Myung-Jin Cha

Trends in the incidence and prevalence of atrial fibrillation and estimated thromboembolic risk using the CHA2DS2-VASc score in the entire Korean population

BACKGROUND Data on the epidemiology of atrial fibrillation (AF) and temporal trends are not well established in the Korean population. We aimed to estimate the incidence and prevalence of AF in Korea between 2008 and 2015. METHODS Using the National Health Insurance Service database, we analyzed as a nationwide cohort the entire Korean adult population from 2008 to 2015 (n=41,505,679 in 2015). AF was identified by using diagnostic codes. RESULTS During an 8-year period representing 314,311,360 person-years of follow-up, 496,341 individuals were newly diagnosed with AF. The incidence of AF increased to >1.12-fold as follows: from 15.34 to 17.14 per 10,000 person-years (p<0.001). We also found a 1.68-fold increase in the prevalence of AF, from 0.46% in 2008 to 0.67% in 2015 (p<0.001). The incidence and prevalence of AF increased with advancing age. The median age of the AF patients increased from 68 to 71years (p<0.001). The prevalence of diabetes and heart failure in AF subjects increased (p<0.001). The percentage of patients with a CHA2DS2-VASc score of ≥2, who were strongly recommended for anticoagulation treatment, increased from 80.2% to 86.8% (p<0.001). CONCLUSION The incidence and prevalence of AF gradually increased from 2008 to 2015. The proportion of AF patients who were candidates for anticoagulation therapy also significantly increased owing to population aging and increasing comorbidities (i.e., heart failure and diabetes). These findings may provide a framework to understand the actual disease burden and establish the optimal management strategy for AF.

Evaluation of the association between diabetic retinopathy and the incidence of atrial fibrillation: A nationwide population-based study.

BACKGROUND Atrial fibrillation (AF) is prevalent among type 2 diabetic patients. However, the association between diabetic retinopathy (DR) and AF is controversial. METHODS We included 40,500 patients with type 2 diabetes (≥40years, mean age 62±11years, 53% men) without AF from the Korean National Insurance Service-National Sample Cohort (2002-2007). Subjects were classified without DR (non-DR, n=30,178), with DR (DR, n=8920), and with proliferative DR (PDR, n=1402). RESULTS During a mean 5.9-year follow-up, 1261 (3.1%) patients were newly diagnosed as having AF (4.9, 6.0, and 8.3 per 1000 person-years in the non-DR, DR, and PDR groups, respectively). In multivariate Cox proportional hazard models, patients in the DR and PDR groups had a significantly higher risk of AF than those in the non-DR group (DR group: hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.00-1.30; PDR group: HR 1.46, 95% CI 1.13-1.87); p for trend <0.001). The risk of AF increased in patients with DR and end-stage renal disease (ESRD) (HR 2.39, 95% CI 1.31-3.96, p<0.001) and in those with PDR and ESRD (HR 3.59, 95% CI 1.96-5.97, p<0.001) compared to those without DR and ESRD. CONCLUSIONS The presence and severity of DR was significantly associated with the incidence of AF. Also, the presence of ESRD had an impact on the incidence of AF in patients with DR.

Prevalence of and risk factors for silent ischemic stroke in patients with atrial fibrillation as determined by brain magnetic resonance imaging.

