Early rhythm control on diabetes-related complications and mortality in patients with type 2 diabetes mellitus and atrial fibrillation.

AIMS: We evaluated the impact of early rhythm control (ERC) on diabetes-related complications and mortality in subjects with type 2 diabetes mellitus (T2DM) and atrial fibrillation (AF). METHODS: This observational cohort study based on the Korean National Health Insurance Service claims database from 2009 to 2016, divided newly diagnosed AF patients with T2DM into ERC or usual care groups based on receiving rhythm control treatment within 1 year of AF diagnosis. The primary outcome was ischemic stroke, and the secondary outcomes were macro/microvascular complications, and all-cause death. RESULTS: Among 47,509 subjects (mean age 66.7 ± 10.5 years; 61.8 % men; mean CHA2DS2-VASc score 4.6 ± 1.8; mean follow-up 4.3 ± 2.3 years; mean DM duration 5.6 ± 4.7 years), 23.1 % received ERC, and 76.9 % did not (usual care group). ERC was associated with lower risks of ischemic stroke, macrovascular and microvascular complications, and all-cause death compared to usual care (adjusted hazard ratios [95 % confidence interval]: 0.77 [0.70-0.85], 0.79 [0.73-0.86], 0.86 [0.82-0.90], and 0.92 [0.87-0.98], p < 0.001, <0.001, <0.001, and 0.012, respectively). CONCLUSIONS: Early rhythm control was associated with reduced risks of diabetes-related complications and mortality in subjects with T2DM and AF. Rhythm control within 1 year of AF diagnosis with proper anticoagulation should be considered to prevent adverse outcomes.

Hederacolchiside A1 Suppresses Autophagy by Inhibiting Cathepsin C and Reduces the Growth of Colon Cancer.

While autophagy degrades non-functional or unnecessary cellular components, producing materials for synthesizing cellular components, it can also provide energy for tumor development. Hederacolchiside A1 (HA1) derived from anemone raddeana has anticancer effects on several carcinomas by inducing apoptosis or exhibiting cytotoxicity, but the relationship with autophagy has not been studied. We investigated the association between HA1 and autophagy and evaluated its anticancer effect on colon cancer. HA1 induced accumulation of the autophagy-related markers LC3B and SQSTM1, with distinct vacuolar formation, unlike other autophagy inhibitors; the effects were similar to those of chloroquine. In addition, HA1 decreased the expression and proteolytic activity of lysosomal protein cathepsin C, reduced the growth of colon cancer cells in vitro, and inhibited tumor growth in vivo. It also reduced the expression of Ki-67 and cathepsin C in mouse tissues and reduced the growth of spheroids and organoids composed of cancer cells. Taken together, these results imply that HA1 regulates cell growth and autophagy and has potential as a promising therapeutic agent in colon cancer.

Feasibility and measurement stability of smartwatch-based cuffless blood pressure monitoring: A real-world prospective observational study.

Cuffless wearable devices are currently being developed for long-term monitoring of blood pressure (BP) in patients with hypertension and in apparently healthy people. This study evaluated the feasibility and measurement stability of smartwatch-based cuffless BP monitoring in real-world conditions. Users of the first smartwatch-based cuffless BP monitor approved in Korea (Samsung Galaxy Watch) were invited to upload their data from using the device for 4 weeks post calibration. A total of 760 participants (mean age 43.7 ± 11.9, 80.3% men) provided 35,797 BP readings (average monitoring 22 ± 4 days [SD]; average readings 47 ± 42 per participant [median 36]). Each participant obtained 1.5 ± 1.3 readings/day and 19.7% of the participants obtained measurements every day. BP showed considerable variability, mainly depending on the day and time of the measurement. There was a trend towards higher BP levels on Mondays than on other days of the week and on workdays than in weekends. BP readings taken between 00:00 and 04:00 tended to be the lowest, whereas those between 12:00 and 16:00 the highest. The average pre-post calibration error for systolic BP (difference in 7-day BP before and after calibration), was 6.8 ± 5.6 mmHg, and was increased with higher systolic BP levels before calibration. Smartwatch-based cuffless BP monitoring is feasible for out-of-office monitoring in the real-world setting. The stability of BP measurement post calibration and the standardization and optimal time interval for recalibration need further investigation.

Accumulated hypertension burden on atrial fibrillation risk in diabetes mellitus: a nationwide population study.

