Young Duk Yun

A coronary heart disease prediction model: the Korean Heart Study

Objective The objectives of this study were to develop a coronary heart disease (CHD) risk model among the Korean Heart Study (KHS) population and compare it with the Framingham CHD risk score. Design A prospective cohort study within a national insurance system. Setting 18 health promotion centres nationwide between 1996 and 2001 in Korea. Participants 268 315 Koreans between the ages of 30 and 74 years without CHD at baseline. Outcome measure Non-fatal or fatal CHD events between 1997 and 2011. During an 11.6-year median follow-up, 2596 CHD events (1903 non-fatal and 693 fatal) occurred in the cohort. The optimal CHD model was created by adding high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides to the basic CHD model, evaluating using the area under the receiver operating characteristic curve (ROC) and continuous net reclassification index (NRI). Results The optimal CHD models for men and women included HDL-cholesterol (NRI=0.284) and triglycerides (NRI=0.207) from the basic CHD model, respectively. The discrimination using the CHD model in the Korean cohort was high: the areas under ROC were 0.764 (95% CI 0.752 to 0.774) for men and 0.815 (95% CI 0.795 to 0.835) for women. The Framingham risk function predicted 3–6 times as many CHD events than observed. Recalibration of the Framingham function using the mean values of risk factors and mean CHD incidence rates of the KHS cohort substantially improved the performance of the Framingham functions in the KHS cohort. Conclusions The present study provides the first evidence that the Framingham risk function overestimates the risk of CHD in the Korean population where CHD incidence is low. The Korean CHD risk model is well-calculated alternations which can be used to predict an individuals risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.

Impaired Fasting Glucose and Risk of Cardiovascular Disease in Korean Men and Women: The Korean Heart Study

OBJECTIVE The relationship between impaired fasting glucose (IFG) and risk of cardiovascular disease (CVD) or ischemic heart disease (IHD) varies widely according to sex and ethnicity. We evaluated the relationship between IFG and CVD or IHD among Korean men and women. RESEARCH DESIGN AND METHODS A total of 408,022 individuals who underwent voluntary private health examinations in 17 centers in South Korea were followed for 10 years. Data regarding CVD or IHD events were obtained from the Korean National Health Insurance database. IFG was categorized as grade 1 (fasting glucose 100–109 mg/dL) or grade 2 (110–125 mg/dL). RESULTS Incidence rates of CVD (per 100,000 person-years) were 2,203 for diabetes. Age-adjusted hazard ratios (HRs) for CVD were 1.17 (95% CI 1.13–1.20) for grade 1 IFG, 1.30 (1.24–1.35) for grade 2 IFG, and 1.81 (1.75–1.86) for diabetes. The increased risk for women was similar to that of men. Age-adjusted HRs for IHD and ischemic stroke were also significantly increased for men and women with IFG and diabetes. After multivariate adjustment of conventional risk factors (hypertension, dyslipidemia, smoking, obesity, and family history of CVD), the overall risk of CVD was greatly attenuated in all categories. However, the HRs for IHD and ischemic stroke remained significantly increased in men for grade 2 IFG but not in women. CONCLUSIONS In Korea, grade 2 IFG is associated with increased risk of IHD and ischemic stroke, independent of other conventional risk factors, in men but not in women.

Fasting Glucose Level and the Risk of Incident Atherosclerotic Cardiovascular Diseases

OBJECTIVE Although diabetes increases the risk of cardiovascular disease (CVD) and mortality, the dose-response relationship between fasting glucose levels below those diagnostic of diabetes with cardiovascular events has not been well characterized. RESEARCH DESIGN AND METHODS A prospective cohort study of more than one million Koreans was conducted with a mean follow-up of 16 years. A total of 1,197,384 Korean adults with no specific medical conditions diagnosed were classified by baseline fasting serum glucose level. Associations of fasting glucose level with CVD incidence and mortality, stroke incidence and mortality, and all-cause mortality were analyzed using multivariate proportional hazards regression. RESULTS The relationships between fasting glucose levels and CVD risks generally followed J-shape curves, with lowest risk in the glucose range of 85–99 mg/dL. As fasting glucose levels increased to >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increased, but risk for hemorrhagic stroke did not. Fasting glucose levels <70 mg/dL were associated with increased risk of all stroke (hazard ratio 1.06, 95% CI 1.01–1.11) in men and (hazard ratio 1.11, 1.05–1.17) in women. CONCLUSIONS Both low glucose level and impaired fasting glucose should be considered as predictors of risk for stroke and coronary heart disease. The fasting glucose level associated with the lowest cardiovascular risk may be in a narrow range.

