Clinical Implications of Polypharmacy for Patients with New-Onset Atrial Fibrillation Based on Real-World Data: Observations from the Korea National Health Insurance Service Data.

Background: Polypharmacy is commonly observed in atrial fibrillation (AF) and is associated with poorer clinical outcomes. Our study aimed to elucidate the polypharmacy prevalence, its associated risk factors, and its relationship with adverse clinical outcomes using a 'real-world' database. Methods: This study included 451,368 subjects without prior history of AF (median age, 54 [interquartile range, 48.0-63.0] years; 207,748 [46.0%] female) from the Korea National Health Insurance Service-Health Screening (NHIS-HealS) database between 2002 and 2013. All concomitant medications prescribed were collected, and the intake of five or more concomitant drugs was defined as polypharmacy. During the follow-up, all-cause death, major bleeding events, transient ischemic attack (TIA) or ischemic stroke, and admission due to worsened heart failure were recorded. Results: Based on up to 7.7 (6.8-8.3) years of follow-up and 768,306 person-years, there were 12,241 cases of new-onset AF identified. Among patients with new-onset AF (40.0% females, median age 63.0 [54.0-70.0] years), the polypharmacy prevalence was 30.9% (3784). For newly diagnosed AF, factors, such as advanced age (with each increase of 10 years, odds ratios (OR) 1.32, 95% confidence interval (CI) 1.26-1.40), hypertension (OR 4.00, 95% CI 3.62-4.43), diabetes mellitus (OR 3.25, 95% CI 2.86-3.70), chronic obstructive pulmonary disease (COPD) (OR 3.00, 95% CI 2.51-3.57), TIA/ischemic stroke (OR 2.36, 95% CI 2.03-2.73), dementia history (OR 2.30, 95% CI 1.06-4.98), end-stage renal disease (ESRD) or chronic kidney disease (CKD) (OR 1.97, 95% CI 1.38-2.82), and heart failure (OR 1.95, 95% CI 1.69-2.26), were found to be independently correlated with the incidence of polypharmacy. Polypharmacy significantly increased the incidence and risk of major bleeding (adjusted hazard ratio (aHR) 1.26, 95% CI 1.12-1.41). The study observed a statistically significant increase in the incidence of all-cause mortality, however, the risk for all-cause mortality elevated but did not show significance (aHR 1.11, 95% CI 0.99-1.24). The risk of stroke and admission for heart failure did not change with polypharmacy. Conclusions: In our investigation using data from a nationwide database, polypharmacy was widespread in new-onset AF population and was related to major bleeding events. However, polypharmacy does not serve as an independent risk factor for adverse outcomes, with exception of major bleeding event. For AF patients, ensuring tailored medication for comorbidities as well as reducing polypharmacy are essential considerations.

All-Cause Death and Major Adverse Events in Atrial Fibrillation with Frailty: Observations from the Korea National Health Insurance Service Data.

Background: Atrial fibrillation (AF) is an indicator of frailty in old patients. This study aimed to investigate the effect of frailty on the use of oral anticoagulants (OAC) and clinical outcomes in a nationwide cohort of patients with new-onset AF. Methods: This study included 451,368 participants without AF from the Korea National Health Insurance Service-Health Screening cohort between 2002 and 2009. The Hospital Frailty Risk Score was retrospectively calculated for each patient using all available International Classification of Disease 10th revision diagnostic codes. According to the aggregate score, patients were divided into two groups: the participants without frailty ( < 5 points) and the participants with frailty ( ≥ 5 points). The primary outcome was death from any cause, and the secondary outcomes were cardiovascular death, ischemic stroke, major bleeding, and heart failure admission. Results: With up to 7.2 ± 1.5 years of follow-up, 11,953 participants (median age, 67 [interquartile range, 59.5-74.5] years; 7200 [60.2%] males) developed new-onset AF. Among the patients with AF, 3224 (26.9%) had frailty. Frailty was significantly associated with old age, female sex, polypharmacy, and other comorbidities. In patients with AF, frailty was negatively associated with OAC prescription after new-onset AF (p < 0.001). Compared to patients without frailty, patients with frailty had a significantly higher incidence and risk of all-cause death (hazard ratio [HR] 2.88, 95% confidence interval [CI] 2.65-3.14), cardiovascular death (HR 2.42, 95% CI 2.10-2.80), ischemic stroke (HR 2.25, 95% CI 2.02-2.51), major bleeding (HR 2.44, 95% CI 2.17-2.73), and heart failure admission (HR 1.29, 95% CI 1.09-1.52). In subgroup analysis, when compared to the non-OAC group, the risks associated with frailty were significantly lower in the OAC group for all-cause death, cardiovascular death, ischemic stroke, and heart failure admission. Conclusions: Frailty was negatively associated with the use of OAC and was a predictor of poor prognosis owing to the association of frailty with death, thromboembolic events, bleeding, and heart failure admission. However, OAC use was associated with lower risks related to frailty for all-cause death and major adverse cardiovascular events in patients with AF.

