Sang Baek Koh

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 268u2005315 Koreans between the ages of 30 and 74u2005years 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.

Prospective Study of Serum Adiponectin and Incident Metabolic Syndrome: The ARIRANG study

OBJECTIVE Increased adiponectin levels may play a protective role in the development of metabolic abnormalities, but prospective studies of the predictive value of serum adiponectin to identify individuals at high risk of new-onset metabolic syndrome are lacking. We investigated whether serum adiponectin predicts incident cases of the metabolic syndrome in a population-based longitudinal study. RESEARCH DESIGN AND METHODS A prospective cohort study was conducted of 2,044 adults (831 men and 1,213 women) aged 40–70 years without metabolic syndrome examined in 2005–2008 (baseline) and 2008–2011 (follow-up). Baseline serum adiponectin concentrations were measured by radioimmunoassay. RESULTS During an average of 2.6 years of follow-up, 153 men (18.4%) and 199 women (16.4%) developed metabolic syndrome. In multivariable-adjusted models, the odds ratio for incident metabolic syndrome comparing the highest with the lowest quartiles of adiponectin levels was 0.25 (95% CI 0.14–0.47) in men and 0.45 (0.28–0.74) in women. While serum adiponectin did not improve the area under the ROC curve for predicting new-onset metabolic syndrome based on information from metabolic syndrome components, the net reclassification improvement and the integrated discrimination improvement of prediction models including adiponectin were significantly higher compared with those of models not including adiponectin among men, with a significant difference between men and women (P = 0.001). CONCLUSIONS Increased adiponectin is an independent protective factor for incident metabolic syndrome in men and women, and it may have a clinical role in predicting new-onset metabolic syndrome among men.

Effects of NADPH oxidase inhibitor on diabetic nephropathy in OLETF rats: The role of reducing oxidative stress in its protective property

Diabetic nephropathy is the most serious complication in diabetes mellitus. Oxidative stress via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and vascular endothelial growth factor (VEGF) pathway play critical roles in the development of diabetic nephropathy. We evaluated the effects of apocynin, NADPH oxidase inhibitor on diabetic nephropathy in a type 2 diabetic rat model. Sixteen Otsuka Long Evans Tokushima Fatty (OLETF) rats and 9 Long Evans Tokushima Otsuka (LETO) were divided into the following three groups: LETO rats (n=9), control OLETF rats (n=7) and apocynin-treated OLETF rats (n=9). We examined body weights, plasma glucose levels, urinary albumin-creatinine ratio (ACR) and protein-creatinine ratio (PCR). At 50 weeks, experimental rats were sacrificed and their kidneys were extracted for hematoxylin eosin stain, immunohistochemical VEGF stain and VEGF mRNA real-time RT-PCR. To examine oxidative stress, we checked 24h urinary 8-OHdG (8-hydroxy-2-deoxyguanosine) and MDA (malondialdehyde). Urinary protein and albumin excretions were reduced after apocynin treatment, though apocynin could not significantly decrease serum glucose levels. There were improvements of glomerular and mesangial expansion in the apocynin-treated OLETF rats. Apocynin significantly decreased optical density of glomerular VEGF expression in immunohistochemical stain and reduced the concentration of 24h urinary 8-OHdG and MDA. From these results, it was suggested that apocynin may have the potential to protect against diabetic nephropathy via amelioration of oxidative stress.

Hepatic venous pressure gradient can predict the development of hepatocellular carcinoma and hyponatremia in decompensated alcoholic cirrhosis.

Objective Portal hypertension is closely associated with serious complications of cirrhosis, which contribute to bad prognosis. Hepatocellular carcinoma (HCC) and low serum sodium (SNa) are manifestations of end-stage liver disease and are associated with poor survival in decompensated cirrhosis patients. We aimed to determine the relationship between hepatic venous pressure gradient (HVPG) and the development of HCC or low SNa in decompensated alcoholic cirrhosis patients. Methods Child-Pugh scores, Model for End-Stage Liver Disease scores, and HVPG at baseline, and the development of HCC or low SNa (SNa <130u2009mEq/l) during follow-up were analyzed prospectively in 170 patients with decompensated alcoholic cirrhosis from December 1999 to January 2008 (mean follow-up period of 33.9±27.9 months). The predictive value of different risk factors for the development of HCC and low SNa and survival were investigated. Results Twenty-four patients developed HCC during the follow-up period. In the multivariate analysis, only baseline HVPG greater than 15u2009mmHg was an independent predictive factor for the development of HCC (relative risk=1.128, P<0.05) and which showed a significantly shorter time for the development of HCC on the Kaplan–Meier analysis. Twenty patients developed low SNa during follow-up. Initial HVPG was also an independent predictive factor for the new development of low SNa in the multivariate analysis (relative risk=1.169, P<0.05) and which also showed significantly shorter times for the development of low SNa on the Kaplan–Meier analysis. Conclusion In decompensated alcoholic cirrhosis, HVPG may be a useful predictive factor for the development of HCC and low SNa.

