Sindrome coronario agudo Marcadores de lesion miocardica (1) (1)
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Enfermedad cardiovascular (ECV) is a major public health problem worldwide
Diagnostic tools are needed to recognize ischemic myocardic and establish timely treatment
Recognition of individuals with risk factors for acute coronary syndrome (SCA) is important
Review of biomarkers of myocardic leasures frequently used as predictors for coronary disease
Síndrome coronario agudo: Marcadores de lesión miocárdica
Introduction to ECV as the leading cause of death and consumption of economic resources
Primary and secondary prevention of ECV are priorities in public health systems
According to WHO, 15,000,000 people die annually from ischemic heart disease
ECV starts with the evolution of risk factors such as diabetes mellitus
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Síndrome coronario agudo y síndrome metabólico
El síndrome metabólico contribuye al desarrollo de la aterosclerosis subclínica
El elevado número de enfermos que acuden al servicio de urgencias por presentar dolor torácico
Necesidad de identificar el riesgo temprano para establecer una estrategia de tratamiento apropiado
Cinco etapas principales en SCA
Ruptura de la placa con trombosis aguda
Obstrucción mecánica progresiva
Inflamación
Angina inestable secundaria
Obstrucción dinámica (vasoconstricción coronaria)
SCA sin elevación del segmento ST
Población de alto riesgo con un índice de mortalidad en el primer año después del evento inicial de 7 a 8%
Diagnóstico evaluado principalmente por síntomas, electrocardiograma y biomarcadores séricos
Uso de biomarcadores séricos en el diagnóstico del IAM
No todos los pacientes con dolor precordial sugestivo de IAM muestran cambios en el ECG
El ECG arroja aproximadamente 75% de la exactitud en el diagnóstico del IAM
La sensibilidad de la elevación del segmento ST para la detección de IAM es de 35 a 50%
Es importante contar con herramientas diagnósticas adicionales que sean rápidas y capaces de detectar necrosis miocárdica con alta especificidad y sensibilidad durante las primeras horas de evolución del cuadro isquémico
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Definition of a biomarker
1989 definition: measurable and quantifiable biological parameter related to health and disease evaluation, risk, and diagnosis
2001 definition: objectively measurable characteristic indicating normal biological processes, pathological processes, or response to therapeutic intervention
Types of biomarkers
Measured from biomaterials (blood, urine, tissue)
Obtained from a person's record (blood pressure, electrocardiogram)
Derived from imaging (echocardiogram)
Uses of biomarkers
Indicator of disease (risk marker)
Staging of disease (preclinical or clinical)
Prognosis of disease (progression)
Characteristics of a myocardial injury biomarker
Cardiovascular risk factors in the general population
Dyslipidemia, smoking, hypertension, and diabetes mellitus
Not fully explain cardiovascular risk
Importance of biomarkers related to myocardial damage
Extent of myocardial necrosis is a determinant of death risk
Allows for treatment to minimize future necrosis
Identifies individuals at risk for cardiovascular disease
Biomarkers associated with cardiovascular risk
C-reactive protein, B-type natriuretic peptide, fibrinogen, D-dimer, myeloperoxidase, and homocysteine
Simultaneous measurement of multiple biomarkers can enhance risk assessment
Cardiac biomarkers of ischemic risk
Inflammation and platelet activation markers
Protein C-reactive is associated with prognosis in select patients
Not useful in symptomatic patients
Platelet activation markers like P-selectin and integrins are theoretically attractive
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A marker of myocardial injury should have the following characteristics:
High concentrations in the myocardium
Not found in other tissues
Rapid and complete release after injury
Released in proportion to the extent of the injury
Persist in the plasma for several hours
Low cost
High sensitivity and specificity
Factors determining these characteristics are sensitivity, specificity, size, cellular localization, solubility, release rate, presence in plasma, myocardial specificity, specificity for irreversible injury, and detectability
