On-treatment blood pressure and long-term outcomes in chronic kidney disease.

BACKGROUND: The treatment blood pressure (BP) target in chronic kidney disease (CKD) remains unclear, and whether the benefit of intensive BP-lowering is comparable between CKD and non-CKD patients is debated. METHODS: Using the Korean National Health Information Database, 359 492 CKD patients who had received antihypertensives regularly were identified from 12.1 million participants of nationwide health screening. The composite risk of major cardiovascular events, kidney failure and all-cause mortality was assessed according to time-averaged, on-treatment systolic BP. RESULTS: Over a 9-year follow-up, the composite outcome was noted in 18.4% of 239 700 participants with eGFR <60 mL/min/1.73 m2 and 18.9% of 155 004 with dipstick albuminuria. The thresholds of systolic BP, above which the composite risk increased significantly, in the reduced eGFR and the proteinuric population were 135 mmHg and 125 mmHg, respectively. For all-cause mortality, the respective thresholds were 145 mmHg and 135 mmHg. When comparing the composite risk between propensity score-matched groups, the hazard ratios of on-treatment BP of systolic 135-144 mmHg (reference, 115-124 mmHg) in the reduced eGFR and non-CKD pairs were 1.18 and 0.98, respectively (P = 0.13 for interaction), and those in the proteinuria and non-CKD pairs were 1.30 and 1.01, respectively (P = 0.003 for interaction). CONCLUSIONS: The findings support the recommendation that, based on office BP, the systolic target in CKD with proteinuria is ≤130 mmHg, and the target in CKD with no proteinuria is ≤140 mmHg. The benefit of intensive BP-lowering may be greater in CKD patients, particularly those with proteinuria, than in their non-CKD counterparts.

Optimal fasting glucose levels with regard to cardiovascular and mortality outcomes in people treated with or without antidiabetic medication.

AIMS: To investigate the optimal fasting blood glucose (FBG) levels among individuals actively treated or untreated with antidiabetic drugs. METHODS: In two population-based cohorts of Korean adults extracted from the National Health Information Database, multivariable-adjusted hazard ratios of outcomes over 10 and 8 years of follow-up were estimated according to achieved FBG levels and antidiabetic drug use. The primary outcomes were major cardiovascular disease (CVD) events and all-cause mortality. RESULTS: In total, 66 533 of 450 537 and 100 556 of 767 382 participants in the respective cohorts received antidiabetic treatment. For untreated FBG, the CVD risk and mortality increased linearly from an FBG threshold of 5.6 mmol/L; however, for FBG treated with antidiabetic drugs there were J-shaped associations with the outcome risks. For treated FBG levels of 4.4 to 5.5 mmol/L, 7.8 to 8.8 mmol/L, 8.9 to 9.9 mmol/L and ≥ 10.0 mmol/L, vs 6.1 to 6.9 mmol/L, the hazard ratios for major CVD events were 1.17 (95% confidence interval [CI] 1.04-1.32), 1.06 (95% CI 0.96-1.18), 1.37 (95% CI 1.22-1.53) and 1.61 (95% CI 1.46-1.78), respectively, and those for all-cause mortality were 1.20 (95% CI 1.11-1.29), 1.05 (95% CI 0.99-1.12), 1.29 (95% CI 1.10-1.50) and 1.69 (95% CI 1.59-1.81), respectively. CONCLUSIONS: These findings indicate that pharmacological therapy achieving FBG levels of <7.8 to 8.9 mmol/L and a non-pharmacological approach to maintaining normal glucose levels help reduce the risk of adverse outcomes, while lowering FBG to normal levels through antidiabetic drugs is not beneficial or may even be harmful.

CKD and Health-Related Quality of Life: The Korea National Health and Nutrition Examination Survey.

BACKGROUND: Quality of life is increasingly viewed as an important health outcome. However, the association of chronic kidney disease (CKD) and its severity with health-related quality of life is uncertain. STUDY DESIGN: Nationwide population-based cross-sectional study. SETTING & PARTICIPANTS: 46,676 adults participating in the Korea National Health and Nutrition Examination Survey (KNHANES) 2005 to 2013. PREDICTOR: CKD ascertained as dipstick-positive proteinuria or estimated glomerular filtration rate (eGFR)<60mL/min/1.73m(2). 5 eGFR categories of CKD were compared: ≥90 (with proteinuria), 60 to 89 (with proteinuria), 45 to 59, 30 to 44, and <30mL/min/1.73m(2). OUTCOMES: The EQ-5D index for health status (range, 0 [death] to 1 [optimal health]). RESULTS: The total crude CKD prevalence estimate for adults 20 years or older in Korea was 5.5%. After adjustments for age, sex, risk factors, and comorbid conditions, the EQ-5D index was lower in those with versus without CKD, with mean differences of -0.004 (95% CI, -0.015 to 0.007), -0.016 (95% CI, -0.032 to -0.000), -0.020 (95% CI, -0.029 to -0.011), -0.052 (95% CI, -0.072 to -0.032), and -0.067 (95% CI, -0.101 to -0.032), respectively, for CKD eGFR categories of ≥90, 60 to 89, 45 to 59, 30 to 44, and <30mL/min/1.73m(2). In the subgroup of older (≥60 years) individuals, the adjusted mean difference in the EQ-5D index was lower in the CKD eGFR category of 60 to 89mL/min/1.73m(2), but not in the eGFR category of 45 to 59mL/min/1.73m(2), compared to non-CKD. LIMITATIONS: The survey was conducted on noninstitutionalized civilians, and the chronicity of kidney disease was not verified. Caution is required if our results are applied to special settings and specific populations. CONCLUSIONS: There was a graded but complex association between CKD and poor health-related quality of life in this large community-based population.

