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Background Several studies have reported conflicting results regarding the relationship between alcohol consumption and cortisol levels. However, the causality between alcohol consumption and cortisol levels has not been evaluated. Methods This study examined 8,922 participants from the Dong-gu Study. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol consumption. The association between the genetically predicted alcohol consumption and cortisol level was evaluated with Mendelian randomization (MR) using two-stage least squares regression. Results Alcohol consumption was positively associated with the serum cortisol level in both sexes in the observational analysis. In the MR analysis, the genetically predicted alcohol consumption was positively related to the cortisol level in men, with cortisol levels increasing by 0.18 µg/dL per drink per day. However, there was no relationship in women in the MR analysis. Conclusion The predicted alcohol consumption according to the ALDH2 rs671 polymorphism was positively related to the cortisol levels, suggesting a causal relationship between alcohol consumption and cortisol levels., Graphical Abstract

Background Elevated blood pressure is a major preventable cause of cardiovascular diseases. Alcohol consumption is a well-known risk factor of elevated blood pressure. The aldehyde dehydrogenase 2 (ALDH2) polymorphism is common in Eastern Asians, and inactive ALDH2 genotypes are associated with both avoiding alcohol consumption and aldehyde accumulation. Therefore, this study assessed the associations between alcohol consumption and hypertension and blood pressure according to the ALDH2 genotypes. Methods This study consists of 8,526 participants in the Dong-gu Study. Multivariate logistic regression was used to calculate the odds ratio (OR) according to alcohol consumption after stratifying by gender and ALDH2 genotypes. Multivariate linear regression was performed to estimate the systolic blood pressure (SBP) and diastolic blood pressure (DBP) according to the amount of alcohol consumed. Results In men, alcohol consumption was positively associated with both SBP and DBP in active ALDH2 carriers, but not in inactive ALDH2 carriers. In active ALDH2 carriers, compared to non-drinkers, the OR of hypertension was 1.16 (95% confidence interval [CI], 0.91–1.49) for < 1 drink/day, and 1.44 (95% CI, 1.15–1.80) for ≥ 1 drink/day in men. With each 1 drink/day increase, SBP and DBP increased by 3 and 1 mmHg in men, respectively. There was no significant association between ALDH2 genotypes and hypertension and blood pressure in women. Conclusion ALDH2 genotype modified the association between alcohol consumption and blood pressure in men. There was a positive relationship between alcohol consumption and blood pressure in active ALDH2 carriers, but no significant relationship in inactive ALDH2 carriers., Graphical Abstract

Background Apolipoprotein E (APOE) gene polymorphism is associated with neurodegenerative and cardiovascular diseases. Although the effects of the gene differ by ethnic group, few studies have examined Asians. Therefore, the association between APOE polymorphism and mortality in Koreans was evaluated in this study. Methods This study population included participants from the Dong-gu and Namwon Studies. APOE genotypes were categorized as E2 (E2/E2 and E2/E3), E3 (E3/E3), and E4 (E3/E4 and E4/E4). Multivariate Cox proportional hazard models were constructed using the E3 allele as a reference. Results In the model adjusting for study site, age, gender, and lifestyle, the hazard ratio (HR) of mortality for those with the E4 allele was 1.08 (95% confidence interval [CI], 0.97–1.20), while that for those with the E2 allele was 0.84 (95% CI, 0.74–0.96). After adjusting for blood lipids to evaluate their mediating effects, the HRs of mortality for those with E4 and E2 alleles were 1.08 (95% CI, 0.97–1.20) and 0.80 (95% CI, 0.70–0.92), respectively. These associations were more evident in younger groups, with HRs of 0.70 (95% CI, 0.52–0.92) for the E2 allele and 1.25 (95% CI, 1.03–1.53) for the E4 allele. Conclusion In two large population-based cohort studies, the E2 allele was associated with a lower risk of mortality compared with the E3 allele, whereas the E4 genotype was not associated with mortality in Koreans., Graphical Abstract