Proteins are released from myocardial ischemia and necrosis through loss of membrane integrity and diffusion into the interstitium and then into the intravascular and/or lymphatic flow
First investigations on proteins related to myocardial necrosis were reported in the 1950s
Transaminase glutamic oxalacetic (SGOT or AST) activity increased in the serum of patients with acute myocardial infarction (AMI)
Lactate dehydrogenase (LDH) and its isoenzymes replaced AST for confirming myocardial injury due to their higher myocardial specificity
Creatine kinase (CK) and its MB fraction (CKMB) became the main enzymes used for AMI diagnosis, but CKMB has limitations and loses diagnostic value in some cases
Structural and contractile proteins of the heart, such as cardiac troponins T and I, are now used for AMI diagnosis due to their higher specificity and longer diagnostic window
Protein C-reactive (PCR) is used to identify high-risk patients with normal lipid levels
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Acute coronary syndrome (ACS) is a leading cause of morbidity and mortality worldwide
ACS includes unstable angina, non-ST-segment elevation myocardial infarction (NSTEMI), and ST-segment elevation myocardial infarction (STEMI)
ACS is caused by the rupture of an atherosclerotic plaque, leading to platelet activation, thrombus formation, and myocardial ischemia
ACS diagnosis is based on clinical presentation, electrocardiogram (ECG) findings, and cardiac biomarkers
Cardiac biomarkers are proteins released from myocardial injury and can be used to diagnose and assess the severity of ACS
Cardiac troponins T and I are the preferred biomarkers for ACS diagnosis due to their high sensitivity and specificity
Other biomarkers, such as creatine kinase (CK) and its MB fraction (CKMB), and protein C-reactive (PCR), can also be used in combination with troponins for ACS diagnosis and risk stratification
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Various markers have been proposed to assess the risk of acute coronary syndrome
These markers include homocysteine, fibrinogen levels, fibrinolytic capacity, apolipoprotein A-I levels, apolipoprotein B-100 levels, and lipoprotein levels
Inflammation markers have also been evaluated as potential predictors of coronary events
Systemic inflammation markers produced in the liver include high-sensitivity C-reactive protein (CRP), amyloid A protein, interleukin-6, and soluble intercellular adhesion molecule-1 (sICAM-1)
However, the clinical and prognostic value of many of these markers is uncertain due to inadequate standardization, inconsistent prospective data, or lack of evidence as risk predictors
PCR as a Marker of Systemic Inflammation
PCR is a sensitive marker of systemic inflammation
It was discovered in 1930 and named for its reaction with C-polysaccharide in the plasma of patients with acute pneumococcal pneumonia
Prospective studies have shown that elevated levels of high-sensitivity PCR provide short- and long-term prognostic value for various coronary events
These events include the first presentation of acute myocardial infarction (AMI), morbidity and mortality associated with myocardial cell damage, sudden death from cardiac causes, peripheral arterial disease, and activation of the hemostatic system
The precise mechanisms linking PCR levels to these adverse events have not been fully described
Theoretically, reducing atherogenic lipoprotein levels can reduce systemic inflammation and therefore lower PCR levels
PCR levels <1, 1-3, and >3 mg/L correspond to low, moderate, and high-risk groups for future cardiovascular events
PCR is composed of five subunits and plays an important role in the innate immune response
It has a long plasma half-life, is stable for long periods of time, is not affected by food intake, and does not require special storage procedures
Creatine Kinase (CK) as a Marker of Myocardial Damage
CK and its MB fraction have been used as biochemical markers to confirm myocardial damage
However, they are not specific to the myocardium and have limited prognostic power
CK is an enzyme involved in energy transfer from mitochondria to the cytosol
It consists of three different isoenzymes: CKBB or CK-1, CKMB or CK-2, and CKMM or CK-
