Association between physical activity changes and risk of incident ischemic stroke following cancer diagnosis: A nationwide retrospective cohort study.

BACKGROUND: Physical inactivity is prevalent after cancer treatment, which could increase ischemic stroke risk in cancer survivors. This study investigated the association between physical activity change from pre- to post-diagnosis and ischemic stroke risk among cancer survivors. METHODS: Using data from the Korean National Health Insurance Service database, 269,943 cancer survivors (mean [SD] age, 56.3 [12.1] years; 45.7% male) with no history of cardiovascular disease were evaluated based on changes in physical activity from pre- to post-diagnosis. Using the Fine-Gray model, subdistribution hazard ratios (sHRs) and 95% confidence intervals (CIs) for ischemic stroke risk were calculated, considering death as a competing risk. RESULTS: After cancer diagnosis, 62.0% remained inactive, 10.1% remained active, 16.6% became active, and 11.4% became inactive. During a mean (SD) follow-up of 4.1 (2.0) years, being active both pre- and post-diagnosis was associated with a 15% decreased risk of ischemic stroke (sHR, 0.85; 95% CI, 0.75-0.96), compared with those who remained inactive. Cancer survivors who became active and inactive post-diagnosis showed a 16% and 11% lower ischemic stroke risk (sHR, 0.84; 95% CI, 0.75-0.93; sHR, 0.89; 95% CI, 0.79-0.99), respectively, than those who remained inactive. Analysis by the primary cancer site did not substantially differ from the main findings. CONCLUSIONS: Physical activity is associated with reduced ischemic stroke risk among cancer survivors. The potential benefits of physical activity are not limited to individuals who were physically active before cancer diagnosis, thus preventive strategies against ischemic stroke should emphasize physical activity throughout the cancer journey.

Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Early-Onset Ocular Motor Cranial Neuropathy Is a Strong Predictor of Dementia: A Nationwide, Population-Based Cohort Study.

PURPOSE: To assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DESIGN: A nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). PARTICIPANTS: This study included 60 781 patients with OMCN who received a diagnosis between 2010 and 2017 and were followed up through 2018, with an average follow-up of 3.37 ± 2.21 years with a 1-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis, a total of 52 076 patients with OMCN were established. Of these, 23 642 patients who had participated in the National Health Screening Program (NHSP) within 2 years before the OMCN diagnosis were included. After applying the exclusion criteria, the final cohort comprised 19 243 patients and 96 215 age and sex-matched control participants without OMCN. METHODS: We identified patients with newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study end point was determined by the first claim with a dementia diagnostic code and antidementia medications. The association of OMCN with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: The main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) development in patients with OMCN relative to those without OMCN. RESULTS: Patients with newly diagnosed OMCN demonstrated higher metabolic comorbidities than those without OMCN. New OMCN was associated with an elevated risk of ACD (HR, 1.203; 95% CI, 1.113-1.300), AD (HR, 1.137; 95% CI, 1.041-1.243), and VaD (HR, 1.583; 95% CI, 1.286-1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR, 8.690 [< 50 years] vs. 1.192 [≥ 50 years]; P = 0.0004; HR, 2.517 [< 65 years] vs. 1.099 [≥ 65 years]; P < 0.0001). CONCLUSIONS: This nationwide population-based study assessed the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of dementia, particularly in the younger population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Association of physical activity with fractures in kidney transplant recipients: A Korean nationwide cohort study.

