Association Between Premature Menopause and Cardiovascular Diseases and All-Cause Mortality in Korean Women.

Background Mortality from cardiovascular diseases in Asian populations is considerable. Menopause is a risk-enhancing factor for cardiovascular disease, but it is unclear whether menopause is an independent risk factor for cardiovascular disease and mortality in Asian women. Methods and Results A total of 1 159 405 postmenopausal women, who had participated in the health examinations of the Korean National Health Insurance Service in 2009, were analyzed, and their reproductive histories were taken. A multivariable Cox proportional hazard model assessed the hazard ratios (HRs) of myocardial infarction (MI), ischemic stroke, and all-cause mortality, according to the history of premature menopause and age at menopause. After an average 10-year follow-up, there were 31 606, 45 052, and 77 680 new cases of MI, ischemic stroke, and all-cause mortality, respectively. The women with premature menopause exhibited increased risks of MI (HR, 1.40 [95% CI, 1.31-1.50]), ischemic stroke (HR, 1.24 [95% CI, 1.17-1.31]), and all-cause mortality (HR, 1.19 [95% CI, 1.14-1.24]) when compared with women with menopause aged ≥50 years. The highest risk was evident with menopause between the ages of 30 and 34 years (HR for MI, 1.52 [95% CI, 1.30-1.78]; HR for ischemic stroke, 1.29 [95% CI, 1.12-1.48]; HR for all-cause mortality, 1.33 [95% CI, 1.20-1.47]) when compared with women with menopause aged ≥50 years. Conclusions Earlier age at menopause was associated with increased risks for MI, ischemic stroke, and all-cause mortality. Future guidelines and risk assessment tools should consider menopause as an independent risk factor of cardiovascular disease in Korean women.

Population Prevalence, Cancer Risk, and Mortality Risk of Turner Syndrome in South Korean Women Based on National Health Insurance Service Data.

PURPOSE: In South Korea, investigations into Turner syndrome (TS) prevalence and TS-associated cancer and mortality are lacking. Accurate data were estimated from the National Health Insurance Service (NHIS) and the Rare Diseases Registry (RDR) records. MATERIALS AND METHODS: Data on patients with TS who were registered in the RDR between 2007 and 2017 were collected. To estimate TS-associated cancer and mortality risk, the data were compared with data of 1:3 age-matched controls. RESULTS: In 2017, 2054 patients with TS were identified from a total population of 26186952 South Korean women; therefore, the prevalence was 7.84 per 100000 persons. TS prevalence across 10-year interval age groups were 11.82, 23.17, 18.37, 10.49, 4.09, and 0.38 for age under 10 years, teenagers, 20s, 30s, 40s, and older than 50, respectively (per 100000 persons). The cancer risk in patients with TS was higher than that of age-matched controls over 5.3 person-years [hazard ratio (HR)=1.82, 95% confidence interval (CI) 1.01-3.27, p=0.045]. Among different types of cancer, thyroid cancer risk in patients with TS was significantly higher than that of age-matched controls (HR=2.78, 95% CI 1.06-7.26, p=0.037). We also observed that TS-associated all-cause mortality risk was higher than that of age-matched controls (HR=3.36, 95% CI 1.59-7.10, p=0.002). CONCLUSION: National prevalence of TS was suggested, and an increased risk of TS-associated thyroid cancer and mortality were observed in this study.

A Regio- and Diastereoselective Stille Coupling/Intramolecular Diels-Alder Cascade for the Generation of Fused Pyridines and Application in the Synthesis of (+)-Lycopladine A and (-)-Lycoposerramine R.

2-Pyrones with a chiral branched allylic silyl ether substituent underwent intramolecular Diels-Alder reactions with remarkably high π-facial- and endo-selectivities. The resulting diastereomerically and enantiomerically pure cycloadducts were transformed into the natural products (+)-lycopladine A and (-)-lycoposerramine R.

