89]. Compared with the low RC group, the moderate RC group was associated with a 9% increased risk of all-cause premature mortality [hazard ratio (HR) = 1.09, 95% CI: 1.05-1.14], while the high RC group had an 11% higher risk (HR = 1.11, 95% CI: 1.07-1.16). At the age of 50 years, high RC group was associated with an average 2.2 lower years of life expectancy for females, and an average 0.1 lower years of life expectancy for males when compared with their counterparts in the low RC group., Conclusions: Elevated RC was significantly related to an increased risk of premature mortality and a reduced life expectancy. Premature death in the general population would benefit from measurement to aid risk stratification and proactive management of RC to improve cardiovascular risk prevention efforts., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background:  This study aimed to evaluate racial differences in bleeding incidence by conducting an ecological epidemiological study using data from Korea and the United Kingdom., Methods:  We included healthy participants from the Korean National Health Insurance Service-Health Screening and the UK Biobank who underwent health examinations between 2006 and 2010 and had no comorbidities or history of medication use. Finally, 112,750 East Asians (50.7% men, mean age 52.6 years) and 210,995 Caucasians (44.7% men, mean age 55.0 years) were analyzed. The primary outcome was composed of intracranial hemorrhage (ICH) and bleeding from the gastrointestinal, respiratory, and genitourinary systems., Results:  During the follow-up, primary outcome events occurred in 2,110 East Asians and in 6,515 Caucasians. East Asians had a 38% lower 5-year incidence rate compared with Caucasians (3.88 vs. 6.29 per 1,000 person-years; incidence rate ratio [IRR]: 0.62, 95% confidence interval [CI]: 0.59-0.65). East Asians showed a lower incidence of major bleeding (IRR: 0.86, 95% CI: 0.81-0.91), bleeding from the gastrointestinal (IRR: 0.53, 95% CI: 0.49-0.56), and genitourinary systems (IRR: 0.49, 95% CI: 0.44-0.53) compared with Caucasians. The incidence rates of ICH (IRR: 3.20, 95% CI: 2.67-3.84) and bleeding from the respiratory system (IRR: 1.28, 95% CI: 1.11-1.47) were higher in East Asians. Notably, East Asians consuming alcohol ≥3 times/week showed a higher incidence of the primary outcome than Caucasians (IRR: 1.12, 95% CI: 1.01-1.25)., Conclusion:  This ecological study revealed significant racial differences in bleeding incidence, influenced by anatomical sites and lifestyle habits, underscoring the need for tailored approaches in bleeding management based on race., Competing Interests: B.J. has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi-Sankyo and received research funds from Medtronic and Abbott. No fees have been received directly or personally. G.Y.H.L. has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthos. No fees are received personally. He is co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union's Horizon 2020 Research and Innovation Program under grant agreement number 899871. The remaining authors have nothing to declare., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

The importance of integrated care for complex, multiple long term conditions was acknowledged before the COVID pandemic but remained a challenge. The pandemic and consequent development of Long COVID required rapid adaptation of health services to address the population's needs, requiring service redesigns including integrated care. This Delphi consensus study was conducted in the UK and found similar integrated care priorities for Long COVID and complex, multiple long term conditions, provided by 480 patients and health care providers, with an 80% consensus rate. The resultant recommendations were based on more than 1400 responses from survey participants and were supported by patients, health care professionals, and by patient charities. Participants identified the need to allocate resources to: support integrated care, provide access to care and treatments that work, provide diagnostic procedures that support the personalization of treatment in an integrated care environment, and enable structural consultation between primary and specialist care settings including physical and mental health care. Based on the findings we propose a model for delivering integrated care by a multidisciplinary team to people with complex multisystem conditions. These recommendations can inform improvements to integrated care for complex, multiple long term conditions and Long COVID at international level., (© 2024. The Author(s).)

Objective: We aimed to investigate the independent and joint associations between metabolic status, PA (physical activity) and risk of CVD (cardiovascular disease) in participants with obesity., Methods: We included 109,301 adults with obesity free of baseline CVD enrolled from 2006 to 2010 in the UK Biobank cohort (aged 56 ± 7.9 years). Based on metabolic status, obesity was grouped into metabolically healthy obesity (MHO; free of hypertension, hypercholesterolemia and diabetes; n = 26,989; BMI 33 ± 3.3 kg/m 2 ) and metabolically unhealthy obesity (MUO; n = 82,312; BMI 34 ± 4.0 kg/m 2 ). PA was categorized into four groups according to moderate-to-vigorous PA (MVPA): none, low, medium, and high. Multivariable Cox regression models were used for the main analyses adjusting for sociodemographic factors, lifestyles and comorbidities., Results: There were 8,059 CVD events during a median follow-up of 8.1 years. MHO was associated with a 42% reduced risk of CVD compared with MUO (HR = 0.58, 95% CI: 0.53-0.63). A significant interaction effect between PA and metabolic status on CVD risk was found. Among MUO participants, individuals with PA had significantly decreased CVD risk when compared with no MVPA (HR = 0.87, 95% CI: 0.81-0.94 for low PA; HR = 0.85, 95% CI: 0.78-0.93 for medium PA; and HR = 0.86, 95% CI: 0.80-0.92 for high PA). The lowest CVD risk was observed in MHO & medium PA group when compared with MUO & no MVPA (HR = 0.45, 95% CI: 0.37-0.56)., Conclusions: Both MHO and any MVPA were associated with reduced risk of CVD in adults with obesity, while PA could modify the relationship between metabolic status and CVD risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The reason for higher incidence of atrial fibrillation (AF) in Europe compared with East Asia is unclear. We aimed to investigate the association between modifiable lifestyle factors and lifetime risk of AF in Europe and East Asia, along with race/ethnic similarities and disparities., Methods: 1:1 propensity score matched pairs of 242,763 East Asians and 242,763 White Europeans without AF were analyzed. Modifiable lifestyle factors considered were blood pressure, body mass index, cigarette smoking, diabetes, alcohol consumption, and physical activity, categorized as non-adverse or adverse levels. Lifetime risk of AF was estimated from the index age of 45 years to the attained age of 85 years, accounting for the competing risk of death., Results: The overall lifetime risk of AF was higher in White Europeans than East Asians (20.9% vs 15.4%, p < 0.001). The lifetime risk of AF was similar between the two races in individuals with non-adverse lifestyle factor profiles (13.4% vs 12.9%, p = 0.575), whereas it was higher in White Europeans with adverse lifestyle factor profiles (22.1% vs 15.8%, p < 0.001). The difference in the lifetime risk of AF between the two races increased as the burden of adverse lifestyle factors worsened (1 adverse lifestyle factor; 4.3% to ≥ 3 adverse lifestyle factors; 11.2%). Compared with East Asians, the relative risk of AF in White Europeans was 23% and 62% higher for one (hazard ratio [HR] 1.23, 95% confidence interval [CI] 1.16-1.29) and ≥ 3 adverse lifestyle factors (HR 1.62, 95% CI 1.51-1.75), respectively., Conclusions: The overall higher lifetime risk of AF in White Europeans compared with East Asians might be attributable to adverse lifestyle factors. Adherence to healthy lifestyle factors was associated with the lifetime risk of AF of about 1 in 8 regardless of race/ethnicity., (© 2024. The Author(s).)