Kidney transplant recipients are at high risk for fractures, primarily due to post-transplant bone disease. This retrospective cohort study analyzed data from the Korean National Health Insurance Service, including 10 083 kidney transplant recipients examined from 2009 to 2017. We assessed fracture incidence, emphasizing vertebral and hip fractures, and the association of physical activity and traditional risk factors with fracture risk. Kidney transplant recipients were categorized into three groups according to physical activity levels: non-activity, metabolic equivalent of task (MET) 1-499, and MET ≥500. Physical activity was associated with a decreased risk of all types of fractures: any (MET 1-499: adjusted hazard ratio (aHR) .75; 95% confidence interval (CI) .62-.92, MET ≥500: aHR .84; 95% CI .70-1.00), vertebral (MET 1-499: aHR .69; 95% CI .49-.98, MET ≥500: aHR .67; 95% CI .49-.91), and hip (MET 1-499: aHR .43; 95% CI .23-.81) fractures. Additionally, older age, female sex, and diabetes were associated with an increased fracture risk. The assessment of physical activity and traditional risk factors could improve fracture risk prediction. Our findings emphasize the need for further research to establish optimal physical activity recommendations for fracture prevention in kidney transplant recipients.

Increased Risk of Incident Chronic Obstructive Pulmonary Disease and Related Hospitalizations in Tuberculosis Survivors: A Population-Based Matched Cohort Study.

BACKGROUND: Tuberculosis (TB) survivors have an increased risk of developing chronic obstructive pulmonary disease (COPD). This study assessed the risk of COPD development and COPD-related hospitalization in TB survivors compared to controls. METHODS: We conducted a population-based cohort study of TB survivors and 1:1 age- and sex-matched controls using data from the Korean National Health Insurance Service database collected from 2010 to 2017. We compared the risk of COPD development and COPD-related hospitalization between TB survivors and controls. RESULTS: Of the subjects, 9.6% developed COPD, and 2.8% experienced COPD-related hospitalization. TB survivors had significantly higher COPD incidence rates (36.7/1,000 vs. 18.8/1,000 person-years, P < 0.001) and COPD-related hospitalization (10.7/1,000 vs. 4.3/1,000 person-years, P < 0.001) than controls. Multivariable Cox regression analyses revealed higher risks of COPD development (adjusted hazard ratio [aHR], 1.63; 95% confidence interval [CI], 1.54-1.73) and COPD-related hospitalization (aHR, 2.03; 95% CI, 1.81-2.27) in TB survivors. Among those who developed COPD, the hospitalization rate was higher in individuals with post-TB COPD compared to those with non-TB COPD (10.7/1,000 vs. 4.9/1,000 person-years, P < 0.001), showing an increased risk of COPD-related hospitalization (aHR, 1.84; 95% CI, 1.17-2.92). CONCLUSION: TB survivors had higher risks of incident COPD and COPD-related hospitalization compared to controls. These results suggest that previous TB is an important COPD etiology associated with COPD-related hospitalization.

Cranial Nerve Palsy and Risk of Kidney Cancer: A Nationwide Population-Based Study.

Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.

Long-Term Mortality of Tuberculosis Survivors in Korea: A Population-based Longitudinal Study.

BACKGROUND: When assessing long-term tuberculosis (TB) mortality, few studies addressed the impact of behavior habits and socioeconomic status. Therefore, we aimed to evaluate long-term TB mortality and risk factors while accounting for potential confounders. METHODS: This cohort study included TB survivors (n = 82 098) aged ≥20 years between 2010 and 2017, and 1:1 age- and sex-matched controls (n = 82 098). The participants were followed up for death 1 year after study enrollment until December 2018. Long-term mortality was adjusted for behavior habits (smoking, alcohol consumption, or exercise), income level, body mass index (BMI), and comorbidities. RESULTS: During a median of 3.7 years of follow-up, the incidence rate of mortality was significantly higher in TB survivors than those in the matched controls (18.2 vs. 8.8 per 1000 person-years, P < .001). Even after adjusting for potential confounders, the mortality risk was 1.62-fold (95% confidence interval [CI], 1.54-1.70) higher in TB survivors than those in the matched controls. In addition, the hazard of mortality in TB survivors relative to matched controls significantly increased in participants aged ≥30 years, with the highest risk in those in their 40s. Male sex (adjusted hazard ratio [HR]: 2.31; 95% CI, 2.16-2.47), smoking pack-years (HR: 1.005; 95% CI, 1.004-1.006), heavy alcohol consumption (HR: 1.12; 95% CI, 1.01-1.23), and lowest income (HR: 1.27; 95% CI, 1.18-1.37) were positively associated with increased hazards for mortality, whereas higher BMI (HR: 0.91; 95% CI, .90-.92) and regular exercise (HR: 0.82; 95% CI, .76-.88) reduced the hazards of long-term mortality in TB survivors. CONCLUSIONS: The long-term mortality risk was significantly higher in TB survivors than those in the matched controls, even after adjusting for potential confounders.

