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BACKGROUNDLongitudinal investigations of murine acute kidney injury (AKI) suggest that injury and inflammation may persist long after the initial insult. However, the evolution of these processes and their prognostic values are unknown in patients with AKI.METHODSIn a prospective cohort of 656 participants hospitalized with AKI, we measured 7 urine and 2 plasma biomarkers of kidney injury, inflammation, and tubular health at multiple time points from the diagnosis to 12 months after AKI. We used linear mixed-effect models to estimate biomarker changes over time, and we used Cox proportional hazard regressions to determine their associations with a composite outcome of chronic kidney disease (CKD) incidence and progression. We compared the gene expression kinetics of biomarkers in murine models of repair and atrophy after ischemic reperfusion injury (IRI).RESULTSAfter 4.3 years, 106 and 52 participants developed incident CKD and CKD progression, respectively. Each SD increase in the change of urine KIM-1, MCP-1, and plasma TNFR1 from baseline to 12 months was associated with 2- to 3-fold increased risk for CKD, while the increase in urine uromodulin was associated with 40% reduced risk for CKD. The trajectories of these biological processes were associated with progression to kidney atrophy in mice after IRI.CONCLUSIONSustained tissue injury and inflammation, and slower restoration of tubular health, are associated with higher risk of kidney disease progression. Further investigation into these ongoing biological processes may help researchers understand and prevent the AKI-to-CKD transition.FUNDINGNIH and NIDDK (grants U01DK082223, U01DK082185, U01DK082192, U01DK082183, R01DK098233, R01DK101507, R01DK114014, K23DK100468, R03DK111881, K01DK120783, and R01DK093771).

BackgroundManagement of adults with atrial fibrillation (AF) or atrial flutter in the emergency department (ED) includes rate reduction, cardioversion, and stroke prevention. Different approaches to these components of care may lead to variation in frequency of hospitalization and stroke prevention actions, with significant implications for patient experience, cost of care, and risk of complications. Standardization using evidence-based recommendations could reduce variation in management, preventable hospitalizations, and stroke risk.MethodsWe describe the rationale for our ED-based AF treatment recommendations. We also describe the development of an electronic clinical decision support system (CDSS) to deliver these recommendations to emergency physicians at the point of care. We implemented the CDSS at three pilot sites to assess feasibility and solicit user feedback. We will evaluate the impact of the CDSS on hospitalization and stroke prevention actions using a stepped-wedge cluster randomized pragmatic clinical trial across 13 community EDs in Northern California.DiscussionWe hypothesize that the CDSS intervention will reduce hospitalization of adults with isolated AF or atrial flutter presenting to the ED and increase anticoagulation prescription in eligible patients at the time of ED discharge and within 30days. If our hypotheses are confirmed, the treatment protocol and CDSS could be recommended to other EDs to improve management of adults with AF or atrial flutter.Trial registrationClinicalTrials.gov NCT05009225 .Registered on17 August 2021.

BACKGROUND: Atrial fibrillation (AF) is highly prevalent in CKD and is associated with worse cardiovascular and kidney outcomes. Limited data exist on use of AF pharmacotherapies and AF-related procedures by CKD status. We examined a large “real-world” contemporary population with incident AF to study the association of CKD with management of AF. METHODS: We identified patients with newly diagnosed AF between 2010 and 2017 from two large, integrated health care delivery systems. eGFR (≥60, 45–59, 30–44, 15–29, 60 ml/min per 1.73 m(2), patients with eGFR 30–44 (adjusted hazard ratio [aHR] 0.91; 95% CI, 0.99 to 0.93), 15–29 (aHR, 0.78; 95% CI, 0.75 to 0.82), and 60 ml/min per 1.73 m(2). These associations were even stronger for eGFR 60 ml/min per 1.73 m(2)): eGFR 30–44 ml/min per 1.73 (aHR, 0.78; 95% CI, 0.70 to 0.87), eGFR 15–29 ml/min per 1.73 m(2) (aHR, 0.73; 95% CI, 0.61 to 0.88), and eGFR

Additional file 1: Table S1. Raw urine biomarker levels without normalization to urine creatinine. Table S2. Urine biomarker-to-creatinine ratio changes in mixed effects models by AKI stage.

Rationale & objectiveThe clearance of protein-bound solutes by the proximal tubules is an innate kidney mechanism for removing putative uremic toxins that could exert cardiovascular toxicity in humans. However, potential associations between impaired kidney clearances of secretory solutes and cardiovascular events among patients with chronic kidney disease (CKD) remains uncertain.Study designA multicenter, prospective, cohort study.Setting & participantsWe evaluated 3,407 participants from the Chronic Renal Insufficiency Cohort (CRIC) study.ExposuresBaseline kidney clearances of 8 secretory solutes. We measured concentrations of secretory solutes in plasma and paired 24-hour urine specimens using liquid chromatography-tandem mass spectrometry (LC-MS/MS).OutcomesIncident heart failure, myocardial infarction, and stroke events.Analytical approachWe used Cox regression to evaluate associations of baseline secretory solute clearances with incident study outcomes adjusting for estimated GFR (eGFR) and other confounders.ResultsParticipants had a mean age of 56 years; 45% were women; 41% were Black; and the median estimated glomerular filtration rate (eGFR) was 43 mL/min/1.73 m2. Lower 24-hour kidney clearance of secretory solutes were associated with incident heart failure and myocardial infarction but not incident stroke over long-term follow-up after controlling for demographics and traditional risk factors. However, these associations were attenuated and not statistically significant after adjustment for eGFR.LimitationsExclusion of patients with severely reduced eGFR at baseline; measurement variability in secretory solutes clearances.ConclusionsIn a national cohort study of CKD, no clinically or statistically relevant associations were observed between the kidney clearances of endogenous secretory solutes and incident heart failure, myocardial infarction, or stroke after adjustment for eGFR. These findings suggest that tubular secretory clearance provides little additional information about the development of cardiovascular disease events beyond glomerular measures of GFR and albuminuria among patients with mild-to-moderate CKD.

BackgroundStudies in the general population suggest that atrial fibrillation (AF) is an independent risk factor for decline in cognitive function, but this relationship has not been examined in adults with chronic kidney disease (CKD). We investigated the association between incident AF and changes in cognitive function over time in this population.Methods and resultsWe studied a subgroup of 3254 adults participating in the Chronic Renal Insufficiency Cohort Study. Incident AF was ascertained by 12-lead electrocardiogram (ECG) obtained at a study visit and/or identification of a hospitalization with AF during follow-up. Cognitive function was assessed biennially using the Modified Mini-Mental State Exam. Linear mixed effects regression was used to evaluate the association between incident AF and longitudinal change in cognitive function. Compared with individuals without incident AF (n= 3158), those with incident AF (n= 96) were older, had a higher prevalence of cardiovascular disease and hypertension, and lower estimated glomerular filtration rate. After median follow-up of 6.8 years, we observed no significant multivariable association between incident AF and change in cognitive function test score.ConclusionIn this cohort of adults with CKD, incident AF was not associated with a decline in cognitive function.

