Associations of hypertension burden on subsequent dementia: a population-based cohort study

In this nationwide cohort study, we assessed the effects of hypertension burden and blood pressure (BP) control on dementia in different age subgroups. From the Korean National Health Insurance Service-Health Screening cohort from January 1, 2005 to December 31, 2013, we enrolled 428,976 subjects aged 40-79 years without previous diagnosis of dementia or stroke. During a mean follow-up of 7.3 ± 1.5 years, 9435 (2.2%) were diagnosed with dementia. Per 10 mmHg increase in systolic BP (SBP), risk of dementia was increased by 22% (95% confidence interval [CI] 1.15-1.30) in subjects aged 40-59 years and 8% (95% CI 1.04-1.11) in subjects aged 60-69 years. No significant associations were observed in subjects aged ≥ 70 years. Among subjects aged 40-59 years, both vascular and Alzheimer's dementia risks were increased with increasing SBP. Increasing hypertension burden (proportion of days with increased BP) was associated with higher dementia risk (hazard ratio [HR] 1.09 per 10% increase, 95% CI 1.08-1.10). Among patients with baseline SBP ≥ 140 mmHg, optimal follow-up SBP (120-139 mmHg) was associated with decreased dementia risk (HR 0.69, 95% CI 0.50-0.95). Hypertension burden was associated with higher risks of dementia. Adequate BP control was associated with lower risk of dementia in individuals aged < 70 years.ope

Changes in Cardiovascular Risk Factors and Cardiovascular Events in the Elderly Population

Background This study examines changes in the ideal cardiovascular health (CVH) status and whether these changes are associated with incident cardiovascular disease (CVD) and mortality in the elderly Asian population. Methods and Results In the Korea National Health Insurance Service-Senior cohort aged ≥60 years, 208 673 participants without prior CVD, including 109 431 who showed changes in CVH status, were assessed. The association of the changes in cardiovascular risk factors with incident CVD was assessed from 2004 to 2014 in the elderly (aged 60-74 years) and very elderly (≥75 years) groups. During the follow-up period (7.1 years for CVD and 7.2 years for mortality), 19 429 incident CVD events and 24 225 deaths occurred. In both the elderly and very elderly participants, higher CVH status resulted in a lower risk of CVD and mortality. In the very elderly participants, compared with consistently low CVH, consistently high CVH (subhazard ratio, 0.41; 95% CI, 0.23-0.73) was associated with a lower risk of CVD. This trend was consistently observed in the elderly population. In the very elderly participants, total cholesterol level was not informative enough for the prediction of CVD events. In both the elderly and very elderly groups, body mass index and total cholesterol were not informative enough for the prediction of all-cause mortality. Conclusions In both the elderly and very elderly Asian populations without CVD, a consistent relationship was observed between the improvement of a composite metric of CVH and the reduced risk of CVD. Body mass index and total cholesterol were not informative enough for the prediction of all-cause mortality in both the elderly and very elderly groups.ope

Changes in Cardiovascular Health Status and Risk of Sudden Cardiac Death in Older Adults

Purpose: Cardiovascular health (CVH) status is associated with several cardiovascular outcomes; however, correlations between changes in CVH status and risk of sudden cardiac death (SCD) are unknown. We aimed to evaluate associations between changes in CVH status and risk of SCD and all-cause death in older adults. Materials and methods: We used data from the Korea National Health Insurance Service-Senior cohort database (2005-2012). Six metrics from the American Heart Association (smoking, body mass index, physical activity, blood pressure, total cholesterol, and fasting blood glucose) were used to calculate CVH scores. Changes in CVH status between two health checkups were categorized as low to low, low to high, high to low, and high to high. Results: We included 105200 patients whose CVH status for an initial and follow-up health checkup (2-year interval) was available. During a median of 5.2 years of follow-up after a second health checkup, 688 SCDs occurred. Compared to patients with a persistent low CVH status, those with a consistently high CVH status had a reduced risk of SCD [adjusted hazard ratio (HR), 0.69; 95% confidence interval (CI), 0.56-0.86] and all-cause death (adjusted HR, 0.74; 95% CI, 0.69-0.78). The risk of all-cause death followed similar trends. However, an inconsistent linear relationship was observed for changes in CVH status and the risk of SCD, but not of all-cause death. Conclusion: Maintaining a high CVH status was associated with future risks of SCD and all-cause death among an older adult population.ope

