A Long-Term Incidence of Heart Failure and Predictors Following Newly Developed Acute Myocardial Infarction: A 10 Years Retrospective Cohort Study with Korean National Health Insurance Data.

Heart failure (HF) is the major mechanism of mortality in acute myocardial infarction (AMI) during early or intermediate post-AMI period. But heart failure is one of the most common long-term complications of AMI. Applied the retrospective cohort study design with nation representative population data, this study traced the incidence of late-onset heart failure since 1 year after newly developed acute myocardial infarction and assessed its risk factors. Methods and Results: Using the Korea National Health Insurance database, 18,328 newly developed AMI patients aged 40 years or older and first hospitalized in 2010 for 3 days or more, were set up as baseline cohort (12,403). The incidence rate of AMI per 100,000 persons was 79.8 overall, and 49.6 for women and 112.3 for men. A total of 2010 (1073 men, 937 women) were newly developed with HF during 6 years following post AMI. Cumulative incidences of HF per 1000 AMI patients for a year at each time period were 37.4 in initial hospitalization, 32.3 in 1 year after discharge, and 8.9 in 1-6 years. The overall and age-specific incidence rates of HF were higher in women than men. For late-onset HF, female, medical aid, pre-existing hypertension, severity of AMI, duration of hospital stay during index admission, reperfusion treatment, and drug prescription pattern including diuretics, affected the occurrence of late-onset HF. Conclusion: With respect to late-onset HF following AMI, appropriate management including hypertension and medical aid program in addition to quality improvement of AMI treatment are required to reduce the risk of late-onset heart failure.

Factors affecting the survival of early COVID-19 patients in South Korea: An observational study based on the Korean National Health Insurance big data.

OBJECTIVES: This study aimed to identify the survival rate and explore factors affecting survival among early COVID-19 patients in South Korea. METHODS: Data reported by the Korea Disease Control and Prevention Agency (KDCA), up to 15 July, when COVID-19 was confirmed were used as research data in connection with the National Health Insurance Service's (NHIS) national health information database. The final analysis targets were 12,646 confirmed patients and 303 deaths. The survival rate of patients with COVID-19 was estimated through Kaplan-Meier survival analysis. Cox proportional hazard regression analysis was performed to search for factors affecting survival. RESULTS: When looking at the survival rate by age group for men and women, the 28-day survival rate for men aged >80 years was 77% and 73% at 42 days, while 83% and 81% for women. Men had a worse survival rate than women. For chronic diseases, the highest risk of mortality was observed in malignant neoplasms of the respiratory and urogenital systems, followed by diseases of the urinary system and diabetes. CONCLUSIONS: The number of COVID-19 deaths was highest the next day after initial diagnosis. The case fatality rate was high in males, older age, and chronic diseases.

Factors Affecting the Incidence of Hospitalized Pneumonia after Influenza Infection in Korea Using the National Health Insurance Research Database, 2014-2018: Focusing on the Effect of Antiviral Therapy in the 2017 Flu Season.

