The relationship of plasma creatinine (as eGFR) and high-sensitivity cardiac troponin and NT-proBNP concentrations in a hospital and community outpatient population.

OBJECTIVES: While persons with overt renal failure have a well-described rise in troponin and NT-proBNP, it is less well described what the relationship is between cardiac markers and persons with impaired renal function, not requiring dialysis. DESIGN & METHODS: We have collected ALL samples referred to our pathology practice over a 24h period and measured hs-cTnI, hs-cTnT, NT-proBNP, calculated the eGFR, and related our measurements to clinical outcomes. RESULTS: For both men and women, for all of hs-cTnI, hs-cTnT and NT-proBNP, there was a graded response, as renal function worsened, the concentration of the cardiac marker increased. CONCLUSIONS: There is a graded inverse relationship between eGFR and the concentrations of hs-cTnI, hs-cTnT and NT-proBNP. For women only there appeared to be an increase in mortality at lowest eGFR.

Cross-sectional study of high-sensitivity cardiac troponins T and I in a hospital and community outpatient setting.

OBJECTIVES: Cardiac troponins are specific for the heart, but not for the acute coronary syndrome. We wanted to assess how common elevated cardiac troponin concentrations were, in a population with significant non-cardiac disease. DESIGN & METHODS: We measured both hs-cTnT and hs-cTnI on all samples submitted to the laboratory during one 24h period, and assessed the magnitude of the cTn concentration with the location and severity of disease of the patient. RESULTS: Community patients and patients from the maternity ward had the lowest cTn concentrations with results above the 99th percentile being only 0-2% of the total. As expected, the highest proportion of results >99th percentile came from Coronary Care and Intensive Care. However, substantial numbers of persons on Medical and Surgical wards, without a primary diagnosis of cardiac disease, also had cTn >99th percentile. Particularly for cTnT, there was a highly significant odds ratio predicting mortality when results above and below the 99th percentile were compared. CONCLUSIONS: Significant illnesses apart from the acute coronary syndrome are important causes of a rise in cTn to above the 99th percentile, and appear to reflect the total body burden of disease. Even when the high hs-cTn concentration is not due to the acute coronary syndrome, there is a significant association with all-cause mortality.

Opportunistic pathology-based screening for diabetes.

OBJECTIVE: To determine the potential of opportunistic glycated haemoglobin (HbA1c) testing of pathology samples to detect previously unknown diabetes. DESIGN: Pathology samples from participants collected for other reasons and suitable for HbA1c testing were utilised for opportunistic diabetes screening. HbA1c was measured with a Biorad Variant II turbo analyser and HbA1c levels of ≥6.5% (48 mmol/mol) were considered diagnostic for diabetes. Confirmation of previously unknown diabetes status was obtained by a review of hospital medical records and phone calls to general practitioners. SETTING: Hospital pathology laboratory receiving samples from hospital-based and community-based (CB) settings. PARTICIPANTS: Participants were identified based on the blood sample collection location in the CB, emergency department (ED) and inpatient (IP) groups. Exclusions pretesting were made based on the electronic patient history of: age <18 years, previous diabetes diagnosis, query for diabetes status in the past 12 months, evidence of pregnancy and sample collected postsurgery or transfusion. Only one sample per individual participant was tested. RESULTS: Of the 22 396 blood samples collected, 4505 (1142 CB, 1113 ED, 2250 IP) were tested of which 327 (7.3%) had HbA1c levels ≥6.5% (48 mmol/mol). Of these 120 (2.7%) were determined to have previously unknown diabetes (11 (1%) CB, 21 (1.9%) ED, 88 (3.9%) IP). The prevalence of previously unknown diabetes was substantially higher (5.4%) in hospital-based (ED and IP) participants aged over 54 years. CONCLUSIONS: Opportunistic testing of referred pathology samples can be an effective method of screening for diabetes, especially in hospital-based and older persons.

Establishment of pediatric reference intervals on a large cohort of healthy children.

BACKGROUND: Reference intervals are essential in assessing the significance of laboratory results. There have been limited studies generating reference intervals from pediatric populations. We have studied a large cohort of healthy children on 3 separate occasions at 2yearly intervals. METHODS: 852 healthy 8year old children were enrolled in a community-based multidisciplinary longitudinal study investigating how early physical activity contributes to health. The same children came back for reassessment at ages 10 and 12years. Blood samples were analyzed for a total of 37 different chemistries, immunoassays or derived values. RESULTS: Reference intervals were derived for all the analytes for males and females separately. CONCLUSION: Whilst our results are largely in agreement with previously published work, we have shown that for a number of analytes, previously published work is distorted by subclinical disease.

Cardiac troponin may be released by ischemia alone, without necrosis.

