The short-term effect of ambient particulate matter on suicide death.

BACKGROUND: Air pollution can cause various respiratory and neurological diseases and continuous exposure can lead to death. Previous studies have reported that particulate matter (PM) exposure increases the risk of depression, suicidal thoughts, and suicidal death; however, the results are inconsistent and limited. This study aimed to examine the relationship between short-term PM exposure and suicide deaths, as well as investigate the short-term effects of PM on suicide death within vulnerable groups based on factors such as sex, age group, suicide-related information (note, method, and cause), psychiatric disorders, and physical diseases. METHODS: Data on a total of 28,670 suicide deaths from 2013 to 2017, provided by the Korea Foundation for Suicide Prevention, were analyzed. The study design employed a time-series analysis with a two-stage approach. In the first step, a generalized additive model combined with a distributed lag nonlinear model was used to estimate the short-term effect of PM exposure on suicide risk specific to each city. In the second step, the estimated results from each city were pooled through a meta-analysis to derive the overall effect. We determined the effects of single lag, cumulative lag, and moving average PM concentrations from days 0-7 before suicide. RESULTS: We confirmed an association between exposure to PM10 (≤ 10 µm in diameter) and deaths due to suicide. In particular, among individuals with psychiatric disorders and those who employed non-violent suicide methods, increased exposure to PM10 was associated with a higher risk of death by suicide, with percentage changes of 5.92 (95% confidence interval [CI]: 3.95-7.92) and 11.47 (95% CI: 7.95-15.11), respectively. Furthermore, in the group with psychiatric disorders, there was an observed tendency of increasing suicide risk as PM10 levels increased up to 120 µg/m3, whereas in the group with non-violent suicide deaths, there was a pronounced trend of rapid increase in suicide risk with an increase in PM10 up to 100 µg/m3. CONCLUSIONS: These results show an association between short-term exposure to PM and suicide. Our study adds evidence for the benefits of reducing PM in preventing diseases and improving mental health.

Trends in commonly used and potentially inappropriate medications in older Korean patients with polypharmacy.

BACKGROUND: Polypharmacy is a global public health concern. This study aimed to determine the prevalence of polypharmacy and trends in the use of commonly used and potentially inappropriate medications among older Korean patients. METHODS: Individuals aged ≥ 65 years who were prescribed any medication between 2014 and 2018 were selected from the Korean National Health Information Database. Joinpoint regression analyses were used to determine trends in the age-adjusted polypharmacy rates by age group. The prescription rates of the most commonly used medications and the most commonly used potentially inappropriate medications were analysed by year or age group for patients with polypharmacy using the chi-square and proportion difference tests. RESULTS: This study included 1,849,968 patients, 661,206 (35.7%) of whom had polypharmacy. Age-adjusted polypharmacy rates increased significantly between 2014 and 2018 (P = 0.046). Among patients with polypharmacy, the most commonly prescribed medications were aspirin (100 mg), atorvastatin, metformin, glimepiride, and rosuvastatin. The most commonly prescribed and potentially inappropriate medications were alprazolam, diazepam, amitriptyline, zolpidem, and dimenhydrinate. There was a significant decrease in the prescription rates for each of these drugs in 2018 compared with 2014 among patients with polypharmacy (all P < 0.001), whereas there was a significant increase in alprazolam prescription among patients aged ≥ 85 years when analysed by age group (P < 0.001). CONCLUSIONS: This study revealed an increasing prevalence of polypharmacy among older adults. Additionally, it highlighted that the utilisation of commonly prescribed potentially inappropriate medications, such as benzodiazepines and tricyclic antidepressants, has remained persistent, particularly among patients aged ≥ 85 years who practiced polypharmacy. These findings provide evidence-based guidance for the development of robust polypharmacy management strategies to ensure medication safety among older adults.

Contrast Agent Selection to Prevent Recurrent Severe Hypersensitivity Reaction to Iodinated Contrast Media Based on Nationwide Database.

