OBJECTIVES: We aimed to evaluate the association between early-life weight status and urinary tract infection (UTI) risk in children. METHODS: A nationwide study was conducted using Korean National Health Screening (NHS) data and National Health Insurance Service data. A sample cohort was selected using data from the 2014 and 2015 NHS for infants and children (4-71 months) and followed up until the end of 2017. Participants were divided into 4 groups (underweight, normal weight, overweight, and obese) based on the weight-for-age (< 2 years) or body mass index (≥ 2 years). Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing UTIs, cystitis, and acute pyelonephritis (APN) were calculated using a Cox proportional hazard model. RESULTS: Of 1,653,106 enrolled children, 120,142 (7.3%) developed UTIs, cystitis, and APN during follow-up. The underweight, overweight, and obese groups had higher risks of UTIs than the reference group after adjusting for age, sex, birth weight, and preterm birth. Between 2 years and 6 years of age, boys with underweight had a high risk of UTI and APN, while girls with overweight and obesity revealed elevated risks of UTIs, cystitis, and APN. The HRs for APN in boys with underweight and in girls with obesity were 1.46 (95% CI, 1.03 to 2.07) and 1.41 (95% CI, 1.13 to 1.75), respectively, after adjusting for age, sex, birth weight, and preterm birth. The incidence of APN did not decrease with age in underweight and obese children aged 2-6 years. CONCLUSIONS Children with underweight, overweight, and obesity may be at high risk for UTIs.

OBJECTIVES: We aimed to evaluate the association between early-life weight status and urinary tract infection (UTI) risk in children. METHODS: A nationwide study was conducted using Korean National Health Screening (NHS) data and National Health Insurance Service data. A sample cohort was selected using data from the 2014 and 2015 NHS for infants and children (4-71 months) and followed up until the end of 2017. Participants were divided into 4 groups (underweight, normal weight, overweight, and obese) based on the weight-for-age (< 2 years) or body mass index (≥ 2 years). Hazard ratios (HRs) with 95% confidence intervals (CIs) for developing UTIs, cystitis, and acute pyelonephritis (APN) were calculated using a Cox proportional hazard model. RESULTS: Of 1,653,106 enrolled children, 120,142 (7.3%) developed UTIs, cystitis, and APN during follow-up. The underweight, overweight, and obese groups had higher risks of UTIs than the reference group after adjusting for age, sex, birth weight, and preterm birth. Between 2 years and 6 years of age, boys with underweight had a high risk of UTI and APN, while girls with overweight and obesity revealed elevated risks of UTIs, cystitis, and APN. The HRs for APN in boys with underweight and in girls with obesity were 1.46 (95% CI, 1.03 to 2.07) and 1.41 (95% CI, 1.13 to 1.75), respectively, after adjusting for age, sex, birth weight, and preterm birth. The incidence of APN did not decrease with age in underweight and obese children aged 2-6 years. CONCLUSIONS Children with underweight, overweight, and obesity may be at high risk for UTIs.

Objective: We compared the effects of high-intensity statin monotherapy versus moderateintensity statin and ezetimibe combination therapy on major adverse cardiovascular events (MACE) in patients with acute myocardial infarction (AMI). Methods: Using the Korean National Health Insurance Service database, we screened 82,941 patients with AMI who underwent percutaneous coronary intervention (PCI) between 2013 and 2016. Among them, we identified 9,908 patients treated with atorvastatin 40 mg (A40, n=4,041), atorvastatin 20 mg + ezetimibe 10 mg (A20+E10, n=233), rosuvastatin 20 mg (R20, n=5,251), or rosuvastatin 10 mg + ezetimibe 10 mg (R10+E10, n=383). The primary outcome was MACE, a composite of all-cause death, non-fatal myocardial infarction undergoing PCI, repeat revascularization, and ischemic stroke. Multivariable analyses were performed using the inverse probability of treatment weighting method. Results: The incidence rate of MACE in the overall population was 42.97 cases per 1,000 person-years. There was no significant difference in the risk of composite outcomes of MACE between the groups. However, the R10+E10 group showed a higher risk of all-cause death (hazard ratio, 2.07; 95% confidence interval, 1.08–3.94) than the A40 group (reference group) in the weighted multivariable model. Conclusions In this study, there was no significant difference in the composite outcome of MACE between high-intensity statin monotherapy and moderate-intensity statin and ezetimibe combination therapy.

