Biomarkers in Acute Cardiac Disease Biomarkers in Acute Cardiac - - PowerPoint PPT Presentation
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
Samir Arnaout, M.D.FESC Samir Arnaout, M.D.FESC
Associate Professor of Medicine Associate Professor of Medicine I t l M di i & C di l I t l M di i & C di l I nternal Medicine & Cardiology I nternal Medicine & Cardiology 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
Creatine kinase-MB
ld b d t d fi i f t ti i ft PCI could be used to define infarct timing or after PCI.
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
% of patients with + cTn % of patients with + cTn
Abnormal troponin levels are associated with an increased risk of death after adjustment
100
% of patients with + cTn % of patients with + cTn
9294 9597 9797
cTn T cTn I
j for age and ST segment Δ. The risk increases with progressively higher levels
80
81 77
p g y g
60
77
60
About 15% of patients with initially normal Tn T levels will show elevated values in sub-
40
show elevated values in sub- sequent samples, regardless
TRIM, Lüscher et al, Circulation 1997
B 12 24 48 h
N= 510, median time to B sampling 12 h
10
Mortality at Mortality at 42 42 days (%) days (%)
Abnormal troponin levels are
10 8 7.5
Abnormal troponin levels are associated with an increased risk of death after adjustment for age and ST segment Δ
6 6.0 N= 1,404
for age and ST segment Δ. The risk increases with progressively higher levels f t i
4 3.4 3.7
2 1.0 1.7
<0.04 0.4-0.9 1-1.9 2-4.9 5-8.9 >9 Troponin I (ng/ml)
831 174 148 134 50 67
Troponin I (ng/ml) 1.0 1.8 3.5 3.9 6.2 7.8
0.5-6.7 1.2-10.6 1.3-11.7 1.7-22.3 2.6-23
Risk ratio 95% CI TIMI IIIB, Antman et al, NEJM 1996
reactive protein is an acute phase reactant phase reactant
reactive protein is an acute-phase reactant phase reactant protein made in the liver . protein made in the liver .
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/ y y g/ y y disease. disease.
Values > 3 mg/l mg/l are associated with higher risk are associated with higher risk
Values > 3 3 mg/l mg/l are associated with higher risk. are associated with higher risk.
values < 1 1 1 mg/l mg/l are associated with low risk . are associated with low risk .
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
Is a
Is a
There is an immunoassay for NT
There is an immunoassay for NT
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 unlikely with a negative predictive value of 90 90%. %.
For NT NT-proBNP levels > proBNP levels > 450 450 ng/l for patients < ng/l for patients < 50 50
For NT NT proBNP, levels > proBNP, levels > 450 450 ng/l for patients < ng/l for patients < 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 P ti t ith i ht P ti t ith i ht id d h t f il i id d h t f il i
Patients with right
Patients with right-sided heart failure, sepsis, sided heart failure, sepsis, volume overload, stroke, and left ventricular volume overload, stroke, and left ventricular h t h l h hi h l h t h l h hi h l hypertrophy also have higher values hypertrophy also have higher values
TACTICS
Higher BNP values identify patients with
Elevated values also predict an adverse
A degranulation product, comes from
I schemia
Ischemia-
modified albumin has been touted as a way to detect ischemia even if necrosis is not way to detect ischemia even if necrosis is not way to detect ischemia even if necrosis is not way to detect ischemia even if necrosis is not present. present.
The theory is that the metal binding site on the
The theory is that the metal binding site on the amino terminus of albumin is damaged by ischemia. amino terminus of albumin is damaged by ischemia. It is marketed for its "negative predictive value It is marketed for its "negative predictive value It is marketed for its negative predictive value. It is marketed for its negative predictive value.
is thought to be released when neovascularization
rupture rupture
identify patients at risk for subsequent events identify patients at risk for subsequent events identify patients at risk for subsequent events
Choline
Choline is a biomarker that is released when phospholipids are cleaved which suggests that phospholipids are cleaved which suggests that phospholipids are cleaved, which suggests that phospholipids are cleaved, which suggests that perhaps it could be a marker of ischemia and/or perhaps it could be a marker of ischemia and/or necrosis necrosis necrosis. necrosis.
Several studies suggest that the marker might improve prognostication in patients with ACS improve prognostication in patients with ACS improve prognostication in patients with ACS improve prognostication in patients with ACS
Cystatin C
a low-
molecular-
weight basic protein (13 13 kDa) that is kDa) that is freely filtered and metabolized after tubular freely filtered and metabolized after tubular freely filtered and metabolized after tubular freely filtered and metabolized after tubular reabsorption. reabsorption.
It seems that it is less influenced by age gender and
It seems that it is less influenced by age, gender, and muscle mass than serum creatinine. muscle mass than serum creatinine. Some studies suggest that it is useful for Some studies suggest that it is useful for
Some studies suggest that it is useful for prognostication in heart failure and ACS prognostication in heart failure and ACS
Fatty acid binding protein
Fatty acid binding protein is rapidly released after infarction and thus has been touted as an alternative infarction and thus has been touted as an alternative to myoglobin. It has been reported to perform better, to myoglobin. It has been reported to perform better, but it still lacks cardiac specificity . but it still lacks cardiac specificity .
The present and future for cardiac biomarkers is exciting.
The present and future for cardiac biomarkers is exciting.
In the near future, many of these biomarkers will provide important new insights into pathophysiology and aid in the important new insights into pathophysiology and aid in the diagnosis and management of cardiovascular patients diagnosis and management of cardiovascular patients diagnosis and management of cardiovascular patients. diagnosis and management of cardiovascular patients.
We are likely to be able to multiplex assays, personalizing
We are likely to be able to multiplex assays, personalizing y p y , p g y p y , p g biomarker strategies and providing large numbers of values biomarker strategies and providing large numbers of values quickly and cheaply. quickly and cheaply.
However, before we implement such a strategy, we must
In the interim, to provide optimal clinical care, clinicians need to learn more about the biomarkers that they rely on in to learn more about the biomarkers that they rely on in to learn more about the biomarkers that they rely on in to learn more about the biomarkers that they rely on in current clinical practice, i.e., cTn, natriuretic peptides, and current clinical practice, i.e., cTn, natriuretic peptides, and CRP, both analytically and clinically CRP, both analytically and clinically