OBJECTIVE: To investigate the incidence of severe iodinated contrast media (ICM)-related hypersensitivity reaction (HSR) and to find the optimal alternative ICM to reduce the risk of severe HSR recurrence. METHODS: We retrospectively reviewed 23,383,183 cases of ICM administration between January 2015 and December 2019 from the nationwide health insurance database. We classified ICMs based on generic profiles and the presence of N-(2,3-dihydroxypropyl) carbamoyl side chains. The incidence of severe and recurrent severe HSRs was calculated, and χ2 tests were performed to compare the prevalence of severe HSR according to ICM groups. In addition, logistic regression analyses were used to assess differences between ICM groups. RESULTS: The incidence of severe HSRs was 1.92% (450,067 of 23,282,183). Among 1,875,245 individuals who received ICM twice on different days, severe HSR occurred in 40,850 individuals, and severe HSR recurred in 3319 individuals (8.12%). The risk of recurrence significantly decreased when the ICM changed (9.24% vs 7.08%, P < 0.001), especially when the ICM changed to one with a different side chain (6.74%, P < 0.001). In addition, compared with the reuse of the culprit agent, using combinations of iobitridol/iohexol (odds ratio [OR], 0.696; P = 0.04), iohexol/iopamidol (OR, 0.757; P = 0.007), iopamidol/iohexol (OR, 0.447; P < 0.001), and ioversol/iohexol (OR, 0.683; P = 0.04) reduced the risk of recurrence of severe HSR. CONCLUSIONS: Changing the culprit ICM to that with a different side chain can reduce severe HSR recurrence. The optimal choice of an alternative ICM depends on the causative agent.

Randomized, triple-blind, placebo-controlled study to evaluate the safety of 6'-Sialyllactose in healthy adults.

Sialyllactoses (SL) are an abundant component of human milk. There have been many studies on the biological effects of SL in humans. SL can be produced using an economical method of enzyme synthesis. Although the European Food Safety Authority has published the human safety and appropriate intake dose of 6'-SL sodium salt as a novel food, it has suggested that the appropriate dose for particular medical purposes be judged on a case-by-case basis. Also, as revealed in the same report, there are no data on toxicity when 6'-SL is used in human intervention. However, clinical studies have only confirmed the safety of 3'-SL for therapeutic intervention in humans, and the safety for therapeutic use of 6'-SL, which is more abundant than 3'-SL in human milk, has not been confirmed. In this study, to determine the safety of 6'-SL use in humans, participants were randomly assigned to the placebo (maltodextrin) and 6'-SL groups, and then 3 g of powder was orally administered twice a day for 12 weeks. There were no serious adverse reactions, such as life-threatening complications requiring hospitalization, causing disability, or causing deformity during the use of 6'-SL. There were no clinically significant differences among the baseline, sixth, and twelfth week clinical chemistry tests, such as aspartate aminotransferase, alanine aminotransferase, and creatinine. Most of the adverse reactions were gastrointestinal problems such as diarrhea, abdominal discomfort, and bloating, with no significant difference in the proportions between the placebo and 6'-SL groups. These results support the safety of the 6'-SL for human use.

Age and sex dependent association of uric acid and incident hypertension.

BACKGROUND AND AIMS: A previous meta-analysis suggested that the relationship between hyperuricemia and hypertension may be stronger in younger individuals and women. We aimed to investigate the age and sex dependent association of uric acid (UA) and incident hypertension. METHODS AND RESULTS: We analyzed data from the Health Examinees Study, a community-based prospective cohort study conducted in Korea from 2004 to 2013. It included 29,088 non-hypertensive subjects aged 40-79 (age, 52.5 ± 7.8 years; men, 31.4%) who had serum UA measurement and participated in the follow-up survey. The risk factors of hypertension were assessed using Cox regression. Over a mean 3.8 years of follow-up, 1388 men (15.2%) and 1942 women (9.7%) were newly diagnosed with hypertension. Upon age- and sex-based stratification, the risk of hypertension was highest in hyperuricemic subjects aged 40-49 years (HR: women, 2.16; men, 1.30). Across the entire cohort, the risk of incident hypertension was higher in groups with higher serum UA levels, and highest in women aged 40-49 years (HR, 1.44; P < 0.001). On multivariable linear regression analysis, the higher the baseline serum UA level, the greater the increase in blood pressure during follow-up, and this effect was strongest in women aged 40-49 years (ß = 0.87 and P < 0.01 for systolic blood pressure). CONCLUSIONS: The relationship between uric acid and incident hypertension tended to be dependent on age and sex. Younger women are at highest risk of UA-related incident hypertension.

