Short- and long-term biological variation of cardiac troponin I in healthy individuals, and patients with end-stage renal failure requiring haemodialysis or cardiomyopathy

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Objectives</jats:title><jats:p>High-sensitivity (hs) cardiac troponin (cTn) assays can quantitate small fluctuations in cTn concentration. Determining biological variation allows calculation of reference change values (RCV), to define significant changes. We assessed the short- and long-term biological variation of cardiac troponin I (cTnI) in healthy individuals and patients with renal failure requiring haemodialysis or cardiomyopathy.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Plasma samples were collected hourly for 4 h and weekly for seven further weeks from 20 healthy individuals, 9 renal failure patients and 20 cardiomyopathy patients. Pre- and post-haemodialysis samples were collected weekly for 7 weeks. Samples were analysed using a hs-cTnI assay (Abbott Alinity ci-series). Within-subject biological variation (CV<jats:sub>I</jats:sub>), analytical variation (CV<jats:sub>A</jats:sub>) and between-subject biological variation (CV<jats:sub>G</jats:sub>) was used to calculate RCVs and index of individuality (II).</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>For healthy individuals, CV<jats:sub>I</jats:sub>, CV<jats:sub>A</jats:sub>, CV<jats:sub>G</jats:sub>, RCV and II values were 8.8, 14.0, 43.1, 45.8% and 0.38 respectively for short-term, and 41.4, 14.0, 25.8, 121.0% and 1.69 for long-term. For renal failure patients, these were 2.6, 5.8, 50.5, 17.6% and 0.30 respectively for short-term, and 19.1, 5.8, 11.2, 55.2% and 1.78 for long-term. For cardiomyopathy patients, these were 4.2, 10.0, 65.9, 30.0% and 0.16 respectively for short-term, and 17.5, 10.0, 63.1, 55.8% and 0.32 for long-term. Mean cTnI concentration was lower post-haemodialysis (15.2 vs. 17.8 ng/L, p &lt; 0.0001), with a 16.9% mean relative change.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The biological variation of cTnI is similar between end-stage renal failure and cardiomyopathy patients, but proportionately greater in well-selected healthy individuals with very low baseline cTnI concentrations.</jats:p></jats:sec>

Biological variation of cardiac myosin-binding protein C in healthy individuals

“…Our data demonstrate a within-subject CV I and between-subject CV G of 17.8% (14.8-21.0%), and 66.9% (50.4-109.9%), respectively. Both fall within the range of respective CV calculated in similar cTn long term biological variability studies (Table 3) [15][16][17][18][19][20][21][22][23]. The derived index individuality II was also similar to that for cTn.…”

Clinical relevance of biological variation of cardiac troponins

“…From a clinical point of view, some important issues should be taken into consideration about the evaluation of cardiovascular risk in the general population [6, 15-17, 52, 69, 83]. Due to the very low intra-individual biological variation of cardiac troponins, serial measurements of hs-cTn significantly improve prognostic accuracy [29,[46][47][48][49][50]. However, practically, a single measurement of cTn using high-sensitivity methods should be adequate for the prediction of cardiovascular risk [29,82].…”

“…To make the diagnosis of myocardial injury, clinicians should compare a single value of hs-cTn, which has a very low intra-individual (CV i ) ( Table 1), with the 99th percentile URL value, which, on the contrary, has both inter-individual variability (CV g ) and confidence interval very large (Table 2). Furthermore, other confounding variables may affect the 99th percentile URL value, such as the analytical performance of immunoassay methods and the demographic characteristics related to the reference population, such as sex, age, genetic determinants and ethnicity [18,21,50,51,95,96]. Unfortunately, a lot of cardiac and even extracardiac clinical conditions may cause an increase in hs-cTn levels above the 99th percentile URL value [1,3,18,21,38,50,51,95,96].…”

“…Furthermore, other confounding variables may affect the 99th percentile URL value, such as the analytical performance of immunoassay methods and the demographic characteristics related to the reference population, such as sex, age, genetic determinants and ethnicity [18,21,50,51,95,96]. Unfortunately, a lot of cardiac and even extracardiac clinical conditions may cause an increase in hs-cTn levels above the 99th percentile URL value [1,3,18,21,38,50,51,95,96]. Accordingly, only a minority of patients admitted to the emergency department with a hs-cTn value above the 99th percentile URL values actually has an AMI [1,3,51,95,96].…”

Cardiac Troponin Serum Concentration Measurement Is Useful Not Only in the Diagnosis of Acute Cardiovascular Events

“…Ischemic myocardial damage may also result from disproportions between oxygen supply and demand due to conditions such as bradyarrhythmia [ 60 ], tachyarrhythmia [ 61 ], poorly controlled hypertension resulting in left ventricular hypertrophy [ 62 ], respiratory failure [ 63 ], hypotension [ 64 ], shock (different types, both cardiogenic and non-cardiogenic) [ 65 , 66 , 67 ], or severe anemia [ 68 ]. Moreover, important diseases in which elevated cardiac troponin levels are observed include heart failure [ 69 , 70 , 71 ], myocarditis [ 72 , 73 ], and chronic renal failure [ 74 , 75 ].…”