Acute kidney injury (AKI) has been reported to be associated with excess risks of death, kidney disease progression and cardiovascular events although previous studies have important limitations. To further examine this, we prospectively studied adults from four clinical centers surviving three months and more after hospitalization with or without AKI who were matched on center, pre-admission CKD status, and an integrated priority score based on age, prior cardiovascular disease or diabetes mellitus, preadmission estimated glomerular filtration rate (eGFR) and treatment in the intensive care unit during the index hospitalization between December 2009-February 2015, with follow-up through November 2018. All participants had assessments of kidney function before (eGFR) and at three months and annually (eGFR and proteinuria) after the index hospitalization. Associations of AKI with outcomes were examined after accounting for pre-admission and three-month post-discharge factors. Among 769 AKI (73% Stage 1, 14% Stage 2, 13% Stage 3) and 769 matched non-AKI adults, AKI was associated with higher adjusted rates of incident CKD (adjusted hazard ratio 3.98, 95% confidence interval 2.51-6.31), CKD progression (2.37,1.28-4.39), heart failure events (1.68, 1.22-2.31) and all-cause death (1.78, 1.24-2.56). AKI was not associated with major atherosclerotic cardiovascular events in multivariable analysis (0.95, 0.70-1.28). After accounting for degree of kidney function recovery and proteinuria at three months after discharge, the associations of AKI with heart failure (1.13, 0.80-1.61) and death (1.29, 0.84-1.98) were attenuated and no longer significant. Thus, assessing kidney function recovery and proteinuria status three months after AKI provides important prognostic information for long-term clinical outcomes.

Additional file 1.

Rationale & objectivesFew studies have investigated racial disparities in survival among dialysis patients in a manner that considers risk factors and mortality during the phase of kidney disease before maintenance dialysis. Our objective was to explore racial variations in survival among dialysis patients and relate them to racial differences in comorbid conditions and rates of death in the setting of kidney disease not yet requiring dialysis therapy.Study designRetrospective cohort study.Settings & participants3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment.ExposureRace.OutcomeMortality.Analytic approachCox proportional hazards regression was used to examine the association between race and mortality starting at: (1) time of dialysis initiation and (2) entry into the CRIC.ResultsDuring 7.1 years of median follow-up, 678 CRIC participants started dialysis. Starting from the time of dialysis initiation, blacks had lower risk for death (unadjusted HR, 0.67; 95% CI, 0.51-0.87) compared with whites. Starting from baseline CRIC enrollment, the strength of the association between some risk factors and dialysis was notably stronger for whites than blacks. For example, the HR for dialysis onset in the presence (vs absence) of heart failure at CRIC enrollment was 1.30 (95% CI, 1.01-1.68) for blacks versus 2.78 (95% CI, 1.90-4.50) for whites, suggesting differential severity of these risk factors by race. When we included deaths occurring both before and after dialysis, risk for death was higher among blacks (vs whites) starting from CRIC enrollment (HR, 1.41; 95% CI, 1.22-1.64), but this finding was attenuated in adjusted models (HR, 1.08; 95% CI, 0.91-1.28).LimitationsResidual confounding.ConclusionsThe apparent survival advantage among blacks over whites treated with dialysis may be attributed to selected transition of a subset of whites with more severe comorbid conditions onto dialysis.

Background:Observational studies relying on clinically obtained data have shown that acute kidney injury (AKI) is linked to accelerated chronic kidney disease (CKD) progression. However, prior reports lacked uniform collection of important confounders such as proteinuria and pre-AKI kidney function trajectory, and may be susceptible to ascertainment bias, as patients may be more likely to undergo kidney function testing after AKI. Methods:We studied 444 adults with CKD who participated in the prospective Chronic Renal Insufficiency Cohort (CRIC) Study and were concurrent members of a large integrated healthcare delivery system. We estimated glomerular filtration rate (eGFR) trajectories using serum creatinine measurements from (i) the CRIC research protocol (yearly) and (ii) routine clinical care. We used linear mixed effects models to evaluate the associations of AKI with acute absolute change in eGFR and post-AKI eGFR slope, and explored whether these varied by source of creatinine results. Models were adjusted for demographic characteristics, diabetes status and albuminuria. Results:During median follow-up of 8.5 years, mean rate of eGFR loss was -0.31 mL/min/1.73m2/year overall, and 73 individuals experienced AKI (55% Stage 1). A significant interaction existed between AKI and source of serum creatinine for acute absolute change in eGFR level after discharge; in contrast, AKI was independently associated with a faster rate of eGFR decline (mean additional loss of -0.67 mL/min/1.73m2/year), which was not impacted by source of serum creatinine. Conclusions:AKI is independently associated with subsequent steeper eGFR decline regardless of the serum creatinine source used, but the strength of association is smaller than observed in prior studies after taking into account key confounders such as pre-AKI eGFR slope and albuminuria.

BACKGROUND:Few studies describe both inpatient and outpatient treatment and outcomes of patients with acute venous thromboembolism in the United States. METHODS:A multi-institutional cohort of patients diagnosed with confirmed pulmonary embolism or deep venous thrombosis during the years 2004 through 2010 was established from 4 large, US-based integrated health care delivery systems. Computerized databases were accessed and medical records reviewed to collect information on patient demographics, clinical risk factors, initial antithrombotic treatment, and vital status. Multivariable Cox regression models were used to estimate the risk of death at 90 days. RESULTS:The cohort comprised 5497 adults with acute venous thromboembolism. Pulmonary embolism was predominantly managed in the hospital setting (95.0%), while 54.5% of patients with lower extremity thrombosis were treated as outpatients. Anticoagulant treatment differed according to thromboembolism type: 2688 patients (92.8%) with pulmonary embolism and 1625 patients (86.9%) with lower extremity thrombosis were discharged on anticoagulants, compared with 286 patients (80.1%) with upper extremity thrombosis and 69 (54.8%) patients with other thrombosis. While 4.5% of patients died during the index episode, 15.4% died within 90 days. Pulmonary embolism was associated with a higher 90-day death risk than lower extremity thrombosis (adjusted hazard ratio 1.23; 95% confidence interval, 1.04-1.47), as was not being discharged on anticoagulants (adjusted hazard ratio 5.56; 95% confidence interval, 4.76-6.67). CONCLUSIONS:In this multicenter, community-based study of patients with acute venous thromboembolism, anticoagulant treatment and outcomes varied by thromboembolism type. Although case fatality during the acute episode was relatively low, 15.4% of people with thromboembolism died within 90 days of the index diagnosis.

Background We tested associations of cardiac biomarkers of myocardial stretch, injury, inflammation, and fibrosis with the risk of incident atrial fibrillation (AF) in a prospective study of chronic kidney disease patients. Methods and Results The study sample was 3053 participants with chronic kidney disease in the multicenter CRIC (Chronic Renal Insufficiency Cohort) study who were not identified as having AF at baseline. Cardiac biomarkers, measured at baseline, were NT-proBNP (N-terminal pro-B-type natriuretic peptide), high-sensitivity troponin T, galectin-3, growth differentiation factor-15, and soluble ST-2. Incident AF ("AF event") was defined as a hospitalization for AF. During a median follow-up of 8years, 279 (9%) participants developed a new AF event. In adjusted models, higher baseline log-transformed NT-proBNP (N-terminal pro-B-type natriuretic peptide) was associated with incident AF (adjusted hazard ratio [HR] per SD higher concentration: 2.11; 95% CI, 1.75, 2.55), as was log-high-sensitivity troponin T (HR 1.42; 95% CI, 1.20, 1.68). These associations showed a dose-response relationship in categorical analyses. Although log-soluble ST-2 was associated with AF risk in continuous models (HR per SD higher concentration 1.35; 95% CI, 1.16, 1.58), this association was not consistent in categorical analyses. Log-galectin-3 (HR 1.05; 95% CI, 0.91, 1.22) and log-growth differentiation factor-15 (HR 1.16; 95% CI, 0.96, 1.40) were not significantly associated with incident AF. Conclusions We found strong associations between higher NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity troponin T concentrations, and the risk of incident AF in a large cohort of participants with chronic kidney disease. Increased atrial myocardial stretch and myocardial cell injury may be implicated in the high burden of AF in patients with chronic kidney disease.

