Troponin I, cardiac muscle is a protein that in humans is encoded by the TNNI3 gene. It is a tissue-specific subtype of troponin I, which in turn is a part of the troponin complex.
The TNNI3 gene encoding cardiac troponin I (cTnI) is located at 19q13.4 in the human chromosomal genome. Human cTnI is a 24 kDa protein consisting of 210 amino acids with isoelectric point (pI) of 9.87. cTnI is exclusively expressed in adult cardiac muscle.
cTnI has diverged from the skeletal muscle isoforms of TnI (slow TnI and fast TnI) mainly with a unique N-terminal extension. The amino acid sequence of cTnI is strongly conserved among mammalian species (Fig. 1). On the other hand, the N-terminal extension of cTnI has significantly different structures among mammal, amphibian and fish.
TNNI3 is expressed as a heart specific gene. Early embryonic heart expresses solely slow skeletal muscle TnI. cTnI begins to express in mouse heart at approximately embryonic day 10, and the level gradually increases to one-half of the total amount of TnI in the cardiac muscle at birth. cTnI completely replaces slow TnI in the mouse heart approximately 14 days after birth
Based on in vitrostructure-function relationship studies, the structure of cTnI can be divided into six functional segments: a) a cardiac-specific N-terminal extension (residue 1âÂÂ30) that is not present in fast TnI and slow TnI; b) an N-terminal region (residue 42âÂÂ79) that binds the C domain of TnC; c) a TnT-binding region (residue 80âÂÂ136); d) the inhibitory peptide (residue 128âÂÂ147) that interacts with TnC and actinâÂÂtropomyosin; e) the switch or triggering region (residue 148âÂÂ163) that binds the N domain of TnC; and f) the C-terminal mobile domain (residue 164âÂÂ210) that binds actinâÂÂtropomyosin and is the most conserved segment highly similar among isoforms and across species. Partially crystal structure of human troponin has been determined.
Multiple mutations in cTnI have been found to cause cardiomyopathies. cTnI mutations account for approximately 5% of familial hypertrophic cardiomyopathy cases and to date, more than 20 myopathic mutations of cTnI have been characterized.
The half-life of cTnI in adult cardiomyocytes is estimated to be ~3.2 days and there is a pool of unassembled cardiac TnI in the cytoplasm. Cardiac TnI is exclusively expressed in the myocardium and is thus a highly specific diagnostic marker for cardiac muscle injuries, and cTnI has been universally used as indicator for myocardial infarction. An increased level of serum cTnI also independently predicts poor prognosis of critically ill patients in the absence of acute coronary syndrome.
For more than 15 years cTnI has been known as a reliable marker of cardiac muscle tissue injury. It is considered to be more sensitive and significantly more specific in the diagnosis of myocardial infarction than the "golden marker" of the last decades â CK-MB, as well as total creatine kinase, myoglobin and lactate dehydrogenase isoenzymes. Troponin I is not entirely specific for myocardial damage secondary to infarction. Other causes of raised troponin I include chronic kidney failure, heart failure, subarachnoid haemorrhage and pulmonary embolus.
In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle.
The high sensitive troponin I (hs-cTnI) test is a chemiluminescence microparticle immunoassay, which is used to quantitatively determine cardiac troponin I in human plasma and serum. ÃÂ The test can be used to aid in diagnosing myocardial infarction, as a prognostic marker in patients with acute coronary syndrome and to identify the risk (low, moderate and elevated) of future cardiovascular diseases such as myocardial infarction, heart failure, ischaemic stroke, coronary revascularization, and cardiovascular death in asymptomatic people.
High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment and skeletal muscle disease. It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD.
The basis for the modern prevention of CVD lies in the prognosis of the risk of the development of myocardial infarction, stroke or heart failure in the future. Currently, most prognostic models of cardiovascular risk (European SCORE scale, Framingham scale, etc.) are based on the evaluation of traditional risk factors of CVD. This stratification system is indirect and has several limitations, which include the inaccurate forecasting of risks. These risk scales are heavily dependent on the age of the person. Research data bears evidence that the high sensitive troponin I test enables higher precision in determining the cardiovascular risk group of the individual, if used together with the results of clinical and diagnostic examinations.
The efficiency of the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects.
The ability of high sensitive troponin I to identify individual's cardiovascular risk in asymptomatic people enables physicians to use it in outpatient/ambulatory practice during preventive check-ups, complex health examinations, or examinations of patients with known risk factors. Knowing which cardiovascular risk group a person belongs to allows physicians to promptly determine patient care tactics well before the development of symptoms, and to prevent adverse outcomes.
High sensitive troponin I test is recommended for asymptomatic women and men to assess and stratify their cardiovascular risk.
Individuals may or may not have known established cardiovascular risk factors:
Incorporating the high sensitive troponin I test into initial screening will improve the prediction of future CV events and help individuals be more compliant with lifestyle changes and possible medication recommended by their physician.
This might be a step forward for personalized preventive medicine, being especially relevant at an individual level, when clinicians need to weigh the importance of each risk factor and determine if the person needs therapy in addition to lifestyle advice.
The precise frequency of examinations is not pre-determined; it depends on the specific case, risk category and individual characteristics of a patient. The test may be added to the check-up programs or used as a stand along in conjunction with other clinical and diagnostic findings.
Lateral-flow tests ("rapid diagnostic kits") have been developed for cardiac troponin I. The more basic kinds are qualitative and detect cTnI > 0.5 ng/L, sufficient to "rule in" serious cases in less than a minute. More advanced types allow a quantitative readout using colorimetry, electrochemical fluorescence, or a magnetic detector.