Assays for NTproBNP
Commercially available assays for NT-proBNP do not crossreact with proANP, NT-proANP, fragments of NT-proANP, natriuretic peptides ANP, BNP, CNP, urodilatin , or other peptide hormones. The crossreactivity with proBNP is unknown. The immuno-metric automated assay manufactured by Roche was the first to be approved for clinical application. The assay employs polyclonal antibodies that detect epitopes 1-21 and 3950 ofproBNP 12 . Synthetic NT-proBNP 1-76, which is identical to human NT-proBNP 1-76...
BNP and NTproBNP and Risk ofHeart Failure and Death After STEMI
The use of BNP to diagnose heart failure can be expanded to patients presenting with ACS. In patients presenting with AMI, BNP was equivalent to echocardiography, and superior to clinical evaluation in the detection of LVEF lt 40 39 . In addition, BNP levels drawn on admission help to identify patients who are likely to develop chronic LVSD 11 , with adverse left ventricular remodeling and dilatation 40,41 . Given the association between BNP and heart failure, it is not surprising that higher...
Chemokines
Chemokines are potent proinflammatory and immune modulators. Chemokines regulate several biological processes such as chemotaxis, activation and migration of leukocytes to areas ofinflammation, collagen turnover, angiogenesis, and apoptosis 4 . TNF-a and other proinflammatory cytokines, such as IL-1P and IL-6 or IFN-y, are known to induce these chemotactic polypeptides 96,97 . Potent chemokines such as macrophage chemo-attractant protein-1 and macrophage inflammatory protein-1a MIP-1a not only...
I
Background Biomarkers of Cardiac Necrosis Necrosis Biomarkers Still in Development Future Markers of Myocardial Necrosis Biochemical markers play a crucial role in accurate diagnosis of myocardial necrosis and, more importantly, for assessing risk and directing appropriate therapy that improves clinical outcome. Development and utilization of biomarkers has evolved substantially over the past three decades. The earliest biomarkers, such as alanine aminotransferase and lactate dehydrogenase,...
Nader Rifai PhD
What Inflammatory Marker Should Be Measured Analytic Issues Sources of Variability in CRP Testing Interpretation of CRP Results Conclusion References The serum concentration of C-reactive protein CRP has historically been used to detect active infection and inflammation. Recent evidence has demonstrated that slight increases in CRP concentration, within the normal range, can predict future vascular events, thus reflecting the inflammatory component of atherosclerosis. It was necessary to...
Prognostic Role of BNP and NTproBNP Across Spectrum of ACS
A substudy ofthe Orbofiban in Patients with Unstable Coronary Syndromes-Thrombo-lysis in Myocardial Infarction 16 OPUS-TIMI 16 trial was among the first to evaluate the prognostic capabilities of BNP in a large population of patients across the entire spectrum of ACS 45 . In this study, BNP was measured in 2525 patients at a mean of 40 h after presenting with STEMI, NSTEMI, or unstable angina. BNP levels on admission correlated with age, male gender, white race, hypertension, CHF, peripheral...
elevated troponin levels after cabg
The concentration of troponin is elevated in almost all patients after bypass surgery, with marked increases in 20-40 of patients 7,49-54 . Several studies have shown lower postoperative troponin levels with minimally invasive and off-pump surgical techniques 55-62 . The type and route of delivery of cardioplegia may also influence the perioperative release of troponin 63-65 . Postoperative troponin levels have greater sensitivity and specificity for the diagnosis of perioperative MI based on...
Luigi M Biasucci MD FACC FAHA FESC and Antonio Abbate MD
Acute Coronary Syndrome An Inflammatory Disease C-Reactive Protein as Preferred Inflammatory Marker for Risk Stratification CRP and Other Inflammatory Markers Role of CRP in a Multimarker Assessment Approach Inflammatory Markers Beyond Risk Stratification and Back to Mechanisms of Disease Practical Considerations Conclusion References This chapter summarizes the rationale and evidence in support of the clinical use of inflammatory markers for risk prediction in patients with ischemic heart...
and Jennifer E Van Eyk PhD
Physiological and Pathological Status of Troponin in Heart Potential for Different Fragments for Different Pathophysiological Processes Potential of Fragment Analysis Potential Biological Effects Conclusion References The use of highly sensitive and very specific measurements of cardiac troponin I and troponin T has revolutionized the detection of cardiac injury. Although the most common use of these tests is the diagnosis of acute myocardial infarction, it has become clear that there are a...