RATIONALE & OBJECTIVE:Coronary artery calcification (CAC) is prevalent among patients with chronic kidney disease (CKD) and increases risks for cardiovascular disease events and mortality. We hypothesized that a novel serum measure of calcification propensity is associated with CAC among patients with CKD stages 2 to4. STUDY DESIGN:Prospective cohort study. SETTING & PARTICIPANTS:Participants from the Chronic Renal Insufficiency Cohort (CRIC) Study with baseline (n=1,274) and follow-up (n=780) CAC measurements. PREDICTORS:Calcification propensity, quantified as transformation time (T50) from primary to secondary calciprotein particles, with lower T50 corresponding to higher calcification propensity. Covariates included age, sex, race/ethnicity, clinical site, estimated glomerular filtration rate, proteinuria, diabetes, systolic blood pressure, number of antihypertensive medications, current smoking, history of cardiovascular disease, total cholesterol level, and use of statin medications. OUTCOMES:CAC prevalence, severity, incidence, and progression. ANALYTICAL APPROACH:Multivariable-adjusted generalized linear models. RESULTS:At baseline, 824 (65%) participants had prevalent CAC. After multivariable adjustment, T50 was not associated with CAC prevalence but was significantly associated with greater CAC severity among participants with prevalent CAC: 1-SD lower T50 was associated with 21% (95% CI, 6%-38%) greater CAC severity. Among 780 participants followed up an average of 3 years later, 65 (20%) without baseline CAC developed incident CAC, while 89 (19%) with baseline CAC had progression, defined as annual increase≥100 Agatston units. After multivariable adjustment, T50 was not associated with incident CAC but was significantly associated with CAC progression: 1-SD lower T50 was associated with 28% (95% CI, 7%-53%) higher risk for CAC progression. LIMITATIONS:Potential selection bias in follow-up analyses; inability to distinguish intimal from medial calcification. CONCLUSIONS:Among patients with CKD stages 2 to 4, higher serum calcification propensity is associated with more severe CAC and CAC progression.

Background Patient satisfaction with therapy is an important metric of care quality and has been associated with greater medication persistence. We evaluated the association of patient satisfaction with warfarin therapy to other metrics of anticoagulation care quality and clinical outcomes among patients with atrial fibrillation ( AF ). Methods and Results Using data from the ORBIT - AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) registry, patients were identified with AF who were taking warfarin and had completed an Anti-Clot Treatment Scale ( ACTS ) questionnaire, a validated metric of patient-reported burden and benefit of oral anticoagulation. Multivariate regressions were used to determine association of ACTS burden and benefit scores with time in therapeutic international normalized ratio range ( TTR ; both ≥75% and ≥60%), warfarin discontinuation, and clinical outcomes (death, stroke, major bleed, and all-cause hospitalization). Among 1514 patients with AF on warfarin therapy (75±10 years; 42% women; CHA 2 DS 2- VAS c 3.9±1.7), those most burdened with warfarin therapy were younger and more likely to be women, have paroxysmal AF , and to be treated with antiarrhythmic drugs. After adjustment for covariates, ACTS burden scores were independent of TTR ( TTR ≥75%: odds ratio, 1.01 [95% CI , 0.99-1.03]; TTR ≥60%: odds ratio, 1.01 [95% CI , 0.98-1.05]), warfarin discontinuation (odds ratio, 0.99; 95% CI , 0.97-1.01), or clinical outcomes. ACTS benefit scores were also not associated with TTR , warfarin discontinuation, or clinical outcomes. Conclusions In a large registry of patients with AF taking warfarin, ACTS scores provided independent information beyond other traditional metrics of oral anticoagulation care quality and identified patient groups at high risk for dissatisfaction with warfarin therapy.

RATIONALE & OBJECTIVE:Traditional risk estimates for atherosclerotic vascular disease (ASVD) and death may not perform optimally in the setting of chronic kidney disease (CKD). We sought to determine whether the addition of measures of inflammation and kidney function to traditional estimation tools improves prediction of these events in a diverse cohort of patients with CKD. STUDY DESIGN:Observational cohort study. SETTING & PARTICIPANTS:2,399 Chronic Renal Insufficiency Cohort (CRIC) Study participants without a history of cardiovascular disease at study entry. PREDICTORS:Baseline plasma levels of biomarkers of inflammation (interleukin 1β [IL-1β], IL-1 receptor antagonist, IL-6, tumor necrosis factor α [TNF-α], transforming growth factor β, high-sensitivity C-reactive protein, fibrinogen, and serum albumin), measures of kidney function (estimated glomerular filtration rate [eGFR] and albuminuria), and the Pooled Cohort Equation probability (PCEP) estimate. OUTCOMES:Composite of ASVD events (incident myocardial infarction, peripheral arterial disease, and stroke) and death. ANALYTICAL APPROACH:Cox proportional hazard models adjusted for PCEP estimates, albuminuria, and eGFR. RESULTS:During a median follow-up of 7.3 years, 86, 61, 48, and 323 participants experienced myocardial infarction, peripheral arterial disease, stroke, or death, respectively. The 1-decile greater levels of IL-6 (adjusted HR [aHR], 1.12; 95% CI, 1.08-1.16; P

BACKGROUND:Advanced chronic kidney disease is associated with elevated risk for cognitive impairment. However, it is not known whether and how cognitive impairment is associated with planning and preparation for end-stage renal disease. STUDY DESIGN:Retrospective observational study. SETTING & PARTICIPANTS:630 adults participating in the CRIC (Chronic Renal Insufficiency Cohort) Study who had cognitive assessments in late-stage CKD, defined as estimated glome-rular filtration rate≤ 20mL/min/1.73m2, and subsequently initiated maintenance dialysis therapy. PREDICTOR:Predialysis cognitive impairment, defined as a score on the Modified Mini-Mental State Examination lower than previously derived age-based threshold scores. Covariates included age, race/ethnicity, educational attainment, comorbid conditions, and health literacy. OUTCOMES:Peritoneal dialysis (PD) as first dialysis modality, preemptive permanent access placement, venous catheter avoidance at dialysis therapy initiation, and preemptive wait-listing for a kidney transplant. MEASUREMENTS:Multivariable-adjusted logistic regression. RESULTS:Predialysis cognitive impairment was present in 117 (19%) participants. PD was thefirst dialysis modality among 16% of participants (n=100), 75% had preemptive access placed (n=473), 45% avoided using a venous catheter at dialysis therapy initiation (n=279), and 20%were preemptively wait-listed (n=126).Predialysis cognitive impairment wasindependently associated with 78% lower odds of PD as the first dialysis modality (adjusted OR [aOR], 0.22; 95% CI, 0.06-0.74; P=0.02) and 42% lower odds of venous catheter avoidance at dialysis therapy initiation (aOR, 0.58; 95% CI, 0.34-0.98; P=0.04). Predialysis cognitive impairment was not independently associated with preemptive permanent access placement or wait-listing. LIMITATIONS:Potential unmeasured confounders; single measure of cognitive function. CONCLUSIONS:Predialysis cognitive impairment is associated with a lower likelihood of PD as a first dialysis modality and of venous catheter avoidance at dialysis therapy initiation. Future studies may consider addressing cognitive function when testing strategies to improve patient transitions to dialysis therapy.

