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Although hyperkalemia is much more common in patients with chronic kidney disease (CKD), the reported frequency of hyperkalemia varies markedly across studies, primarily due to differences in the ascertainment of hyperkalemia and the severity of CKD. Major risk factors for hyperkalemia among CKD patients include lower estimated glomerular filtration rate (eGFR), use of renin–angiotensin–aldosterone system inhibitors (RAASis), diabetes, older age and male gender. The use of two drugs to inhibit RAAS in diabetic CKD markedly increases the risk of hyperkalemia, as demonstrated in large multicenter clinical trials. Hyperkalemia has consistently been associated with an increased risk of adverse events compared with normokalemia, including all-cause mortality and cardiovascular morbidity and mortality. This risk is not explained by differences in comorbidity or estimated GFR, nor concomitant metabolic abnormalities such as acidosis among those with hyperkalemia. Sodium polystyrene sulfonate has been used commonly for decades to treat hyperkalemia in CKD patients, but without any high-quality clinical data to support its efficacy and with an increased risk of rare but serious colonic complications. The newer oral potassium-binding agents, patiromer and sodium zirconium cyclosilicate, have been shown to be effective and safe for the non-emergent treatment of hyperkalemia in CKD patients, including patients treated with RAASis. Although the long-term use of these medications may permit continuation of RAASis in CKD patients with hyperkalemia, the overall impact of this approach (as compared with down-titration of RAASis and/or up-titration of diuretics) on long-term morbidity, mortality and quality of life remains uncertain. [ABSTRACT FROM AUTHOR]

Background: Although small elevations of high-sensitive cardiac troponin T (hs-cTnT) are associated with incident heart failure (HF) in the general population, the underlying mechanisms are not well defined. Evaluating the association of hs-cTnT with replacement fibrosis and progression of structural heart disease before symptoms is fundamental to understanding the potential of this biomarker in a HF prevention strategy.Methods: We measured hs-cTnT at baseline among 4986 participants in MESA (Multi-Ethnic Study of Atherosclerosis), a cohort initially free of overt cardiovascular disease (CVD). Cardiac magnetic resonance imaging was performed at baseline. Repeat cardiac magnetic resonance was performed 10 years later among 2831 participants who remained free of interim CVD events; of these, 1723 received gadolinium-enhanced cardiac magnetic resonance for characterization of replacement fibrosis by late gadolinium enhancement. Progression of subclinical CVD was defined by 10-year change in left ventricular structure and function. Associations of hs-cTnT with incident HF, CV-related mortality, and coronary heart disease were estimated using Cox regression models.Results: Late gadolinium enhancement for replacement fibrosis was detectable in 6.3% participants without interim CVD events by follow-up cardiac magnetic resonance. A graded association was observed between higher baseline hs-cTnT categories and late gadolinium enhancement (≥7.42 ng/L versus 12% (highest category versus Conclusions: hs-cTnT levels are associated with replacement fibrosis and progressive changes in left ventricular structure in CVD-free adults, findings that may precede HF symptoms by years. Minor elevations of hs-cTnT may represent a biochemical signature of early subclinical cardiac disease, providing an opportunity for targeted preventive interventions. [ABSTRACT FROM AUTHOR]

It is well known that the population with chronic kidney disease (CKD) is at greater risk for cardiovascular disease and death than the general population. The use and interpretation of high sensitivity cardiac troponin (hs-cTn) assays have been particularly challenging in these patients with the majority having elevated levels at baseline. The diagnostic accuracy of acute myocardial infarction (AMI) may be decreased in patients with CKD when using these newer troponins. In order to improve the sensitivity and specificity for the diagnosis of AMI, one must look at the change in cTn and consider using higher cut-off values. In asymptomatic patients with CKD, research has shown increased prevalence of cardiovascular risk factors and underlying structural heart disease with increasing cTn levels. Prognostically, elevated cTn has been associated with adverse outcomes including incident heart failure and cardiovascular mortality. The purpose of the review is to evaluate hs-cTn in patients with CKD for the diagnosis of AMI and for the prognostic significance of elevated levels in CKD patients without AMI. Although the underlying etiology of persistently elevated cTn in the CKD population remains unclear, the review will also evaluate studies attempting to explain whether the source of cTn is from increased cardiac production versus decreased renal clearance. Further longitudinal studies are required in order to bridge the gap between the prognostic importance of elevated cTn and clinical management to prevent symptomatic cardiac disease. [ABSTRACT FROM AUTHOR]

This research letter presents findings on the variability of cardiac biomarkers, specifically NT-proBNP and high-sensitivity troponin T, in patients with chronic kidney disease (CKD). The study, which included 4615 individuals from the SPRINT trial, found that the levels of these biomarkers remained stable over time regardless of the level of kidney function. The results suggest that baseline values of these biomarkers can be used for comparison when CKD patients present with symptoms of acute heart failure or myocardial infarction. The study acknowledges its limitations, such as the exclusion of patients with lower kidney function or on dialysis, and the potential impact of acute kidney injury on biomarker concentrations. [Extracted from the article]

The article focuses on the role of cardiac troponin (cTn) as diagnostic and prognostic blood-based biomarkers in renal disease diagnosis. It mentions the emergence of a new consensus definition of acute myocardial infarction (AMI) which reflected an increased emphasis on a biochemical basis for the diagnosis of the disease as well as reports of the diagnostic accuracy for AMI with cTn assays in patients with renal disease.

