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In megacities, road traffic is a major source of particulate matter (PM), requiring a critical understanding of effective air pollution control. Despite existing methods to determine PM emission factors (EFs) of vehicles, accurate estimation of PM emissions under real driving conditions remains challenging. We aimed to assess the EFs of organic aerosol (OA) and equivalent black carbon (eBC) from vehicles through on-road measurements in Seoul, Korea, to understand real-world PM emissions. We used a mobile laboratory equipped with an aerosol mass spectrometer and an aethalometer to measure the composition of PM. On-road measurements were conducted in vehicle tunnels, urban roadways, and residential areas, and the characteristics of measurement points were compared and analyzed. Our results showed that concentrations of OA increased proportionally with the influence of vehicle exhaust, while oxidation states of the OA decreased. Mobile measurements revealed spatial heterogeneities in aerosols, highlighting distinct characteristics of fresh OA on vehicle roads and elevated oxidation state values in residential areas. Active nitrate formation near vehicles led to elevated NO3 concentrations on roads compared to residential areas. Our study shows that mobile PM measurements, including OA and eBC, are valuable for the direct evaluation of emission inventories. However, given that the calculated EFs may not be applicable to other cities due to differences in vehicle composition and traffic conditions, the development of city-specific EFs will be necessary in the future. Furthermore, it is recommended to integrate this methodology with conventional emission inventories to identify vehicle-type-specific emissions. [ABSTRACT FROM AUTHOR]

This paper examines the impact of e-commerce on local retail employment and its heterogeneity by employment and regional types, using Korean retail survey. Our findings reveal that the positive impact of online sales expansion is mainly confined to the growth of wage workers, though its elasticity with respect to online sales is much smaller than that of offline sales. When dividing the full sample by regional type, the positive employment effect of online sales on wage workers is significant only in non-metropolitan regions. In addition, the negative impact of online sales on non-wage workers is found only in metropolitan regions. [ABSTRACT FROM AUTHOR]

Background: Sacubitril acts to inhibit neprilysin and as neprilysin is involved in amyloid-beta degradation in the central nervous system, and there is concern that sacubitril/valsartan may increase the risk of dementia. We aimed to compare the risk of incident dementia associated with sacubitril/valsartan and angiotensin II receptor blockers (ARBs). Methods: Patients with heart failure with reduced ejection fraction treated with either sacubitril/valsartan or ARB, identified from the Korean National Health Insurance Service database, were matched in a 1:2 ratio using propensity scores (6789 on sacubitril/valsartan and 13,578 on ARBs) and followed up for incident dementia. Results: During a mean follow-up of 2.5 years, 526 (2.6%) patients were newly diagnosed with dementia: Alzheimer dementia in 282, vascular dementia in 8, and other dementia in 236. There was no significant difference in the risk of overall dementia (hazard ratio [HR] 0.84, 95% confidence interval [CI] 0.70–1.01), Alzheimer dementia (HR 0.85, 95% CI 0.67–1.10), vascular dementia (HR 0.98, 95% CI 0.23–4.11), and all other dementias (HR 0.81, 95% CI 0.62–1.07) between sacubitril/valsartan users and ARB users. These results were consistent regardless of initial sacubitril/valsartan dose and subgroups including old age, previous mild cognitive impairment, previous stroke, and concomitant antiplatelet or anticoagulation. Sensitivity analysis with a 1-year lag period for dementia assessment confirmed the main analysis. Meanwhile, risk of incident stroke was lower in sacubitril/valsartan users compared to ARBs users. Conclusions: In a nationwide propensity-matched cohort of patients with heart failure, sacubitril/valsartan was not associated with an increased risk of incident dementia compared to ARBs. Sacubitril/valsartan and the risk of incident dementia in heart failure. ARB, angiotensin II receptor blocker; ARNI, angiotensin receptor neprilysin inhibitor. [ABSTRACT FROM AUTHOR]