Rationale & objectiveAbnormal cardiac structure and function are common in chronic kidney disease (CKD) and end-stage renal disease (ESRD) and linked with mortality and heart failure. We examined changes in echocardiographic measures during the transition from CKD to ESRD and their associations with post-ESRD mortality.Study designProspective study.Setting & participantsWe studied 417 participants with CKD in the Chronic Renal Insufficiency Cohort (CRIC) who had research echocardiograms during CKD and ESRD.PredictorWe measured change in left ventricular mass index, left ventricular ejection fraction (LVEF), diastolic relaxation (normal, mildly abnormal, and moderately/severely abnormal), left ventricular end-systolic (LVESV), end-diastolic (LVEDV) volume, and left atrial volume from CKD to ESRD.OutcomesAll-cause mortality after dialysis therapy initiation.Analytical approachCox proportional hazard models were used to test the association of change in each echocardiographic measure with postdialysis mortality.ResultsOver a mean of 2.9 years between pre-and postdialysis echocardiograms, there was worsening of mean LVEF (52.5% to 48.6%; P

Background Current American College of Cardiology/American Heart Association guidelines suggest that for patients with atrial fibrillation who are at low risk for stroke (CHA2DS2VASc=1) (or women with CHA2DS2VASc=2) a variety of treatment strategies may be considered. However, in clinical practice, patterns of treatment in these "low-risk" patients are not well described. The objective of this analysis is to define thromboembolic event rates and to describe treatment patterns in patients with low-risk CHA2DS2VASc scores. Methods and Results We compared characteristics, treatment strategies, and outcomes among patients with a CHA2DS2VASc=0, CHA2DS2VASc=1, females with a CHA2DS2VASc=2, and CHA2DS2VASc ≥2 in ORBIT-AF (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation) I & II. Compared with CHA2DS2VASc ≥2 patients (84.2%), those with a CHA2DS2VASc=0 (60.3%), 1 (69.9%), and females with a CHA2DS2VASc score=2 (72.4%) were significantly less often treated with oral anticoagulation ( P

BackgroundFew studies have investigated the changes in weight that may occur over time among adults with the progression of chronic kidney disease (CKD). Whether such weight changes are independently associated with death after the onset of end-stage renal disease has also not been rigorously examined.Study designProspective cohort study.Setting & participantsWe studied 3,933 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a longitudinal cohort of patients with CKD. We also performed similar analyses among 1,067 participants of the African American Study of Kidney Disease and Hypertension (AASK).PredictorsEstimated glomerular filtration rate (eGFR) and weight change during CKD.OutcomeWeight and all-cause mortality after dialysis therapy initiation.ResultsDuring a median follow-up of 5.7 years in CRIC, weight change was not linear. Weight was stable until cystatin C-based eGFR (eGFRcys) decreased to5% annualized weight loss after eGFR decreased to&nbsp

Renal recovery after dialysis-requiring acute kidney injury (AKI-D) is an important clinical and patient-centered outcome. Here we examined whether the pre-admission proteinuria level independently influences risk for non-recovery after AKI-D in a community-based population. All adult members of Kaiser Permanente Northern California who experienced AKI-D between January 1, 2009 and September 30, 2015 were included. Pre-admission proteinuria levels were determined by dipstick up to four years before the AKI-D hospitalization and the outcome was renal recovery (survival and dialysis-independence four weeks and more) at 90 days after initiation of renal replacement therapy. We used multivariable logistic regression to adjust for baseline estimated glomerular filtration rate (eGFR), age, sex, ethnicity, short-term predicted risk of death, comorbidities, and medication use. Among 5,347 adults with AKI-D, the mean age was 66 years, 59% were men, and 50% were white. Compared with negative/trace proteinuria, the adjusted odds ratios for non-recovery (continued dialysis-dependence or death) were 1.47 (95% confidence interval 1.19-1.82) for 1+proteinuria and 1.92 (1.54-2.38) for 2+ or more proteinuria. Among survivors, the crude probability of recovery ranged from 83% for negative/trace proteinuria with baseline eGFR over 60 mL/min/1.73m2 to 25% for 2+ or more proteinuria with eGFR 15-29 mL/min/1.73m2. Thus, the pre-AKI-D level of proteinuria is a graded, independent risk factor for non-recovery and helps to improve short-term risk stratification for patients with AKI-D.

BACKGROUND AND AIMS:Coronary artery calcification (CAC) is common among patients with chronic kidney disease (CKD) and predicts the risk for cardiovascular disease (CVD). We examined the associations of novel risk factors with CAC progression among patients with CKD. METHODS:Among 1123 CKD patients in the Chronic Renal Insufficiency Cohort (CRIC) Study, CAC was measured in Agatston units at baseline and a follow-up visit using electron beam computed tomography or multidetector computed tomography. RESULTS:Over an average 3.3-year follow-up, 109 (25.1%) participants without CAC at baseline had incident CAC and 124 (18.0%) participants with CAC at baseline had CAC progression, defined as an annual increase of ≥100 Agatston units. After adjustment for established atherosclerotic risk factors, several novel risk factors were associated with changes in CAC over follow-up. Changes in square root transformed CAC score associated with 1 SD greater level of risk factors were-0.20 (95% confidence interval,-0.31 to-0.10; p < 0.001) for estimated glomerular filtration rate, 0.14 (0.02-0.25; p = 0.02) for 24-h urine albumin, 0.25 (0.15-0.34; p < 0.001) for cystatin C,-0.17 (-0.27 to-0.07; p < 0.001) for serum calcium, 0.14 (0.03-0.24; p = 0.009) for serum phosphate, 0.24 (0.14-0.33; p < 0.001) for fibroblast growth factor-23, 0.13 (0.04-0.23; p = 0.007) for total parathyroid hormone, 0.17 (0.07-0.27; p < 0.001) for interleukin-6, and 0.12 (0.02-0.22; p = 0.02) for tumor necrosis factor-α. CONCLUSIONS:Reduced kidney function, calcium and phosphate metabolism disorders, and inflammation, independent of established CVD risk factors, may progress CAC among CKD patients.

OBJECTIVES: To determine the efficacy and safety of statins for primary prevention of atherosclerotic cardiovascular disease (ASCVD) events in older adults, especially those aged 80 and older and with multimorbidity. METHODS: The National Institute on Aging and the National Heart, Lung and Blood Institute convened A multidisciplinary expert panel from July 31 to August 1, 2017, to review existing evidence, identify knowledge gaps, and consider whether statin safety and efficacy data in persons aged 75 and older without ASCVD are sufficient; whether existing data can inform the feasibility, design, and implementation of future statin trials in older adults; and clinical trial options and designs to address knowledge gaps. This article summarizes the presentations and discussions at that workshop. RESULTS: There is insufficient evidence regarding the benefits and harms of statins in older adults, especially those with concomitant frailty, polypharmacy, comorbidities, and cognitive impairment; a lack of tools to assess ASCVD risk in those aged 80 and older; and a paucity of evidence of the effect of statins on outcomes of importance to older adults, such as statin-associated muscle symptoms, cognitive function, and incident diabetes mellitus. Prospective, traditional, placebo-controlled, randomized clinical trials (RCTs) and pragmatic RCTs seem to be suitable options to address these critical knowledge gaps. Future trials have to consider greater representation of very old adults, women, underrepresented minorities, and individuals of differing health, cognitive, socioeconomic, and educational backgrounds. Feasibility analyses from existing large healthcare networks confirm appropriate power for death and cardiovascular outcomes for future RCTs in this area. CONCLUSION: Existing data cannot address uncertainties about the benefits and harms of statins for primary ASCVD prevention in adults aged 75 and older, especially those with comorbidities, frailty, and cognitive impairment. Evidence from 1 or more RCTs could address these important knowledge gaps to inform person-centered decision-making.