Objectives: The study sought to determine the 99th percentile upper reference limit for the high-sensitivity cardiac troponin T assay (hs-cTnT) in 3 large independent cohorts. Background: The presently recommended 14 ng/l cut point for the diagnosis of myocardial infarction using the hs-cTnT assay was derived from small studies of presumably healthy individuals, with relatively little phenotypic characterization. Methods: Data were included from 3 well-characterized population-based studies: the Dallas Heart Study (DHS), the Atherosclerosis Risk in Communities (ARIC) Study, and the Cardiovascular Health Study (CHS). Within each cohort, reference subcohorts were defined excluding individuals with recent hospitalization, overt cardiovascular disease, and kidney disease (subcohort 1), and further excluding those with subclinical structural heart disease (subcohort 2). Data were analyzed stratified by age, sex, and race. Results: The 99th percentile values for the hs-cTnT assay in DHS, ARIC, and CHS were 18, 22, and 36 ng/l (subcohort 1) and 14, 21, and 28 ng/l (subcohort 2), respectively. These differences in 99th percentile values paralleled age differences across cohorts. Analyses within sex/age strata yielded similar results between cohorts. Within each cohort, 99th percentile values increased with age and were higher in men. More than 10% of men 65 to 74 years of age with no cardiovascular disease in our study had cardiac troponin T values above the current myocardial infarction threshold. Conclusions: Use of a uniform 14 ng/l cutoff for the hs-cTnT assay may lead to over-diagnosis of myocardial infarction, particularly in men and the elderly. Clinical validation is needed of new age- and sex-specific cutoff values for this assay. [ABSTRACT FROM AUTHOR]

Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). A recent trial in diabetic patients with CKD, however, suggested a greater risk of stroke associated with full correction of anemia with ESAs. Using national Veterans Affairs data we performed a case-control study examining the association of incident ESA use with acute stroke in patients with estimated glomerular filtration rate <60 cm3/min per 1.73 m2 and outpatient hemoglobin <12 g/dl. Using diagnosis codes, we identified 2071 acute hospitalized stroke cases and matched them 1:5 with controls without stroke, resulting in 12,426 total patients for analysis. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use in 1026 patients was associated with greater odds of stroke (odds ratio 1.30). There was significant interaction between ESA use and cancer, with greater odds of stroke among ESA-treated cancer patients (odds ratio 1.85), but not in ESA-treated patients without cancer (odds ratio 1.07). ESA-treated patients with cancer received a median initial dose 2.5-4 times greater than ESA-treated patients without cancer, but pre-ESA hemoglobin and its rate of change did not differ between these groups. Hence, in a large national sample of anemic patients with CKD, ESA treatment was associated with an increased risk of acute stroke with the greatest effect among patients with cancer. [ABSTRACT FROM AUTHOR]

Parathyroidectomy rates among United States dialysis patients: 1990–1999. Background. Medical therapy for secondary hyperparathyroidism (SHPTH) has evolved considerably during the past decade. It is not known how changes in medical therapy might impact the parathyroidectomy (PTX) rate among dialysis patients. Relatively low parathyroid hormone (PTH) levels have been found among elderly dialysis patients and those with diabetes. Clinical factors associated with differing PTX rates among United States dialysis patients have not been reported. We report PTX rates in the United States from 1990 to 1999 among persons with end-stage renal disease, accounting for changes in patient characteristics. Methods. Data from the United States Renal Database were utilized. Patients insured by Medicare or Medicaid and receiving renal replacement therapy between January 1, 1990, and December 31, 1999 were considered for analysis. PTX was determined by ICD-9 procedure codes. Multivariate Poisson models were used to estimate adjusted PTX rates. Results. The overall observed PTX rate in the study sample was 7.16 per 1000 person-years at risk. After a slight rise during the early 1990s, adjusted PTX rates declined by approximately 30% between 1995 and 1999. Adjusted PTX rates were higher among patients who were younger, female, nondiabetic, receiving peritoneal dialysis, and those with a longer cumulative duration of dialysis. Conclusion. PTX rates have recently decreased in the United States, independent of changes in patient characteristics. The effectiveness of medical therapy in targeting secondary hyperparathyroidism may be improving. Younger, nondiabetic patients with a longer cumulative dialysis burden are at particularly high risk for PTX. [ABSTRACT FROM AUTHOR]

Elevated risk of stroke among patients with end-stage renal disease. Background. Although end-stage renal disease (ESRD) has been associated with accelerated vascular disease of the cerebral circulation, there are no prior studies that have estimated the risk of hemorrhagic and ischemic stroke among the United States dialysis population relative to the general population. Methods. We performed a population-based cohort study to compare rates of hospitalized ischemic and hemorrhagic stroke among incident dialysis patients in the United States Renal System database and non-ESRD subjects from the general population identified in the National Hospital Discharge Survey. Results. After adjustment for age, gender, and race, estimated rates of hospitalized stroke were markedly higher for dialysis patients compared to the general population. The age-adjusted relative risk (RR) of stroke among dialysis patients compared to the general population was 6.1 [95% Confidence Interval (95% CI) 5.1, 7.1] for Caucasian males, 4.4 (95% CI 3.3, 5.5) for African American males, 9.7 (95%CI 8.2, 11.2) for Caucasians females and 6.2 (95%CI 4.8, 7.6) for African American females. When considered as separate outcomes, hospitalization rates for hemorrhagic and ischemic stroke were both markedly elevated for subjects treated with dialysis (ischemic, RR = 4.3 to 10.1; hemorrhagic, RR = 4.1 to 6.7). Conclusion. Incident dialysis patients are at markedly higher risk for hospitalized stroke when compared to the general population. Although prior public health initiatives have focused primarily on cardiac disease among patients treated with dialysis, our data suggest that new initiatives are needed to control the high risk of stroke in this population. [ABSTRACT FROM AUTHOR]

Patients with end-stage renal disease (ESRD) treated with dialysis have a dramatically elevated rate of cardiovascular disease (CVD) compared to the general population. Lipid-lowering therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors ("statins") has been shown to markedly reduce cardiovascular risk in patients without renal failure, but their effect has not been fully studied in the dialysis population. In this article we will first discuss the known benefits of statin therapy in the general population and summarize the current guidelines for such therapy. We will then examine the evidence linking dyslipidemia and cardiac disease in the dialysis population and discuss possible pathophysiologic mechanisms by which statins could prevent cardiac disease in these patients. We will also review prior clinical studies of the effects of statins in patients on dialysis, with particular attention to the safety and efficacy of these drugs in this population. Finally, we will review how statins are currently being used in the care of dialysis patients and suggest whether an expanded utilization of these drugs could help reduce the enormously high rates of cardiac disease in this patient population. [ABSTRACT FROM AUTHOR]