We identified traditional risk factors and investigated poorly understood risk factors for suicide attempts according to gender in a large Korean population. We analyzed the data from 6,768 males and 12,475 females with suicidal ideation obtained from the nationwide 2013 Korean Community Health Survey. The dependent variable was suicide attempts within the past year. There was a significant trend towards an increase in suicide attempts with decreasing age in both genders. Compared with those who were married, suicide attempts were significantly higher among those who were widowed, divorced, or separated for males (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.34–3.20), but lower for females (OR, 0.66; 95% CI, 0.45–0.98). Current smoking and depression were significant risk factor for suicide attempts in males and females. However, monthly household income, myocardial infarction, and osteoporosis were significantly associated with suicide attempts only in males, whereas education level, recipient of National Basic Livelihood Security, family contact, leisure activity, and drinking frequency were significantly associated only in females. These findings indicate that gender difference should be considered in the assessment, prevention, and management of future suicide attempts by community policy-makers and clinicians., Graphical Abstract

Background We investigated the association between pentraxin 3 (PTX3), a novel inflammatory marker, and bone mineral density (BMD) in the general Korean population. Methods We selected a sub-cohort of 1,440 subjects (757 men and 683 women) from participants in the community-based Dong-gu Study. The mean age was 66.0 ± 8.1 years for men and 63.7 ± 7.9 years for women. The plasma PTX3 levels were measured using an enzyme-linked immunosorbent assay, and BMD was measured in the femoral neck and lumbar spine using dual-energy X-ray absorptiometry. Linear regression analyses were used to evaluate the association between the plasma PTX3 levels and BMD. Results PTX3 was inversely associated with the BMD of the lumbar spine (P = 0.010) and femoral neck (P < 0.001) in men but not in women. For men, the association with the BMD of the femoral neck remained after adjustment for multiple comparison (P = 0.020). Conclusion This study suggests that PTX3 levels might be inversely associated with BMD in elderly men., Graphical Abstract

The reference interval for plasma total homocysteine (tHcy) and serum folate concentrations were estimated. Total of 3,154 reference individuals (1,029 men and 2,125 women) were selected based on stringent exclusion criteria. For plasma tHcy concentration (µM/L), reference values (median [5-95 percentile]) were 7.72 (5.03 to 13.80) and 6.09 (3.95-10.19) in men and women, respectively. For serum folate concentration (nM/L), reference values were 23.71 (11.73-38.44) and 28.95 (15.23-40.44) in men and women, respectively. The tHcy levels of both genders in the present study were lower than those in previous reports from other countries and Korea. Graphical Abstract

Vitamin D plays an important role in bone metabolism and maintaining bone health. Recently, new evidence has revealed that vitamin D affects chronic diseases such as autoimmune diseases, cardiovascular diseases and certain cancers. The aim of this study was to evaluate the vitamin D status and the prevalence of vitamin D deficiency in an urban Korean population. This study included 8,976 participants (3,587 men and 5,389 women) aged 50 yr and older. Serum 25(OH)D level was measured by chemiluminescent microparticle immunoassay. The prevalence of vitamin D deficiency [25(OH)D < 20 ng/mL] was 59.7% and 86.5% in men and women, respectively. The prevalence of vitamin D deficiency increased significantly with age in men, but not in women and it decreased from April to July, more prominently in men than in women. These results suggest that sun exposure, intake of vitamin D supplement, and regular physical activities is recommended in an urban Koreans, especially in women.