BACKGROUND: This study aimed to investigate the effect of antiviral therapy following influenza outpatient episodes on the incidence of hospitalized pneumonia episodes, one of secondary complications of influenza. METHODS: In the National Health Insurance Research Database, data from July 2013 to June 2018 were used. All of the claim data with diagnoses of influenza and pneumonia were converted to episodes of care after applying 100 days of window period. With the 100-day episodes of care, the characteristics of influenza outpatient episodes and antiviral therapy for influenza, the incidence of hospitalized pneumonia episodes following influenza, and the effect of antiviral therapy for influenza on hospitalized pneumonia episodes were investigated. RESULTS: The crude incidence rate of hospitalized pneumonia after influenza infection was 0.57% in both males and females. Factors affecting hospitalized pneumonia included age, income level except self-employed highest (only in females), municipality, medical institution type, precedent chronic diseases except hepatitis (only in females) and antiviral therapy. In the 2017 flu season, the relative risk was 0.38 (95% confidence interval [CI], 0.29-0.50) in males aged 0-9 and 0.43 (95% CI, 0.32-0.57) in females aged 0-9 without chronic diseases, and it was 0.51 (95% CI, 0.42-0.61) in males aged 0-9 and 0.42 (95% CI, 0.35-0.50) in females aged 0-9 with one or more chronic diseases in the aspect of the effect of antiviral therapy on pneumonia. It suggests that antiviral therapy may decrease the incidence of pneumonia after influenza infection. CONCLUSION: After outpatient episode incidence of influenza, antiviral treatment has been shown to reduce the incidence of hospitalized pneumonia, especially in infants and children, during pandemic season 2017. Antiviral therapy for influenza is recommended to minimize burden caused by influenza virus infection and to reduce pneumonia. In addition, medical costs of hospitalization may decrease by antiviral therapy, especially in infants and children.

Age-Period-Cohort Analysis of Influenza in Koreans: the National Health Insurance Research Database, 2009-2018.

BACKGROUND: This study aimed to identify the incidence rate of episodes diagnosed with influenza and the effects of age-period-cohort (APC) in Koreans. METHODS: The 2009-2018 National Health Insurance Research Database was used for analysis. All time-related claims connected relatively short window period in 100 days. The case definition was defined by all codes diagnosed with J09, J10, and J11. Calculation of the incidence rate and APC analysis adjusted income levels by insurance type, metropolitan city was performed to identify the characteristics of episodes diagnosed with influenza. RESULTS: Incidence rate by age and cohort gradually increased since 2014. The incidence rate of males aged 0-4 years was 171.02 and that of females was 173.31 in 2015-2016 season. In males, 29.19 in 1963 cohort and 243.79 in 2013 cohort were confirmed as high incidence rates in 2017-2018 season. In the females, a high incidence was confirmed in 1953-1967 cohort and 1978-1987 cohort, and the incidence was 251.38 in 2013-2017 cohort. APC effects showed a high relative risk in the infants, the pandemic influenza season in 2010 (1/7/2009 to 30/6/2010) and the adults of 1978-1987 cohort. CONCLUSION: Since 2014, influenza outbreaks have been increasing every year. The start year of free vaccination decreased the incidence in infants and adults over 65 years of age but the incidence increased from the following year. Because influenza can be primarily prevented by vaccination, reinforcement of vaccination in infants may reduce the disease burden in their parents, and also the risk of infection caused by family transmission. A new vaccination strategy is needed to reduce the incidence and burden of diseases caused by influenza infection.

The cross-sectional relationships of dietary and serum vitamin D with cardiometabolic risk factors: Metabolic components, subclinical atherosclerosis, and arterial stiffness.

OBJECTIVE: There has been increasing interest in non-skeletal interactions between vitamin D insufficiency, which is common, and cardiovascular event and cardiovascular disease (CVD) risk factors. METHODS: To evaluate cross-sectional associations between dietary and serum vitamin D status and metabolic abnormalities and arterial changes among 1054 adults aged ≥40 y (404 men and 650 women) in a rural area of South Korea. Study subjects were divided into three groups according to dietary vitamin D intake (tertiles) measured by food frequency questionnaire and serum 25(OH)D levels (≤20, 21-29, and ≥30 ng/mL). Metabolic components (blood pressure, lipid profiles, and glycemic index) and arterial changes (brachial ankle pulse wave velocity [baPWV] and carotid artery intima-media wall thickness [cIMT]) were measured. RESULTS: Dietary vitamin D was inversely associated with diastolic blood pressure (DBP) and baPWV among men, but the association disappeared after multinutrient supplement users were excluded. Among women, there was an inverse association between dietary vitamin D and triacylglycerol (TG) levels. However, serum 25(OH)D showed a significant positive relationship with HDL cholesterol in both men and women, while a positive linear trend or nonlinear trend with serum 25(OH)D levels was shown in TG levels among men and in systolic blood pressure (SBP), DBP, total cholesterol, and baPWV among women. The positive relationship between serum 25(OH)D with baPWV disappeared after adjustment for blood pressure. CONCLUSIONS: Serum 25(OH)D may be favorably related to HDL cholesterol. However, serum 25(OH)D may not favorably related to subclinical atherosclerosis and arterial stiffness measured by cIMT and baPWV. The positive relationship between 25(OH)D and baPWV is likely to be mediated by blood pressure.

