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Background: Protein carbamylation, a post-translational protein modification primarily driven by urea, independently associates with adverse clinical outcomes in patients with CKD. Biomarkers used to quantify carbamylation burden have mainly included carbamylated albumin (C-Alb) and homocitrulline (HCit, carbamylated lysine). In this study, we aimed to compare the prognostic utility of these two markers in order to facilitate comparisons of existing studies employing either marker alone, and to inform future carbamylation studies. Methods: Both serum C-Alb and free HCit levels were assayed from the same timepoint in 1632 individuals with CKD stages 2–4 enrolled in the prospective Chronic Renal Insufficiency Cohort (CRIC) study. Adjusted Cox proportional hazard models were used to assess risks for the outcomes of death (primary) and end stage kidney disease (ESKD) using each marker. C-statistics, net reclassification improvement, and integrated discrimination improvement were used to compare the prognostic value of each marker. Results: Participant demographics included mean (SD) age 59 (11) years; 702 (43%) females; 700 (43%) white. C-Alb and HCit levels were positively correlated with one another (Pearson correlation coefficient 0.64). Higher C-Alb and HCit levels showed similar increased risk of death (e.g., the adjusted hazard ratio [HR] for death in the 4th carbamylation quartile compared to the 1st was 1.90 (95% confidence interval [CI] 1.35–2.66) for C-Alb, and 1.89 [1.27–2.81] for HCit; and on a continuous scale, the adjusted HR for death using C-Alb was 1.24 [1.11 to 1.39] per standard deviation increase, and 1.27 [1.10–1.46] using HCit). Both biomarkers also had similar HRs for ESKD. The C-statistics were similar when adding each carbamylation biomarker to base models (e.g., for mortality models, the C-statistic was 0.725 [0.707–0.743] with C-Alb and 0.725 [0.707–0.743] with HCit, both compared to a base model 0.723). Similarities were also observed for the net reclassification improvement and integrated discrimination improvement metrics. Conclusions: C-Alb and HCit had similar performance across multiple prognostic assessments. The markers appear readily comparable in CKD epidemiological studies. [ABSTRACT FROM AUTHOR]

Background: There has recently been considerable interest in better understanding how blood pressure should be managed after an episode of hospitalized AKI, but there are scant data regarding the associations between blood pressure measured after AKI and subsequent adverse outcomes. We hypothesized that among AKI survivors, higher blood pressure measured three months after hospital discharge would be associated with worse outcomes. We also hypothesized these associations between blood pressure and outcomes would be similar among those who survived non-AKI hospitalizations.Methods: We quantified how systolic blood pressure (SBP) observed three months after hospital discharge was associated with risks of subsequent hospitalized AKI, loss of kidney function, mortality, and heart failure events among 769 patients in the prospective ASSESS-AKI cohort study who had hospitalized AKI. We repeated this analysis among the 769 matched non-AKI ASSESS-AKI enrollees. We then formally tested for AKI interaction in the full cohort of 1538 patients to determine if these associations differed among those who did and did not experience AKI during the index hospitalization.Results: Among 769 patients with AKI, 42 % had subsequent AKI, 13 % had loss of kidney function, 27 % died, and 18 % had heart failure events. SBP 3 months post-hospitalization did not have a stepwise association with the risk of subsequent AKI, loss of kidney function, mortality, or heart failure events. Among the 769 without AKI, there was also no stepwise association with these risks. In formal interaction testing using the full cohort of 1538 patients, hospitalized AKI did not modify the association between post-discharge SBP and subsequent risks of adverse clinical outcomes.Conclusions: Contrary to our first hypothesis, we did not observe that higher stepwise blood pressure measured three months after hospital discharge with AKI was associated with worse outcomes. Our data were consistent with our second hypothesis that the association between blood pressure measured three months after hospital discharge and outcomes among AKI survivors is similar to that observed among those who survived non-AKI hospitalizations. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) and obesity are independent risk factors for chronic kidney disease (CKD). This study aimed to determine if obesity modifies risk for CKD outcomes after AKI.Methods: This prospective multisite cohort study followed adult survivors after hospitalization, with or without AKI. The primary outcome was a combined CKD event of incident CKD, progression of CKD and kidney failure, examined using time-to-event Cox proportional hazards models, adjusted for diabetes status, age, pre-existing CKD, cardiovascular disease status and intensive care unit admission, and stratified by study center. Body mass index (BMI) was added as an interaction term to examine effect modification by body size.Results: The cohort included 769 participants with AKI and 769 matched controls. After median follow-up of 4.3 years, among AKI survivors, the rate of the combined CKD outcome was 84.7 per1000-person-years with BMI ≥30 kg/m2, 56.4 per 1000-person-years with BMI 25-29.9 kg/m2, and 72.6 per 1000-person-years with BMI 20-24.9 kg/m2. AKI was associated with a higher risk of combined CKD outcomes; adjusted-HR 2.43 (95%CI 1.87-3.16), with no evidence that this was modified by BMI (p for interaction = 0.3). After adjustment for competing risk of death, AKI remained associated with a higher risk of the combined CKD outcome (subdistribution-HR 2.27, 95%CI 1.76-2.92) and similarly, there was no detectable effect of BMI modifying this risk.Conclusions: In this post-hospitalization cohort, we found no evidence for obesity modifying the association between AKI and development or progression of CKD. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is an increasing epidemic globally that is associated with adverse health outcomes including end stage kidney disease (ESKD), cardiovascular disease (CVD), and death. American Indians (AIs) have a higher prevalence of CKD than most other racial/ethnic groups, due in part to a high prevalence of type 2 diabetes. Other genetic and environmental factors not yet identified may also contribute to the disproportionate burden of CKD in AIs.Method: We will establish 3 clinical centers to recruit AIs from the Southwest United States (US) to expand the Chronic Renal Insufficiency Cohort (CRIC) study. We will follow the current CRIC protocol for kidney and cardiovascular measures and outcomes, which include ambulatory monitoring of kidney function and the use of mobile health technologies for CVD sub-phenotyping, and compare the outcomes in AIs with those in other racial/ethnic groups in CRIC.Discussion: AI-CRIC will identify the role of various risk factors for rapid loss of kidney function among AIs of the Southwest US. In addition, to better understand the natural history of CKD and CVD in this high-risk population, we will identify unique risk factors for CKD and CVD progression in AIs. We will also compare event rates and risk factors for kidney and cardiovascular events in AIs with the other populations represented in CRIC. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) patients are routinely prescribed medications to prevent and treat complications, including those from common co-occurring comorbidities. However, adherence to such medications may be suboptimal. Therefore, we sought to identify risk factors for general medication non-adherence in a population of patients with atrial fibrillation.Methods: Data were collected from a large, ethnically-diverse cohort of Kaiser Permanente Northern and Southern California adult members with incident diagnosed AF between January 1, 2006 and June 30, 2009. Self-reported questionnaires were completed between May 1, 2010 and September 30, 2010, assessing patient socio-demographics, health behaviors, health status, medical history and medication adherence. Medication adherence was assessed using a previously validated 3-item questionnaire. Medication non-adherence was defined as either taking medication(s) as the doctor prescribed 75% of the time or less, or forgetting or choosing to skip one or more medication(s) once per week or more. Electronic health records were used to obtain additional data on medical history. Multivariable logistic regression analyses examined the associations between patient characteristics and self-reported general medication adherence among patients with complete questionnaire data.Results: Among 12,159 patients with complete questionnaire data, 6.3% (n = 771) reported medication non-adherence. Minority race/ethnicity versus non-Hispanic white, not married/with partner versus married/with partner, physical inactivity versus physically active, alcohol