Bone Mineral Density and the Risk of Parkinson's Disease in Postmenopausal Women.

BACKGROUND: Whether bone mineral density (BMD) is related to the risk of Parkinson's disease (PD) is unclear. OBJECTIVES: The objective of this study was to examine the association between BMD status and incident PD in postmenopausal women. METHODS: We retrospectively examined a nationwide cohort of 272,604 women aged 66 years who participated in the 2009-2012 Korean national health screening for transitional ages. BMD was evaluated using dual-energy X-ray absorptiometry of the central bones. The use of antiosteoporosis medications (AOMs) was assessed. We performed multivariable Cox proportional hazards regression to evaluate the association between BMD and PD risk by calculating hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: During the median follow-up of 7.7 years, 2,884 (1.1%) incident PD cases developed. After adjusting for confounding factors, lower BMD was associated with an increased risk of PD (P for trend <0.001). Individuals with osteoporosis had a 1.40-fold higher HR (1.40, 95% CI: 1.25-1.56) than those with a normal BMD. Sensitivity analyses suggested the associations robust to longer lag periods and further adjustment. These associations were prominent in individuals without AOM use before or after enrollment (P for interaction = 0.031 and 0.014). Increased risks of PD in individuals with osteopenia and osteoporosis who did not use AOMs were attenuated by the medication use during the follow-up period, regardless of previous AOM use. CONCLUSIONS: Lower postmenopausal BMD and osteoporosis were associated with an increased risk of PD. In addition, this association could be mitigated using AOMs. Proper management of BMD in postmenopausal women may help prevent PD. © 2023 International Parkinson and Movement Disorder Society.

Histamine-2 Receptor Antagonists and Proton Pump Inhibitors Are Associated With Reduced Risk of SARS-CoV-2 Infection Without Comorbidities Including Diabetes, Hypertension, and Dyslipidemia: A Propensity Score-Matched Nationwide Cohort Study.

BACKGROUND: This study aimed to identify the effect of histamine-2 receptor antagonist (H2RA) and proton pump inhibitor (PPI) use on the positivity rate and clinical outcomes of coronavirus disease 2019 (COVID-19). METHODS: We performed a nationwide cohort study with propensity score matching using medical claims data and general health examination results from the Korean National Health Insurance Service. Individuals aged ≥ 20 years who were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) between 1 January and 4 June 2020 were included. Patients who were prescribed H2RA or PPI within 1 year of the test date were defined as H2RA and PPI users, respectively. The primary outcome was SARS-CoV-2 test positivity, and the secondary outcome was the instance of severe clinical outcomes of COVID-19, including death, intensive care unit admission, and mechanical ventilation administration. RESULTS: Among 59,094 patients tested for SARS-CoV-2, 21,711 were H2RA users, 12,426 were PPI users, and 24,957 were non-users. After propensity score matching, risk of SARS-CoV-2 infection was significantly lower in H2RA users (odds ratio [OR], 0.85; 95% confidence interval [CI], 0.74-0.98) and PPI users (OR, 0.62; 95% CI, 0.52-0.74) compared to non-users. In patients with comorbidities including diabetes, dyslipidemia, and hypertension, the effect of H2RA and PPI against SARS-CoV-2 infection was not significant, whereas the protective effect was maintained in patients without such comorbidities. Risk of severe clinical outcomes in COVID-19 patients showed no difference between users and non-users after propensity score matching either in H2RA users (OR, 0.89; 95% CI, 0.52-1.54) or PPI users (OR, 1.22; 95% CI, 0.60-2.51). CONCLUSION: H2RA and PPI use is associated with a decreased risk for SARS-CoV-2 infection but does not affect clinical outcome. Comorbidities including diabetes, hypertension, and dyslipidemia seem to offset the protective effect of H2RA and PPI.

Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study.

AIMS: This study aimed to examine the association of premature menopause and age at menopause with the risk of heart failure (HF) and atrial fibrillation (AF). METHODS AND RESULTS: A total of 1 401 175 postmenopausal women, who had undergone health examination provided by the Korean National Health Insurance Service, were included, and their reproductive histories were collected. Multivariable Cox proportional hazard models were performed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF and AF, according to the history of premature menopause and age at menopause. At a mean follow-up of 9.1 years, there were 42 699 (3.0%) and 44 834 (3.2%) new cases of HF and AF, respectively. Women with history of premature menopause had an increased risk of HF (HR: 1.33, 95% CI: 1.26-1.40) and AF (HR: 1.09, 95% CI: 1.02-1.16), compared to women without the history. Compared with women aged ≥50 years at menopause, those aged 45-49, 40-44, and <40 years at menopause showed a significantly increased trend in HRs for the incident risk of both HF and AF (P for trend <0.001). The robustness of the results of a series of sensitivity analyses further strengthens the main findings. CONCLUSION: Our findings suggest that postmenopausal women with a history of premature menopause or early menopausal age may have an increased risk of HF and AF. These reproductive factors need to be considered for preventing the future risk of HF and AF.

Acute myocardial infarction risk in multiple sclerosis and neuromyelitis optica spectrum disorder: A nationwide cohort study in South Korea.

BACKGROUND: The link between neuromyelitis optica spectrum disorder (NMOSD) and cardiovascular disease is currently unclear. OBJECTIVE: To determine the acute myocardial infarction (MI) risk in patients with MS and NMOSD. METHODS: This study analyzed the Korean National Health Insurance Service database between January 2010 and December 2017. The included patients comprised 1503/1675 adults with MS/NMOSD who had not experienced ischemic heart disease or ischemic stroke at the index date. Matched controls were selected based on age, sex, and the presence of hypertension, diabetes mellitus (DM), and dyslipidemia. RESULTS: The risks of developing MI were 2.61 (hazard ratio (HR), 95% confidence interval (CI) 1.73-3.95) and 1.95 (95% CI = 1.18-3.22) times higher in MS and NMOSD compared with the control populations. Patients with NMOSD had a similar MI risk compared with patients with MS, after adjusting for age, sex, income, hypertension, DM, and dyslipidemia (HR = 0.59, 95% CI = 0.34-1.02, p = 0.059). Among each patient group, the MI risk did not differ significantly with age (20-39, 40-64 or ⩾65 years), sex, or the presence of hypertension, DM, or dyslipidemia. CONCLUSION: The MI risk increased in MS and NMOSD and seemed to be comparable between NMOSD and MS.

Proton Pump Inhibitor Co-Therapy in Patients with Atrial Fibrillation Treated with Oral Anticoagulants and a Prior History of Upper Gastrointestinal Tract Bleeding.

