Will K. W. H. Wodzig

Reference Population and Marathon Runner Sera Assessed by Highly Sensitive Cardiac Troponin T and Commercial Cardiac Troponin T and I Assays

BACKGROUND Endurance exercise can increase cardiac troponin (cTn) concentrations as high as those seen in cases of minor myocardial infarction. The inability of most cTn assays to reliably quantify cTn at very low concentrations complicates a thorough data analysis, and the clinical implications of such increases remain unclear. The application of recently developed highly sensitive cTn immunoassays may help resolve these problems. METHODS We evaluated the precommercial highly sensitive cardiac troponin T (hs-cTnT) assay from Roche Diagnostics and the Architect cardiac troponin I (cTnI-Architect) assay from Abbott Diagnostics by testing samples from a reference population of 546 individuals and a cohort of 85 marathon runners. We also measured the samples with the current commercial cTnT assay for comparison. RESULTS Although the hs-cTnT and cTnI-Architect assays were capable of measuring cTn concentrations at low concentrations (<0.01 microg/L), only the hs-cTnT assay demonstrated a CV of <10% at the 99th percentile of the reference population and a near-gaussian distribution of the measurements. After a marathon, 86% of the runners had cTnT concentrations greater than the 99th percentile with the hs-cTnT assay, whereas only 45% of the runners showed increased concentrations with the current cTnT assay. cTn concentrations remained significantly increased the day after the marathon. A multiple regression analysis demonstrated marathon experience and age to be significant predictors of postmarathon cTn concentrations (P < 0.05). CONCLUSIONS The hs-cTnT assay was the only assay tested with a performance capability sufficient to detect cTn concentrations in healthy individuals. The number of runners with increased cTn concentrations after a marathon depends highly on an assays limit of detection (LOD). The assay with the lowest LOD, the hs-cTnT assay, showed that almost all runners had increased cTn concentrations. The clinical implications of these findings require further investigation.

Protein supplementation before and after exercise does not further augment skeletal muscle hypertrophy after resistance training in elderly men

BACKGROUND Considerable discrepancy exists in the literature on the proposed benefits of protein supplementation on the adaptive response of skeletal muscle to resistance-type exercise training in the elderly. OBJECTIVE The objective was to assess the benefits of timed protein supplementation on the increase in muscle mass and strength during prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. DESIGN Healthy elderly men (n = 26) aged 72 +/- 2 y were randomly assigned to a progressive, 12-wk resistance-type exercise training program with (protein group) or without (placebo group) protein provided before and immediately after each exercise session (3 sessions/wk, 20 g protein/session). One-repetition maximum (1RM) tests were performed regularly to ensure a progressive workload during the intervention. Muscle hypertrophy was assessed at the whole-body (dual-energy X-ray absorptiometry), limb (computed tomography), and muscle fiber (biopsy) level. RESULTS The 1RM strength increased approximately 25-35% in both groups (P < 0.001). Dual-energy X-ray absorptiometry and computed tomography scans showed similar increases in leg muscle mass (6 +/- 1% in both groups; P < 0.001) and in the quadriceps (9 +/- 1% in both groups), from 75.9 +/- 3.7 and 73.8 +/- 3.2 to 82.4 +/- 3.9 and 80.0 +/- 3.0 cm2 in the placebo and protein groups, respectively (P < 0.001). Muscle fiber hypertrophy was greater in type II (placebo: 28 +/- 6%; protein: 29 +/- 4%) than in type I (placebo: 5 +/- 4%; protein: 13 +/- 6%) fibers, but the difference between groups was not significant. CONCLUSION Timed protein supplementation immediately before and after exercise does not further augment the increase in skeletal muscle mass and strength after prolonged resistance-type exercise training in healthy elderly men who habitually consume adequate amounts of dietary protein. This trial was registered at clinicaltrials.gov as NCT00744094.

