Biomarkers in Acute Cardiac Disease Biomarkers in Acute Cardiac Disease Samir Arnaout, M.D.FESC Samir Arnaout, M.D.FESC Associate Professor of Medicine Associate Professor of Medicine I nternal Medicine & Cardiology I I I nternal Medicine & Cardiology t t l M di i l M di i & C & C di l di l American University of Beirut American University of Beirut
Time course of the appearance of various markers in the blood after acute myocardial infarction (AMI) y ( ) AST LDH Jaffe, A. S. et al. J Am Coll Cardiol 2006;48:1-11
Potentially outdated markers • CK-MB. Creatine kinase-MB could be used to define infarct timing or after PCI. ld b d t d fi i f t ti i ft PCI • Myoglobin and CK isoforms • Myoglobin and CK isoforms have been used with the hope of shortening the time to a more definitive diagnosis in patients with chest pain They have been relied on particularly for their negative predictive value Myoglobin may identify additional patients at risk Myoglobin may identify additional patients at risk.
Sensitivity of cardiac troponin (cTn)I compared with myoglobin and creatine kinase (CK)-MB for the detection of myocardial injury creatine kinase (CK) MB for the detection of myocardial injury Jaffe, A. S. et al. J Am Coll Cardiol 2006;48:1-11
Cardiac events after emergency department discharge based on levels of cardiac troponin T Jaffe, A. S. et al. J Am Coll Cardiol 2006;48:1-11
Risk stratification in acute coronary Risk stratification in acute coronary syndromes: role of troponin syndromes: role of troponin syndromes: role of troponin syndromes: role of troponin % of patients with + cTn % of patients with + cTn % of patients with + cTn % of patients with + cTn Abnormal troponin levels are 100 associated with an increased cTn T 9597 9797 9294 cTn I risk of death after adjustment j for age and ST segment Δ . 81 The risk increases with 80 p progressively higher levels g y g 77 77 of troponin 60 60 About 15% of patients with initially normal Tn T levels will show elevated values in sub- show elevated values in sub- sequent samples, regardless 40 of time since onset of symptoms B 12 24 48 h TRIM, Lüscher et al, Circulation 1997 N= 510, median time to B sampling 12 h
Risk stratification in acute coronary Risk stratification in acute coronary syndromes: role of troponin syndromes: role of troponin syndromes: role of troponin syndromes: role of troponin Mortality at Mortality at 42 42 days (%) days (%) 10 10 7.5 8 Abnormal troponin levels are Abnormal troponin levels are N= 1,404 associated with an increased 6.0 risk of death after adjustment 6 for age and ST segment Δ for age and ST segment Δ . The risk increases with 3.7 4 progressively higher levels 3.4 of troponin f t i 1.7 2 1.0 831 50 174 148 134 67 0 <0.04 0.4-0.9 1-1.9 2-4.9 5-8.9 >9 Troponin I (ng/ml) Troponin I (ng/ml) 1.0 1.8 3.5 3.9 6.2 7.8 Risk ratio 95% CI 0.5-6.7 1.2-10.6 1.3-11.7 1.7-22.3 2.6-23 TIMI IIIB, Antman et al, NEJM 1996
Emerging markers Emerging markers
High High- -sensitive CRP or hsCRP sensitive CRP or hsCRP . C reactive protein is an acute C-reactive protein is an acute reactive protein is an acute phase reactant reactive protein is an acute-phase reactant phase reactant phase reactant � � protein made in the liver . protein made in the liver . Its most proximate stimulator is interleukin Its most proximate stimulator is interleukin 6 6. . � Values above Values above 10 10 mg/l are likely caused by acute mg/l are likely caused by acute g/ g/ y y y y disease. disease. Values Values Values > 3 mg/l Values > 3 3 mg/l mg/l are associated with higher risk. mg/l are associated with higher risk are associated with higher risk. are associated with higher risk � � values values < 1 1 1 mg/l mg/l are associated with low risk . are associated with low risk . � values values and and 3 3 mg/l mg/l are considered intermediate are considered intermediate �
Synergistic prognostic value of C-reactive protein (CRP) and low-density lipoprotein (LDL) in PROVE-IT study Jaffe, A. S. et al. J Am Coll Cardiol 2006;48:1-11
B- -type natriuretic peptide type natriuretic peptide yp yp p p p p � Is a � Is a Is a 32 Is a 32 32-amino 32 amino amino acid counterregulatory amino-acid counterregulatory acid counterregulatory acid counterregulatory peptide released in response to cardiac peptide released in response to cardiac st etch It is s nthesi ed as a p o peptide st etch It is s nthesi ed as a p o peptide stretch. It is synthesized as a pro peptide stretch. It is synthesized as a pro peptide and then cleaved to the active moiety by a and then cleaved to the active moiety by a protease called corin . protease called corin . � There is an immunoassay for NT � There is an immunoassay for NT There is an immunoassay for NT-proBNP There is an immunoassay for NT proBNP proBNP proBNP which detects the which detects the 76 76 amino acid carrier amino acid carrier protein which with the active protein which with the active 32 protein, which with the active protein, which with the active 32 32 amino 32 amino amino amino acid compound is called proBNP. acid compound is called proBNP.