PURPOSE: The risk of gastrointestinal bleeding (GIB) can be mitigated by proton pump inhibitor (PPI) co-therapy in patients with atrial fibrillation (AF) treated with anticoagulants. We aimed to evaluate the effect of PPIs on the risk of GIB in Asian patients with AF, treated with oral anticoagulants (OACs), and with a prior history of upper GIB. METHODS: Using a nationwide claims database, OAC-naïve patients with AF and a history of upper GIB before initiating OAC treatment between January 2010 and April 2018 were included. Patients were categorized into 10 groups according to the index OAC (warfarin, rivaroxaban, dabigatran, apixaban, and edoxaban) and whether or not they received PPI co-therapy, and were followed up for incidence of major GIB. RESULTS: Among a total of 42,048 patients, 40% were prescribed PPIs as co-therapy with OACs. Over a median 0.6 years (interquartile ranges 0.2-1.7 years) of follow-up, rivaroxaban use without PPIs showed the highest crude incidence of major GIB (2.62 per 100 person-years), followed by the use of warfarin without a PPI (2.20 per 100 person-years). Compared to the patients without PPI use, PPI co-therapy was associated with a significantly lower risk of major GIB, by 40% and 36%, in the rivaroxaban and warfarin groups, respectively. In dabigatran, apixaban, and edoxaban users, PPI co-therapy did not show a significant reduction in the risk of major GIB. CONCLUSION: Among patients with AF receiving anticoagulant treatment and with a prior history of upper GIB, PPI co-therapy was associated with a significant reduction in the risk of major GIB in patients treated with rivaroxaban and warfarin.

Risk Assessment of Mortality in Elderly Individuals: A Nationwide Cohort Study.

INTRODUCTION: There are several methods that are used to predict emergency room visits or rehospitalization for the elderly. However, existing risk assessment models of mortality in elderly people are limited. The purpose of this study was to ascertain the factors that affect all-cause mortality and to show the risk assessment model of mortality in elderly Koreans. METHODS: This was a cohort study conducted using the health checkup data of 246,422 individuals aged ≥60 years, which was provided by the National Health Insurance Service of South Korea between January 1, 2009, and December 31, 2012. The hazard ratios and 95% confidence intervals (CIs) of several conditions and all-cause deaths were estimated using a multivariable Cox proportional hazards model. A nomogram was constructed to visualize the risk factors of mortality; a calibration plot and area under the curve (AUC) were also used to verify the nomogram. RESULTS: Being 85 years or older (100 points) had the greatest influence on all-cause mortality, followed by being underweight (57 points), having more than five chronic diseases (49 points), and ages 78-84 years (45 points); smoking and lack of regular exercise affected mortality to a similar degree. The calibration curves showed good agreement between predictions and observations. The AUC of our nomogram was 0.73 (95% CI: 0.72-0.73). CONCLUSIONS: Our results showed the relationship between each condition and mortality rate among elderly individuals in Korea. Our nomogram showed a satisfactory performance in the assessment of the risk of all-cause mortality in elderly Korean people.

Lower risk of stroke after alcohol abstinence in patients with incident atrial fibrillation: a nationwide population-based cohort study.

AIMS: The aim of this study was to evaluate the association between alcohol consumption status (and its changes) after newly diagnosed atrial fibrillation (AF) and the risk of ischaemic stroke. METHODS AND RESULTS: Using the Korean nationwide claims and health examination database, we included subjects who were newly diagnosed with AF between 2010 and 2016. Patients were categorized into three groups according to the status of alcohol consumption before and after AF diagnosis: non-drinkers; abstainers from alcohol after AF diagnosis; and current drinkers. The primary outcome was incident ischaemic stroke during follow-up. Non-drinkers, abstainers, and current drinkers were compared using incidence rate differences after the inverse probability of treatment weighting (IPTW). Among a total of 97 869 newly diagnosed AF patients, 51% were non-drinkers, 13% were abstainers, and 36% were current drinkers. During 310 926 person-years of follow-up, 3120 patients were diagnosed with incident ischaemic stroke (10.0 per 1000 person-years). At 5-year follow-up, abstainers and non-drinkers were associated with a lower risk for stroke than current drinkers (incidence rate differences after IPTW, -2.03 [-3.25, -0.82] for abstainers and -2.98 [-3.81, -2.15] for non-drinkers, per 1000 person-years, respectively; and incidence rate ratios after IPTW, 0.75 [0.70, 0.81] for non-drinkers and 0.83 [0.74, 0.93] for abstainers, respectively). CONCLUSION: Current alcohol consumption was associated with an increased risk of ischaemic stroke in patients with newly diagnosed AF, and alcohol abstinence after AF diagnosis could reduce the risk of ischaemic stroke. Lifestyle intervention, including attention to alcohol consumption, should be encouraged as part of a comprehensive approach to AF management to improve clinical outcomes.