BackgroundOral anticoagulation (OAC) therapy is associated with increased periprocedural risks after cardiac implantable electronic device (CIED) implantation. Patterns of anticoagulation management involving non-vitamin K antagonist oral anticoagulants (NOACs) have not been characterized.HypothesisAnticoagulation strategies and outcomes differ by anticoagulant type in patients undergoing CIED implantation.MethodsUsing the nationwide Outcomes Registry for Better Informed Treatment of Atrial Fibrillation, we assessed how atrial fibrillation (AF) patients undergoing CIED implantation were cared for and their subsequent outcomes. Outcomes were compared by oral anticoagulant therapy (none, warfarin, or NOAC) as well as by anticoagulation interruption status.ResultsAmong 9129 AF patients, 416 (5%) underwent CIED implantation during a median follow-up of 30 months (interquartile range, 24-36). Of these, 60 (14%) had implantation on a NOAC. Relative to warfarin therapy, those on a NOAC were younger (70.5 years [range, 65-77.5 years] vs 77 years [range, 70-82 years]), had less valvular heart disease (15.0% vs 31.3%), higher creatinine clearance (67.3 [range, 59.7-99.0] vs 65.8 [range, 50.0-91.6]), were more likely to have persistent AF (26.7% vs 22.9%), and use concomitant aspirin (51.7% vs 35.2%). OAC therapy was commonly interrupted for CIED in 64% (n = 183 of 284) of warfarin patients and 65% (n = 39 of 60) of NOAC patients. Many interrupted patients received intravenous bridging anticoagulation: 33/183 (18%) interrupted warfarin and 4/39 (10%) interrupted NOAC patients. Thirty-day periprocedure bleeding and stroke adverse events were infrequent.ConclusionsManagement of anticoagulation among AF patients undergoing CIED implantation is highly variable, with OAC being interrupted in more than half of both warfarin- and NOAC-treated patients. Bleeding and stroke events were infrequent in both warfarin and NOAC-treated patients.

We recently reported a linear association between higher systolic blood pressure (SBP) and risk of mortality in hemodialysis patients when SBP is measured outside of the dialysis unit (out-of-dialysis-unit-SBP), despite there being a U-shaped association between SBP measured at the dialysis unit (dialysis-unit-SBP) with risk of mortality. Here, we explored the relationship between SBP with cardiovascular events, which has important treatment implications but has not been well elucidated. Among 383 hemodialysis participants enrolled in the prospective CRIC study (Chronic Renal Insufficiency Cohort), multivariable splines and Cox models were used to study the association between SBP and adjudicated cardiovascular events (heart failure, myocardial infarction, ischemic stroke, and peripheral artery disease), controlling for differences in demographics, cardiovascular disease risk factors, and dialysis parameters. Dialysis-unit-SBP and out-of-dialysis-unit-SBP were modestly correlated (r=0.34; P2-fold increased risk of cardiovascular events compared with those with out-of-dialysis-unit-SBP ≤112 mm Hg (3rd SBP quartile: adjusted hazard ratio, 2.08 [95% confidence interval, 1.12-3.87] and fourth SBP quartile: adjusted hazard ratio, 2.76 [95% confidence interval, 1.42-5.33]). In conclusion, among hemodialysis patients, although there is a U-shaped (paradoxical) association of dialysis-unit-SBP and risk of cardiovascular disease, there is a linear association of out-of-dialysis-unit-SBP with risk of cardiovascular disease. Out-of-dialysis-unit blood pressure provides key information and may be an important therapeutic target.

The association of dialysis initiation with changes in cognitive function among patients with advanced chronic kidney disease is poorly described. To better define this, weenrolled participants with advanced chronic kidney disease from the Chronic Renal Insufficiency Cohort inaprospective study of cognitive function. Eligible participants had a glomerular filtration rate of 20ml/min/1.73m2 or less, or dialysis initiation within thepast two years. We evaluated cognitive function by avalidated telephone battery at regular intervals over twoyears and analyzed test scores as z scores. Of 212 participants, 123 did not transition to dialysis during follow-up, 37 transitioned to dialysis after baseline, and 52transitioned to dialysis prior to baseline. In adjusted analyses, the transition to dialysis was associated with a significant loss of executive function, but no significant changes in global cognition or memory. The estimated netdifference in cognitive z scores at two years for participants who transitioned to dialysis during follow-up compared to participants who did not transition to dialysis was -0.01 (95% confidence interval -0.13, 0.11) for global cognition, -0.24 (-0.51, 0.03) for memory, and -0.33 (-0.60,-0.07) for executive function. Thus, among adults with advanced chronic kidney disease, dialysis initiation was associated with loss of executive function with no change in other aspects of cognition. Larger studies are needed to evaluate cognition during dialysis initiation.

IntroductionChronic kidney disease (CKD) is associated with an increased risk of cognitive decline, but the mechanisms remain poorly defined. We sought to determine the relation between serum inflammatory markers and risk of cognitive decline among adults with CKD.MethodsWe studied 757 adults aged ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort Cognitive study. We measured interleukin (IL)-1β, IL-1 receptor antagonist, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hs-CRP), and fibrinogen in baseline plasma samples. We assessed cognitive function at regular intervals in 4 domains and defined incident impairment as a follow-up score more than 1 SD poorer than the group mean.ResultsThe mean age of the sample was 64.3 ± 5.6 years, and the mean follow-up was 6.2 ± 2.5 years. At baseline, higher levels of each inflammatory marker were associated with poorer age-adjusted performance. In analyses adjusted for baseline cognition, demographics, comorbid conditions, and kidney function, participants in the highest tertile of hs-CRP, the highest tertile of fibrinogen, and the highest tertile of IL-1β had an increased risk of impairment in attention compared to participants in the lowest tertile of each marker. Participants in the highest versus lowest tertile of TNF-α had a lower adjusted risk of impairment in executive function. There was no association between other inflammatory markers and change in cognitive function.DiscussionAmong adults with CKD, higher levels of hs-CRP, fibrinogen, and IL-1β were associated with a higher risk of impairment in attention. Higher levels of TNF-α were associated with a lower risk of impaired executive function.

Blood pressure is a modifiable risk for cardiovascular disease (CVD). Among hemodialysis patients, there is a U-shaped association between blood pressure and risk of death. However, few studies have examined the association between blood pressure and CVD in patients with stage 4 and 5 chronic kidney disease. Here we studied 1795 Chronic Renal Insufficiency Cohort (CRIC) Study participants with estimated glomerular filtration rate90 mmHg versus68 mmHg versus68 mmHg versus&nbsp

BackgroundIt is not clear whether the pattern of kidney function decline in patients with chronic kidney disease (CKD) may relate to outcomes after reaching end-stage renal disease (ESRD). We hypothesize that an abrupt decline in kidney function prior to ESRD predicts early death after initiating maintenance hemodialysis therapy.Study designProspective cohort study.Setting & participantsThe Chronic Renal Insufficiency Cohort (CRIC) Study enrolled men and women with mild to moderate CKD. For this study, we studied 661 individuals who developed chronic kidney failure that required hemodialysis therapy initiation.PredictorsThe primary predictor was the presence of an abrupt decline in kidney function prior to ESRD. We incorporated annual estimated glomerular filtration rates (eGFRs) into a mixed-effects model to estimate patient-specific eGFRs at 3 months prior to initiation of hemodialysis therapy. Abrupt decline was defined as having an extrapolated eGFR≥30mL/min/1.73m(2) at that time point.OutcomesAll-cause mortality within 1 year after initiating hemodialysis therapy.MeasurementsMultivariable Cox proportional hazards.ResultsAmong 661 patients with CKD initiating hemodialysis therapy, 56 (8.5%) had an abrupt predialysis decline in kidney function and 69 died within 1 year after initiating hemodialysis therapy. After adjustment for demographics, cardiovascular disease, diabetes, and cancer, abrupt decline in kidney function was associated with a 3-fold higher risk for death within the first year of ESRD (adjusted HR, 3.09; 95% CI, 1.65-5.76).LimitationsRelatively small number of outcomes; infrequent (yearly) eGFR determinations; lack of more granular clinical data.ConclusionsAbrupt decline in kidney function prior to ESRD occurred in a significant minority of incident hemodialysis patients and predicted early death in ESRD.