The associations of leukocyte telomere length and intermediary cardiovascular phenotype with adverse cardiovascular outcomes in the white population.

The evidence about the associations of leukocyte telomere length (LTL) and intermediary cardiovascular phenotypes with adverse cardiovascular outcomes is inconclusive. This study assessed these relationships with cardiovascular imaging, electrocardiography, and the risks of sudden cardiac death (SCD), coronary events, and heart failure (HF) admission. We conducted a cross-sectional analysis of UK Biobank participants enrolled between 2006 and 2010. LTL was measured using quantitative polymerase chain reactions. Electronic health records were used to determine the incidence of SCD, coronary events, and HF admission. Cardiovascular measurements were made using cardiovascular magnetic resonance imaging and machine learning. The associations of LTL with SCD, coronary events, and HF admission and cardiac magnetic resonance imaging, electrocardiogram parameters of 33,043 and 19,554 participants were evaluated by multivariate regression. The median (interquartile range) follow-up period was 11.9 (11.2-12.6) years. Data was analyzed from January to May 2023. Among the 403,382 white participants without coronary artery disease or HF, 181,637 (45.0%) were male with a mean age of 57.1 years old. LTL was independently negatively associated with a risk of SCD (LTL third quartile vs first quartile: hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.72-0.92), coronary events (LTL third quartile vs first quartile: HR: 0.88, 95% CI: 0.84-0.92), and HF admission (LTL fourth quartile vs first quartile: HR: 0.84, 95% CI: 0.74-0.95). LTL was also independently positively associated with cardiac remodeling, specifically left ventricular mass index, left-ventricular-end systolic and diastolic volumes, mean left ventricular myocardial wall thickness, left ventricular stroke volume, and with electrocardiogram changes along the negative degree of T-axis. Cross-sectional study results showed that LTL was positively associated with heart size and cardiac function in middle age, but electrocardiography results did not show these associations, which could explain the negative association between LTL and risk of SCD, coronary events, and HF admission in UK Biobank participants.

Modifiable lifestyle factors and lifetime risk of atrial fibrillation: longitudinal data from the Korea NHIS-HealS and UK Biobank cohorts.

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.

European and US Guideline-Based Statin Eligibility, Genetically Predicted Coronary Artery Disease, and the Risk of Major Coronary Events.

BACKGROUND: A study was designed to investigate whether the coronary artery disease polygenic risk score (CAD-PRS) may guide lipid-lowering treatment initiation as well as deferral in primary prevention beyond established clinical risk scores. METHODS AND RESULTS: Participants were 311 799 individuals from the UK Biobank free of atherosclerotic cardiovascular disease, diabetes, chronic kidney disease, and lipid-lowering treatment at baseline. Participants were categorized as statin indicated, statin indication unclear, or statin not indicated as defined by the European and US guidelines on statin use. For a median of 11.9 (11.2-12.6) years, 8196 major coronary events developed. CAD-PRS added to European-Systematic Coronary Risk Evaluation 2 (European-SCORE2) and US-Pooled Cohort Equation (US-PCE) identified 18% and 12% of statin-indication-unclear individuals whose risk of major coronary events were the same as or higher than the average risk of statin-indicated individuals and 16% and 12% of statin-indicated individuals whose major coronary event risks were the same as or lower than the average risk of statin-indication-unclear individuals. For major coronary and atherosclerotic cardiovascular disease events, CAD-PRS improved C-statistics greater among statin-indicated or statin-indication-unclear than statin-not-indicated individuals. For atherosclerotic cardiovascular disease events, CAD-PRS added to the European evaluation and US equation resulted in a net reclassification improvement of 13.6% (95% CI, 11.8-15.5) and 14.7% (95% CI, 13.1-16.3) among statin-indicated, 10.8% (95% CI, 9.6-12.0) and 15.3% (95% CI, 13.2-17.5) among statin-indication-unclear, and 0.9% (95% CI, 0.6-1.3) and 3.6% (95% CI, 3.0-4.2) among statin-not-indicated individuals. CONCLUSIONS: CAD-PRS may guide statin initiation as well as deferral among statin-indication-unclear or statin-indicated individuals as defined by the European and US guidelines. CAD-PRS had little clinical utility among statin-not-indicated individuals.

