Associations between long chain polyunsaturated fatty acids and cardiovascular lipid risk factors in youth with type 1 diabetes: SEARCH Nutrition Ancillary Study

In this longitudinal study we explored the relationships between plasma n-3 and n-6 polyunsaturated fatty acids (PUFAs) and Δ5 and Δ6 desaturase activities (D5D and D6D, respectively) and fasting lipids in youth with type 1 diabetes (T1D)

Development and validation of anthropometric prediction equations for estimation of lean body mass and appendicular lean soft tissue in Indian men and women.

Lean body mass (LBM) and muscle mass remain difficult to quantify in large epidemiological studies due to the unavailability of inexpensive methods. We therefore developed anthropometric prediction equations to estimate the LBM and appendicular lean soft tissue (ALST) using dual-energy X-ray absorptiometry (DXA) as a reference method. Healthy volunteers (n = 2,220; 36% women; age 18-79 yr), representing a wide range of body mass index (14-44 kg/m(2)), participated in this study. Their LBM, including ALST, was assessed by DXA along with anthropometric measurements. The sample was divided into prediction (60%) and validation (40%) sets. In the prediction set, a number of prediction models were constructed using DXA-measured LBM and ALST estimates as dependent variables and a combination of anthropometric indices as independent variables. These equations were cross-validated in the validation set. Simple equations using age, height, and weight explained >90% variation in the LBM and ALST in both men and women. Additional variables (hip and limb circumferences and sum of skinfold thicknesses) increased the explained variation by 5-8% in the fully adjusted models predicting LBM and ALST. More complex equations using all of the above anthropometric variables could predict the DXA-measured LBM and ALST accurately, as indicated by low standard error of the estimate (LBM: 1.47 kg and 1.63 kg for men and women, respectively), as well as good agreement by Bland-Altman analyses (Bland JM, Altman D. Lancet 1: 307-310, 1986). These equations could be a valuable tool in large epidemiological studies assessing these body compartments in Indians and other population groups with similar body composition

Influence of age on the diagnosis of myocardial infarction

The 99th centile of cardiac troponin, derived from a healthy reference population, is recommended as the diagnostic threshold for myocardial infarction, but troponin concentrations are strongly influenced by age. Our aim was to assess the diagnostic performance of cardiac troponin in older patients presenting with suspected myocardial infarction. METHODS: In a secondary analysis of a multicenter trial of consecutive patients with suspected myocardial infarction, we assessed the diagnostic accuracy of high-sensitivity cardiac troponin I at presentation for the diagnosis of type 1, type 2, or type 4b myocardial infarction across 3 age groups (<50, 50–74, and ≥75 years) using guideline-recommended sex-specific and age-adjusted 99th centile thresholds. RESULTS: In 46 435 consecutive patients aged 18 to 108 years (mean, 61±17 years), 5216 (11%) had a diagnosis of myocardial infarction. In patients <50 (n=12 379), 50 to 74 (n=22 380), and ≥75 (n=11 676) years, the sensitivity of the guideline-recommended threshold was similar at 79.2% (95% CI, 75.5–82.9), 80.6% (95% CI, 79.2–82.1), and 81.6% (95% CI, 79.8–83.2), respectively. The specificity decreased with advancing age from 98.3% (95% CI, 98.1–98.5) to 95.5% (95% CI, 95.2–95.8), and 82.6% (95% CI, 81.9–83.4). The use of age-adjusted 99th centile thresholds improved the specificity (91.3% [90.8%–91.9%] versus 82.6% [95% CI, 81.9%–83.4%]) and positive predictive value (59.3% [57.0%–61.5%] versus 51.5% [49.9%–53.3%]) for myocardial infarction in patients ≥75 years but failed to prevent the decrease in either parameter with increasing age and resulted in a marked reduction in sensitivity compared with the use of the guideline-recommended threshold (55.9% [53.6%–57.9%] versus 81.6% [79.8%–83.3%]. CONCLUSIONS: Age alters the diagnostic performance of cardiac troponin, with reduced specificity and positive predictive value in older patients when applying the guideline-recommended or age-adjusted 99th centiles. Individualized diagnostic approaches rather than the adjustment of binary thresholds are needed in an aging population

Burden of Cardiovascular Risk Factors Over Time and Arterial Stiffness in Youth With Type 1 Diabetes Mellitus: The SEARCH for Diabetes in Youth Study

Background: The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus–related vascular dysfunction. Methods and Results: We examined cardiovascular risk factors (CVRFs) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi�square tests were used to test for differences in measures of arterial parameters by CVRF. Area under the curve of CVRFs was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non�Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions: In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRFs are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRFs may prevent future cardiovascular events in young individuals with T1DM

Implementation of high-sensitivity cardiac troponin and risk of myocardial infarction or death at 5 years: stepped-wedge, cluster-randomised controlled trial