Varied silent ischemic stroke (SS) prevalence occurs in patients with atrial fibrillation (AF). Stroke history is worth 2 points in the CHADS2 scoring system. An unknown proportion of patients with AF with a CHADS2 score of 0 or 1 have been undertreated for stroke prevention. We investigated SS risk factors using magnetic resonance imaging and estimated SS impact on clinical outcomes in patients with AF. We analyzed a total of 1,200 patients (400 with AF and 800 with sinus rhythm) who had brain magnetic resonance imaging performed for routine health checkups. Clinical outcomes including symptomatic stroke, dementia, and cognitive disorder were also evaluated in patients with AF (follow-up duration: 66.7 ± 35.9 months; range 10 to 162). SS was observed in 113 patients with AF (28.3%), which was significantly higher than that in 53 subjects (6.6%) with sinus rhythm (p <0.001, odds ratio [OR] 5.549). Independent risk factors for SS in patients with AF were age (OR 1.049), hypertension (OR 2.086), dyslipidemia (OR 2.073), and valvular AF (OR 3.157). Symptomatic stroke incidence during the follow-up was significantly greater in patients with AF with SS than without SS (5.6% vs 2.7% per year, respectively; p = 0.022, hazard ratio 1.787, 95% confidence interval 1.089 to 2.933). Using current scoring systems without correcting for subclinical stroke, clinicians have likely underestimated the stroke risk in low-risk patients with AF; thus many patients with AF might not receive optimal anticoagulation treatment. In conclusion, a screening tool for detecting SS could be considered for stroke risk evaluation in patients with AF, especially those with valvular AF, elderly patients, and patients with dyslipidemia or hypertension.

Increased prevalence of metabolic syndrome among hypertensive population: Ten years' trend of the Korean National Health and Nutrition Examination Survey

PURPOSE The implication of metabolic syndrome (MetS) in the hypertensive population has not been known. The prevalence and the risk factors of MetS among the hypertensive population were investigated. METHOD The first to the fourth Korean National Health and Nutrition Examination Survey (KNHANES) held from 1998 to 2008, nationally representative cross-sectional survey, were analyzed. MetS was defined following NCEP-ATP III guideline. RESULTS In the general population, MetS prevalence was about 27%, however, it was doubled in the hypertensive population, reaching almost 60%. This trend was consistent through the first to the fourth KNHANES. Moreover, although the prevalence of hypertension as well as MetS among the general population has been slightly decreasing, MetS prevalence among the hypertensive population continues to rise which is more obvious among younger patients than the general population both in men and in women. In a multivariate analysis, high BMI, menopause, smoking and daily alcohol intake were suggested as independent risk factors of MetS in hypertensive population. Finally, the presence of MetS was associated with increased prevalence of target organ damage, such as stroke, coronary artery disease and chronic renal disease. CONCLUSION MetS prevalence among hypertensives was much higher than expected. Moreover, MetS increased target organ damage in hypertensives. Investigation of metabolic status when initiating hypertension control could help establish more effective overall risk control.

Effectiveness and Safety of Non-Vitamin K Antagonist Oral Anticoagulants in Asian Patients With Atrial Fibrillation

Background and Purpose— There are limited real-world data comparing the effectiveness and safety of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in Asians with nonvalvular atrial fibrillation. We aimed to compare the effectiveness and safety between NOACs and warfarin users in the Korean atrial fibrillation population, with particular focus on high-risk patients. Methods— Using the Korean National Health Insurance Service database, we analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH) events, and all-cause death in NOAC users (n=11 611 total, n=5681 taking rivaroxaban, n=3741 taking dabigatran, and n=2189 taking apixaban) compared with propensity score-matched warfarin users (n=23 222) among patients with high-risk atrial fibrillation (CHA2DS2-VASc score ≥2) between 2014 and 2015. Results— NOAC treatment was associated with similar risk of ischemic stroke and lower risk of ICH and all-cause mortality compared with warfarin. All 3 NOACs were associated with a similar risk of ischemic stroke and a lower risk of ICH compared with warfarin. Dabigatran and apixaban were associated with a lower risk of total mortality and the composite net clinical outcome (ischemic stroke, ICH, and all-cause death) compared with warfarin, whereas this was nonsignificant for rivaroxaban. Among previously oral anticoagulant–naive patients (n=23 262), dabigatran and apixaban were superior to warfarin for ICH prevention, whereas rivaroxaban and warfarin were associated with similar risk of ICH. Conclusions— In real-world practice among a high-risk Asian atrial fibrillation population, all 3 NOACs demonstrated similar risk of ischemic stroke and lower risk of ICH compared with warfarin. All-cause mortality was significantly lower only with dabigatran and apixaban.