Evaluation of Adherence to Guideline for Heart Failure with Reduced Ejection Fraction in Heart Failure with Preserved Ejection Fraction and with or without Atrial Fibrillation.

BACKGROUND: This study evaluated the relationship between guideline adherence for heart failure (HF) with reduced ejection fraction (HFrEF) at discharge and relevant clinical outcomes in patients with acute HF with preserved ejection fraction (HFpEF) with or without atrial fibrillation (AF). METHODS: We analyzed Korean Acute Heart Failure Registry data for 707 patients with HFpEF with documented AF and 687 without AF. Guideline adherence was defined as good or poor according to the prescription of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, ß-blockers, and mineralocorticoid receptor antagonists. Anticoagulation adherence was also incorporated for the AF group. RESULTS: Among patients with normal sinus rhythm, those with poor guideline adherence had a reduced prevalence of comorbidities and favorable clinical characteristics when compared with those with good guideline adherence. Using inverse probability of treatment weighting (IPTW) to address the bias of nonrandom treatment assignment, good adherence was associated with a poor 60-day composite endpoint in the multivariable Cox model (weighted hazard ratio [wHR], 1.74; 95% confidence interval [CI], 1.01-3.00; P = 0.045). For patients with AF, baseline clinical characteristics were similar according to the degree of adherence. The IPTW-adjusted analysis indicated that good adherence was significantly associated with the 60-day composite endpoint (wHR, 0.47; 95% CI, 0.27-0.79; P = 0.005). In the analysis excluding warfarin, good adherence was associated with 60-day re-hospitalization (wHR, 0.60; 95% CI, 0.37-0.98; P = 0.040), 1-year re-hospitalization (wHR, 0.67; 95% CI, 0.48-0.93; P = 0.018), and the composite endpoint (wHR, 0.77; 95% CI, 0.59-0.99; P = 0.041). CONCLUSION: Our findings indicate that good adherence to guidelines for HFrEF is associated with a better 60-day composite endpoint in patients with HFpEF with AF.

Quantitative pupillary light reflex assessment for prognosis of carbon monoxide poisoning.

Background: A non-reactive pupil in standard pupillary light reflex (sPLR) is regarded as a factor predicting neurological sequelae at 1-month after carbon monoxide (CO) poisoning. An automated pupillometer is used in the intensive care unit to quantitatively assess PLR. Quantitative PLR (qPLR) was superior to sPLR using penlight for prognosis of various neurological diseases. Therefore, this study aimed to analyze whether quantitative pupillary variables (neurological Pupil index [NPi] and qPLR) are superior to sPLR in predicting 1-month neurocognitive sequelae after acute CO poisoning. Methods: We performed a prospective observational study of consecutive patients with acute CO poisoning admitted to an emergency department (ED) between August 2019 and December 2020 in a single academic medical center. sPLR and pupillometer examinations (qPLR and NPi) were performed by emergency physicians at the ED on hospital days 0-2. The lowest values among those recorded within 24 h and during the total measurement period were considered the 24-h and total lowest values, respectively. Global Deterioration Scale scores were measured at 1 month as an outcome and were dichotomized into favorable (1-4) or poor (5-7) outcomes. Results: We analyzed the data of 104 adult patients with acute CO poisoning. qPLR was significantly higher in the favorable outcome group than in the poor outcome group 24-h and total lowest values (21.2% vs. 15.0%, p = 0.006 and 21.0% vs. 14.8%, p = 0.006). qPLR <18% had fair predictive power for poor neurocognitive outcomes [area under the curve (AUC), 0.70; 95% confidence interval (0.60-0.78)]. Among the patients with decreased mental status (Glasgow Coma Scale ≤12), the power of NPi and qPLR increased [AUC, 0.72 and AUC, 0.80]. NPi < 1 and qPLR <18% showed sensitivity (9.5% vs. 76.2%) and specificity (98.8% vs. 67.5%) for the prediction of poor outcomes. qPLR was significantly superior to sPLR in predicting poor neurocognitive outcomes at 1 month after CO poisoning (p = 0.007). Conclusion: qPLR and NPi were superior to sPLR in terms of predicting poor neurocognitive outcomes. qPLR and NPi measured from hospital days 0-2 may be valuable in predicting neurocognitive outcome.