Prevalence of Chronic Kidney Disease in Korea: the Korean National Health and Nutritional Examination Survey 2011-2013.

Chronic kidney disease is a leading public health problem related to poor quality of life and premature death. As a resource for evidence-informed health policy-making, we evaluated the prevalence of chronic kidney disease using the data of non-institutionalized adults aged ≥ 20 years (n = 15,319) from the Korean National Health and Nutrition Examination Survey in 2011-2013. Chronic kidney disease was defined as a urine albumin-to-creatinine ratio ≥ 30 mg/g or an estimated glomerular filtration rate < 60 mL/min/1.73 m(2) using the Chronic Kidney Disease-Epidemiology Collaboration equation. The total prevalence estimate of chronic kidney disease for adults aged ≥ 20 years in Korea was 8.2%. By disease stage, the prevalence of chronic kidney disease was as follows: stage 1, 3.0%; stage 2, 2.7%; stage 3a, 1.9%; stage 3b, 0.4%; and stages 4-5, 0.2%. When grouped into three risk categories according to the 2012 Kidney Disease: Improving Global Outcomes guidelines, the proportions for the moderately increased risk, high risk, and very high risk categories were 6.5%, 1.2%, and 0.5%, respectively. Factors including older age, diabetes, hypertension, cardiovascular disease, body mass indexes of ≥ 25 kg/m(2) and < 18.5 kg/m(2), and rural residential area were independently associated with chronic kidney disease. Based on this comprehensive analysis, evidence-based screening strategies for chronic kidney disease in the Korean population should be developed to optimize prevention and early intervention of chronic kidney disease and its associated risk factors.

Blood pressure control in patients aged above and below 75 years.

It remains unclear what the blood pressure target is and at which point in life it is appropriate for antihypertensive treatment. This study aimed to determine age-specific systolic blood pressure (SBP) targets. In a nationwide cohort of 296,470 hypertensive patients aged ≥75 years and a representative cohort of 259,028 hypertensives aged 45-74 years, multivariable-adjusted incidence rates of cardio-kidney composite events, overt dementia, and all-cause deaths were estimated across yearly-averaged on-treatment SBP levels according to age and the presence of 4 additional risk factors (diabetes, dyslipidemia, albuminuria, and smoking). For cardio-kidney events, on-treatment SBP showed positive curvilinear associations with higher risks at ≥135 mm Hg in most while an attenuated association in age ≥85 years. For overt dementia, SBP showed flat or slightly inverted associations in elderly while a small positive association in age 45-64 years. For all-cause mortality, SBP showed J-shaped associations having right-shifting tendency with age. For risk categories with ≥2, 1, and no additional risk factors, the respective mortality rate differences between SBP 145-154 mm Hg and 125-134 mm Hg were 4.6 (95% confidence interval [CI], 2.0 to 7.3), 1.2 (95% CI, -0.3 to 2.8), and 0.1 (95% CI, -1.4 to 1.8) per 1000 person-years in age ≥75 years and 2.9 (95% CI, 1.7 to 4.3), 0.7 (95% CI, 0.1 to 1.4), and 0.9 (95% CI, 0.2 to 1.6) per 1000 person-years in age 45-74 years. In conclusion, the BP target can be relaxed in very old patients and in elderly patients with few risk factors. However, strict BP control may be needed in patients with multiple risk factors even in those with advanced age.

Glycemic control and dementia risk in patients aged above and below 75 years.