Habitual dietary intake of ß-carotene, vitamin C, folate, or vitamin E may interact with single nucleotide polymorphisms on brachial-ankle pulse wave velocity in healthy adults.

PURPOSE: The interaction between genetics and diet may explain the present disagreement in the protective role of vitamin intake on cardiovascular disease. We cross-sectionally assessed the interaction of habitual dietary intake of ß-carotene, vitamin C, folate, and vitamin E with single nucleotide polymorphisms (SNPs) on brachial-ankle pulse wave velocity (baPWV), a measure of arterial stiffness. METHODS: Dietary intakes of ß-carotene, vitamin C, folate, and vitamin E were quantified by a food frequency questionnaire in 3198 healthy men and women (≥ 40 years) from the Korea Multi-Rural communities Cohort study. baPWV was measured, and 19 SNPs were genotyped. The associations and interactions between dietary vitamin intake, SNP genotype, and baPWV were assessed using general linear models. RESULTS: In both men and women, dietary intake of ß-carotene, vitamin C, folate, or vitamin E and baPWV were not directly associated. Vitamin C, folate, and vitamin E intake had an interaction with rs4961 (ADD1) genotype on baPWV in men. rs4961 also interacted with folate intake on baPWV in women. In women, rs10817542 (ZNF618) and rs719856 (CD2AP) had an interaction with ß-carotene and folate intake and rs5443 (GNB3) had an interaction with vitamin E intake on baPWV. In general, minor allele homozygotes with low vitamin intake had higher baPWV than other subgroups. Results were similar when supplement users were excluded. CONCLUSIONS: Higher intake of dietary vitamin C, folate, and vitamin E may be related to high baPWV in healthy Korean men who are minor allele homozygotes of rs4961. In healthy Korean women, dietary folate, ß-carotene, and vitamin E intake may affect baPWV differently according to rs4961, rs10817542, rs719856, or rs5443 genotype. Greater dietary intake of these nutrients may protect those that are genetically vulnerable to stiffening of the arteries.

The beneficial effects of Tai Chi exercise on endothelial function and arterial stiffness in elderly women with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) has been known to be associated with increased risk of cardiovascular disease (CVD). The aim of this study was to investigate the effects of Tai Chi exercise on CVD risk in elderly women with RA. METHOD: In total, 56 female patients with RA were assigned to either a Tai Chi exercise group (29 patients) receiving a 3-month exercise intervention once a week or a control group (27 patients) receiving general information about the benefits of exercise. All participants were assessed at baseline and at 3 months for RA disease activity (Disease Activity Score 28 and Routine Assessment of Patient Index Data 3), functional disability (Health Assessment Questionnaire), CVD risk factors (blood pressure, lipids profile, body composition, and smoking), and three atherosclerotic measurements: carotid intima-media thickness, flow-mediated dilatation (FMD), and brachial-ankle pulse wave velocity (baPWV). RESULTS: FMD, representative of endothelial function, significantly increased in the Tai Chi exercise group (initial 5.85 ± 2.05 versus 3 months 7.75 ± 2.53%) compared with the control group (initial 6.31 ± 2.12 versus 3 months 5.78 ± 2.13%) (P = 1.76 × 10(-3)). Moreover, baPWV, representative of arterial stiffness, significantly decreased in the Tai Chi exercise group (initial 1693.7 ± 348.3 versus 3 months 1600.1 ± 291.0 cm/s) compared with the control group (initial 1740.3 ± 185.3 versus 3 months 1792.8 ± 326.1 cm/s) (P = 1.57 × 10(-2)). In addition, total cholesterol decreased significantly in the Tai Chi exercise group compared with the control group (-7.8 ± 15.5 versus 2.9 ± 12.2 mg/dl, P = 2.72 × 10(-2)); other changes in RA-related characteristics were not significantly different between the two groups. Tai Chi exercise remained significantly associated with improved endothelial function (FMD; P = 4.32 × 10(-3)) and arterial stiffness (baPWV; P = 2.22 × 10(-2)) after adjustment for improvement in total cholesterol level. CONCLUSION: Tai Chi exercise improved endothelial dysfunction and arterial stiffness in elderly women with RA, suggesting that it can be a useful behavioral strategy for CVD prevention in patients with RA.