Background and Aims Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF. Methods Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes—the composite of heart failure, ischaemic stroke, or death—according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort. Results The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A , 13.5%; TET2 , 6.6%; and ASXL1 , 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P <.001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10–1.74, P <.01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14–1.99, P =.004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05–2.60, P =.030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E / E ′, and a more severely enlarged left atrium than those without CHIP mutations (all P <.05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death). Conclusions CHIP mutations, primarily DNMT3A or TET2 , are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Sodium-glucose co-transporter-2 inhibitors displayed cardiovascular benefits in type 2 diabetes mellitus in previous studies; however, there were some heterogeneities regarding respective cardiovascular outcomes within the class. Furthermore, their efficacies in Asians, females, and those with low cardiovascular risks were under-represented. Thus, we compared the cardiovascular outcomes between new users of dapagliflozin and empagliflozin in a broad range of patients with type 2 diabetes mellitus using a nationwide population-based real-world cohort from Korea. Methods: Korean National Health Insurance registry data between May 2016 and December 2018 were extracted, and an active-comparator new-user design was applied. The primary outcome was a composite of heart failure (HF)-related events (i.e., hospitalization for HF and HF-related death), myocardial infarction, ischemic stroke, and cardiovascular death. The secondary outcomes were individual components of the primary outcome. Results: A total of 366,031 new users of dapagliflozin or empagliflozin were identified. After 1:1 nearest-neighbor propensity score matching, 72,752 individuals (mean age approximately 56 years, 42% women) from each group were included in the final analysis, with a follow-up of 150,000 ~ person-years. Approximately 40% of the patients included in the study had type 2 diabetes mellitus as their sole cardiovascular risk factor, with no other risk factors. The risk of the primary outcome was not different significantly between dapagliflozin and empagliflozin users (hazard ratio [HR] 0.93, 95% confidence interval [CI] 0.855–1.006). The risks of secondary outcomes were also similar, with the exception of the risks of HF-related events (HR 0.84, 95% CI 0.714–0.989) and cardiovascular death (HR 0.76, 95% CI 0.618–0.921), which were significantly lower in the dapagliflozin users. Conclusions: This large-scale nationwide population-based real-world cohort study revealed no significant difference in composite cardiovascular outcomes between new users of dapagliflozin and empagliflozin. However, dapagliflozin might be associated with lower risks of hospitalization or death due to HF and cardiovascular death than empagliflozin in Asian patients with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background We aimed to evaluate dynamic alterations in cerebral total hemoglobin concentration (HbT) in individuals with orthostatic hypotension (OH) and orthostatic intolerance (OI) symptoms using a portable near-infrared spectroscopy (NIRS) system. Methods Participants comprised 238 individuals (mean age, 47.9 years) without a history of cardiovascular, neurodegenerative, or cerebrovascular diseases, including those with unexplained OI symptoms and healthy volunteers. Participants were categorized by the presence of OH based on the supine-to-stand blood pressure (BP) drop and OI symptoms using on OH questionnaires: classic OH (OH-BP), OH symptoms alone (OH-Sx), and control groups. Random case–control matching sets were constructed, resulting in 16 OH-BP and 69 OH-Sx-control sets. The time-derivative of HbT change in the prefrontal cortex during the squat-to-stand maneuver was measured using a portable NIRS system. Results There were no differences in demographics, baseline BP, and heart rate among matched sets. The peak time of maximum slope variation in HbT change, indicating the recovery rate and speed of cerebral blood volume (CBV) change, was significantly longer in OH-Sx and OH-BP groups than in the control group under transition to a standing position after squatting. In the OH-BP subgrouping, the peak time of maximum slope variation in HbT change was significantly longer only in OH-BP with OI symptoms, but did not differ between OH-BP without OI symptoms and controls. Conclusions Our results suggest that OH and OI symptoms are associated with dynamic alterations in cerebral HbT. Regardless of the severity of the postural BP drop, OI symptoms are associated with prolonged CBV recovery. [ABSTRACT FROM AUTHOR]

Background: Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity. Methods: From an institutional cohort of a routine health check‐up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions. Results: Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log‐transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log‐transformed total WMH and the lower log‐transformed periventricular WMH volume, but not with the log‐transformed subcortical WMH volumes. Conclusions: Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH. [ABSTRACT FROM AUTHOR]

Limited data are available on the long-term outcomes in patients with hypertrophic cardiomyopathy (HCM) patients with significant coronary artery disease (CAD) requiring revascularization. We investigated the risk of cardiovascular outcomes in HCM patients who underwent coronary revascularization compared to the control group without HCM. HCM patients aged ≥ 20 years were enrolled from the Korean National Health Insurance Database. Information on the diagnosis and previous medical history was obtained from the claims data. Cardiovascular outcomes were identified during 8-year after coronary revascularization in HCM patients (HCM group) and matched controls without HCM (non-HCM control group). A total of 431 patients in the HCM group and 1968 in the non-HCM control group were analyzed. The risk of all-cause death, cardiovascular death, sudden cardiac death (SCD), ischemic stroke, and hospitalization due to heart failure was significantly higher in the HCM group than in the non-HCM group, with prominent risk increase of cardiovascular death (adjusted hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.63–3.15, P < 0.001) and ischemic stroke (adjusted HR 2.38, 95% CI 1.55–3.64, P < 0.001). Beyond 1-year after revascularization, the HCM group still had a significantly higher risk of cardiovascular death, SCD, and ventricular fibrillation/tachycardia compared to the non-HCM group. Mortality and major cardiovascular outcomes occurred more frequently in HCM patients with significant CAD requiring revascularization, compared to the matched non-HCM control group. Active and regular surveillance for concomitant risk factors and relevant intervention are warranted in HCM patients at increased risk for CAD. [ABSTRACT FROM AUTHOR]

Background : To assess the association between the reproductive factors of age at menarche, age at menopause, and reproductive span and the incidence of myocardial infarction (MI) and ischemic stroke (IS). Methods: We used a population-based retrospective cohort study from the National Health Insurance Service database of Korea including a total of 1,224,547 postmenopausal women. Associations between age at menarche (≤ 12, 13–14 [reference], 15, 16, and ≥ 17 years), age at menopause (< 40, 40–45, 46–50, 51–54 [reference], and ≥ 55 years), and reproductive span (< 30, 30–33, 34–36, 37–40 [reference], and ≥ 41 years) and the incidence of MI and IS were assessed by Cox proportional hazard models with adjustment for traditional cardiovascular risk factors and various reproductive factors. Results: During a median follow-up of 8.4 years, 25,181 MI and 38,996 IS cases were identified. Late menarche (≥ 16 years), early menopause (≤ 50 years), and short reproductive span (≤ 36 years) were linearly associated with a 6%, 12–40%, and 12–32% higher risk of MI, respectively. Meanwhile, a U-shaped association between age at menarche and risk of IS was found, with a 16% higher risk in early menarche (≤ 12 years) and a 7–9% higher risk in late menarche (≥ 16 years). Short reproductive span was linearly associated with an increased risk of MI, whereas both shorter and longer reproductive spans were associated with an increased risk of IS. Conclusions: This study demonstrated different patterns of association between age at menarche and incidence of MI and IS: a linear association for MI versus a U-shaped association for IS. Female reproductive factors in addition to traditional cardiovascular risk factors should be considered when assessing overall cardiovascular risk in postmenopausal women. [ABSTRACT FROM AUTHOR]

