OBJECTIVE:We sought to determine the effect of patient selection on the 99th reference percentile of 2 sensitive and 1 high-sensitivity (hs) cardiac troponin assays in a well-defined reference population.METHODS: Individuals Ͼ45 years old were randomly selected from 7 representative local community practices. Detailed information regarding the participants was collected via questionnaires. The healthy reference population was defined as individuals who had no history of vascular disease, hypertension, or heavy alcohol intake; were not receiving cardiac medication; and had blood pressure Ͻ140/90 mmHg, fasting blood glucose Ͻ110 mg/dL (approximately 6 mmol/L), estimated creatinine clearance, and normal cardiac function according to results of echocardiography. Samples were stored at Ϫ70°C until analysis for cardiac troponin I (cTnI) and cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide. RESULTS:Application of progressively more stringent population selection strategies to the initial baseline population of 545 participants until the only individuals who remained were completely healthy according to the study criteria reduced the number of outliers seen and led to a progressive decrease in the 99th-percentile value obtained for the Roche hs-cTnT assay and the sensitive Beckman cTnI assay but not for the sensitive Siemens Ultra cTnI assay. Furthermore, a sex difference found in the baseline population for the hscTnT (P ϭ 0.0018) and Beckman cTnI assays (P Ͻ 0.0001) progressively decreased with more stringent population selection criteria. CONCLUSIONS:The reference population selection strategy significantly influenced the 99th percentile reference values determined for troponin assays and the observed sex differences in troponin concentrations.

Background. Equations for estimating glomerular filtration rate (GFR) have not been validated in Sub-Saharan African populations, and data on GFR are few.Methods. GFR by creatinine clearance (Ccr) using 24-hour urine collections and estimated GFR (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD-4)[creatinine calibrated to isotope dilution mass spectrometry (IDMS) standard], Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft–Gault equations were obtained in Ghanaians aged 40–75. The population comprised 1013 inhabitants in 12 villages; 944 provided a serum creatinine and two 24-hour urines. The mean weight was 54.4 kg; mean body mass index was 21.1 kg/m2.Results. Mean GFR by Ccr was 84.1 ml/min/1.73 m2; 86.8% of participants had a GFR of ≥60 ml/min/1.73 m2. Mean MDRD-4 eGFR was 102.3 ml/min/1.73 m2 (difference vs. Ccr, 18.2: 95% CI: 16.8–19.5); when the factor for black race was omitted, the value (mean 84.6 ml/min/1.73 m2) was close to Ccr. Mean CKD-EPI eGFR was 103.1 ml/min/1.73 m2, and 89.4 ml/min/1.73 m2 when the factor for race was omitted. The Cockcroft–Gault equation underestimated GFR compared with Ccr by 9.4 ml/min/1.73 m2 (CI: 8.3–10.6); particularly in older age groups. GFR by Ccr, and eGFR by MDRD-4, CKD-EPI and Cockcroft–Gault showed falls with age: MDRD-4 5.5, Ccr 7.7, CKD-EPI 8.8 and Cockcroft–Gault 11.0 ml/min/1.73 m2/10 years. The percentage of individuals identified with CKD stages 3–5 depended on the method used: MDRD-4 1.6% (7.2 % without factor for black race; CKD-EPI 1.7% (4.7% without factor for black race), Ccr 13.2% and Cockcroft–Gault 21.0%.Conclusions. Mean eGFR by both MDRD-4 and CKD-EPI was considerably higher than GFR by Ccr and Cockcroft–Gault, a difference that may be attributable to leanness. MDRD-4 appeared to underestimate the fall in GFR with age compared with the three other measurements; the fall with CKD-EPI without the adjustment for race was the closest to that of Ccr. An equation tailored specifically to the needs of the lean populations of Africa is urgently needed. For the present, the CKD-EPI equation without the adjustment for black race appears to be the most useful.

The cardiac troponins form part of the regulatory mechanism for muscle contraction. Specific cardiac isoforms of cardiac troponin T and cardiac troponin I exist and commercially available immunoassay systems have been developed for their measurement. A large number of clinical and analytical studies have been performed and the measurement of cardiac troponins is now considered the 'gold standard' biochemical test for diagnosis of myocardial damage. There have been advances in understanding the development and structure of troponins and their degradation following myocardial cell necrosis. This has contributed to the understanding of the problems with current assays. Greater clinical use has also highlighted areas of analytical and clinical confusion. The assays are reviewed based on manufacturers' information, current published material as well as the authors' in-house experience.

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BackgroundCardiovascular events are frequent and vascular endothelial function is abnormal in patients with chronic kidney disease (CKD). We demonstrated endothelial dysfunction with vitamin D deficiency in CKD patients; however the impact of cholecalciferol supplementation on vascular stiffness and vasomotor function, endothelial and bone biomarkers in CKD patients with low 25-hydroxy vitamin D [25(OH)D] is unknown, which this study investigated.MethodsWe assessed non-diabetic patients with CKD stage 3/4, age 17–80 years and serum 25(OH)D <75 nmol/L. Brachial artery Flow Mediated Dilation (FMD), Pulse Wave Velocity (PWV), Augmentation Index (AI) and circulating blood biomarkers were evaluated at baseline and at 16 weeks. Oral 300,000 units cholecalciferol was administered at baseline and 8-weeks.ResultsClinical characteristics of 26 patients were: age 50±14 (mean±1SD) years, eGFR 41±11 ml/min/1.73 m2, males 73%, dyslipidaemia 36%, smokers 23% and hypertensives 87%.At 16-week serum 25(OH)D and calcium increased (43±16 to 84±29 nmol/L, p<0.001 and 2.37±0.09 to 2.42±0.09 mmol/L; p = 0.004, respectively) and parathyroid hormone decreased (10.8±8.6 to 7.4±4.4; p = 0.001). FMD improved from 3.1±3.3% to 6.1±3.7%, p = 0.001.Endothelial biomarker concentrations decreased: E-Selectin from 5666±2123 to 5256±2058 pg/mL; p = 0.032, ICAM-1, 3.45±0.01 to 3.10±1.04 ng/mL; p = 0.038 and VCAM-1, 54±33 to 42±33 ng/mL; p = 0.006. eGFR, BP, PWV, AI, hsCRP, von Willebrand factor and Fibroblast Growth Factor-23, remained unchanged.ConclusionThis study demonstrates for the first time improvement of endothelial vasomotor and secretory functions with vitamin D in CKD patients without significant adverse effects on arterial stiffness, serum calcium or FGF-23.Trial RegistrationClinicalTrials.gov NCT02005718