Risk for Behçet's disease gauged via high-density lipoprotein cholesterol: a nationwide population-based study in Korea.

Behçet's disease (BD) is a chronic inflammatory disease. Low levels of plasma high-density lipoprotein cholesterol (HDL-C) are associated with Crohn's disease, another chronic inflammatory disease. However, the effects of low HDL-C levels on BD are unclear. We investigated the effects of HDL-C levels, and variability therein, on the risk for BD. We used the Korean National Health Insurance System database to identify 5,587,754 adults without a history of BD who underwent ≥ 3 medical examinations between 2010 and 2013. Mean HDL-C levels at each visit were used to calculate variability independent of the mean (VIM) and the coefficient of variation (CV). There were 676 new cases of BD (0.012%). The risk for BD was increased in participants with highly variable and low mean HDL-C levels. In a multivariate-adjusted model, the hazard ratios (95% confidence intervals) for BD incidence were 1.335 (1.058-1.684) in a high mean/high VIM group, 1.527 (1.211-1.925) in a low mean/low VIM group, and 2.096 (1.67-2.63) in a low mean/high VIM group compared to a high mean/low VIM group. Low mean HDL-C levels, and high variability therein, are independent risk factors for BD.

A Longitudinal Retrospective Observational Study on Obesity Indicators and the Risk of Impaired Fasting Glucose in Pre- and Postmenopausal Women.

The impact of obesity could differ according to menopausal status since women undergo significant physiologic and metabolic changes due to menopause. We investigated the association between various major obesity indicators and the risk of impaired fasting glucose (IFG) according to menopausal status using nationally representative data. A total of 571,286 premenopausal and 519,561 postmenopausal women who underwent both Korean National Health Insurance Service (NHIS) cancer screening in 2009 and health check-ups in 2017 were analyzed. Multivariate logistic regression analyses were used to assess the effect of independent variables of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in 2009, on dependent variable IFG in 2017. After adjusting for potential confounders, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of developing IFG were analyzed. In the premenopausal group, the OR of obese BMI (≥25 kg/m2, <30 kg/m2) women was increased to 2.228 (95% CI: 2.139−2.321) compared to the normal BMI (≥18.5, <23 kg/m2) women as a reference. In the postmenopausal group, there was also a higher OR of 1.778 (95% CI: 1.715−1.843) in the obese BMI women compared to the normal group. A similar association of increasing ORs for IFG was shown in both groups when stratified by WC and WHtR. This nationwide study revealed that obesity and abdominal obesity, defined by various obesity indicators, consistently increased odds of acquiring IFG after 8 years in both pre- and postmenopausal groups, with the association being more robust in the premenopausal group. Our findings suggest that weight management and lifestyle modification may require more attention in premenopausal women.

Non-Alcoholic Fatty Liver Disease Defined by Fatty Liver Index and Incidence of Heart Failure in the Korean Population: A Nationwide Cohort Study.

Fatty liver index (FLI) is a simple and useful index that evaluates non-alcoholic fatty liver disease (NAFLD), particularly in large epidemiologic studies. Heart failure (HF) is becoming a burden to public health as the global trend toward an aging society continues. Thus, we investigated the effect of FLI on the incidence of HF using large cohort data from the Korean National Health Insurance health database. Methods and Results: A total of 7,958,538 subjects aged over 19 years without baseline HF (men = 4,142,264 and women = 3,816,274) were included. Anthropometric and biochemical measurements were evaluated. FLI scores were calculated and FLI ≥ 60 was considered as having NAFLD. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HF incidence were analysed using multivariable time-dependent Cox proportional hazard models. During a mean follow up of 8.26 years, 17,104 participants developed HF. The FLI components associated with the incidence of HF and FLI showed a causal relationship with HF; the FLI ≥ 60 group had a higher HR for HF (HR 1.493; 95% CIs 1.41−1.581) than the FLI < 30 group. Subgroup analysis showed that fatty liver (FLI ≥ 60) with age ≥ 65 years or women displayed higher HR for HF than fatty liver with age < 65 or men, respectively. An increase in FLI score significantly increased the HR for HF except for those with a FLI score change from <30 to 30−60. Conclusion: NAFLD defined by FLI and increase in FLI score were associated with the incidence of HF. Further detailed prospective studies are needed.