Body Mass Index and Clinical Outcomes in Asian Patients With Atrial Fibrillation Receiving Oral Anticoagulation.

BACKGROUND AND PURPOSE: The influence of body mass index (BMI) on clinical outcomes in patients with atrial fibrillation remains controversial, especially among Asians. We aimed to evaluate the association between BMI and clinical outcomes in Asian patients with atrial fibrillation receiving oral anticoagulants. METHODS: Using the Korean National Health Insurance database between January 2015 and December 2017, we identified oral anticoagulant new users among patients with nonvalvular atrial fibrillation who had BMI information. We analyzed ischemic stroke, intracranial hemorrhage, hospitalization for gastrointestinal bleeding, major bleeding, all-cause death, and the composite clinical outcome according to BMI categories. RESULTS: A total of 43 173 patients were included across BMI categories (kg/m2): underweight (<18.5) in 3%, normal (18.5 to <23) in 28%, overweight (23 to <25) in 24%, obese I (25 to <30) in 39%, and obese II (≥30) in 6%. Higher BMI (per 5 kg/m2 increase) was significantly associated with lower risks of ischemic stroke (hazard ratio [HR], 0.891 [95% CI, 0.801-0.992]), hospitalization for gastrointestinal bleeding (HR, 0.785 [95% CI, 0.658-0.937]), major bleeding (HR, 0.794 [95% CI, 0.686-0.919]), all-cause death (HR, 0.658 [95% CI, 0.605-0.716]), and the composite clinical outcome (HR, 0.751 [95% CI, 0.706-0.799]), except for intracranial hemorrhage (HR, 0.815 [95% CI, 0.627-1.061]). The underweight group was associated with an increased risk of composite clinical outcome (HR, 1.398 [95% CI, 1.170-1.671]), mainly driven by an increased risk of all-cause death. The effects of non-vitamin K antagonist oral anticoagulant versus warfarin on clinical outcomes were similar across BMI groups. CONCLUSIONS: Higher BMI was independently associated with a lower risk of ischemic stroke, major bleeding, and better survival. Underweight patients had a higher risk of all-cause death and composite clinical outcome. The optimal BMI for patients with atrial fibrillation should be defined and managed according to an integrated care pathway.

Comparing Warfarin and 4 Direct Oral Anticoagulants for the Risk of Dementia in Patients With Atrial Fibrillation.

Background and Purpose: Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin. Methods: Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant­naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia. Results: Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular dementia and 3.30 per 100 person-years for Alzheimer dementia). Compared with warfarin, DOAC showed a comparable risks of dementia, vascular dementia, and Alzheimer dementia. In subgroup analyses, DOAC was associated with a lower risk of dementia than warfarin, particularly in patients aged 65 to 74 years (hazard ratio, 0.815 [95% CI, 0.709­0.936]) and in patients with prior stroke (hazard ratio, 0.891 [95% CI, 0.820­0.968]). When comparing individual DOACs with warfarin, edoxaban was associated with a lower risk of dementia (hazard ratio, 0.830 [95% CI, 0.740­0.931]). Conclusions: In this large Asian population with atrial fibrillation, DOAC showed a comparable risk of dementia with warfarin overall. DOACs appeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.

Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation and Prior Gastrointestinal Bleeding.