BACKGROUND: Patients with diabetes mellitus have an increased risk of incident atrial fibrillation (AF). The effect of accumulated hypertension burden is a less well-known modifiable risk factor. We explored the relationship between accumulated hypertension burden and incident AF in these patients. METHODS: We evaluated data for 526,384 patients with diabetes who underwent three consecutive health examinations, between 2009 and 2012, from the Korean National Health Insurance Service. Hypertension burden was calculated by assigning points to each stage of hypertension in each health examination: 1 for stage 1 hypertension (systolic blood pressure [SBP] 130-139 mmHg; diastolic blood pressure [DBP] 80-89 mmHg); 2 for stage 2 (SBP 140-159 mmHg and DBP 90-99 mmHg); and 3 for stage 3 (SBP ≥ 160 mmHg or DBP ≥ 100 mmHg). Patients were categorized into 10 hypertensive burden groups (0-9). Groups 1-9 were then clustered into 1-3, 4-6, and 7-9. RESULTS: During a mean follow-up duration of 6.7 ± 1.7 years, AF was newly diagnosed in 18,561 (3.5%) patients. Compared to patients with hypertension burden 0, those with burden 1 to 9 showed a progressively increasing risk of incident AF: 6%, 11%, 16%, 24%, 28%, 41%, 46%, 57%, and 67% respectively. Clusters 1-3, 4-6, and 7-9 showed increased risks by 10%, 26%, and 45%, respectively, when compared to a hypertension burden of 0. CONCLUSIONS: Accumulated hypertension burden was associated with an increased risk of incident AF in patients with diabetes. Strict BP control should be emphasized for these patients.

Cumulative Alcohol Consumption Burden and the Risk of Stroke in Young Adults: A Nationwide Population-Based Study.

BACKGROUND AND OBJECTIVE: Alcohol consumption is one of the important modifiable risk factors for stroke in young adults. The association between the cumulative burden of alcohol consumption and its impact on incident stroke in young adults is unknown. We aimed to investigate the association between cumulative alcohol burden and the risk for stroke among young adults. METHODS: Using data from the Korean National Health Insurance Service database, patients age between 20 and 39 years, who underwent 4 consecutive annual health examinations between 2009 and 2012, were included. The cumulative alcohol burden score of moderate-to-heavy drinking was evaluated by assigning a score of 1 for alcohol consumption ≥105 g/wk at the health examination each year and calculating the sum of 4 years (0-4). The main outcome was incident stroke and its subtypes, ischemic stroke, and hemorrhagic stroke during the follow-up period. RESULTS: Of 1 536 668 patients (mean age of 29.5 years, 71.5% male, and median follow-up of 6-year), 3 153 experienced an incident stroke (incidence rate, 0.37 per 1,000 person-years). After multivariable adjustment, patients with alcohol burden scores of 2, 3, and 4, who consumed more than 105 g/wk of alcohol for 2, 3, and 4 years, demonstrated significantly higher risks for stroke (hazard ratio [HR] 1.19, 95% CI 1.05-1.34 for 2; HR 1.22, 95% CI 1.09-1.38 for 3; HR 1.23, 95% CI 1.10-1.38 for 4) compared with those with a burden score of 0. This positive dose-response relationship was primarily driven by hemorrhagic rather than ischemic stroke. High alcohol burden scores (i.e., 2, 3, and 4) were significantly associated with higher risks for hemorrhagic stroke (HR 1.30, 95% CI 1.10-1.54 for 2; HR 1.42, 95% CI 1.21-1.67 for 3; HR 1.36, 95% CI 1.16-1.59 for 4) compared with a burden score of 0. DISCUSSION: Young adults who engaged in moderate-to-heavy drinking demonstrated a higher risk for incident stroke, especially hemorrhagic stroke. Reducing alcohol consumption should be emphasized in young adults with heavy drinking habits as part of any stroke prevention strategy.

The impact of socioeconomic deprivation on the risk of atrial fibrillation in patients with diabetes mellitus: A nationwide population-based study.

Objective: To evaluate the relationship between socioeconomic status and the risk of atrial fibrillation (AF) in patients with diabetes mellitus (DM). Research design and methods: From the National Health Insurance Service (NHIS) database, we identified 2,429,610 diabetic patients who underwent national health check-ups between 2009 and 2012. Tracing back the subjects for 5 years from the date of health check-up, we determined the subjects' income and whether they received medical aid (MA) during the past 5 years. Subjects were divided into six groups according to the number of years of receiving (MA groups 0 through 5) and into four groups according to socioeconomic status change during the past 5 years. We estimated the risk of AF for each group using the Cox proportional-hazards model. Results: During a median follow-up of 7.2 ± 1.7 years, 80,257 were newly identified as AF. The MA groups showed a higher risk of AF than the non-MA group with the hazard ratios (HRs) and 95% confidence interval (CI) 1.32 (1.2-1.44), 1.33 (1.22-1.45), 1.23 (1.13-1.34), 1.28 (1.16-1.4), and 1.50 (1.39-1.63) for MA groups 1 through 5, respectively. Dividing subjects according to socioeconomic condition change, those who experienced worsening socioeconomic status (non-MA to MA) showed higher risk compared to the persistent non-MA group (HR 1.54; 95% CI 1.38-1.73). Conclusion: Low socioeconomic status was associated with the risk of AF in patients with diabetes. More attention should be directed at alleviating health inequalities, targeting individuals with socioeconomic deprivation to provide timely management for AF.

