Acute Kidney Injury After Repeated Exposure to Contrast Material for Coronary Angiography.

OBJECTIVE: To assess the incidence of contrast-associated acute kidney injury (CAAKI) after repeated exposure to contrast material for computed tomography (CT) and conventional coronary angiography within short intervals. METHODS: We studied 651 patients enrolled in the CorE-64 (November 5, 2005-January 30, 2007) and CORE320 (October 21, 2009-August 17, 2011) multicenter studies. Participants with suspected obstructive coronary heart disease were referred for diagnostic cardiac catheterization and underwent coronary CT angiography for research before invasive angiography. Nonionic, low-osmolality iodinated contrast material was used for all imaging. RESULTS: The median age of the patients was 62 years, and 190 (29%) were women. Major risk factors for acute kidney injury were present in 277 of 651 (43%) patients. The median interval between CT imaging and invasive angiography was 3.1 days (interquartile range, 0.9-8.0 days). The median volume of contrast material was 100 mL for each test. In 16 (2.5%) of 651 patients, CAAKI developed. Of these cases, 1 occurred after the CT scan, whereas 6 were documented after invasive angiography (compared with post-CT creatinine concentration assessment). In 9 patients, CAAKI was found in comparing creatinine concentration after completion of both tests with baseline values (but not compared with post-CT imaging). CONCLUSION: Acute kidney injury after repeated exposure to iodinated contrast media within a few days is uncommon even in a population of patients with highly prevalent risk factors. Withholding of clinically indicated contrast-enhanced imaging may therefore not be justified in this setting.

Coffee and tea consumption in the early adult lifespan and left ventricular function in middle age: the CARDIA study.

AIMS: The long-term impact of coffee or tea consumption on subclinical left ventricular (LV) systolic or diastolic function has not been previously studied. We examined the association between coffee or tea consumption beginning in early adulthood and cardiac function in midlife. METHODS AND RESULTS: We investigated 2735 Coronary Artery Risk Development in Young Adults (CARDIA) study participants with long-term total caffeine intake, coffee, and tea consumption data from three visits over a 20 year interval and available echocardiography indices at the CARDIA Year-25 exam (2010-2011). Linear regression models were used to assess the association between caffeine intake, tea, and coffee consumption (independent variables) and echocardiography outcomes [LV mass, left atrial volume, and global longitudinal strain (GLS), LV ejection fraction (LVEF), and transmitral Doppler early filling velocity to tissue Doppler early diastolic mitral annular velocity (E/e´)]. Models were adjusted for standard cardiovascular risk factors, socioeconomic status, physical activity, alcohol use, and dietary factors (calorie intake, whole and refined grain intake, and fruit and vegetable consumption). Mean (standard deviation) age was 25.2 (3.5) years at the CARDIA Year-0 exam (1985-1986), 57.4% were women, and 41.9% were African-American. In adjusted multivariable linear regression models assessing the relationship between coffee consumption and GLS, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.30%, P < 0.05; ß = -0.35%, P < 0.05; ß = -0.32%, P < 0.05; ß = -0.40%, P > 0.05; respectively (more negative values implies better systolic function). In adjusted multivariable linear regression models assessing the relationship between coffee consumption and E/e´, beta coefficients when comparing coffee drinkers of <1, 1-2, 3-4, and >4 cups/day with non-coffee drinkers were ß = -0.29, P < 0.05; ß = -0.38, P < 0.01; ß = -0.20, P > .05; and ß = -0.37, P > 0.05, respectively (more negative values implies better diastolic function). High daily coffee consumption (>4 cups/day) was associated with worse LVEF (ß = -1.69, P < 0.05). There were no associations between either tea drinking or total caffeine intake and cardiac function (P > 0.05 for all). CONCLUSIONS: Low-to-moderate daily coffee consumption from early adulthood to middle age was associated with better LV systolic and diastolic function in midlife. High daily coffee consumption (>4cups/day) was associated with worse LV function. There was no association between caffeine or tea intake and cardiac function.