Nonalcoholic Fatty Liver Disease Is Associated With Coronary Artery Calcification Development: A Longitudinal Study

CONTEXT Nonalcoholic fatty liver disease (NAFLD) is associated with coronary artery calcification (CAC) in cross-sectional studies. However, whether NAFLD itself affects CAC development or progression remains unknown. OBJECTIVE This study investigated the longitudinal association between NAFLD and CAC score. DESIGN AND SETTING This study is a longitudinal cohort study performed in a healthcare center. PARTICIPANTS Among 1732 subjects who underwent serial CAC evaluation, we evaluated 846 subjects with NAFLD and 886 subjects without NAFLD, as diagnosed via ultrasonography. MAIN OUTCOME MEASURES CAC score was compared at baseline and follow-up. In subjects without calcification (CAC score = 0) at baseline, any incidental calcification (CAC score >0) at follow-up was defined as development of CAC. In subjects with CAC (CAC score > 0) at baseline, confirmed CAC aggravation was defined as progression. Logistic regression analysis was performed. RESULTS More subjects with NAFLD than without showed CAC development or progression (48.8 vs 38.4%; P < .001). The impact of NAFLD on a change in CAC score significantly differed according to the CAC score at baseline. In subjects without calcification at baseline, NAFLD significantly affected the development of calcification (odds ratio, 1.49; 95% confidence interval, 1.01-2.21; P = .045) after adjusting for traditional metabolic risk factors. However, in subjects with baseline CAC, NAFLD did not significantly affect progression (P = .734). Additionally, the severity of NAFLD was important. The severity of NAFLD was dose-dependently associated with the development of CAC (P for trend = .043). CONCLUSIONS NAFLD plays a role in the early development of CAC, but not the progression. Ultrasonographic severity of NAFLD is dose-dependently associated with CAC development in subjects with a CAC score of 0 at baseline, independent of traditional risk factors.

Increased risk of major bleeding in underweight patients with atrial fibrillation who were prescribed non-vitamin K antagonist oral anticoagulants

BACKGROUND There is a paucity of evidence regarding the effects of non-vitamin K antagonist oral anticoagulants (NOACs) in underweight patients with atrial fibrillation (AF). OBJECTIVE The purpose of this study was to evaluate the efficacy and safety of NOACs in underweight AF patients. METHODS We analyzed 1353 AF patients who were prescribed NOACs according to their body mass index (BMI): underweight (UW: n = 62, BMI <18.5 kg/m2), normal weight (NW: n = 753, BMI 18.5-24.9 kg/m2), and overweight to obese (OW: n = 538, BMI ≥25.0 kg/m2). We analyzed the association between clinical outcomes and BMI. RESULTS During the median 7 months (interquartile range 3-10 months) of follow-up, there were 29 major bleeding events, 11 thromboembolic events, and 15 deaths. The risks of major bleeding and all-cause death were significantly higher in the UW group compared to the NW group (adjusted hazard ratio [HR] 4.135, 95% confidence interval [CI] 1.442-11.854, P = .008; adjusted HR 10.524, 95% CI 2.949-37.561, P < .001) and the OW group (adjusted HR 5.352, 95% CI 1.597-17.935, P = .007; adjusted HR 11.385, 95% CI 2.523-51.386, P = .002). However, there was no significant difference in the risk of thromboembolism among these groups. CONCLUSION In AF patients taking NOACs, being underweight was associated with an increased risk of major bleeding and all-cause death compared with being normal weight or overweight to obese, whereas the risk of thromboembolism was not different. Dose reduction should be considered in underweight patients who are at high risk for bleeding.