Risk Assessment of Mortality in Elderly Individuals: A Nationwide Cohort Study.

INTRODUCTION: There are several methods that are used to predict emergency room visits or rehospitalization for the elderly. However, existing risk assessment models of mortality in elderly people are limited. The purpose of this study was to ascertain the factors that affect all-cause mortality and to show the risk assessment model of mortality in elderly Koreans. METHODS: This was a cohort study conducted using the health checkup data of 246,422 individuals aged ≥60 years, which was provided by the National Health Insurance Service of South Korea between January 1, 2009, and December 31, 2012. The hazard ratios and 95% confidence intervals (CIs) of several conditions and all-cause deaths were estimated using a multivariable Cox proportional hazards model. A nomogram was constructed to visualize the risk factors of mortality; a calibration plot and area under the curve (AUC) were also used to verify the nomogram. RESULTS: Being 85 years or older (100 points) had the greatest influence on all-cause mortality, followed by being underweight (57 points), having more than five chronic diseases (49 points), and ages 78-84 years (45 points); smoking and lack of regular exercise affected mortality to a similar degree. The calibration curves showed good agreement between predictions and observations. The AUC of our nomogram was 0.73 (95% CI: 0.72-0.73). CONCLUSIONS: Our results showed the relationship between each condition and mortality rate among elderly individuals in Korea. Our nomogram showed a satisfactory performance in the assessment of the risk of all-cause mortality in elderly Korean people.

Behçet's Disease Is Associated with Multiple Sclerosis and Rheumatoid Arthritis: A Korean Population-Based Study.

BACKGROUND: No epidemiologic study has previously reported on the associations among Behçet's disease (BD) and autoimmune disorders. OBJECTIVES: To investigate the association between BD and the autoimmune disorders multiple sclerosis and rheumatoid arthritis. METHODS: Medical records of patients newly diagnosed with BD (n = 6,214) in 2012-2017 were analyzed using data entered into a large, nationwide database from 2007 to 2017. An age- and sex-matched control population of individuals without BD was sampled at a ratio of controls:BD cases of 3:1 (n = 18,642). Both cohorts were analyzed for the presence of multiple sclerosis or rheumatoid arthritis within a minimum of 5 years prior to their BD diagnosis. RESULTS: Patients with BD had significantly higher odds ratios (ORs) for multiple sclerosis (8.85 [95% CI 2.36-33.17]) and rheumatoid arthritis (4.62 [95% CI 3.35-6.35]) than the control group after adjustment for diabetes mellitus, hypertension, and dyslipidemia. BD patients aged <40 years had a higher proportion of rheumatoid arthritis (OR 23.91, 95% CI 5.50-103.9) than older patients (OR 3.96, 95% CI 2.83-5.54). CONCLUSION: Our results suggest that BD is associated with multiple sclerosis and rheumatoid arthritis.

Changes in Patterns of Physical Activity and Risk of Heart Failure in Newly Diagnosed Diabetes Mellitus Patients.

