Significant race and gender differences exist in the population distribution of CRP. Further research is needed to determine whether race and gender differences in CRP levels contribute to differences in cardiovascular outcomes, and whether thresholds for cardiovascular risk assessment should be adjusted for different race and gender groups.

Background-The association between higher body mass index (BMI) and lower B-type natriuretic peptide (BNP) level is thought to be mediated by expression of the natriuretic peptide clearance receptor (NPR-C) in adipose tissue. To explore this association, we tested 2 hypotheses: (1) that N-terminal (NT)-proBNP, which is not believed to bind NPR-C, would not be associated with BMI and (2) that lower BNP would be more closely associated with fat mass than with lean mass. Methods and Results-Measurements of BNP, NT-proBNP, and body composition by direct dual energy x-ray absorptiometry (DEXA) were performed in 2707 subjects from the Dallas Heart Study. The associations between obesity and low BNP (Ͻ4 ng/L) or low NT-proBNP (lowest sex-specific quartile) were evaluated with multivariable logistic regression models stratified by sex and adjusted for age, race/ethnicity, hypertension, left ventricular mass, and end-diastolic volume. Higher BMI was independently associated with lower BNP and NT-proBNP (all PϽ0.001). When BMI was replaced with both DEXA-derived lean and fat mass, greater lean mass, but not fat mass, was associated with low BNP and NT-proBNP levels. Conclusions-In a large, population-based cohort, we confirm the previously described association between higher BMIand lower BNP and demonstrate a similar inverse association between BMI and NT-proBNP. Interestingly, both BNP and NT-proBNP are more closely associated with lean mass than with fat mass. These findings do not support the hypothesis that the lower BNP levels seen in obesity are driven by enhanced BNP clearance mediated via NPR-C.

Background-The prevalence and determinants of cardiac troponin T (cTnT) elevation in the general population are unknown, and the significance of minimally increased cTnT remains controversial. Our objective was to determine the prevalence and determinants of cTnT elevation in a large, representative sample of the general population. Methods and Results-cTnT was measured from stored plasma samples in 3557 subjects of the Dallas Heart Study, a population-based sample. cTnT elevation (Ն0.01 g/L) was correlated with clinical variables and cardiac MRI findings. The sample weight-adjusted prevalence of cTnT elevation in the general population was 0.7%. In univariable analyses, cTnT elevation was associated with older age, black race, male sex, coronary artery calcium by electron beam CT, a composite marker of congestive heart failure (CHF), left ventricular hypertrophy (LVH), diabetes mellitus (DM), and chronic kidney disease (CKD) (PϽ0.001 for each). Subjects with minimally increased (0.01 to 0.029 g/L) and increased (Ն0.03 g/L) cTnT had a similar prevalence of these characteristics. In multivariable logistic regression analysis, LVH, CHF, DM, and CKD were independently associated with cTnT elevation. Conclusions-In the general population, cTnT elevation is rare in subjects without CHF, LVH, CKD, or DM, suggesting that the upper limit of normal for the immunoassay should be Ͻ0.01 g/L.

Background: ROC curves have become the standard for describing and comparing the accuracy of diagnostic tests. Not surprisingly, ROC curves are used often by clinical chemists. Our aims were to observe how the accuracy of clinical laboratory diagnostic tests is assessed, compared, and reported in the literature; to identify common problems with the use of ROC curves; and to offer some possible solutions. Methods: We reviewed every original work using ROC curves and published in Clinical Chemistry in 2001 or 2002. For each article we recorded phase of the research, prospective or retrospective design, sample size, presence/absence of confidence intervals (CIs), nature of the statistical analysis, and major analysis problems. Results: Of 58 articles, 31% were phase I (exploratory), 50% were phase II (challenge), and 19% were phase III (advanced) studies. The studies increased in sample size from phase I to III and showed a progression in the use of prospective designs. Most phase I studies were powered to assess diagnostic tests with ROC areas >0.70. Thirty-eight percent of studies failed to include CIs for diagnostic test accuracy or the CIs were constructed inappropriately. Thirty-three percent of studies provided insufficient analysis for comparing diagnostic tests. Other problems included dichotomization of the gold standard scale and inappropriate analysis of the equivalence of two diagnostic tests. Conclusion: We identify available software and make some suggestions for sample size determination, testing for equivalence in diagnostic accuracy, and alternatives to a dichotomous classification of a continuous-scale

BACKGROUND:The improved detection limit and precision in new-generation commercial assays for cardiac troponin I (cTnI) have lowered the 99th-percentile cutoff value, yielding higher frequencies of positive test results. Because serial testing is important in interpreting low concentrations, we evaluated the biological variation of cTnI in both the short (hours) and long (weeks) terms and determined reference change values (RCVs) and the index of individuality (II) for cTnI.

Osteocalcin, a major noncollagenous matrix protein of bone, dentin, and cementum, is found in tight association with the calcium phosphate mineral phase of these tissues. This article reviews the structural data for osteocalcin relevant to mineral adsorption. The equilibrium-binding properties for Ca2+ ions and hydroxyapatite are considered, along with the apparent physicochemical effects of osteocalcin on bone mineral dynamics. Several of osteocalcin's possible biological activities (involvement in mineralization, chemoattraction, and leukocyte elastase inhibition) are discussed in relation to the mineral-adsorption characteristics of this protein.

Background-Elevated levels of C-reactive protein (CRP) are associated with increased risk for incident cardiovascular events on the basis of observations from several prospective epidemiological studies. However, less is known regarding the relationship between CRP levels and atherosclerotic burden. Methods and Results-We measured CRP in 3373 subjects 30 to 65 years of age who were participating in the Dallas Heart Study, a multiethnic, population-based, probability sample. Electron-beam CT scans were used to measure coronary artery calcification (CAC) in 2726 of these subjects, and MRI was used to measure aortic plaque in 2393. CRP levels were associated with most traditional cardiovascular risk factors. Subjects with CAC had higher median CRP levels than those without CAC (men: median, 2.4 versus 1.8 mg/L, PϽ0.001; women: median, 5.2 versus 3.6 mg/L, PϽ0.001), and there was a modest trend toward increasing CRP levels with increased CAC levels in men (P for trendϭ0.003) but not in women (P for trendϭ0.08). Male subjects with aortic plaque also had higher CRP levels than those without (median, 2.3 versus 1.8; PϽ0.001). In multivariate analysis adjusted for traditional cardiovascular risk factors, body mass index, and estrogen and statin medication use, the associations between CRP levels and CAC and CRP levels and aortic plaque were no longer statistically significant. Conclusions-In a large, population-based sample, subjects with higher CRP levels had a modest increase in the prevalence of subclinical atherosclerosis, but this association was not independent of traditional cardiovascular risk factors. CRP is a poor predictor of atherosclerotic burden.

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