Anti-tuberculosis treatment can cause significant drug-drug interaction and interfere with effective anticoagulation. However, there is a lack of evidence and conflicting data on the optimal oral anticoagulation in patients treated for tuberculosis. We investigated the safety and effectiveness of anticoagulation with non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin in patients on anti-tuberculosis treatment. Patients on concomitant oral anticoagulation and anti-tuberculosis treatment including rifampin were identified from the Korean nationwide healthcare database. Subjects were censored at discontinuation of either anticoagulation or rifampin. The outcomes of interest were major bleeding, death, and ischemic stroke. A total 2090 patients (1153 on warfarin, 937 on NOAC) were included. NOAC users, compared to warfarin users, were older, had a lower prevalence of hypertension, heart failure, ischemic stroke, and aspirin use and a higher prevalence of cancer, with no significant differences in CHA2DS2-VASc or HAS-BLED scores. There were 18 major bleeding events, 106 deaths, and 50 stroke events during a mean follow-up of 2.9 months. After multivariable adjustment, the use of NOAC was associated with a lower risk of incident ischemic stroke (HR 0.51, 95% CI 0.27–0.94), while there was no significant difference in risk for major bleeding or death compared with warfarin. These results suggest that NOACs have better effectiveness for stroke prevention and similar safety compared with warfarin in patients on concomitant anti-tuberculosis treatment. This is the first study assessing the safety and effectiveness of NOACs compared to warfarin in this clinical scenario. [ABSTRACT FROM AUTHOR]

Although atrial fibrillation (AF) is a well-established risk factor for ischemic stroke (IS) in hypertrophic cardiomyopathy (HCM), the risk of IS in HCM patients without documented AF is less recognized. This nationwide population-based cohort study using Korean National Health Insurance database included 8,328 HCM patients without documented AF and 1:2 propensity score-matched 16,656 non-HCM controls between 2010 and 2016. The primary outcome was an incident IS. During a mean follow-up of 6.1 years, IS occurred in 328/8,328 (3.9%) patients with HCM and 443/16,656 (2.7%) controls. The overall incidence of IS was 0.72/100 person-years in the HCM group, which was significantly higher than that in the control group (0.44/100 person-years) (HR 1.64; 95% CI 1.424–1.895; P < 0.001). The overall incidence of IS was 1.36/100 person-years in HCM patients aged ≥ 65 and 2.32/100 person-years years in those with heart failure, respectively. In the HCM group, age ≥ 65 years (adjusted HR 2.74; 95% CI 2.156–3.486; P < 0.001) and chronic heart failure (adjusted HR 1.75; 95% CI 1.101–2.745; P = 0.018) were independent risk factors for IS. HCM patients without documented AF are at a greater risk of IS, especially in those 65 years of age or older or those with chronic heart failure. [ABSTRACT FROM AUTHOR]

Background: Dementia is a big medical and socioeconomic problem on aging society, and cardiac diseases have already shown a significant contribution to developing dementia. However, the risk of dementia related to hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has never been evaluated. Methods: In a large-scale longitudinal cohort using National Health Insurance database, 4,645 subjects with HCM aged ≥50 years between 2010 and 2016 were collected and matched with 13,935 controls, based on propensity scores (1:3). We investigated the incidence and risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) between groups. Results: During follow-up (median 3.9 years after 1-year lag), incident dementia occurred in 739 subjects (4.0%): 78.2% for AD and 13.0% for VaD. The incidence of dementia, AD, and VaD were 23.0, 18.0, and 2.9/1,000 person-years, respectively, and was generally more prevalent in HCM. HCM group had a 50% increased risk of dementia, particularly AD, whereas there was no difference in the risk of VaD. The impact of HCM on AD (HR 1.52, 95% CI 1.26–1.84, p<0.001) was comparable with that of diabetes mellitus and smoking. Increased risk of AD in relation to HCM was consistent in various subgroups including younger healthier population. Conclusions: This is the first to demonstrate the increased risk of dementia, mainly AD rather than VaD, in subjects with HCM. Early surveillance and active prevention for cognitive impairment could help for a better quality of life in an era that HCM is considered a chronic manageable disease with low mortality. [ABSTRACT FROM AUTHOR]

Despite the increasing burden of hypertrophic cardiomyopathy (HCM) on healthcare resources, data on emergency department (ED) utilization in HCM are lacking. This nationwide population-based study extracted 14,542 HCM patients from the National Health Insurance Service database between 2015–2016, and investigated their ED utilization during a one-year period. The reason for ED utilization was defined as the primary diagnosis upon discharge from EDs. The clinical outcome was defined as hospitalization or all-cause mortality within 90 days after the ED visits. A total of 3209 (22.1%) HCM patients visited EDs within a one-year period (mean age, 66.8 ± 13.8 years; male, 57.4%). The majority (71.1%) of HCM patients who visited the EDs were aged ≥ 60 years. The ED utilization rate was higher in women than in men (26.3% versus 19.7%, P < 0.001). Cardiovascular diseases were the most common reason for ED visits (n = 1333, 41.5%). Among HCM patients who visited EDs, 1195 (37.2%) were hospitalized, and 231 (7.2%) died within 90 days. ED visits for cardiovascular disease was associated with a higher 90-day all-cause mortality (adjusted odds ratio, 2.72; 95% confidence interval 1.79–4.12). These findings would serve as a basis for future research to establish medical policies on ED utilization in HCM. [ABSTRACT FROM AUTHOR]