Sex Differences in the Association of Cumulative Body Mass Index from Early Adulthood to Middle Age and Left Atrial Remodeling Evaluated by Three-Dimensional Echocardiography: The Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: The relationship between long-term obesity and left atrial (LA) structure and function is not entirely understood. We examined the association of cumulative body mass index (cBMI) with LA remodeling using three-dimensional (3D) speckle-tracking echocardiography (STE). METHODS: The Coronary Artery Risk Development in Young Adults (CARDIA) study is a community-based cohort of black and white, men and women, ages 18-30 years at baseline in 1985-86 from four U.S. centers. This study included 2,144 participants who had satisfactory image quality and body mass index measurements during the entire follow-up period. The 3D STE-derived LA parameters were maximum, minimum, and pretrial contraction volumes; total, passive, and active emptying fraction; maximum systolic longitudinal strain; and early and late diastolic longitudinal strain rates. Multivariable linear regression analyses stratified by sex assessed the relationship between cBMI and 3D STE-derived LA parameters, adjusting for demographics and traditional cardiovascular. RESULTS: The mean age of the cohort was 55 ± 3.6 years; 54.8% were women, and 46.5% were black. There were statistically significant additive sex interactions for the association between cBMI and LA minimum contraction value, maximum systolic longitudinal strain, and early and late diastolic longitudinal strain rates. In the fully adjusted model, greater cBMI was associated with lower magnitude LA longitudinal deformation (maximum systolic longitudinal strain and early and late diastolic longitudinal strain rates) in men and with higher LA emptying fraction in women. In addition, greater cBMI was associated with higher LA phasic volumes indices in both men and women. CONCLUSIONS: This study showed that while greater cBMI from early adulthood throughout middle age was associated with higher LA volumes in both genders, differences were found for LA function, with lower longitudinal deformation in men and higher reservoir and active LA function in women.

Application of measurement error models to correct for systematic differences among readers and vendors in echocardiography measurements: the CARDIA study.

We illustrate the application of linear measurement error models to calibrate echocardiography measurements acquired 20 years apart in the CARDIA study. Of 4242 echocardiograms acquired at Year-5 (1990-1991), 36% were reread 20 years later. Left ventricular (LV) mass and 8 other measurements were assessed. A machine reproducibility study including 96 additional patients also compared Year-5 and Year-25 equipment. A linear measurement error model was developed to calibrate the original Year-5 measurements, incorporating the additional Year-5 reread and machine reproducibility study data, and adjusting for differences among readers and machines. Median (quartiles) of original Year-5 LV mass was 144.4 (117.6, 174.2) g before and 129.9 (103.8, 158.6) g, after calibration. The correlation between original and calibrated LV mass was 0.989 (95% confidence interval: 0.988, 0.990). The original and calibrated measurements had similar distributions. Additional comparisons of original and calibrated data supported the use of the model. We conclude that systematic differences among readers and machines have been accounted for, and that the calibrated Year-5 measurements can be used in future longitudinal comparisons. It is hoped that this paper will encourage the wider application of measurement error models.

Coronary Calcium Characteristics as Predictors of Major Adverse Cardiac Events in Symptomatic Patients: Insights From the CORE 320 Multinational Study.

Background The predictive value of coronary artery calcium ( CAC ) has been widely studied; however, little is known about specific characteristics of CAC that are most predictive. We aimed to determine the independent associations of Agatston score, CAC volume, CAC area, CAC mass, and CAC density score with major adverse cardiac events in patients with suspected coronary artery disease. Methods and Results A total of 379 symptomatic participants, aged 45 to 85 years, referred for invasive coronary angiography, who underwent coronary calcium scanning and computed tomography angiography as part of the CORE 320 (Combined Noninvasive Coronary Angiography and Myocardial Perfusion Imaging Using 320 Detector Computed Tomography) study, were included. Agatston score, CAC volume, area, mass, and density were computed on noncontrast images. Stenosis measurements were made on contrast-enhanced images. The primary outcome of 2-year major adverse cardiac events (30 revascularizations [>182 days of index catheterization], 5 myocardial infarctions, 1 cardiac death, 9 hospitalizations, and 1 arrhythmia) occurred in 32 patients (8.4%). Associations were estimated using multivariable proportional means models. Median age was 62 (interquartile range, 56-68) years, 34% were women, and 56% were white. In separate models, the Agatston, volume, and density scores were all significantly associated with higher risk of major adverse cardiac events after adjustment for age, sex, race, and statin use; density was the strongest predictor in all CAC models. CAC density did not provide incremental value over Agatston score after adjustment for diameter stenosis, age, sex, and race. Conclusions In symptomatic patients, CAC density was the strongest independent predictor of major adverse cardiac events among CAC scores, but it did not provide incremental value beyond the Agatston score after adjustment for diameter stenosis.

