Abstract: In clinical practice, no organ system disorder like cardiovascular disease is more prominent in terms of timeliness of treatment:
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| Which cardiovascular biomarkers do you know? |
- Acute myocardial infarction: reperfusion therapy within 1 hour after (acutemyocardialinfarction, AMI), the mortality rate is 1%, and the treatment is within 6 hours, and the mortality rate is about 10% to 12%;
- Acute aortic dissection: If the diagnosis and treatment are not timely and accurate, the early mortality rate is about 1% per hour, and about half of them will die within 48 hours after the onset;
- Cardiac arrest: The cardio-pulmonary resuscitation (CPR) is reduced by 7% to 10% for every 1 minute delay. If effective CPR is given within 4 minutes, the survival rate can reach 50%.
Therefore, one of the keys to the implementation of early, effective and targeted “life-saving treatment” is to accurately diagnose and identify cardiovascular emergencies and to assess the criticality and severity of the disease, in addition to a detailed understanding of the medical history and comprehensive and focused physical examination. In addition to basic electrocardiogram and X-ray examination, point-of-care testing (POCT) of cardiovascular biomarkers is also crucial.
Cardiovascular biomarker
Cardiovascular biomarkers currently used in clinical practice include: cardiac troponin (cTn), creatine kinase isoenzyme-MB (CK-MB), myoglobin (Myo), which reflects myocardial damage. Heart-type fatty acid-binding protein (H-FABP), such as B-type natriuretic peptides (BNP) or N-terminal natriuretic peptide precursor (NT-proBNP), reflecting cardiovascular function State of C-reactive protein (CRP), interleukin-6 (IL-6), and D-dimer, fibrin, which reflect the body's platelet function and coagulation mechanism Original.
It is generally believed that ideal markers that reflect acute myocardial damage or functional changes should have the following characteristics:
- High myocardial specificity;
- High sensitivity, ie release soon after myocardial injury or functional involvement abnormalities It can be detected in the blood circulation, and the duration in the blood circulation is long enough in the window period;
- The concentration of myocardial injury or dysfunctional markers in the blood circulation is related to the degree of damage or the degree of dysfunction;
- The detection method is simple and fast;
- Its application value has been clinically confirmed. Among the above markers, cTn and BNP/NT-proBNP meet the characteristics of ideal markers reflecting myocardial damage and cardiac function, and their POCT has outstanding emergency treatment significance.
Myocardial injury marker
cTnI/T was released into the blood 2 to 4 hours after the onset of AMI, and was used to diagnose AMI better than other markers such as CK-MB. However, because it stays in the blood circulation for a long time (about 1-2 weeks), it can not be used to diagnose early reinfarction, and it is quite difficult to evaluate the effect of reperfusion therapy. It should also be noted that acute heart failure, cardiac contusion, myocardial inflammatory disease, pulmonary embolism and pulmonary hypertension, renal failure, acute neurological diseases including stroke, hyperthyroidism, etc. can also cause elevated cTn.
98% to 99% of CK-MB is present in the myocardium. It rises 4 to 6 hours after AMI and peaks at 18 to 20 hours, lasting about 24 to 72 hours. At 4-6 hours, the sensitivity of diagnosing AMI was about 90% and the specificity was 95%. If the CK-MB enzyme peak is advanced during thrombolysis, the reperfusion is marked. CK-MB quality determination has better accuracy and is suitable for automation.
Myo is a heme protein present in the cytoplasm of myocardium and skeletal muscle. It can be detected in the blood circulation 1 to 3 hours after AMI, peaking at 6-8 hours, and highly sensitive; but no myocardial specificity. A single positive is not enough to diagnose AMI, while a negative one helps to rule out AMI diagnosis; it disappears early in the blood circulation (within 24 hours of onset) and can be used for the diagnosis of reinfarction.
H-FABP is a cytoplasmic protein of cardiomyocytes. It is released into the blood when the heart muscle is damaged. It begins to rise 1 to 3 hours after AMI, peaks at 6 to 8 hours, and returns to normal after 12 to 24 hours. Compared with Myo, there are more skeletal muscles (the concentration in skeletal muscle is about 2 times that in myocardium), and the concentration of H-FABP in cardiomyocytes is higher, reflecting better specificity of myocardial injury. Early markers for diagnosing AMI have received attention.