Adjuvant intravenous immunoglobulin administration on postoperative critically ill patients with secondary peritonitis: a retrospective study.

BACKGROUND: The use of intravenous immunoglobulin (IVIG) in sepsis patients from bowel perforation is still debatable. However, few studies have evaluated the effect of IVIG as an adjuvant therapy after source control. This study aimed to analyze the effect of IVIG in critically ill patients who underwent surgery due to secondary peritonitis. METHODS: In total, 646 medical records of surgical patients who were treated for secondary peritonitis were retrospectively analyzed. IVIG use, initial clinical data, and changes in Sequential Organ Failure Assessment (SOFA) score over the 7-day admission in the intensive care unit for sepsis check, base excess, and delta neutrophil index (DNI) were analyzed. Mortalities and periodic profiles were assessed. Propensity scoring matching as comparative analysis was performed in the IVIG group and non-IVIG group. RESULTS: General characteristics were not different between the two groups. The survival curve did not show a significantly reduced mortality in the IVIG. Moreover, the IVIG group did not have a lower risk ratio for mortality than the non-IVIG group. However, when the DNI were compared during the first 7 days, the reduction rate in the IVIG group was statistically faster than in the non-IVIG group (P<0.01). CONCLUSIONS: The use of IVIG was significantly associated with faster decrease in DNI which means faster reduction of inflammation. Since the immune system is rapidly activated, the additional use of IVIG after source control surgery in abdominal sepsis patients, especially those with immunocompromised patients can be considered. However, furthermore clinical studies are needed.

Remnant cholesterol, low-density lipoprotein cholesterol, and incident cardiovascular disease among Koreans: a national population-based study.

AIMS: The synergistic association of remnant cholesterol (remnant-C) and low-density lipoprotein cholesterol (LDL-C) levels with incident cardiovascular disease (CVD) in various subgroups of Koreans was investigated. METHODS AND RESULTS: Using the national health insurance data, we included subjects aged between 40 and 70 years without a history of CVD and at least two health screenings between 2009 and 2011. The subjects were divided into four groups by LDL-C and remnant-C levels. The primary outcome was CVD, which occurred between 2014 and 2017. Among 3 686 034 (45.6% women) subjects, 144 004 cardiovascular events occurred. Individuals in both high LDL-C and high remnant-C [hazard ratio (HR) 1.266, 95% confidence interval (CI) 1.243-1.289; 7.9%], high LDL-C only (HR 1.098, 95% CI 1.083-1.113; 21.2%), and high remnant-C only groups (HR 1.102, 95% CI 1.087-1.118; 19.1%) had higher risks of CVD than those in the reference group (LDL-C < 3.4 mmol/L and remnant-C < 0.8 mmol/L; 51.8%). A continuous and linear increase in CVD risk was found in those with higher remnant-C levels after adjustment for several confounders, including LDL-C levels. The association of remnant-C ≥ 0.8 mmol/L with an increased CVD risk was consistent across various strata. CONCLUSIONS: Combined high remnant-C and LDL-C levels confer a higher CVD risk than that individually. Elevated remnant-C values independent of LDL-C levels were associated with a risk of incident CVD. Remnant cholesterol levels in addition to LDL-C levels are important considerations in risk stratification for the primary prevention of CVD.

Since remnant-C has recently emerged as a potential risk factor for CVD, the synergistic association of LDL-C and remnant-C with CVD has been investigated among 3 686 034 Koreans (45.6% women) without preceding CVD using nationwide population-based big data. Remnant cholesterol remained proportional to the risk of incident CVD after adjusting for multiple variables, including LDL-C levels.Low-density lipoprotein cholesterol and remnant-C synergistically contributed to incident CVD.

High Platelet Reactivity Combined with CYP2C19 Genotype in Predicting Outcomes in East Asian Patients Undergoing Percutaneous Coronary Intervention.