Comparative Effectiveness of CT-Derived Atherosclerotic Plaque Metrics for Predicting Myocardial Ischemia.

OBJECTIVES: This study sought to investigate the performance of various cardiac computed tomography (CT)-derived atherosclerotic plaque metrics for predicting provocable myocardial ischemia. BACKGROUND: The association of coronary arterial diameter stenosis with myocardial ischemia is only modest, but cardiac CT provides several other, readily available atherosclerosis metrics, which may have incremental value. METHODS: The study analyzed 873 nonstented coronary arteries and their myocardial perfusion territories in 356 patients (mean 62 years of age) enrolled in the CORE320 (Coronary Artery Evaluation using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) study. Myocardial perfusion defects in static CT perfusion imaging were graded at rest and after adenosine in 13 myocardial segments using a 4-point scale. The summed difference score was calculated by subtracting the summed rest score from the summed stress score. Reversible ischemia was defined as summed difference score ≥1. In a sensitivity analysis, results were also provided using single-photon emission computed tomography (SPECT) as the reference standard. Vessel based predictor variables included maximum percent diameter stenosis, lesion length, coronary calcium score, maximum cross-sectional calcium arc, percent atheroma volume (PAV), low-attenuation atheroma volume, positive (external) vascular remodeling, and subjective impression of "vulnerable plaque." The study used logistic regression models to assess the association of plaque metrics with myocardial ischemia. RESULTS: In univariate analysis, all plaque metrics were associated with reversible ischemia. In the adjusted logistic model, only maximum percent diameter stenosis (1.26; 95% confidence interval: 1.15 to 1.38) remained an independent predictor. With SPECT as outcome variable, PAV and "vulnerable" plaque remained predictive after adjustment. In vessels with intermediate stenosis (40% to 70%), no single metric had clinically meaningful incremental value. CONCLUSIONS: Various plaque metrics obtained by cardiac CT predict provocable myocardial ischemia by CT perfusion imaging through their association with maximum percent stenosis, while none had significant incremental value. With SPECT as reference standard, PAV and "vulnerable plaque" remained predictors of ischemia after adjustment but the predictive value added to stenosis assessment alone was small.

Parental health literacy and progression of chronic kidney disease in children.

BACKGROUND: Limited health literacy has been associated with adverse outcomes in children. We evaluated this association in the setting of chronic kidney disease (CKD). METHODS: We assessed the parental health literacy of 367 children enrolled in the Chronic Kidney Disease in Children (CKiD) Study, using the Short Test of Functional Health Literacy (STOFHLA). We evaluated the association between parental health literacy and CKD progression, defined as time to the composite event of renal replacement therapy (RRT, dialysis, or kidney transplant) or 50% decline in estimated glomerular filtration rate (eGFR). RESULTS: Median CKiD participant age was 9.5 years, 63% were male, and 59% non-Hispanic white. Median eGFR at baseline was 63 ml/min/1.73 m2, and median urine protein-to-creatinine ratio was 0.22. The median STOFHLA score was 98. Over a median follow-up of 3.7 years, the overall CKD progression rate was 2.8 per 100 person-years. After adjustment for demographic and clinical factors, the relative time to CKD progression was 28% longer per 1 SD increase in STOFHLA score (relative time, 95% CI, 1.28, 1.06-1.53). CONCLUSIONS: In this cohort of children with CKD, higher parental health literacy was associated with a nearly 30% longer time to the composite CKD progression outcome.

FGF23 and Left Ventricular Hypertrophy in Children with CKD.