Habitual Alcohol Intake and Risk of Atrial Fibrillation in Young Adults in Korea.

Importance: Guidelines recommend that all risk factors for early-onset atrial fibrillation, including lifestyle factors, be proactively managed, considering the poor prognosis of the disease. Not much is known about the association of cumulative alcohol intake with the risk of atrial fibrillation in young adults aged 20 to 39 years, especially among heavy drinkers. Objective: To explore the association of alcohol consumption with the risk of incident atrial fibrillation in young adults. Design, Setting, and Participants: Using the National Health Insurance Service database, a nationwide population-based cohort study of adults aged 20 to 39 years without prior atrial fibrillation who underwent 4 serial annual health examinations between 2009 and 2012 was conducted. The cumulative alcohol consumption burden over 4 years was calculated by assigning 1 point to more than moderate drinking (≥105 g of alcohol per week) each year. Additionally, a semiquantitative cumulative burden was calculated by assigning 0, 1, 2, and 3 points to non, mild (<105 g per week), moderate (105-210 g per week), and heavy (≥210 g per week) drinking, respectively. Data were analyzed from May to June 2021. Exposure: Amount of alcohol intake in 4 years. Main Outcomes and Measures: The primary outcome was incident atrial fibrillation during the follow-up period. Results: A total of 1 537 836 participants (mean [SD] age 29.5 [4.1] years, 1 100 099 [71.5%] male) were included in the final analysis. According to the 4-year cumulative burden of alcohol consumption stratified by moderate to heavy drinking, 889 382 participants (57.8%) were in the burden 0 group, 203 374 participants (13.2%) in the burden 1 group, 148 087 participants (9.6%) in the burden 2 group, 144 023 participants (9.4%) in the burden 3 group, and 152 970 participants (9.9%) in the burden 4 group. During a median (IQR) follow-up of 6.13 (4.59-6.48) years, atrial fibrillation was newly diagnosed in 3066 participants (0.36 per 1000 person-years). Participants with a cumulative burden of 4 points who continued more than moderate drinking for 4 years showed a 25% higher risk of atrial fibrillation compared with 0-point participants who kept non-to-mild drinking over 4 years (adjusted HR, 1.25; 95% CI, 1.12-1.40). In a semiquantitative analysis, participants who sustained heavy drinking for 4 consecutive years were associated with a 47% higher atrial fibrillation risk than those who remained nondrinkers over 4 years (aHR, 1.47, CI 1.18-1.83). Conclusions and Relevance: Persistent moderate to heavy drinking and higher cumulative alcohol consumption burden might increase the risk of atrial fibrillation even in young adults aged 20 to 39 years.

Risk of Dementia After Smoking Cessation in Patients With Newly Diagnosed Atrial Fibrillation.

Importance: Incident atrial fibrillation (AF) is associated with an increased risk of dementia. However, data on the association between smoking cessation after AF diagnosis and dementia risk are limited. Objective: To evaluate the association between changes in smoking status after AF diagnosis and dementia risk. Design, Setting, and Participants: This nationwide cohort study with 126 252 patients used data from the Korean National Health Insurance Service database, including patients who had a national health checkup examination within 2 years before and after AF diagnosis between January 1, 2010, and December 31, 2016. Based on their smoking status, participants were classified as never smokers, ex-smokers, quit smokers, and current smokers. Ex-smokers were defined as those who had quit smoking before the first examination and remained quit until the second examination. Patients who were current smokers at the first health examination but had quit smoking before the second examination were classed as quit smokers. The index date was the second health examination. Patients were followed up until dementia, death, or the study period ended (December 31, 2017), whichever occurred first. Data were analyzed from January 13, 2020, to March 29, 2022. Exposures: Smoking cessation after newly diagnosed AF. Main Outcomes and Measures: Dementia, including Alzheimer disease and vascular dementia, was the primary outcome. Cox proportional hazards regression model was used to estimate hazard ratios. Results: A total of 126 252 patients (mean [SD] age, 62.6 [12.0] years; 61.9% men) were included in the analysis. The mean (SD) CHA2DS2-VASc score, which measures the risk of ischemic stroke, was 2.7 (1.7). Smoking status of the total study population was as follows: 65 579 never smokers (51.9%), 34 670 ex-smokers (27.5%), 8919 quit smokers (7.1%), and 17 084 current smokers (13.5%). During a median of 3 years of follow-up, dementia occurred in 5925 patients (1.11 per 1000 person-years). After multivariable adjustment, the risk of quit smokers was significantly lower than that of current smokers (hazard ratio, 0.83 [95% CI, 0.72-0.95]). Conclusions and Relevance: The findings of this cohort study suggest that all types of smoking were associated with a significantly higher risk of dementia in patients with new-onset AF. Smoking cessation after AF diagnosis was associated with a lower risk of dementia than among current smokers. These findings may support promoting smoking cessation to reduce dementia risk in patients with new-onset AF.