HMG-CoA reductase inhibitors are associated with reduced mortality in ESRD patients.. Background: Patients with end-stage renal disease (ESRD) suffer from markedly higher rates of cardiovascular disease than the general population. Although therapy with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (“statins”) has been demonstrated to reduce the mortality from cardiovascular disease in patients without ESRD, only 10% of patients on dialysis are treated with these medications by day 60 of ESRD. We determined whether the use of statins is associated with a reduction in cardiovascular-specific death and total mortality in ESRD patients. Methods: Data were analyzed from the U.S. Renal Data System Dialysis Morbidity and Mortality Wave-2 study, a cohort of randomly selected patients who were initiating dialysis in 1996. Information about the use of statins as well as other baseline characteristics was abstracted from the patients' dialysis records by dialysis personnel. Cox proportional hazards models were developed to determine the association between use of statins at baseline and subsequent risk of mortality, with adjustment for known mortality risk factors. Results: Follow-up data were available for 3716 patients through July 1998. At baseline, 362 (9.7%) of patients were using statins. These patients had a mortality rate of 143/1000 person-years, compared with a rate of 202/1000 person-years for patients not using statins. Statin use was independently associated with a reduced risk of total mortality [relative risk (RR) = 0.68, 95% confidence interval (CI) = 0.54, 0.87] as well as cardiovascular-specific mortality (RR = 0.64, 95% CI = 0.45, 0.91). In contrast, the use of fibrates was not associated with reduced mortality (RR = 1.29). Conclusions: Statin use was associated with a reduction in cardiovascular-specific death and total mortality in patients on dialysis. [ABSTRACT FROM AUTHOR]

In the epidemiologic study of end-stage renal disease (ESRD), accurate adjustment for comorbidity is essential to controlling bias in the comparison of outcomes across groups of patients or dialysis facilities. Liu et al. derive and validate a novel comorbidity index using data from the United States Renal Data System. This novel index represents an important tool for observational research in ESRD but will not by itself overcome the potential problems of residual and unmeasured confounding in observational research. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Limited data are available on the continuation of outpatient sodium glucose cotransporter 2 inhibitors (SGLT2is) during hospitalization. The objective was to evaluate associations of SGLT2i continuation in the inpatient setting with hospital outcomes. RESEARCH DESIGN AND METHODS: This nationwide cohort study used Veterans Affairs health care system data of acute care hospitalizations between 1 April 2013 and 31 August 2021. A total of 36,505 admissions of patients with diabetes with an outpatient prescription for an SGLT2i prior to hospitalization were included. The exposure was defined as SGLT2i continuation during hospitalization. Admissions where SGLT2i was continued were compared with admissions where it was discontinued. The primary outcome was in-hospital mortality. Secondary outcomes were acute kidney injury (AKI) and length of stay (LOS). Negative binomial propensity score–weighted and zero-truncated analyses were used to compare outcomes and adjusted for multiple covariates, including demographics and comorbidities. RESULTS: Mean (SE) age was 67.2 (0.1) and 67.5 (0.1) years (P = 0.03), 97.0% and 96.6% were male (P = 0.1), 71.3% and 72.1% were White, and 20.8% and 20.5% were Black (P = 0.52) for the SGLT2i continued and discontinued groups, respectively. After adjustment for covariates (age, sex, race, BMI, Elixhauser comorbidity index, procedures/surgeries, and insulin use), the SGLT2i continued group had a 45% lower mortality rate (incidence rate ratio [IRR] 0.55, 95% CI 0.42–0.73, P < 0.01), no difference in AKI (IRR 0.96, 95% CI 0.90–1.02, P = 0.17), and decreased LOS (4.7 vs. 4.9 days) (IRR 0.95, 95% CI 0.93–0.98, P < 0.01) versus the SGLT2i discontinued group. Similar associations were observed across multiple sensitivity analyses. CONCLUSIONS: Continued SGLT2i during hospitalization among patients with diabetes was associated with lower mortality, no increased AKI, and shorter LOS. [ABSTRACT FROM AUTHOR]

Introduction: High-sensitivity cardiac troponin T (hs-cTnT) plasma levels are associated with cardiac injury and incident heart failure. The mechanisms for biomarker release leading to cardiac injury are unclear, and the sole previous genome-wide association study (GWAS; Yu, 2013) suggested genetic variants near NCOA2 and TNNT2 are associated with hs-cTnT. Hypothesis: The Multi-Ethnic Study of Atherosclerosis (MESA), by incorporating multi-omics data, will validate previous findings, refine loci mapping, provide mechanistic insights, and identify novel loci of cardiac injury. Methods: Baseline plasma hs-cTnT levels were measured in 6,131 MESA participants free of clinical cardiovascular disease (mean age 62.2±10.2 yrs; 47.6% men, 39% White, 26% African-American, 23% Hispanic, 12% Chinese). We conducted a GWAS of the log hs-cTnT level (>11M post-QC single nucleotide polymorphisms (SNPs)) and specific candidate SNPs for hs-cTnT dichotomized at the upper percentile of risk. We meta-analyzed the four ethnic groups under fixed effects and ancestry-adjusted meta-regression models. Results: We validated the NCOA2 locus with a different index SNP (rs10091864) 44kb upstream of NCOA2 (p=3x10-9), consistent in all ethnic groups. In Genotype-Tissue Expression analysis, rs10091864 is an expression quantitative trait locus (eQTL) for XKR9 and is co-localized with eQTLs for an intergenic non-coding RNA (LOC101926892). We identified a novel association with a missense coding SNP (rs79412473) in TBCK (imputed well only in whites, p=4x10-8). A gene with strong physiological impact and gene expression evidence (BCL2) had an associated intronic SNP (rs899967) that was consistent in effect, directionally and size, with the Yu report, but did not reach GWAS significance (joint p=1.5x10-7). The dichotomous trait (TNNT2) association was replicated only in African-Americans (p=0.03). Conclusions: In summary, we have evidence for additional novel genetic loci associated with cardiac injury as measured by hs-cTnT and replicated the NCOA2 association in MESA. Use of these genetic findings may provide better mechanistic insights into the pathophysiology of cardiac injury and incident heart failure. [ABSTRACT FROM AUTHOR]