Racial Differences in Ischemic and Hemorrhagic Stroke: An Ecological Epidemiological Study.

BACKGROUND: This study aimed to evaluate racial differences in the incidence of stroke by conducting an ecological epidemiological study using UK Biobank and Korean nationwide data. METHODS: This study used individual data from the Korean National Health Insurance Service-Health Screening and UK Biobank, which included participants who underwent health examinations between 2006 and 2010. We included 112,750 East Asians (50.7% men, mean age: 52.6 years) and 210,995 Caucasians (44.7% men, mean age: 55.0 years) who were not diagnosed with atrial fibrillation, cardiovascular diseases, chronic kidney disease, chronic obstructive pulmonary disease, or cancer. The primary outcome was defined as a composite of ischemic and hemorrhagic stroke. RESULTS: East Asians tended to have a lower body mass index (23.7 vs. 26.4 kg/m2, p < 0.001) and a higher proportion of participants who did not engage in moderate-to-vigorous physical activity (49.6% vs. 10.7%, p < 0.001) than Caucasians. During the follow-up, East Asians had higher 5-year incidence rates (presented as per 1,000 person-years) for primary outcome (1.73 vs. 0.50; IR ratio [IRR]: 3.48, 95% confidence interval [CI]: 3.13-3.88), ischemic stroke (1.23 vs. 0.33; IRR: 3.70, 95% CI: 3.25-4.21), hemorrhagic stroke (0.56 vs. 0.18; IRR: 3.20, 95% CI: 2.67-3.84), and atrial fibrillation-related stroke (0.19 vs. 0.09; IRR: 2.04, 95% CI: 1.55-2.68). CONCLUSION: Based on this ecological epidemiological study, racial differences in stroke incidence were robust to a variety of statistical analyses, regardless of the subtype. This suggests the need for region-specific approaches to stroke prevention.

Racial Differences in Bleeding Risk: An Ecological Epidemiological Study Comparing Korea and United Kingdom Subjects.

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.

Multimorbidity in atrial fibrillation for clinical implications using the Charlson Comorbidity Index.

BACKGROUND: Predicting survival in atrial fibrillation (AF) patients with comorbidities is challenging. This study aimed to assess multimorbidity in AF patients using the Charlson Comorbidity Index (CCI) and its clinical implications. METHODS: We analyzed 451,368 participants from the Korea National Health Insurance Service-Health Screening cohort (2002-2013) without prior AF diagnoses. Patients were categorized into new-onset AF and non-AF groups, with a high CCI defined as ≥4 points. Antithrombotic treatment and outcomes (all-cause death, stroke, major bleeding, and heart failure [HF] hospitalization) were evaluated over 9 years. RESULTS: In total, 9.5% of the enrolled patients had high CCI. During follow-up, 12,241 patients developed new-onset AF. Among AF patients, antiplatelet drug use increased significantly in those with high CCI (adjusted odds ratio [OR] 1.05, 95%confidence interval [CI] 1.02-1.08, P < .001). However, anticoagulants were significantly less prescribed in patients with high CCI (OR 0.97, 95%CI 0.95-0.99, P = .012). Incidence of adverse events (all-cause death, stroke, major bleeding, HF hospitalization) progressively increased in this order: low CCI without AF, high CCI without AF, low CCI with AF, and high CCI with AF (all P < .001). Furthermore, high CCI with AF had a significantly higher risk compared to low CCI without AF (all-cause death, adjusted hazard ratio [aHR] 2.52, 95% CI 2.37-2.68, P < .001; stroke, aHR 1.43, 95% CI 1.29-1.58, P < .001; major bleeding, aHR 1.14, 95% CI 1.04-1.26, P = .007; HF hospitalization, aHR 4.75, 95% CI 4.03-5.59, P < .001). CONCLUSIONS: High CCI predicted increased antiplatelet use and reduced oral anticoagulant prescription. AF was associated with higher risks of all-cause death, stroke, major bleeding, and HF hospitalization compared to high CCI.