Loss-of-function (LoF) alleles of cytochrome P450 2C19 (CYP2C19), which are prevalent in East Asians, are linked to high platelet reactivity (HPR) phenotype and poor prognosis. We aimed to investigate the incremental predictive value of HPR combined with CYP2C19 genotype in predicting outcomes after drug-eluting stent (DES) implantation. The patients treated with platelet function and genotype-related long-term prognosis in drug-eluting stent (PTRG-DES) consortium enrolled a total of 13,160 Korean patients treated with DES who had platelet function test (PFT) or CYP2C19 genotype, of which, 6,717 patients with PFT and genotype together were categorized. HPR was defined as VerifyNow ≥ 252 P2Y12 reaction unit. The primary outcome was the incidence of major adverse cardiac and cerebrovascular event (MACCE) 5 years after treatment. The patients with both HPR and CYP2C19 LoF/LoF had the highest MACCE rates (6.2%) and increased MACCE risk (adjusted hazard ratio: 1.89, 95% confidence interval: 1.20-2.91, P = 0.006) compared with those without both HPR and CYP2C19 LoF/LoF. There was no effect of interaction between HPR and CYP2C19 genotype on the primary outcome (P = 0.424). Adding combined HPR and CYP2C19 genotype to the conventional model had an incremental influence in predicting MACCE and stent thrombosis. Compared to the model including HPR or CYP2C19 genotype alone, a combination model significantly improved the risk stratification for stent thrombosis but not MACCE. In DES-treated East Asian patients, the combined evaluation of PFT results and CYP2C19 genotyping might improve risk prediction of ischemic events during clopidogrel treatment.

Association between lifestyle factors and metabolic syndrome in general populations with depressive symptoms in cross-setional based cohort study of Ansung-Ansan.

BACKGROUND: Metabolic syndrome (MetS) is caused by both genetic and environmental factors, such as daily calorie intake, smoking, and alcohol consumption. Lifestyle factors, such as alcohol consumption, are considered to be related to the prevalence of MetS and plays an essential role in the pathogenesis and prognosis of depression. METHODS: We investigated the bidirectional association between lifestyle factors and MetS among Korean adults with depressive symptoms in third wave of a community-based cohort study. A total of 1,578 individuals, aged 39-72 years, who had MetS at baseline were recruited. Participants were divided into two groups according to depressive symptoms. Logistic regression models were used to estimate the risk of MetS. RESULTS: The percentage of heavy drinkers was lower in men with depressive symptoms compared to those who did not (7.0% vs. 7.1%), while the percentage of current smokers were higher in participants who had depressive symptoms (40.2% vs. 30.0%). After adjusting for age, education, monthly income, body mass index (BMI), sleep duration, and volume of drinking and smoking status, logistic regression analysis demonstrated that male heavy drinkers with depressive symptoms were 2.75 times more likely to have MetS than those without depressive symptom. Conversely, depressive women with a high BMI were 3.70 times more likely to have MetS than in those with lower BMI. Limitations The cross-sectional nature of the study, and the study population ethnicity and ages were limitations. CONCLUSIONS: Lifestyle factors, such as alcohol consumption, may be associated with the risk of MetS in adults with depressive symptoms.

Digital Biomarkers in Living Labs for Vulnerable and Susceptible Individuals: An Integrative Literature Review.

PURPOSE: The study aimed to identify which digital biomarkers are collected and which specific devices are used according to vulnerable and susceptible individual characteristics in a living-lab setting. MATERIALS AND METHODS: A literature search, screening, and appraisal process was implemented using the Web of Science, Pubmed, and Embase databases. The search query included a combination of terms related to "digital biomarkers," "devices that collect digital biomarkers," and "vulnerable and susceptible groups." After the screening and appraisal process, a total of 37 relevant articles were obtained. RESULTS: In elderly people, the main digital biomarkers measured were values related to physical activity. Most of the studies used sensors. The articles targeting children aimed to predict diseases, and most of them used devices that are simple and can induce some interest, such as wearable device-based smart toys. In those who were disabled, digital biomarkers that measured location-based movement for the purpose of diagnosing disabilities were widely used, and most were measured by easy-to-use devices that did not require detailed explanations. In the disadvantaged, digital biomarkers related to health promotion were measured, and various wearable devices, such as smart bands and headbands were used depending on the purpose and target. CONCLUSION: As the digital biomarkers and devices that collect them vary depending on the characteristics of study subjects, researchers should pay attention not only to the purpose of the study but also the characteristics of study subjects when collecting and analyzing digital biomarkers from living labs.