Background and Objective: Hypoglycemia is a common safety event when attempting to optimize glycemic control in diabetes (DM). While electronic medical records provide a natural ground for detecting and analyzing hypoglycemia, ICD codes used in the databases may be invalid, insensitive or non-specific in detecting new hypoglycemic events. We developed text preprocessing methods to improve automatic detection of hypoglycemia from analysis of clinical encounter text notes.Methods: We set out to improve hypoglycemia detection from clinical notes by introducing three preprocessing methods: stop word filtering, medication signaling, and ICD narrative enrichment. To test the proposed methods, we selected clinical notes from VA Maryland Healthcare System, based on various combinations of three criteria that are suggestive of hypoglycemia, including ICD-9 code of diabetes and hypoglycemia, laboratory glucose values < 70 md/dL, and text reference to a proximate hypoglycemia event. In addition, we constructed one dataset of 395 clinical notes from year 2009 and another of 460 notes from year 2014 to test the generality of the proposed methods. For each of the datasets, two physician judges manually reviewed individual clinical notes to determine whether hypoglycemia was present or absent. A third physician judge served as a final adjudicator for disagreements.Results: Each of the proposed preprocessing methods contributed to the performance of hypoglycemia detection by significantly increasing the F1 score in the range of 5.3∼7.4% on one dataset (p < .01). Among the methods, stop word filtering contributed most to the performance improvement (7.4%). Combining all the preprocessing methods led to greater performance gain (p < .001) compared with using each method individually. Similar patterns were observed for the other dataset with the F1 score being increased in the range of 7.7%∼9.4% by individual methods (p < .001). Nevertheless, combining the three methods did not yield additional performance gain.Conclusion: The proposed text preprocessing methods improved the performance of hypoglycemia detection from clinical text notes. Stop word filtering achieved the most performance improvement. ICD narrative enrichment boosted the recall of detection. Combining the three preprocessing methods led to additional performance gains. [ABSTRACT FROM AUTHOR]

Objectives: To examine the hypothesis that the inflammatory state of aging is a risk factor for accelerated renal function (RF) decline using inflammatory biomarkers and RF measures collected over 9 years of follow‐up in relatively healthy individuals enrolled in the Invecchiare in Chianti study. Design: Longitudinal. Setting: Community. Participants: Individuals aged 60 and older with baseline estimated glomerular filtration rate (eGFR) of 60 mL/min per 1.73 m2 and greater and no diabetes mellitus (DM) (N = 687). Measures: eGFR, as a proxy for RF, was determined using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation at baseline and 3‐, 6‐, and 9‐year follow‐up. Incident chronic kidney disease (CKD) was defined as new‐onset eGFR less than 60 mL/min per 1.73 m2 at each follow‐up. Predictors included baseline and time‐dependent inflammatory biomarkers: soluble tumor necrosis factor alpha receptors (sTNFα‐R1 and ‐R2), interleukin (IL)‐6, IL‐18, IL‐1β, IL‐1 receptor antagonist, and high‐sensitivity C‐reactive protein. Results: Higher baseline sTNFα‐R1 was significantly associated with lower eGFR over 9 years, independent of DM or blood pressure (baseline: β ^ = −0.39, P = .001; 3‐year: β ^ = −0.26, P = .001; 6‐year: β ^ = −0.36, P = .001; 9‐year: β ^ = −0.47, P = .001). The rate of TNFα‐R1 change was significantly associated with rate of eGFR change ( β ^ = −0.18, P = .001). Baseline sTNFα‐R1 predicted incident CKD (per 1‐standard deviation increment: 3‐year: relative risk (RR) = 1.3, 95% confidence interval (CI) = 1.1–1.5; 6‐year: RR = 1.5, 95% CI = 1.1–2.2; 9‐year RR = 1.6, 95% CI = 1.1–2.2). Similar results were found for sTNFα‐R2. Conclusion: Baseline TNFα‐R levels and their rates of change were significantly associated with RF decline and incident CKD in older adults independent of DM or blood pressure. [ABSTRACT FROM AUTHOR]

