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.

Outcomes of Pregnancy after Breast Cancer in Korean Women:A Large Cohort Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#The purpose of this study was to determine the rate and outcomes of pregnancies subsequentto breast cancer in Korea, and the effect of such pregnancies on the prognosis ofwomen who survived breast cancer and subsequently conceived. @*Materials and Methods@#We followed a total of 31,761 Korean women 45 years of age or younger who were treatedfor primary breast cancer from 2002 to 2010. We also included follow-up surveys that wereconducted through December 2011. We identified recurrence and mortality from breastcancer using data linked to the Korea National Health Insurance database. We used propensityscore matching of the study cohort to analyze the risks of recurrence and mortality frombreast cancer depending on pregnancy. @*Results@#Within our sample, 992 women (3.1%) became pregnant after receiving treatment for breastcancer. Of those, 622 (67.5%) successfully delivered; the remaining 370 (32.5%) failed todeliver. After propensity score matching, we found that the women who became pregnantafter breast cancer did not have a different risk of recurrence (hazard ratio [HR], 0.503;95% confidence interval [CI], 0.434 to 0.584) and death (HR, 0.520; 95% CI, 0.397 to0.681), compared with those who did not conceive after breast cancer treatment. @*Conclusion@#Our study is the first to report outcomes for Korean women who survived breast cancer andsubsequently conceived. Women who survived breast cancer and subsequently becamepregnant did not show a poorer survival outcome, compared with those who did not becomepregnant.

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 J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES: The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population. METHODS: We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models. RESULTS: A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased. CONCLUSION: A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

The J-curve between Diastolic Blood Pressure and Risk of All-cause and Cardiovascular Death

BACKGROUND AND OBJECTIVES@#The J-curve phenomenon between diastolic blood pressure (DBP) and mortality has been reported repeatedly in treated patients. However, the baseline risk of low DBP has not been fully explored. This study was to examine the relationship between DBP and risk of mortality from all-cause, atherosclerotic vascular diseases (ASCVD), and ischemic heart disease (IHD) using a prospective cohort of general population.@*METHODS@#We analyzed 1,234,435 participants of the Korean Cancer Prevention Study cohort (789,255 men, 30–95 years of age) who had a medical evaluation from 1992 to 1995 using Cox proportional hazards models.@*RESULTS@#A total of 22.5 million person-years were followed up (mean age 46.6 years, deaths 193,903 cases). The hazard ratios of mortality from all-cause and ASCVD, among those with DBP < 60 mmHg compared to 70–79 mmHg were 1.23 (95% confidence interval [CI], 1.16–1.30) and 1.37 (95% CI, 1.20–1.57), respectively, after adjustment for multivariable including systolic blood pressure. Increased risks of all-cause death in the lowest DBP category group were maintained in men or women, 30–59 or ≥60 years of age, smoker or non-smoker and diabetes mellitus (DM) or non-DM subgroups. The risk in DBP 60–69 mmHg groups increased in several subgroups. However, the risk for ASCVD death in 30–59 years and DM group, and risk for IHD death in most subgroups except for elderly (≥60 years) decreased.@*CONCLUSION@#A J-curve relationship between low DBP and all-cause death was found consistently. The baseline risk in the general population may be considered for risk assessment, particularly in case of interventions that lower DBP below 60 mmHg.

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.

Cost-Benefit Analysis of Malaria Chemoprophylaxis and Early Diagnosis for Korean Soldiers in Malaria Risk Regions

BACKGROUND: Chemoprophylaxis has been used to prevent malaria among soldiers and secondary transmission, as it effectively facilitates a decline in disease occurrence and secondary prevention. However, poor compliance and decreased risk of exposure to malaria necessitate that control strategies be reestablished. METHODS: To predict the incidence of malaria according to a control strategy, we proposed a mathematical model for its transmission using epidemiological data from 2010 to 2012. The benefit component included in the analyses was the averted cost with each control strategy, and the cost components were the cost of implementing chemoprophylaxis and early diagnosis. RESULTS: The chemoprophylaxis regimen with hydroxychloroquine sulfate and primaquine was Intervention 1, the regimen with primaquine only was Intervention 2, and diagnosis with a rapid diagnostic test (RDT) kit within 5 days of fever was Intervention 3. The simulation indicated that the combined control program with chemoprophylaxis and early diagnosis would be the most effective strategy, whereas sole early diagnosis would be the least effective strategy. However, the cost-benefit ratio of chemoprophylaxis was less than Intervention 1, irrespective of the varying range of chemoprophylaxis compliance, and that of early diagnosis was more than Intervention 1, regardless of the varying early diagnosis rate and demand for the RDT kit. Although chemoprophylaxis would be more effective at reducing the incidence of malaria than early diagnosis, it is less economical due to the higher cost. CONCLUSION: Our results support the introduction of early diagnosis with a RDT kit to control malaria in the Republic of Korea Army.