Association between Obesity and Heart Failure and Related Atrial Fibrillation: Patient-Level Data Comparisons of Two Cohort Studies.

PURPOSE: Heart failure (HF) and atrial fibrillation (AF) frequently coexist, with over 50% patients with HF having AF, while one-third of those with AF develop HF. Differences in obesity-mediated association between HF and HF-related AF among Asians and Europeans were evaluated. MATERIALS AND METHODS: Using the Korean National Health Insurance Service-Health Screening (K-NHIS-HealS) cohort and the UK Biobank, we included 394801 Korean and 476883 UK adults, respectively aged 40-70 years. The incidence and risk of HF were evaluated based on body mass index (BMI). RESULTS: The proportion of obese individuals was significantly higher in the UK Biobank cohort than in the K-NHIS-HealS cohort (24.2% vs. 2.7%, p<0.001). The incidence of HF and HF-related AF was higher among the obese in the UK than in Korea. The risk of HF was higher among the British than in Koreans, with adjusted hazard ratios of 1.82 [95% confidence interval (CI), 1.30-2.55] in K-NHIS-HealS and 2.00 (95% CI, 1.69-2.37) in UK Biobank in obese participants (p for interaction <0.001). A 5-unit increase in BMI was associated with a 44% greater risk of HF-related AF in the UK Biobank cohort (p<0.001) but not in the K-NHIS-HealS cohort (p=0.277). CONCLUSION: Obesity was associated with an increased risk of HF and HF-related AF in both Korean and UK populations. The higher incidence in the UK population was likely due to the higher proportion of obese individuals.

Association Between the Combined Effects of Physical Activity Intensity and Particulate Matter and All-Cause Mortality in Older Adults.

OBJECTIVE: To investigate the association between the combined effects of physical activity (PA) intensity and particulate matter ≤10 µm in diameter (PM10) and mortality in older adults. METHODS: This nationwide cohort study included older adults without chronic heart or lung disease who engaged in regular PA. Physical activity was assessed by a standardized, self-reported questionnaire that asked the usual frequency of PA sessions with low (LPA), moderate (MPA), or vigorous intensity (VPA). Each participant's annual average cumulative PM10 was categorized as low to moderate and high PM10 on the basis of a cutoff value of 90th percentile. RESULTS: A total of 81,326 participants (median follow-up, 45 months) were included. For participants engaged in MPA or VPA sessions, every 10% increase in the proportion of VPA to total PA sessions resulted in a 4.9% (95% CI, 1.0% to 9.0%; P=.014) increased and 2.8% (95% CI, -5.0% to -0.5%; P=.018) decreased risk of mortality for those exposed to high and low to moderate PM10, respectively (Pinteraction, <.001). For participants engaged only in LPA or MPA sessions, every 10% increase in the proportion of MPA to total PA sessions resulted in a 4.8% (95% CI, -8.9% to -0.4%; P=.031) and 2.3% (95% CI, -4.2% to -0.3%; P=.023) decreased risk of mortality for those exposed to high and low to moderate PM10, respectively (Pinteraction, .096). CONCLUSION: We found that for the same level of total PA, MPA was associated with delayed mortality whereas VPA was associated with hastened mortality of older adults in high levels of PM10.

Association of obesity with incident atrial fibrillation in Korea and the United Kingdom.

Obesity has been linked to atrial fibrillation (AF) burden and severity, and epidemiological studies suggest that AF is more prevalent in whites than Asian. We aimed to investigate whether obesity mediates associations with AF in Europe and Asia using patient-level data comparisons of two cohort studies. Using Korean National Health Insurance Service's Health Screening (NHIS-HealS) and U.K. Biobank data, we included 401,206 Korean and 477,926 British aged 40-70 years without previous AF who received check-ups. The incidence and risk of AF were evaluated regarding different body mass index (BMI) values. The obese proportion (BMI ≥ 30.0 kg/m2, 2.8% vs. 24.3%, P < 0.001) was higher in the U.K. than the Korean. In the Korean and U.K. cohort, the age- and sex-adjusted incidence rates of AF were 4.97 and 6.54 per 1000 person-years among obese individuals. Compared to Koreans, the risk of AF was higher in the British population, with adjusted hazard ratios of 1.41 (Korea, 95% CI 1.26-1.58) and 1.68 (UK, 95% CI 1.54-1.82) in obese participants (P for interaction < 0.05). Obesity was associated with AF in both populations. British subjects had a greater incidence of AF related to the high proportion of obese individuals, especially participants in the obesity category, the risk of AF also increased.