Whilst it is formally stated that cardiac troponin is only released when cardiac myocytes undergo necrosis, there are a number of clinical situations where troponin is present in the circulation, without any apparent cardiac injury. In these cases, troponin half-life in the circulation is usually substantially shorter than that seen when troponin is released following myocardial infarction with frank necrosis. A mechanism has been described in liver, where large cytoplasmic molecules can pass from the intra- to extra-cellular space without cellular necrosis occurring. This occurs by the formation of membranous blebs which bud off from the plasma membrane of the cell. Blebs develop during cellular ischemia. If the ischemia is limited and re-oxygenation occurs, the blebs may be released into the circulation without rupture of the plasma membrane, resulting in a one-off release of cytoplasmic contents including macromolecules. Evidence from cardiac studies is presented supporting the presence of membranous blebs in cardiac myocytes, enabling troponin to be released from cardiac cells due to ischemia alone, without necrosis.

Contrasting longitudinal and cross-sectional relationships between insulin resistance and percentage of body fat, fitness, and physical activity in children-the LOOK study.

BACKGROUND: Knowledge of individual changes in insulin resistance (IR) and longitudinal relationships of IR with lifestyle-associated factors are of important practical significance, but little longitudinal data exist in asymptomatic children. We aimed to determine (a) changes in the homeostatic model of insulin resistance (HOMA-IR) over a 2-yr period and (b) comparisons of longitudinal and cross-sectional relationships between HOMA-IR and lifestyle-related risk factors. METHODS: Our subjects, 241 boys and 257 girls, were assessed at age 8.1 yr (SD 0.35) and again 2 yr later for fasting blood glucose and insulin, dual X-ray absorptiometry-assessed percentage of body fat (%BF), pedometer-assessed physical activity (PA), and cardio-respiratory fitness (CRF) by multistage running test. RESULTS: HOMA-IR was initially 9% greater in girls than boys and 27% greater 2 yr later. There was no evidence of longitudinal relationships between HOMA-IR and %BF in boys or girls, despite significant cross-sectional relationships (p < 0.001). In boys, there was evidence of a longitudinal relationship between HOMA-IR and both PA (p < 0.001) and CRF (p = 0.05). In girls, we found a cross-sectional relationship between HOMA-IR and CRF (p < 0.001). CONCLUSIONS: HOMA-IR increases between 8 and 10 yr of age and to a greater extent in girls. Longitudinal, unlike cross-sectional, relationships do not support the premise that body fat has any impact on HOMA-IR during this period or that PA or CRF changes affect HOMA-IR in girls. These data draw attention to difficulties in interpreting observational studies in young children.

The lifestyle of our kids (LOOK) project: outline of methods.

This methods paper outlines the overall design of a community-based multidisciplinary longitudinal study with the intent to stimulate interest and communication from scientists and practitioners studying the role of physical activity in preventive medicine. In adults, lack of regular exercise is a major risk factor in the development of chronic degenerative diseases and is a major contributor to obesity, and now we have evidence that many of our children are not sufficiently active to prevent early symptoms of chronic disease. The lifestyle of our kids (LOOK) study investigates how early physical activity contributes to health and development, utilizing a longitudinal design and a cohort of eight hundred and thirty 7-8-year-old (grade 2) school children followed to age 11-12 years (grade 6), their average family income being very close to that of Australia. We will test two hypotheses, that (a) the quantity and quality of physical activity undertaken by primary school children will influence their psychological and physical health and development; (b) compared with existing practices in primary schools, a physical education program administered by visiting specialists will enhance health and development, and lead to a more positive perception of physical activity. To test the first hypothesis we will monitor all children longitudinally over the 4 years. To test the second we will involve an intervention group of 430 children who receive two 50min physical education classes every week from visiting specialists and a control group of 400 who continue with their usual primary school physical education with their class-room teachers. At the end of grades 2, 4, and 6 we will measure several areas of health and development including blood risk factors for chronic disease, cardiovascular structure and function, physical fitness, psychological characteristics and perceptions of physical activity, bone structure and strength, motor control, body composition, nutritional intake, influence of teachers and family, and academic performance.

Bovine colostrum supplementation during running training increases intestinal permeability.

Endurance exercise training can increase intestinal permeability which may contribute to the development of gastrointestinal symptoms in some athletes. Bovine colostrum (BC) supplementation reduces intestinal permeability induced by non-steroidal anti-inflammatory drugs. This study aimed to determine whether BC could also reduce intestinal permeability induced by endurance exercise. Thirty healthy adult males (25.0 ± 4.7 yr; mean ± SD) completed eight weeks of running three times per week for 45 minutes at their lactate threshold while consuming 60 g/day of BC, whey protein (WP) or control (CON). Intestinal permeability was assessed at baseline and after eight weeks by measuring the ratio of urinary lactulose (L) and rhamnose (R) excretion. After eight weeks the L/R ratio increased significantly more in volunteers consuming BC (251 ± 140%) compared with WP (21 ± 35%, P < 0.05) and CON (-7 ± 13%, P < 0.02). The increase in intestinal permeability with BC may have been due to BC inducing greater leakiness of tight junctions between enterocytes or by increasing macromolecular transport as it does in neonatal gut. Further research should investigate the potential for BC to increase intestinal macromolecular transport in adults.

