Low Systolic Blood Pressure and Vascular Mortality Among More Than 1 Million Korean Adults.

BACKGROUND: The association between low systolic blood pressure (SBP) and vascular disease is unclear, especially in nonclinical populations. METHODS AND RESULTS: We studied 1 235 246 individuals who participated in routine medical examinations between 1992 and 1995. The hazard ratios (HRs) were adjusted for potential confounders. During 22.7 million person-years of follow-up, 34 816 individuals died of atherosclerotic vascular diseases. An increase in SBP was directly related to an increase in vascular mortality at SBP above ≈100 mmHg. The group with the lowest SBP (<90 mm Hg) had a higher HR for mortality from atherosclerotic vascular disease (HR, 1.53; 95% confidence interval, 1.15-2.03) in comparison with those with an SBP of 90 to 99 mm Hg. The HR associated with the lowest SBP was 2.54 (95% confidence interval, 1.51-4.29) for ischemic heart disease and 1.21 (95% confidence interval, 0.79-1.85) for stroke. Regarding stroke subtype, mortality from hemorrhagic stroke (HR per 10 mm Hg increase, 0.53; 95% confidence interval, 0.29-0.96), rather than mortality from ischemic stroke (HR per 10 mm Hg increase, 1.00; 95% confidence interval, 0.51-1.97), was inversely associated with SBP when SBP fell to <100 mm Hg. Even when excluding the first 5 years of follow-up, the HRs associated with the lowest SBP did not decrease. The inverse association between SBP and vascular mortality in the range <100 mm Hg tended to be apparent in people aged 60 to 95 years in comparison with individuals aged 30 to 59 years. CONCLUSIONS: J-curve associations exist between SBP and vascular mortality, which reach a nadir at ≈100 mm Hg. SBP of <90 mm Hg may portend death from vascular disease, particularly from ischemic heart disease.

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.

Hazard Ratio of Smoking on Lung Cancer in Korea According to Histological Type and Gender.

PURPOSE: Using nationwide cancer incidence data, we examined whether the strength of the association of cigarette smoking with lung cancer risk differs according to major histological type and gender, taking account of other risk factors in the Korean population. METHODS: The study population derived from government employees and teachers aged 20 years and over who participated in a national health examination program in 1998 or 1999. Total study subjects were 1,357,447. After excluding 1556 subjects who were treated with lung cancer during 1998-2000, we restricted our analysis to 1,355,891 cases. We followed up those 1,355,891 subjects who were cancer-free at baseline until December 31, 2010. The incident cancer cases were identified from the Korea Central Cancer Registry, which is a nationwide hospital-based cancer registry system that includes 94 % of the university hospitals and 96 % of the resident training hospitals of the country. RESULTS: A higher risk for having ever smoked was observed for squamous-cell and small-cell carcinoma in both men and women. Heavy and long-term smokers were at higher risk for these carcinomas. Significant associations with quantity and duration-related factors were observed mainly among men. These findings indicate that smoking is closely related to the risk of squamous-cell and small-cell carcinoma among women as well as men. However, the magnitude of smoking-related lung cancer risk is likely to differ between men and women. CONCLUSION: The hazard ratios for all types of lung cancer were significantly higher in male current smokers than in male never smokers. In case of women, the hazard ratios for adenocarcinoma were not different between current smokers and never smokers. The hazard ratios we found, however, were lower than those reported in Western countries and in Korea, but consistent with those reported in North-eastern Asian countries.

Age-related differences in diabetes care outcomes in Korea: a retrospective cohort study.

BACKGROUND: Age-related differences in diabetes outcomes are important both for clinical and policy considerations. To clarify the basis of such differences, we investigated patterns of associations for age in relation to hospitalization and glycemic control and examined the role of other factors. METHODS: 4471 patients with diabetes aged 40-79 years were drawn from a retrospectively retrieved National Health Insurance Cohort. Using logistic regression, risk factors measured over the two years (2007-2008) were examined for their associations with hospitalization and poor glycemic control during the last year (2009) of follow-up. RESULTS: Compared to the middle-aged patients, older patients were more likely to have been hospitalized (Adjusted odds ratio (OR(adjusted)) = 1.97(95% CI = 1.28, 3.04) for the oldest group (ages 70-79) vs youngest group (ages 40-49)) but less likely to have poor glycemic control (OR(adjusted) = 0.45 (95% CI = 0.37, 0.56) for the oldest group vs youngest group). Older patients were also less likely to be obese but had more complications, longer duration of diabetes, lower continuity of care, and higher blood pressure and total cholesterol level. The pattern of associations for hospitalization and glycemic control was not uniform across the risk factors, sharing only a few common factors such as the duration of diabetes and blood pressure. In general, poor glycemic control was affected predominantly by metabolic management, while hospitalization was strongly related to functional status (i.e., number of complications) and care quality measures (i.e., continuity of care). CONCLUSION: Hospitalization was higher among the older diabetic patients, despite better glycemic control. Factors were differently associated with the two diabetes-related outcomes, providing more comprehensive risk profiles for hospitalization. The co-existence of improved glycemic control and increased hospitalization among older diabetic patients suggests an extension of a geriatric evaluation to wider functional and comorbidity status.

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.

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.