BACKGROUND: Exercise is recommended for type 2 diabetes mellitus (T2DM) patients to prevent cardiovascular disease. However, the effects of physical activity (PA) for reducing the risk of heart failure (HF) has yet to be elucidated. We aimed to assess the effect of changes in patterns of PA on incident HF, especially in newly diagnosed diabetic patients. METHODS: We examined health examination data and claims records of 294,528 participants from the Korean National Health Insurance Service who underwent health examinations between 2009 and 2012 and were newly diagnosed with T2DM. Participants were classified into the four groups according to changes in PA between before and after the diagnosis of T2DM: continuously inactive, inactive to active, active to inactive, and continuously active. The development of HF was analyzed until 2017. RESULTS: As compared with those who were continuously inactive, those who became physically active after diagnosis showed a reduced risk for HF (adjusted hazard ratio [aHR], 0.79; 95% confidence interval [CI], 0.66 to 0.93). Those who were continuously active had the lowest risk for HF (aHR, 0.77; 95% CI, 0.62 to 0.96). As compared with those who were inactive, those who exercised regularly, either performing vigorous or moderate PA, had a lower HF risk (aHR, 0.79; 95% CI, 0.69 to 0.91). CONCLUSION: Among individuals with newly diagnosed T2DM, the risk of HF was reduced in those with higher levels of PA after diagnosis was made. Our results suggest either increasing or maintaining the frequency of PA after the diagnosis of T2DM may lower the risk of HF.

Relationship between blood pressure levels and ischemic stroke, myocardial infarction, and mortality in very elderly patients taking antihypertensives: a nationwide population-based cohort study.

BACKGROUND: In the very elderly, "the lower the better" hypothesis has constantly been contradicted by randomized control trials and various cohort studies, but inconsistency in results led to unclear blood pressure treatment targets. This study aimed to assess the relationship between baseline blood pressure (BP) and ischemic stroke, myocardial infarction, and all-cause mortality in very elderly people treated for hypertension. METHODS: This large population-based retrospective cohort study was based on the national claims database of the Korean National Health Insurance System, which covers the entire Korean population. 374,250 participants aged ≥ 75 years taking antihypertensive agents were recruited, excluding patients with a history of previous ischemic stroke or myocardial infarction. RESULTS: Systolic BP (SBP) followed a J curve for ischemic stroke and a U curve for all-cause mortality, with nadir ranges of 120 to 129 mmHg and 140 to 149 mmHg, respectively. While increasing diastolic BP (DBP) generally resulted in higher HRs for ischemic stroke, HRs for myocardial infarction and all-cause mortality significantly increased only when DBP was ≥ 80 mmHg and ≥ 90 mmHg, respectively. The SBP/DBP combination analysis showed that even with SBP < 130 mmHg, higher DBP ≥ 90 mmHg had higher HRs for all three outcomes compared to the reference group (130 to 149 / < 80 mmHg). CONCLUSIONS: There were no further benefits or even harm below certain BP levels for ischemic stroke, myocardial infarction, and all-cause mortality in very elderly hypertensive patients.

Positive association between actinic keratosis and internal malignancies: a nationwide population-based cohort study.

Little is known about the comorbidities in actinic keratosis patients. To evaluate the association of actinic keratosis with certain malignancies. All patients with actinic keratosis (n = 61,438) and age- and sex-matched control subjects (n = 307,190) at a 5:1 ratio were enrolled using data from the Korean National Health Insurance Service between the years 2007 and 2014. In subjects with actinic keratosis, overall cancer incidence was higher than that for controls after income level, habitat, diabetes, hypertension, and dyslipidemia were adjusted (Hazard Ratio [HR] = 1.43 [95% confidence interval 1.38-1.47]). The positive association of specific cancers were observed in the following order: skin cancer (HR = 3.43 [2.47-4.75]), oral cavity and pharyngeal cancer (HR = 1.99 [1.57-2.52]), lymphoma (HR = 1.59 [1.28-1.96]), leukemia (HR = 1.35 [1.03-1.77]), prostate cancer (HR = 1.35 [1.21-1.51]), renal cancer (HR = 1.29 [1.02-1.63]), liver cancer (HR = 1.21 [1.09-1.35]), thyroid cancer (HR = 1.20 [1.05-1.38]), and gastric cancer (HR = 1.13 [1.03-1.23]). Although further research on pathologic mechanism is needed, the implications of a positive correlation between actinic keratosis and internal organ malignancies has great significance.