This study attempted to calculate and investigate the incidence of hospitalized acute myocardial infarction (AMI) and stroke in Korea. Using the National Health Insurance claim data, we investigated patients whose main diagnostic codes included AMI or stroke during 2006 to 2010. As a result, we found out that the number of AMI hospitalized patients had decreased since 2006 and amounted to 15,893 in 2010; and that the number of those with stroke had decreased since 2006 and amounted to 73,501 in 2010. The age-standardized incidence rate of hospitalized AMI, after adjustment for readmission, was 41.6 cases per 100,000-population in 2006, and had decreased to 29.4 cases in 2010 (for trend P < 0.001). In the case of stroke was estimated at 172.8 cases per 100,000-population in 2006, and had decreased to 135.1 cases in 2010 (for trend P < 0.001). In conclusion, the age-standardized incidence rates of both hospitalized AMI and stroke in Korea had decreased continuously during 2006 to 2010. We consider this decreasing trend due to the active use of pharmaceuticals, early vascular intervention, and the national cardio-cerebrovascular disease care project as the primary and secondary prevention efforts.

The aim of this study was to investigate time trends in the public awareness of stroke and its predicting factors. The target population was 9,600 community-dwelling adults, aged 19–79 years, in 16 metropolitan cities and provinces in Korea. The survey samples in 2012 and 2014 were selected separately (entirely different sets of subjects) using a proportionate quota sampling method. Information concerning knowledge of stroke and demographics was collected by trained telephone interviewers using random digit dialing. After excluding subjects with a non-response or refusal to answer any question, the analyses included 8,191 subjects in 2012 and 8,127 subjects in 2014. Respondents’ awareness of stroke warning signs (numbness or weakness, difficulty speaking or understanding speech, dizziness, visual impairment, and severe headache) was highest for difficulty speaking or understanding speech (80.9% in 2012 and 86.4% in 2014). There were significant increases in the proportion of respondents understanding the appropriate action (i.e., calling an ambulance) at the time of stroke occurrence (59.6% to 67.1%), and in the proportion aware of the general need for prompt treatment (86.7% to 89.8%). In multivariable logistic regression analysis, older age, higher education level, higher household income, current non-smoking, exposure to stroke-related public relations materials, and experience of stroke education were significantly associated with both high knowledge of stroke warning signs and awareness of the need for prompt treatment. Between 2012 and 2014, the public’s awareness of stroke increased significantly. More specialized interventions, including public relations materials and education, should focus on subgroups who have lower stroke knowledge., Graphical Abstract

Recent studies have shown that bilirubin is negatively associated with hemoglobin A1c (HbA1c) in the general population. The association between bilirubin and HbA1c in serum of diabetes patients has not yet been studied. The aim of the present study was to evaluate the association between total bilirubin and HbA1c in Korean patients with type 2 diabetes. A total of 690 of the 1,275 type 2 diabetes patients registered with the public health centers in Seo-gu, Gwangju and Gokseong-gun, Jeollanam-do participated in this study. Following an overnight fast, venous blood and urine samples were collected and analyzed. The mean HbA1c values differed significantly according to total bilirubin (≤ 0.4 mg/dL, 7.6%; 0.5 mg/dL, 7.3%; 0.6-0.7 mg/dL, 7.2%; and ≥ 0.8 mg/dL, 7.1%; P for trend = 0.016) after we adjusted for other confounding factors. When the odds ratio (OR) was adjusted for other confounding factors, there was a significant association between total bilirubin and HbA1c (OR, 0.4 [95% confidence interval, 0.2-0.8] for total bilirubin ≥ 0.8 mg/dL versus ≤ 0.4 mg/dL. In conclusion, total bilirubin concentrations in serum are negatively associated with HbA1c levels after adjustment for sex, age, and other confounding factors in type 2 diabetes patients.