Background The clinical implications of ankle‐brachial index ( ABI ) cutpoints are not well defined in patients with chronic kidney disease ( CKD ) despite increased prevalence of high ABI attributed to arterial stiffness. We examined the relationship of ABI with cardiovascular disease ( CVD ) and all‐cause mortality among CKD patients. Methods and Results Three thousand six hundred twenty‐seven participants without clinical peripheral artery disease ( PAD ) at baseline from the Chronic Renal Insufficiency Cohort Study were included. ABI was obtained per standard protocol and CVD events were confirmed by medical record adjudication. A U‐shaped association of ABI with PAD , myocardial infarction ( MI ), composite CVD , and all‐cause mortality was observed. Individuals with an ABI between 1.0 and ABI between 1.0 and ABI of PAD ; 1.67 (1.23, 2.29), 1.85 (1.33, 2.57), and 2.08 (1.10, 3.93) for MI ; 1.51 (1.27, 1.79), 1.39 (1.15, 1.68), and 1.23 (0.82, 1.84) for composite CVD ; and 1.55 (1.28, 1.89), 1.36 (1.10, 1.69), and 1.00 (0.62, 1.62) for all‐cause mortality, respectively. Conclusions This study indicates that ABI PAD , MI , composite CVD , and all‐cause mortality whereas ABI ≥1.4 was related to clinical PAD . These findings suggest that ABI cutpoints of PAD and ABI CVD risk stratification should be further evaluated among CKD patients.

BackgroundDiagnosed diabetes mellitus (DM) is a consistently documented risk factor for ischemic stroke in patientswith atrial fibrillation (AF).ObjectivesThe purpose of this study was to assess the association between duration of diabetes and elevated hemoglobinA1c (HbA1c) with risk of stroke among diabetic patients with AF.MethodsWe assessed this association in the ATRIA (Anticoagulation and Risk Factors in Atrial Fibrillation) California community-based cohort of AF patients (study years 1996 to 2003) where all events were clinician adjudicated. We used Cox proportional hazards regression to estimate the rate of ischemic stroke in diabetic patients according to time-varying measures of estimated duration of diabetes (≥3 years compared with&nbsp

BackgroundCardiometabolic disease is a major cause of morbidity and mortality in persons with chronic kidney disease (CKD). Fractalkine (CX3CL1) is a potential mediator of both atherosclerosis and metabolic disease. Studies of the relationship of CX3CL1 with risk of cardiovascular disease (CVD) events and metabolic traits are lacking, particularly in the high-risk setting of CKD.Study designCross-sectional and longitudinal observational analysis.Setting & participantsAdults with CKD from 7 US sites participating in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorQuartiles of plasma CX3CL1 levels at baseline.OutcomesBaseline estimated glomerular filtration rate from a creatinine and cystatin C-based equation, prevalent and incident CVD, diabetes, metabolic syndrome and its criteria, homeostatic model assessment of insulin resistance, hemoglobin A1c level, myocardial infarction, all-cause mortality, and the composite outcome of myocardial infarction/all-cause mortality.ResultsAmong 3,687 participants, baseline CX3CL1 levels were associated positively with several CVD risk factors and metabolic traits, lower estimated glomerular filtration rate, and higher levels of inflammatory cytokines, as well as prevalent CVD (OR, 1.09; 95% CI, 1.01-1.19; P=0.03). Higher CX3CL1 level also was associated with prevalent diabetes (OR, 1.26; 95% CI, 1.16-1.38; P

BackgroundChronic kidney disease is a risk factor for heart failure (HF). Patients with chronic kidney disease without diagnosed HF have an increased burden of symptoms characteristic of HF. It is not known whether these symptoms are associated with occurrence of new onset HF.Methods and resultsWe studied the association of a modified Kansas City Cardiomyopathy Questionnaire with newly identified cases of hospitalized HF among 3093 participants enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study who did not report HF at baseline. The annually updated Kansas City Cardiomyopathy Questionnaire score was categorized into quartiles (Q1-4) with the lower scores representing the worse symptoms. Multivariable-adjusted repeated measure logistic regression models were adjusted for demographic characteristics, clinical risk factors for HF, N-terminal probrain natriuretic peptide level and left ventricular hypertrophy, left ventricular systolic and diastolic dysfunction. Over a mean (±SD) follow-up period of 4.3±1.6 years, there were 211 new cases of HF hospitalizations. The risk of HF hospitalization increased with increasing symptom quartiles; 2.62, 1.85, 1.14, and 0.74 events per 100 person-years, respectively. The median number of annual Kansas City Cardiomyopathy Questionnaire assessments per participant was 5 (interquartile range, 3-6). The annually updated Kansas City Cardiomyopathy Questionnaire score was independently associated with higher risk of incident HF hospitalization in multivariable-adjusted models (odds ratio, 3.30 [1.66-6.52]; P=0.001 for Q1 compared with Q4).ConclusionsSymptoms characteristic of HF are common in patients with chronic kidney disease and are associated with higher short-term risk for new hospitalization for HF, independent of level of kidney function, and other known HF risk factors.

BackgroundAlthough digoxin has long been used to treat atrial fibrillation (AF) and heart failure (HF), its safety remains controversial.ObjectivesThis study sought to describe digoxin use over time in patients with AF who were stratified by the presence or absence of HF, to characterize the predictors of digoxin use and initiation, and to correlate digoxin use with outcomes.MethodsLongitudinal patterns of digoxin use and its association with a variety of outcomes were assessed in a prospective outpatient registry conducted at 174 U.S. sites with enrollment from June 2010 to August 2011.ResultsAmong 9,619 patients with AF and serial follow-up every 6 months for up to 3 years, 2,267 (23.6%) received digoxin at study enrollment, 681 (7.1%) were initiated on digoxin during follow-up, and 6,671 (69.4%) were never prescribed digoxin. After adjusting for other medications, heart rate was 72.9 beats/min among digoxin users and 71.5 beats/min among nonusers (p < 0.0001). Prevalent digoxin use at registry enrollment was not associated with subsequent onset of symptoms, hospitalization, or mortality (in patients with HF, adjusted hazard ratio [HR] for death: 1.04; without HF, HR: 1.22). Incident digoxin use during follow-up was not associated with subsequent death in patients with HF (propensity adjusted HR: 1.05), but was associated with subsequent death in those without HF (propensity adjusted HR: 1.99).ConclusionsAfter adjustment for detailed clinical factors, digoxin use in registry patients with AF had a neutral association with outcomes under most circumstances. Because of the multiple conflicting observational reports about digoxin's safety and possible concerns in specific clinical situations, a large pragmatic trial of digoxin therapy in AF is needed.