Under-Utilization of Donor Hearts in the Initial Era of the Heart Transplant Program in Korea

BACKGROUND Heart transplantation (HTPL) is the effective treatment option to improve quality of life as well as survival of terminal heart failure patients. Shortage of donors, however, limits HTPL to all indicated cases. The temporal trend and clinical characteristics of HTPL donors in Korea were therefore investigated. METHODS AND RESULTS Among 2,001 brain-death donors registered in Korean Network for Organ Sharing from February 2000 to May 2012, a total of 28% of hearts (n=552) were utilized for HTPL. The mean age of Korean heart donors was 10 years younger than that of heart recipients (33.2 ± 12 years vs. 43.2 ± 17 years, respectively). The oldest was 56 years old, and donors aged over 50 accounted for only 6.2% (n=34) of total cases. Female donors were utilized less than male donors (23.6% vs. 29.6%, respectively). To determine characteristics of declined donor heart candidates, subgroup analysis of echocardiographic data was done, and 74.6% had normal ventricular function and structure, although only 42.3% were actually transplanted. The utilization rate of donor hearts with minor echocardiography abnormalities was only 15.2%. Clinical outcomes of marginal heart donors were not different from non-marginal donors. CONCLUSIONS Although shortage of donor organs is an emerging issue, most donor hearts have been under-utilized in the past in Korea. In particular, aged and female donor hearts with minor echocardiographic abnormalities had a low rate of utilization.

Risk of Ischemic Stroke in Patients With Non-Valvular Atrial Fibrillation Not Receiving Oral Anticoagulants ― Korean Nationwide Population-Based Study ―

BACKGROUND Atrial fibrillation, the most common cardiac arrhythmia, is associated with an elevated thromboembolic risk, including ischemic stroke. Guidelines recommend the stratification of individual stroke risk and tailored antithrombotic therapy. This study investigated the demographics, comorbidities, and prognosis of non-valvular AF (NVAF) in Korean patients.Methods and Results:We extracted data on 10,846 patients with newly diagnosed NVAF who were naïve to oral anticoagulants from the National Health Insurance Service-National Sample Cohort. CHADS2and CHA2DS2-VASc scores were calculated for each subject using claims data. The study endpoints were ischemic stroke, thromboembolism, and mortality. Mean age was 63.7 years, and 46.8% of the patients were women. Women were older and had higher CHADS2and CHA2DS2-VASc scores. During 30,138 person-years of follow-up, ischemic stroke occurred at a rate of 2.95/100 person-years. CHADS2and CHA2DS2-VASc scores showed good performance in risk prediction. CHA2DS2-VASc score performed better at discriminating stroke risk in patients with low-risk profiles. The presence of female sex and vascular disease added little improvement in risk prediction. CONCLUSIONS Korean NVAF patients had high risk of stroke and mortality, and had multiple comorbidities. While both CHADS2and CHA2DS2-VASc schema had good performance in risk prediction, CHA2DS2-VASc score was superior in identifying truly low-risk patients. Given that Asian ethnicity is associated with bleeding events, individualized accurate risk prediction is necessary to improve patient outcomes.

Temporal trends of antithrombotic therapy for stroke prevention in Korean patients with non-valvular atrial fibrillation in the era of non-vitamin K antagonist oral anticoagulants: A nationwide population-based study

Background Following their introduction, the non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly prescribed in Asia for stroke prevention in patients with non-valvular atrial fibrillation (AF). Few contemporary data are available on temporal trends in antithrombotic therapy use in Asian countries, in the era of NOACs. Methods and results Using the National Health Insurance Service database of the entire Korean adult AF population, the use of aspirin, vitamin K antagonist, and NOACs between 2008 and 2015 were analyzed (n = 276,246 in 2015). Most of the included cohort had CHA2DS2-VASc score ≥ 2 (78.2% in 2008 and 83.2% in 2015), yet approximately 17% were prescribed no antithrombotic therapy throughout the study period. Aspirin prescription consistently decreased (from 48.2% to 31.5%) over time, while OAC prescription significantly increased from 34.7% to 50.6%. NOAC prescriptions accounted for 50% of total OAC prescription in 2015. Similar trends in antithrombotic therapy were found both in men and in women, but women were more likely to be undertreated with OAC. Female gender, presence of vascular disease and prior intracranial hemorrhage were associated with OAC underuse. Conclusions Between 2008 and 2015, a greater proportion of AF patients received OAC treatment with increasing NOAC prescription trends in the recent 3 years. A substantial proportion (approx. 50%) of Korean patients with AF still remain undertreated.