use versus no alcohol use, any days of self-reported poor physical health, mental health and/or sleep quality in the past 30 days versus 0 days, memory decline versus no memory decline, inadequate versus adequate health literacy, low-dose aspirin use versus no low-dose aspirin use, and diabetes mellitus were associated with higher adjusted odds of non-adherence, whereas, ages 65-84 years versus < 65 years of age, a Charlson Comorbidity Index score ≥ 3 versus 0, and hypertension were associated with lower adjusted odds of non-adherence.Conclusions: Several potentially preventable and/or modifiable risk factors related to medication non-adherence and a few non-modifiable risk factors were identified. These risk factors should be considered when assessing medication adherence among patients diagnosed with AF. [ABSTRACT FROM AUTHOR]

Background: The long-term downward national U.S. trend in heart disease-related mortality slowed substantially during 2011-2014 before turning upward in 2015. Examining mortality trends in the major subgroups of heart disease may provide insight into potentially more targeted and effective prevention and treatment approaches to promote favorable trajectories. We examined national trends between 2000 and 2015 in mortality attributed to major heart disease subgroups including ischemic heart disease, heart failure, and all other types of heart disease.Methods: Using the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (WONDER) data system, we determined national trends in age-standardized mortality rates attributed to ischemic heart disease, heart failure, and other heart diseases from January 1, 2000, to December 31, 2011, and from January 1, 2011, to December 31, 2015. Annual rate of changes in mortality attributed to ischemic heart disease, heart failure, and other heart diseases for 2000-2011 and 2011-2015 were compared.Results: Death attributed to ischemic heart disease declined from 2000 to 2015, but the rate of decline slowed from 4.96% (95% confidence interval 4.77%-5.15%) for 2000-2011 to 2.66% (2.00%-3.31%) for 2011-2015. In contrast, death attributed to heart failure and all other causes of heart disease declined from 2000 to 2011 at annual rates of 1.94% (1.77%-2.11%) and 0.64% (0.44%-0.82%) respectively, but increased from 2011 to 2015 at annual rates of 3.73% (3.21% 4.26%) and 1.89% (1.33-2.46%). Differences in 2000-2011 and 2011-2015 decline rates were statistically significant for all 3 endpoints overall, by sex, and all race/ethnicity groups except Asian/Pacific Islanders (heart failure only significant) and American Indian/Alaskan Natives.Conclusions: While the long-term decline in death attributed to heart disease slowed between 2011 and 2014 nationally before turning upward in 2015, heterogeneity existed in the trajectories attributed to heart disease subgroups, with ischemic heart disease mortality continuing to decline while death attributed to heart failure and other heart diseases switched from a downward to upward trend. While systematic efforts to prevent and treat ischemic heart disease continue to be effective, urgent attention is needed to address the challenge of heart failure. [ABSTRACT FROM AUTHOR]

Background: Ambulatory electrocardiographic (ECG) monitoring is the standard to screen for high-risk arrhythmias. We evaluated the clinical utility of a novel, leadless electrode, single-patient-use ECG monitor that stores up to 14 days of a continuous recording to measure the burden and timing of potentially high-risk arrhythmias.Methods: We examined data from 122,815 long term continuous ambulatory monitors (iRhythm ZIO® Service, San Francisco) prescribed from 2011 to 2013 and categorized potentially high-risk arrhythmias into two types: (1) ventricular arrhythmias including non-sustained and sustained ventricular tachycardia and (2) bradyarrhythmias including sinus pauses >3 s, atrial fibrillation pauses >5 s, and high-grade heart block (Mobitz Type II or third-degree heart block).Results: Of 122,815 ZIO® recordings, median wear time was 9.9 (IQR 6.8-13.8) days and median analyzable time was 9.1 (IQR 6.4-13.1) days. There were 22,443 (18.3%) with at least one episode of non-sustained ventricular tachycardia (NSVT), 238 (0.2%) with sustained VT, 1766 (1.4%) with a sinus pause >3 s (SP), 520 (0.4%) with a pause during atrial fibrillation >5 s (AFP), and 1486 (1.2%) with high-grade heart block (HGHB). Median time to first arrhythmia was 74 h (IQR 26-149 h) for NSVT, 22 h (IQR 5-73 h) for sustained VT, 22 h (IQR 7-64 h) for SP, 31 h (IQR 11-82 h) for AFP, and 40 h (SD 10-118 h) for HGHB.Conclusions: A significant percentage of potentially high-risk arrhythmias are not identified within 48-h of ambulatory ECG monitoring. Longer-term continuous ambulatory ECG monitoring provides incremental detection of these potentially clinically relevant arrhythmic events. [ABSTRACT FROM AUTHOR]