Relationships between myocardial injury, all-cause mortality, vitamin D, PTH, and biochemical bone turnover markers in older patients with hip fractures.

This study examined the relationships between myocardial injury as indicated by serum cardiac troponin I (cTnI) elevation, 25 hydroxyvitamin D [25(OH)D], and PTH status and biochemical markers of bone metabolism in older patients with hip fracture (HF). In 238 consecutive patients (mean age 81.9 +/- 7.8 yr; 72% women) with low trauma HF, serum concentrations of cTnI, 25(OH)D, PTH, calcium, phosphorus, magnesium, osteocalcin, bone-specific alkaline phosphatase (BAP), and urine excretion of free deoxypyridinoline (DPD) and N-terminal cross-linked teleopeptide of type I collagen (NTx) were measured and clinical data were collected prospectively. Myocardial injury (cTnI >0.06 microg/L) presented in 29%, 25(OH)D deficiency (<50 nmol/L) in 81.6%, elevated PTH (>6.5 pmol/L) in 53%, and excessive bone resorption (increased DPD and/or NTx excretion) in 93.7%. Multivariate logistic regression showed that elevated serum PTH level is a major predictor of peri-operative myocardial injury (OR = 2.13; 95% CI 1.01-4.51; p = 0.049) and in-hospital all-cause mortality (OR = 18.5; 95% CI 2.0-72.3; p = 0.010), independent of age, sex, 25(OH)D status, and comorbidities. The degree of hyperparathyroidism was associated with the risk of cTnI elevation and the mortality rate. In cTnI positive patients, PTH levels correlated with cTnI concentrations (r = 0.28; p = 0.026) and urine DPD exretion (r = 0.37; p = 0.004). These results suggest for the first time that in older patients with HF, elevated PTH level is associated with peri-operative myocardial injury and in-hospital all-cause mortality, and that elevated PTH level contributes to both disturbed bone metabolism and poor outcomes.

Newer cardiac troponin I assays have similar performance to troponin T in patients with end-stage renal disease.

BACKGROUND: Troponin T is present in the blood of a majority of patients with endstage renal disease (ESRD) undergoing regular dialysis and presence of troponin T is a predictor of adverse outcome in these patients. With several new formulations of troponin I assays available, this study was performed to see whether these newer assays were able to detect troponin I in these patients more effectively than the older assays. METHODS: One hundred and forty-three patients undergoing regular haemodialysis or peritoneal dialysis had plasma collected and troponin T and troponin I measured by a variety of assays. RESULTS: The newer troponin I assays (Abbott Architect, Bayer Centaur and Beckman Accu-TnI) were able to detect troponin I (>75% of samples) as effectively as the Roche assay was able to detect troponin T, while other troponin I assays had a much lower rate of detection of troponin - DPC Immulite 2000 16% and Abbott AxSYM 35%. However, the troponin T assay had more samples detected at concentrations corresponding to an assay CV of 10% (59% of samples) than did the newer troponin I assays (highest on the Bayer Centaur at 37%). CONCLUSIONS: Newer assays demonstrate that troponin I is present in a similar number of samples as is troponin T, in the blood of patients with dialysis-dependent renal failure, and these newer troponin I assays identify patients at risk of experiencing a cardiac event.

Pharmacokinetics of digoxin cross-reacting substances in patients with acute yellow Oleander (Thevetia peruviana) poisoning, including the effect of activated charcoal.

Intentional self-poisonings with seeds from the yellow oleander tree (Thevetia peruviana) are widely reported. Activated charcoal has been suggested to benefit patients with yellow oleander poisoning by reducing absorption and/or facilitating elimination. Two recent randomized controlled trials (RCTs) assessing the efficacy of activated charcoal yielded conflicting outcomes in terms of mortality. The effect of activated charcoal on the pharmacokinetics of Thevetia cardenolides has not been assessed. This information may be useful for determining whether further studies are necessary. Serial blood samples were obtained from patients enrolled in an RCT assessing the relative efficacy of single-dose and multiple-dose activated charcoal (SDAC and MDAC, respectively) compared with no activated charcoal (NoAC). The concentration of Thevetia cardenolides was estimated with a digoxin immunoassay. The effect of activated charcoal on cardenolide pharmacokinetics was compared between treatment groups by determining the area under the curve for each patient in the 24 hours following admission, the 24-hour mean residence time, and regression lines obtained from serial concentration points, adjusted for exposure. Erratic and prolonged absorption patterns were noted in each patient group. The apparent terminal half-life was highly variable, with a median time of 42.9 hours. There was a reduction in 24-hour mean residence time and in the apparent terminal half-life estimated from linear regression in patients administered activated charcoal, versus the control group (NoAC). This effect was approximately equal in patients administered MDAC or SDAC. Activated charcoal appears to favorably influence the pharmacokinetic profile of Thevetia cardenolides in patients with acute self-poisoning and may have clinical benefits. Given the conflicting clinical outcomes noted in previous RCTs, these mechanistic data support the need for further studies to determine whether a particular subgroup of patients (eg, those presenting soon after poisoning) will benefit from activated charcoal.