Elevated plasma neurofilament light chain (NfL) is associated with dementia though underlying mechanisms remain unknown. We examined cross-sectional relationships of time-dependent plasma NfL with selected brain structural magnetic resonance imaging (sMRI) prognostic markers of dementia. The sample was drawn from the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study, selecting participants with complete v 1 (2004–2009) and v 2 (2009–2013) plasma NfL exposure and ancillary sMRI data at v scan (2011–2015, n = 179, mean v 1 to v scan time: 5.4 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, and race, correcting for multiple testing with q-values. NfL (v1) was associated with larger WMLV (both Log e transformed), after 5–6 years' follow-up, overall (β = +2.131 ± 0.660, b = +0.29, p = 0.001, and q = 0.0029) and among females. NfLv 2 was linked to a 125 mm3 lower left hippocampal volume (p = 0.004 and q = 0.015) in reduced models, mainly among males, as was observed for annualized longitudinal change in NfL (δNfL bayes). Among African American adults, NfL v1 was inversely related to total, gray and white matter volumes. Plasma NfL may reflect future brain pathologies in middle-aged adults. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a significant risk factor for cognitive impairment. Previous studies have examined differences in cognitive impairment between persons with and without CKD using multiple cognitive outcomes, but few have done this for an extensive battery of cognitive tests. We relate early-stage CKD to two indices of impairment for 22 measures of cognitive ability. Methods: The study was community-based and cross-sectional with 898 individuals free from dementia and end-stage renal disease. Estimated glomerular filtration rate (eGFR) was calculated using the chronic kidney disease epidemiology collaboration equation and classified as <60 or ⩾60 mL/min/1.73 m2 , based on consensus definitions of Stage 3 or greater CKD. The eGFR classifications were related to modest [⩾1 standard deviation (SD) below the mean] and severe (⩾1.5 SD below the mean) impairment on each measure using logistic regression analyses adjusting for potential risk factors. Results: A total of 146 individuals (16.3%) had eGFR <60 mL/ min/1.73m2 (mean 51±10.1 mL/min/1.73m2 ). These participants had significantly greater risk for modestly impaired abilities in the scanning and tracking and visual-spatial organization/ memory (VSOM) domains after accounting for comorbidity-related risk factors [odds ratios (ORs) between 1.68 and 2.16], as well as greater risk for severely impaired functioning in the language domain (OR = 2.65). Conclusions: Participants with eGFR <60 mL/min/1.73 m2 were at higher risk for cognitive impairment than those with eGFR ⩾60 mL/min/1.73 m2 on the majority of cognitive abilities, specifically those within the VSOM, Language, and scanning and tracking domains. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted. [ABSTRACT FROM AUTHOR]

Plasma neurofilament light chain (NfL)'s link to dementia may be mediated through white matter integrity (WMI). In this study, we examined plasma NfL's relationships with diffusion tensor magnetic resonance imaging markers: global and cortical white matter fractional anisotropy (FA) and trace (TR). Plasma NfL measurements at 2 times (v 1 : 2004–2009 and v 2 : 2009–2013) and ancillary dMRI (v scan : 2011–2015) were considered (n = 163, mean time v 1 to v scan = 5.4 years and v 2 to v scan : 1.1 years). Multivariable-adjusted regression models, correcting for multiple-testing revealed that, overall, higher NfL v1 was associated with greater global TR (β ± SE: +0.0000560 ± 0.0000186, b = 0.27, p = 0.003, q = 0.012), left frontal WM TR (β ± SE: + 0.0000706 ± 0.0000201, b ± 0.30, p = 0.001, q = 0.0093) and right frontal WM TR (β ± SE: + 0.0000767 ± 0.000021, b ± 0.31, p < 0.001, q = 0.0093). These associations were mainly among males and White adults. Among African American adults only, NfL v2 was associated with greater left temporal lobe TR. "Tracking high" in NfL was associated with reduced left frontal FA (Model 2, body mass index-adjusted: β ± SE:-0.01084 ± 0.00408, p = 0.009). Plasma NfL is a promising biomarker predicting future brain white matter integrity (WMI) in middle-aged adults. [ABSTRACT FROM AUTHOR]

Vitamin K is linked to cognitive function, but studies in individuals with chronic kidney disease (CKD), who are at risk for vitamin K insufficiency and cognitive impairment, are lacking. The cross-sectional association of vitamin K status biomarkers with cognitive performance was evaluated in ≥55-y-old adults with CKD (N  = 714, 49% female, 44% black). A composite score of a cognitive performance test battery, calculated by averaging the z scores of the individual tests, was the primary outcome. Vitamin K status was measured using plasma phylloquinone and dephospho-uncarboxylated matrix Gla protein [(dp)ucMGP]. Participants with low plasma (dp)ucMGP, reflecting higher vitamin K status, had better cognitive performance than those in the two higher (dp)ucMGP categories based on the composite outcome (P  = 0.03), whereas it did not significantly differ according to plasma phylloquinone categories (P  = 0.08). Neither biomarker was significantly associated with performance on individual tests (all P  > 0.05). The importance of vitamin K to cognitive performance in adults with CKD remains to be clarified. [ABSTRACT FROM AUTHOR]