Background: Anemia is common among patients with chronic kidney disease (CKD) but its health consequences are poorly defined. The aim of this study was to determine the relationship between anemia and cognitive decline in older adults with CKD.Methods: We studied a subgroup of 762 adults age ≥55 years with CKD participating in the Chronic Renal Insufficiency Cohort (CRIC) study. Anemia was defined according to the World Health Organization criteria (hemoglobin <13 g/dL for men and <12 g/dL for women). Cognitive function was assessed annually with a battery of six tests. We used logistic regression to determine the association between anemia and baseline cognitive impairment on each test, defined as a cognitive score more than one standard deviation from the mean, and mixed effects models to determine the relation between anemia and change in cognitive function during follow-up after adjustment for demographic and clinical characteristics.Results: Of 762 participants with mean estimated glomerular filtration rate of 42.7 ± 16.4 ml/min/1.73 m(2), 349 (46 %) had anemia. Anemia was not independently associated with baseline cognitive impairment on any test after adjustment for demographic and clinical characteristics. Over a median 2.9 (IQR 2.6-3.0) years of follow-up, there was no independent association between anemia and change in cognitive function on any of the six cognitive tests.Conclusions: Among older adults with CKD, anemia was not independently associated with baseline cognitive function or decline. [ABSTRACT FROM AUTHOR]

Background: Few studies have focused on investigating hypoalbuminemia in patients during earlier stages of chronic kidney disease (CKD). In particular, little is known about the role of gastrointestinal (GI) symptoms. Our goal in this paper is to study how GI symptoms relate to serum albumin levels in CKD, especially in the context of and compared with inflammation.Methods: We performed a cross-sectional study of 3599 patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. All subjects were asked to complete the Modification of Diet in Renal Disease (MDRD) study patient symptom form. Our main predictor is GI symptom score. Serum level of C-reactive protein (CRP) was measured as well. Main outcome measures are serum albumin levels and prevalence of hypoalbuminemia.Results: Of the participants assessed, mean serum albumin was 3.95 ± 0.46 g/dL; 12.7 % had hypoalbuminemia. Patients with lower estimated glomerular filtration rate (eGFR) were likely to have more GI symptoms (apparent at an eGFR <45 ml/min/1.73 m(2)). Patients with worse GI symptoms had lower dietary protein intake. GI symptoms, like inflammation, were risk factors for lower serum albumin levels. However, adding GI symptom score or CRP into the multivariable regression analysis, did not attenuate the association between lower eGFR and lower albumin or hypoalbuminemia.Conclusions: Increased prevalence of GI symptoms become apparent among CKD patients at relatively high eGFR levels (45 ml/min/1.73 m(2)), long before ESRD. Patients with more severe GI symptoms scores are more likely to have hypoalbuminemia. But our data do not support GI symptoms/decreased protein intake or inflammation as being the main determinants of serum albumin level in CKD patients. [ABSTRACT FROM AUTHOR]

Figure 1 Scatter plot with a locally weighted scatterplot smoothing line showing that 24- hrs urinary albumin is not correlated with CrCl/iGFR (rs = 0.02, P = 0.40 by Spearman's correlation test) (two outlier with CrCl/iGFR ratio of 6.40, 0.04 were omitted)" And the corrected Figure has also been included. After the publication of our paper Lin et al. "Determinants of the creatinine clearance to glomerular filtration rate ratio in patients with chronic kidney disease: a cross-sectional study" BMC Nephrology 2013, 14:268, we became aware of errors in the manuscript arising from to a misunderstanding of serum creatinine calibration in the released Chronic Renal Insufficiency Cohort (CRIC) study data obtained from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Data Repository. Specifically further multiplication by 0.95 was actually not necessary to arrive at the standardized creatinine values. Here we present the revised results of the re-analyses along with revisions of the relevant tables. Mean CrCl/iGFR ratio should be 1.13 ± 0.46 instead of 1.19 ± 0.48. The main conclusion of the paper remain unchanged: "Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature." [ABSTRACT FROM AUTHOR]

