Prognostic Significance of High-Sensitivity Cardiac Troponin T Concentrations between the Limit of Blank and Limit of Detection in Community-Dwelling Adults: A Metaanalysis Ravi H. Parikh, 1 Stephen L. Seliger, 2 James de Lemos, 3 Vijay Nambi, 4 Robert Christenson, 5 Colby Ayers, 6 Wensheng Sun, 7 John S. Gottdiener, 1 Lewis H. Kuller, 8 Christie Ballantyne, 7 and Christopher R. deFilippi 1* BACKGROUND: There is controversy regarding whether to report concentrations of high-sensitivity cardiac tro- ponin T (hs-cTnT) to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay in community-based cohorts. We hypothesized that hs- cTnT concentrations between the LOB and LOD would be associated with poorer cardiovascular outcomes com- pared to concentrations below the LOB. METHODS: hs-cTnT was analyzed in a total of 10 723 participants from the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities (ARIC) study, and Dallas Heart Study (DHS). Participants were divided into 2 groups, those with hs-cTnT concentra- tions below the limit of blank (LOB) (3 ng/L) and those with hs-cTnT between the LOB and limit of detection (LOD) (3– 4.99 ng/L). Cross-sectional associ- ations with traditional cardiovascular risk factors and cardiac structural measurements, and longitudinal asso- ciations with long-term cardiovascular outcomes of incident heart failure and cardiovascular death, were determined. RESULTS: Participants with hs-cTnT between the LOB and LOD for all 3 cohorts were older, more likely to be male, and have a higher burden of cardiovascular risk factors and structural pathology. A metaanalysis of the 3 cohorts showed participants with hs-cTnT between the LOB and LOD were at increased risk of new-onset heart failure (hazard ratio, 1.18; 95% CI, 1.02–1.38) and cardiovascular mortality (hazard ratio, 1.29; 95% CI, 1.06 –1.57). CONCLUSIONS: hs-cTnT concentrations between the LOB and LOD (3– 4.99 ng/L) are associated with a higher prevalence of traditional risk factors, more cardiac pathology, and worse outcomes than concentrations be- low the LOB (3 ng/L). © 2015 American Association for Clinical Chemistry Measurement of cardiac troponins with high-sensitivity (hs) 9 assays has improved risk stratification in patients with chronic cardiovascular disease and in individuals from the general population (1–5 ). Currently, controversy surrounds whether concentrations of hs cardiac troponin T (hs-cTnT) should be reported to the limit of blank (LOB) (3 ng/L) or the limit of detection (LOD) (5 ng/L) of the assay. The LOB is defined as the highest apparent concentration of cTnT in an analyte-free sample. The LOD is defined as the lowest actual concentration of cTnT that can be reliably quantified in a given sample (6–8). The controversy has resulted in inconsistent report- ing in the literature and challenges in prospectively plan- ning studies utilizing the hs-cTnT test. This is particu- larly relevant when the assay is applied to asymptomatic general populations in which a sizable minority of indi- viduals have values that fall between the LOB and LOD. Several large-scale epidemiological community cohort studies have evaluated the prognostic significance of 1 Department of Medicine, Division of Cardiovascular Medicine, University of Maryland School of Medicine, Baltimore, MD; 2 Department of Medicine, Division of Nephrology, University of Maryland School of Medicine, Baltimore, MD; 3 Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX; 4 Department of Medicine, Baylor College of Medicine, Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Michael E. DeBakey Veterans Affairs Hos- pital, Houston, TX; 5 Department of Pathology, University of Maryland School of Medi- cine, Baltimore, MD; 6 Department of Internal Medicine, Department of Clinical Science, University of Texas Southwestern Medical Center, Dallas, TX; 7 Department of Medicine, Baylor College of Medicine, Center for Cardiovascular Disease Prevention, Methodist DeBakey Heart and Vascular Center, Houston, TX; 8 Department of Epidemiology, Uni- versity of Pittsburgh Graduate School of Public Health, Pittsburgh, PA. * Address correspondence to this author at: University of Maryland School of Medicine, Division of Cardiovascular Medicine, 110 S Paca St., 7th Floor, Baltimore, MD 21201. Fax 410-328-6956; e-mail cdefilip@medicine.umaryland.edu. Received June 6, 2015; accepted October 1, 2015. Previously published online at DOI: 10.1373/clinchem.2015.244160  2015 American Association for Clinical Chemistry 9 Nonstandard abbreviations: hs, high sensitivity; hs-cTnT, hs cardiac troponin T; LOB, limit of blank; LOD, limit of detection; CHS, Cardiovascular Health Study; ARIC, Atherosclerosis Risk In Communities; DHS, Dallas Heart Study; cMRI, cardiac MRI; CT, computed tomog- raphy; HDL-c, HDL cholesterol; NT-proBNP, N-terminal pro–type B natriuretic peptide; HR, hazard ratio. Clinical Chemistry 61:12 1524–1531 (2015) Proteomics and Protein Markers 1524