Clinical practice has found that about 25% of AMI patients have no typical clinical symptoms in the early stage of onset, and about 30% of AMI patients lack specific changes in electrocardiogram; about 1/3 to 1/5 of patients with acute chest pain have normal ECG, and in these patients About 5% to 40% have myocardial infarction. In this case, the detection of biomarkers reflecting acute myocardial injury appears to be more important, especially in the early stage of AMI or when the clinical symptoms are not typical and the electrocardiogram does not change significantly.
At present, myocardial injury markers are widely used clinically:
- Early diagnosis and evaluation of acute coronary syndrome: patients with related symptoms should be tested for biomarkers, cTnI/T for myocardial infarction diagnosis, if cTn cannot be detected, Can be replaced by CK-MB quality detection. Patients within 6 hours of symptom onset, in addition to cTn, should also detect early necrotic markers Myo (currently the most commonly used) or H-FABP;
- To assess the size of infarct size and early thrombolytic therapy: CK- during thrombolytic therapy The MB enzyme peak advances and marks reperfusion;
- CK-MB is a marker for detecting the presence or absence of reinfarction during the early stage of cTn increase in the early stage of the disease.
2. Heart function markers
In recent years, more and more studies have consistently shown that plasma BNP/NT-proBNP levels can reflect hemodynamic changes very sensitively, in the diagnosis of acute cardiogenic (heart failure) and non-cardiac dyspnea. The role of differential diagnosis is increasingly prominent and has excellent application value. It should be emphasized that although BNP or NT-proBNP detection is one of the important basis for the diagnosis of heart failure, especially BNP or NT-proBNP is not particularly helpful to exclude left ventricular systolic dysfunction, but BNP or NT-proBNP is not increased. Equivalent to heart failure, and the value of BNP or NT-proBNP in diastolic cardiac insufficiency needs further confirmation.
BNP or NT-proBNP contributes to the assessment of the severity and prognosis of heart failure. The more severe the heart failure, the higher the BNP or NT-proBNP level, the worse the prognosis. Although overall, patients with different cardiac function grading have a wide range of BNP or NT-proBNP elevations with overlapping or overlapping, it is difficult to achieve a single level of BNP or NT-proBNP to the extent of individual heart failure. Quantitative judgment, but continuous dynamic observation is very helpful for the judgment of the individual's condition and development trend, and even has the role of guiding clinical treatment.
Age, gender and body weight are the main physiological factors affecting BNP or NT-proBNP; many pathological conditions such as renal failure, cirrhosis with ascites, pulmonary thromboembolism, thyroid disease, severe sepsis can cause plasma BNP or NT-proBNP is elevated, and some drugs such as beta blockers and angiotensin-converting enzyme inhibitors may also affect plasma BNP concentrations, which should be noted.
3. Coagulation and fibrinolysis markers
D-dimer is a product of the degradation of fibrin by fibrinolytic enzymes, which mainly reflects the fibrinolytic function. D-dimer mass (concentration) increases when there is activated thrombosis and fibrinolytic activity in the blood vessels of the body (such as acute pulmonary embolism, deep vein thrombosis, acute aortic dissection, acute coronary syndrome, etc.) .
Studies have confirmed that the diagnostic value of D-dimer for the exclusion of deep vein thrombosis (DVT) and pulmonary embolism is very prominent and has been used as one of the primary screening indicators: D-dimer negative and improved wellsscore less than 2 points, DVT can be excluded; D-dimer <0.5mg / L, can basically exclude acute pulmonary embolism, also has high sensitivity and negative predictive value for the exclusion of aortic dissection; not only that, D-dimer significantly increased may also represent the tear The range of fissures is broader and the risk of poor prognosis is increased.