The Korean Heart Study: rationale, objectives, protocol, and preliminary results for a new prospective cohort study of 430,920 men and women.

Background To describe the rationale, objectives, protocol, and preliminary results for a new prospective cohort study of cardiovascular disease (CVD) risk factors in South Korea. Methods Study members were recruited from participants in routine health assessments at health promotion centres across South Korea. Established and emerging CVD risk factors were measured. Eighteen centres holding electronic health records agreed to linkage of participants’ records to future health insurance claims for monitoring of disease events. The recruitment of 430,920 participants (266,782 men, 164,138 women), aged 30–74 years, provides broad geographical reach across South Korea. Results Risk factor prevalence was more favourable in women than men, and, in general, in the younger rather than older study members. There was also close similarity between the characteristics of the present sample and the Korean National Health and Nutrition Examination Survey. The expected associations between risk factors and both CVD and death were also apparent. Conclusions Data from the present sample, based on data linkage, show close agreement with South Korea-wide surveys (for risk factor prevalence) and the extant literature (for risk factor associations). These findings gives confidence in future results anticipated from this cohort study of east Asians – a group that has been traditionally under-researched.

γ‐Glutamyltransferase and cancer risk: The Korean cancer prevention study

Elevated serum γ‐glutamyltransferase (GGT) is a marker of hepatic injury and is associated with risk of chronic disease. However, the value of GGT as a biomarker for cancer risk remains unclear. Therefore, we evaluated the association of serum GGT with cancer incidence among more than 1.6 million Koreans. We included 1,662,087 Koreans (1,108,121 men and 553,966 women aged 20–95 years) who received health insurance from the National Health Insurance Service and had a biennial medical evaluation between 1995 and 1998. Follow‐up was through December 2012. Using Cox proportional hazards models, we adjusted for age, smoking status, alcohol consumption, exercise and body mass index after exclusion of early cases (cancer diagnosis or death within 5 years of starting follow‐up) and estimated hazard ratios (HRs) of overall and organ‐specific cancer incidence by GGT quintiles. During the 17‐year follow‐up, 129,087 new cancer cases occurred among the participants. Across levels of GGT, there was a positive gradient of HR and the highest quintile of GGT (≥60 IU/L) had the highest HR for all cancers in both men and women. By cancer site, the association was strongest for liver cancer, comparing the highest and lowest strata in men [HR, 6.67; 95% confidence interval (95%CI), 5.88–7.57] and in women (HR, 7.57; 95%CI, 6.41–8.94). Significant associations were also observed for cancers of the esophagus, larynx, stomach, colorectal, bile duct and lung in men and of the bile duct in women. Increased serum GGT level is independently associated with risk of cancer.

Serum Adiponectin and Type 2 Diabetes: A 6-Year Follow-Up Cohort Study

Background Studies on factors which may predict the risk of diabetes are scarce. This prospective cohort study was conducted to determine the association between adiponectin and type 2 diabetes among Korean men and women. Methods A total of 42,845 participants who visited one of seven health examination centers located in Seoul and Gyeonggi province, Republic of Korea between 2004 and 2008 were included in this study. The incidence rates of diabetes were determined through December 2011. To evaluate the effects of adiponectin on type 2 diabetes, the Cox proportional hazard model was used. Results Of the 40,005 participants, 959 developed type 2 diabetes during a 6-year follow-up. After the adjustment for age, body mass index (BMI), and waist circumference, the risks for type 2 diabetes in participants with normoglycemia had a 1.70-fold (95% confidence interval [CI], 1.21 to 2.38) increase in men and a 1.83-fold (95% CI, 1.17 to 2.86) increase in women with the lowest tertile of adiponectin when compared to the highest tertile of adiponectin. For participants with impaired fasting glucose (IFG), the risk for type 2 diabetes had a 1.46-fold (95% CI, 1.17 to 1.83) increase in men and a 2.52-fold (95% CI, 1.57 to 4.06) increase in women with the lowest tertile of adiponectin. Except for female participants with normoglycemia, all the risks remained significant after the adjustment for fasting glucose and other confounding variables. Surprisingly, BMI and waist circumference were not predictors of type 2 diabetes in men or women with IFG after adjustment for fasting glucose and other confounders. Conclusion A strong association between adiponectin and diabetes was observed. The use of adiponectin as a predictor of type 2 diabetes is considered to be useful.

