Association between High Sensitivity C-Reactive Protein and Metabolic Syndrome in South Korea: A Gender-Specific Analysis / 보건행정학회지

Background@#Metabolic syndrome has been known as a risk of cardiovascular disease. Meanwhile, high sensitivity C-reactive protein (hs-CRP) is used as a predictor of cardiovascular disease. In this paper, we aimed to investigate the association between hs-CRP and metabolic syndrome.Method: A total of 7,633 were chosen as the study population from the 7th Korea National Health and Nutrition Examination Survey dataset (2016–2017). Our dependent variable was whether an individual had metabolic syndrome or not, and the independent variable of interest was hs-CRP which was categorized into three groups. The chi-square tests and hierarchical logistic regression analyses reflecting survey characteristics were conducted. All analyses were stratified by gender. @*Results@#According to the adjusted model with all covariates, compared to individuals having the low risk of hs-CRP, those having its average risk were more likely to have metabolic syndrome in men (odds ratio [OR], 1.41; 95% confidence interval [CI], 1.12–1.76) and women (OR, 1.69; 95% CI, 1.33–2.16). Individuals having the high risk was not significantly different in men; however, they were more likely to have metabolic syndrome in women (OR, 2.03; 95% CI, 1.28–3.23). @*Conclusion@#In an upcoming aging society, it is important to reduce the risk of metabolic syndrome to improve population health. This study suggests that hs-CRP may be used as a marker of the risk of metabolic syndrome in a gender-specific way, thereby contributing to enhancing awareness of the risk of metabolic syndrome among the general public.

Two-Sample Mendelian Randomization Study of Lipid levels and Ischemic Heart Disease

Background and Objectives@#Associations between blood lipids and risk of ischemic heart disease (IHD) have been reported in observational studies. However, due to confounding and reverse causation, observational studies are influenced by bias, thus their results show inconsistency in the effects of lipid levels on IHD. In this study, we evaluate whether lipid levels have an effect on the risk of IHD in a Korean population. @*Methods@#A 2-sample Mendelian randomization (MR) study, using the genetic variants associated with lipid levels as the instrumental variables was performed. Genetic variants significantly associated with lipid concentrations were obtained from the Korean Genome and Epidemiology Study (n=35,000), and the same variants on IHD were obtained from the Korean Cancer Prevention Study-II (n=13,855). Inverse variance weighting (IVW), weighted median, and MR-Egger approaches were used to assess the causal association between lipid levels and IHD. Radial MR methods were applied to remove outliers subject to pleiotropic bias. @*Results@#Causal association between low-density lipoprotein-cholesterol (LDL-C) and IHD was observed in the IVW method (odds ratio, 1.013; 95% confidence interval, 1.007–1.109).However, high-density lipoprotein-cholesterol (HDL-C) and triglyceride (TG) did not show causal association with IHD. In the Radial MR analysis of the relationship between HDL-C, TG and IHD, outliers were detected. Interestingly, after removing the outliers, a causal association between TG and IHD was found. @*Conclusions@#High levels LDL-C and TG were causally associated with increased IHD risk in a Korean population, these results are potentially useful as evidence of a significant causal relationship.

Precision Medicine and Cardiovascular Health: Insights from Mendelian Randomization Analyses

Cardiovascular disease (CVD) is considered a primary driver of global mortality and is estimated to be responsible for approximately 17.9 million deaths annually. Consequently, a substantial body of research related to CVD has developed, with an emphasis on identifying strategies for the prevention and effective treatment of CVD. In this review, we critically examine the existing CVD literature, and specifically highlight the contribution of Mendelian randomization analyses in CVD research. Throughout this review, we assess the extent to which research findings agree across a range of studies of differing design within a triangulation framework. If differing study designs are subject to non-overlapping sources of bias, consistent findings limit the extent to which results are merely an artefact of study design. Consequently, broad agreement across differing studies can be viewed as providing more robust causal evidence in contrast to limiting the scope of the review to a single specific study design. Utilising the triangulation approach, we highlight emerging patterns in research findings, and explore the potential of identified risk factors as targets for precision medicine and novel interventions.