Objectives: Recommendations on physical activity (PA) for adults with hypertrophic cardiomyopathy (HCM) are not well established. We investigated the association of PA intensity with mortality in the general adult HCM population.Methods: A nationwide population-based cohort of individuals with HCM who underwent health check-ups including questionnaires on PA levels were identified from the years 2009 to 2016 in the National Health Insurance Service database. Subjects who reported no PA at baseline were excluded. To estimate each individual's PA level, the PA score (PAS) was calculated based on the self-reported questionnaires, and the study population was categorised into three groups according to tertiles of PAS. The associations of PAS with all-cause and cardiovascular mortality were analysed.Results: A total of 7666 participants (mean age 59.5 years, 29.9% were women) were followed up for a mean 5.3±2.0 years. All-cause and cardiovascular mortality progressively decreased from the lowest to the highest tertiles of PA intensity: 9.1% (4.7%), 8.9% (3.8%) and 6.4% (2.7%), respectively (p-for-trend=0.0144 and 0.0023, respectively). Of note, compared with the middle PA group, the highest PA group did not have an increased risk of all-cause and cardiovascular mortality (HR 0.78, (95% CI 0.63 to 0.95) and HR 0.75 (95% CI 0.54 to 1.03), respectively). All subgroup and sensitivity analyses consistently showed that all-cause and cardiovascular mortality did not increase with higher PA levels.Conclusions: Moderate-to-vigorous-intensity PA, in a middle-aged population of patients with HCM, was associated with progressive reduction of all-cause and cardiovascular mortality. The impact of vigorous-intensity PA on a younger age group requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are known to reduce the risk of upper gastrointestinal bleeding in patients on oral anticoagulants, and patients are increasingly on oral anticoagulants and PPI co-therapy. However, evidence is lacking on the safety and effectiveness of oral anticoagulants when co-administered with PPIs. Methods: Among patients initiating oral anticoagulants (warfarin and non-vitamin K antagonist oral anticoagulants [NOACs], i.e. rivaroxaban, dabigatran, apixaban, and edoxaban) during 2013–2017, those concomitantly prescribed PPIs were identified (n = 19,851). The primary endpoint was hospitalization for major upper gastrointestinal bleeding, and secondary endpoints were death and ischemic stroke. Results: During a mean 1.4 years of follow-up, the primary endpoint occurred in 512 (2.58%) patients. Overall, NOACs were associated with lower upper gastrointestinal bleeding risk after adjustment for age, sex, comorbidities and concomitant medications (adjusted hazard ratio 0.78, 95% confidence interval 0.65–0.94), compared to warfarin. There was no significant difference in upper gastrointestinal bleeding risk among the individual NOACs. This trend of reduced risk for upper gastrointestinal bleeding in NOACs compared to warfarin was consistent for both regular and reduced doses, throughout bleeding risk groups, and other subgroup analyses. NOACs were also associated with lower risk of death compared to warfarin. The risk for ischemic stroke was not significantly different among the oral anticoagulants in patients with atrial fibrillation. Conclusion: In patients on oral anticoagulant and PPI co-therapy, NOACs were associated with lower risk of upper gastrointestinal bleeding and mortality compared to warfarin, while there was no difference among the oral anticoagulants for stroke prevention. In patients on PPI therapy, NOACs may preferred over warfarin for decreasing risk of upper gastrointestinal bleeding and mortality. [ABSTRACT FROM AUTHOR]

Even with increasing awareness of sex-related differences in atherosclerotic cardiovascular disease (ASCVD), it remains unclear whether the progression of coronary atherosclerosis differs between women and men. We sought to compare coronary artery calcium (CAC) progression between women and men. From a retrospective, multicentre registry of consecutive asymptomatic individuals who underwent CAC scoring, we identified 9,675 men and 1,709 women with follow-up CAC scoring. At baseline, men were more likely to have a CAC score >0 than were women (47.8% vs. 28.6%). The probability of CAC progression at 5 years, defined as [√CAC score (follow-up)—√CAC score (baseline)] ≥2.5, was 47.4% in men and 29.7% in women (p<0.001). When we stratified subjects according to the 10-year ASCVD risk (<5%, ≥5% and <7.5%, and ≥7.5%), a sex difference was observed in the low risk group (CAC progression at 5 years, 37.6% versus 17.9%; p<0.001). However, it became weaker as the 10-year ASCVD risk increased (64.2% versus 46.2%; p<0.001, and 74.8% versus 68.7%; p = 0.090). Multivariable analysis demonstrated that male sex was independently associated with CAC progression rate among the entire group (p<0.001). Subgroup analyses showed an independent association between male sex and CAC progression rate only in the low-risk group. The CAC progression rate is higher in men than in women. However, the difference between women and men diminishes as the 10-year ASCVD risk increases. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia in the elderly. Arterial stiffness may predict the risk of AF, but this relationship has not been fully evaluated. We assessed the association between arterial stiffness and prevalent AF. All subjects who had electrocardiography performed and a cardio-ankle vascular index (CAVI) calculated during a screening examination between 2010 and 2019 were enrolled. To evaluate the association between increased arterial stiffness and AF, we divided the population according to their Framingham risk score (FRS) into low-, intermediate-, and high-risk groups. A total of 8048 subjects were evaluated. The multivariate analysis revealed that increased arterial stiffness was significantly associated with AF prevalence, even after adjusting cardiovascular risk factors [odds ratio (OR) 1.685, 95% confidence interval (CI) 1.908–2.588, p = 0.017]. When we subcategorized the subjects according to their FRS, increased arterial stiffness was significantly associated with AF in the intermediate- and high-risk groups (OR 3.062, 95% CI 1.39-6.740 and OR3.877, 95% CI 1.142-13.167, respectively, BMI adjusted. High arterial stiffness shows a significant association with AF in those with intermediate or high cardiovascular risk, and can be used for further risk stratification of patients. [ABSTRACT FROM AUTHOR]