Cost-of-Illness Trends Associated with Thyroid Disease in Korea

BACKGROUND: The purpose of this study is to analyze the scale of and trends associated with the cost-of-illness of thyroid disease in Korea at 2-year intervals during the last 10 years for which data are available. METHODS: Cost-of-illness was estimated in terms of direct and indirect costs. Direct costs include direct medical costs due to hospitalization, outpatient and pharmacy sectors, transportation, and care-giver costs. Indirect costs include future income loss due to premature death and loss of productivity as a result of absence from work. RESULTS: The cost-of-illness of thyroid disease in Korea was estimated at 224.2 billion won in 2002, 303.4 billion won in 2004, 400.3 billion won in 2006, 570.4 billion won in 2008, and 762.2 billion won in 2010. For example, the cost-of-illness of thyroid disease in 2010 was 3.4 times greater compared to 2002. The direct cost of the total cost-of-illness was 69.7%, which accounted for the highest proportion of costs. Cost-of-illness for individuals between the ages of 30 and 50 accounted for the greatest share of costs. CONCLUSION: The cost-of-illness of thyroid disease was relatively large in economically active age groups, and demonstrated a very rapid growth rate compared to other major diseases in Korea. Therefore, we suggest nationwide recognition of the importance of prevention and management of thyroid disease and prioritization of the management of thyroid disease among current and future health promotion policies in Korea.

Socioeconomic costs of liver disease in Korea / 대한간학회지

BACKGROUND/AIMS: This study analyzed the scale and trends of the social and economic costs of liver disease in Korea for the past 5 years. METHODS: The social aspects of socioeconomic costs were projected for viral hepatitis (B15-B19), liver cirrhosis, malignant neoplasm of the liver (C22) and other liver diseases (K70-K76), as representative diseases by dividing costs into direct and indirect from 2004 to 2008. Direct costs include hospitalization, outpatient, and pharmacy costs in the health-care sector, and transportation and caregiver costs. Indirect costs include the future income loss due to premature death and the loss of productivity resulting from absence from work. RESULTS: The social and economic costs of liver disease were projected to be KRW 5,858 billion in 2004, KRW 5,572 billion in 2005, KRW 8,104 billion in 2006, KRW 6,095 billion in 2007, and KRW 5,689 billion in 2008. The future income loss resulting from premature death is thus greatest, from 73.9% to 86.1%, followed by the direct medical costs, from 9.0% to 18.1%. The productivity loss resulting from absence from work accounts for 3.3-5.5%, followed by the direct nonmedical costs such as transportation and caregiver costs, at 1.5-2.5%. CONCLUSIONS: Among the socioeconomic costs of liver disease in Korea, the future income loss resulting from premature death is showing a decreasing trend, whereas direct medical costs are increasing dramatically.

Association Between Socioeconomic Status and All-Cause Mortality After Breast Cancer Surgery: Nationwide Retrospective Cohort Study / 예방의학회지

OBJECTIVES: This study aims to evaluate and explain the socioeconomic inequalities of all-cause mortality after breast cancer surgery in South Korea. METHODS: This population based study included all 8868 females who underwent radical mastectomy for breast cancer between January 2002 and June 2003. Follow-up for mortality continued from January 2002 to June 2006. The patients were divided into 4 socioeconomic classes according to their socioeconomic status as defined by the National Health Insurance contribution rate. The relationship between socioeconomic status and all-cause mortality after breast cancer surgery was assessed using the Cox proportional hazards model with adjusting for age, the Charlson's index score, emergency hospitalization, the type of hospital and the hospital ownership. RESULTS: Those in the lowest socioeconomic status group had a significantly higher hazard ratio of 2.09 (95% CI =1.50 - 2.91) compared with those in the highest socioeconomic group after controlling for all the identifiable confounding variables. For all-cause mortality after radical mastectomy, all the other income groups showed significantly higher 3-year mortality rates than did the highest income group. CONCLUSIONS: The socioeconomic status of breast cancer patients should be considered as an independent prognostic factor that affects all-cause mortality after radical mastectomy, and this is possibly due to a delayed diagnosis, limited access or minimal treatment leading to higher mortality. This study may provide tangible support to intensify surveillance and treatment for breast cancer among low socioeconomic class women.