Use of the marker the BNP and/ or NT Use of the marker the BNP and/ or NT- -proBNP proBNP � detection of congestive heart failure in patients in detection of congestive heart failure in patients in whom one is unsure of the cause of dyspnea. whom one is unsure of the cause of dyspnea. � For BNP, values < For BNP, values < 100 , 100 ng/l make heart failure ng/l make heart failure g/ g/ unlikely with a negative predictive value of 90 unlikely with a negative predictive value of 90%. %. For For For NT For NT NT-proBNP levels > NT proBNP, levels > proBNP levels > 450 proBNP, levels > 450 450 ng/l for patients < 450 ng/l for patients < ng/l for patients < 50 ng/l for patients < 50 50 50 � � years of age and > years of age and > 900 900 ng/l for patients ng/l for patients 50 50 years of years of age are sensitive and specific for heart failure age are sensitive and specific for heart failure age are sensitive and specific for heart failure age are sensitive and specific for heart failure � Patients with right P ti P ti Patients with right-sided heart failure, sepsis, t t ith i ht ith i ht sided heart failure, sepsis, id d h id d h t f il t f il i i volume overload, stroke, and left ventricular volume overload, stroke, and left ventricular hypertrophy also have higher values h hypertrophy also have higher values h t t h h l l h h hi h hi h l l
I n ACS patients, BNP and NT I n ACS patients, BNP and NT- - proBNP elevations proBNP elevations � TACTICS TACTICS– –TIMI TIMI- -18 18 study study: : Women with elevated BNP or CRP values Women with elevated BNP or CRP values � seemed to benefit from early PCI even if seemed to benefit from early PCI even if seemed to benefit from early PCI even if seemed to benefit from early PCI even if they had normal cTn values. they had normal cTn values. � Higher BNP values identify patients with Hi h Hi h Higher BNP values identify patients with BNP BNP l l id id tif tif ti ti t t ith ith ACS who are at higher risk . ACS who are at higher risk . � Elevated values also predict an adverse Elevated values also predict an adverse outcome in stroke outcome in stroke outcome in stroke outcome in stroke
D D Developing markers Developing markers l l i i k k
sCD sCD40 sCD sCD40 40 ligand 40 ligand ligand ligand • I s a signaling protein that reflects I s a signaling protein that reflects i i li li i i h h fl fl both inflammatory and platelet both inflammatory and platelet y y p p interactions with the plaque. interactions with the plaque. • I ncreased sCD I ncreased sCD40 40 ligand has been ligand has been shown in patients with ACS Moreover shown in patients with ACS Moreover shown in patients with ACS. Moreover, shown in patients with ACS. Moreover, articles have suggested that is has articles have suggested that is has prognostic significance in these Patients prognostic significance in these Patients i i i i ifi ifi i i h h P P i i
Myeloperoxidase Myeloperoxidase � A degranulation product, comes from A degranulation product, comes from white cells. Elevations occur even when white cells. Elevations occur even when hit hit ll ll El El ti ti h h values are obtained from the coronary values are obtained from the coronary effluent draining a nonculprit coronary effluent draining a nonculprit coronary ffl ffl t d t d i i i i l l it it vessel. vessel. Used to prognosticate in patients Used to prognosticate in patients � presenting to the emergency presenting to the emergency p p g g g g y y department with chest pain . department with chest pain .
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