Background: There is a lack of data about the treatment effect of glycemic control on incident dementia in patients with advanced age. Methods: In a nationwide Korean cohort of 79,076 diabetic patients 75 years or older and a representative cohort of 74,672 diabetics aged 50 to 74 years, multivariable-adjusted incidence of overt dementia was estimated across yearly-averaged on-treatment fasting blood glucose (FBG) levels. Results: During 9-year follow-up, overt dementia was noted in 24,710 (31.2%) patients 75 years or older and in 5237 (7.0%) patients aged 50 to 74 years. For dementia risk, J-shaped associations were observed across on-treatment FBG levels (80-99, 100-109, 110-125, 126-139, 140-159, 160-179, and 180-900 mg/dl) in patients 75 years or older (respective incidence: 49.3, 45.7, 45.9, 45.7, 48.5, 51.5, and 57.9 per 1000 person-years) and in those aged 50 to 74 years (respective incidence: 8.9, 8.3, 7.7, 7.6, 8.0, 8.6, and 10.6 per 1000 person-years) with a significant interaction of FBG level and age group (P = 0.001). For all-cause mortality, the J-shaped association curve was left-shifted in patients 75 years or older (respective incidence: 64.9, 59.1, 57.6, 60.4, 64.0, 70.9, and 90.4 per 1000 person-years) relative to that in patients aged 50 to 74 years (respective incidence: 15.7, 13.4, 12.3, 12.2, 13.4, 15.7, and 21.8 per 1000 person-years; P < 0.001 for interaction). Conclusion: The achieved glycemic level with the lowest risk for dementia and mortality was lower in older patients, and absolute risk increase related to poorly controlled glucose was greater in the elderly compared with younger patients. Supplementary Information: The online version contains supplementary material available at 10.1007/s13340-023-00684-4.

Albuminuria, estimated glomerular filtration rate, and traditional predictors for composite cardiovascular and kidney outcome: a population-based cohort study in Korea.

BACKGROUND: Certain pharmacotherapies have shown to be effective for both cardiac and kidney outcomes. Although risk prediction is important in treatment decision-making, few studies have evaluated prediction models for composite cardiovascular and kidney outcomes. METHODS: This study included 2,195,341 Korean adults from a nationwide cohort for chronic kidney disease and a representative sample of the general population, with a 9-year follow-up. This study evaluated prediction models for a composite of major cardiovascular events or kidney disease progression that included albuminuria and estimated glomerular filtration rate (eGFR) and/or traditional cardiovascular disease predictors. RESULTS: The addition of albuminuria and eGFR to a model for the composite outcome that included age, sex, and traditional predictors increased a C statistic by 0.0459, while the addition of traditional predictors to age, sex, albuminuria, and eGFR increased a C statistic by 0.0157. When age and sex-adjusted incidence rates were calculated across the combined Pooled-Cohort-Equations (PCEs) and Kidney Disease: Improving Global Outcomes (KDIGO) risk categories in diabetic or hypertensive participants, the incidence of ≥10 per 1,000 person-years was observed among all categories with high or very high KDIGO risk and among categories with moderate (or low) KDIGO risk and a PCEs 10-year risk of ≥10% (or ≥20%), accounting for 36% of diabetic and 18% of hypertensive populations. CONCLUSION: This study strongly supports the utility of the KDIGO risk matrix combined with a conventional cardiovascular risk score for the prediction of composite cardiovascular and kidney outcome and provides epidemiologic data relevant to the development of efficient treatment strategies.

Improvement of sleep-related breathing disorder in patients with end-stage renal disease after kidney transplantation.

Sleep-related breathing disorder (SRBD) is a common symptom of end-stage renal disease (ESRD). The aim of this study was to determine whether kidney transplantation improves SRBD. Twenty-four patients with ESRD, who were admitted for kidney transplantation, underwent a sleep study using a portable ventilation effort recorder on the night before transplantation. Of these patients, 20 could repeat the overnight monitoring two wk after the transplantation. The median apnea-hypopnea index (AHI) of the 20 patients was 13.5 (range, 2-40), and significantly reduced to 4.5 (range, 0-20) after transplantation (p = 0.003). This reduction was most prominent in 12 patients with SRBD, for whom the median AHI fell from 22 (range, 10-40) to 6.5 (range, 1-20; p = 0.010). SRBD improvement, defined as an AHI equal to or >50% and/or reduced to <10/h, was observed in eight of the 12 apneic patients. These results suggest that kidney transplantation may immediately improve SRBD in patients with ESRD. However, conclusions from this study should be taken with caution because of the limitations of our method, specifically the use of a portable recorder and a small number of patients.

Statin use and outcome risks according to predicted CVD risk in Korea: A retrospective cohort study.