The Effects of Glucose Lowering Agents on the Secondary Prevention of Coronary Artery Disease in Patients with Type 2 Diabetes.

BACKGROUND: Patients with diabetes have a higher risk of requiring repeated percutaneous coronary intervention (PCI) than non-diabetic patients. We aimed to evaluate and compare the effects of anti-diabetic drugs on the secondary prevention of myocardial infarction among type 2 diabetes mellitus patients. METHODS: We analyzed the general health check-up dataset and claims data of the Korean National Health Insurance Service of 199,714 participants (age ≥30 years) who underwent PCIs between 2010 and 2013. Those who underwent additional PCI within 1 year of their first PCI (n=3,325) and those who died within 1 year (n=1,312) were excluded. Patients were classified according to their prescription records for glucose-lowering agents. The primary endpoint was the incidence rate of coronary revascularization. RESULTS: A total of 35,348 patients were included in the study. Metformin significantly decreased the risk of requiring repeat PCI in all patients (adjusted hazard ratio [aHR], 0.77). In obese patients with body mass index (BMI) ≥25 kg/m2, patients treated with thiazolidinedione (TZD) exhibited a decreased risk of requiring repeat revascularization than those who were not treated with TZD (aHR, 0.77; 95% confidence interval, 0.63 to 0.95). Patients treated with metformin showed a decreased risk of requiring revascularization regardless of their BMI. Insulin, meglitinide, and alpha-glucosidase inhibitor were associated with increased risk of repeated PCI. CONCLUSION: The risk of requiring repeat revascularization was lower in diabetic patients treated with metformin and in obese patients treated with TZD. These results suggest that physicians should choose appropriate glucose-lowering agents for the secondary prevention of coronary artery disease.

Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

PURPOSE: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. METHODS: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FINDINGS: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. IMPLICATIONS: We present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

Evaluation of the association between periodontitis and risk of Parkinson's disease: a nationwide retrospective cohort study.

The objective of this study was to examine the association between periodontitis and risk of incident Parkinson's disease using large-scale cohort data on the entire population of South Korea. Health checkup data from 6,856,180 participants aged 40 and older were provided by the National Health Insurance Service of South Korea between January 1, 2009, and December 31, 2009, and the data were followed until December 31, 2017. The hazard ratio (HR) of Parkinson's disease and 95% confidence interval (CI) were estimated using a Cox proportional hazards model adjusted for potential confounders. The incidence probability of Parkinson's disease was positively correlated with the presence of periodontitis. The HR of Parkinson's disease for the participants without the need of further dentist visits was 0.96 (95% CI 0.921-1.002); the HR of Parkinson's disease increased to 1.142 (95% CI 1.094-1.193) for the individuals who needed further dentist visits. Compared to individuals without periodontitis and without metabolic syndrome, the HR of incident Parkinson's disease gradually increased for individuals with periodontitis, with metabolic syndrome, and with both periodontitis and metabolic syndrome. People with periodontitis and metabolic syndrome had the highest HR of incident Parkinson's disease, at 1.167 (95% CI 1.118-1.219). In conclusion, a weak association between periodontitis and Parkinson's disease was suggested after adjusting for confounding factors from the population-based large-scale cohort of the entire South Korean population.

Effects of education, income, and occupation on prevalence and symptoms of knee osteoarthritis.

To examine the effect of socioeconomic status (SES) as measured by three components of education level, income level, and occupation on prevalence and symptom severity of knee osteoarthritis (OA) and to determine which of these factors has the strongest association. We conducted a cross-sectional study using data from the Fifth Korean National Health and Nutrition Examination Survey that were collected between 2010 and 2012. Male and female participants 50 years or older were included. Analyses to examine the associations of the three SES components with prevalence and symptom severity of knee OA were performed. A total 9,071 participants was included in the study. As expected, lower education, lower income level, and non-managerial or no job were associated with higher prevalence of knee OA and knee symptoms. Among the three SES components, lower education was most strongly associated with knee pain and radiographic knee OA after adjusting for the other two. Lower education level is the component of SES that most strongly relates to higher prevalence of knee OA and knee symptoms. Improving societal education level might decrease the socioeconomic burden of knee OA.