Social Inequalities of Oral Anticoagulation After the Introduction of Non-Vitamin K Antagonists in Patients With Atrial Fibrillation

Background and objectives: Nationwide social inequalities of oral anticoagulation (OAC) usage after the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) have not been well identified in patients with atrial fibrillation (AF). This study assessed overall rate and social inequalities of OAC usage after the introduction of NOAC in Korea. Methods: Between January 2002 and December 2016, we identified 888,540 patients with AF in the Korea National Health Insurance system database. The change of OAC rate in different medical systems after the introduction of NOAC were evaluated. Results: In all population, overall OAC use increased from 13.2% to 23.4% (p for trend <0.001), and NOAC use increased from 0% to 14.6% (p for trend <0.001). Compared with pre-reimbursement (0.48%), the annual increase of OAC use was significantly higher after partial (1.16%, p<0.001), and full reimbursement of OAC (3.72%, p<0.001). Full reimbursement of NOAC (adjusted odds ratio, 2.10; 95% confidence interval, 2.04-2.15) was independently associated with higher OAC use. However, the difference of overall OAC usage between tertiary referral hospitals and nursing or public health centers increased from 17.9% in 2010 to 36.8% in 2016. Moreover, usage rate of NOAC was significantly different among different medical systems from 37.2% at the tertiary referral hospital and 5.5% at nursing or public health centers. Conclusions: Introduction of NOACs in routine practice for stroke prevention in AF was associated with improved rates of overall OAC use. However, significant practice-level variations in OAC and NOAC use remain producing social inequalities of OAC despite full reimbursement.ope

Comparative Effectiveness of Early Rhythm Control Versus Rate Control for Cardiovascular Outcomes in Patients With Atrial Fibrillation

Background Rhythm control is associated with better cardiovascular outcomes than usual care among patients with recently diagnosed atrial fibrillation (AF). This study investigated the effects of rhythm control compared with rate control on the incidence of stroke, heart failure, myocardial infarction, and cardiovascular death stratified by timing of treatment initiation. Methods and Results We conducted a retrospective population-based cohort study including 22 635 patients with AF newly treated with rhythm control (antiarrhythmic drugs or ablation) or rate control in 2011 to 2015 from the Korean National Health Insurance Service database. Propensity overlap weighting was used. Compared with rate control, rhythm control initiated within 1 year of AF diagnosis decreased the risk of stroke. The point estimates for rhythm control initiated at selected time points after AF diagnosis are as follows: 6 months (hazard ratio [HR], 0.76; 95% CI, 0.66-0.87), 1 year (HR, 0.78; 95% CI, 0.66-0.93), and 5 years (HR, 1.00; 95% CI, 0.45-2.24). The initiation of rhythm control within 6 months of AF diagnosis reduced the risk of hospitalization for heart failure: 6 months (HR, 0.84; 95% CI, 0.74-0.95), 1 year (HR, 0.96; 95% CI, 0.82-1.13), and 5 years (HR, 2.88; 95% CI, 1.34-6.17). The risks of myocardial infarction and cardiovascular death did not differ between rhythm and rate control regardless of treatment timing. Conclusions Early initiation of rhythm control was associated with a lower risk of stroke and heart failure-related admission than rate control in patients with recently diagnosed AF. The effects were attenuated as initiating the rhythm control treatment later.ope

The Effect of Integrated Care Management on Dementia in Atrial Fibrillation

Clinical outcomes of patients with atrial fibrillation (AF) can be improved by an integrated care approach. We analyzed whether adherence with the AF Better Care (ABC) pathway for integrated care management would reduce the risk of dementia in a nationwide AF cohort. Using the National Health Insurance Service database of Korea, 228,026 non-valvular AF patients were retrospectively evaluated between 2005 and 2015. Patients meeting all criteria of the ABC pathway were classified as the "ABC" group and those not classified as the "non-ABC" group. During a median (25th, 75th percentiles) follow-up of 6.0 (3.3, 9.5) years, the ABC group had lower rates and risk of overall dementia (0.17 vs. 1.11 per 100 person-years, p < 0.001; hazard ratio (HR) 0.80; 95% CI 0.73-0.87) and both Alzheimer's (HR 0.79, 95% CI 0.71-0.88) and vascular dementia (HR 0.76, 95% CI 0.59-0.98) than the non-ABC group. The stratified analysis showed that the ABC pathway reduced the risk of dementia regardless of sex, comorbidities, and in patients with high stroke risk. Adherence with the ABC pathway is associated with a reduced risk of dementia in AF patients. Due to the high medical burden of AF, it is necessary to implement integrated AF management to reduce the risk of dementia.ope