Validation of age- and sex-dependent association of uric acid and incident hypertension in rural areas.

BACKGROUND: A previous study based on urban areas suggested the age- and sex-dependent association of uric acid (UA) and incident hypertension. We aimed to investigate whether this association is valid even in rural areas with different lifestyle. METHODS: Data from the cardiovascular disease association study, a prospective cohort study based on rural residents, was analyzed. A total of 4,592 subjects (mean age, 60.1 ± 9.5 years; men, 37.7%) without hypertension were included. We first investigated whether UA was a risk factor for incident hypertension using Cox regression, and then compared the relative risk by stratification according to age and sex. RESULTS: During the follow-up period (mean, 2.0 years), 579 subjects (12.6%) were newly diagnosed with hypertension. The risk factors for incident hypertension were age (Hazard ratios [HR] for ≥ 65, 1.26), systolic blood pressure (HR per 1 mmHg increase, 1.07), and serum UA concentration (HR per 1 mmHg increase, 1.10). The risk of UA-related incident hypertension was higher in the non-elderly than in the elderly for both men and women (HR, 1.74 for non-elderly men; 1.88 for non-elderly women; 1.66 for elderly men; 1.10 for elderly women). Even after adjusting for multiple confounders, the risk of UA-related incident hypertension was significantly higher in non-elderly women (HR, 1.59; P < 0.05). CONCLUSIONS: Age- and sex-dependent association of UA with incident hypertension suggested in cohort study based on urban areas was consistently found in rural areas as well. In particular, non-elderly women were at a higher risk for UA-related incident hypertension.

Patterns of patients with polypharmacy in adult population from Korea.

Polypharmacy and its rising global prevalence is a growing public health burden. Using a large representative nationwide Korean cohort (N = 761,145), we conducted a retrospective cross-sectional study aiming to identify subpopulations of patients with polypharmacy and characterize their unique patterns through cluster analysis. Patients aged ≥ 30 years who were prescribed at least one medication between 2014 and 2018 were included in our study. Six clusters were identified: cluster 1 mostly included patients who were hospitalized for a long time (4.3 ± 5.3 days); cluster 2 consisted of patients with disabilities (100.0%) and had the highest mean number of prescription drugs (7.7 ± 2.8 medications); cluster 3 was a group of low-income patients (99.9%); cluster 4 was a group of high-income patients (80.2%) who frequently (46.4 ± 25.9 days) visited hospitals/clinics (7.3 ± 2.7 places); cluster 5 was mostly elderly (74.9 ± 9.8 years) females (80.3%); and cluster 6 comprised mostly middle-aged (56.4 ± 1.5 years) males (88.6%) (all P < 0.001). Patients in clusters 1-5 had more prescribed medications and outpatient visit days than those in cluster 6 (all P < 0.001). Given limited health care resources, individuals with any of the identified phenotypes may be preferential candidates for participation in intervention programs for optimal medication use.

Reference diameter and characteristics of the distal radial artery based on ultrasonographic assessment.

BACKGROUND/AIMS: While distal radial artery (DRA) access is increasingly being used for diagnostic coronary angiography, limited information is available regarding DRA size. We aimed to determine the DRA reference diameters of Korean patients and identify the predictors of DRA diameter < 2.3 mm. METHODS: The outer bilateral DRA diameters were assessed using a linear ultrasound probe in 1,162 consecutive patients who underwent transthoracic echocardiography. The DRA diameter was measured by the perpendicular angle in the dorsum of the hand, and the average values were compared by sex. DRA diameter < 2.3 mm was defined as unsuitable for routine diagnostic coronary angiography using a 5 Fr introducer sheath. RESULTS: The mean DRA diameters were 2.31 ± 0.43 mm (right) and 2.35 ± 0.45 mm (left). The DRA was smaller in women than men (right: 2.15 ± 0.38 mm vs. 2.43 ± 0.44 mm, p < 0.001; left: 2.18 ± 0.39 mm vs. 2.47 ± 0.45 mm, p < 0.001). The DRA diameter was approximately 20% smaller than the radial artery diameter. A total of 630 (54.2%) and 574 (49.4%) patients had DRA diameter < 2.3 mm in the right and left hands, respectively. Female sex, low body mass index (BMI), and low body surface area (BSA) were significant predictors of DRA diameter < 2.3 mm. CONCLUSION: We provided reference DRA diameters for Korean patients. Approximately 50% of the studied patients had DRA diameter < 2.3 mm. Female sex, low BMI, and low BSA remained significant predictors of DRA diameter < 2.3 mm.