We investigated sex-related differences in the prognosis of patients with hypertrophic cardiomyopathy (HCM) using the Korea National Health Insurance Service database. From 2010 to 2016, 9524 patients diagnosed with HCM and had more than 1-year follow-up period were analyzed. The primary endpoint was the composite of cardiovascular death or new-onset heart failure (HF) admission. Propensity score-matching analysis was performed to adjust for different baseline characteristics. With a 4.4-years' median follow-up interval (range 2.0–6.6 years) and male predominance (77.6%), women with HCM were older (52.6 ± 9.7 vs. 51.4 ± 9.1, p < 0.001), had lower incomes, more comorbidities based on Charlson comorbidity index. Women with HCM had a higher incidence of the primary endpoint than men (incidence rate: 34.15 vs. 22.83 per 1000 person-years, log-rank p < 0.001). Multivariable Cox analysis showed that female sex was a poor prognostic factor for the primary endpoint (HR 1.43, 95% CI 1.24–1.64, p < 0.001). This was mainly driven by a higher incidence of new-onset HF admission (HR 1.55, 95% CI 1.34–1.80). However, there was no difference in the incidence of cardiovascular death between the sexes. This result was concordant in the propensity score-matched cohort. In conclusion, women with HCM have worse prognosis, which was mainly driven by a higher new-onset HF admission. [ABSTRACT FROM AUTHOR]

Previous epidemiological studies focusing on the association between liver disease and atrial fibrillation (AF) show interesting but inconsistent findings. Patients with liver disease have a higher AF risk; however, it is unknown whether the liver fibrosis index can predict AF risk. The medical records of a healthy population undergoing routine health examinations at Healthcare System Gangnam Center, Seoul National University Hospital, were reviewed retrospectively. After excluding subjects with a history of liver disease and known cardiovascular disease, 74,946 subjects with nonalcoholic fatty liver disease (NAFLD) were evaluated. The mean age was 51 ± 11 years, and 71.9% were male. AF was found in 380 (0.5%) subjects. Using univariate analyses, age, male sex, body mass index, hypertension, and diabetes were significantly associated with AF. The fibrosis 4 index (FIB 4) showed significant correlations with AF [unadjusted odds ratio (OR) 3.062 and 95% confidence interval (CI) 2.605–3.600, p = 0.000; adjusted OR 2.255 and 95% CI 1.744–2.915, p = 0.000, with cardiometabolic risk factors adjusted]. In conclusion, NAFLD subjects with higher FIB 4 were associated with increased AF risk. The noninvasive determination of liver fibrosis indices can have clinical implications on the early identification of NAFLD in patients at risk for AF. [ABSTRACT FROM AUTHOR]

Temporal trends of the prevalence and incidence of hypertrophic cardiomyopathy (HCM) have not been well established in Asian populations. Using the Korean National Health Insurance Services database, we identified patients with a confirmed diagnosis of HCM between 2010 and 2016. The annual prevalence and incidence of HCM, and their clinical characteristics were investigated. The prevalence of HCM has increased from 0.016% (n = 6313) in 2010 to 0.031% (n = 13,035) in 2016. During a 7-year period, 13,229 patients were newly diagnosed with HCM. The incidence rate increased from 4.15 (per 100,000 person-years) in 2010 to 5.6 in 2016. The prevalence and incidence of HCM increased with age and peaked during the 70s, with male predominance in all age groups. Chest pain is the most frequent clinical presentation followed by shortness of breath and syncope. Hypertension and dyslipidemia were the two most common comorbidities. Heart failure and atrial fibrillation was diagnosed in about 1/3 and 1/4 of patients with HCM, respectively. The prevalence and incidence of HCM gradually increased from 2010 to 2016, possibly due to heightened recognition of the disease. Given the progressively high incidence of HCM with age and high prevalence of coexisting modifiable risk factors, continued efforts are required to increase awareness regarding HCM-related symptoms and potential complications. [ABSTRACT FROM AUTHOR]

Aims We aimed to investigate whether long-term exposure to particulate matter with an aerodynamic diameter <2.5 μm (PM2.5) in the ambient air is related to the development or growth of coronary plaques. Methods and results This study involved 364 residents of Seoul, Korea, who underwent serial coronary computed tomographic angiography (CCTA) at an interval of ≥2 years. Each participant's average concentration of residential PM2.5 between the two CCTAs was calculated. Primary endpoint was the development of high-risk plaque (HRP), defined as a plaque with low attenuation, spotty calcium, and positive remodelling. Secondary endpoints were the volume increase of total plaque and its component volume. Among those without HRP at baseline (n  = 341), 20 patients developed HRP at follow-up CCTA, the residential PM2.5 concentration of which was significantly higher than those without HRP at follow-up (25.8 ± 2.0 vs. 25.0 ± 1.7 μg/m3 for patients with newly developed HRP vs. patients without HRP at follow-up; P  = 0.047). An increase in PM2.5 concentration was associated with increased incidence of HRP at follow-up [adjusted hazard ratio (aHR) 1.62, 95% confidence interval (CI) 1.22–2.15, P  < 0.001]. In a secondary analysis, the PM2.5 concentration was associated with an increased risk of the formation of either fibrofatty or necrotic core component in newly developed plaques (aHR 1.41, 95% CI 1.23–1.61, P  < 0.001), and with a higher risk of total plaque volume progression in the pre-existing plaques (aHR 1.14, 95% CI 1.05–1.23, P  = 0.002). Conclusion Exposure to higher concentration of PM2.5 in the ambient air is significantly associated with the development of high-risk coronary plaques. [ABSTRACT FROM AUTHOR]