Associations of high-normal blood pressure and impaired fasting glucose with atrial fibrillation.

OBJECTIVE: To investigate the association of high-normal blood pressure (BP) and impaired fasting glucose (IFG) with the risk of atrial fibrillation (AF) in two cohorts. METHODS: The Korean National Health Insurance Service-Health Screening (K-NHIS-HealS, 2002-2003, follow-up until 2013) Study and the UK Biobank (2007-2010, follow-up until 2021) were evaluated. We used Cox proportional hazards regression models to evaluate the associations of high-normal BP and IFG with incident AF. RESULTS: In the K-NHIS-HealS and the UK Biobank, 2346 and 5314 incident AF events were recorded during the mean follow-up of 7.4 and 11.8 years. The adjusted HRs (95% CIs) for AF in the Korean and UK cohorts were 1.11 (1.02 to 1.21) and 1.07 (1.01 to 1.13) in individuals with high-normal BP; and 1.14 (1.04 to 1.25) and 1.10 (1.01 to 1.20) in individuals with IFG, respectively. The AF risk showed a dose-response relationship with BP and fasting blood glucose level. The risk of incident AF was increased by the combination of high-normal BP and IFG. CONCLUSIONS: In healthy individuals, high-normal BP and IFG were important risk factors for AF. When high-normal BP and IFG were combined, the risk of new-onset AF was significantly increased. These findings may suggest that lifestyle interventions for high-normal BP and IFG should be considered to reduce the risk of AF.

Association of changes in cardiovascular health levels with incident cardiovascular events and mortality in patients with atrial fibrillation.

BACKGROUND: Risk factor management is crucial in the management of atrial fibrillation (AF). We investigated the association of changes in cardiovascular health (CVH) levels after AF diagnosis with incident cardiovascular events and mortality. METHODS: From the Korea National Health Insurance Service database, 76,628 patients newly diagnosed with AF (2005-2015) with information on health examinations before and after AF diagnosis were assessed. According to the change in the 12-point CVH score before and after AF diagnosis, patients were stratified into four groups: consistently low (score 0-7 to 0-7), high-to-low (8-12 to 0-7), low-to-high (0-7 to 8-12), and consistently high (8-12 to 8-12) CVH levels. Risks of cardiovascular events and death were analyzed using weighted Cox regression models with inverse probability of treatment weighting (IPTW) for balance across study groups. RESULTS: The mean age of study participants was 58.3 years, 50,285 were men (63.1%), and the mean follow-up was 5.5 years. After IPTW, low-to-high (hazard ratio [95% confidence interval], 0.83 [0.76-0.92]) and consistently high (0.80 [0.74-0.87]) CVH levels were associated with a lower risk of ischemic stroke than consistently low CVH. Low-to-high (0.66 [0.52-0.84]) and consistently high (0.52 [0.42-0.64]) CVH levels were associated with a lower risk of acute myocardial infarction. Maintaining high CVH was associated with reduced risks of heart failure hospitalization (0.85 [0.75-0.95]) and all-cause death (0.82 [0.77-0.88]), respectively, compared with consistently low CVH. CONCLUSIONS: Improving CVH levels and maintaining high CVH levels after AF diagnosis is associated with lower risks of subsequent cardiovascular events and mortality.

Sex Difference in Effectiveness of Early Rhythm- over Rate-Control in Patients with Atrial Fibrillation.

Background: This study aimed to investigate the associations between sex and the relative effect of rhythm control over rate control in patients with atrial fibrillation. Methods: We used the National Health Insurance Service database to select patients treated for atrial fibrillation within one year after diagnosis. The primary composite outcome comprised cardiovascular death, ischemic stroke, heart failure hospitalization, or acute myocardial infarction. Results: During the mean follow-up (4.9 ± 3.2 years), the benefit of rhythm control over rate control on the primary composite outcome became statistically insignificant after 3 months from atrial fibrillation diagnosis in women while remained steadily until 12 months in men. The risk of primary composite outcome for rhythm control was lower than that for rate control in both sexes if it was initiated within 6 months (men: HR = 0.86, 95%CI = 0.79-0.94; women: HR = 0.85, 95%CI = 0.78-0.93; P for interaction = 0.844). However, there was significant interaction between sex and the relative effect of rhythm control if it was initiated after 6 months (men: HR = 0.72, 95%CI = 0.52-0.99; women: HR = 1.32, 95%CI = 0.92-1.88; P for interaction = 0.018). Conclusion: Rhythm control resulted in lower risk of primary composite outcome than rate control in both sexes; however, the treatment initiation at an earlier stage might be considered in women.