BACKGROUND: The validity of cardiovascular disease (CVD) risk calculators in decision for statin therapy has not been fully evaluated at a population level. This study aimed to examine the net benefits of statins according to predicted CVD risk. METHODS AND FINDINGS: A cohort of 40 to 79-year-old Korean adults without CVD was generated from the National Health Information Database 2006-2017. Major CVD event rates and all-cause mortality in 58,265 users who initiated statins during 2007-2010 were compared with those in 58,265 nonusers matched on propensity scores, from January 1, 2012 through December 31, 2017. Additionally, simulation was performed for the population-based cohort of 659,759 adults. CVD risk was predicted using the 2018 revised Pooled Cohort Equations. In propensity score-matched cohort, the CVD hazard ratios (95% CIs) in occasional, intermittent, and regular statin users were 1.06 (0.93-1.20), 0.82 (0.70-0.97), and 0.57 (0.50-0.64), respectively. The corresponding mortality hazard ratios were 1.01 (0.92-1.10), 0.87 (0.78-0.98), and 0.71 (0.66-0.77), respectively. In stratified analyses, the relative risk reductions were similar, irrespective of age, sex, or predicted CVD risk. Accordingly, absolute risk reductions were greater in higher risk categories. In 6-year follow-up simulation cohorts, regular statin use could reduce 17 CVDs and 28 deaths in 1000 adults with a 10-year risk of ≥10.0% vs 10 CVDs and 14 deaths in 1000 with ≥2 major risk factors. However, in actual adults with a risk of ≥10%, statin use was insufficient and estimated to reduce 3 CVDs and 4 deaths in 1000. Limitations of this study include assessment of medication use based on the prescription data, lack of information on the intensity of statins, and limited generalizability to individuals with very old age or other ethnicity. CONCLUSIONS: CVD risk calculators were valid in decision-making for primary prevention statin therapy. Proper risk assessment and regular statin use in patients at high predicted risk would reduce outcome risks much more than present in Asian populations.

Evaluation of Serum Glucose and Kidney Disease Progression Among Patients With Diabetes.

Importance: The appropriate target of glycemic control in diabetic kidney disease is unclear. Objective: To investigate optimal on-treatment glycemic levels associated with slowing of diabetic kidney disease progression. Design, Setting, and Participants: This retrospective cohort study was conducted using nationwide Korean cohorts from the National Health Information Database from 2005 to 2019. Included individuals were adults with diabetes using antihyperglycemic agents with and without chronic kidney disease (CKD) identified from participants aged 40 to 74 years in a nationwide health screening survey conducted from 2009 to 2010. Data were analyzed from October 2020 through March 2021. Exposure: On-treatment fasting blood glucose (FBG) level. Main Outcomes and Measures: The primary outcome was a composite of doubling of serum creatinine, end-stage kidney disease, or death from CKD. Results: Among 183 049 adults with diabetes using antihyperglycemic agents (mean [SD] age, 61.7 [8.4] years; 99 110 [54.1%] men), there were 131 401 individuals with dipstick albuminuria or an estimated glomerular filtration rate (eGFR) of 15 to 59 mL/min/1.73 m2 (mean [SD] age, 62.4 [8.3] years; 71 280 [54.2%] men) and 51 648 individuals with no CKD (mean [SD] age, 59.6 [8.4] years; 27 830 [53.9%] men). During 9 years of follow-up, the primary outcome occurred among 13 802 individuals with CKD (10.5%) and 1421 individuals with no CKD (2.8%). On-treatment FBG level had a J-shaped hazard ratio (HR) curve for the primary outcome. Among patients with albuminuria, FBG levels of 126 mg/dL to less than 140 mg/dL (HR, 0.87; 95% CI, 0.81-0.94) and 140 mg/dL to less than 160 mg/dL (HR, 0.90; 95% CI, 0.84-0.96) were associated with decreased risk and levels of 160 mg/dL to less than 180 mg/dL were associated with increased risk (HR, 1.10; 95% CI, 1.03-1.18) compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with decreased eGFR, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.30; 95% CI, 1.20-1.42) and levels of 160 mg/dL to less than 180 mg/dL (HR, 1.13; 95% CI, 1.04-1.23) were associated with increased risk of the primary outcome compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no CKD, FBG levels of 80 mg/dL to less than 100 mg/dL (HR, 1.29; 95% CI, 1.01-1.65) and levels of 126 mg/dL to less than 140 mg/dL (HR, 1.23; 95% CI, 1.03-1.47) were associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. Among patients with no albuminuria at baseline, FBG levels of 140 mg/dL to less than 160 mg/dL (HR, 1.14; 95% CI, 1.09-1.20) were associated with increased risk of new-onset albuminuria, while levels of 100 mg/dL to less than 110 mg/dL were not associated with increased risk compared with FBG levels of 110 mg/dL to less than 126 mg/dL. For all-cause mortality, while FBG levels of 160 mg/dL to less than 180 mg/dL (HR, 1.20; 95% CI, 1.12-1.28) were associated with increased risk among patients with albuminuria, FBG levels of 140 mg/dL to less than 160 mg/dL were associated with increased risk among patients with decreased eGFR (HR, 1.10; 95% CI, 1.04-1.16) and those with no CKD (HR, 1.10; 95% CI, 1.00-1.21) compared with levels of 110 mg/dL to less than 126 mg/dL. Conclusions and Relevance: These findings suggest that intensive vs standard glucose control may not be associated with increased protection for the progression of established diabetic kidney disease and that timely control is important for prevention. However, careful glycemic control would still be associated with improved overall outcomes among patients with CKD, particularly those with no albuminuria.

Hypertension Management in Patients with Chronic Kidney Disease in the Post-SPRINT Era.