The Relationship between Zinc Status and Inflammatory Marker Levels in Rural Korean Adults Aged 40 and Older.

BACKGROUND: Serum cytokines and C-reactive protein (CRP) are known as one of the major risk factors in atherosclerosis. The antioxidant and anti-inflammatory properties of zinc have been suggested, but few data are available on the relationship between zinc status and inflammatory markers in epidemiological studies. OBJECTIVE: The present study aims to investigate the cross-sectional relationships of serum cytokines and CRP with dietary zinc intake and serum zinc levels in healthy men and women aged 40 and older in rural areas of South Korea. MATERIALS AND METHODS: A group of 1,055 subjects (404 men, 651 women) was included in dietary zinc analysis while another group of 695 subjects (263 men, 432 women) was included in serum zinc analysis. Serum IL-6, TNF-α, and CRP were measured as inflammatory markers. RESULTS: There was no significant inverse relationship between dietary zinc intake and inflammatory markers. We found a significant inverse relationship between serum zinc levels and all three inflammatory markers in women (P for trend = 0.0236 for IL-6; P for trend = 0.0017 for TNF-α; P for trend = 0.0301 for CRP) and between serum zinc levels and a single inflammatory marker (IL-6) in men (P for trend = 0.0191), although all R2 values by regression were less than 10%. CONCLUSION: In conclusion, serum zinc levels may be inversely related to inflammatory markers (IL-6, TNF-α, and CRP), particularly in women.

The cross-sectional relationship between dietary calcium intake and metabolic syndrome among men and women aged 40 or older in rural areas of Korea.

BACKGROUND/OBJECTIVES: Studies conducted in Western populations have suggested that dietary calcium may protect against metabolic abnormalities, but there is little evidence of this effect in Asians, who have relatively low calcium intake. We evaluated the cross-sectional relationship between dietary calcium and metabolic syndrome among Korean men and women aged 40 years and over. SUBJECTS/METHODS: A total of 6,375 subjects aged 40 years and over and were recruited between January 2005 and February 2010 from the baseline study of the Multi-Rural Communities Cohort Study in Rural Communities (MRCohort). A food frequency questionnaire was used to collect dietary information. Metabolic syndrome was defined using the modified criteria published in the Third Report of the National Cholesterol Education Program Adult Treatment Panel. RESULTS: Calcium intake was related inversely to metabolic syndrome in women (P-value = 0.0091), but not in men (P = 0.1842). Among metabolic components, high waist circumference (WC) (P = 0.0426) and high blood glucose (P = 0.0027) in women and hypertriglyceridemia (P = 0.0017) in men were inversely correlated with calcium intake. Excluding those who used calcium or multinutrient supplements did not attenuate the relationship between dietary calcium and metabolic abnormalities. CONCLUSION: Dietary calcium intake from foods may be inversely related to metabolic syndrome, WC, and blood glucose among women in rural areas of Korea.

Gene polymorphisms in the ornithine decarboxylase-polyamine pathway modify gastric cancer risk by interaction with isoflavone concentrations.