Association of cardiovascular health with the risk of dementia in older adults.

It has been becoming important to identify modifiable risk factors to prevent dementia. We investigated the association of individual and combined cardiovascular health (CVH) on dementia risk in older adults. From the National Health Insurance Service of Korea-Senior database, 191,013 participants aged ≥ 65 years without prior dementia or cerebrovascular diseases who had check-ups between 2004 and 2012 were assessed. Participants were stratified into three groups according to the number of optimal levels of CVH (low, 0-2; moderate, 3-4; and high CVH status, 5-6) and grouped by levels of individual CVH metrics, the number of optimal CVH metrics, and the CVH score. Over a median follow-up of 6.2 years, 34,872 participants were diagnosed with dementia. Compared with low CVH status, moderate and high CVH status were associated with a decreased risk of dementia (hazard ratio [95% confidence interval], 0.91 [0.89-0.92] for moderate; 0.78 [0.75-0.80] for high CVH status) including Alzheimer's and vascular dementia. The risk of dementia decreased with an increase in the number of optimal CVH metrics (0.94 [0.93-0.94] per additional optimal metric) and with an increase in the CVH score (0.93 [0.93-0.94] per 1-point increase). After censoring for stroke, the association of CVH metrics with dementia risk was consistently observed. Among individual metrics, physical activity had the strongest association with the risk of dementia. In an older Asian population without prior dementia or cerebrovascular disease, a consistent relationship was observed between the improvement of a composite metric of CVH and the reduced risk of dementia.

Early Rhythm Control Therapy for Atrial Fibrillation in Low-Risk Patients : A Nationwide Propensity Score-Weighted Study.

BACKGROUND: Rhythm control is associated with lower risk for adverse cardiovascular outcomes compared with usual care among patients recently diagnosed with atrial fibrillation (AF) with a CHA2DS2-VASc score of approximately 2 or greater in EAST-AFNET 4 (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial). OBJECTIVE: To investigate whether the results can be generalized to patients with low stroke risk. DESIGN: Population-based cohort study. SETTING: Nationwide claims database of the Korean National Health Insurance Service. PARTICIPANTS: 54 216 patients with AF having early rhythm control (antiarrhythmic drugs or ablation) or rate control therapy that was initiated within 1 year of the AF diagnosis. MEASUREMENTS: The effect of early rhythm control on the primary composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared between eligible and ineligible patients for EAST-AFNET 4 (CHA2DS2-VASc score, approximately 0 to 1) using propensity overlap weighting. RESULTS: In total, 37 557 study participants (69.3%) were eligible for the trial (median age, 70 years; median CHA2DS2-VASc score, 4), among whom early rhythm control was associated with lower risk for the primary composite outcome than rate control (hazard ratio, 0.86 [95% CI, 0.81 to 0.92]). Among the 16 659 low-risk patients (30.7%) who did not meet the inclusion criteria (median age, 54 years; median CHA2DS2-VASc score, 1), early rhythm control was consistently associated with lower risk for the primary outcome (hazard ratio, 0.81 [CI, 0.66 to 0.98]). No significant differences in safety outcomes were found between the rhythm and rate control strategies regardless of trial eligibility. LIMITATION: Residual confounding. CONCLUSION: In routine clinical practice, the beneficial association between early rhythm control and cardiovascular complications was consistent among low-risk patients regardless of trial eligibility. PRIMARY FUNDING SOURCE: The Ministry of Health and Welfare and the Ministry of Food and Drug Safety, Republic of Korea.

Age and Outcomes of Early Rhythm Control in Patients With Atrial Fibrillation: Nationwide Cohort Study.