Precision Medicine and Cardiovascular Health: Insights from Mendelian Randomization Analyses

Cardiovascular disease (CVD) is considered a primary driver of global mortality and is estimated to be responsible for approximately 17.9 million deaths annually. Consequently, a substantial body of research related to CVD has developed, with an emphasis on identifying strategies for the prevention and effective treatment of CVD. In this review, we critically examine the existing CVD literature, and specifically highlight the contribution of Mendelian randomization analyses in CVD research. Throughout this review, we assess the extent to which research findings agree across a range of studies of differing design within a triangulation framework. If differing study designs are subject to non-overlapping sources of bias, consistent findings limit the extent to which results are merely an artefact of study design. Consequently, broad agreement across differing studies can be viewed as providing more robust causal evidence in contrast to limiting the scope of the review to a single specific study design. Utilising the triangulation approach, we highlight emerging patterns in research findings, and explore the potential of identified risk factors as targets for precision medicine and novel interventions.

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES@#Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.@*METHODS@#A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.@*RESULTS@#Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES: Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population. METHODS: A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort. RESULTS: Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10−105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust. CONCLUSIONS: Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.

Bilirubin and risk of ischemic heart disease in Korea: a two-sample Mendelian randomization study / 한국역학회지

OBJECTIVES: Bilirubin is an endogenous antioxidant that protects cells against oxidative stress. Increased plasma levels of bilirubin have been associated with a reduced risk of ischemic heart disease (IHD) in previous studies. Nonetheless, whether those associations reflect a true protective effect of bilirubin on IHD, rather than confounding or reverse causation, remains unknown. Therefore, we applied two-sample Mendelian randomization to evaluate the causal association between bilirubin levels and IHD risk in a Korean population.METHODS: A total of 5 genetic variants—TRPM8 (rs10490012), USP40 (rs12993249), ATG16L1 (rs2119503), SLCO1B1 (rs4149014), and SLCO1B3 (rs73233620)—were selected as genetic instruments for serum bilirubin levels using a community-based cohort, the Korean Genome and Epidemiology Study, comprising 33,598 subjects. We then evaluated their impact on IHD using the Korean Cancer Prevention Study-II cohort.RESULTS: Among the 5 instrumental variables that showed significant associations with serum bilirubin levels, rs12993249 (USP40) showed the most significant association (p<2.36×10−105). However, we found no significant association between serum bilirubin levels and IHD. Sensitivity analyses demonstrated a consistent association, suggesting that our observations were robust.CONCLUSIONS: Using two-sample Mendelian randomization, we found no association between serum bilirubin levels and IHD. Further studies that confirm the observed interactions among other ethnicities are warranted.

Traditional and Genetic Risk Score and Stroke Risk Prediction in Korea

BACKGROUND AND OBJECTIVES@#Whether using both traditional risk factors and genetic variants for stroke as opposed to using either of the 2 alone improves the prediction of stroke risk remains unclear. The purpose of this study was to compare the predictability of stroke risk between models using traditional risk score (TRS) and genetic risk score (GRS).@*METHODS@#We used a case-cohort study from the Korean Cancer Prevention Study-II (KCPS-II) Biobank (n=156,701). We genotyped 72 single nucleotide polymorphisms (SNPs) identified in genome-wide association study (GWAS) on the KCPS-II sub-cohort members and stroke cases. We calculated GRS by summing the number of risk alleles. Prediction models with or without GRS were evaluated in terms of the area under the receiver operating characteristic curve (AUROC).@*RESULTS@#Sixteen out of 72 SNPs identified in GWAS showed significant associations with stroke, with an odds ratio greater than 2.0. For participants aged < 40 years, AUROCs for incident stroke were 0.58, 0.65, and 0.67 in models using modifiable TRS only, GRS only, and TRS plus GRS, respectively, showing that GRS only model had better prediction than TRS only. For participants aged ≥40 years, however, TRS only model had better prediction than GRS only model. Favorable levels of traditional risk were associated with significantly lower stroke risks within each genetic risk category.@*CONCLUSIONS@#TRS and GRS were both independently associated with stroke risk. Using genetic variants in addition to traditional risk factors may be the most accurate way of predicting stroke risk, particularly in relatively younger individuals.