These isoenzymes catalyze the irreversible phosphorylation of creatine, transferring high-energy phosphate from adenosine triphosphate (ATP) to creatine
CKMB is the isoform most commonly used to assess myocardial damage, but it lacks specificity in certain patients and can be elevated due to skeletal muscle damage, thyroid disease, or renal disease
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CK (creatine kinase) is an enzyme found in various tissues
CKBB is mostly found in the brain, prostate, intestines, lungs, bladder, uterus, placenta, and thyroid
CKMM and CKMB are present in both skeletal and smooth muscle
After myocardial injury, CKMB concentration increases
Elevated levels of CKMB have been observed in hypertension, skeletal muscle disease, chronic renal failure, left ventricular hypertrophy, coronary artery disease, and cocaine use
CK is inactivated by proteolysis in the lymph and is not excreted in urine
CK levels are not influenced by changes in renal or hepatic blood flow
Hypothyroidism delays the disappearance of CK in serum, while exogenous thyroid hormones increase its level
There are two atypical variants of CK (MCK) with a considerable molecular mass (> 200 kDa)
MCK type I (MCK-I) is formed as a result of immune complex formation between CKBB and the light chain of monoclonal immunoglobulin G
MCK type II (MCK-II) is also known as mitochondrial CK or cathodic CK
MCK-I, MCK-II, and CKBB can cause false increases in CKMB and a false relative index of CKMB:CK
CK-MB measurement is often used for the diagnosis of myocardial infarction (IAM)
Plasma levels of CK-MB increase 6-10 hours after the onset of infarction
Peak levels of CK-MB occur at 12-24 hours and return to normal between 36-72 hours
Measurements of CK-MB every 12 hours are recommended for diagnostic sensitivity
CK-MB levels disappear faster than total CK
DHL (lactic dehydrogenase) is a tetramer composed of subunits "M" and "H"
It is used in combination with CK-MB for the diagnosis of IAM
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DHL (deshidrogenasa láctica)
Responsable de la interconversión de piruvato y lactato
Formas de DHL: DL-1, DL-2, DL-3, DL-4, DL-5
DL-1 es la forma predominante en el corazón
DL-5 es la isoenzima predominante en el músculo esquelético
Remoción de la DHL vía sistema reticuloendotelial
Troponinas cardiacas
Proteínas estructurales que intervienen en el acoplamiento actina-miosina
Función de las troponinas: regular la fuerza y velocidad de la contracción muscular
Troponinas cardiacas como predictoras de efectos adversos en pacientes con SCA
Complejo troponina formado por T, I y C
Troponina T (TnT): fija el complejo de troponina a la tropomiosina
Troponina C (TnC): regula la activación de los filamentos delgados durante la contracción muscular
Troponina I (TnI): ejerce un efecto inhibitorio en la actividad ATPasa
Tres isoformas de la troponina I específica de tejido en humanos
Troponinas cardiacas tienen una pequeña fracción disuelta en el citoplasma de los cardiomiocitos
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Multiple binding sites between troponin T and troponin I have been identified.
Troponin I rolls around the central helix of troponin C in the presence of calcium.
Troponin T facilitates the binding of troponin C and troponin I to actin-tropomyosin filaments.
Troponin T interacts with troponin I, but not as strongly as the TnI-TnC complex.
Troponin T and troponin I are good predictors of short and long-term adverse events in patients with acute coronary syndrome (SCA).
Troponin T and troponin I have high sensitivity and specificity for detecting myocardial damage.
Troponin T and troponin I have a dual kinetic release, with a rapid release (3-4 hours), a peak at 14-18 hours, and a sustained release (elevated concentrations up to 5-9 days, with a maximum of 14 days).
It is recommended to perform the troponin test between 4 to 6 hours after the onset of chest pain to avoid false negative results.
A radioimmunoassay (RIA) was developed in 1987 for the measurement of troponin I in human serum, but it was impractical due to the long processing time and high minimum detectable concentration.
Currently, there are quantitative solid-phase enzyme immunoassays (EIA) available for the measurement of troponin T and troponin I.