We investigated the association of depressive symptoms with carotid intima-media thickness (IMT) and plaques in the general Korean population. A total of 7,554 Korean males and females aged 45-74 yr who were free from cardiovascular diseases were included in the analyses. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). Subjects with a score of ≥16 were classified as having clinically significant depressive symptoms. Carotid ultrasonography was used to measure mean carotid IMT (C-IMT) and to determine the presence of plaques. A significant association between depressive symptoms and C-IMT was observed only in females. After adjustment for established cardiovascular risk factors, females with depressive symptoms had significantly greater C-IMT than females without depressive symptoms (mean difference 0.011±0.004 mm; 95% confidence interval, 0.003-0.019 mm). Compared with controls, the fully adjusted risk of females with depressive symptoms for abnormal C-IMT (≥1.0 mm) was significant (odds ratio, 1.63; 95% confidence interval, 1.16-2.30). No significant association between depressive symptoms and carotid plaques was observed in either gender. This study shows a significant association between depressive symptoms and C-IMT in middle-aged and older females. Graphical Abstract

We evaluated the association of the APOE polymorphism with serum C-reactive protein levels and white blood cell count in two large population-based studies in Korean. The datasets included the Dong-gu study (n = 8,893) and the Namwon Study (n = 10,032). APOE genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism. Multivariable linear regression analysis was performed to evaluate the relationship of APOE genotypes with C-reactive protein levels and white blood cell count with adjustments for age, sex, body mass index, smoking, diabetes, hypertension, and serum lipids. In the multivariate model, carriers of E3E4 or E4E4 genotype had significantly lower C-reactive protein levels compared with carriers of E3E3 genotype group (0.50 mg/L vs. 0.67 mg/L; 0.37 mg/L vs. 0.67 mg/L, respectively, for the Dong-gu Study and 0.47 mg/L vs. 0.66 mg/L; 0.45 mg/L vs. 0.66 mg/L, respectively, for the Namwon Study). However, there was no difference in white blood cell count among APOE genotypes. We found that the APOE E4 allele is associated with lower C-reactive protein levels, but not white blood cell count. Our results suggest that APOE genotype may influence C-reactive protein levels through non-inflammatory pathway. Graphical Abstract

The purpose of this study was to examine the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and bone mineral density (BMD). Two large cohort studies were performed: the Dong-gu Study (3,621 men and 5,409 women) and the Namwon Study (3,703 men and 5,672 women). We assessed lumbar spine and femoral neck BMD by dual-energy X-ray absorptiometry. Genotypes were determined by real-time polymerase chain reaction. Multiple linear regression analysis was performed to evaluate the association between MTHFR C677T and BMD, adjusting for age, weight and height. The MTHFR C677T genotype frequencies for CC, CT, and TT genotypes were 34.5, 48.7, and 16.8%, respectively, in the Dong-gu Study and 33.6, 49.2, and 17.2%, respectively, in the Namwon Study. There are no significant differences between the MTHFR C677T genotype and the BMD at the lumbar spine and femoral neck in men or women in both cohorts.

We examined whether the presence and severity of preoperative hydronephrosis have prognostic significance in patients who underwent radical cystectomy for transitional cell carcinoma of the bladder. The medical records of 457 patients who underwent radical cystectomy for bladder cancer between 1986 and 2005 were retrospectively reviewed. Following the Society for Fetal Urology grading system, patients were divided into low-, and high-grade hydronephrosis groups. Clinicopathologic factors associated with preoperative hydronephrosis and survival were evaluated. Of a total of 406 patients, unilateral hydronephrosis was found in 74 (18.2%), bilateral hydronephrosis in 11 (2.7%), and no hydronephoris in 321 (79.1%). Low-grade hydronephrosis was found in 57 (12.2%) patients and high-grade hydronephrosis in 28 (6%). Preoperative hydronephrosis was related to higher pT stage and lymph node invasion. In univariate analysis, the presence of hydronephrosis, hydronephrosis grade, age, pT and pN stage, tumor grade, surgical margin, number of retrieved nodes, carcinoma in situ, and lymphovascular invasion were significant prognostic factors for cancer-specific survival. In multivariate analysis, bilateral hydronephrosis and high-grade hydronephrosis remained significant predictors for decreased survival. The presence of preoperative hydronephrosis, and high-grade hydronephrosis are significant prognostic factors in patients with bladder cancer after radical cystectomy.