Effectiveness and safety of non-vitamin K direct oral anticoagulants in atrial fibrillation patients with bioprosthetic valve.

BACKGROUND: Non-vitamin K direct oral anticoagulant (DOAC) is effective for prevention of embolic events in nonvalvular atrial fibrillation (AF) patients. However, the effectiveness and safety of DOAC in AF patients who have bioprosthetic heart valve (BPHV) is largely unknown. METHODS: We retrospectively identified patients with AF and BPHV, using the diagnostic code and medical device and surgery information from the Korean National Health Insurance Service database, between 2013 and 2018. A 1:2 propensity score-matched cohort (n = 724 taking warfarin; n = 362 taking DOAC) was constructed and analyzed for the primary clinical outcome, a composite of ischemic stroke and systemic embolism. Important secondary outcomes included major bleeding, all-cause death, and the net clinical outcome, defined as a composite of all embolic events, major bleeding, and death. RESULTS: The mean age was 78.9±6.8 years old, and 45% (n = 489) were male. The mean CHA2DS2-VASc score was 4.7±1.4. DOAC was non-inferior to warfarin for preventing ischemic stroke and systemic embolism (hazard ratio [HR] 1.14, 95% confidence interval [CI] 0.56-2.34), major bleeding (HR 0.80, 95% CI 0.32-2.03) and all-cause death (HR 1.09, 95% CI 0.73-1.63). As for the net clinical outcome, DOAC was also similar to warfarin (HR 1.06, 95% CI 0.76-1.47). These outcomes were not different in various subgroups analyzed. CONCLUSION: In this nationwide Korean AF population with a BPHV, DOAC was at least as effective and safe as warfarin for the prevention of systemic embolic events. These results suggest that DOAC may be an excellent alternative to warfarin in AF patients with BPHV.

Differential association of metabolic syndrome and low-density lipoprotein cholesterol with incident cardiovascular disease according to sex among Koreans: a national population-based study.

AIMS: To investigate sex differences in the association of metabolic syndrome (MetS) and/or low-density lipoprotein cholesterol (LDL-C) with the incidence of cardiovascular and cerebrovascular disease (CCVD). METHODS AND RESULTS: A total of 4 702 458 individuals, aged between 40 and 70, without a previous diagnosis of CCVD, underwent at least two health screenings between 2009 and 2011. Of them, 4 193 878 individuals (48.6% women) fulfilled the study requirements. The main outcome measured was the incidence of CCVD. By the end of 2017, 68 921 CCVD events occurred. Men in high LDL-C only, MetS only, and both MetS and high LDL-C groups had higher risks of CCVD. Women in MetS only and both MetS and high LDL-C groups, but not those in high LDL-C only group, had higher risks of CCVD than those in the reference group. The effect of the interaction between the presence of MetS and high LDL-C levels on the primary outcome was found among women (P for interaction 0.016) but not among men (P for interaction 0.897). A combination of MetS and LDL-C > 3.4 mmol/L increased the risk of CCVD as compared to MetS or LDL-C > 3.4 mmol/L alone in both men and women. CONCLUSIONS: Metabolic syndrome confers an increased risk of CCVD irrespective of sexes; LDL-C > 3.4 mmol/L alone has a greater influence on CCVD occurrence in men than in women. Metabolic syndrome and high LDL-C beget a synergistically detrimental impact on the incidence of CCVD in both men and women. Treatment of dyslipidaemia and metabolic syndrome should be tailored according to patient characteristics.

Optimal Low-Density Lipoprotein Cholesterol Levels in Adults Without Diabetes Mellitus: A Nationwide Population-Based Study Including More Than 4 Million Individuals From South Korea.