Background Cardiac troponin T is independently associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). Serum levels of high sensitivity cardiac troponin T (hs-TnT) reflect subclinical myocardial injury in ambulatory patients. We sought to determine the distribution and predictors of hs-TnT in CKD patients without overt cardiovascular disease (CVD). Methods We studied 2464 participants within the multi-ethnic Chronic Renal Insufficiency Cohort (CRIC) who did not have self-reported CVD. We considered renal and non-renal factors as potential determinants of hs-TnT, including demographics, comorbidities, left ventricular (LV) mass, serologic factors, estimated glomerular filtration rate (eGFR) and albumin to creatinine ratio. Results Hs-TnT was detectable in 81% of subjects, and the median (IQR) hs-TnT was 9.4 pg/ml (4.3- 18.3). Analysis was performed using Tobit regression, adjusting for renal and non-renal factors. After adjustment, lower eGFR was associated with higher expected hs-TnT; participants with eGFR <30 ml/min/1.73m2 had 3-fold higher expected hs-TnT compared to subjects with eGFR >60. Older age, male gender, black race, LV mass, diabetes and higher blood pressure all had strong, independent associations with higher expected hs-TnT. Conclusions Knowledge of the determinants of hs-TnT in this cohort may guide further research on the pathology of heart disease in patients with CKD and help to stratify sub-groups of CKD patients at higher cardiovascular risk. [ABSTRACT FROM AUTHOR]

Background Creatinine secretion, as quantified by the ratio of creatinine clearance (CrCl) to glomerular filtration rate (GFR), may introduce another source of error when using serum creatinine concentration to estimate GFR. Few studies have examined determinants of the CrCl/GFR ratio. We sought to study whether higher levels of albuminuria would be associated with higher, and being non-Hispanic black with lower, CrCl/GFR ratio. Methods We did a cross-sectional analysis of 1342 patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR) and 24-hour urine collections. Our predictors included urine albumin as determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999 and ≥3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion. Results Mean iGFR was 48.0 ± 19.9 mL/min/1.73 m2, median albuminuria was 84 mg per day, and 36.8% of the study participants were non-Hispanic black. Mean CrCl/iGFR ratio was 1.19 ± 0.48. There was no association between the CrCl/iGFR ratio and urine albumin (coefficient 0.11 [95% CI-0.01-0.22] for higest verus lowest levels of albuminuria, p = 0.07). Also, there was no association between race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was-0.03 [95% CI-0.09-0.03] compared with whites, p = 0.38). Conclusions Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a predictor of cardiovascular events that has been shown to vary with race. The objective of this study was to examine factors associated with this racial variation. Methods: We measured Lp-PLA2 mass and activity in 714 healthy older adults with no clinical coronary heart disease and not taking dyslipidemia medication. We evaluated the association between race and Lp-PLA2 mass and activity levels after adjustment for various covariates using multivariable linear regression. These covariates included age, sex, diabetes, hypertension, body mass index, lipid measurements, C-reactive protein, smoking status, physical activity, diet, income, and education level. We further examined genetic covariates that included three single nucleotide polymorphisms shown to be associated with Lp-PLA2 activity levels. Results: The mean age was 66 years. Whites had the highest Lp-PLA2 mass and activity levels, followed by Hispanics and Asians, and then African-Americans; in age and sex adjusted analyses, these differences were significant for each non-White race as compared to Whites (p < 0.0001). For example, African-Americans were predicted to have a 55.0 ng/ml lower Lp-PLA2 mass and 24.7 nmol/ml-min lower activity, compared with Whites, independent of age and sex (p < 0.0001). After adjustment for all covariates, race remained significantly correlated with Lp-PLA2 mass and activity levels (p < 0.001) with African-Americans having 44.8 ng/ml lower Lp-PLA2 mass and 17.3 nmol/ml-min lower activity compared with Whites (p < 0.0001). Conclusion: Biological, lifestyle, demographic, and select genetic factors do not appear to explain variations in Lp-PLA2 mass and activity levels between Whites and non-Whites, suggesting that Lp-PLA2 mass and activity levels may need to be interpreted differently for various races. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DES) reduce rates of restenosis compared with bare metal stents (BMS). A number of observational studies have also found lower rates of mortality and non-fatal myocardial infarction with DES compared with BMS, findings not observed in randomized clinical trials. In order to explore reasons for this discrepancy, we compared outcomes after percutaneous coronary intervention (PCI) with DES or BMS by multiple statistical methods. Methods: We compared short-term rates of all-cause mortality and myocardial infarction for patients undergoing PCI with DES or BMS using propensity-score adjustment, propensity-score matching, and a stent-era comparison in a large, integrated health system between 1998 and 2007. For the propensity-score adjustment and stent era comparisons, we used multivariable logistic regression to assess the association of stent type with outcomes. We used McNemar's Chi-square test to compare outcomes for propensity-score matching. Results: Between 1998 and 2007, 35,438 PCIs with stenting were performed among health plan members (53.9% DES and 46.1% BMS). After propensity-score adjustment, DES was associated with significantly lower rates of death at 30 days (OR 0.49, 95% CI 0.39 - 0.63, P < 0.001) and one year (OR 0.58, 95% CI 0.49 - 0.68, P < 0.001), and a lower rate of myocardial infarction at one year (OR 0.72, 95% CI 0.59 - 0.87, P < 0.001). Thirty day and one year mortality were also lower with DES after propensity-score matching. However, a stent era comparison, which eliminates potential confounding by indication, showed no difference in death or myocardial infarction for DES and BMS, similar to results from randomized trials. Conclusions: Although propensity-score methods suggested a mortality benefit with DES, consistent with prior observational studies, a stent era comparison failed to support this conclusion. Unobserved factors influencing stent selection in observational studies likely account for the observed mortality benefit of DES not seen in randomized clinical trials. [ABSTRACT FROM AUTHOR]

Background: The incidence of acute kidney injury (AKI) has been increasing over time and is associated with a high risk of short-term death. Previous studies on hospital-acquired AKI have important methodological limitations, especially their retrospective study designs and limited ability to control for potential confounding factors. Methods: The Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) Study was established to examine how a hospitalized episode of AKI independently affects the risk of chronic kidney disease development and progression, cardiovascular events, death, and other important patient-centered outcomes. This prospective study will enroll a cohort of 1100 adult participants with a broad range of AKI and matched hospitalized participants without AKI at three Clinical Research Centers, as well as 100 children undergoing cardiac surgery at three Clinical Research Centers. Participants will be followed for up to four years, and will undergo serial evaluation during the index hospitalization, at three months post-hospitalization, and at annual clinic visits, with telephone interviews occurring during the intervening six-month intervals. Biospecimens will be collected at each visit, along with information on lifestyle behaviors, quality of life and functional status, cognitive function, receipt of therapies, interim renal and cardiovascular events, electrocardiography and urinalysis. Conclusions: ASSESS-AKI will characterize the short-term and long-term natural history of AKI, evaluate the incremental utility of novel blood and urine biomarkers to refine the diagnosis and prognosis of AKI, and identify a subset of high-risk patients who could be targeted for future clinical trials to improve outcomes after AKI. [ABSTRACT FROM AUTHOR]