Estimating the Socioeconomic Costs of Alcohol Drinking Among Adolescents in Korea / 예방의학회지

OBJECTIVES: The purpose of this study was to estimate the socioeconomic costs resulting from alcohol drinking among adolescents as of 2006 from a societal perspective. METHODS: The costs were classified into direct costs, indirect costs, and other costs. The direct costs consisted of direct medical costs and direct non-medical costs. The indirect costs were computed by future income losses from premature death, productivity losses from using medical services and reduction of productivity from drinking and hangover. The other costs consisted of property damage, public administrative expenses, and traffic accident compensation. RESULTS: The socioeconomic costs of alcohol drinking among adolescents as of 2006 were estimated to be 387.5 billion won (0.05% of GDP). In the case of the former, the amount included 48.25% for reduction of productivity from drinking and hangover, 39.38% for future income losses from premature death, and 6.71% for hangover costs. CONCLUSIONS: The results showed that the socioeconomic costs of alcohol drinking among adolescents in Korea were a serious as compared with that of the United States. Therefore, the active interventions such as a surveillance system and a prevention program to control adolescents drinking by government and preventive medicine specialist are needed.

The Study about the Construct Validity of Type D Personality Scale : With Normal College Students Group as a Data Base / 신경정신의학

OBJECTIVES: The purpose of this study was to test the construct validity of the Type D personality scale (DS14). METHODS: The DS14 and other personality scales, which have good construct validity (MMPI-2), TCI-RS, MBTI, NEO-PI-R) were administered to 151 college students. Correlation and regression analyses were performed to evaluate the validity of the DS14. RESULTS: There were significant positive correlations between the DS14 total score and scores on the F, D, Pa, Pt, Sc, Si and 'negative emotionality' scales (MMPI-2), the 'harm avoidance' scale (TCI), the 'neuroticism' scale (NEO-PI-R), and the 'introversion' scale (MBIT). Additionally, there were significant negative correlations between the DS14 total score and extroversion, agreeableness, openness to experience, cooperativeness, and reward dependence scales. Stepwise regression analysis also showed coherent RESULTS: negative emotionality, introversion, RCd and RC2 (MMPI-2), harm avoidance (TCI), neuroticism (NEO-PI-R), introversion, thinking (MBIT) scales were selected as significant explanatory variables. CONCLUSION: Individuals with a Type-D personality, as assessed by the DS14, seem to have a tendency to experience negative emotions such as depression and anxiety. As a construct, Type-D personality also seems to be closely related to neuroticism and introversion. These results indicate that the DS14 has sound construct validity as a screening tool for measuring stress-vulnerability traits, that is to say, type-D personality.

Analysis of Willingness-to-Quit Cigarette Price among Korean Male Adults / 예방의학회지

OBJECTIVES: The purpose of this study was to estimate the willingness to quit cigarette price among Korean male adults, and to examine he factors affecting the willingness to quit cigarette price. METHODS: The data was collected by a random digit dial telephone survey. 702 samples were analyzed by using ttests, ANOVA and OLS regression analysis. To estimate the willingness to quit cigarette price, smokers were asked dichotomous questions with open-ended follow-up and the starting point of the price was randomized by one of 5 bid prices elicited from a pilot study. RESULTS: The mean of the willingness to quit cigarette price was 4,287 Won per package, which was about 2,000 Won higher than the mean of the actual price the smokers now paid. About 41% of respondents were willing to quit smoking if the price of cigarette would be increased by 3,000 Won, and if the price would be increased by 20,000 Won, all respondents were willing to quit smoking. The factors associated with the willingness to quit cigarette price were the place of residence, the amount of smoking and the degree of exposure to smoking through the mass media. CONCLUSIONS: The results showed that to get people to quit smoking, increasing the cigarette price would obviously be effective and much higher prices have a greater effect. Furthermore, to enlarge the effect of increased cigarette prices, providing more cessation programs to small towns, reducing the amount of smoking and decreasing or prohibiting advertisements of cigarettes and smoking in the mass media will be efficient.