BACKGROUND AND OBJECTIVES: High plasma concentration of fibroblast growth factor 23 (FGF23) is a risk factor for left ventricular hypertrophy (LVH) in adults with CKD, and induces myocardial hypertrophy in experimental CKD. We hypothesized that high FGF23 levels associate with a higher prevalence of LVH in children with CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We performed echocardiograms and measured plasma C-terminal FGF23 concentrations in 587 children with mild-to-moderate CKD enrolled in the Chronic Kidney Disease in Children (CKiD) study. We used linear and logistic regression to analyze the association of plasma FGF23 with left ventricular mass index (LVMI) and LVH (LVMI ≥95th percentile), adjusted for demographics, body mass index, eGFR, and CKD-specific factors. We also examined the relationship between FGF23 and LVH by eGFR level. RESULTS: Median age was 12 years (interquartile range, 8-15) and eGFR was 50 ml/min per 1.73 m2 (interquartile range, 38-64). Overall prevalence of LVH was 11%. After adjustment for demographics and body mass index, the odds of having LVH was higher by 2.53 (95% confidence interval, 1.28 to 4.97; P<0.01) in participants with FGF23 concentrations ≥170 RU/ml compared with those with FGF23<100 RU/ml, but this association was attenuated after full adjustment. Among participants with eGFR≥45 ml/min per 1.73 m2, the prevalence of LVH was 5.4%, 11.2%, and 15.3% for those with FGF23 <100 RU/ml, 100-169 RU/ml, and ≥170 RU/ml, respectively (Ptrend=0.01). When eGFR was ≥45 ml/min per 1.73 m2, higher FGF23 concentrations were independently associated with LVH (fully adjusted odds ratio, 3.08 in the highest versus lowest FGF23 category; 95% confidence interval, 1.02 to 9.24; P<0.05; fully adjusted odds ratio, 2.02 per doubling of FGF23; 95% confidence interval, 1.29 to 3.17; P<0.01). By contrast, in participants with eGFR<45 ml/min per 1.73 m2, FGF23 did not associate with LVH. CONCLUSIONS: Plasma FGF23 concentration ≥170 RU/ml is an independent predictor of LVH in children with eGFR≥45 ml/min per 1.73 m2.

Vascular Stiffness in Children With Chronic Kidney Disease.

Carotid-femoral pulse wave velocity (cfPWV) is a measure of arterial stiffness associated with cardiovascular events in the general population and in adults with chronic kidney disease. However, few data exist regarding cfPWV in children with chronic kidney disease. We compared observed cfPWV assessed via applanation tonometry in children enrolled in the CKiD cohort study (Chronic Kidney Disease in Children) to normative data in healthy children and examined risk factors associated with elevated cfPWV. cfPWV Z score for height/gender and age/gender was calculated from and compared with published pediatric norms. Multivariable linear regression was used to assess the relationship between cfPWV and age, gender, race, body mass index, diagnosis, urine protein-creatinine ratio, mean arterial pressure, heart rate, number of antihypertensive medications, uric acid, and serum low-density lipoprotein. Of the 95 participants with measured cfPWV, 60% were male, 19% were black, 46% had glomerular cause of chronic kidney disease, 22% had urine protein-creatinine ratio 0.5 to 2.0 mg/mg and 9% had >2.0 mg/mg, mean age was 15.1 years, average mean arterial pressure was 80 mm Hg, and median glomerular filtration rate was 63 mL/min per 1.73 m2 Mean cfPWV was 5.0 m/s (SD, 0.8 m/s); mean cfPWV Z score by height/gender norms was -0.1 (SD, 1.1). cfPWV increased significantly with age, mean arterial pressure, and black race in multivariable analysis; no other variables, including glomerular filtration rate, were independently associated with cfPWV. In this pediatric cohort with mild kidney dysfunction, arterial stiffness was comparable to that of normal children. Future research is needed to examine the impact of chronic kidney disease progression on arterial stiffness and associated cardiovascular parameters in children.

The Effect of Heart Rate on Exposure Window and Best Phase for Stress Perfusion Computed Tomography: Lessons From the CORE320 Study.

OBJECTIVES: The aim of this study is to evaluate the effect of heart rate on exposure window, best phase, and image quality for stress computed tomography perfusion (CTP) in the CORE320 study. METHODS: The CTP data sets were analyzed to determine the best phase for perfusion analysis. A predefined exposure window covering 75% to 95% of the R-R cycle was used. RESULTS: Of the 368 patients included in the analysis, 93% received oral ß blockade before the rest scan. The median heart rate during the stress acquisition was 69 bpm (interquartile range [IQR], 60-77). The median best phase was 81% (IQR, 76-90), and length of exposure window was 22% (IQR, 19-24). The best phase was significantly later in the cardiac cycle with higher heart rates (P < 0.001), and higher heart rates resulted in a small, but higher number of poor quality scans (6%, P < 0.001). The median effective dose of the stress scan was 5.3 mSv (IQR, 3.8-6.1). CONCLUSIONS: Stress myocardial CTP imaging can be performed using prospective electrocardiography triggering, an exposure window of 75% to 95%, and ß-blockade resulting in good or excellent image quality in the majority (80%) of patients while maintaining a low effective radiation dose.