AbstractObjective: To evaluate the impact of implementing a high-sensitivity cardiac troponin I assay on long-term outcomes in patients with suspected acute coronary syndromeDesign: Secondary observational analysis of a stepped-wedge cluster-randomised controlled trial.Setting: Ten secondary and tertiary care centresParticipants: Consecutive patients with suspected acute coronary syndrome (n=48,282; 47% women) were included in this trial. Myocardial injury was defined as any high-sensitivity cardiac troponin I concentration &gt;99th centile of 16 ng/L in women and 34 ng/L in men.Intervention: Hospital sites were randomly allocated to early (n=5 hospitals) or late (n=5 hospitals) implementation of a high-sensitivity cardiac troponin I assay with sex-specific diagnostic thresholds.Main Outcome Measures: Subsequent myocardial infarction or death at 5 years.Results: Overall, 10,360 patients had cardiac troponin concentrations greater than the 99th centile of whom 1,771 (17%) were reclassified by the high-sensitivity assay. The 5-year incidence of subsequent myocardial infarction or death before and after implementation of the high-sensitivity assay was 29% (5,588/18,978) versus 26% (7,591/29,304), respectively, in all patients (adjusted hazard ratio [aHR] 0.97 [95% CI 0.93 to 1.01]), and 63% (456/720) versus 54% (567/1,051) in those reclassified by the high-sensitivity assay (aHR 0.82 [0.72-0.94]). Following implementation, a reduction in subsequent myocardial infarction or death was observed in patients with non-ischemic myocardial injury (aHR 0·83 [0·75-0·91]), but not in those with type 1 or type 2 myocardial infarction (aHR 0·92 [0·83-1·01] and 0·98 [0·84-1·14]).Conclusions: In patients with suspected acute coronary syndrome, implementation of a high-sensitivity cardiac troponin assay reduced the risk of subsequent myocardial infarction or death at 5 years in those reclassified by the high-sensitivity assay. Improvements in outcome were greatest in patients with non-ischemic myocardial injury suggesting a broader benefit beyond the identification of myocardial infarction.<br/

Outcomes and resource usage of infants born at ≤ 25 weeks gestation in Canada

Objectives: To determine the outcomes and resource usage of infants born at ≤ 25 weeks gestational age (GA). Methods: Retrospective study of infants born between April 2009 and September 2011 at ≤ 25 weeks\u27 GA in all neonatal intensive care units in Canada with follow-up in the neonatal follow-up clinics. Short-term morbidities, neurodevelopmental impairment, significant neurodevelopmental impairment, and resource utilization of infants born at ≤ 24 weeks were compared with neonates born at 25 weeks. Results: Of 803 neonates discharged alive, 636 (80.4%) infants born at ≤ 25 weeks\u27 GA were assessed at 18 to 24 months. Caesarean delivery, lower birth weight, and less antenatal steroid exposure were more common in infants born ≤ 24 weeks as compared with 25 weeks. They had significantly higher incidences of ductus arteriosus ligation, severe intracranial hemorrhage, retinopathy of prematurity as well as longer length of stay, central line days, days on respiratory support, days on total parenteral nutrition, days on antibiotics, and need for postnatal steroids. Neurodevelopmental impairment rates were 68.9, 64.5, and 55.6% (P=0.01) and significant neurodevelopmental impairment rates were 39.3, 29.6, and 20.9% (P\u3c0.01) for infants ≤ 23, 24, and 25 weeks GA, respectively. Postdischarge service referrals were higher for those ≤ 23 weeks. Nonsurviving infants born at 25 weeks GA had higher resource utilization during admission than infants born less than 25 weeks. Conclusions: Adverse outcomes and resource usage were significantly higher among infants born ≤ 24 weeks GA as compared with 25 weeks GA

Correlates of Medical Nutrition Therapy and Cardiovascular Outcomes in Youth With Type 1 Diabetes

To examine whether the types of medical nutrition therapies (MNTs) taught to and used by youth with type 1 diabetes (T1D) varies by socio-demographic characteristics and cardiovascular (CVD) risk factor

<i>HLA</i> and autoantibodies define scleroderma subtypes and risk in African and European Americans and suggest a role for molecular mimicry

Systemic sclerosis (SSc) is a clinically heterogeneous autoimmune disease characterized by mutually exclusive autoantibodies directed against distinct nuclear antigens. We examined HLA associations in SSc and its autoantibody subsets in a large, newly recruited African American (AA) cohort and among European Americans (EA). In the AA population, the African ancestry-predominant HLA-DRB1*08:04 and HLA-DRB1*11:02 alleles were associated with overall SSc risk, and the HLA-DRB1*08:04 allele was strongly associated with the severe antifibrillarin (AFA) antibody subset of SSc (odds ratio = 7.4). These African ancestry-predominant alleles may help explain the increased frequency and severity of SSc among the AA population. In the EA population, the HLA-DPB1*13:01 and HLA-DRB1*07:01 alleles were more strongly associated with antitopoisomerase (ATA) and anticentromere antibody-positive subsets of SSc, respectively, than with overall SSc risk, emphasizing the importance of HLA in defining autoantibody subtypes. The association of the HLA-DPB1*13:01 allele with the ATA+ subset of SSc in both AA and EA patients demonstrated a transancestry effect. A direct correlation between SSc prevalence and HLA-DPB1*13:01 allele frequency in multiple populations was observed (r = 0.98, P = 3 × 10−6). Conditional analysis in the autoantibody subsets of SSc revealed several associated amino acid residues, mostly in the peptide-binding groove of the class II HLA molecules. Using HLA &#x3B1; / &#x3B2; allelic heterodimers, we bioinformatically predicted immunodominant peptides of topoisomerase 1, fibrillarin, and centromere protein A and discovered that they are homologous to viral protein sequences from the Mimiviridae and Phycodnaviridae families. Taken together, these data suggest a possible link between HLA alleles, autoantibodies, and environmental triggers in the pathogenesis of SSc

Fructose intake and cardiovascular risk factors in youth with type 1 diabetes: SEARCH for diabetes in youth study

High consumption of dietary fructose has been shown to contribute to dyslipidemia and elevated blood pressure in adults, but there are few data in youth, particularly those at greater risk of cardiovascular disease (CVD). The aim of this study was to examine the association between fructose intake and CVD risk factors in a diverse population of youth with type 1diabetes (T1D)