Background: Chronic systemic inflammation is an important causative factor in the pathogenesis of atherosclerosis. However, the effect of chronic Helicobacter pylori (Hp) infection on arterial stiffness, a predictor of cardiovascular events, remains unclear. We evaluated the association between Hp infection and arterial stiffness in asymptomatic healthy individuals. Methods: Arterial stiffness was evaluated using the cardio-ankle vascular index (CAVI). We included subjects who underwent CAVI and anti-Hp IgG antibody evaluations, simultaneously, between March 2013 and July 2017. Demographic characteristics and metabolic and cardiovascular parameters were compared with respect to anti-Hp IgG antibody status. Multivariable logistic regression analyses were performed to determine the effect of Hp-seropositivity and conventional cardiovascular risk factors on arterial stiffness. Results: Of 2,251 subjects, 1,326 (58.9%) were included in the Hp-seropositive group. Median age (P < 0.001) and systolic blood pressure (P = 0.027) were significantly higher in the Hp-seropositive than in the Hp-seronegative group. Levels of LDL-cholesterol were significantly higher in the Hp-seropositive than in the Hp-seronegative group (P = 0.016). Other serum metabolic parameters were not significantly different between the two groups. The median CAVI value and the proportion of subjects with a CAVI ≥ 8 were significantly higher in the Hp-seropositive than in the Hp-seronegative group (both P < 0.001). On multivariable logistic regression analyses, Hp-seropositivity, age, body mass index, waist circumference, smoking, hypertension, diabetes mellitus, and dyslipidemia were significantly associated with high CAVI values. In the subgroup analysis conducted according to age group, a tendency towards an increased association between Hp-seropositivity and CAVI was observed with increasing age, even though the difference did not reach the statistical significance. Conclusions: Hp-seropositivity was significantly associated with arterial stiffness. Hp infection may contribute to the development of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. The aim of this study was to evaluate arterial stiffness by CAVI in PCOS patients (n = 26) and in the age-matched controls (n = 59). The CAVI was measured by a single medical professional. The mean age of the women with PCOS was 33.3 (±6.6) years, and that of the matched controls was 33.1 (±5.9) years (p = .861). The mean CAVIs were similar between the patients and controls (6.49 ± 0.41 and 6.39 ± 0.65, respectively, p = .452). The CAVI increased linearly with age in both groups, but in the women with PCOS, CAVI showed relatively strong negative correlations with body mass index (BMI) in both the unadjusted (r = -0.537, p = .005) and adjusted models (r = -0.474, p = .003 after age and BMI adjustment and r = -0.604, p = .033 after age, BMI, sitting auscultatory systolic BP and square root hs-CRP adjustment). In conclusion, relatively young women with PCOS may not have increased arterial stiffness. A negative correlation between CAVI and BMI in women with PCOS requires further study to determine whether vascular adaptation to adiposity occurred in these women. Impact Statement What is already known on this subject? Increased arterial stiffness is one of the earliest adverse structural and functional alterations in blood vessels, potentially leading to later cardiovascular disease. Many studies have reported an increased arterial stiffness using pulse wave velocity (PWV) in women with polycystic ovary syndrome (PCOS). However, PWV is essentially dependent on blood pressure (BP) at the time of measurement. The cardio-ankle vascular index (CAVI) is a relatively new index for measuring arterial stiffness, and its conspicuous feature is its independency from the BP at the time of measurement. What do the results of this study add? The CAVIs were similar between the women with PCOS and the age-matched controls. The CAVI increased linearly with age in both groups, but in women with PCOS, CAVI showed a relatively strong negative correlation with the body mass index (BMI). What are the implications of these findings for clinical practice and/or further research? Relatively young women with PCOS may not have increased arterial stiffness. However, CAVI showed a negative correlation with BMI only in the women with PCOS, suggesting that adiposity itself is associated with the decreased arterial stiffness in these women. This finding requires a replication, and whether adaptation to the hemodynamic consequences of adiposity occurred in the PCOS patients remains to be established. Further longitudinal studies are needed to verify the relationships among vascular stiffness, adiposity and PCOS. [ABSTRACT FROM AUTHOR]

Epidemiologic evidence indicates that the prevalence and severity of coronary artery disease vary depending on ethnicity. In this study, a genome-wide association study for coronary artery calcification (CAC) was performed in a Korean population-based sample of 400 subjects without prior coronary artery disease and replicated in another of 1,288 subjects. CAC score, as assessed by multi-detector computed tomography, was evaluated in volunteers for screening purposes as part of a routine health examination. CAC score greater than the 90th percentile across the age in each sex group was considered severe CAC. Single nucleotide polymorphisms (SNPs) associated with severe CAC after adjusting for age, sex, hypertension, and diabetes were investigated using the additive model of logistic regression. One SNP (rs10757272 in the intronic region of the CDKN2B-AS1 gene in chromosome 9p21.3) met Bonferroni correction in the discovery set (p = 7.55E-08) and was also significant in the validation set by TaqMan assay (p = 0.036). Subjects with rs10757272 were found to have an increased odds ratio (OR) of having severe CAC in multivariate logistic regression analysis after adjusting for age, sex, hypertension, and diabetes (adjusted OR 3.24 and 95% CI 2.11–4.97). In conclusion, SNP rs10757272 in chromosome 9p21.3 was associated with severe CAC based on age and sex in an asymptomatic community-based Korean population. Therefore, it was associated with promotion of coronary artery calcification in subclinical state. [ABSTRACT FROM AUTHOR]

Background: Nonalcoholic fatty liver disease (NAFLD) plays a significant role in coronary atherosclerosis, independent of shared metabolic risk factors. The measurement of the controlled attenuation parameter (CAP) has shown to allow early and noninvasive detection of NAFLD at subclinical stage. We evaluated the significance of CAP-defined NAFLD in association with the presence of any type of coronary plaques and different plaque compositions.Methods: We conducted a retrospective cohort of apparently healthy subjects who had liver Fibroscan and coronary computed tomography during health screening exams.Results: A greater number of subjects with CAP-defined NAFLD was found in group with coronary plaques (61.3% vs. 73.5%, p = 0.005 without vs. with any type of plaque). From multivariate regression model, CAP ≥ 222 dB/m was an independent and significant parameter associated with the presence of coronary plaques, after adjusting possible confounders (OR 1.624, 95% 1.047-2.518, p = 0.030). Interestingly, CAP ≥ 222 dB/m was significantly associated with non-calcified plaque (adjusted OR 3.528, 95% CI 1.463-8.511, p = 0.005), whereas it was not significant in calcified plaques (p = 0.171).Conclusion: CAP-defined NAFLD is independently associated with coronary plaques, especially non-calcified plaques. The association between NAFLD and non-calcified plaques suggests that particular attention should be given to the subjects with NAFLD for primary prevention. [ABSTRACT FROM AUTHOR]

