Determinants and prognostic implications of cardiac troponin T measured by a sensitive assay in type 2 diabetes mellitus

Jonas Hallén, Odd Erik Johansen, Kåre I Birkeland, Lars Gullestad, Svend Aakhus, Knut Endresen, Solve Tjora, Allan S Jaffe, Dan Atar, Jonas Hallén, Odd Erik Johansen, Kåre I Birkeland, Lars Gullestad, Svend Aakhus, Knut Endresen, Solve Tjora, Allan S Jaffe, Dan Atar

Abstract

Background: The cardiac troponins are biomarkers used for diagnosis of myocardial injury. They are also powerful prognostic markers in many diseases and settings. Recently introduced high-sensitivity assays indicate that chronic cardiac troponin elevations are common in response to cardiovascular (CV) morbidity. Type 2 diabetes mellitus (T2DM) confers a high risk of CV disease, but little is known about chronic cardiac troponin elevations in diabetic subjects. Accordingly, we aimed to understand the prevalence, determinants, and prognostic implications of cardiac troponin T (cTnT) elevations measured with a high-sensitivity assay in patients with T2DM.

Methods: cTnT was measured in stored, frozen serum samples from 124 subjects enrolled in the Asker and Bærum Cardiovascular Diabetes trial at baseline and at 2-year follow-up, if available (96 samples available). Results were analyzed in relation to baseline variables, hospitalizations, and group assignment (multifactorial intensive versus conventional diabetes care for lowering CV risk).

Results: One-hundred thirteen (90%) had detectable cTnT at baseline and of those, 22 (18% of the total population) subjects had values above the 99th percentile for healthy controls (13.5 ng/L). Levels at baseline were associated with conventional CV risk factors (age, renal function, gender). There was a strong correlation between cTnT levels at the two time-points (r=0.92, p>0.001). Risk for hospitalizations during follow-up increased step-wise by quartiles of hscTnT measured at baseline (p=0.058).

Conclusions: Elevations of cTnT above the 99th percentile measured by a highly sensitive assay were encountered frequently in a population of T2DM patients. cTnT levels appeared to be stable over time and associated with conventional CV risk factors. Although a clear trend was present, no statistically robust associations with adverse outcomes could be found.

Figures

Figure 1
Figure 1
Flow chart showing number of patients included for cross-sectional and prospective investigation and reasons for exclusion; and the number of patients who had troponin T measured at the two time points.
Figure 2
Figure 2
Distribution of cardiac troponin T by the high-sensitivity assay in patients with type 2 diabetes mellitus.
Figure 3
Figure 3
Scatter plot of cardiac troponin T values at baseline and 2 years.
Figure 4
Figure 4
Bar charts of all-cause and diabetes-related hospitalizations according to cardiac troponin T levels stratified by quartiles at baseline. P-value for trend is 0.058 (all-cause) and .055 (diabetes-related). CV = cardiovascular