Association between idiopathic pulmonary fibrosis and coronary artery disease: a case-control study and cohort analysis.

BACKGROUND: Although the increased risk of coronary artery disease (CAD) in the patients with idiopathic pulmonary fibrosis (IPF) has been reported, there was few detailed information on the risk factors for CAD in IPF. The aim of this study was to investigate the prevalence of CAD in IPF with analysis of other risk factors. METHODS: The subjects were 460 patients (mean age, 65 years; 79% male; 74% current or ex-smoker) diagnosed as IPF at Asan Medical Center and 1,925 controls matched with age, gender, smoking habits, and date of IPF diagnosis from the cohort of Korean Heart Study. Cardiovascular risk factors and prevalence of CAD in both groups were compared and the incidence of newly developed CAD during follow-up was also analyzed. RESULTS: IPF group was more diabetic, and control group had a higher proportion of hypertension and hypercholesterolemia. The prevalence of CAD in IPF group (7%) was two times higher than that of control group (3%). Multivariate analysis revealed that age (OR, 1.04; 95% CI, 1.02-1.07), hypertension (OR, 2.13; 95% CI, 1.36-3.33), hypercholesterolemia (OR, 3.85; 95% CI, 2.51-5.88), and IPF (OR, 2.64; 95% CI, 1.68-4.14) were significant risk factors for CAD. During follow-up (median: 2.5 years for IPF and 4.4 years for controls), the incidence of newly diagnosed CAD was higher in the patients with IPF (6.8%) compared to controls (2.8%) (RR, 1.92; 95% CI, 1.08-3.43). CONCLUSIONS: IPF itself was an independent risk factor for CAD after the adjustment of age, hypertension, diabetes, and hypercholesterolemia.

The ACC/AHA 2013 pooled cohort equations compared to a Korean Risk Prediction Model for atherosclerotic cardiovascular disease.

BACKGROUND AND AIMS: To evaluate the performance of the American College of Cardiology/American Heart Association (ACC/AHA) 2013 Pooled Cohort Equations in the Korean Heart Study (KHS) population and to develop a Korean Risk Prediction Model (KRPM) for atherosclerotic cardiovascular disease (ASCVD) events. METHODS: The KHS cohort included 200,010 Korean adults aged 40-79 years who were free from ASCVD at baseline. Discrimination, calibration, and recalibration of the ACC/AHA Equations in predicting 10-year ASCVD risk in the KHS cohort were evaluated. The KRPM was derived using Cox model coefficients, mean risk factor values, and mean incidences from the KHS cohort. RESULTS: In the discriminatory analysis, the ACC/AHA Equations' White and African-American (AA) models moderately distinguished cases from non-cases, and were similar to the KRPM: For men, the area under the receiver operating characteristic curve (AUROCs) were 0.727 (White model), 0.725 (AA model), and 0.741 (KRPM); for women, the corresponding AUROCs were 0.738, 0.739, and 0.745. Absolute 10-year ASCVD risk for men in the KHS cohort was overestimated by 56.5% (White model) and 74.1% (AA model), while the risk for women was underestimated by 27.9% (White model) and overestimated by 29.1% (AA model). Recalibration of the ACC/AHA Equations did not affect discriminatory ability but improved calibration substantially, especially in men in the White model. Of the three ASCVD risk prediction models, the KRPM showed best calibration. CONCLUSIONS: The ACC/AHA Equations should not be directly applied for ASCVD risk prediction in a Korean population. The KRPM showed best predictive ability for ASCVD risk.

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 individual's risk of CHD and provides a useful guide to identify the groups at high risk for CHD among Koreans.

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.

Adiponectin as predictor for diabetes among pre-diabetic groups.

Adiponectin is found to associate with diabetes in studies apart from cohort studies. This prospective cohort study is to evaluate the predictive role of adiponectin in diabetes among participants with impaired fasting glucose (IFG). A total of 42,845 participants who visited 7 health examination centers located in Seoul and Kyunggi province, South Korea, during 2004-2008 were first included. Of the 42,845 participants, 5,085 participants had IFG. IFG was categorized as stage 1 (fasting glucose 100-109 mg/dL) or stage 2 (110-125 mg/dL). The incidence rates of diabetes were followed up to December, 2011. Hazard ratios (HRs) and 95 % confidence intervals (CI) were performed by Cox proportional hazard model. Of the 5,085 participants, 652 participants developed diabetes during a mean follow-up of 4.4 years. Low adiponectin was associated with diabetes among men with stage 2 IFG (HR, 1.78; 95 %CI, 1.33-2.38) while it was associated with diabetes among women with stage 1 IFG (HR, 2.64; 95 %CI, 1.38-5.03) and stage 2 IFG (HR, 2.17; 95 %CI, 1.07-4.42). When combined men and women, the association between adiponectin and diabetes was statistically significant in stage 2 IFG with an increase of about 82 % (HR, 1.82; 95 %CI, 1.40-2.39) after adjusting for age, sex, body mass index, waist circumference, and fasting serum glucose. There was an interaction by sex and stage 1 IFG in the association between adiponectin and risk of diabetes (P < 0.001). Adiponectin was independently associated with diabetes among participants with IFG. This association was apparent in stage 2 IFG. Adiponectin may be used as a predictor of diabetes in patients having IFG.

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.

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.

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.

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.