It is important to note that D-dimer has more detection methods, among which enzyme-linked fluorescence analysis has higher sensitivity and negative predictive value, while bedside POCT method is still less mature; age and pregnancy status affect D- The dimer concentration, the age-adjusted D-dimer mass (concentration) threshold is suitable for screening the elderly population, and the D-dimer threshold for pregnant women except acute pulmonary embolism is controversial. In addition, a variety of clinical diseases such as severe infection or sepsis, surgery and trauma, DIC, malignant tumors, severe liver and kidney disease, etc. can also cause an increase in D-dimer quality (concentration).
4. Other biomarkers
Soluble carcinogenesis inhibitory factor (sST2) is a new member of the IL-1 receptor family. As a decoy receptor for IL-33, it binds to IL-33, thereby blocking the binding of IL-33 to ST2L, which in turn weakens IL- Cardiovascular protection of the 33/ST2L signaling pathway. During the process of myocardial injury caused by excessive traction, a large amount of soluble ST2 (sST2) is produced, which makes the myocardial lack of sufficient protection of IL-33, thereby accelerating myocardial remodeling and ventricular dysfunction, leading to an increased risk of death.
Recent studies have shown that sST2 in peripheral blood of patients with congestive heart failure is slowly elevated, but abnormally elevated in acute exacerbation or acute decompensation. The level of sST2 is used to identify whether acute dyspnea is a cardiogenic cause, ie, to diagnose heart failure. Efficacy is highly sensitive and specific, and its changes are not affected by gender. ST2 is also an independent predictor of adverse events in heart failure, and our previous work has yielded similar results.
Copeptin is a part of the C-terminus of pro-prostaglandin (pre-proAVP) and consists of 39 amino acids. When hemodynamics or osmolality changes, it is accompanied by AVP by the pituitary gland. Moore is released into the blood. Many studies have found that plasma and copeptin increase significantly and reach peaks within 0 to 4 hours after AMI, and the elevated time is earlier than cTn, suggesting that patients with early AMI have not significantly increased cTn have a good diagnostic value. All studies have agreed that combined determination of peptide and cTn can increase the value of cTn alone in the diagnosis of AMI, especially in patients with intracerebral pain within 3 to 4 hours. If both cTn and copeptin are negative, AMI can be excluded in emergency department. In vivo and copeptin levels are closely related to the severity of heart failure in patients with heart failure, and can be used as an auxiliary biomarker for early diagnosis, disease monitoring and prognosis of patients with heart failure. The BiomarkersinAcuteHeartFailureTrial assay is considered to be a good predictor of adverse events in patients with acute heart failure for 90 days, and is more valuable if used in combination with BNP. However, from the currently recognized mechanism, copeptin is associated with stress response, but stress hormones are elevated in a variety of pathological conditions, so its specificity is difficult to meet the characteristics of an ideal biomarker. Therefore, its diagnostic value for a specific disease is limited. There is no separate study on the diagnostic efficacy of peptin, but it is evaluated in combination with known biomarkers such as TnI and BNP.
5. Combined application of cardiovascular markers
Clinical studies have shown that a heart disease state is often accompanied by several biochemical markers with abnormal changes. For example, in AMI, myocardial injury not only leads to an increase in cTn, but also increases the tensile tension of cardiomyocytes, leading to BNP/NT-proBNP secretion. Increase; AMI has an increased CRP due to the involvement of an acute inflammatory response. Similarly, in heart failure, increased myocardial cell tension not only increases BNP/NT-proBNP, but also increases myocardial damage and increases cTn due to long-term chronic ischemia, hypoxia, or even exacerbation. Combined determination of cTn and BNP/NT-proBNP can be used as a good indicator for evaluating the condition and prognosis of patients with AMI or heart failure. In addition, considering the different phases of AMI, the myocardial injury markers will exhibit different abnormal changes. When it is difficult to determine the specific onset time, it may be objective to select a certain marker detection. If combined with Myo (or H-FABP) ), CK-MB, cTn should improve the detection rate to avoid missed diagnosis and misdiagnosis.
The reasonable combination of cardiac biomarkers not only helps to improve the sensitivity and specificity of clinical application, but also helps us to understand the damage or functional changes of heart tissue from different aspects, understand the pathological changes of disease development and increase the disease. Cognitive ability and, to a certain extent, guide clinical decision making.