Background: Leukocytosis is a powerful predictor of incident chronic kidney disease (CKD) and related outcomes. However, the association between periodontitis measures and increased leukocytosis in the context of CKD has not been well described. We sought to identify which individual measures of periodontal disease may best associate with reduced estimated glomerular filtration rate (eGFR) and albuminuria, and to test if these measures were associated with increased leukocytosis in subjects with established CKD. Methods: We estimated, among 13,270 participants in the National Health and Nutrition Examination Survey III study, the associations between case-based definition of periodontitis, clinical attachment loss (CAL) and pocket depth (PD) as individual measures of periodontal disease, with renal function measures and leukocytosis. Results: In adjusted multivariate analyses, case-based definition of severe periodontitis was associated with albuminuria (β = 0.003, p = 0.01) but not with eGFR. However, CAL and PD were all individually associated with both albuminuria (β = 0.08, p < 0.001 and β = 0.06, p < 0.001, respectively) and eGFR (β = -0.05, p < 0.001 and β = -0.03, p < 0.001, respectively). We found significant associations between elevated CAL and PD with leukocytosis. Lastly, we found a marked association between the joint presence of CKD and elevated CAL or PD with leukocytosis (odds ratio (OR) 3.3, 95% confidence interval (CI) 1.4-7.5 and OR 3.2, 95% CI 1.1-9.7, respectively). Conclusion: Individual measures of periodontal disease are associated with renal function and heightened leukocytosis in CKD subjects. The significantly added inflammatory burden noted in CKD subjects with periodontal disease argue for targeting periodontitis treatment as part of our multifaceted approach to CKD patients. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the relations between the use of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and age-related change in multiple domains of cognitive function in community-dwelling individuals without dementia. DESIGN: Longitudinal, with measures obtained on one to 18 occasions over up to 45 years. SETTING: General community. PARTICIPANTS: A volunteer sample of up to 2,300 participants from the Baltimore Longitudinal Study of Aging free of diagnosed dementia. MEASUREMENTS: At each visit, reported NSAID or aspirin use (yes/no) and tests of verbal and visual memory, attention, perceptuo-motor speed, confrontation naming, executive function, and mental status. RESULTS: Mixed-effects regression models revealed that NSAID use was associated with less prospective decline on the Blessed Information-Memory-Concentration (I-M-C) Test, a mental status test weighted for memory and concentration ( P<.001), and Part B of the Trail Making Test, a test of perceptuo-motor speed and mental flexibility ( P<.05). In contrast, aspirin use was related to greater prospective decline on the Blessed I-M-C Test ( P<.05) and the Benton Visual Retention Test, a test of visual memory ( P<.001). CONCLUSION: Consistent with studies of incident dementia, NSAID users without dementia displayed less prospective decline in cognitive function, but on only two cognitive measures. In contrast, aspirin use was associated with greater prospective cognitive decline on select measures, potentially reflecting its common use for vascular disease prophylaxis. Effect sizes were small, calling into question clinical significance, although overall public health significance may be meaningful. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Cardiovascular disease (CVD) is the leading cause of death in patients with serious mental illness (SMI) and in patients with Type 2 diabetes. Inadequate pharmacologic care for CVD may partially explain poor health outcomes in individuals with both conditions. We sought to identify patients in this group at greatest risk for suboptimal pharmacologic management. Methods: Among individuals with Type 2 diabetes and SMI identified from Maryland Medicaid data, we evaluated patient and service utilization factors associated with the prescription of HMG-CoA reductase inhibitors (“statins”) for hyperlipidemia and angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) for chronic kidney disease, congestive heart failure, and hypertension. Results: From 2001 to 2003, the annual prevalence of use of statins and ACE-inhibitors/ARBs ranged from 44 to 59%, with rates increasing each year. Being female, having certain cardiovascular conditions, and having a greater number of outpatient visits for diabetes increased the odds of receiving statins and ACE-inhibitors/ARBs. More frequent contact with the mental health system was associated with a lower likelihood of receipt of both medication classes; having a substance use disorder was associated with reduced use of statins. African-Americans were less likely than Caucasians to receive statins, but more likely to receive prescriptions for ACE-inhibitors/ARBs. Conclusions: Although the use of cardioprotective medications in individuals with Type 2 diabetes and SMI increased over the study period, a considerable proportion of patients remained inadequately managed despite their considerable cardiac risk. Further study should focus on observed racial variations and strategies to increase the capacity of mental health contacts to improve prescribing of these agents. [Copyright &y& Elsevier]

We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle–brachial index (ABI). Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3–10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively. Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes. NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD. • Hs-cTnT and NT-proBNP levels are associated with an increased risk of PAD in predominantly white populations. • We expanded these findings to a multi-ethnic cohort without baseline cardiovascular disease. • Future studies are needed to determine whether these biomarkers can actually improve PAD risk prediction. [ABSTRACT FROM AUTHOR]

Background Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD. Methods We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors. Results In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08–1.40]}, QRS [OR 1.28 (95% CI 1.16–1.42)] and QTc [OR 1.94 (95% CI 1.50–2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06–1.16)] and QTc [OR 1.82 (95% CI 1.58–2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters. Conclusions hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD. [ABSTRACT FROM AUTHOR]

• Greater RDW v1 was associated with poorer WMI, among males only, particularly in terms of lower mean global fractional anisotropy (FA). • No such associations were found for anemia and δRDW (overall or sex-specific), or for RDW exposures among females and the non-anemic group. Anemia (blood hemoglobin [Hb] <13 g/dL among males; <12 g/dL among females) and elevated red cell distribution width (RDW) are potential risk factors for reduced brain white matter integrity (WMI), reflected by lower fractional anisotropy or increased mean diffusivity. Cross-sectional data with exposure-outcome lag time was used, whereby hematological exposures (RDW and Hb) and covariates were compiled from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study with available visit 1 (v 1 ; 2004–2009) and/or v 2 (2009–2013) data; while diffusion tensor magnetic resonance imaging (dMRI) outcome data were collected at HANDLS SCAN visit (v scan : 2011–2015, n = 214, mean follow-up from v 1 ±SD: 5.6 ± 1.8 year). Multivariable-adjusted linear regression analyses were conducted, overall, stratifying by sex, and further restricting to the nonanemic for RDW exposures in part of the analyses. Among males, RDW (v1) was linked with lower global mean fractional anisotropy (standardized effect size b = −0.30, p = 0.003, q < 0.05; basic model), an association only slightly attenuated with further covariate adjustment. Anemia was not a risk factor for poor WMI, independently of RDW. Ultimately, pending further longitudinal evidence, initial RDW appears to be associated with poorer WMI among males. [ABSTRACT FROM AUTHOR]