Several studies have reported that depression is prevalent in patients with diabetes or chronic kidney disease. However, the relationship between weight changes and the risk of depression has not been elucidated in patients with diabetic kidney disease (DKD). Methods: From the Korean National Health Insurance Service database, we selected 67,866 patients with DKD and body weight data from two consecutive health examinations with a 2-year interval between 2009 and 2012. Weight change over 2 years was categorized into five groups: ≥–10%, <–10% to ≥–5%, <–5% to <5%, ≥5% to <10%, and ≥10%. The occurrence of depression was monitored via the codes of International Statistical Classification of Diseases, 10th revision through the end of 2018. Results: During the 5.24-year follow-up, 17,023 patients with DKD developed depression. Weight change and the risk of depression had a U-shaped relationship: patients with ≥–10% weight change (hazard ratio [HR], 1.12) and those with ≥10% weight change (HR, 1.11) showed higher HRs for depression than those with <–5% to <5% weight change, even after adjusting for several confounding factors. In the subgroup analyses, the risk of depression tended to increase as weight gain or weight loss increased in all subgroups. Conclusion: Both weight loss and weight gain increased the risk of depression in patients with DKD.

BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders. RESULTS: Compared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p < 0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p < 0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p < 0.001) for gemigliptin. CONCLUSIONS: Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.
Atrial Fibrillation ; Cardiovascular Diseases ; Comorbidity ; Diabetes Mellitus, Type 2 ; Dipeptidyl-Peptidase IV Inhibitors ; Dyslipidemias ; Hypertension ; Infarction ; Korea ; Linagliptin ; National Health Programs ; Platelet Aggregation Inhibitors ; Proportional Hazards Models ; Renal Insufficiency, Chronic ; Sitagliptin Phosphate ; Stroke

Background/Aims: The obesity paradox has been known in end-stage renal disease (ESRD). However, the effect of body mass index (BMI) or waist circumference (WC) prior to percutaneous coronary intervention (PCI) on the development of ESRD is not clear. Methods: Using nationally representative data from the Korean National Health Insurance System, we enrolled 140,164 subjects without ESRD at enrolment who underwent PCI between 2010 and 2015, and were followed-up until 2017. Patients were stratified into five levels based on their baseline BMI and six levels based on their WC with 5-cm increments. BMI and WC were measured at least 2 years prior to PCI. The primary outcome was the development of ESRD. Results: During a median follow-up of 5.4 years, 2,082 (1.49%) participants developed ESRD. The underweight group (hazard ratio [HR], 1.331; 95% confidence interval [CI], 0.955 to 1.856) and low WC (< 80/< 75) (HR, 1.589; 95% CI, 1.379 to 1.831) showed the highest ESRD risk and the BMI 25 to 30 group showed the lowest ESRD risk (HR, 0.604; 95% CI, 0542 to 0.673) in all participants after adjusting for all covariates. In the subgroup analysis for diabetes mellitus (DM) duration, WC < 85/80 cm (men/women) increased ESRD risk in only the DM group (DM < 5 years and DM ≥ 5 years) compared to the reference group (85–90/80–85 of WC), but not the normal or impaired fasting glucose group. Conclusions Low WC prior to PCI showed an increased ESRD risk in patients with DM undergoing PCI as compared to those without DM.

Background: Hypertension is the most important modifiable risk factor for mortality and morbidity in chronic kidney disease and coronary artery syndrome. The effect of hypertension prior to percutaneous coronary intervention (PCI) on the development of end-stage renal disease (ESRD) is unknown. Methods: We used nationally representative data from the Korean National Health Insurance System—140,164 subjects were enrolled during 2010–2015; they were free of ESRD at enrolment, underwent PCI, and were followed up until 2017. Blood pressure (BP) was measured within at least 2 years prior to PCI. The primary outcome was the development of ESRD. Results: During a median follow-up of 5.4 years, 2,082 participants (1.5%) developed ESRD. The highest systolic BP group (>160 mmHg) showed a higher hazard ratio (3.69; 95% confidence interval, 2.61–5.23) than the reference group (110–119 mmHg). Similar results were observed in the highest diastolic BP group (>120 mmHg), which showed a higher hazard ratio than the reference group (70–79 mmHg). However, ESRD risk showed a J-shaped relationship with baseline systolic and diastolic BP at 113 and 74 mmHg in diabetes mellitus subgroup, respectively, after adjustment for potential confounders. Conclusion Our study showed that a high systolic or diastolic BP prior to PCI was independently associated with an increased incidence of ESRD.