Purpose. Left ventricular (LV) mass is determined by the wall thickness and diameter. LV hypertrophy (LVH), the increase in LV mass, is usually screened with electrocardiography but is often insensitive. We tried to fortify the rule to detect LVH using cardiothoracic ratio (CTR) in chest X-ray and well-known risk factors besides electrocardiography. Materials and Methods. This retrospective cross-sectional study included asymptomatic hypertensive individuals aged ≥40 y who underwent voluntary checkups including echocardiography. Independent variables to explain LVH (LV mass index>115 g/m2 for men and >95 g/m2 for women calculated on echocardiography) were chosen among Sokolow-Lyon voltage amplitude (SLVA), CTR and cardiovascular risk factors by multiple logistic regression analysis. The diagnostic rule to detect LVH was made by summing up the rounded-off odds ratio of each independent variable and was validated using bootstrapping method. Results. Among the 789 cases enrolled (202 females (25.6%), mean age 59.6±8.8 y), 168 (21.3%) had LVH. The diagnostic rule summed female, age≥65 y, BMI≥25 kg/m2, SLVA≥35 mm, and CTR≥0.50 (scoring 1 per each). Its c-statistics was 0.700 (95% CI: 0.653, 0.747), significantly higher (p<0.001) than that of SLVA≥35 mm, 0.522 (95% CI: 0.472, 0.572). The sensitivity and specificity of the model were 61.9% and 72.1% for score≥2 and 30.4% and 92.9% for score≥3. The SLVA≥35 mm criteria showed sensitivity of 12.5% and specificity of 91.9%. Conclusions. The rule to sum up the number of the risk factors of female, age≥65 y, BMI≥25 kg/m2, SLVA≥35 mm, and CTR≥0.50 may be a better diagnostic tool for screening LVH, than the electrocardiography-only criteria, at the score≥2. [ABSTRACT FROM AUTHOR]

Objectives: Hyponatraemia is a well-known predictor of clinical outcomes in heart failure (HF). However, the mechanism remains poorly understood. Previous reports suggest that hyponatraemia is related to right HF. We sought to evaluate the association between right ventricular (RV) dysfunction and hyponatraemia, and the impact of this relationship on the prognosis of patients with acute heart failure (AHF).Methods: This is a nested case-control study of the Korean Acute Heart Failure registry. Among 2935 AHF patients enrolled prospectively and consecutively at four tertiary hospitals in Korea from 2011 to 2014, 116 patients with severe persistent hyponatraemia, defined as serum sodium level <130 mmol/L at admission and <135 mmol/L before discharge, were matched with 232 controls, based on propensity scores for hyponatraemia. RV function was assessed with fractional area change (FAC) by echocardiography.Results: RV dysfunction (FAC <35%) was more prevalent in patients with severe persistent hyponatraemia than in those without (81.0% vs 33.6%, p<0.001). Hyponatraemia was strongly associated with RV dysfunction (adjusted OR 8.00, 95% CI 4.50 to 14.22, p<0.001), but not with left ventricular dysfunction (adjusted OR 1.21, 95% CI 0.74 to 1.50, p=0.308). RV dysfunction was an independent predictor of all-cause mortality, after adjustment for hyponatraemia (adjusted HR 2.20, 95% CI 1.53 to 3.15, p<0.001), while hyponatraemia was not (adjusted HR 1.33, 95% CI 0.94 to 1.87, p=0.108).Conclusions: In patients with AHF, hyponatraemia was more common with RV dysfunction. RV dysfunction, rather than hyponatraemia, was more significantly related with patients' prognosis. Thus, the utility of RV dysfunction instead of hyponatraemia per se should be considered in HF risk models.Trial Registration Number: Korean Acute Heart Failure registry NCT01389843; Results. [ABSTRACT FROM AUTHOR]

Background: Gestational hypertensive diseases (GHD) and gestational diabetes mellitus (GDM) increase the risk of cardiovascular disease (CVD) later in life. However, the association between gestational medical diseases and familial history of CVD has not been investigated to date. In the present study, we examined the association between familial history of CVD and GHD or GDM via reliable questionnaires in a large cohort of registered nurses. Methods: The Korean Nurses’ Survey was conducted through a web-based computer-assisted self-interview, which was developed through consultation with cardiologists, gynecologists, and statisticians. We enrolled a total of 9,989 female registered nurses who reliably answered the questionnaires including family history of premature CVD (FHpCVD), hypertension (FHH), and diabetes mellitus (FHDM) based on their medical knowledge. Either multivariable logistic regression analysis or generalized estimation equation was used to clarify the effect of positive family histories on GHD and GDM in subjects or at each repeated pregnancy in an individual. Results: In this survey, 3,695 subjects had at least 1 pregnancy and 8,783 cumulative pregnancies. Among them, 247 interviewees (6.3%) experienced GHD and 120 (3.1%) experienced GDM. In a multivariable analysis adjusted for age, obstetric, and gynecologic variables, age at the first pregnancy over 35 years (adjusted OR 1.61, 95% CI 1.02–2.43) and FHpCVD (adjusted OR 1.60, 95% CI 1.16–2.22) were risk factors for GHD in individuals, whereas FHH was not. FHDM and history of infertility therapy were risk factors for GDM in individuals (adjusted OR 2.68, 95% CI 1.86–3.86; 1.84, 95% CI 1.05–3.23, respectively). In any repeated pregnancies in an individual, age at the current pregnancy and at the first pregnancy, and FHpCVD were risk factors for GHD, while age at the current pregnancy, history of infertility therapy, and FHDM were risk factors for GDM. Conclusions: The FHpCVD and FHDM are significantly associated with GHD and GDM, respectively. Meticulous family histories should be obtained, and women with family histories of these conditions should be carefully monitored during pregnancy. [ABSTRACT FROM AUTHOR]