References

    1. Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta-analysis: glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med. 2004;141:421–431.
    1. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321:405–412. doi: 10.1136/bmj.321.7258.405.
    1. Gerstein HC, Miller ME, Byington RP, Goff DC Jr, Bigger JT, Buse JB, Cushman WC, Genuth S, Ismail-Beigi F, Grimm RH Jr. et al.Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–2559. doi: 10.1056/NEJMoa0802743.
    1. Patel A, MacMahon S, Chalmers J, Neal B, Billot L, Woodward M, Marre M, Cooper M, Glasziou P, Grobbee D. et al.Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–2572. doi: 10.1056/NEJMicm066227.
    1. Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580–591. doi: 10.1056/NEJMoa0706245.
    1. Kumler T, Gislason GH, Kober L, Torp-Pedersen C. Diabetes is an independent predictor of survival 17 years after myocardial infarction: follow-up of the TRACE registry. Cardiovasc Diabetol. 2010;9:22. doi: 10.1186/1475-2840-9-22.
    1. Johansen OE, Gullestad L, Blaasaas KG, Orvik E, Birkeland KI. Effects of structured hospital-based care compared with standard care for Type 2 diabetes-The Asker and Baerum Cardiovascular Diabetes Study, a randomized trial. Diabet Med. 2007;24:1019–1027. doi: 10.1111/j.1464-5491.2007.02198.x.
    1. Thygesen K, Alpert JS, White HD. Universal definition of myocardial infarction. J Am Coll Cardiol. 2007;50:2173–2195. doi: 10.1016/j.jacc.2007.09.011.
    1. Atar D. New definition of myocardial infarction. BMJ. 2008;337:a3078. doi: 10.1136/bmj.a3078.
    1. Wallace TW, Abdullah SM, Drazner MH, Das SR, Khera A, McGuire DK, Wians F, Sabatine MS, Morrow DA, de Lemos JA. Prevalence and determinants of troponin T elevation in the general population. Circulation. 2006;113:1958–1965. doi: 10.1161/CIRCULATIONAHA.105.609974.
    1. Johansen OE, Birkeland KI, Orvik E, Flesland O, Wergeland R, Ueland T, Smith C, Endresen K, Aukrust P, Gullestad L. Inflammation and coronary angiography in asymptomatic type 2 diabetic subjects. Scand J Clin Lab Invest. 2007;67:306–316. doi: 10.1080/00365510601045088.
    1. Giannitsis E, Kurz K, Hallermayer K, Jarausch J, Jaffe AS, Katus HA. Analytical Validation of a High-Sensitivity Cardiac Troponin T Assay. Clin Chem. 2010;56:254–261. doi: 10.1373/clinchem.2009.132654.
    1. Pellikka PA, Nagueh SF, Elhendy AA, Kuehl CA, Sawada SG. American Society of Echocardiography recommendations for performance, interpretation, and application of stress echocardiography. J Am Soc Echocardiogr. 2007;20:1021–1041. doi: 10.1016/j.echo.2007.07.003.
    1. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS. et al.Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18:1440–1463. doi: 10.1016/j.echo.2005.10.005.
    1. Stevens RJ, Kothari V, Adler AI, Stratton IM. The UKPDS risk engine: a model for the risk of coronary heart disease in Type II diabetes (UKPDS 56) Clin Sci (Lond) 2001;101:671–679. doi: 10.1042/CS20000335.
    1. Latini R, Masson S, Anand IS, Missov E, Carlson M, Vago T, Angelici L, Barlera S, Parrinello G, Maggioni AP. et al.Prognostic value of very low plasma concentrations of troponin T in patients with stable chronic heart failure. Circulation. 2007;116:1242–1249. doi: 10.1161/CIRCULATIONAHA.106.655076.
    1. Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, Tjora S, Domanski MJ, Gersh BJ, Rouleau JL, A Sensitive Cardiac Troponin T Assay in Stable Coronary Artery Disease. N Engl J Med. 2009.
    1. Miller WL, Hartman KA, Burritt MF, Grill DE, Jaffe AS. Profiles of serial changes in cardiac troponin T concentrations and outcome in ambulatory patients with chronic heart failure. J Am Coll Cardiol. 2009;54:1715–1721. doi: 10.1016/j.jacc.2009.07.025.
    1. Bakshi TK, Choo MK, Edwards CC, Scott AG, Hart HH, Armstrong GP. Causes of elevated troponin I with a normal coronary angiogram. Intern Med J. 2002;32:520–525. doi: 10.1046/j.1445-5994.2002.00270.x.
    1. Jeremias A, Gibson CM. Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded. Ann Intern Med. 2005;142:786–791.
    1. Blair SN, Kampert JB, Kohl HW III, Barlow CE, Macera CA, Paffenbarger RS Jr, Gibbons LW. Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA. 1996;276:205–210. doi: 10.1001/jama.276.3.205.
    1. Peterson PN, Magid DJ, Ross C, Ho PM, Rumsfeld JS, Lauer MS, Lyons EE, Smith SS, Masoudi FA. Association of exercise capacity on treadmill with future cardiac events in patients referred for exercise testing. Arch Intern Med. 2008;168:174–179. doi: 10.1001/archinternmed.2007.68.
    1. Yamaoka-Tojo M, Tojo T, Takahira N, Matsunaga A, Aoyama N, Masuda T, Izumi T. Elevated circulating levels of an incretin hormone, glucagon-like peptide-1, are associated with metabolic components in high-risk patients with cardiovascular disease. Cardiovasc Diabetol. 2010;9:17. doi: 10.1186/1475-2840-9-17.
    1. Knudsen EC, Seljeflot I, Abdelnoor M, Eritsland J, Mangschau A, Muller C, Arnesen H, Andersen GO. Increased levels of CRP and MCP-1 are associated with previously unknown abnormal glucose regulation in patients with acute STEMI: a cohort study. Cardiovasc Diabetol. 2010;9:47. doi: 10.1186/1475-2840-9-47.
    1. Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115:949–952. doi: 10.1161/CIRCULATIONAHA.106.683110.
    1. Lindahl B, Venge P, James S. The new high-sensitivity cardiac troponin T assay improves risk assessment in acute coronary syndromes. Am Heart J. 2010;160:224–229. doi: 10.1016/j.ahj.2010.05.023.
    1. Jaffe AS. Chasing troponin: how low can you go if you can see the rise? J Am Coll Cardiol. 2006;48:1763–1764. doi: 10.1016/j.jacc.2006.08.006.

Source: PubMed

スポンサーと協力者

医学的状態

薬物療法

3
購読する