Proinflammatory Cytokines
Overview of Proinflammatory Cytokines Involved in Heart Failure The term cytokine is applied to a group of relatively small molecular weight protein molecules generally 15-30 kDa that are secreted by cells in response to a variety of different inducing stimuli. Classically, cytokines are thought to be secreted by neighboring producer cells to act in an autocrine, ajuxtacrine, or a paracrine fashion to influence the biological behavior of neighboring target cells 14,15 . Although similar in many...
Shuaib M Abdullah MD and James A de Lemos MD
Patterns of BNP Synthesis and Release in Cardiac Ischemia Possible Mechanisms of BNP Synthesis and Release in Ischemic Heart Disease BNP as a Diagnostic Tool in Ischemic Heart Disease Natriuretic Peptides as Prognostic Tools in Ischemic Heart Disease Using BNP and NT-proBNP to Select Patients for an Early Interventional Strategy Proposed Application of BNP in ACS Incorporating Natriuretic Peptides With Other Clinical and Biochemical Markers of Risk Conclusion References In addition to their...
Info Tnd
High Prevalence H Low Prevalence H High Accuracy Fig. 10. Bayesian statistics for cardiac troponin for 1000 hypothetical patients as function of disease prevalence and assay accuracy. A Prevalence of 50 , accuracy of90 B prevalence of10 , accuracy of 90 C prevalence of10 accuracy of 99 . TP, true positive TN, true negative FP, false positive FN, false negative. Regarding the definition of MI, the British Cardiac Society Working Group has recommended the use of two cutoff concentrations for...
Markers of Plaque Vulnerability Rupture and Thrombosis
C-reactive protein CRP is a hepatically derived pentraxin that serves as the prototypic acute-phase reactant it has been extensively evaluated for detection of cardiac risk 9 . Most studies of CRP have focused on its ability to augment risk assessment for both primary and secondary prevention of cardiovascular events. However, in addition to these uses of CRP, studies have also evaluated CRP in the context of acute presentation with chest discomfort. CRP is elevated in some patients with...
Patterns Of Bnp Synthesis And Release In Cardiac Ischemia
Natriuretic peptide levels are elevated both in animal models and in patients with coronary ischemia. In rats that underwent coronary artery ligation, BNP concentration in the left ventricle increased twofold at 12 h and fivefold at 24 h postinfarction, whereas atrial natriuretic peptide ANP levels were unchanged 8 . Elevated levels of BNP were found in noninfarcted as well as in infarcted areas of the myocardium, suggesting that increased African-American race Female gender Comorbidities CHF...
Frequency and Clinical Correlates
Figure 1 represents the pathophysiological concept that CHF is characterized by a chronic low level of myocardial injury leading to degradation of structurally bound proteins, including cardiac troponin 9 . The concept of measuring cardiac troponin in patients with CHF was introduced in 1995. In a pilot study, Missov et al. measured cTnI in 11 endstage heart failure patients and in 11 control subjects 10 . They found that 2 of11 patients with CHF had levels of cTnI above the upper reference...
BNP and Prediction ofSudden Cardiac Death
Several studies suggest that the level of BNP, perhaps by reflecting ventricular dilatation and stretch, may indicate risk of ventricular arrhythmias and sudden cardiac death. In a study of452 ambulatory patients with mild to moderate heart failure NYHA functional classes I and II and LV ejection fraction lt 35 , the level of BNP was independently associated with the risk of sudden cardiac death 42 . Only 1 1 of110 of patients with BNP lt 130 pg mL died suddenly compared with 19 43 of 227 of...
pathophysiology of crp
Atherothrombosis is now recognized as a chronic inflammatory disease, and accumulating data indicate a potential role for CRP at all stages of the atherosclerotic process Fig. 2 . A member of the pentraxin family of innate immune response proteins, CRP not only is synthesized in the liver in response to IL-6 but may also be produced by smooth muscle cells within coronary arteries 25-27 . Laboratory studies suggest that CRP may directly influence vascular vulnerability via many mechanisms,...
myocarditis
Several studies in both humans and a murine model have established that cTnI and cTnT are superior to CK-MB for detection of myocyte injury in myocarditis Fig. 6 3841 . Cardiac troponin monitoring provided sensitive evidence of clinically suspected myocarditis in the first month after the onset of heart failure symptoms. However, as for other methods for the diagnosis of myocarditis, negative results do not exclude the presence of the disease. Nevertheless, the finding of increased levels of...