Background: Coronary computed tomographic angiography (CCTA) facilitates comprehensive evaluation of coronary artery disease (CAD), including plaque characterization, and can provide additive diagnostic value to single-photon emission computed tomography (SPECT). However, data regarding the incremental prognostic value of CCTA to SPECT remain sparse. We evaluated the independent and incremental prognostic value of CCTA, as compared with clinical risk factors and SPECT. Materials and methods: A total of 1,077 patients with suspected CAD who underwent both SPECT and cardiac CT between 2004 and 2012 were enrolled retrospectively. Presence of reversible or fixed perfusion defect (PD) and summed stress score were evaluated on SPECT. Presence, extent of coronary atherosclerosis and diameter stenosis (DS) were evaluated on CCTA. Plaque composition was categorized as non-calcified, mixed, or calcified according to the volume of calcified component (>130 Hounsfield Units). Patients were followed up for the occurrence of adverse cardiac events including cardiac death, non-fatal myocardial infarction, unstable angina, and late revascularization (>90 days after imaging studies). Results: During follow-up (median 23 months), adverse cardiac events were observed in 71 patients (6.6%). When adjusted for clinical risk factors and SPECT findings, the presence of any coronary plaque, any plaque in ≥3 segments, coronary artery calcium score (CACS) ≥400, a plaque ≥50% DS, presence of non-calcified plaque (NCP) or mixed plaque (MP), and NCP/MP in ≥2 segments were independent predictors of adverse cardiac events; however, the presence of calcified plaque (CP) was not. Conventional CCTA findings, including CACS ≥400 and a plaque ≥50% DS, demonstrated incremental prognostic value over clinical risk factors and SPECT (χ² 54.19 to 101.03; p <0.001). Addition of NCP/MP in ≥2 segments resulted in further significantly improved prediction (χ² 101.03 to 113.29; p <0.001). Conclusion: Comprehensive CCTA evaluation of coronary atherosclerosis provides independent and incremental prognostic value in relation to SPECT evaluation of myocardial ischemia. Specifically, segmentally-analyzed plaque composition with CCTA provides further risk stratification in addition to CACS and DS. [ABSTRACT FROM AUTHOR]

Although ischemic stroke and coronary artery disease (CAD) share common risk factors and pathophysiology, the risk of stroke in patients with CAD remains unclear. We sought to evaluate the risk of ischemic stroke in patients with suspected CAD according to coronary computed tomographic angiography (CCTA) and single-photon emission computed tomography (SPECT) findings. Presence, severity, and extent of CAD were evaluated in 1137 patients with suspected CAD who underwent CCTA and SPECT. Primary outcome was the occurrence of ischemic stroke. During follow-up (median 26 months), ischemic stroke was observed in 25 patients (2.2%). The presence of coronary plaque on CCTA was associated with the occurrence of ischemic stroke (2.8 vs. 0.6%; p = 0.029), while the presence of PD on SPECT was not (2.0 vs. 2.3%; p = 0.768). Stroke occurrence was not increased by the presence of significant stenosis of ≥50% DS (2.8%; p = 0.943), but was further increased by the plaque presence in ≥2 vessels (6.1 %; p = 0.001) or ≥3 segments (4.1%; p = 0.019). Presence of calcified plaque, and calcified plaque in ≥2 segments were also associated with ischemic stroke occurrence (4.3%; p < 0.001, and 5.6%; p < 0.001, respectively) and were the independent risk factors when adjusted to age of ≥65, hypertension, presence of any coronary plaque and plaque in ≥3 segments (adjusted HR 6.09; 95% CI 1.38-26.87; p = 0.017, and adjusted HR 5.47; 95% CI 1.85-16.19; p = 0.002, respectively). The risk of ischemic stroke was associated with the presence and extent of coronary atherosclerotic plaque evaluated by CCTA, but not with the presence and extent of myocardial ischemia evaluated by SPECT. Especially, calcified coronary plaque presence and extent were the independent predictors of ischemic stroke and allowed further risk stratification. [ABSTRACT FROM AUTHOR]

Although hypertrophic cardiomyopathy (HCM), the most common inherited cardiomyopathy, has mortality rate as low as general population, previous studies have focused on identifying high-risk of sudden cardiac death. Thus, long-term systemic impact of HCM is still unclear. We sought to investigate the association between HCM and end-stage renal disease (ESRD). This was a nationwide population-based cohort study using the National Health Insurance Service database. We investigated incident ESRD during follow-up in 10,300 adult patients with HCM (age 62.1 years, male 67.3%) and 51,500 age-, sex-matched controls. During follow-up (median 2.8 years), ESRD developed in 197 subjects; 111 (1.08%) in the HCM, and 86 (0.17%) in the non-HCM (incidence rate 4.14 vs. 0.60 per 1,000 person-years, p < 0.001). In the HCM, the incidence rate for ESRD gradually increased with age, but an initial peak and subsequent plateau in age-specific risk were observed. HCM was a significant predictor for ESRD (unadjusted HR 6.90, 95% CI 5.21–9.15, p < 0.001), as comparable to hypertension and diabetes mellitus. Furthermore, after adjusting for all variables showing the association in univariate analysis, HCM itself remained a robust predictor of ESRD development (adjusted HR 3.93, 95% CI 2.82–5.46, p < 0.001). The consistent associations between HCM and ESRD were shown in almost all subgroups other than smokers and subjects with a history of stroke. Conclusively, HCM increased the risk of ESRD, regardless of known prognosticators. It provides new insight into worsening renal function in HCM, and active surveillance for renal function should be considered. [ABSTRACT FROM AUTHOR]