BACKGROUND AND PURPOSE: Limited data support the benefits of non-vitamin K oral anticoagulants (NOACs) among atrial fibrillation patients with prior gastrointestinal bleeding (GIB). We aimed to evaluate the effectiveness and safety of NOACs compared with those of warfarin among atrial fibrillation patients with prior GIB. METHODS: Oral anticoagulant-naive individuals with atrial fibrillation and prior GIB between January 2010 and April 2018 were identified from the Korean claims database. NOAC users were compared with warfarin users by balancing covariates using the inverse probability of treatment weighting method. The primary outcomes were ischemic stroke, major bleeding, and the composite outcome (combined ischemic stroke and major bleeding). Fatal events from each outcome were evaluated as secondary outcomes. RESULTS: A total of 42 048 patients were included (24 781 in the NOAC group and 17 267 in the warfarin group). The mean time from prior GIB to the initiation of oral anticoagulant was 3.1±2.6 years. After inverse probability of treatment weighting, baseline characteristics were balanced between the two groups (mean age, 72 years; men, 56.8%; and mean CHA2DS2-VASc score, 3.7). Lower risks of ischemic stroke, major bleeding, and the composite outcome were associated with NOAC use than with warfarin use (weighted hazard ratio, 0.608 [95% CI, 0.543-0.680]; hazard ratio, 0.731 [95% CI, 0.642-0.832]; and hazard ratio, 0.661 [95% CI, 0.606-0.721], respectively). For all secondary outcomes, NOACs showed greater risk reductions compared with warfarin. CONCLUSIONS: NOACs were associated with lower risks of ischemic stroke and major bleeding than warfarin among atrial fibrillation patients with prior GIB.

Association between exercise habits and stroke, heart failure, and mortality in Korean patients with incident atrial fibrillation: A nationwide population-based cohort study.

BACKGROUND: There is a paucity of information about cardiovascular outcomes related to exercise habit change after a new diagnosis of atrial fibrillation (AF). We investigated the association between exercise habits after a new AF diagnosis and ischemic stroke, heart failure (HF), and all-cause death. METHODS AND FINDINGS: This is a nationwide population-based cohort study using data from the Korea National Health Insurance Service. A retrospective analysis was performed for 66,692 patients with newly diagnosed AF between 2010 and 2016 who underwent 2 serial health examinations within 2 years before and after their AF diagnosis. Individuals were divided into 4 categories according to performance of regular exercise, which was investigated by a self-reported questionnaire in each health examination, before and after their AF diagnosis: persistent non-exercisers (30.5%), new exercisers (17.8%), exercise dropouts (17.4%), and exercise maintainers (34.2%). The primary outcomes were incidence of ischemic stroke, HF, and all-cause death. Differences in baseline characteristics among groups were balanced considering demographics, comorbidities, medications, lifestyle behaviors, and income status. The risks of the outcomes were computed by weighted Cox proportional hazards models with inverse probability of treatment weighting (IPTW) during a mean follow-up of 3.4 ± 2.0 years. The new exerciser and exercise maintainer groups were associated with a lower risk of HF compared to the persistent non-exerciser group: the hazard ratios (HRs) (95% CIs) were 0.95 (0.90-0.99) and 0.92 (0.88-0.96), respectively (p < 0.001). Also, performing exercise any time before or after AF diagnosis was associated with a lower risk of mortality compared to persistent non-exercising: the HR (95% CI) was 0.82 (0.73-0.91) for new exercisers, 0.83 (0.74-0.93) for exercise dropouts, and 0.61 (0.55-0.67) for exercise maintainers (p < 0.001). For ischemic stroke, the estimates of HRs were 10%-14% lower in patients of the exercise groups, yet differences were statistically insignificant (p = 0.057). Energy expenditure of 1,000-1,499 MET-min/wk (regular moderate exercise 170-240 min/wk) was consistently associated with a lower risk of each outcome based on a subgroup analysis of the new exerciser group. Study limitations include recall bias introduced due to the nature of the self-reported questionnaire and restricted external generalizability to other ethnic groups. CONCLUSIONS: Initiating or continuing regular exercise after AF diagnosis was associated with lower risks of HF and mortality. The promotion of exercise might reduce the future risk of adverse outcomes in patients with AF.