Long-term leucine supplementation does not increase muscle mass or strength in healthy elderly men

BACKGROUND It has been reported that the blunted muscle protein synthetic response to food intake in the elderly can be normalized by increasing the leucine content of a meal. OBJECTIVE The objective was to assess the effect of 3 mo of leucine supplementation on muscle mass and strength in healthy elderly men. DESIGN Thirty healthy elderly men with a mean (+/-SEM) age of 71 +/- 4 y and body mass index (BMI; in kg/m(2)) of 26.1 +/- 0.5 were randomly assigned to either a placebo-supplemented (n = 15) or leucine-supplemented (n = 15) group. Leucine or placebo (2.5 g) was administered with each main meal during a 3-mo intervention period. Whole-body insulin sensitivity, muscle strength (one-repetition maximum), muscle mass (measured by computed tomography and dual-energy X-ray absorptiometry), myosin heavy chain isoform distribution, and plasma amino acid and lipid profiles were assessed before, during, and/or after the intervention period. RESULTS No changes in skeletal muscle mass or strength were observed over time in either the leucine- or placebo-supplemented group. No improvements in indexes of whole-body insulin sensitivity (oral glucose insulin sensitivity index and the homeostasis model assessment of insulin resistance), blood glycated hemoglobin content, or the plasma lipid profile were observed. CONCLUSION Long-term leucine supplementation (7.5 g/d) does not augment skeletal muscle mass or strength and does not improve glycemic control or the blood lipid profile in healthy elderly men. This trial was registered at clinicaltrials.gov as NCT00807508.

Exhaled nitric oxide and biomarkers in exhaled breath condensate indicate the presence, severity and control of childhood asthma

Background Exhaled nitric oxide and inflammatory biomarkers in exhaled breath condensate may be useful to diagnose and monitor childhood asthma. Their ability to indicate an asthma diagnosis, and to assess asthma severity and control, is largely unknown.

Prolonged Leucine Supplementation Does Not Augment Muscle Mass or Affect Glycemic Control in Elderly Type 2 Diabetic Men

The loss of muscle mass with aging has been, at least partly, attributed to a blunted muscle protein synthetic response to food intake. Leucine coingestion has been reported to stimulate postprandial insulin release and augment postprandial muscle protein accretion. We assessed the clinical benefits of 6 mo of leucine supplementation in elderly, type 2 diabetes patients. Sixty elderly males with type 2 diabetes (age, 71 ± 1 y; BMI, 27.3 ± 0.4 kg/m(2)) were administered 2.5 g L-leucine (n = 30) or a placebo (n = 30) with each main meal during 6 mo of nutritional intervention (7.5 g/d leucine or placebo). Body composition, muscle fiber characteristics, muscle strength, glucose homeostasis, and basal plasma amino acid and lipid concentrations were assessed prior to, during, and after intervention. Lean tissue mass did not change or differ between groups and at 0, 3, and 6 mo were 61.9 ± 1.1, 62.2 ± 1.1, and 62.0 ± 1.0 kg, respectively, in the leucine group and 62.2 ± 1.3, 62.2 ± 1.3, and 62.2 ± 1.3 kg in the placebo group. There also were no changes in body fat percentage, muscle strength, and muscle fiber type characteristics. Blood glycosylated hemoglobin did not change or differ between groups and was 7.1 ± 0.1% in the leucine group and 7.2 ± 0.2% in the placebo group. Consistent with this, oral glucose insulin sensitivity and plasma lipid concentrations did not change or differ between groups. We conclude that prolonged leucine supplementation (7.5 g/d) does not modulate body composition, muscle mass, strength, glycemic control, and/or lipidemia in elderly, type 2 diabetes patients who habitually consume adequate dietary protein.

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individuals risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase–α1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin–antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

Inflammation, overhydration and cardiac biomarkers in haemodialysis patients: a longitudinal study

BACKGROUND Inflammation, overhydration and elevated cardiac biomarkers are related to outcome in haemodialysis (HD) patients. Here, we explored the relationship between the body composition (BC), inflammation and cardiac biomarker concentrations in HD patients longitudinally. METHODS A total of 44 HD patients were followed for 6 months. BC was assessed by multifrequency bioimpedance (BIA). Serum concentrations of cardiac troponin T (cTnT), high-sensitive C-reactive protein (hsCRP), brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) were assessed at 2 monthly intervals. The longitudinal data analysis was conducted with a marginal model. RESULTS During the follow-up, the parameters describing the BC were highly predictive of both BNP and NT-proBNP and independent of gender, time, hsCRP and cTnT concentrations. The intracellular water (ICW)/body weight (BW) ratio (reflecting malnutrition) exerted a negative effect, whereas the extracellular water (ECW)/BW ratio (reflecting overhydration) had a positive effect on BNP and NT-proBNP concentrations. HsCRP and cTnT concentrations were significantly associated with each other. Furthermore, NT-proBNP concentrations were predictive of cTnT and hsCRP concentrations. CONCLUSIONS In the present study, we find a significant relation between BIA-derived BC parameters and natriuretic peptide concentrations. This relationship was independent of the cardiac history of the patient and suggests that the natriuretic peptide levels are to some degree modifiable by changing a patients fluid distribution. Moreover, cTnT, BNP, NT-proBNP and hsCRP were significantly related, showing a complex relation between overhydration, malnutrition, inflammation and cardiac biomarkers in dialysis patients.

