Heejin Kimm

Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis.

BACKGROUND Substantial controversy surrounds the use of estimated glomerular filtration rate (eGFR) and albuminuria to define chronic kidney disease and assign its stages. We undertook a meta-analysis to assess the independent and combined associations of eGFR and albuminuria with mortality. METHODS In this collaborative meta-analysis of general population cohorts, we pooled standardised data for all-cause and cardiovascular mortality from studies containing at least 1000 participants and baseline information about eGFR and urine albumin concentrations. Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause and cardiovascular mortality associated with eGFR and albuminuria, adjusted for potential confounders. FINDINGS The analysis included 105,872 participants (730,577 person-years) from 14 studies with urine albumin-to-creatinine ratio (ACR) measurements and 1,128,310 participants (4,732,110 person-years) from seven studies with urine protein dipstick measurements. In studies with ACR measurements, risk of mortality was unrelated to eGFR between 75 mL/min/1.73 m(2) and 105 mL/min/1.73 m(2) and increased at lower eGFRs. Compared with eGFR 95 mL/min/1.73 m(2), adjusted HRs for all-cause mortality were 1.18 (95% CI 1.05-1.32) for eGFR 60 mL/min/1.73 m(2), 1.57 (1.39-1.78) for 45 mL/min/1.73 m(2), and 3.14 (2.39-4.13) for 15 mL/min/1.73 m(2). ACR was associated with risk of mortality linearly on the log-log scale without threshold effects. Compared with ACR 0.6 mg/mmol, adjusted HRs for all-cause mortality were 1.20 (1.15-1.26) for ACR 1.1 mg/mmol, 1.63 (1.50-1.77) for 3.4 mg/mmol, and 2.22 (1.97-2.51) for 33.9 mg/mmol. eGFR and ACR were multiplicatively associated with risk of mortality without evidence of interaction. Similar findings were recorded for cardiovascular mortality and in studies with dipstick measurements. INTERPRETATION eGFR less than 60 mL/min/1.73 m(2) and ACR 1.1 mg/mmol (10 mg/g) or more are independent predictors of mortality risk in the general population. This study provides quantitative data for use of both kidney measures for risk assessment and definition and staging of chronic kidney disease. FUNDING Kidney Disease: Improving Global Outcomes (KDIGO), US National Kidney Foundation, and Dutch Kidney Foundation.Background A comprehensive evaluation of the independent and combined associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality is required for assessment of the impact of kidney function on risk in the general population, with implications for improving the definition and staging of chronic kidney disease (CKD).

Associations of estimated glomerular filtration rate and albuminuria with mortality and renal failure by sex : a meta-analysis

Objective To assess for the presence of a sex interaction in the associations of estimated glomerular filtration rate and albuminuria with all-cause mortality, cardiovascular mortality, and end stage renal disease. Design Random effects meta-analysis using pooled individual participant data. Setting 46 cohorts from Europe, North and South America, Asia, and Australasia. Participants 2 051 158 participants (54% women) from general population cohorts (n=1 861 052), high risk cohorts (n=151 494), and chronic kidney disease cohorts (n=38 612). Eligible cohorts (except chronic kidney disease cohorts) had at least 1000 participants, outcomes of either mortality or end stage renal disease of ≥50 events, and baseline measurements of estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (mL/min/1.73 m2) and urinary albumin-creatinine ratio (mg/g). Results Risks of all-cause mortality and cardiovascular mortality were higher in men at all levels of estimated glomerular filtration rate and albumin-creatinine ratio. While higher risk was associated with lower estimated glomerular filtration rate and higher albumin-creatinine ratio in both sexes, the slope of the risk relationship for all-cause mortality and for cardiovascular mortality were steeper in women than in men. Compared with an estimated glomerular filtration rate of 95, the adjusted hazard ratio for all-cause mortality at estimated glomerular filtration rate 45 was 1.32 (95% CI 1.08 to 1.61) in women and 1.22 (1.00 to 1.48) in men (Pinteraction<0.01). Compared with a urinary albumin-creatinine ratio of 5, the adjusted hazard ratio for all-cause mortality at urinary albumin-creatinine ratio 30 was 1.69 (1.54 to 1.84) in women and 1.43 (1.31 to 1.57) in men (Pinteraction<0.01). Conversely, there was no evidence of a sex difference in associations of estimated glomerular filtration rate and urinary albumin-creatinine ratio with end stage renal disease risk. Conclusions Both sexes face increased risk of all-cause mortality, cardiovascular mortality, and end stage renal disease with lower estimated glomerular filtration rates and higher albuminuria. These findings were robust across a large global consortium.

Adiponectin concentrations: a genome-wide association study.