Cumulative burden of metabolic syndrome and its components on the risk of atrial fibrillation: a nationwide population-based study.

BACKGROUND: The metabolic syndrome (MetS) and its components are associated with the development of atrial fibrillation (AF). However, the impact of time-burden of MetS on the risk of AF is unknown. We investigated the effect of the cumulative longitudinal burden of MetS on the development of AF. METHODS: We included 2 885 189 individuals without AF who underwent four annual health examinations during 2009-2013 from the database of the Korean national health insurance service. Metabolic burdens were evaluated in the following three ways: (1) cumulative number of MetS diagnosed at each health examination (0-4 times); (2) cumulative number of each MetS component diagnosed at each health examination (0-4 times per MetS component); and (3) cumulative number of total MetS components diagnosed at each health examination (0 to a maximum of 20). The risk of AF according to the metabolic burden was estimated using Cox proportional-hazards models. RESULTS: Of all individuals, 62.4%, 14.8%, 8.7%, 6.5%, and 7.6% met the MetS diagnostic criteria 0, 1, 2, 3, and 4 times, respectively. During a mean follow-up of 5.3 years, the risk of AF showed a positive association with the cumulative number of MetS diagnosed over four health examinations: adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) of 1, 2, 3, and 4 times compared to 0 times were 1.18 (1.13-1.24), 1.31 (1.25-1.39), 1.46 (1.38-1.55), and 1.72 (1.63-1.82), respectively; P for trend < 0.001. All five components of MetS, when diagnosed repeatedly, were independently associated with an increased risk of AF: adjusted HR (95% CI) from 1.22 (1.15-1.29) for impaired fasting glucose to 1.96 (1.87-2.07) for elevated blood pressure. As metabolic components were accumulated from 0 to 20 counts, the risk of AF also gradually increased up to 3.1-fold (adjusted HR 3.11, 95% CI 2.52-3.83 in those with 20 cumulative components of MetS), however, recovery from MetS was linked to a decreased risk of AF. CONCLUSIONS: Given the positive correlations between the cumulative metabolic burdens and the risk of incident AF, maximal effort to detect and correct metabolic derangements even before MetS development might be important to prevent AF and related cardiovascular diseases.

Association between body weight variability and incidence of Parkinson disease: A nationwide, population-based cohort study.

BACKGROUND AND PURPOSE: Although body weight variability has been associated with mortality, cardiovascular disease, and dementia, the relationship between body weight variability and Parkinson disease (PD) has rarely been studied. We aimed to investigate the longitudinal association between body weight variability and PD incidence. METHODS: A nationwide population-based, cohort study was conducted using the database from the Health Insurance Review and Assessment Service of the whole Korean population. We analyzed 2,815,135 participants (≥40 years old, mean age = 51.7 ± 8.6 years, 66.8% men) without a previous PD diagnosis. We determined individual body weight variability from baseline weight and follow-up visits. We used Cox proportional hazards regression models. RESULTS: The highest quartile group was associated with increased PD incidence compared with the lowest quartile group after adjustment for confounding factors (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.08-1.29). In contrast, baseline body mass index, baseline waist circumference, and waist circumference variability were not associated with increased PD incidence. In the body weight loss group, individuals within the quartile of the highest variation in body weight showed a higher HR of PD risk than those within other quartiles (HR = 1.41, 95% CI = 1.18-1.68). CONCLUSIONS: Body weight variability, especially weight loss, was associated with higher PD incidence. This finding has important implications for clinicians and supports the need for preventative measures and surveillance for PD in individuals with fluctuating body weight.