Background: Creatinine secretion, as quantified by the ratio of creatinine clearance (CrCl) to glomerular filtration rate (GFR), may introduce another source of error when using serum creatinine concentration to estimate GFR. Few studies have examined determinants of the CrCl/GFR ratio. We sought to study whether higher levels of albuminuria would be associated with higher, and being non-Hispanic black with lower, CrCl/GFR ratio.Methods: We did a cross-sectional analysis of 1342 patients with chronic kidney disease from the Chronic Renal Insufficiency Cohort (CRIC) who had baseline measure of iothalamate GFR (iGFR) and 24-hour urine collections. Our predictors included urine albumin as determined from 24-hour urine collections (categorized as: <30, 30-299, 300-2999 and ≥3000 mg), and race/ethnicity (non-Hispanic white, non-Hispanic black, Hispanic). Our outcome was CrCl/iGFR ratio, a measure of creatinine secretion.Results: Mean iGFR was 48.0 ± 19.9 mL/min/1.73 m², median albuminuria was 84 mg per day, and 36.8% of the study participants were non-Hispanic black. Mean CrCl/iGFR ratio was 1.19 ± 0.48. There was no association between the CrCl/iGFR ratio and urine albumin (coefficient 0.11 [95% CI-0.01-0.22] for higest verus lowest levels of albuminuria, p = 0.07). Also, there was no association between race/ethnicity and CrCl/iGFR ratio (coefficient for non-Hispanic blacks was-0.03 [95% CI-0.09-0.03] compared with whites, p = 0.38).Conclusions: Contrary to what had been suggested by prior smaller studies, CrCl/GFR ratio does not vary with degree of proteinuria or race/ethnicity. The ratio is also closer to 1.0 than reported by several frequently cited reports in the literature. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein-associated phospholipase A₂ (Lp-PLA₂) is a predictor of cardiovascular events that has been shown to vary with race. The objective of this study was to examine factors associated with this racial variation.Methods: We measured Lp-PLA₂ mass and activity in 714 healthy older adults with no clinical coronary heart disease and not taking dyslipidemia medication. We evaluated the association between race and Lp-PLA₂ mass and activity levels after adjustment for various covariates using multivariable linear regression. These covariates included age, sex, diabetes, hypertension, body mass index, lipid measurements, C-reactive protein, smoking status, physical activity, diet, income, and education level. We further examined genetic covariates that included three single nucleotide polymorphisms shown to be associated with Lp-PLA₂ activity levels.Results: The mean age was 66 years. Whites had the highest Lp-PLA₂ mass and activity levels, followed by Hispanics and Asians, and then African-Americans; in age and sex adjusted analyses, these differences were significant for each non-White race as compared to Whites (p < 0.0001). For example, African-Americans were predicted to have a 55.0 ng/ml lower Lp-PLA₂ mass and 24.7 nmol/ml-min lower activity, compared with Whites, independent of age and sex (p < 0.0001). After adjustment for all covariates, race remained significantly correlated with Lp-PLA₂ mass and activity levels (p < 0.001) with African-Americans having 44.8 ng/ml lower Lp-PLA₂ mass and 17.3 nmol/ml-min lower activity compared with Whites (p < 0.0001).Conclusion: Biological, lifestyle, demographic, and select genetic factors do not appear to explain variations in Lp-PLA₂ mass and activity levels between Whites and non-Whites, suggesting that Lp-PLA₂ mass and activity levels may need to be interpreted differently for various races. [ABSTRACT FROM AUTHOR]

Background: Drug-eluting stents (DES) reduce rates of restenosis compared with bare metal stents (BMS). A number of observational studies have also found lower rates of mortality and non-fatal myocardial infarction with DES compared with BMS, findings not observed in randomized clinical trials. In order to explore reasons for this discrepancy, we compared outcomes after percutaneous coronary intervention (PCI) with DES or BMS by multiple statistical methods.Methods: We compared short-term rates of all-cause mortality and myocardial infarction for patients undergoing PCI with DES or BMS using propensity-score adjustment, propensity-score matching, and a stent-era comparison in a large, integrated health system between 1998 and 2007. For the propensity-score adjustment and stent era comparisons, we used multivariable logistic regression to assess the association of stent type with outcomes. We used McNemar's Chi-square test to compare outcomes for propensity-score matching.Results: Between 1998 and 2007, 35,438 PCIs with stenting were performed among health plan members (53.9% DES and 46.1% BMS). After propensity-score adjustment, DES was associated with significantly lower rates of death at 30 days (OR 0.49, 95% CI 0.39 - 0.63, P < 0.001) and one year (OR 0.58, 95% CI 0.49 - 0.68, P < 0.001), and a lower rate