Association between body weight variability and incidence of Parkinson disease: A nationwide, population-based cohort study.

BACKGROUND AND PURPOSE: Although body weight variability has been associated with mortality, cardiovascular disease, and dementia, the relationship between body weight variability and Parkinson disease (PD) has rarely been studied. We aimed to investigate the longitudinal association between body weight variability and PD incidence. METHODS: A nationwide population-based, cohort study was conducted using the database from the Health Insurance Review and Assessment Service of the whole Korean population. We analyzed 2,815,135 participants (≥40 years old, mean age = 51.7 ± 8.6 years, 66.8% men) without a previous PD diagnosis. We determined individual body weight variability from baseline weight and follow-up visits. We used Cox proportional hazards regression models. RESULTS: The highest quartile group was associated with increased PD incidence compared with the lowest quartile group after adjustment for confounding factors (hazard ratio [HR] = 1.18, 95% confidence interval [CI] = 1.08-1.29). In contrast, baseline body mass index, baseline waist circumference, and waist circumference variability were not associated with increased PD incidence. In the body weight loss group, individuals within the quartile of the highest variation in body weight showed a higher HR of PD risk than those within other quartiles (HR = 1.41, 95% CI = 1.18-1.68). CONCLUSIONS: Body weight variability, especially weight loss, was associated with higher PD incidence. This finding has important implications for clinicians and supports the need for preventative measures and surveillance for PD in individuals with fluctuating body weight.

Association of Dynamic Changes in Metabolic Syndrome Status with the Risk of Parkinson's Disease: A Nationwide Cohort Study.

BACKGROUND: The longitudinal association between dynamic changes in the metabolic syndrome (MS) status and Parkinson's disease (PD) has been poorly studied. OBJECTIVE: We examined whether dynamic changes in MS status are associated with altered risk for PD. METHODS: This study was a nationwide retrospective cohort study. We enrolled 5,522,813 individuals aged≥40 years who had undergone health examinations under the National Health Insurance Service between 2009 and 2010 (two health examinations with a 2-year interval). Participants were followed up until the end of 2017. The participants were categorized into four groups according to MS status changes over 2 years: non-MS, improved MS, incident MS, and persistent MS groups. Multivariable Cox hazard regression was performed. RESULTS: During the 7-year median follow-up, there were 20,524 cases of newly developed PD. Compared with non-MS group, improved, incident, and persistent MS groups for 2 years were significantly associated with higher risks of PD (model 3; hazard ratio: 1.12, 95%confidence interval: 1.06-1.19 [improved MS]; 1.15, 1.09-1.22 [incident MS]; and 1.25, 1.20-1.30 [persistent MS]). Individuals with incident and persistent abdominal obesity, low levels of high-density lipoprotein cholesterol, hypertriglyceridemia, and hyperglycemia had a significantly increased risks of PD compared with those without either condition over 2 years. CONCLUSION: Persistent and incident MS and its components may be risk factors for incident PD. Ever exposure to MS may also be associated with PD risk. Appropriate intervention for preventing and improving MS may be crucial in decreasing the PD incidence.

Association between metabolic syndrome and Behçet's disease: A nationwide population-based study.