BACKGROUND AND OBJECTIVES: To compare cardiovascular disease (CVD) risk associated with 5 different dipeptidyl peptidase-4 inhibitors (DPP-4is) in people with type 2 diabetes. METHODS: We identified 534,327 people who were newly prescribed sitagliptin (n=167,157), vildagliptin (n=67,412), saxagliptin (n=29,479), linagliptin (n=220,672), or gemigliptin (n=49,607) between January 2013 and June 2015 using the claims database of the Korean National Health Insurance System. A Cox proportional hazards model was used to estimate hazard ratios (HRs) for major CVD events (myocardial infarction, stroke, or death) among users of different DPP-4is. The model was adjusted for sex, age, duration of DPP-4i use, use of other glucose-lowering drugs, use of antiplatelet agents, hypertension, dyslipidemia, atrial fibrillation, chronic kidney disease, microvascular complications of diabetes, Charlson comorbidity index, and the calendar index year as potential confounders. RESULTS: Compared to sitagliptin users, the fully adjusted HRs for CVD events were 0.97 (95% confidence interval [CI], 0.94–1.01; p=0.163) for vildagliptin, 0.76 (95% CI, 0.71–0.81; p < 0.001) for saxagliptin, 0.95 (95% CI, 0.92–0.98; p < 0.001) for linagliptin, and 0.84 (95% CI, 0.80–0.88; p < 0.001) for gemigliptin. CONCLUSIONS Compared to sitagliptin therapy, saxagliptin, linagliptin, and gemigliptin therapies were all associated with a lower risk of cardiovascular events.

Background: Elevated γ-glutamyl transferase (γ-GTP) levels are associated with metabolic syndrome. We investigated the association of cumulative exposure to high γ-GTP with the risk of cardiovascular disease (CVD) in a large-scale population. Methods: Using nationally representative data from the Korean National Health Insurance system, 1,640,127 people with 4 years of consecutive γ-GTP measurements from 2009 to 2012 were included and followed up until the end of 2019. For each year of the study period, participants were grouped by the number of exposures to the highest γ-GTP quartile (0–4), and the sum of quartiles (0–12) was defined as cumulative γ-GTP exposure. The hazard ratio for CVD was evaluated using the Cox proportional hazards model. Results: During the 6.4 years of follow-up, there were 15,980 cases (0.97%) of myocardial infarction (MI), 14,563 (0.89%) of stroke, 29,717 (1.81%) of CVD, and 25,916 (1.58%) of death. Persistent exposure to high γ-GTP levels was associated with higher risks of MI, stroke, CVD, and death than those without such exposure. The risks of MI, stroke, CVD, and mortality increased in a dose-dependent manner according to total cumulative γ-GTP (all P for trend <0.0001). Subjects younger than 65 years, with a body mass index <25 kg/m2, and without hypertension or fatty liver showed a stronger relationship between cumulative γ-GTP and the incidence of MI, CVD, and death. Conclusion Cumulative γ-GTP elevation is associated with CVD. γ-GTP could be more widely used as an early marker of CVD risk, especially in individuals without traditional CVD risk factors.

Background: Hyperthyroidism is associated with an increased glomerular filtration rate (GFR) in the hyperdynamic state, which is reversible after restoring euthyroidism. However, long-term follow-up of renal dysfunction in patients with hyperthyroidism has not been performed. Methods: This was a retrospective cohort study using the Korean National Health Insurance database and biannual health checkup data. We included 41,778 Graves’ disease (GD) patients and 41,778 healthy controls, matched by age and sex. The incidences of end-stage renal disease (ESRD) were calculated in GD patients and controls. The cumulative dose and duration of antithyroid drugs (ATDs) were calculated for each patient and categorized into the highest, middle, and lowest tertiles. Results: Among 41,778 GD patients, 55 ESRD cases occurred during 268,552 person-years of follow-up. Relative to the controls, regardless of smoking, drinking, or comorbidities, including chronic kidney disease, GD patients had a 47% lower risk of developing ESRD (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.37 to 0.76). In particular, GD patients with a higher baseline GFR (≥90 mL/min/1.73 m2; HR, 0.33; 95% CI, 0.11 to 0.99), longer treatment duration (>33 months; HR, 0.31; 95% CI, 0.17 to 0.58) or higher cumulative dose (>16,463 mg; HR, 0.29; 95% CI, 0.15 to 0.57) of ATDs had a significantly reduced risk of ESRD. Conclusion This was the first epidemiological study on the effect of GD on ESRD, and we demonstrated that GD population had a reduced risk for developing ESRD.