Dietary sources of energy and nutrient intake among children and adolescents with chronic kidney disease.

BACKGROUND: Our purpose was to identify the main food contributors to energy and nutrient intake in children with chronic kidney disease (CKD). METHODS: In this cross-sectional study of dietary intake assessed using Food Frequency Questionnaires (FFQ) in the Chronic Kidney Disease in Children (CKiD) cohort study, we estimated energy and nutrient intake and identified the primary contributing foods within this population. RESULTS: Completed FFQs were available for 658 children. Of those, 69.9% were boys, median age 12 (interquartile range (IQR) 8-15 years). The average daily energy intake was 1968 kcal (IQR 1523-2574 kcal). Milk was the largest contributor to total energy, protein, potassium, and phosphorus intake. Fast foods were the largest contributors to fat and sodium intake, the second largest contributors to energy intake, and the third largest contributors to potassium and phosphorus intake. Fruit contributed 12.0%, 8.7%, and 6.7% to potassium intake for children aged 2-5, 6-13, and 14-18 years old, respectively. CONCLUSIONS: Children with CKD consumed more sodium, protein, and calories but less potassium than recommended by the National Kidney Foundation (NKF) guidelines for pediatric CKD. Energy, protein, and sodium intake is heavily driven by consumption of milk and fast foods. Limiting contribution of fast foods in patients with good appetite may be particularly important for maintaining recommended energy and sodium intake, as overconsumption can increase the risk of obesity and cardiovascular complications in that population.

Renin-angiotensin II-aldosterone system blockers and time to renal replacement therapy in children with CKD.

BACKGROUND: Clinical care decisions to treat chronic kidney disease (CKD) in a growing child must often be made without the benefit of evidence from clinical trials. We used observational data from the Chronic Kidney Disease in Children cohort to estimate the effectiveness of renin-angiotensin II-aldosterone system blockade (RAAS) to delay renal replacement therapy (RRT) in children with CKD. METHODS: A total of 851 participants (median age: 11 years, median glomerular filtration rate [GFR]: 52 ml/min/1.73 m2, median urine protein to creatinine ratio: 0.35 mg/mg) were included. RAAS use was reported at annual study visits. Both Cox proportional hazards models with time-varying RAAS exposure and Cox marginal structural models (MSM) were used to evaluate the effect of RAAS use on time to RRT. Analyses were adjusted or weighted to control for age, male sex, glomerular diagnosis, GFR, nephrotic range proteinuria, anemia, elevated blood pressure, acidosis, elevated phosphate and elevated potassium. RESULTS: There were 217 RRT events over a 4.1-year median follow-up. At baseline, 472 children (55 %) were prevalent RAAS users, who were more likely to be older, have a glomerular etiology, have higher urine protein, be anemic, have elevated serum phosphate and potassium, take more medications, but less likely to have elevated blood pressure, compared with non-users. RAAS use was found to reduce the risk of RRT by 21 % (hazard ratio: 0.79) to 37 % (hazard ratio: 0.63) from standard regression adjustment and MSM models, respectively. CONCLUSIONS: These results support inferences from adult studies of a substantial benefit of RAAS use in pediatric CKD patients.

Assessment of dietary intake of children with chronic kidney disease.

OBJECTIVE: Our aim was to characterize the nutrient intake of children with chronic kidney disease (CKD) relative to recommended intake levels. METHODS: We conducted a cross-sectional study of dietary intake assessed by Food Frequency Questionnaire (FFQ) in The North American Chronic Kidney Disease in Children (CKiD) prospective cohort study. Nutrient intake was analyzed to estimate the daily consumption levels of various nutrients and compared with national guidelines for intake. RESULTS: There were 658 FFQs available for analysis; 69.9 % of respondents were boys, with a median age [Interquartile range (IQR)] of 11 years (8-15). Median daily sodium, potassium, and phosphorus intake was 3089 mg (2294-4243), 2384 mg (1804-3076), and 1206 mg (894-1612) respectively. Sodium and phosphorus consumptions were higher than recommended in all age groups. Caloric intake decreased with dropping glomerular filtration rate (GFR) (p = 0.003). The median daily caloric intakes were 1307 kcal in male children 2-3 years old, 1875 kcal in children 4-8 years old, 1923 kcal in those 9-13 years old, and 2427 kcal in those 14-18 years old. Respective levels for girls were 1467 kcal, 1736 kcal, 1803 kcal, and 2281 kcal. Median protein intake exceeded recommended levels in all age groups, particularly among younger participants. Younger children were more likely than older children to exceed the recommended intakes for phosphorus (p < 0.001) and the age-specific recommended caloric intake (p < 0.001). Macronutrient distribution (carbohydrate:fat:protein) was consistent with recommendation. CONCLUSIONS: Children in the CKiD cohort consumed more sodium, phosphorus, protein, and calories than recommended. The gap between actual consumption and recommendations indicates a need for improved nutritional counseling and monitoring.

