Results between different clinical laboratory measurement procedures (CLMP) should be equivalent, within clinically meaningful limits, to enable optimal use of clinical guidelines for disease diagnosis and patient management. When laboratory test results are neither standardized nor harmonized, a different numeric result may be obtained for the same clinical sample. Unfortunately, some guidelines are based on test results from a specific laboratory measurement procedure without consideration of the possibility or likelihood of differences between various procedures. When this happens, aggregation of data from different clinical research investigations and development of appropriate clinical practice guidelines will be flawed. A lack of recognition that results are neither standardized nor harmonized may lead to erroneous clinical, financial, regulatory, or technical decisions. Standardization of CLMPs has been accomplished for several measurands for which primary (pure substance) reference materials exist and/or reference measurement procedures (RMPs) have been developed. However, the harmonization of clinical laboratory procedures for measurands that do not have RMPs has been problematic owing to inadequate definition of the measurand, inadequate analytical specificity for the measurand, inadequate attention to the commutability of reference materials, and lack of a systematic approach for harmonization. To address these problems, an infrastructure must be developed to enable a systematic approach for identification and prioritization of measurands to be harmonized on the basis of clinical importance and technical feasibility, and for management of the technical implementation of a harmonization process for a specific measurand.

BACKGROUND: High-sensitivity cardiac troponin (hscTn) assays are now available that can detect measurable troponin in significantly more individuals in the general population than conventional assays. The clinical use of these hs-cTn assays depends on the development of proper reference values. Therefore, our objective was to define hs-cTnI reference values and determinants in the general community, in a healthy reference cohort, and in subsets with diseases.

In this prospective cohort of women, higher plasma concentrations and dietary magnesium intakes were associated with lower risks of SCD. If the observed association is causal, interventions directed at increasing dietary or plasma magnesium might lower the risk of SCD.

Background-Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease. Methods and Results-In a prospective, nested, case-control analysis within the 121 700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratioϭ2.37 for comparison of the highest and lowest quartile; P for trendϭ0.05) but not for high-sensitivity C-reactive protein (P for trendϭ0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age-and fasting-adjusted models (P for linear trendϭ0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD incrementϭ1.49; 95% confidence interval, 1.09 to 2.05; Pϭ0.01) but eliminated the relationship with high-sensitivity C-reactive protein (Pϭ0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratioϭ5.68; 95% confidence interval, 1.78 to 18.2; Pϭ0.003). Conclusions-In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD.If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women.