OBJECTIVES: This study sought to investigate whether the effects of early rhythm control differ according to age. BACKGROUND: Rhythm control, compared with usual care among patients recently diagnosed with atrial fibrillation (AF), was found to be associated with a lower risk of adverse cardiovascular outcomes. It is unclear whether the results can be generalized for older adults. METHODS: This retrospective population-based cohort study included 31,220 patients with AF, from the Korean National Health Insurance Service database, undergoing rhythm control (antiarrhythmic drugs or ablation) or rate control therapy, initiated within 1 year of AF diagnosis. A composite outcome of cardiovascular death, ischemic stroke, hospitalization for heart failure, or myocardial infarction was compared in subgroups stratified by age. RESULTS: Compared with rate control, early rhythm control was associated with a lower risk of the primary composite outcome in patients <75 years of age (HR: 0.80; 95% CI: 0.72-0.88). The protective association between early rhythm control and cardiovascular outcomes exhibited a linear decrease with advancing age, with declined benefits in patients ≥75 years of age (HR: 0.94; 95% CI: 0.87-1.03; Pinteraction = 0.045). Trends toward lower risks of ischemic stroke (HR: 0.78; 95% CI: 0.67-0.90) and acute myocardial infarction (HR: 0.63; 95% CI: 0.41-0.97) were observed in the older adults. No significant differences in safety outcomes were found across different ages. CONCLUSIONS: The beneficial association of early rhythm control with cardiovascular outcomes was attenuated with increasing age, with the larger benefits in younger patients <75 years of age. No differences were found by age in treatment-related safety outcomes.

Association between exercise habit changes and mortality following a cardiovascular event.

OBJECTIVE: To investigate the associations between exercise habit changes following an incident cardiovascular event and mortality in older adults. METHODS: We analysed the relationship between exercise habit change and all-cause, cardiovascular and non-cardiovascular deaths in adults aged ≥60 years between 2003 and 2012 who underwent two consecutive health examinations within 2 years before and after diagnosis of cardiovascular disease (CVD). They were categorised into four groups according to exercise habit changes: persistent non-exercisers, exercise dropouts, new exercisers and exercise maintainers. Differences in baseline characteristics were adjusted using inverse probability of treatment weighting. RESULTS: Of 6076 participants, the median age was 72 (IQR 69-76) years and men accounted for 50.6%. Compared with persistent non-exercisers (incidence rate (IR) 4.8 per 100 person-years), new exercisers (IR 3.5, HR 0.73, 95% CI 0.58 to 0.91) and exercise maintainers (IR 2.9, HR 0.53, 95% CI 0.38 to 0.73) were associated with reduced risk of all-cause death. The rate of non-cardiovascular death was significantly lower in new exercisers (IR 2.3, HR 0.73, 95% CI 0.56 to 0.95) and exercise maintainers (IR 2.3, HR 0.61, 95% CI 0.42 to 0.90) than in persistent non-exercisers (IR 3.2). Also, trends towards reduced cardiovascular death in new exercisers and exercise maintainers were observed (p value for trend <0.001). CONCLUSIONS: More virtuous exercise trajectories in older adults with CVD are associated with lower mortality rates. Our results support public health recommendations for older adults with CVD to perform physical activity.

Impact of Physical Activity on All-Cause Mortality According to Specific Cardiovascular Disease.

BACKGROUND: Patients with cardiovascular disease (CVD) tend to have higher mortality rates and reduced physical activity (PA). We aimed to evaluate the effect of PA on mortality in older adults with specific CVD. METHODS: We enrolled 68,223 participants (n = 23,871 with CVD, n = 44,352 without CVD) aged ≥65 years with available physical activity data between 2005 and 2012 from the Korean National Health Insurance Service of Korea-Senior database. CVD was defined as a history of ischemic stroke, transient ischemic attack, heart failure, myocardial infarction, and peripheral artery disease. RESULTS: Patients with CVD were older than those without CVD. Compared with the sedentary group, the physically active groups with and without CVD had a lower incidence and risk of all-cause death during a median follow up period of 42 (interquartile range 30-51) months. A 500 metabolic equivalent task-min/week increase in PA resulted in an 11% and 16% reduction in the risk of mortality in the non-CVD and CVD groups, respectively. With regard to specific CVDs, the risk of mortality progressively reduced with increasing PA in patients with heart failure or myocardial infarction. However, the reduction reached a plateau in patients with stroke or peripheral artery disease, but was significantly greater in patients with stroke (20% vs. without stoke, 11%, Pint = 0.006) or heart failure (13% vs. without heart failure, 11%; Pint = 0.045). CONCLUSIONS: PA was associated with a reduced risk of all-cause mortality in older adults with and without CVD. The benefits of PA in patients with CVD, especially patients with stroke or heart failure, were greater than those without.

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

BACKGROUND: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF. METHODS: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately. RESULTS: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3. CONCLUSIONS: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.