Adiponectin is associated with obesity and insulin resistance. To date, there has been no genome-wide association study (GWAS) of adiponectin levels in Asians. Here we present a GWAS of a cohort of Korean volunteers. A total of 4,001 subjects were genotyped by using a genome-wide marker panel in a two-stage design (979 subjects initially and 3,022 in a second stage). Another 2,304 subjects were used for follow-up replication studies with selected markers. In the discovery phase, the top SNP associated with mean log adiponectin was rs3865188 in CDH13 on chromosome 16 (p = 1.69 × 10(-15) in the initial sample, p = 6.58 × 10(-39) in the second genome-wide sample, and p = 2.12 × 10(-32) in the replication sample). The meta-analysis p value for rs3865188 in all 6,305 individuals was 2.82 × 10(-83). The association of rs3865188 with high-molecular-weight adiponectin (p = 7.36 × 10(-58)) was even stronger in the third sample. A reporter assay that evaluated the effects of a CDH13 promoter SNP in complete linkage disequilibrium with rs3865188 revealed that the major allele increased expression 2.2-fold. This study clearly shows that genetic variants in CDH13 influence adiponectin levels in Korean adults.

Low Serum Bilirubin Level as an Independent Predictor of Stroke Incidence A Prospective Study in Korean Men and Women

Background and Purpose— Bilirubin is not only a waste end-product but also an antioxidant. Bilirubin is known to be associated with decrease in cardiovascular risk in men, but its relationship to stroke was not clearly understood. Methods— Serum bilirubin concentrations were measured in 78 724 health examinees (41 054 men, aged 30–89 years) from 1994 to 2001. The subjects with potential hepatobiliary diseases or Gilbert syndrome were excluded from analysis. Stroke incidence outcome was collected from hospital records of admission attributable to stroke from 1994 to 2007. Results— Serum bilirubin measurements were divided into 4 levels: 0 to 10.2, 10.3 to 15.3, 15.4 to 22.1, and 22.2 to 34.2 μmol/L. The number of stroke cases was 1137 in men and 827 in women. In Cox proportional hazard models, participants with a higher level of bilirubin showed lower hazard ratios in men with ischemic stroke after adjustment for multiple confounding factors compared to the lowest level of bilirubin (hazard ratio [HR], 0.72; 95% CI, 0.58–0.90 in level 3; HR, 0.66; 95% CI, 0.49–0.89 in level 4; P for trend=0.016). The risk of all stroke types also decreased as bilirubin levels increased (HR, 0.81; 95% CI, 0.68–0.97 in level 3; HR, 0.74; 95% CI, 0.58–0.94 in level 4; P for trend=0.0071). However, these associations were not seen in hemorrhagic stroke or in women. Conclusions— These findings suggest that serum bilirubin might have some protective function against stroke risk in men.

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.

A Meta-analysis of the Association of Estimated GFR, Albuminuria, Age, Race, and Sex With Acute Kidney Injury

BACKGROUND Acute kidney injury (AKI) is a serious global public health problem. We aimed to quantify the risk of AKI associated with estimated glomerular filtration rate (eGFR), albuminuria (albumin-creatinine ratio [ACR]), age, sex, and race (African American and white). STUDY DESIGN Collaborative meta-analysis. SETTING & POPULATION 8 general-population cohorts (1,285,049 participants) and 5 chronic kidney disease (CKD) cohorts (79,519 participants). SELECTION CRITERIA FOR STUDIES Available eGFR, ACR, and 50 or more AKI events. PREDICTORS Age, sex, race, eGFR, urine ACR, and interactions. OUTCOME Hospitalized with or for AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results. RESULTS 16,480 (1.3%) general-population cohort participants had AKI over a mean follow-up of 4 years; 2,087 (2.6%) CKD participants had AKI over a mean follow-up of 1 year. Lower eGFR and higher ACR were strongly associated with AKI. Compared with eGFR of 80mL/min/1.73m(2), the adjusted HR of AKI at eGFR of 45mL/min/1.73m(2) was 3.35 (95% CI, 2.75-4.07). Compared with ACR of 5mg/g, the risk of AKI at ACR of 300mg/g was 2.73 (95% CI, 2.18-3.43). Older age was associated with higher risk of AKI, but this effect was attenuated with lower eGFR or higher ACR. Male sex was associated with higher risk of AKI, with a slight attenuation in lower eGFR but not in higher ACR. African Americans had higher AKI risk at higher levels of eGFR and most levels of ACR. LIMITATIONS Only 2 general-population cohorts could contribute to analyses by race; AKI identified by diagnostic code. CONCLUSIONS Reduced eGFR and increased ACR are consistent strong risk factors for AKI, whereas associations of AKI with age, sex, and race may be weaker in more advanced stages of CKD.

Mid-life and late-life vascular risk factors and dementia in Korean men and women.