BACKGROUND: The study aimed to examine the association between genes encoding molecules in the ornithine decarboxylase (ODC)-polyamine pathway (ODC1, AMD1, NQO1, NOS2A, and OAZ2) and gastric cancer risk and whether the gene-phytoestrogen interaction modifies gastric cancer risk. METHODS: Among 76 gastric cancer cases and their 1:4 matched controls within the Korean Multi-center Cancer Cohort, a total of 30 SNPs in five genes involved in the ODC pathway were primarily analyzed. The second-stage genotyping in 388 matched case-control sets was conducted to reevaluate the significant SNPs interacting with phytoestrogens during the primary analysis. The summary odds ratios (ORs) [95 % confidence intervals (CIs)] for gastric cancer were estimated. Interaction effects between the SNPs and plasma concentrations of phytoestrogens (genistein, daidzein, equol, and enterolactone) were evaluated. RESULTS: In the pooled analysis, NQO1 rs1800566 showed significant genetic effects on gastric cancer without heterogeneity [OR 0.83 (95 % CI 0.70-0.995)] and a greater decreased risk at high genistein/daidzein levels [OR 0.36 (95 % CI 0.15-0.90) and OR 0.26 (95 % CI 0.10-0.64), respectively; p interaction < 0.05]. Risk alleles of AMD1 rs1279599, AMD1 rs7768897, and OAZ2 rs7403751 had a significant gene-phytoestrogen (genistein and daidzein) interaction effect to modify the development of gastric cancer. They had an increased gastric cancer risk at low isoflavone levels, but a decreased risk at high isoflavone levels (p interaction < 0.01). CONCLUSIONS: Our findings suggest that common variants in the genes involved in the ODC pathway may contribute to the risk of gastric cancer possibly by modulating ODC polyamine biosynthesis or by interaction between isoflavones and NQO1, OAZ2, and AMD1.

The effect of coffee, tea, and caffeine consumption on serum uric acid and the risk of hyperuricemia in Korean Multi-Rural Communities Cohort.

Caffeine, a commonly consumed food constituent, is known to exert beneficial physiological effects in humans. There is a lack of comprehensive population data for the effects of caffeine intake on urate metabolism. Therefore, the aim of this study was to determine whether coffee, tea, and caffeine intake influences serum uric acid and the risk of hyperuricemia in the Korean Multi-Rural Communities Cohort. We enrolled 9,400 participants in this study. An assessment of various dietary intake amounts of substances such as coffee and tea was performed using a food frequency questionnaire. The content of caffeine was calculated from coffee (74 mg/cup) and tea (15 mg/cup) intake information from the past year. Multivariate logistic regression models, multiple linear regression models, and analysis of covariance were applied to identify any association of dietary intake with serum uric acid levels or the risk of hyperuricemia. No trends for coffee, tea, or caffeine intake were found according to each quintile with serum uric acid in males, although there were weak, marginally significant trends between the content of coffee and caffeine intake and serum uric acid level in females (p = 0.07 for both). Tea intake in males and caffeine intake in females were significantly different between non-hyperuricemia and hyperuricemia (p = 0.04 and p = 0.04, respectively). In addition, a significant association of serum uric acid level with tea intake in males (ß = 0.0006, p = 0.02) and with tea intake and caffeine intake in females (ß = 0.0003, p = 0.04 and ß = 0.0006, p = 0.02, respectively) was observed. There was no effect of coffee, tea, or caffeine intake on the risk of hyperuricemia in either males or females. This study suggests that caffeine consumption might have an effect on serum uric acid in females. However, coffee, tea, and caffeine intake amounts were not associated with the risk of hyperuricemia.

Interaction effects between genes involved in the AKT signaling pathway and phytoestrogens in gastric carcinogenesis: a nested case-control study from the Korean Multi-Center Cancer Cohort.