Other laboratory techniques used for troponin I determination include chemiluminescence and fluoroinmunoassay.
Troponin T levels can be elevated in patients with end-stage renal failure, rhabdomyolysis, non-myocardial ischemic heart failure, sepsis, and septic shock, reducing its specificity compared to troponin I.
When troponins are used for the diagnosis of myocardial infarction, it is recommended to repeat the test 12 hours after the onset of symptoms.
Troponin T has the advantage of being rapid and requiring a minimal sample size.
Troponin T can identify patients with myocardial infarction from the second hour of symptom onset.
Troponin T can detect most myocardial infarctions from the sixth hour of evolution, even in the absence of characteristic clinical and electrocardiographic signs.
Troponin T can be applied and interpreted immediately.
The accepted reference levels for indicating myocardial infarction with troponin T are below a certain threshold.
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Utilidad clínica de las Tnc (troponinas cardíacas):
Confirmación y exclusión de infarto
Valoración del riesgo en pacientes con angina de pecho inestable y diagnóstico de microinfartos
Monitoreo de la evolución de la terapia trombolítica
Diagnóstico del daño miocárdico periope- ratorio
Mioglobina:
Primer marcador que se eleva después del daño celular miocárdico
Función principal de transportar oxígeno de la membrana celular a la mitocondria
Puede ser detectada 2 horas después del infarto, con nivel sérico "pico" entre 3 a 15 horas
Sensibilidad al momento de la presentación del evento es de 49% y su especificidad de 91%
Factores que pueden afectar los niveles normales de mioglobina: desórdenes neuromusculares o de músculo esquelético, ejercicio extremo, falla renal, inyecciones intramusculares, cirugía de revascularización cardiaca
Controversia sobre el nivel de referencia que varía de 50 a 120 μg/mL de mioglobina como indicador de IAM
Péptido natriurético:
Conexión entre el descubrimiento de los péptidos natriuréticos y su papel en la clínica
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Discovery of secretory granules in the atrium of experimental animals through electron microscopy.
In 1981, de Bold et al. observed that administration of atrial homogenate to rats caused an increase in urine volume, natriuresis, and a decrease in blood pressure.
The "atrial natriuretic factor" was the first demonstration of the endocrine function of the heart.
The family of mammalian natriuretic peptides includes atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), type C natriuretic peptide (CNP), dendroaspis natriuretic peptide (DNP), and urodilatin.
All peptides have a similar structure, with 17 central amino acids covered by disulfide bonds between two cysteine residues.
ANP is the first natriuretic peptide discovered and is excreted by both atrial and ventricular myocytes.
BNP is a neurohormone synthesized in the cardiac ventricles and released by myocyte distension.
Figure 1: Biochemical structure of natriuretic peptides
ANP: Atrial natriuretic peptide
BNP: Brain natriuretic peptide
CNP: Type C natriuretic peptide
DNP: Dendroaspis natriuretic peptide
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BNP (B-type natriuretic peptide) is a marker used in the diagnosis and prognosis of acute coronary syndrome (ACS).
BNP is divided enzymatically into N-terminal-proBNP (NT-proBNP) and BNP.
BNP has been shown to predict the risk of mortality, heart failure, and new myocardial infarction (MI) when measured a few days after ACS.
NT-proBNP can be detected early, even when myocardial damage is asymptomatic, with greater sensitivity than BNP.
BNP production is influenced by factors such as wall tension, hemodynamic load, and neurohormones that promote hypertrophy.
BNP levels are influenced by sex, age, renal function, and body mass index.
After an MI, BNP levels rapidly increase within the first 24 hours and then stabilize.
BNP levels also increase in healthy athletes after ultramarathons and in healthy individuals after cycling exercise.
Other natriuretic peptides include CNP (C-type natriuretic peptide), urodilatin, and DNP (dendroaspis natriuretic peptide).