Traditional and Genetic Risk Score and Stroke Risk Prediction in Korea

BACKGROUND AND OBJECTIVES: Whether using both traditional risk factors and genetic variants for stroke as opposed to using either of the 2 alone improves the prediction of stroke risk remains unclear. The purpose of this study was to compare the predictability of stroke risk between models using traditional risk score (TRS) and genetic risk score (GRS). METHODS: We used a case-cohort study from the Korean Cancer Prevention Study-II (KCPS-II) Biobank (n=156,701). We genotyped 72 single nucleotide polymorphisms (SNPs) identified in genome-wide association study (GWAS) on the KCPS-II sub-cohort members and stroke cases. We calculated GRS by summing the number of risk alleles. Prediction models with or without GRS were evaluated in terms of the area under the receiver operating characteristic curve (AUROC). RESULTS: Sixteen out of 72 SNPs identified in GWAS showed significant associations with stroke, with an odds ratio greater than 2.0. For participants aged < 40 years, AUROCs for incident stroke were 0.58, 0.65, and 0.67 in models using modifiable TRS only, GRS only, and TRS plus GRS, respectively, showing that GRS only model had better prediction than TRS only. For participants aged ≥40 years, however, TRS only model had better prediction than GRS only model. Favorable levels of traditional risk were associated with significantly lower stroke risks within each genetic risk category. CONCLUSIONS: TRS and GRS were both independently associated with stroke risk. Using genetic variants in addition to traditional risk factors may be the most accurate way of predicting stroke risk, particularly in relatively younger individuals.

The effect of smoking on lung cancer: ethnic differences and the smoking paradox / 한국역학회지

The objectives of this review were to determine whether the smoking paradox still exists and to summarize possible explanations for the smoking paradox. Based on published data, we compared the risk of cigarette smoking for lung cancer in Western and Asian countries. We extracted data from the relevant studies about annual tobacco consumption, lung cancer mortality rates according to smoking status from each country, and possible explanations for the smoking paradox. A significantly greater risk of lung cancer death was found among current smokers in Asian countries than among nonsmokers, with relative risks (RRs) of 4.0 to 4.6 for Koreans, 3.7 to 5.1 for Japanese, and 2.4 to 6.5 for Chinese. Although a significantly greater risk of lung cancer was present among current smokers in Asian countries, the RRs in Asian countries were much lower than those reported in Western countries (range, 9.4 to 23.2). Possible explanations for the smoking paradox included epidemiologic characteristics, such as the smoking amount, age at smoking initiation, and the use of filtered or mild tobacco. The smoking paradox definitely exists, but may be explained by major epidemiologic characteristics. Therefore, the smoking paradox should not be interpreted as indicating that tobacco is safer or less harmful for Asians.

Impaired fasting glucose, single-nucleotide polymorphisms, and risk for colorectal cancer in Koreans / 한국역학회지

OBJECTIVES: Numerous studies have demonstrated that fasting serum glucose (FSG) levels and certain single-nucleotide polymorphisms (SNPs) are related to an increased risk of colorectal cancer (CRC); however, their combined effects are still unclear. METHODS: Of a total of 144,527 men and women free of cancer at baseline, 317 developed CRC during 5.3 years of follow-up. A case-cohort study (n=1,691) was used, consisting of participants with a DNA sample available. Three well-known SNPs (rs3802842, rs6983267, rs10795668) were genotyped. Hazard ratios (HR) and 95% confidence intervals (CI) of CRC, colon and rectal cancer were calculated, with the Cox proportional hazard models. RESULTS: The crude incidence rates per 100,000 person-years were 41.1 overall, 48.4 for men, and 29.3 for women. Among participants with dysglycemia, SNPs rs3802842 and rs6983267 were both associated with an increased risk of CRC (HR, 3.2; 95% CI, 1.9 to 5.5 and HR, 1.8; 95% CI, 1.1 to 3.1, respectively) and rectal cancer (HR, 3.4; 95% CI, 1.8 to 6.6 and HR, 3.3; 95% CI, 1.6 to 7.1, respectively). The interaction effect of dysglycemia and SNPs was positive, that is, resulted in an elevated risk of CRC, but was not statistically significant. CONCLUSIONS: This study demonstrates that both high FSG and certain SNPs are major risk factors for CRC and rectal cancer but that they did not interact synergistically. The difference in effect size of the SNPs according to CRC subtype (i.e., colon or rectal cancer) and presence of dysglycemia merits further research.