Metabolic syndrome (MetS) is characterized by insulin resistance, high blood pressure/sugar, dyslipidemia, and obesity. Whether MetS and its components affect the development of Behçet's disease (BD) remains unclear. This study was performed to investigate the associations between metabolic syndrome and risk of BD using nationwide population data. We conducted a retrospective cohort study of 10 505 818 Korean subjects who received health checkups in 2009-2012. Patients were classified into a MetS and its components group and were followed-up until 2016 for new-onset BD. A Cox proportional hazards model was used to assess the independent or synergistic effects of MetS and its components on the risk of incident BD. Compared to subjects without MetS components, the hazard ratio (HR) for development of BD in patients with MetS was 0.874 (95% confidence interval [CI]: 0.819-0.933) and this association was more prominent when all components of MetS were present (HR = 0.675, 95% CI = 0.571-0.798). Subjects with low high density lipoprotein (HDL) has a significantly increased risk of the development of BD (HR = 1.51, 95% CI = 1.4-1.594) compared to controls. This study showed that the incidence of Behçet's disease was reduced in subjects with MetS. Moreover, the presence of MetS components, with the exception of HDL, was negatively related to the development of BD.

Non-genetic risk factors for atrial fibrillation are equally important in both young and old age: A nationwide population-based study.

AIMS: There are several non-genetic risk factors for new-onset atrial fibrillation, including age, sex, obesity, hypertension, diabetes, and alcohol consumption. However, whether these non-genetic risk factors have equal significance among different age groups is not known. We performed a nationwide population-based analysis to compare the clinical significance of non-genetic risk factors for new-onset atrial fibrillation in various age groups. METHODS AND RESULTS: A total of 9,797,409 people without a prior diagnosis of atrial fibrillation who underwent a national health check-up in 2009 were included. During 80,130,090 person-years of follow-up, a total of 196,136 people were diagnosed with new-onset atrial fibrillation. The impact of non-genetic risk factors on new-onset atrial fibrillation was examined in different age groups. Obesity, male sex, heavy alcohol consumption, smoking, hypertension, diabetes and chronic kidney disease were associated with an increased risk of new-onset atrial fibrillation. With minor variations, these risk factors were consistently associated with the risk of new-onset atrial fibrillation among various age groups. Using these risk factors, we created a scoring system to predict future risk of new-onset atrial fibrillation in different age groups. In receiver operating characteristic curve analysis, the predictive value of these risk factors ranged between 0.556 and 0.603, and no significant trends were observed. CONCLUSIONS: Non-genetic risk factors for new-onset atrial fibrillation may have a similar impact on different age groups. Except for sex, these non-genetic risk factors can be modifiable. Therefore, efforts to control non-genetic risk factors might have relevance for both the young and old.

Dose-Dependent Effect of Smoking on Risk of Diabetes Remains after Smoking Cessation: A Nationwide Population-Based Cohort Study in Korea.

BACKGROUND: This study aimed to evaluate the dose-dependent effects of smoking on risk of diabetes among those quitting smoking. METHODS: We analyzed clinical data from a total of 5,198,792 individuals age 20 years or older who received health care check-up arranged by the national insurance program of Korea between 2009 and 2016 using the Korean National Health Insurance Service database. Cumulative smoking was estimated by pack-years. Smokers were classified into four categories according to the amount of smoking: light smokers (0.025 to 5 smoking pack-years), medium smokers (5 to 14 smoking pack-years), heavy smokers (14 to 26 smoking pack-years), and extreme smokers (more than 26 smoking pack-years). RESULTS: During the study period, 164,335 individuals (3.2% of the total population) developed diabetes. Compared to sustained smokers, the risk of diabetes was significantly reduced in both quitters (hazard ratio [HR], 0.858; 95% confidence interval [CI], 0.838 to 0.878) and nonsmokers (HR, 0.616; 95% CI, 0.606 to 0.625) after adjustment for multiple risk factors. The risk of diabetes gradually increased with amount of smoking in both quitters and current smokers. The risk of diabetes in heavy (HR, 1.119; 95% CI, 1.057 to 1.185) and extreme smokers (HR, 1.348; 95% CI, 1.275 to 1.425) among quitters was much higher compared to light smokers among current smokers. CONCLUSION: Smoking cessation was effective in reducing the risk of diabetes regardless of weight change. However, there was a potential dose-dependent association between smoking amount and the development of diabetes. Diabetes risk still remained in heavy and extreme smokers even after smoking cessation.