Troponin I

Troponin I is a cardiac and skeletal muscle protein family. It is a part of the troponin protein complex, where it binds to actin in thin myofilaments to hold the actin-tropomyosin complex in place. Troponin I prevents myosin from binding to actin in relaxed muscle. When calcium binds to the troponin C, it causes conformational changes which lead to dislocation of troponin I. Afterwards, tropomyosin leaves the binding site for myosin on actin leading to contraction of muscle. The letter I is given due to its inhibitory character. It is a useful marker in the laboratory diagnosis of heart attack.^[2] It occurs in different plasma concentration but the same circumstances as troponin T - either test can be performed for confirmation of cardiac muscle damage and laboratories usually offer one test or the other.^[3]

Three

• Slow-twitch skeletal muscle isoform troponin I, TNNI1 (1q31.3, 191042)
• Fast-twitch skeletal muscle isoform troponin I, TNNI2 (11p15.5, 191043)
• Cardiac troponin I, TNNI3 (19q13.4, 191044)

cTnI

Cardiac troponin I, often denoted as cTnI, is presented in cardiac muscle tissue by a single isoform with a molecular weight of 23.9 kDa. It consists of 209 amino acid residues. The theoretical pI of cTnI is 9.05.

In veterinary medicine, increased cTnI has been noted from myocardial damage after ionophore toxicity in cattle.[11]

High-sensitivity troponin I testing

The high sensitive troponin I test is a chemiluminescence microparticle immunoassay, which is used to quantitatively determine cardiac troponin I in human plasma and serum.  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 revascularisation, and cardiovascular death in asymptomatic people.^{[12][13][14][15][16]}

High sensitive troponin I has been proven to have superior clinical performance versus high sensitivity troponin T in patients with renal impairment^[17] and skeletal muscle disease.^[18][19] It is also not affected by diurnal rhythm, which is important when the test is used as a screening tool for CVD.^[20]

Prognostic use

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.^[21] 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.

• High sensitive troponin I test can help to proactively identify individuals at high cardiovascular risk long before symptoms appear.^[21][22] The higher the troponin I level in asymptomatic individuals, the higher the likelihood if subclinical myocardial injury.
• It provides greater accuracy in identifying persons at low CVD risk.^[22][21]
• Troponin I is a biomarker that responds to treatment interventions. Reductions in troponin I levels proved to reduce the risk of future CVD.^[23][24][25]
• High sensitive troponin I used as a screening tool to assess a person's cardiovascular risk and has the potential to reduce the growing cost burden of the healthcare system.^[26]

The efficiency of  the new test has been confirmed by data collected by international studies with the participation of more than 100,000 subjects.^[27]

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.

Indications for testing

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 cardio-vascular risk factors:

1. high blood pressure;
2. obesity;
3. congenital factors, history of cardiovascular diseases;
4. pre-diabetes, diabetes;
5. sedentary lifestyle;
6. metabolic syndrome;
7. dislipidaemia;
8. smoking.

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.^[25]

History

Troponin was discovered in 1965. It was initially named heart myofibrillar apparatus protein component but was later renamed troponin. In 1971, Grieser and Gergely proved that troponin complex consists of three components, which, considering their specific properties, were named TnC, TnI and TnT. Over the following ten years, several groups of researchers started to demonstrate interest in the research of troponin, and the awareness of these proteins increased rapidly. When, finally, the amino acid sequences of troponin isoforms were determined, the opportunity to research functionally significant regions appeared.^[28]

See also

• Troponin
• Troponin T
• Troponin C
• Sliding filament model

References