SCOPE: To investigate whether genes involved in AKT/nuclear factor kappa B signaling and/or gene-environment interactions between the genes and phytoestrogens may be susceptible factors for gastric cancer. METHODS AND RESULTS: The representative single nucleotide polymorphisms (SNPs) identified during the primary analysis (screening a total of 622 SNPs within ± 5 kbp of the 51 target gene locations) were further investigated in 317 matched case-control sets. The summary odds ratios (ORs) and 95% confidence intervals (CIs) for gastric cancer were calculated. Interaction effects between the SNPs and phytoestrogen biomarkers (genistein, daidzein, equol, and enterolactone) were computed. CDK1 rs4145643, FAS rs6586161, and FAS rs1468063 in the AKT signaling pathway presented significant genetic effects on gastric cancer (OR = 0.81 (95% CI: 0.66-0.99) for CDK1 rs4145643; OR = 1.27 (95% CI: 1.03-1.58) for FAS rs6586161; OR = 1.29 (95% CI: 1.03-1.56) for FAS rs1468063; Cochran Q statistics > 0.10). Risk alleles of FAS rs6586161, FAS rs1468063, MAP3K1 rs16886448, and MAP3K1 rs252902 showed significant interaction effects with enterolactone (p(interaction) < 0.05). CONCLUSION: CDK1 and FAS genes involved in AKT signaling and influenced by anti-carcinogenic property of phytoestrogens can play a role as susceptible genetic factors in gastric carcinogenesis. FAS and MAP3K1 genes significantly interact with enterolactone, thereby modifying the individual's risk for gastric cancer.

Genetic susceptibility on CagA-interacting molecules and gene-environment interaction with phytoestrogens: a putative risk factor for gastric cancer.

OBJECTIVES: To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk. METHODS: In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay. RESULTS: SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05-7.65], 1.24 [95% CI = 1.01-1.53], 1.19 [95% CI = 1.01-1.41], and 1.37 [95% CI = 1.15-1.62], respectively; meta OR = 4.59 [95% CI 2.74-7.70], 1.36 [95% CI = 1.09-1.70], 1.20 [95% CI = 1.00-1.44], and 1.32 [95% CI = 1.10-1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05). CONCLUSIONS: Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk.

Effect of nutrient intake and Helicobacter pylori infection on gastric cancer in Korea: a case-control study.

To examine the effects of dietary factor and Helicobacter pylori (H. pylori) infection with emphasis on vitamin intake on the risk of gastric cancer (GC), we conducted a case-control study in South Korea, a high-risk area for GC. Trained dietitians interviewed 136 cases histologically diagnosed with GC. An equal number of hospital controls was selected by matching sex and age. High dietary intakes of vegetable fat [odds ratio (OR) = 0.35; 95% confidence interval (CI) = 0.15-0.83], folate (OR = 0.35; 95% CI = 0.13-0.96), and antioxidants, such as vitamin A (OR = 0.34; 95% CI = 0.13-0.83), beta-carotene (OR = 0.33; 95% CI = 0.13-0.82), vitamin C (OR = 0.26; 95% CI = 0.09-0.72), and vitamin E (OR = 0.41; 95% CI = 0.17-1.01), were shown to have a protective effect on GC risk using a multivariate model adjusting for foods significantly related to GC in our previous study (charcoal grilled beef, spinach, garlic, mushroom, and a number of types of kimchi) and supplement use. When stratified according to H. pylori infection, high intakes of vitamin C (OR = 0.10; 95% CI = 0.02-0.63) and vitamin E (OR = 0.16; 95% CI = 0.03-0.83) exhibited highly significant inverse associations with GC among the H. pylori-infected subjects compared with noninfected individuals. GC risk was significantly decreased only when consumption levels for two of these vitamins were high. Our findings suggest that high intake of antioxidant vitamins contribute to the reduction of GC risk and that GC risk in Korea may be decreased by encouraging those with H. pylori infection to increase their intake of antioxidant vitamins.