Computed Tomographic Perfusion Improves Diagnostic Power of Coronary Computed Tomographic Angiography in Women: Analysis of the CORE320 Trial (Coronary Artery Evaluation Using 320-Row Multidetector Computed Tomography Angiography and Myocardial Perfusion) According to Gender.

BACKGROUND: Coronary computed tomographic angiography (CTA) and myocardial perfusion imaging (CTP) is a validated approach for detection and exclusion of flow-limiting coronary artery disease (CAD), but little data are available on gender-specific performance of these modalities. In this study, we aimed to evaluate the diagnostic accuracy of combined coronary CTA and CTP in detecting flow-limiting CAD in women compared with men. METHODS AND RESULTS: Three hundred and eighty-one patients who underwent both CTA-CTP and single-photon emission computed tomography myocardial perfusion imaging preceding invasive coronary angiography as part of the CORE320 multicenter study (Coronary Artery Evaluation Using 320-row Multidetector Computed Tomography Angiography and Myocardial Perfusion) were included in this ancillary study. All 4 image modalities were analyzed in blinded, independent core laboratories. Prevalence of flow-limiting CAD defined by invasive coronary angiography equal to 50% or greater with an associated single-photon emission computed tomography myocardial perfusion imaging defect was 45% (114/252) and 23% (30/129) in males and females, respectively. Patient-based diagnostic accuracy defined by the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone in females was 0.83 (0.75-0.89) and for CTA-CTP was 0.92 (0.86-0.97; P=0.003) compared with men where the area under the receiver operating curve for detecting flow-limiting CAD by CTA alone was 0.82 (0.77-0.87) and for CTA-CTP was 0.84 (0.80-0.89; P=0.29). CONCLUSIONS: The combination of CTA-CTP was performed similarly in men and women for identifying flow-limiting coronary stenosis; however, in women, CTP had incremental value over CTA alone, which was not the case in men. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.

Accuracy of Computed Tomographic Angiography and Single-Photon Emission Computed Tomography-Acquired Myocardial Perfusion Imaging for the Diagnosis of Coronary Artery Disease.

BACKGROUND: Establishing the diagnosis of coronary artery disease (CAD) in symptomatic patients allows appropriately allocating preventative measures. Single-photon emission computed tomography (CT)-acquired myocardial perfusion imaging (SPECT-MPI) is frequently used for the evaluation of CAD, but coronary CT angiography (CTA) has emerged as a valid alternative. METHODS AND RESULTS: We compared the accuracy of SPECT-MPI and CTA for the diagnosis of CAD in 391 symptomatic patients who were prospectively enrolled in a multicenter study after clinical referral for cardiac catheterization. The area under the receiver operating characteristic curve was used to evaluate the diagnostic accuracy of CTA and SPECT-MPI for identifying patients with CAD defined as the presence of ≥1 coronary artery with ≥50% lumen stenosis by quantitative coronary angiography. Sensitivity to identify patients with CAD was greater for CTA than SPECT-MPI (0.92 versus 0.62, respectively; P<0.001), resulting in greater overall accuracy (area under the receiver operating characteristic curve, 0.91 [95% confidence interval, 0.88-0.94] versus 0.69 [0.64-0.74]; P<0.001). Results were similar in patients without previous history of CAD (area under the receiver operating characteristic curve, 0.92 [0.89-0.96] versus 0.67 [0.61-0.73]; P<0.001) and also for the secondary end points of ≥70% stenosis and multivessel disease, as well as subgroups, except for patients with a calcium score of ≥400 and those with high-risk anatomy in whom the overall accuracy was similar because CTA's superior sensitivity was offset by lower specificity in these settings. Radiation doses were 3.9 mSv for CTA and 9.8 for SPECT-MPI (P<0.001). CONCLUSIONS: CTA is more accurate than SPECT-MPI for the diagnosis of CAD as defined by conventional angiography and may be underused for this purpose in symptomatic patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00934037.