The management of high blood pressure (BP) is crucial for improving outcomes in patients with chronic kidney disease (CKD). The updated Kidney Disease: Improving Global Outcomes 2021 BP guideline proposes treating adults with CKD to a target systolic BP (SBP) of <120 mmHg based on the standardized office BP measurement. This suggestion is largely based on the finding of SPRINT (Systolic Blood Pressure Intervention Trial) that targeting an SBP of <120 mmHg versus <140 mmHg is beneficial for cardiovascular and mortality outcomes, regardless of the patient's kidney disease status. However, extended follow-up studies of CKD trials showed that intensive versus usual BP control was associated with a lower risk of kidney failure in patients with, but not in those without, proteinuria. Similarly, a recent population-based study in Korea demonstrated that the optimal on-treatment BP for composite cardiorenal and mortality outcomes was left-shifted in adults with CKD, particularly in those with albuminuria, relative to that in patients without CKD. Moreover, in meta-analyses of randomized trials, more intensive versus standard BP control was associated with a lower risk of all-cause mortality in patients with CKD and albuminuria but not in those without CKD. Meanwhile, a 2020 Cochrane review reported that lower BP targets (≤135/85 mmHg), compared with standard targets (≤140/90 mmHg), resulted in a small reduction in cardiovascular events, an increase in other serious adverse events, and no reduction in total serious adverse events. Lowering SBP to <120 mmHg can potentially increase the risk of treatment-related adverse events beyond the cardioprotective benefits, and standardized BP measurement increases the burden on patients and resources. Thus, targeting a BP of <130/80 mmHg with appropriate office BP measurement can be an option in patients with CKD. The presence of albuminuria would need to be additionally considered to determine individualized BP targets.

SGLT2 Inhibitors and Kidney and Cardiac Outcomes According to Estimated GFR and Albuminuria Levels: A Meta-analysis of Randomized Controlled Trials.

RATIONALE & OBJECTIVE: There are few data on the absolute effects of sodium/glucose cotransporter 2 (SGLT2) inhibitors, despite their importance in treatment decision making. We investigated absolute treatment effects according to baseline kidney disease status. STUDY DESIGN: Meta-analysis. STUDY POPULATIONS: Adults with type 2 diabetes, chronic kidney disease, or heart failure. SELECTION CRITERIA FOR STUDIES: Randomized controlled trials of SGLT2 inhibitors (10 trials to November 20, 2020) for clinical outcomes of kidney disease progression, heart failure events, and major cardiovascular events. DATA EXTRACTION: Publications of 10 trials to November 20, 2020. ANALYTICAL APPROACH: The incidence rate difference (IRD) between SGLT2 inhibitor and placebo was compared across estimated glomerular filtration rate (eGFR) or urinary albumin-creatinine ratio (UACR) subgroups. RESULTS: Subgroup analyses included data from seven trials (61,821 participants with diabetes or chronic kidney disease). SGLT2 inhibitor treatment, in eGFR subgroups of <45, 45 to <60, and ≥60 mL/min/1.73 m2, reduced 16.0, 9.5, and 1.9 heart failure events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity). In urine UACR subgroups of >300, 30 to 300, and <30 mg/g, SGLT2 inhibitors reduced 17.3, 1.4, and 2.2 kidney disease events per 1,000 patient-year, respectively (P < 0.001 for heterogeneity), and 14.8, 8.7, and 2.1 heart failure events per 1,000 patient-year, respectively (P = 0.006 for heterogeneity). The pooled IRDs for major cardiovascular events were also greater in lower eGFR or overt albuminuria subgroups. In secondary analyses, risk differences calculated using pooled baseline and relative risks were comparable to the pooled IRDs, while the relative risk reductions for kidney and heart failure outcomes were consistent across the subgroups. For treatment-related harms, IRDs were similar between eGFR subgroups. LIMITATIONS: Study-level data rather than individual patient data were used. CONCLUSIONS: SGLT2 inhibitor treatment resulted in greater reductions of cardiovascular events in patients with lower eGFR and higher albuminuria and had substantially greater absolute benefits of renoprotection in patients with overt albuminuria than in their counterparts.

Association of Optimal Blood Pressure With Critical Cardiorenal Events and Mortality in High-Risk and Low-Risk Patients Treated With Antihypertension Medications.