Haemodialysis patients longitudinally assessed by highly sensitive cardiac troponin T and commercial cardiac troponin T and cardiac troponin I assays

Background Elevated cardiac troponin (cTn) concentrations predict an increased mortality in patients suffering from end-stage renal disease (ESRD). This study compares the performance of a precommercial high-sensitive cTnT assay (hs-cTnT) with two contemporary cTn assays in detecting cTn elevations in ESRD patients during a six-month follow-up. Methods Thirty-two ESRD patients were followed for six months, during which cTn concentrations were assessed every two months. Baseline biomarker concentrations were compared with those in a simultaneously measured reference population of 501 healthy subjects. Results During follow-up 26 (81%), 32 (100%) and 9 (28%) of the patients showed elevated cTn concentrations according to the current cTnT, the hs-cTnT and the cTnI assays, respectively. The range of concentrations measured in each patient had a median (interquartile range) magnitude of 0.03 μg/L (0.02–0.06), 0.017 μg/L (0.011–0.029) and 0.011 μg/L (0–0.017) according to the aforementioned assays. Conclusion According to the hs-cTnT assay, all of the ESRD patients had elevated cTnT concentrations at least once during the follow-up. As elevated cTn concentrations are highly prognostic of adverse events, the use of serial measurements has thus identified additional patients at risk for such events. The fact that we find cTn concentrations to be higher in patients with a history of cardiac disease is in line with this. Additional studies in ESRD patients are needed to investigate the added diagnostic and prognostic value of the very low cTnT concentrations and variations detected only by the hs-cTnT assay.

Protein Supplementation during Resistance-Type Exercise Training in the Elderly.

INTRODUCTION Resistance training has been well established as an effective treatment strategy to increase skeletal muscle mass and strength in the elderly. We assessed whether dietary protein supplementation can further augment the adaptive response to prolonged resistance-type exercise training in healthy elderly men and women. METHODS Healthy elderly men (n = 31, 70 ± 1 yr) and women (n = 29, 70 ± 1 yr) were randomly assigned to a progressive, 24-wk resistance-type exercise training program with or without additional protein supplementation (15 g·d-1). Muscle hypertrophy was assessed on a whole-body Dual-energy X-ray absorptiometry (DXA), limb (computed tomography), and muscle fiber (biopsy) level. Strength was assessed regularly by 1-repetition maximum (RM) strength testing. Functional capacity was assessed with a sit-to-stand and handgrip test. RESULTS One-RM strength increased by 45% ± 6% versus 40% ± 3% (women) and 41% ± 4% versus 44% ± 3% (men) in the placebo versus protein group, respectively (P < 0.001), with no differences between groups. Leg muscle mass (women, 4% ± 1% vs 3% ± 1%; men, 3% ± 1% vs 3% ± 1%) and quadriceps cross-sectional area (women, 9% ± 1% vs 9% ± 1%; men, 9% ± 1% vs 10% ± 1%) increased similarly in the placebo versus protein groups (P < 0.001). Type II muscle fiber size increased over time in both placebo and protein groups (25% ± 13% vs 30% ± 9% and 23% ± 12% vs 22% ± 10% in the women and men, respectively). Sit-to-stand improved by 18% ± 2% and 19% ± 2% in women and men, respectively (P < 0.001). CONCLUSION Prolonged resistance-type exercise training increases skeletal muscle mass and strength, augments functional capacity, improves glycemia and lipidemia, and reduces blood pressure in healthy elderly men and women. Additional protein supplementation (15 g·d-1) does not further increase muscle mass, strength, and/or functional capacity.