Measuring depression in South Korea: Validity and reliability of a brief questionnaire in the Korean Cancer Prevention Study

OBJECTIVE To examine the validity and reliability of a new questionnaire for measuring depression in a South Korean population, and then to estimate the prevalence of depression in that country using this tool. METHODS In total, 742,600 individuals (123,725 women), aged 30-64 years at entry into the Korean Cancer Prevention Study, completed a depression symptom in 1992 (baseline enrollment) and again in 1994. We examined the concurrent validity of the depression questionnaire by relating data from it to known socio-demographic and behavioral correlates of depression; its predictive capacity by relating scores from the questionnaire to the occurrence of future hospitalization for depression; and the test-retest reliability by comparing scores from its administration in 1992 to those in 1994. RESULTS The prevalence of major depression was 7.5% in men and 10.0% in women. Factors significantly related to major depression were being younger (men), being female, not being married, of lower socioeconomic status, being a smoker, a heavy drinker, and not exercising regularly. Men (hazard ratio; 95% confidence interval: 2.0; 1.8, 2.2) and women (1.6; 1.3, 1.9) with questionnaire-ascertained depression experienced an elevated risk of hospitalization for the disorder during follow-up. The rates of agreement between responses to 1992 and 1994 surveys were 91.3% in men and 88.3% in women. CONCLUSIONS These findings imply validity of the instrument and support its use in future studies directed at links of depression with somatic disease endpoints. LIMITATION The questions do not have a specified time frame of reference.

Duration of ovarian hormone exposure and atherosclerotic cardiovascular disease in Korean women: the Korean Heart Study.

Objective:Although reproductive and hormonal factors, such as menarche and menopause, have been reported as independent risk factors for atherosclerotic cardiovascular disease (ASCVD), few studies have examined these factors in East Asian populations. In the Korean Heart Study, ASCVD risk related to duration of ovarian hormone exposure was examined in a cohort of 66,104 Korean women. Methods:Study members were recruited from participants of routine health examinations at health promotion centers across South Korea in 1996-2004. Ovarian hormone exposure was defined as duration between menarche and menopause. Incidence rates for ASCVD, stroke, and ischemic heart disease were examined in relation to ovarian hormone exposure. Results:The mean duration of ovarian hormone exposure at study baseline was 33.7 years, and risk for ASCVD was negatively associated with duration. Women with shorter ovarian hormone exposure (<30 y) had a higher risk of developing ASCVD (hazard ratio [HR], 1.30; 95% CI, 1.01-1.68) than women with longer ovarian hormone exposure (35-35 y). In similar comparison groups, women with ovarian hormone exposure shorter than 30 years were at increased risk for developing total stroke (HR, 1.18; 95% CI, 1.00-1.38), thrombotic stroke (HR, 1.30; 95% CI, 1.05-1.61), ischemic heart disease (HR, 1.40; 95% CI, 1.19-1.63), and acute myocardial infarction (HR, 1.73; 95% CI, 1.08-2.47). Conclusions:Our study provides further confirmation of increased cardiovascular risk with shorter reproductive years. Therefore, women with reduced lifetime ovarian hormone exposure should focus on minimizing ASCVD risk by lifestyle modifications such as smoking avoidance or increased physical activities.

Duration of ovarian hormone exposure and gynecological cancer risk in Korean women: the Korean Heart Study

BACKGROUND Although reproductive and hormonal factors - such as early menarche and late menopause - have been reported as independent risk factors for cancer, few studies have examined these factors in East Asian populations. METHODS We performed a large prospective cohort study of 66,466 women. Ovarian hormone exposure was defined as length of time between menarche and menopause. Incidence rates for breast, ovarian, endometrial and cervical cancers were examined separately in relation to reproductive lifespan defined as age at menopause minus age at menarche. Multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using the Cox proportional hazards model. RESULTS Women with early menarche were at increased risk for developing breast cancer (HR, 1.57, 95% CI, 1.17-2.10) for age at menarche ≤12 years compared to women with age at menarche ≥17 years. Women with late age at menopause (≥52 years) had increased risks for cancers of the breast (HR, 1.59, 95%CI, 1.11-2.28) and ovary (HR, 3.22, 95% CI, 1.09-9.55) compared to women with early menopause (≤45 years of age). Women with longer duration of ovarian hormone exposure (≥40 years) were at increased risk for developing breast cancer (HR, 2.23, 95% CI, 1.35-3.68) as well as endometrial cancer (p for trend, 0.0209). CONCLUSIONS We showed that longer reproductive spans are associated with an increased risk of breast and endometrial cancer in Korean women.