Importance: There are few studies comparing the optimal level of treated blood pressure (BP) between high- and low-risk patients. Objective: To examine whether optimally treated BP is different according to risk status. Design, Setting, and Participants: Population-based cohort study using data from the National Health Information Database in Korea from 2002 to 2015 and 2006 to 2017. A total of 1 402 975 adults aged 40 to 79 years who had no known cardiorenal disease were included. Exposures: Systolic BP treated with antihypertensive medication. Main Outcomes and Measures: The yearly rates of critical cardiorenal events and all-cause death were estimated according to the levels of treated systolic BP and the presence of 5 risk factors (hypertension, diabetes, hyperlipidemia, proteinuria, and smoking). Results: During the study periods, 225 103 of 487 412 participants (54.0% male; median [interquartile range] age, 50 [44-59] years) in the primary cohort and 360 503 of 915 563 participants (50.1% male; median [interquartile range] age, 52 [46-60] years) in the secondary cohort received antihypertensive treatment. In total, 28 411 of 51 292 cardiorenal incidents and 33 102 of 72 500 deaths were noted in ever-treated participants. The absolute increase in cardiorenal and mortality risk associated with inadequately treated BP was greater in participants with multiple risk factors than in those with 1 or 0 risk factors. The hazard ratios for critical cardiorenal events increased as the treated systolic BP increased to more than 130 to 140 mm Hg. The hazard ratio for all-cause mortality for patients with 3 or more risk factors and treated systolic BP within the range of 110 to 119 mm Hg was 1.21 (95% CI, 1.07-1.37); 130 to 139 mm Hg, 1.04 (95% CI, 0.98-1.11); 140 to 149 mm Hg, 1.12 (95% CI, 1.05-1.20); 150 to 159 mm Hg, 1.21 (95% CI, 1.11-1.32); and 160 mm Hg or greater, 1.46 (95% CI, 1.32-1.62) compared with high-risk patients with BP of 120 to 129 mm Hg. For participants with 1 or 0 risk factors and treated systolic BP within the range of 110 to 119 mm Hg, the hazard ratio was 1.14 (95% CI, 1.07-1.22); 130 to 139 mm Hg, 0.97 (95% CI, 0.93-1.02); 140 to 149 mm Hg, 1.00 (95% CI, 0.91-1.09); 150 to 159 mm Hg, 1.06 (95% CI, 0.99-1.14); and 160 mm Hg or greater, 1.26 (95% CI, 1.15-1.37). However, when categorized using cardiovascular risk calculators, there was no consistent trend in mortality thresholds of BP across the risk score categories. Conclusions and Relevance: These results suggest that intensive BP control is appropriate for reducing all-cause mortality in addition to cardiorenal risk in higher- rather than lower-risk patients. However, caution may be required when determining BP targets using current risk calculators.

Postconditioning with isoflurane reduced ischemia-induced brain injury in rats.

BACKGROUND: Preexposure of brain to isoflurane, a commonly used anesthetic, induces ischemic tolerance. This phenomenon is called isoflurane preconditioning. However, it is not known whether isoflurane application after ischemia provides neuroprotection. METHODS: Corticostriatal slices (400 microm) freshly prepared from adult male Sprague-Dawley rats were subjected to a 15-min oxygen-glucose deprivation (OGD; to simulate ischemia in vitro). Isoflurane was applied after OGD. Brain slices were harvested 2 h after OGD for measuring 2,3,5-triphenyltetrazolium chloride (TTC) conversion to quantify cell injury. Adult male Sprague-Dawley rats were also subjected to middle cerebral arterial occlusion for 90 min and then treated with or without 2% isoflurane for 60 min started at the onset of reperfusion. The infarct volumes, neurologic deficit scores, and performance on rotarod were evaluated at 24 h after the onset of reperfusion. RESULTS: Isoflurane applied immediately after the 15-min OGD for 30 min dose-dependently reversed the OGD-induced decrease of TTC conversion. The TTC conversion was 34 +/- 16% and 58 +/- 28% of the control, respectively, for OGD alone and OGD plus 2% isoflurane (P < 0.05, n = 12). Application of 2% isoflurane for 30 min started at 10 min after the OGD also reduced the OGD-decreased TTC conversion. The presence of 0.3 microm glibenclamide, a general adenosine 5'-triphosphate-sensitive potassium channel blocker, or 500 microm 5-hydroxydecanoic acid, a mitochondrial adenosine 5'-triphosphate-sensitive potassium channel blocker, during the application of 2% isoflurane abolished the isoflurane preservation of TTC conversion. Application of isoflurane during reperfusion also improved neurologic outcome after brain ischemia. CONCLUSIONS: The results suggest that isoflurane administrated after OGD or brain ischemia provides neuroprotection. Mitochondrial adenosine 5'-triphosphate-sensitive potassium channels may be involved in this protection.

Inability of volatile anesthetics to inhibit oxygen-glucose deprivation-induced glutamate release via glutamate transporters and anion channels in rat corticostriatal slices.

Ischemia-induced extracellular glutamate accumulation and the subsequent excitotoxicity contribute significantly to ischemic brain injury. Volatile anesthetics have been shown to reduce ischemic brain injury. Here, we showed that oxygen-glucose deprivation (OGD, to simulate ischemia in vitro) increased extracellular glutamate accumulation in the corticostriatal slices of adult rats. This increased accumulation was reduced by dihydrokinate, a glutamate transporter type 2 inhibitor, and 4,4'-dinitrostilbene-2,2'-disulfonic acid, a blocker for volume-activated anion channels. The volatile anesthetics isoflurane, sevoflurane and desflurane at clinically relevant concentrations did not affect the OGD-induced extracellular glutamate accumulation from brain slices of adult rats. Isoflurane also did not change the OGD-induced extracellular glutamate accumulation from brain slices of newborn/young rats. These results suggest that the OGD-induced glutamate accumulation involves reversed transport of glutamate via glutamate transporters and volume-activated anion channels. Volatile anesthetics may not inhibit this extracellular glutamate accumulation.