Studies of hemodialysis patients have shown a U-shaped association between systolic blood pressure (SBP) and mortality. These studies have largely relied on dialysis-unit SBP measures and have not evaluated whether this U-shape also exists in advanced chronic kidney disease, before starting hemodialysis. We determined the association between SBP and mortality at advanced chronic kidney disease and again after initiation of hemodialysis. This was a prospective study of Chronic Renal Insufficiency Cohort participants with advanced chronic kidney disease followed through initiation of hemodialysis. We studied the association between SBP and mortality when participants (1) had an estimated glomerular filtration rate

Genome-wide association studies (GWAS) have identified more than 100 genetic variants contributing to BMI, a measure of body size, or waist-to-hip ratio (adjusted for BMI, WHRadjBMI), a measure of body shape. Body size and shape change as people grow older and these changes differ substantially between men and women. To systematically screen for age- and/or sex-specific effects of genetic variants on BMI and WHRadjBMI, we performed meta-analyses of 114 studies (up to 320,485 individuals of European descent) with genome-wide chip and/or Metabochip data by the Genetic Investigation of Anthropometric Traits (GIANT) Consortium. Each study tested the association of up to ~2.8M SNPs with BMI and WHRadjBMI in four strata (men ≤50y, men >50y, women ≤50y, women >50y) and summary statistics were combined in stratum-specific meta-analyses. We then screened for variants that showed age-specific effects (G x AGE), sex-specific effects (G x SEX) or age-specific effects that differed between men and women (G x AGE x SEX). For BMI, we identified 15 loci (11 previously established for main effects, four novel) that showed significant (FDR, Author Summary Adult body size and body shape differ substantially between men and women and change over time. More than 100 genetic variants that influence body mass index (measure of body size) or waist-to-hip ratio (measure of body shape) have been identified. While there is evidence that some genetic loci affect body shape differently in men than in women, little is known about whether genetic effects differ in older compared to younger adults, and whether such changes differ between men and women. Therefore, we conducted a systematic genome-wide search, including 114 studies (>320,000 individuals), to specifically identify genetic loci with age- and or sex-dependent effects on body size and shape. We identified 15 loci of which the effect on BMI was different in older compared to younger adults, whereas we found no evidence for loci with different effects in men compared to women. The opposite was seen for body shape as we identified 44 loci of which the effect on waist-to-hip ratio differed between men and women, but no difference between younger and older adults were observed. Our observations may provide new insights into the biology that underlies weight change with age or the sexual dimorphism of body shape.

Selective serotonin reuptake inhibitor (SSRI) medications have been linked to increased bleeding risk; however, the actual association among warfarin, SSRI exposure, and bleeding risk has not been well-established. We studied the AnTicoagulation and Risk factors In Atrial fibrillation cohort of 13,559 adults with atrial fibrillation, restricted to the 9,186 patients contributing follow-up time while taking warfarin. Exposure to SSRIs and tricyclic antidepressants (TCAs) was assessed from pharmacy database dispensing data. The main outcome was hospitalization for major hemorrhage. Results were adjusted for bleeding risk and time in international normalized ratio range >3. We identified 461 major hemorrhages during 32,888 person-years of follow-up, 45 events during SSRI use, 12 during TCA-only use, and 404 without either medication. Hemorrhage rates were higher during periods of SSRI exposure compared with periods on no antidepressants (2.32 per 100 person-years vs 1.35 per 100 person-years, p 3, SSRI exposure was associated with an increased rate of hemorrhage compared with no antidepressants (adjusted relative risk 1.41, 95% confidence interval 1.04 to 1.92, p= 0.03), whereas TCA exposure was not (adjusted relative risk 0.82, 95% confidence interval 0.46 to 1.46, p= 0.50). In conclusion, SSRI exposure was associated with higher major hemorrhage risk in patients taking warfarin, and this riskshould be considered when selecting antidepressant treatments in those patients.

BackgroundRecent clinical trials have demonstrated the safety and efficacy of several non-vitamin K oral anticoagulants (NOACs) for the treatment of atrial fibrillation (AF). However, there are limited data on their use and outcomes in routine clinical practice, particularly among patients newly diagnosed as having AF and patients with AF recently transitioned to a NOAC.Methods/designORBIT-AF II is a multicenter, national registry of patients with AF that is enrolling up to 15,000 newly diagnosed patients with AF and/or those with AF recently transitioned to a NOAC from 300 US outpatient practices. These patients will be followed for up to 2 years, including clinical status, outcomes (major adverse cardiovascular events, bleeding), and management of anticoagulation surrounding bleeding events. In addition, detailed data regarding the use of these agents in and around cardiac procedures, their complications, and management of such complications will be collected.ConclusionsThe ORBIT-AF II registry will provide valuable insights into the safety and effectiveness of NOACs used in AF in community practice settings.

BackgroundAtrial fibrillation (AF) is the most common cardiac dysrhythmia and contributes significantly to health care expenditures. We sought to assess the frequency and predictors of hospitalization in patients with AF.MethodsThe ORBIT-AF registry is a prospective, observational study of outpatients with AF enrolled from June 29, 2010, to August 9, 2011. The current analysis included 9,484 participants with 1-year follow-up. Multivariable, logistic regression was used to identify baseline characteristics that were associated with first cause-specific hospitalization.ResultsOverall, 31% of patients with AF studied (n = 2,963) had 1 or more hospitalizations per year and 10% (n = 983) had 2 or more. The most common hospitalization cause was cardiovascular (20 per 100 patient-years vs 3.3 bleeding vs 17 noncardiovascular, nonbleeding). Compared with those not hospitalized, hospitalized patients were more likely to have concomitant heart failure (42% vs 28%, P < .0001), higher mean CHADS2 (1 point for congestive heart failure, hypertension, age ≥75, or diabetes; 2 points for prior stroke or transient ischemic attack) scores (2.5 vs 2.2, P < .0001), and more symptoms (baseline European Heart Rhythm Association class severe symptoms 18% vs 13%, P < .0001). In multivariable analysis, heart failure (adjusted hazard ratio [HR] 1.57 for New York Heart Association III/IV vs none, P < .0001), heart rate at baseline (adjusted HR 1.11 per 10-beats/min increase >66, P < .0001), and AF symptom class (adjusted HR 1.37 for European Heart Rhythm Association severe vs none, P < .0001) were the major predictors of incident hospitalization.ConclusionsHospitalization is common in outpatients with AF and is independently predicted by heart failure and AF symptoms. Improved symptom control, rate control, and comorbid condition management should be evaluated as strategies to reduce health care use in these patients.