Dietary patterns track from infancy to preschool age: cross-sectional and longitudinal perspectives.

BACKGROUND: Although it has been suggested that dietary patterns emerge early in life, less is known about the extent to which they track through the toddler and preschool ages. OBJECTIVES: The objectives of this study were to derive cross-sectional dietary patterns at 2, 3, and 5 y of age and assess their correlations and to derive multi-time point dietary patterns from ages 2-5 y and assess their associations with sociodemographic factors and infant feeding patterns. METHODS: Depending on the age considered, analyses included 989-1422 children from the EDEN (Étude des Déterminants pré- et postnatals précoces du développement et de la santé de l'ENfant) mother-child cohort. Dietary intake was collected with the use of food-frequency questionnaires at 2, 3, and 5 y of age. Principal component analyses were applied to these data, first cross-sectionally at each age, then longitudinally accounting for the data collected at all 3 ages. Tracking between patterns was estimated by Spearman correlation coefficients and associations with either the infant feeding patterns or the demographic and socioeconomic factors were assessed with the use of multivariable linear regression analyses. RESULTS: Overall, we derived 2 main cross-sectional patterns labeled "Processed and fast foods" and "Guidelines," the latter being characterized by intakes approximating age-specific dietary guidelines; and 2 multi-time point dietary patterns that corresponded to consistent exposures to similar foods across the 3 ages. The first, labeled "Processed and fast foods at 2, 3, and 5 y," was inversely associated with maternal education and age, and positively associated with the presence of older siblings. The second, called "Guidelines at 2, 3, and 5 y," was predicted by maternal education. Moderate tracking was observed between similar patterns assessed at different ages. CONCLUSIONS: Our findings confirmed the emergence of dietary profiles socially differentiated early in life as well as a moderate tracking of the diet. The promotion of healthy dietary trajectories should be encouraged as early as infancy, in particular in the presence of older siblings and among the most socially disadvantaged population groups.

Predictors of Rapid Progression of Glomerular and Nonglomerular Kidney Disease in Children and Adolescents: The Chronic Kidney Disease in Children (CKiD) Cohort.

BACKGROUND: Few studies have prospectively evaluated the progression of chronic kidney disease (CKD) in children and adolescents, as well as factors associated with progression. STUDY DESIGN: Prospective multicenter observational cohort study. SETTING & PARTICIPANTS: 496 children and adolescents with CKD enrolled in the Chronic Kidney Disease in Children (CKiD) Study. PREDICTORS: Proteinuria, hypoalbuminemia, blood pressure, dyslipidemia, and anemia. OUTCOMES: Parametric failure-time models were used to characterize adjusted associations between baseline levels and changes in predictors and time to a composite event of renal replacement therapy or 50% decline in glomerular filtration rate (GFR). RESULTS: 398 patients had nonglomerular disease and 98 had glomerular disease; of these, 29% and 41%, respectively, progressed to the composite event after median follow-ups of 5.2 and 3.7 years, respectively. Demographic and clinical characteristics and outcomes differed substantially according to the underlying diagnosis; hence, risk factors for progression were assessed in stratified analyses, and formal interactions by diagnosis were performed. Among patients with nonglomerular disease and after adjusting for baseline GFR, times to the composite event were significantly shorter with urinary protein-creatinine ratio > 2mg/mg, hypoalbuminemia, elevated blood pressure, dyslipidemia, male sex, and anemia, by 79%, 69%, 38%, 40%, 38%, and 45%, respectively. Among patients with glomerular disease, urinary protein-creatinine ratio >2mg/mg, hypoalbuminemia, and elevated blood pressure were associated with significantly reduced times to the composite event by 94%, 71%, and 67%, respectively. Variables expressing change in patient clinical status over the initial year of the study contributed significantly to the model, which was cross-validated internally. LIMITATIONS: Small number of events in glomerular patients and use of internal cross-validation. CONCLUSIONS: Characterization and modeling of risk factors for CKD progression can be used to predict the extent to which these factors, either alone or in combination, would shorten the time to renal replacement therapy or 50% decline in GFR in children with CKD.

Determinants of infant formula use and relation with growth in the first 4 months.