There are three specific receptors for cardiac natriuretic peptides: Type-A, Type-B, and Type-C.
Type-A and Type-B receptors mediate the biological actions of ANP and BNP.
These actions include promoting natriuresis and diuresis, inhibiting renin and aldosterone secretion, increasing urine flow, causing vasodilation, improving diastolic relaxation, and reducing myocardial fibrosis.
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Receptors for atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP)
ANP, BNP, and CNP are hormones that regulate blood pressure, blood volume, and fluid balance
Receptors are widely distributed in the body
Found in kidney, heart, vascular endothelium, vascular smooth muscle, and central nervous system
ANP and BNP are removed from circulation through internalization and receptor-mediated metabolism, as well as proteolytic degradation
BNP has a longer half-life in circulation compared to ANP
NT-proBNP, an inactive fragment, has an even longer half-life than BNP
Development of sensitive and accurate immunoassays for ANP, BNP, and NT-proBNP has been challenging
Laboratory tests for these peptides have been available since the 1990s
Approved by the Food and Drug Administration (FDA) in November 2000
Fluorescent immunoassay for BNP provides results in 15 minutes
Immunoluminometric assays for NT-proBNP are highly sensitive and specific
Electrochemiluminescent assay for NT-proBNP has a processing time of 18 minutes
Approximately 83% of hospitals in the United States use these tests
Reference ranges for BNP and NT-proBNP vary depending on the method used and the population
Commonly used reference values for BNP are 100 pg/mL and for NT-proBNP are 125 pg/mL in patients under 75 years old, and 450 pg/mL for both markers in patients over 75 years old
Normal values for BNP are 0.5 to 30 pg/mL
Levels of BNP and NT-proBNP are higher in women than in men
Obesity and renal insufficiency can affect the levels of natriuretic peptides
Clinical uses of BNP
Evaluation of acute dyspnea
Diagnosis of left ventricular dysfunction
Diagnosis of systolic dysfunction after myocardial infarction
Diagnosis of right ventricular dysfunction
Prognostic evaluation in non-acute situations: heart failure, left ventricular dysfunction
Prognostic indicator for mortality, development of heart failure, atrial fibrillation in low-risk subjects without a history of heart failure
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Monitoreo de manejo terapéutico de la insuficiencia cardiaca
Enfermedad valvular: estudios que demuestran elevación de péptidos natriuréticos en enfermedad valvular como estenosis aórtica y regurgitación mitral
Other Biomarkers
Glucógeno-fosforilasa: Enzima dimérica que regula el metabolismo de los carbohidratos a través de la movilización del glucógeno
Fragmentos de miosina: Consiste en 6 proteínas que participan en la regulación de la interacción de actina y miosina
Miosina de cadenas ligeras (MLC): Existen en los ventrículos y aurículas, y se encuentran en el músculo esquelético
Potential Causes of Elevated Levels of B-type Natriuretic Peptide (BNP)
Cardiac Causes:
Insuficiencia cardiaca
Disfunción diastólica
Síndrome coronario agudo
Hipertensión con hipertrofia ventricular izquierda
Cardiomiopatía hipertrófica
Enfermedad de válvula cardiaca (estenosis aórtica o mitral, regurgitación de válvula mitral)
Fibrilación auricular
Non-cardiac Causes:
Tromboembolia aguda pulmonar
Enfermedad crónica pulmonar
Hipertensión sistémica
Hipertensión pulmonar (primaria o secundaria)
Sepsis (posiblemente debido a hipoxia tisular o depresión miocárdica secundaria)
Enfermedad pulmonar obstructiva crónica con cor pulmonale o falla respiratoria
Hipertiroidismo
Síndrome de Cushing
Aldosteronismo primario
Enfermedad de Addison
Diabetes mellitus (pacientes con microalbuminuria o disfunción autonómica)