Review on Cardiovascular Disease Prediction Model in Diabetes Patients / 임상당뇨병

The cardiovascular disease (CVD) risk prediction model has been developed based on information on CVD-free subjects, including age, hypertension, diabetes, cholesterol, and smoking status. A methodological review on whether the CVD risk prediction model is appropriate for diabetes patients is necessary. In general, the prediction model consists of three components-relative risk (RR), mean of risk factors, and survival rate. The prediction model would be useable if no differences in those components are found between the general population and diabetes patients. However, in our results, differences were found in the mean of risk factors and survival rate of CVD between the general population and diabetes patients, while no difference was found in RR. In other words, diabetes patients had a significantly increased mean of risk factors and decreased survival rates for CVD. Since the existing CVD risk prediction model for the general population is not applicable to diabetes patients, it is critical to develop a new model for them.

The Korea National Suicide Survey (KNSS): Rationale and Design

Suicide, the fourth leading cause of death in Korea, is a serious national problem. The Korea National Suicide Survey (KNSS) is the result of the first legislation to address this issue, "Article 11 of THE ACT FOR THE PREVENTION OF SUICIDE AND THE CREATION OF A CULTURE OF RESPECT FOR LIFE" (the "Act for the Prevention of Suicide"). To overcome the limitations of previous studies, the KNSS was designed by collaborators from a variety of fields : psychology, epidemiology, social welfare, and psychiatry. The KNSS was composed of four substudies that addressed the multifaceted process involved in suicide-related behavior over time, exploring general attitudes toward suicide and suicidal ideation, suicide planning, suicide attempts, and completed suicides. Study 1 examined the risk factors for suicide based on data regarding completed suicides ; Study 2 adopted the approach of a psychological autopsy ; Study 3 focused on suicide attempters ; and Study 4 explored attitudes toward suicide in the general population. The KNSS was designed to provide a comprehensive understanding of suicide from a longitudinal, multifaceted perspective to serve as a basis for policies aimed at suicide prevention.

The Relationship Between Serum Lipids and Depression

OBJECTIVE: Low cholesterol is associated with depression among western countries. The objective of this study was to examine the relationship between cholesterol and depression in Korean population with low levels of serum cholesterol. METHODS: The data of about 740,000 individuals, aged 30-64 years at entry in the Korean Cancer Prevention Study, were used. Total cholesterol levels were measured in 1992. Depression was measured using the modified DSM-IV (Diagnostic Criteria of Major Depressive Episode in Diagnostic and Statistical Manual of Mental Disorders-IV) scale. Total cholesterol was classified into four groups (quartile). Odds Ratios of low level of cholesterol were evaluated using multi-variable logistic models. RESULTS: The prevalence of major depression was 7.7% in men and 10.4% in women. After adjustment for various confounding variables, an inverse association was detected between cholesterol levels and depression intensity among men and women. The odds ratio (95% confidence interval) of the lowest quartile of cholesterol was 1.16 (1.13-1.20) on major depression compared with the highest quartile of cholesterol in men. The corresponding odds ratio among women was 1.09 (1.04-1.15). The strongest association among 9 items of depression was found at "decreased appetite and lost weight" in both men (OR=1.68) and women (OR=1.43). CONCLUSION: Low cholesterol is associated with major depression in men and women. Further studies are necessary to evaluate the cross-validation, to explore the biological mechanism, and to identify the clinical implication.

The Association between Thigh Circumference and Lipids Profile in Korean Population: The Korea Medical Institute Study

OBJECTIVE: We performed a study of the relationship between thigh circumference and serum lipids. METHODS: A total of 314,842 Korean men and women aged 30 to 79 enrolled in the Korea Medical Institute for medical examination between February 2010 and December 2011 were included. Multiple logistic regression analysis was performed to examine the association of thigh circumference with various lipid profiles after adjustment for age, body mass index (BMI), waist circumference, smoking, and exercise. RESULTS: The average age of study participants was 42.3 years (42.6 years in men and 41.9 years in women). The mean thigh circumference was 53.2 cm (54.3 cm in men and 51.5 cm in women). Thigh circumference was positively correlated with BMI and waist circumference in both men and women. Before adjusting for BMI and waist circumference, thigh circumference was also positively correlated with total cholesterol, triglyceride, high-density lipoprotein (HDL) cholesterol, non-HDL cholesterol, and triglyceride / HDL cholesterol ratio. However, after adjusting for those two variables, the positive correlations became almost disappeared and showed opposite direction indicating that BMI and waist circumference were qualitative confounding variables. CONCLUSIONS: A small thigh circumference was associated with increasing levels of lipid profiles including triglyceride and decreasing level of HDL cholesterol. Through additional researches, establishment of causality is necessary.