Increasing trends in hospital care burden of atrial fibrillation in Korea, 2006 through 2015

ObjectiveTemporal changes in the healthcare burden of atrial fibrillation (AF) are less well known in rapidly ageing Asian countries. We examined trends in hospitalisations, costs, treatment patterns and outcomes related to AF in Korea.MethodsUsing the National Health Insurance Service (NHIS) database involving the entire adult Korean population (n=41 701 269 in 2015), we analysed a nationwide AF cohort representing 931 138 patients with AF. We studied all hospitalisations due to AF from 2006 to 2015.ResultsOverall, hospitalisations for AF increased by 420% from 767 to 3986 per 1 million Korean population from 2006 to 2015. Most admissions occurred in patients aged ≥70 years, and the most frequent coexisting conditions were hypertension, heart failure and chronic obstructive pulmonary disease. Hospitalisations mainly due to major bleeding and AF control increased, whereas hospitalisations mainly due to ischaemic stroke and myocardial infarction decreased. The total cost of care increased even after adjustment for inflation from €68.4 million in 2006 to €388.4 million in 2015, equivalent to 0.78% of the Korean NHIS total expenditure. Overall in-hospital mortality decreased from 7.5% in 2006 to 4.3% in 2015. The in-hospital mortality was highest in patients ≥80 years of age (7.7%) and in patients with chronic kidney disease (7.4%).ConclusionsAF hospitalisations have increased exponentially over the past 10 years in Korea, in association with an increase in comorbid chronic diseases. Mortality associated with AF hospitalisations decreased during the last decade, but hospitalisation costs have markedly increased.</jats:sec

Association of proteinuria and hypertension with incident atrial fibrillation in an elderly population: nationwide data from a community-based elderly cohort

ObjectiveThe excess risk of atrial fibrillation in relation to the presence of proteinuria associated with hypertension has not been well elucidated. We aimed to determine the effect of hypertension and/or proteinuria on the incidence of atrial fibrillation. Second, we evaluated whether the associations with temporal changes in proteinuria status on the incidence of atrial fibrillation.Methods and resultsA total of 85 434 participants with hypertension and 125 912 participants without hypertension with age at least 60 years from the Korea National Health Insurance Service-Senior cohort were included. Amongst controls (participants without proteinuria and hypertension), hypertension only, proteinuria only, and hypertension with proteinuria groups, the adjusted incidences of atrial fibrillation were 0.51, 0.69. 0.78 and 0.99 per 100 person-years, respectively after inverse probability of treatment weighting. Compared with controls, the weighted risks of atrial fibrillation in the hypertension only, proteinuria only and hypertension with proteinuria groups were increased by 37% (hazard ratio 1.37, 95% confidence interval, CI 1.30-1.44, P = 0.001), 55% (hazard ratio 1.55, 95% CI 1.28-1.88, P ConclusionIn conclusion, hypertension and/or proteinuria were associated with increased risk of atrial fibrillation, with the greatest risks when both are present. Proteinuria could be a useful factor for predicting atrial fibrillation development

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

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

BackgroundPatients 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.MethodsWe 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.ResultsPatients 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).ConclusionsPA 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

Impact of frailty on early rhythm control outcomes in older adults with atrial fibrillation: A nationwide cohort study

PurposeRhythm-control therapy administered early following the initial diagnosis of atrial fibrillation (AF) has superior cardiovascular outcomes compared to rate-control therapy. Frailty is a key factor in identifying older patients’ potential for improvement after rhythm-control therapy. This study evaluated whether frailty affects the outcome of early rhythm-control therapy in older patients with AF.MethodsFrom the Korean National Health Insurance Service database (2005–2015), we collected 20,611 populations aged ≥65 years undergoing rhythm- or rate-control therapy initiated within 1 year of AF diagnosis. Participants were emulated by the EAST-AFNET4 trial, and stratified into non-frail, moderately frail, and highly frail groups based on the hospital frailty risk score (HFRS). A composite outcome of cardiovascular-related mortality, myocardial infarction, hospitalization for heart failure, and ischemic stroke was compared between rhythm- and rate-control.ResultsEarly rhythm-control strategy showed a 14% lower risk of the primary composite outcome in the non-frail group [weighted incidence 7.3 vs. 8.6 per 100 person-years; hazard ratio (HR) 0.86, 95% confidence interval (CI) 0.79–0.93, p &lt; 0.001] than rate-control strategy. A consistent trend toward a lower risk of early rhythm-control was observed in the moderately frail (HR 0.91, 95% CI 0.81–1.02, p = 0.09) and highly frail (HR 0.93, 95% CI 0.75–1.17, p = 0.55) groups.ConclusionAlthough the degree attenuated with increasing frailty, the superiority of cardiovascular outcomes of early rhythm-control in AF treatment was maintained without increased risk for safety outcomes. An individualized approach is required on the benefits of early rhythm-control therapy in older patients with AF, regardless of their frailty status