Background: Anemia and red cell distribution width (RDW) have been linked to poor cognitive performance, pending studies of underlying mechanisms.Objective: We examined cross-sectional relationships of initial RDW status (v1), RDW change (δ), and anemia with brain structural magnetic resonance imaging (sMRI) markers, including global and cortical brain and hippocampal and white matter lesion (WML) volumes, 5-6 years later.Methods: Data were used from three prospective visits within the Healthy Aging in Neighborhoods of Diversity Across the Life Span (HANDLS) study with complete v1 (2004-2009) and v2 (2009-2013) exposures and ancillary sMRI data at vscan (2011-2015, n = 213, mean v1 to vscan time: 5.7 years). Multivariable-adjusted linear regression models were conducted, overall, by sex, by race, and within non-anemics, correcting for multiple testing with q-values.Results: In minimally adjusted models (socio-demographics and follow-up time), anemiav1 and RDWv1 were consistently associated with smaller bilateral hippocampal volumes overall, and among females (q < 0.05), without significant sex differences. RDWv1 was related to smaller select regional cortical brain gray and white matter volumes in hematological measure-adjusted models; anemiav1 was associated with larger WML volumes only among whites.Conclusion: In summary, baseline anemia and RDW were consistently associated with smaller bilateral hippocampal volumes, particularly among females, while anemia was linked to larger WML volume among Whites. In hematological measure-adjusted models, baseline RDW was linked to smaller regional gray and white matter volumes. Pending studies with sMRI repeats, randomized controlled trials are needed, demonstrating associations of anemia and elevated RDW with reduced brain volumes and cognitive dysfunction. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text. Background: A malignant subphenotype of left ventricular hypertrophy (LVH) has been described, in which minimal elevations in cardiac biomarkers identify individuals with LVH at high risk for developing heart failure (HF). We tested the hypothesis that a higher prevalence of malignant LVH among blacks may contribute to racial disparities in HF risk. Methods: Participants (n=15 710) without prevalent cardiovascular disease were pooled from 3 population-based cohort studies, the ARIC Study (Atherosclerosis Risk in Communities), the DHS (Dallas Heart Study), and the MESA (Multi-Ethnic Study of Atherosclerosis). Participants were classified into 3 groups: those without ECG-LVH, those with ECG-LVH and normal biomarkers (hs-cTnT (high sensitivity cardiac troponin-T) <6 ng/L and NT-proBNP (N-terminal pro-B-type natriuretic peptide) <100 pg/mL), and those with ECG-LVH and abnormal levels of either biomarker (malignant LVH). The outcome was incident HF. Results: Over the 10-year follow-up period, HF occurred in 512 (3.3%) participants, with 5.2% in black men, 3.8% in white men, 3.2% in black women, and 2.2% in white women. The prevalence of malignant LVH was 3-fold higher among black men and women versus white men and women. Compared with participants without LVH, the adjusted hazard ratio for HF was 2.8 (95% CI, 2.1–3.5) in those with malignant LVH and 0.9 (95% CI, 0.6–1.5) in those with LVH and normal biomarkers, with similar findings in each race/sex subgroup. Mediation analyses indicated that 33% of excess hazard for HF among black men and 11% of the excess hazard among black women was explained by the higher prevalence of malignant LVH in blacks. Of black men who developed HF, 30.8% had malignant LVH at baseline, with a corresponding population attributable fraction of 0.21. The proportion of HF cases occurring among those with malignant LVH, and the corresponding population attributable fraction, were intermediate and similar among black women and white men and lowest among white women. Conclusions: A higher prevalence of malignant LVH may in part explain the higher risk of HF among blacks versus whites. Strategies to prevent development or attenuate risk associated with malignant LVH should be investigated as a strategy to lower HF risk and mitigate racial disparities. [ABSTRACT FROM AUTHOR]

Background: Risk for atherosclerotic cardiovascular disease was a novel consideration for antihypertensive medication initiation in the 2017 American College of Cardiology/American Heart Association Blood Pressure (BP) guideline. Whether biomarkers of chronic myocardial injury (high-sensitivity cardiac troponin T ≥6 ng/L] and stress (N-terminal pro-B-type natriuretic peptide [NT-proBNP] ≥100 pg/mL) can inform cardiovascular (CV) risk stratification and treatment decisions among adults with elevated BP and hypertension is unclear.Methods: Participant-level data from 3 cohort studies (Atherosclerosis Risk in Communities Study, Dallas Heart Study, and Multiethnic Study of Atherosclerosis) were pooled, excluding individuals with prevalent CV disease and those taking antihypertensive medication at baseline. Participants were analyzed according to BP treatment group from the 2017 American College of Cardiology/American Heart Association BP guideline and those with high BP (120 to 159/<100 mm Hg) were further stratified by biomarker status. Cumulative incidence rates for CV event (atherosclerotic cardiovascular disease or heart failure), and the corresponding 10-year number needed to treat to prevent 1 event with intensive BP lowering (to target systolic BP <120 mm Hg), were estimated for BP and biomarker-based subgroups.Results: The study included 12 987 participants (mean age, 55 years; 55% women; 21.5% with elevated high-sensitivity cardiac troponin T; 17.7% with elevated NT-proBNP) with 825 incident CV events over 10-year follow-up. Participants with elevated BP or hypertension not recommended for antihypertensive medication with versus without either elevated high-sensitivity cardiac troponin T or NT-proBNP had a 10-year CV incidence rate of 11.0% and 4.6%, with a 10-year number needed to treat to prevent 1 event for intensive BP lowering of 36 and 85, respectively. Among participants with stage 1 or stage 2 hypertension recommended for antihypertensive medication with BP <160/100 mm Hg, those with versus without an elevated biomarker had a 10-year CV incidence rate of 15.1% and 7.9%, with a 10-year number needed to treat to prevent 1 event of 26 and 49, respectively.Conclusions: Elevations in high-sensitivity cardiac troponin T or NT-proBNP identify individuals with elevated BP or hypertension not currently recommended for antihypertensive medication who are at high risk for CV events. The presence of nonelevated biomarkers, even in the setting of stage 1 or stage 2 hypertension, was associated with lower risk. Incorporation of biomarkers into risk assessment algorithms may lead to more appropriate matching of intensive BP control with patient risk. [ABSTRACT FROM AUTHOR]

This study sought to examine the interactive relations of socioeconomic status and race to corticolimbic regions that may play a key role in translating stress to the poor health outcomes overrepresented among those of lower socioeconomic status and African American race. Participants were 200 community-dwelling, self-identified African American and White adults from the Healthy Aging in Neighborhoods of Diversity across the Life Span SCAN study. Brain volumes were derived using T1-weighted MP-RAGE images. Socioeconomic status by race interactions were observed for right medial prefrontal cortex (B = .26, p = .014), left medial prefrontal cortex (B = .26, p = .017), left orbital prefrontal cortex (B = .22, p = .037), and left anterior cingulate cortex (B = .27, p = .018), wherein higher socioeconomic status Whites had greater volumes than all other groups. Additionally, higher versus lower socioeconomic status persons had greater right and left hippocampal (B = -.15, p = .030; B = -.19, p = .004, respectively) and amygdalar (B = -.17, p = .015; B = -.21; p = .002, respectively) volumes. Whites had greater right and left hippocampal (B = -.17, p = .012; B = -.20, p = .003, respectively), right orbital prefrontal cortex (B = -.34, p < 0.001), and right anterior cingulate cortex (B = -.18, p = 0.011) volumes than African Americans. Among many factors, the higher levels of lifetime chronic stress associated with lower socioeconomic status and African American race may adversely affect corticolimbic circuitry. These relations may help explain race- and socioeconomic status-related disparities in adverse health outcomes. [ABSTRACT FROM AUTHOR]