The ratio of serum leptin to adiponectin provides adjunctive information to the risk of metabolic syndrome beyond the homeostasis model assessment insulin resistance: The Korean Genomic Rural Cohort Study

BACKGROUNDnLeptin and adiponectin are adipokines, shown to have opposing functions for fat metabolism and development of metabolic syndrome. We determined if the ratio of serum leptin to adiponectin (L/A ratio) adjunctively contributes to the risk of metabolic syndrome beyond the homeostasis model assessment of insulin resistance (HOMA-IR).nnnMETHODSnThis study included 1532 men and 1856 women, aged 40-70 y assessed in the Korean Genomic Rural Cohort Study from 2005 to 2008. The serum concentrations of adiponectin and leptin were measured by radioimmunoassay. Area under the receiver operating characteristic curve (AUROC) analyses were used to describe the ability of L/A ratio and HOMA-IR to differentiate between subjects with and without metabolic syndrome.nnnRESULTSnThere were no significant differences in the ability of L/A ratio and HOMA-IR to predict metabolic syndrome (AUROC of L/A ratio vs. HOMA-IR, 0.771 vs. 0.774, p=0.8006 for men; 0.677 vs. 0.691, p=0.3088 for women). There was a significant adjunctive contribution by the L/A ratio, beyond that of HOMA-IR, to the risk of metabolic syndrome in men (p<0.0001 with 0.028 increased AUROC) and women (p=0.025 with 0.017 increased AUROC).nnnCONCLUSIONSnThe L/A ratio provides significant adjunctive information to the risk of metabolic syndrome beyond HOMA-IR alone. The L/A ratio could be a good surrogate marker to assess metabolic syndrome.

Relationship between γ‐glutamyltransferase and metabolic syndrome in a Korean population

Aimsu2003 To investigate associations between γ‐glutamyltransferase (GGT) and components of metabolic syndrome (MS), insulin resistance and inflammatory markers in the Korean population.

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.

Serum levels of angiopoietin-related growth factor are increased in metabolic syndrome.

Angiopoietin-related growth factor (AGF), a novel hepatokine, showed therapeutic implications in diabetic and obese animal models. Although the physiologic functions of human AGF have not yet been identified, serum levels of AGF displayed up-regulation in groups with diseases including preeclampsia and diabetes; and there was little association between genetic variability of AGF and metabolic syndrome-related phenotypes. We analyzed serum levels of AGF and other biochemical and anthropometric markers in 216 Korean persons--the numbers of healthy controls and those with metabolic syndrome were 138 and 78, respectively--to confirm research data from animal models. Women had higher AGF than men (265.01 vs 311.84 ng/mL, P = .003). This study showed that serum AGF levels were significantly higher in subjects with metabolic syndrome (325.89 ng/mL) than those in the healthy group (272.44 ng/mL) (P = .003). Among the components of metabolic syndrome, subjects with high waist circumference or decreased high-density lipoprotein cholesterol had significantly increased serum AGF (271.92 vs 313.68 ng/mL, P = .013; 271.01 vs 310.58 ng/mL, P = .023, respectively). According to multivariate regression analysis, metabolic syndrome itself and waist circumference could be used, in addition to sex and age, as predictors of serum AGF level. In conclusion, serum AGF levels were paradoxically increased in metabolic syndrome, in comparison with data from animal experiments and data on sex, age, and waist circumference. Metabolic syndrome can be a predictor of serum AGF level. Further studies are needed to explore the possibilities of compensatory up-regulation, or AGF resistance, to explain the physiologic roles of AGF in metabolic syndrome.

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

BACKGROUND AND AIMSnTo 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.nnnMETHODSnThe 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.nnnRESULTSnIn 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.nnnCONCLUSIONSnThe 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.

Association between alcohol intake amount and prevalence of metabolic syndrome in Korean rural male population.

Moderate alcohol consumption is known to be associated with a reduced risk of cardiovascular disease and mortality. However, few studies reported that long-term alcohol drinking may increase the prevalence of central obesity, and cardiovascular disease. We examined the association between metabolic syndrome, nutritional factors and alcohol intake amount in Korean male rural population. We performed a cross-sectional analysis on data from Korean Rural Genomic Cohort (KRGC) study. We used multiple logistic regression analysis to estimate the adjusted odds ratio of metabolic syndrome according to alcohol intake amount categories (never, 0-16 g/day, 16-40 g/day, and >40 g/day). The age adjusted odds ratio for the prevalence of metabolic syndrome was significantly increased in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group (1.33; C.I., 1.11-1.59). These results were similar in the high energy intake group, but not in the low energy intake group. Waist circumference, blood pressure, and serum triglyceride levels were significantly higher in the quartile with the highest alcohol consumption compared to the non-alcohol drinking group. These results suggest that large alcohol consumption is associated with metabolic syndrome and may be a modifiable risk factor of metabolic syndrome especially in subjects with high calorie intake.