BACKGROUND: Although the strong association between low-density lipoprotein cholesterol (LDL-C) and cardiovascular disease (CVD) is well-known, the threshold LDL-C level at which the risk of CVD begins to increase in individuals without diabetes mellitus (DM) remains unknown. We aimed to evaluate the association between incident CVD and serum LDL-C levels with or without statin use in individuals without DM. METHODS: We identified 4,182,117 individuals without previous CVD who underwent a health screening examination in 2009 and 2011 from the Korean National Health Insurance Cohort database. The primary endpoint was a composite of cardiovascular deaths, myocardial infarction (MI) cases, and ischemic stroke cases. RESULTS: During the median follow-up of 6 years, there were 51,961 CVD events that included 17,392 MI cases, 33,779 ischemic stroke cases, and 2,039 cardiovascular deaths. The LDL-C levels that were associated with an increased risk of CVD were ≥100 mg/dL in non-statin users and ≥130 mg/dL in statin users. However, even in individuals with lower LDL-C levels, all those with fasting plasma glucose (FPG) levels ≥110 mg/dL had a significantly higher risk of CVD. CONCLUSIONS: We demonstrated that LDL-C levels ≥100 mg/dL were correlated with an increased risk of CVD in individuals without DM and a history of CVD. We found that a glucose, cholesterol interaction increased CVD risk, and modestly elevated FPG levels (110-125 mg/dL) were associated with a higher CVD risk even in individuals with well-controlled LDL-C levels.

Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia.

BACKGROUND/AIMS: Adherence to tyrosine kinase inhibitors (TKIs) has become a critical aspect of care in chronic myeloid leukemia (CML). We aimed to examine the association of TKI adherence with overall survival (OS) outcomes in Korean patients diagnosed with CML and treated with TKIs using data from the National Health Information Database. METHODS: This study included 2,870 CML patients diagnosed between 2005 and 2013. Drug adherence was evaluated according to the medication possession ratio (MPR) and classified as high adherence (i.e., MPR ≥ 0.95 [upper 50%]), moderate adherence (i.e., MPR ≥ 0.68 and < 0.95 [middle 25%]), and low adherence (i.e., MPR < 0.68 [lower 25%]). RESULTS: The median MPR was 0.95 (range, 0 to 4.67). Male sex (p = 0.003), age < 70 years (p < 0.001), high income (≥ 30%, p < 0.001), and maintaining frontline TKI (< 0.001) were associated with better adherence. Adherence to dasatinib was the lowest (vs. imatinib or nilotinib, p < 0.001). Compared with high MPR patients, those with moderate MPR (hazard ratio [HR], 4.90; 95% confidence interval [CI], 3.87 to 6.19; p < 0.001) and low MPR (HR, 11.6; 95% CI, 9.35 to 14.42; p < 0.001) had poorer OS. CONCLUSION: Adherence to TKI treatment is an important factor predicting survival outcomes in Korean CML patients. Male sex, age < 70 years, high income, and maintaining frontline TKI are associated with high adherence to TKI. Thus, those without these characteristics should be closely monitored for treatment adherence.

Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian randomization analysis.

BACKGROUND: It is known in some studies that higher the LDL-C, the greater the risk of developing cardiovascular disease. However, studies of the causal effects between LDL-C and hypertension are limited by their observational study design, and genetic epidemiology studies of associations between LDL-C and hypertension are lacking, as are studies using data for Koreans. In this study, we confirmed the causal effect of LDL-C on hypertension using Korean chip data. METHOD: The epidemiology and genotype data were collected from the Korean Genome and Epidemiology Study conducted by the Korea National Institute of Health and covered 20,701 subjects. Single-nucleotide polymorphisms associated with LDL-C were selected (p-value < 5 × 10- 8) from the Global Lipids Genetics Consortium database, and Mendelian randomization analysis (MRA) was performed with counted genetic risk scores and weighted genetic risk scores (WGRSs) for 24 single-nucleotide polymorphisms. RESULT: The assumptions for MRA were statistically confirmed, and WGRSs showed a strong association with LDL-C. Interestingly, while the relationship between LDL-C and hypertension was not statistically significant in the observational study, MRA study demonstrated that the risk of hypertension increased as LDL-C increased in both men and women. CONCLUSIONS: The results of this study confirmed that the relationship between LDL-C and hypertension is greatly influenced by genetic information.