Label Adherence of Direct Oral Anticoagulants Dosing and Clinical Outcomes in Patients With Atrial Fibrillation

Background Dose adjustment of non-vitamin K antagonist oral anticoagulants (NOACs) is indicated in some patients with atrial fibrillation (AF), based on selected patient factors or concomitant medications. We assessed the frequency of label adherence of NOAC dosing among AF patients and the associations between off-label NOAC dosing and clinical outcomes. Methods and Results We evaluated 53 649 AF patients treated with an NOAC using Korean National Health Insurance Service database during the period from 2013 to 2016. NOAC doses were classified as either underdosed or overdosed, consistent with Korea Food and Drug Administration labeling. Cox proportional hazards regression was performed to investigate the effectiveness and safety outcomes including stroke or systemic embolism, major bleeding, and all-cause mortality. Overall, 16 757 NOAC-treated patients (31.2%) were underdosed, 4492 were overdosed (8.4%), and 32 400 (60.4%) were dosed appropriately according to drug labeling. Compared with patients with label adherence, those who were underdosed or overdosed were older (aged 71±8 and 75±7 years versus 70±9 years, respectively; P<0.001) and had higher CHA2DS2-VASc scores (4.6±1.7 and 5.3±1.7 versus 4.5±1.8, respectively; P<0.001). NOAC overdosing was associated with increased risk for stroke or systemic embolism (5.76 versus 4.03 events/100 patient-years, P<0.001), major bleeding (4.77 versus 2.94 events/100 patient-years, P<0.001), and all-cause mortality (5.43 versus 3.05 events/100 patient-years, P<0.001) compared with label-adherent use. Conclusions In real-world practice, a significant proportion (almost 2 in 5) of AF patients received NOAC doses inconsistent with drug labeling. NOAC overdosing is associated with worse clinical outcomes in Asian AF patients.ope

What Is the Ideal Blood Pressure Threshold for the Prevention of Atrial Fibrillation in Elderly General Population?

Intensive blood pressure (BP) lowering in patients with hypertension at increased risk of cardiovascular disease has been associated with a lowered risk of incident atrial fibrillation (AF). It is uncertain whether maintaining the optimal BP levels can prevent AF in the general elderly population. We included 115,866 participants without AF in the Korea National Health Insurance Service-Senior (≥60 years) cohort from 2002 to 2013. We compared the influence of BP on the occurrence of new-onset AF between octogenarians (≥80 years) and non-octogenarians (<80 years) subjects. With up to 6.7 ± 1.7 years of follow-up, 4393 incident AF cases occurred. After multivariable adjustment for potentially confounding clinical covariates, the risk of AF in non-octogenarians was significantly higher in subjects with BP levels of <120/<80 and ≥140/90 mm Hg, with hazard ratios of 1.15 (95% confidence interval (CI), 1.03-1.28; p < 0.001) and 1.14 (95% CI, 1.04-1.26; p < 0.001), compared to the optimal BP levels (120-129/<80 mm Hg). In octogenarians, the optimal BP range was 130-139/80-89 mm Hg, higher than in non-octogenarians. A U-shaped relationship for the development of incident AF was evident in non-octogenarians, and BP levels of 120-129/<80 mm Hg were associated the lowest risk of incident AF. Compared to non-octogenarians, the lowest risk of AF was associated with higher BP levels of 130-139/80-89 mm Hg amongst octogenarians.ope

Association of Physical Activity Level With Risk of Dementia in a Nationwide Cohort in Korea