Cirrosis hepática con ascitis
Insuficiencia renal (aguda o crónica)
Síndrome paraneoplásico
Hemorragia subaracnoidea
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Fragmentos de MLC (marcador sensible de lesión miocárdica)
Detectados en plasma dentro de las 6 horas de presentado el infarto
Niveles elevados presentes por más de 7 días
Depurado de la circulación por vía renal
Prolongada elevación permite detección retrospectiva después de 2 semanas
Más sensible para la detección de IAM comparada con CK y CKMB
Miosina de cadenas pesadas (MHC)
Niveles de MHC no se encuentran presentes en plasma hasta 2 días después del evento
Niveles pico ocurren 5 a 6 días
Elevación persiste después de 10 días, permitiendo la determinación prolongada de necrosis miocárdica
Limitada especificidad cardiaca debido a múltiples variantes en aurícula, ventrículo y músculo esquelético
Proteínas de unión de ácidos grasos cardíacos (FABPs)
Abundantes proteínas citosólicas de bajo peso molecular
Tres FABPs diferentes se encuentran en corazón, hígado e intestino
Elevación después de lesión miocárdica en ratas
Niveles elevados en suero y orina después del infarto del miocardio
Sensibilidad comparada a la de mioglobina para la detección de reperfusión después de terapia trombolítica
Enolasa
Enzima glicolítica abundante, presente en todos los tejidos
Elevación de isoformas αβ y ββ después del IAM
Niveles de β-enolasa también se elevan después de cirugía de corazón abierto
No distingue entre daño miocárdico y daño de músculo esquelético
Comentarios finales
Grandes avances en la prevención de la enfermedad coronaria cardiaca mediante la modificación de sus causas
Diversas opciones terapéuticas para los pacientes con SCA
Sensibilidad del ECG es baja en la valoración de los pacientes con dolor torácico agudo
ECG continúa siendo la modalidad diagnóstica más accesible e inmediata
En algunos pacientes el ECG es normal y solo muestra isquemia en solamente 50%
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ECG inicial normal o no específico puede asociarse con alto riesgo de muerte
Pérdida de integridad de la membrana debido a la necrosis celular por isquemia provoca liberación de biomarcadores cardiacos
Detección de biomarcadores útil para diagnóstico y pronóstico del daño miocárdico
Concentración plasmática, ritmo de aparición y elevación aumentados en caso de reperfusión eficaz tras tratamiento trombolítico
Marcadores bioquímicos empleados para confirmación de daño miocárdico: CPK y su fracción MB
Cuadro II - Propiedades de los biomarcadores cardiacos para el diagnóstico de IAM
CK
No. estudios: 12
No. sujetos: 3,195
Sensibilidad: 37 (31-44)
Especificidad: 87 (80-91)
CK-MB
No. estudios: 19
No. sujetos: 6,425
Sensibilidad: 42 (36-48)
Especificidad: 97 (95-98)
Mioglobina
No. estudios: 18
No. sujetos: 4,172
Sensibilidad: 49 (53-55)
Especificidad: 91 (87-94)
Troponina I
No. estudios: 4
No. sujetos: 1,149
Sensibilidad: 39 (10-78)
Especificidad: 93 (88-97)
Troponina T
No. estudios: 6
No. sujetos: 1,348
Sensibilidad: 39 (26-53)
Especificidad: 93 (90-96)
CK-MB-Mioglobina
No. estudios: 3
No. sujetos: 2,283
Sensibilidad: 83 (51-96)
Especificidad: 82 (68-90)
Cuadro III - Marcadores moleculares utilizados en el diagnóstico de IAM
Mioglobina
Rango de tiempo para elevación: 1-4 horas
Tiempo de pico: 6-7 horas
Tiempo de retorno a rango normal: 24 horas
Horario más común para la determinación: 1-2 horas después del dolor torácico
Troponina I
Rango de tiempo para elevación: 3-12 horas
Tiempo de pico: 24 horas
Tiempo de retorno a rango normal: 5-10 días
Horario más común para la determinación: 12 horas después del dolor torácico
Troponina T
Rango de tiempo para elevación: 3-12 horas
Tiempo de pico: 12 horas - 12 días
Tiempo de retorno a rango normal: 5-14 días