Non-alcoholic Fatty Liver Disease and the Risk of Incident Atrial Fibrillation in Young Adults: A Nationwide Population-Based Cohort Study.

Background: Non-alcoholic fatty liver disease (NAFLD) is a multisystem disease including cardiovascular. However, the association between NAFLD and the risk of incident atrial fibrillation (AF), especially in young adults, remains unclear. We aimed to evaluate the association between NAFLD as assessed by the fatty liver index (FLI) and the risk of AF in young adults. Methods: We identified individuals aged 20-39 years who underwent health examinations conducted by the Korean National Health Insurance Corporation between January 2009 and December 2012. Individuals with significant liver disease, heavy alcohol consumption, or prevalent AF were excluded. We categorized based on FLI: <30, 30 to <60, and ≥60. Incident AF was evaluated as the primary outcome. Results: We included 5,333,907 subjects (mean age, 31 ± 5 years; men, 57%). During a mean follow-up of 7.4 ± 1.1 years, 12,096 patients had newly diagnosed AF (incidence rate 0.31 per 1,000 person-years). After adjustment, subjects with FLI 30 to <60 and FLI ≥60 showed a higher risk of AF compared to those with FLI <30 (hazard ratio [HR] 1.21, 95% confidence interval [CI, 1.15-1.27] and HR 1.47, 95% CI [1.39-1.55], p < 0.001, respectively). In women, the increased AF risk was accentuated in the higher FLI group than in the individuals with FLI <30, compared with men (p-for-interaction = 0.023). A higher incident AF risk in the higher FLI groups was consistently observed in various subgroups. Conclusion: Among young adults, NAFLD assessed using FLI was positively correlated with the AF risk. These findings support the evidence of AF screening in young adults with high FLI scores.

Low Risk of Dementia in Patients With Newly Diagnosed Atrial Fibrillation and a Clustering of Healthy Lifestyle Behaviors: A Nationwide Population-Based Cohort Study.

Background Limited data are available on the clinical impact of healthy lifestyle behaviors on the risk of dementia in patients with new-onset atrial fibrillation (AF). Here, we aimed to evaluate the association between a combination of healthy lifestyle behaviors and the risk of incident dementia in patients with AF. Methods and Results Using the Korean National Health Insurance database between 2009 and 2016, we identified 199 952 adult patients who were newly diagnosed as AF without dementia. Patients were categorized into 4 groups by healthy lifestyle behavior score (HLS) with 1 point each being assigned for no current smoking, alcohol abstinence, and regular exercise. The HLS 0, 1, 2, and 3 groups included 4.4%, 17.4%, 53.4%, and 24.8% of the patients, respectively. We performed an inverse probability of treatment weighting to balance covariates between HLS groups. The HLS 1, 2, and 3 groups were associated with a lower risk of dementia compared with the HLS 0 group (hazard ratio [HR], 0.769; 95% CI, 0.704-0.842 for HLS 1; HR, 0.770; 95% CI, 0.709-0.836 for HLS 2; and HR, 0.622; 95% CI, 0.569-0.679 for HLS 3). The risk of dementia showed a tendency to decrease with an increase in HLS (P-for-trend <0.001). Conclusions A clustering of healthy lifestyle behaviors was associated with a significantly lower risk of dementia in patients with new-onset AF. These findings support the promotion of a healthy lifestyle within an integrated care approach to AF patient management.

Gaucher disease type 1: Unexpected diagnosis in a 75-year old patient presenting with splenomegaly.

We present a 75-year old Korean female patient harboring novel hemizygous variant mutation in glucosidase beta acid (GBA) gene, who was diagnosed with splenic marginal zone cell lymphoma and Gaucher disease (GD) concurrently. Our case is significant in that (1) it delivers the message that GD can occur at any age regardless of ethnicity and (2) we report a novel variant of pathogenic GBA mutation, and the fact that the patient harbored hemizygous mutation.