Blood Pressure-Related Risk Among Users Versus Nonusers of Antihypertensives: A Population-Based Cohort in Korea.

There have been few studies comparing blood pressure (BP)-related outcomes between users and nonusers of antihypertensive drugs. We constructed a population-based cohort of 492 540 Koreans aged 40 to 79 years, who had no preexisting cardiorenal diseases, from the National Health Insurance Service-Health Screening database. The primary composite outcome was death (or critical care unit admission) from cardiorenal causes, revascularization for myocardial infarction or stroke, and new-onset end-stage renal disease. Using time-dependent Cox models, we estimated hazard ratios according to BP and antihypertensive use, which were determined in each year of follow-up. Over 10 years of follow-up, the primary outcome occurred in 26 122 subjects, and 33 550 deaths were noted. Among nonusers of antihypertensives, the risk for the primary outcome increased linearly from a BP of 105/65 mm Hg, and the risk for all-cause mortality increased from a BP of 115/75 mm Hg. Among irregular users, the risk for the primary outcome increased as the BP increased >115/75 mm Hg. Among active users, the risk for the primary outcome increased in systolic BP <115 mm Hg and >135 mm Hg, and in diastolic BP <65 mm Hg and >85 mm Hg, and the risk for all-cause mortality increased in systolic BP <125 mm Hg and >135 or 145 mm Hg. In conclusion, this population-based study demonstrated that the associations between BP and adverse outcomes were J-shaped among active antihypertensive users, but linear or flat and then increasing among nonusers or irregular users.

Pretreatment with volatile anesthetics, but not with the nonimmobilizer 1,2-dichlorohexafluorocyclobutane, reduced cell injury in rat cerebellar slices after an in vitro simulated ischemia.

A prior exposure to the volatile anesthetic isoflurane has been shown to induce neuroprotection in rats. This phenomenon is called preconditioning. We designed this study to determine whether the potency of volatile anesthetics in inducing neuropreconditioning is related to their potency to induce anesthesia. Cerebellar slices of adult male Sprague-Dawley rats were exposed to various concentrations of isoflurane, halothane, sevoflurane, desflurane or the nonimmobilizer 1,2-dichlorohexafluorocyclobutane for 15 min, followed by a 15-min drug-free period, and then were subjected to oxygen-glucose deprivation for 10 min at 37 degrees C. After a 5-h recovery at 37 degrees C, brain slices were used for quantification of cell injury by spectrophotometric measurement of formazan produced from 2,3,5-triphenyltetrazolium chloride. All four volatile anesthetics induced a concentration-dependent preconditioning effect. The EC50 for this effect induced by isoflurane, halothane, sevoflurane or desflurane was 221, 173, 184 and 929 microM, respectively. This EC50 was linearly correlated with the aqueous concentration of one minimum alveolar concentration. The volatile anesthetic preconditioning-induced neuroprotection was abolished by DL-threo-beta-hydroxyaspartic acid, DL-threo-beta-benzyloxyaspartate or dihydrokainate, glutamate transporter inhibitors. The volatile nonimmobilizer 1,2-dichlorohexafluorocyclobutane at any concentrations tested in the study did not induce a significant preconditioning effect. Isoflurane preconditioning did not change the oxygen-glucose deprivation-induced glutamate accumulation. These results suggest that the preconditioning-induced neuroprotection by volatile anesthetics is not agent-specific. Mechanisms that are involved in inducing anesthesia may contribute to the induction of preconditioning effect by volatile anesthetics. Modification of glutamate transporter activity may be one of such mechanisms to induce these protective effects.

Estimation of years lived with disability due to noncommunicable diseases and injuries using a population-representative survey.

The Global Burden of Disease 2010 and the WHO Global Health Estimates of years lived with disability (YLDs) uses disability-weights obtained from lay health-state descriptions, which cannot fully reflect different disease manifestations, according to severity, treatment, and environment. The aim of this study was to provide population-representative YLDs of noncommunicable diseases and injuries using a prevalence-based approach, with the disability weight measured in subjects with specific diseases or injuries. We included a total of 44969 adults, who completed the EQ-5D questionnaire as participation in the Korea National Health and Nutrition Examination Survey 2007-2014. We estimated the prevalence of each of 40 conditions identified from the noncommunicable diseases and injuries in the WHO list. Modified condition-specific disability-weight was determined from the adjusted mean difference of the EQ-5D index between the condition and reference groups. Condition-specific YLDs were calculated as the condition's prevalence multiplied by the condition's disability-weight. All-cause YLDs, estimated as "number of population × (1 - mean score of EQ-5D)" were 2165 thousands in 39044 thousand adults aged ≥20. The combined YLDs for all 40 conditions accounted for 67.6% of all-cause YLDs, and were 1604, 2126, 8749, and 12847 per 100000 young (age 20-59) males, young females, old (age ≥60) males, and old females, respectively. Back pain/osteoarthritis YLDs were exceptionally large (442/40, 864/146, 2037/836, and 4644/3039 per 100000 young males, young females, old males, and old females, respectively). Back pain, osteoarthritis, depression, diabetes, periodontitis, and stroke accounted for 22.3%, 9.1%, 4.6%, 3.3%, 3.2%, and 2.9% of all-cause YLDs, respectively. In conclusion, this estimation of YLDs using prevalence rates and disability-weights measured in a population-representative survey may form the basis for population-level strategies to prevent age-related worsening of disability.

