Cardiac Troponin T Predicts Long-Term Outcomes in Hemodialysis Patients Daylily S. Ooi, 1,4* Deborah Zimmerman, 2,5 Janet Graham, 2 and George A. Wells 3,5 Background: Increased plasma troponin T (cTnT), but not troponin I (cTnI), is frequently observed in end- stage renal failure patients. Although generally consid- ered spurious, we previously reported an associated increased mortality at 12 months. Methods: We studied long-term outcomes in 244 pa- tients on chronic hemodialysis for up to 34 months, correlating the outcomes to plasma cTnT in routine predialysis samples. In addition, subsequent plasma samples at least 1 year later and within 6 months of data analysis were available in 97 patients and were used to identify patients with increasing plasma cTnT. The endpoints used were death and new or worsening coronary, cerebro-, and peripheral vascular disease and neuropathy. Results: Transplantation occurred more frequently in patients with low initial cTnT: 31%, 13%, and 3% in the groups with cTnT <0.010, 0.010 – 0.099, and >0.100 g/L, respectively. In the same groups, total deaths occurred in 6%, 43%, and 59% and cardiac deaths in 0%, 14%, and 24% of patients. In patients with follow-up samples, the group with increasing cTnT had a significantly in- creased death (relative risk, 2.0; P  0.028). The increase was mainly in cardiac and sudden deaths. Conclusions: Higher plasma cTnT predicts long-term all-cause mortality in hemodialysis patients, even at concentrations <0.100 g/L, as does an increasing cTnT concentration over time. © 2001 American Association for Clinical Chemistry Increased plasma cardiac troponin T (cTnT) 6 (1–5 ), but not troponin I (cTnI) (4, 5), is frequently observed in end-stage renal disease (ESRD) patients without acute coronary disease. This unexplained increase has major clinical implications for these patients who are at high risk of ischemic heart disease, especially silent myocardial infarction. Many consider the increases spurious (6) be- cause older immunohistochemical studies demonstrated the presence of cTnT in skeletal and diaphragmatic mus- cle (7, 8). However, a recent study (9) reported that the cardiac isoform in skeletal muscles of renal failure pa- tients is structurally different from that in cardiac muscle and is not likely to be detected by the commercial assay. We previously reported the pattern of plasma cTnT increases in 172 patients on chronic hemodialysis (10 ) and found that 29% of patients had plasma cTnT concentra- tions 0.1 g/L (the recommended clinical threshold) and 10% had values 0.2 g/L. Serum creatinine, dialysis adequacy, and duration in program were not associated with higher prevalence, but diabetes (57%), especially with multiple complications, and age were. The most intriguing finding was that coronary artery disease (CAD) did not appear to influence cTnT concentrations. At 1 year, we noted a marked increase in mortality in patients with increased cTnT (11 ). Surprisingly, death was attrib- utable mainly to causes other than acute coronary events, and the correlation with increased mortality was signifi- cant mostly in patients traditionally at lower risk: those with no CAD or peripheral vascular disease (PVD), and nondiabetics. We followed this cohort for up to 34 months to confirm these findings. Materials and Methods The study was conducted in accordance with ethical standards of the institution. The initial 172 patients, recruited between August and September 1997, have been Divisions of 1 Biochemistry and 2 Nephrology, Ottawa Hospital–Civic Campus, 1053 Carling Ave., Ottawa, ON K1Y 4E9 Canada. Departments of 3 Epidemiology and Community Medicine, 4 Pathology, and 5 Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada. *Address correspondence to this author at: Division of Biochemistry, Department of Pathology and Laboratory Medicine, Ottawa Hospital–Civic Campus, 1053 Carling Ave., Ottawa, ON K1Y 4E9 Canada. Fax 613-761-5401; e-mail dsooi@ottawahospital.on.ca. Received September 29, 2000; accepted December 12, 2000. 6 Nonstandard abbreviations: cTnT and cTnI, cardiac troponin T and I; ESRD, end-stage renal disease; CAD, coronary artery disease; PVD, peripheral vascular disease; CVD, cerebrovascular disease; CI, confidence interval; and CHF, congestive heart failure. Clinical Chemistry 47:3 412– 417 (2001) Heart Health and the Clinical Laboratory 412