Importance: Current guidelines recommend 500 to 999 metabolic equivalent (MET)-minutes per week (MET-min/wk) of regular physical activity. However, evidence regarding the association between light-intensity physical activity (LPA) and dementia in older adults is inconsistent. Objective: To assess the association between physical activity and new-onset dementia, focusing on the dose-response association between physical activity and dementia and the association of LPA with the incidence of dementia. Design, setting, and participants: For this nationwide retrospective cohort study, we analyzed 62 286 participants aged 65 years or older without preexisting dementia who had available health checkup data from the Korean National Health Insurance Service database from January 2009 to December 2012. Participants were followed up until December 31, 2013, and data analysis was performed from July 2020 to January 2021. Exposures: Physical activity level was assessed using a standardized, self-reported questionnaire at baseline. Physical activity-related energy expenditure (in MET-min/wk) was calculated by summing the product of frequency, intensity, and duration. Main outcomes and measures: Incidence of dementia. Incidence rates were calculated by dividing the number of events by the person-time at risk (presented as the incidence per 1000 person-years). Hazard ratios (HRs) and 95% CIs for dementia were analyzed according to physical activity level. Competing risk regression was performed by using the Fine-Gray subdistribution hazard model, with mortality as the competing risk for dementia events. Multivariable regression models were constructed with adjustment for various patient characteristics. Incident dementia occurring 2 years after enrollment was assessed, and separate analyses included all follow-up periods. Restricted cubic spline curves were used to examine the association of continuous values of physical activity with dementia. Results: Among 62 286 participants, 60.4% were women, and the mean (SD) age was 73.2 (5.3) years. During a median follow-up of 42 months, 3757 participants (6.0%) developed dementia, and the overall incidence was 21.6 per 1000 person-years. Compared with inactive individuals (0 MET-min/wk), insufficiently active (1-499 MET-min/wk; mean, 284 MET-min/wk), active (500-999 MET-min/wk; mean, 675 MET-min/wk), and highly active participants (≥1000 MET-min/wk; mean, 1627 MET-min/wk) showed 10% (adjusted hazard ratio [HR], 0.90; 95% CI, 0.81-0.99), 20% (adjusted HR, 0.80; 95% CI, 0.71-0.92), and 28% (adjusted HR, 0.72; 95% CI, 0.60-0.83) reduced dementia risk, respectively. Thus, a progressive decrease in the adjusted HR of dementia was associated with increasing physical activity level, and a restricted cubic spline curve showed that this association started with a low amount of total physical activity. This association was consistent regardless of age, sex, and other comorbidities or after censoring for stroke. Compared with total sedentary behavior, even a low amount of LPA (1-299 MET-min/wk; mean, 189 MET-min/wk) was associated with reduced dementia risk (adjusted HR, 0.86; 95% CI, 0.74-0.99). Conclusions and relevance: In older adults, an increased physical activity level, including a low amount of LPA, was associated with a reduced risk of dementia. Promotion of LPA might reduce the risk of dementia in older adults.ope

Catheter Ablation Improves Mortality and Other Outcomes in Real-World Patients With Atrial Fibrillation

Background It is still controversial whether catheter ablation for atrial fibrillation (AF) improves survival and other outcomes in patients with AF. This study evaluated whether ablation reduces death and other events in nationwide real-world Asian patients with AF. Methods and Results From the Korean National Health Insurance Service database, 194 928 adult patients (aged ≥18 years) with newly diagnosed AF were treated with ablation or medical therapy (antiarrhythmic or rate control drugs) between January 1, 2005, and December 1, 2015. Among these patients, this study included 9185 with ablation and 18 770 with medical therapy. The time at risk was counted from the first medical therapy, and ablation was analyzed as a time-varying covariate. Inverse probability of treatment weighting was used to correct for differences between the groups. After weighting, the 2 cohorts had similar background characteristics. During a median (25th, 75th percentiles) follow-up of 43 (19, 81) months, ablation of AF was associated with lower incidence and risk of composite outcome, including death, heart failure admission, and stroke/systemic embolism (2.5 and 6.4 per 100 person-years, respectively; hazard ratio [HR], 0.47; 95% CI, 0.43-0.52; P<0.001), all-cause death (1.0 and 3.6 per 100 person-years; HR, 0.41; 95% CI, 0.36-0.47; P<0.001), heart failure admission (0.7 and 1.9 per 100 person-years; HR, 0.43; 95% CI, 0.37-0.50), and ischemic stroke/systemic embolism (1.1 and 2.8 per 100 person-years; HR, 0.39; 95% CI, 0.34-0.44) than medical therapy. Conclusions Ablation may be associated with lower risk of death, heart failure admission, and ischemic stroke/systemic embolism in real-world Asian patients with AF.ope