Socioeconomic Costs of Alcohol Drinking in Korea

BACKGROUND: The purpose of this study was to estimate socioeconomic costs caused by alcohol drinking in Korea as of 2004 in an effort to raise the awareness of the gravity of problems associated with alcohol drinking and the necessity of active intervention by family physicians. METHODS: The costs were classified as direct costs, indirect costs and other costs. The direct costs consisted of direct medical costs and direct non-medical costs. The indirect costs were computed by the reduction and loss of productivity and the loss of workforce. Other costs consisted of property loss, administration costs and costs of alcohol beverage. RESULTS: The annual costs, which seemed to be attributable to alcohol drinking, were estimated to be 200,990 hundred million won (2.9% of GDP). In the case of the former, the amount included 38.83% for reduction of productivity, 26.92% for loss of the workforce, 22.24% for alcoholic beverage, 5.34% for direct medical costs, 2.29% for loss of productivity, 1.87% for direct non- medical costs, 1.54% for administration costs and 0.97% for loss of property. CONCLUSION: Our study confirms that compared with the cases of Japan (1.9% of GNP), Canada (1.09% of GDP), France (1.42% of GDP) and Scotland (1.19% of GDP), alcohol drinking incurs substantial socioeconomic costs to Koreans. An active intervention by family physicians is suggested.

Determinants of Sterilization among Married Couples in Korea / 예방의학회지

OBJECTIVES: The purpose of this study was to examine the determinants of sterilization in South Korea. METHODS: This study was based on the data from the Korea National Fertility Survey carried out in the year 2000 by the Korea Institute of Health and Social Affairs. The subjects of the analysis were 4,604 women and their husbands who were in their first marriage, in the age group of 15-49 years. The data were analyzed by multiple logistic regression analysis. RESULTS: Consistent with the findings of previous studies, the woman's age and the number of total children increased the likelihood of sterilization. In addition, the year of marriage had a strong positive association with sterilization. Interestingly, the number of surviving sons tended to increase the likelihood of sterilization, whereas the woman's education level and age at the time of marriage showed a negative association with sterilization. Religion, place of residence, son preference, and the husband's education level, age and type of occupation were not significant determinants of sterilization. CONCLUSIONS: The sex of previous children and lower level of education are distinct determinants of sterilization among women in South Korea. More studies are needed in order to determine the associations between sterilization rate and decreased fertility.

The Effect of Cigarette Price on Smoking Behavior in Korea / 예방의학회지

OBJECTIVES: To determine the impact of cigarette prices on the decision to initiate and quit smoking by taking into account the interdependence of smoking and other behavioral risk factors. METHODS: The study population consisted of 3,000 male Koreans aged > or =20. A survey by telephone interview was undertaken to collect information on cigarette price, smoking and other behavioral risk factors. A two-part model was used to examine separately the effect of price on the decision to be a smoker, and on the amount of cigarettes smoked. RESULTS: The overall price elasticity of cigarettes was estimated at -0.66, with a price elasticity of -0.02 for smoking participation and -0.64 for the amount of cigarettes consumed by smokers. The inclusion of other behavioral risk factors reduced the estimated price elasticity for smoking participation substantially, but had no effect on the conditional price elasticity for the quantity of cigarettes smoked. CONCLUSIONS: From the public health and financial perspectives, an increase in cigarette price would significantly reduce smoking prevalence as well as cigarette consumption by smokers in Korea.

Type of Alcoholic Beverage and High Risk Drinking for Acute Harm / 예방의학회지

OBJECTIVE: Studies have suggested that beer is associated with a high risk of mortality and morbidity. The purpose of this study was to investigate how types of alcoholic beverage are related to high risk acute harm. METHODS: Data from the 1997 Korea's Behavioral Risk Factor Surveillance System Survey, collected through telephone questionings, were analyzed based on multi-stage stratified random sampling (N=1, 045). Among those who had drunk at least one type of alcoholic beverage in the last month, one episode where the drinker had consumed the highest level of ethanol was selected, and the alcohol consumption per drinking day categorized into four risk levels of short-term, 'acute' harm, according to the WHO guidelines. Employing ordered logistic regression analyses, as the explanatory variables, types of alcoholic beverage, with and without socioeconomic characteristics, were considered. RESULTS: Spirits and soju were more than ten and three times, respectively, more likely than beer, while makkolli and wine were almost as likely as beer, to involve high risk drinking, irrespective of controlling for the socioeconomic characteristics. CONCLUSIONS: Unlike most Western countries, in Korea, beer, rather than spirits or soju, is generally less likely to be associated with high risk drinking for acute harm. The influence of beverage types on high risk drinking for acute harm appears to vary between countries.