BackgroundPhysicians treating patients with atrial fibrillation (AF) must weigh the benefits of anticoagulation in preventing stroke versus the risk of bleeding. Although empirical models have been developed to predict such risks, the degree to which these coincide with clinicians' estimates is unclear.Methods and resultsWe examined 10 094 AF patients enrolled in the Outcomes Registry for Better Informed Treatment of AF (ORBIT-AF) registry between June 2010 and August 2011. Empirical stroke and bleeding risks were assessed by using the congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and previous stroke or transient ischemic attack (CHADS2) and Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) scores, respectively. Separately, physicians were asked to categorize their patients' stroke and bleeding risks: low risk (6%). Overall, 72% (n=7251) in ORBIT-AF had high-risk CHADS2 scores (≥2). However, only 16% were assessed as high stroke risk by physicians. Although 17% (n=1749) had high ATRIA bleeding risk (score ≥5), only 7% (n=719) were considered so by physicians. The associations between empirical and physician-estimated stroke and bleeding risks were low (weighted Kappa 0.1 and 0.11, respectively). Physicians weighed hypertension, heart failure, and diabetes mellitus less significantly than empirical models in estimating stroke risk; physicians weighted anemia and dialysis less significantly than empirical models when estimating bleeding risks. Anticoagulation use was highest among patients with high stroke risk, assessed by either empirical model or physician estimates. In contrast, physician and empirical estimates of bleeding had limited impact on treatment choice.ConclusionsThere is little agreement between provider-assessed risk and empirical scores in AF. These differences may explain, in part, the current divergence of anticoagulation treatment decisions from guideline recommendations.Clinical trial registration urlhttp://www.clinicaltrials.gov. Unique identifier: NCT01165710.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a critical resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best available national data on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, use of medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions. In 2012 alone, the various Statistical Updates were cited ≈3500 times (data from Google Scholar). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year. This year's edition includes a new chapter on peripheral artery disease, as well as new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update. © 2013 American Heart Association, Inc.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update. The Statistical Update is a critical resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best available national data on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, use of medical procedures and operations, and costs associated with the management of these diseases in a single document. Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions. In 2012 alone, the various Statistical Updates were cited ≈3500 times (data from Google Scholar). In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled. For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year. This year's edition includes a new chapter on peripheral artery disease, as well as new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals. Below are a few highlights from this year's Update. © 2013 American Heart Association, Inc.

BackgroundSerum cardiac troponin T (cTnT) is associated with increased risk of heart failure and cardiovascular death in several population settings. We evaluated associations of cTnT levels with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease (CKD) without heart failure.Study designCross-sectional.Setting & participantsChronic Renal Insufficiency Cohort (CRIC; N=3,243).PredictorThe primary predictor was cTnT level. Secondary predictors included demographic and clinical characteristics, hemoglobin level, high-sensitivity C-reactive protein level, and estimated glomerular filtration rate using cystatin C.OutcomesEchocardiography was used to determine left ventricular (LV) mass and LV systolic and diastolic function.MeasurementsCirculating cTnT was measured in stored sera using the highly sensitive assay. Logistic and linear regression models were used to examine associations of cTnT level with each echocardiographic outcome.ResultscTnT was detectable in 2,735 (84%) persons; median level was 13.3 (IQR, 7.7-23.8) pg/mL. Compared with undetectable cTnT (

We evaluated the cross-sectional associations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) with cardiac structural and functional abnormalities in a cohort of patients with chronic kidney disease without clinical heart failure, the Chronic Renal Insufficiency Cohort (n = 3,232). The associations of NT-proBNP with echocardiographically determined left ventricular (LV) mass and LV systolic and diastolic function were evaluated using multivariate logistic and linear regression models. Reclassification of participants' predicted risk of LV hypertrophy (LVH), systolic and diastolic dysfunction was performed using a category-free net reclassification improvement index that compared a clinical model with and without NT-proBNP. The median NT-proBNP was 126.6 pg/ml (interquartile range 55.5 to 303.7). The greatest quartile of NT-proBNP was associated with a nearly threefold odds of LVH (odds ratio 2.7, 95% confidence interval [CI] 1.8 to 4.0) and LV systolic dysfunction (odds ratio 2.7, 95% CI 1.7 to 4.5) and a twofold odds of diastolic dysfunction (odds ratio 2.0, 95% CI 1.3 to 2.9) in the fully adjusted models. When evaluated alone as a screening test, NT-proBNP functioned modestly for the detection of LVH (area under the curve 0.66) and LV systolic dysfunction (area under the curve 0.62) and poorly for the detection of diastolic dysfunction (area under the curve 0.51). However, when added to the clinical model, NT-proBNP significantly reclassified participants' likelihood of having LVH (net reclassification improvement 0.14, 95% CI 0.13-0.15; p

BackgroundRetinal microvascular abnormalities have been associated with cognitive impairment, possibly serving as a marker of cerebral small-vessel disease. This relationship has not been evaluated in persons with chronic kidney disease (CKD), a condition associated with increased risk of both retinal pathology and cognitive impairment.Study designCross-sectional study.Setting & participants588 participants 52 years or older with CKD in the Chronic Renal Insufficiency Cohort (CRIC) Study.PredictorRetinopathy graded using the Early Treatment Diabetic Retinopathy Study severity scale and diameters of retinal vessels.OutcomesNeuropsychological battery of 6 cognitive tests.MeasurementsLogistic regression models were used to evaluate the association of retinopathy, individual retinopathy features, and retinal vessel diameters with cognitive impairment (≤1 SD from the mean), and linear regression models were used to compare cognitive test scores across levels of retinopathy, adjusting for age, race, sex, education, and medical comorbid conditions.ResultsThe mean age of the cohort was 65.3±5.6 (SD) years, 51.9% were nonwhite, and 52.6% were men. The prevalence of retinopathy was 30.1%, and the prevalence of cognitive impairment was 14.3%. Compared with those without retinopathy, participants with retinopathy had an increased likelihood of cognitive impairment on executive function (35.1% vs 11.5%; OR, 3.4 [95% CI, 2.0-6.0]), attention (26.7% vs 7.3%; OR, 3.0 [95% CI, 1.8-4.9]), and naming (26.0% vs 10.0%; OR, 2.1 [95% CI, 1.2-3.4]) after multivariable adjustment. Increased level of retinopathy also was associated with lower cognitive performance on executive function and attention. Microaneurysms were associated with cognitive impairment on some domains, but there were no significant associations with other retinal measures after multivariable adjustment.LimitationsUnknown temporal relationship between retinopathy and impairment.ConclusionsIn adults with CKD, retinopathy is associated with poor performance on several cognitive domains, including executive function and attention. Evaluation of retinal microvascular abnormalities may be a promising tool for identifying patients with CKD who are at increased risk of cognitive impairment.

Each year, the American Heart Association (AHA), in conjunction with the Centers for Disease Control and Prevention, the National Institutes of Health, and other government agencies, brings together the most up-to-date statistics on heart disease, stroke, other vascular diseases, and their risk factors and presents them in its Heart Disease and Stroke Statistical Update*The Statistical Update is a valuable resource for researchers, clinicians, healthcare policy makers, media professionals, the lay public, and many others who seek the best national data available on heart disease, stroke, and other cardiovascular disease-related morbidity and mortality and the risks, quality of care, medical procedures and operations, and costs associated with the management of these diseases in a single document*Indeed, since 1999, the Statistical Update has been cited >10 500 times in the literature, based on citations of all annual versions*In 2011 alone, the various Statistical Updates were cited ≈1500 times (data from ISI Web of Science)*In recent years, the Statistical Update has undergone some major changes with the addition of new chapters and major updates across multiple areas, as well as increasing the number of ways to access and use the information assembled*For this year's edition, the Statistics Committee, which produces the document for the AHA, updated all of the current chapters with the most recent nationally representative data and inclusion of relevant articles from the literature over the past year*This year's edition also implements a new chapter organization to reflect the spectrum of cardiovascular health behaviors and health factors and risks, as well as subsequent complicating conditions, disease states, and outcomes*Also, the 2013 Statistical Update contains new data on the monitoring and benefits of cardiovascular health in the population, with additional new focus on evidence-based approaches to changing behaviors, implementation strategies, and implications of the AHA's 2020 Impact Goals*Below are a few highlights from this year's Update . © 2013 American Heart Association, Inc.