Incidence of diabetes and its mortality according to body mass index in South Koreans aged 40-79 years.

PURPOSE: The purpose of this study was to assess diabetes incidence and all-cause mortality according to baseline body mass index (BMI) and to compare relative risks of mortality associated with incident diabetes across various BMI classes in a cohort of South Korean adults. PATIENTS AND METHODS: Based on data from the National Health Insurance database of Korean individuals aged 40-79 years without preexisting diabetes, we calculated BMI at the baseline health examination. We estimated the relative risk of mortality associated with incident diabetes using time-dependent Cox models and considering the time of diabetes diagnosis. RESULTS: We noted 29,307 incident diabetes cases and 22,940 deaths during an 8-year follow-up of the initial cohort (n=436,692) and 73,756 incident diabetes cases and 57,556 deaths during a 10-year follow-up of the replication cohort (n=850,282). Regarding all-cause mortality, time-dependent Cox models revealed statistically significant interactions between diabetes status and baseline BMI class (P=0.018 and P<0.001 in the initial and replication cohorts, respectively). In separately conducted analyses for each BMI class, diabetes-associated relative risks for BMI values of 16.0-18.4, 18.5-22.9, 23.0-24.9, 25.0-29.9, and 30.0-34.9 kg/m2 were 1.50 (95% confidence interval [CI], 1.09-2.07), 1.39 (95% CI, 1.26-1.54), 1.20 (95% CI, 1.08-1.35), 1.18 (95% CI, 1.07-1.30), and 0.97 (95% CI, 0.74-1.28) in the initial cohort, and 1.44 (95% CI, 1.18-1.74), 1.33 (95% CI, 1.26-1.41), 1.24 (95% CI, 1.16-1.31), 1.11 (95% CI, 1.05-1.17), and 0.99 (95% CI, 0.85-1.16) in the replication cohort. The increasing trend of relative risk with decreasing BMI persisted mostly among subgroups stratified according to age or sex and smoking status. CONCLUSION: Incident diabetes was associated with a greater increase in all-cause mortality risk in adults with lower BMI relative to those with higher BMI. This emphasizes the importance of treatment and prevention of type 2 diabetes among normal weight or underweight adults, particularly in Asia.

Comparison of urine dipstick and albumin:creatinine ratio for chronic kidney disease screening: A population-based study.

Chronic kidney disease (CKD) is usually diagnosed using the estimated glomerular filtration rate (eGFR) or kidney damage markers. The urine dipstick test is a widely used screening tool for albuminuria, a CKD marker. Although the urine albumin:creatinine ratio (ACR) has advantages over the dipstick test in sensitivity and quantification of levels, the two methods have not been compared in the general population. A total of 20,759 adults with urinalysis data in the Korea National Health and Nutrition Examination Survey 2011-2014 were examined. CKD risk categories were created using a combination of eGFR and albuminuria. Albuminuria was defined using an ACR cutoff of 30 mg/g or 300 mg/g and a urine dipstick cutoff of trace or 1+. The EQ-5D index was used for the health outcome. Prevalence estimates of ACR ≥30 mg/g and >300 mg/g vs dipstick ≥trace and ≥1+ in adults aged ≥20 years were 7.2% and 0.9% vs 9.1% and 1.2%, respectively. For ACR ≥30 mg/g detection, the sensitivity, specificity, and positive/negative predictive values of dipstick ≥trace were 43.6%, 93.6%, 34.6%, and 95.5%, respectively. When risk categories created based on dipstick cutoffs were compared with those based on ACR cutoffs, 10.4% of the total population was reclassified to different risk categories, with only 3.9% reclassified to the same CKD category. Akaike information criterion values were lower, and non-fatal disease burdens of CKD were larger, in models predicting EQ-5D index using ACR-based categories compared to those using dipstick-based categories, even after adjusting for confounders. In conclusion, the urine dipstick test had poor sensitivity and high false-discovery rates for ACR ≥30 mg/g detection, and classified a large number of individuals into different CKD risk categories compared with ACR-based categories. Therefore, ACR assessments in CKD screening appear beneficial for a more accurate prediction of worse quality of life.