Horario más común para la determinación: 12 horas después del dolor torácico
CK-MB
Rango de tiempo para elevación: 3-12 horas
Tiempo de pico: 24 horas
Tiempo de retorno a rango normal: 48-72 horas
Horario más común para la determinación: Cada 12 horas por 3 días
CK-MM isoforma tisular
Rango de tiempo para elevación: 1-6 horas
Tiempo de pico: 12 horas
Tiempo de retorno a rango normal: 38 horas
Horario más común para la determinación: 60-90 minutos después del dolor torácico
CK-MB isoforma tisular
Rango de tiempo para elevación: 2-6 horas
Tiempo de pico: 18 horas
Tiempo de retorno a rango normal: Desconocido
Horario más común para la determinación: 60-90 minutos después del dolor torácico
DHL
Rango de tiempo para elevación: 10 horas
Tiempo de pico: 24-48 horas
Tiempo de retorno a rango normal: 10-14 días
Horario más común para la determinación: 24 horas después del dolor torácico
* Tomado y modificado de la referencia 20.
** Incrementa su sensibilidad si se muestrea cada 6 u 8 horas.
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Importance of early diagnosis in discriminating high-risk patients
Minor increases in CK-MB values have limited prognostic value in identifying patients with major cardiac events
Need for earlier and more specific and sensitive biochemical markers for detecting reversible myocardial lesions
American College of Cardiology and American Heart Association guidelines recommend measuring myoglobin, TnT, and TnI
Supplemental measurement of CK-MB may be more useful for diagnosing myocardial infarction (MI) than isolated measurement of each marker
CK total is not recommended for routine diagnosis of MI due to its wide tissue distribution
Other markers such as amyloid A protein, phosphorylated BB isoenzyme, and soluble fibrin have potential use in predicting plaque rupture and thrombosis risk
Cuadro IV. Marcadores moleculares utilizados en el diagnóstico de IAM*
CK-MB: Rapid, cost-effective, accurate, detects early reinfarction
Elevated serum levels 6-8 hours after ischemic event
Loss of specificity in disorders, trauma, or musculoskeletal damage
Diagnostic window ends at 72 hours
Myoglobin: High sensitivity, useful for early detection of MI
Elevates at 2 hours after MI
Loss of specificity due to other disorders
Diagnostic window ends at 24 hours
Cardiac troponins: Sensitive and specific indicators of MI
Less sensitive in early stages of MI (<6 hours after onset)
Diagnostic window of 5-7 days
Requires repeated measurements if negative
Useful for prognosis in unstable angina and therapy selection
Ability to detect late reinfarction is limited
TnT affected by renal disease and elevation-affecting disorders
TnI not affected by cardioversion, renal disease, or surgery
*Taken and modified from references 45 and 78.
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There are a wide range of enzymatic markers used for the diagnosis of acute coronary syndrome (ACS)
Individual biomarkers of myocardial injury have poor negative predictive value in emergency rooms
Combining two or more biomarkers increases early predictive value
Improper use and interpretation of biomarkers can lead to overdiagnosis or underestimation of ACS
Reference values should be determined by each laboratory
Figure 2
Illustration of the different stages of the ischemic cascade
Representation of the evolution of a healthy blood vessel to the formation of atherosclerotic plaque, plaque rupture, thrombosis, ischemia, tissue necrosis, and remodeling
Enzymatic markers, cytokines, and other biomarkers are involved in different stages of the cascade
Figure 3
Comparison of the presentation, peak, and duration of elevation of cardiac biomarkers associated with ACS
Different biomarkers are elevated in each phase of the disease
Examples of biomarkers include myoglobin, CK-MB, troponin I, and troponin T