MicroRNA-Based Therapeutics for Drug-Resistant Colorectal Cancer

Although therapeutic approaches for patients with colorectal cancer (CRC) have improved in the past decades, the problem of drug resistance still persists and acts as a major obstacle for effective therapy. Many studies have shown that drug resistance is related to reduced drug uptake, modification of drug targets, and/or transformation of cell cycle checkpoints. A growing body of evidence indicates that several microRNAs (miRNAs) may contribute to the drug resistance to chemotherapy, targeted therapy, and immunotherapy by regulating the drug resistance-related target genes in CRC. These drug resistance-related miRNAs may be used as promising biomarkers for predicting drug response or as potential therapeutic targets for treating patients with CRC. In this review, we summarized the recent discoveries regarding anti-cancer drug-related miRNAs and their molecular mechanisms in CRC. Furthermore, we discussed the challenges associated with the clinical application of miRNAs as biomarkers for the diagnosis of drug-resistant patients and as therapeutic targets for CRC treatment

<i>Sargassum fusiforme</i> Extract Induces Melanogenesis through the cAMP/PKA/CREB Signaling Pathway

The aim of this study was to investigate the effect of Sargassum fusiforme extract (SFE) on melanogenesis and its mechanism both in vitro and ex vivo. The melanogenic-inducing effect of SFE was evaluated using a melanin contents assay and a cellular tyrosinase activity assay. To investigate whether SFE could protect melanocytes against oxidative stress, hydrogen peroxidase was used. The molecular mechanism underlying the effect of SFE on melanogenesis was determined via Western blot analysis of tyrosinase, a microphthalmia-associated transcription factor (MITF), and a phosphorylated cAMP response element-binding protein (p-CREB) expression. The degree of pigmentation in a 3D skin model was determined by measuring the L* values. Contents of melanin in ex vivo human hair follicles were evaluated via Fontana–Masson staining. SFE significantly increased melanin contents and cellular tyrosinase activity in human epidermal melanocytes. SFE also increased the phosphorylation of CREB and the protein levels of tyrosinase and MITF. Moreover, SFE attenuated oxidative stress-induced cytotoxicity and depigmentation. Finally, the melanogenesis promoting effect of SFE was confirmed in both a 3D skin model and ex vivo human hair follicles. These findings suggest that SFE can induce melanogenesis via the cAMP/PKA/CREB signaling pathway in human epidermal melanocytes through its hyperpigmentation activity

Chlorogenic Acid Isomers Isolated from <i>Artemisia lavandulaefolia</i> Exhibit Anti-Rosacea Effects In Vitro

Rosacea is a chronic inflammatory disease affecting facial skin. It is associated with immune and vascular dysfunction mediated via increased expression and activity of cathelicidin and kallikrein 5 (KLK5), a serine protease of stratum corneum. Therefore, KLK5 inhibitors are considered as therapeutic agents for improving the underlying pathophysiology and clinical manifestation of rosacea. Here, we isolated the active constituents of Artemisia lavandulaefolia (A. lavandulaefolia) and investigated their inhibitory effect on KLK5 protease activity. Using bioassay-guided isolation, two bioactive compounds including chlorogenic acid isomers, 3,5-dicaffeoylquinic acid (isochlorogenic acid A) (1), and 4,5-dicaffeoylquinic acid (isochlorogenic acid C) (2) were isolated from A. lavandulaefolia. In this study, we evaluated the effects of isochlorogenic acids A and C on dysregulation of vascular and immune responses to rosacea, and elucidated their molecular mechanisms of action. The two chlorogenic acid isomers inhibit KLK5 protease activity, leading to reduced conversion of inactive cathelicidin into active LL-37. This inhibition of LL-37 production by isochlorogenic acids A and C reveals the efficacy of suppressing the expression of inflammatory mediators induced by LL-37 in immune cells such as macrophages and mast cells. In addition, both isomers of chlorogenic acid directly inhibited the proliferation and migration of vascular endothelial cells induced by LL-37