The wide variety of infant formula available on the market can be confusing for parents and physicians. We aimed to determine associations between predominant type of formula used from birth to 4 months and parental and child characteristics and type of physician consulted, and then to describe relations between type of formula used and growth. Our analyses included 1349 infants from the EDEN mother-child cohort. Infant's feeding mode and type of formula used were assessed at 4 months by maternal self-report. Infant's weight and height from birth to 4 months, measured in routine follow-up, were documented by health professionals in the infant's personal health record. Anthropometric z-scores were calculated by using World Health Organization growth standards. Multinomial logistic regression was used to identify factors associated with the type of formula predominantly used; relations with growth were analysed by linear regressions. Partially hydrolysed formulas were more likely to be used by primiparous women (P < 0.001), those breastfeeding longer (P < 0.001) and for infants with family history of allergies (P = 0.002). Thickened formulas were more often used by mothers returning to employment in the first 4 months (P = 0.05) and breastfeeding shortly (P < 0.001). No significant relation was found between infant's growth and type of formula (P > 0.20). Infants breastfed shorter showed higher weight-for-age (P < 0.001) and length-for-age (P = 0.001) z-score changes between birth and 4 months. The use of a specific type of infant formula seems to be mainly related to parental characteristics. Infant's growth in the first 4 months is related to other factors than to the type of formula used.

The influence of early feeding practices on fruit and vegetable intake among preschool children in 4 European birth cohorts.

BACKGROUND: Fruit and vegetable intake in children remains below recommendations in many countries. The long-term effects of early parental feeding practices on fruit and vegetable intake are not clearly established. OBJECTIVE: The purpose of the current study was to examine whether early feeding practices influence later fruit and vegetable intake in preschool children. DESIGN: The study used data from 4 European cohorts: the British Avon Longitudinal Study of Parents and Children (ALSPAC), the French Etude des Déterminants pre et postnatals de la santé et du développement de l'Enfant study, the Portuguese Generation XXI Birth Cohort, and the Greek EuroPrevall study. Fruit and vegetable intake was assessed in each cohort by food-frequency questionnaire. Associations between early feeding practices, such as breastfeeding and timing of complementary feeding, and fruit and/or vegetable intake in 2-4-y-old children were tested by using logistic regressions, separately in each cohort, after adjustment for infant's age and sex and maternal age, educational level, smoking during pregnancy, and maternal fruit and vegetable intake. RESULTS: Large differences in early feeding practices were highlighted across the 4 European cohorts with longer breastfeeding duration in the Generation XXI Birth Cohort and earlier introduction to complementary foods in ALSPAC. Longer breastfeeding duration was consistently related to higher fruit and vegetable intake in young children, whereas the associations with age of introduction to fruit and vegetable intake were weaker and less consistent across the cohorts. Mothers' fruit and vegetable intake (available in 3 of the cohorts) did not substantially attenuate the relation with breastfeeding duration. CONCLUSION: The concordant positive association between breastfeeding duration and fruit and vegetable intake in different cultural contexts favors an independent specific effect.

Breastfeeding duration, social and occupational characteristics of mothers in the French 'EDEN mother-child' cohort.

Socio-demographic characteristics of mothers have been associated with exclusive breastfeeding duration, but little is known about the association with maternal full- and part-time employment and return to work in European countries. To study the associations between breastfeeding, any and almost exclusive (infants receiving breast milk as their only milk) breastfeeding, at 4 months of infant's age and the socio-demographic and occupational characteristics of mothers. We used the EDEN mother-child cohort, a prospective study of 2002 singleton pregnant women in two French university hospitals. We selected all mothers (n = 1,339) who were breastfeeding at discharge from the maternity unit. Data on feeding practices were collected at the maternity unit and by postal questionnaires at 4, 8 and 12 months after the birth. Among infants breastfed at discharge, 93% were still receiving any breastfeeding (83% almost exclusive breastfeeding) at the 3rd completed week of life, 78% (63%) at the 1st completed month, and 42% (20%) at the 4th completed month. Time of return to work was a major predictor for stopping breastfeeding: the sooner the mothers returned to work, the less they breastfed their babies at 4 months of infant's age, independently of full-time or part-time employment. The association was stronger for almost exclusive breastfeeding mothers than for any breastfeeding ones. In a society where breastfeeding is not the norm, women may have difficulties combining work and breastfeeding. Specific actions need to be developed and assessed among mothers who return to work and among employers.