Background: Lower serum Cr levels in women as compared to men result in underestimation of renal dysfunction and lower model for end-stage liver disease-sodium scores leading to reduced access to liver transplantation in women compared to men with comparable hepatic dysfunction.Aim: The aim of this study was to determine the gender differences in serum Cr, cystatin C, and other endogenous glomerular filtration rate (GFR) biomarkers, measured and estimated GFR, Cr clearance, and Cr production rates.Methods: We measured GFR by iothalamate plasma clearance in 103 patients with cirrhosis and assessed gender differences in GFR, Cr clearance and production rate, serum Cr, cystatin C and other endogenous GFR biomarkers including beta-trace protein, beta-2 microglobulin, and dimethylarginines.Results: Comparison of men and women showed significantly lower values for mean serum Cr (0.97 vs. 0.82 mg/dl, P = 0.023), and Cr production rate (13.37 vs. 11.02 mg/kg/day, P = 0.022). In contrast to the serum Cr and Cr production rate, men and women exhibited no significant differences in the means of serum cystatin C and other GFR biomarkers, measured GFR, GFR estimated using Cr–cystatin C GFR equation for cirrhosis, measured and estimated Cr clearances. After controlling for age, race, weight, height, and GFR, female gender remained associated with lower serum Cr levels (P = 0.003). Serum cystatin C levels were not associated with gender, age, race, weight, height, C-reactive protein, and history of hypothyroidism.Conclusions: Our results suggest that cystatin C and endogenous GFR biomarkers other than Cr, measured GFR, GFR estimated by Cr–cystatin C GFR equation for cirrhosis, measured and estimated Cr clearance minimized between-gender biases in accounting for renal function in patients with cirrhosis. Therefore, serum cystatin C should be measured as a complementary test to serum Cr when renal function is assessed in patients with cirrhosis, particularly in women and those with sarcopenia. [ABSTRACT FROM AUTHOR]

Background: Current strategies for cardiovascular disease (CVD) risk assessment among adults without known CVD are limited by suboptimal performance and a narrow focus on only atherosclerotic CVD (ASCVD). We hypothesized that a strategy combining promising biomarkers across multiple different testing modalities would improve global and atherosclerotic CVD risk assessment among individuals without known CVD.Methods: We included participants from MESA (Multi-Ethnic Study of Atherosclerosis) (n=6621) and the Dallas Heart Study (n=2202) who were free from CVD and underwent measurement of left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein. Associations of test results with the global composite CVD outcome (CVD death, myocardial infarction, stroke, coronary or peripheral revascularization, incident heart failure, or atrial fibrillation) and ASCVD (fatal or nonfatal myocardial infarction or stroke) were assessed over >10 years of follow-up. Multivariable analyses for the primary global CVD end point adjusted for traditional risk factors plus statin use and creatinine (base model).Results: Each test result was independently associated with global composite CVD events in MESA after adjustment for the components of the base model and the other test results (P<0.05 for each). When the 5 tests were added to the base model, the c-statistic improved from 0.74 to 0.79 (P=0.001), significant integrated discrimination improvement (0.07, 95% confidence interval [CI] 0.06-0.08, P<0.001) and category free net reclassification improvement (0.47; 95% CI, 0.38-0.56; P=0.003) were observed, and the model was well calibrated (χ2=12.2, P=0.20). Using a simple integer score counting the number of abnormal tests, compared with those with a score of 0, global CVD risk was increased among participants with a score of 1 (adjusted hazard ratio, 1.9; 95% CI, 1.4-2.6), 2 (hazard ratio, 3.2; 95% CI, 2.3-4.4), 3 (hazard ratio, 4.7; 95% CI, 3.4-6.5), and ≥4 (hazard ratio, 7.5; 95% CI, 5.2-10.6). Findings replicated in the Dallas Health Study were similar for the ASCVD outcome.Conclusions: Among adults without known CVD, a novel multimodality testing strategy using left ventricular hypertrophy by ECG, coronary artery calcium, N-terminal pro B-type natriuretic peptide, high-sensitivity cardiac troponin T, and high-sensitivity C-reactive protein significantly improved global CVD and ASCVD risk assessment. [ABSTRACT FROM AUTHOR]

The article discusses the sedentary behavior of chronic subclinical myocardial injury. Topics mention including the effects of a higher level of physical activity on troponin levels, association of increase sedentary time with increase cause of mortality and connection of chronic myocardial injury with increase sedentary time.

The article discusses research which examined safety of combined therapeutic use of angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARB) for diabetic nephropathy. It describes necessity of interventions that would reduce risk of progression from diabetic nephropathy to end-stage renal disease. Brief details relating to study design, participants, and administration of treatment are given. The adverse effects recorded following treatment are reported.

Background Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. Methods We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). Results Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b = 0.21SD decline per unit ln(eGFR), 95% CI: 0.04–0.38, P = .018], verbal episodic memory [b = 0.28 SD decline per unit ln(eGFR), 95% CI: 0.02–0.54, P = 0.038] and abstract reasoning [b = 0.36 SD decline per unit ln(eGFR), 95% CI: 0.04–0.67, P = 0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. Conclusions Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline. [ABSTRACT FROM AUTHOR]