of myocardial infarction at one year (OR 0.72, 95% CI 0.59 - 0.87, P < 0.001). Thirty day and one year mortality were also lower with DES after propensity-score matching. However, a stent era comparison, which eliminates potential confounding by indication, showed no difference in death or myocardial infarction for DES and BMS, similar to results from randomized trials.Conclusions: Although propensity-score methods suggested a mortality benefit with DES, consistent with prior observational studies, a stent era comparison failed to support this conclusion. Unobserved factors influencing stent selection in observational studies likely account for the observed mortality benefit of DES not seen in randomized clinical trials. [ABSTRACT FROM AUTHOR]

Background: Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort. Results: Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93∼0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03). Conclusions: Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups. [ABSTRACT FROM AUTHOR]

Background: Few studies have focused on investigating hypoalbuminemia in patients during earlier stages of chronic kidney disease (CKD). In particular, little is known about the role of gastrointestinal (GI) symptoms. Our goal in this paper is to study how GI symptoms relate to serum albumin levels in CKD, especially in the context of and compared with inflammation., Methods: We performed a cross-sectional study of 3599 patients with chronic kidney disease enrolled in the Chronic Renal Insufficiency Cohort (CRIC) study. All subjects were asked to complete the Modification of Diet in Renal Disease (MDRD) study patient symptom form. Our main predictor is GI symptom score. Serum level of C-reactive protein (CRP) was measured as well. Main outcome measures are serum albumin levels and prevalence of hypoalbuminemia., Results: Of the participants assessed, mean serum albumin was 3.95 ± 0.46 g/dL; 12.7 % had hypoalbuminemia. Patients with lower estimated glomerular filtration rate (eGFR) were likely to have more GI symptoms (apparent at an eGFR <45 ml/min/1.73 m(2)). Patients with worse GI symptoms had lower dietary protein intake. GI symptoms, like inflammation, were risk factors for lower serum albumin levels. However, adding GI symptom score or CRP into the multivariable regression analysis, did not attenuate the association between lower eGFR and lower albumin or hypoalbuminemia., Conclusions: Increased prevalence of GI symptoms become apparent among CKD patients at relatively high eGFR levels (45 ml/min/1.73 m(2)), long before ESRD. Patients with more severe GI symptoms scores are more likely to have hypoalbuminemia. But our data do not support GI symptoms/decreased protein intake or inflammation as being the main determinants of serum albumin level in CKD patients.

Background: Patients with chronic kidney disease (CKD) are less likely to receive cardiovascular medications. It is unclear whether differential cardiovascular drug use explains, in part, the excess risk of cardiovascular events and death in patients with CKD and coronary heart disease (CHD)., Methods: The ADVANCE Study enrolled patients with new onset CHD (2001-2003) who did (N = 159) or did not have (N = 1088) CKD at entry. The MDRD equation was used to estimate glomerular filtration rate (eGFR) using calibrated serum creatinine measurements. Patient characteristics, medication use, cardiovascular events and death were ascertained from self-report and health plan electronic databases through December 2008., Results: Post-CHD event ACE inhibitor use was lower (medication possession ratio 0.50 vs. 0.58, P = 0.03) and calcium channel blocker use higher (0.47 vs. 0.38, P = 0.06) in CKD vs. non-CKD patients, respectively. Incidence of cardiovascular events and death was higher in CKD vs. non-CKD patients (13.9 vs. 11.5 per 100 person-years, P < 0.001, respectively). After adjustment for patient characteristics, the rate of cardiovascular events and death was increased for eGFR 45-59 ml/min/1.73 m2 (hazard ratio [HR] 1.47, 95% CI: 1.10 to 2.02) and eGFR < 45 ml/min/1.73 m2 (HR 1.58, 95% CI: 1.00 to 2.50). After further adjustment for statins, β-blocker, calcium channel blocker, ACE inhibitor/ARB use, the association was no longer significant for eGFR 45-59 ml/min/1.73 m2 (HR 0.82, 95% CI: 0.25 to 2.66) or for eGFR < 45 ml/min/1.73 m2 (HR 1.19, 95% CI: 0.25 to 5.58)., Conclusions: In adults with CHD, differential use of cardiovascular medications may contribute to the higher risk of cardiovascular events and death in patients with CKD.