Dementia is one of the most important neurological disorders in the elderly population. The significance of vascular risk factors for dementia remains controversial. This study aimed to determine the effects of vascular risk factors, such as blood pressure, diabetes and smoking in the mid-life or the late-life on dementia risk. The data in this prospective cohort study came from 3252 dementia events occurring over 14 years among 848,505 Koreans aged 40-95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation during 1992-1995. Data on clinical dementia during the period 1993-2006 were examined in relation to vascular risk factors. The age adjusted incidence per 100,000 was 31.9 for men and 45.0 for women, respectively. In multivariate Cox proportional hazard models, diabetes increased the risk of either dementia in Alzheimers disease or vascular dementia in men and women, controlling for age, hypertension, total cholesterol, alcohol drinking, and smoking. Hypertension also increased vascular dementia in both men [Hazard ratio (HR)=2.6, 95% confidence interval (CI)=1.7-3.8] and women (HR=2.3, 95%CI=1.6-3.3). The association of hypertension or diabetes on risk of vascular dementia, however, among the group aged older than 65 was attenuated but remained as significant in men. There was no interaction between hypertension and diabetes on the risk of dementia. This study demonstrates that diabetes and hypertension increased the risk of vascular dementia. Treatment for these risk factors may reduce the risk of vascular dementia.

Validity of the Diagnosis of Acute Myocardial Infarction in Korean National Medical Health Insurance Claims Data: The Korean Heart Study (1)

Background and Objectives Medical insurance claims (MIC) data are one of the largest sources of outcome data in the form of International Classification of Diseases (ICD) codes. We evaluated the validity of the ICD codes from the Korean National MIC data with respect to the outcomes from acute myocardial infarction (AMI) in the Korean Heart Study. Subjects and Methods Baseline information was obtained from health examinations conducted from 1994 to 2001. Outcome information regarding the incidence of AMI came from hospital admission discharge records from 1994 to 2007. Structured questionnaires were sent to 98 hospitals. In total, 107 cases of AMI with ICD codes of I21- (93 men, 26-73 years of age) were included in the final analyses. ICD code accuracy and reliability (kappa) for AMI were calculated. Results A large number of AMI cases were from hospitals located in the Seoul area (75.9%). The accuracy of AMI was 71.4%, according to World Health Organization criteria (1997-2000, n=24, kappa=0.46) and 73.1% according to the European Society of Cardiology/American College of Cardiology (ESC/ACC) criteria (2001-2007, n=83, kappa=0.74). An age of 50 years or older was the only factor related to inaccuracy of codes for AMI (odds ratio, 4.6; 95% confidence interval, 1.2-17.7) in patients diagnosed since January 2001 using ESC/ACC criteria (n=83). Conclusion The accuracy for diagnosing AMI using the ICD-10 codes in Korean MIC data was >70%, and reliability was fair to good; however, more attention is required for recoding ICD codes in older patients.

Serum leptin is associated with metabolic syndrome in obese and nonobese Korean populations

Leptin is mainly secreted from adipose tissue and is known to be associated with cardiovascular diseases. However, there are not many studies on the association between serum leptin and metabolic syndrome. The objective of this study was to determine the association between serum leptin and metabolic syndrome among the Korean adult population. The study population consisted of 3,272 Koreans (men: 1,915, women: 1,357) 30 to 84 years of age who had visited the Health Examination Center. Leptin levels were divided into quintiles and metabolic syndrome was defined by NCEP ATP III. The serum leptin levels increased as the number of components present for metabolic syndrome increased. Controlling for age, smoking, exercise, and LDL cholesterol, subjects with high leptin levels were more likely to have an elevated risk of metabolic syndrome than those with lower levels in both men and women. Subjects in the highest leptin quintile were found to have a higher risk of having metabolic syndrome than those in the lowest quintile (OR = 11.51 for men; OR = 4.65 for women). After further adjustment of the BMI, the risk of metabolic syndrome still increased slightly for men but not for women in increasing leptin categories. This association of leptin levels and metabolic syndrome did not change after stratification into obese and nonobese weight status. Serum leptin is associated with metabolic syndrome in Korean populations independent of body mass index. Thus, the reduction of circulating leptin may confer cardiovascular and metabolic protective effects regardless of weight status.

Public Health Challenges of Electronic Cigarettes in South Korea

Electronic cigarettes (e-cigarrettes) were recently introduced and advertised as a smoking cession device in South Korea. As the social norm to quit smoking has gained hold in the country, the number of e-cigarette users is growing rapidly. This phenomenon should be urgently considered, because of the lack of research that has been conducted to examine the safety of e-cigarettes and its efficacy as a smoking cessation aid. This paper raises several public health concerns on e-cigarettes in South Korea. Uncertain regulations of the government on e-cigarettes are contributing to an increase of e-cigarette users and allowing the e-cigarette industry to circumvent existing regulations. The aggressive marketing activity of this industry is also a core factor that is responsible for the rapid increase of e-cigarette use, in particular among the youth. Following the enforcement of tobacco control, some cigarette smokers may be encouraged to purchase e-cigarettes in order to circumvent the regulations, even though the dual use of e-cigarette and cigarette may be more harmful. Until there is clear evidence of the e-cigarettes safety, it is recommended that the industrys marketing and promotional activities be banned and closely monitored, and public campaigns be initiated to educate the public regarding e-cigarettes.