Use Of Bnp For Risk Stratification In Heart Failure
BNP is a valuable marker for risk stratification in the setting of heart failure. In a study of 78 patients referred to a heart failure clinic, BNP showed a significant correlation to the heart failure survival score 38 . In addition, changes in the plasma concentration of BNP were related to changes in the limitation of physical activities and were associated with the likelihood of deterioration in functional status. As such, BNP levels reflect New Fig. 9. Correlation of BNP with NYHA class....
Methods Of Determination Immunometric Sandwich Assays
The commercially available assays for BNP and NT-proBNP are classified as immuno-metric assays. Such assays incorporate two antibodies that bind to different regions epitopes of the antigen to be detected i.e., BNP or NT-proBNP Fig. 1A . One of these antibodies capture antibody is usually bound to a solid phase, and the second antibody detection antibody is labeled typically with an enzyme that catalyzes a reaction on which the detection ofthe antigen-antibody complex is based e.g.,...
Erythrocyte Sedimentation Rate
ESR has been of particular interest in heart failure owing to its low cost, easy applicability, and reproducibility. However, clinical studies, which are separated from each other by decades, have yielded conflicting results on the role of ESR in heart failure. Based on the potential misinterpretation of the results in a single report published in 1936 115 , physicians have long believed that ESR is low in patients with heart failure 116-119 . To reevaluate this concept in the modern era, Haber...
Helicobacter Pylori
H. pylori is a Gram-negative, spiral, flagulated bacillus that naturally infects humans and monkeys 51 . It is not invasive, either living in the mucus that overlies gastric mucosa or adhering to the mucosa itself. The prevalence of H. pylori infection is about 30 in the United States and other developed countries, and about 80 in most developing countries 52 . In the United States, about 50 ofpeople will have evidence ofprior H. pylori infection by age 60. Most studies show that spontaneous...
and Torbj0rn Omland MD PhD MPH
Discovery of the Natriuretic Peptides Synthesis and Release of Natriuretic Peptides Physiological Actions of Natriuretic Peptides The natriuretic peptide family consists of a group of structurally similar, but genetically distinct, peptide hormones that play a major role in the regulation of cardiovascular, endocrine, and renal homeostasis. Since the discovery of atrial natriuretic peptide almost 25 yr ago, remarkable progress has been made in the field of natriuretic peptide research. This...
references Uha
1. Califf RM, Abdelmeguid AE, Kuntz RE, et al. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998 31 241-251. 2. Tardiff BE, Califf RM, Tcheng JE, et al. Clinical outcomes after detection of elevated cardiac enzymes in patients undergoing percutaneous intervention. IMPACT-II Investigators. Integrilin eptifibatide to Minimize Platelet Aggregation and Coronary Thrombosis-II. J Am Coll Cardiol 1999 33 88-96. 3. Abdelmeguid AE, Topol EJ, Whitlow PL, Sapp SK, Ellis SG....
Sample Stability
The in vitro stability of both BNP and NT-proBNP is sufficient for routine clinical use. The in vitro stability of BNP is dependent on the assay used for determination see Issues for Assay Development . BNP is stable in EDTA whole blood at room temperature for 4 h Biosite and Abbott assays , and at 4 C for 24 h Bayer assay . EDTA plasma is stable at 4 C for 24 Abbott assay and 48 h Bayer assay . A significant decrease in plasma BNP concentrations was noted when BNP was measured after 24 h of...
Prevention of Elevated Troponin Levels After PCI
A number of pharmacological agents have been shown to reduce the frequency and or severity of periprocedural myonecrosis as measured by postprocedural levels of troponin. Because microembolization of thrombus is believed to be one of the primary causes of periprocedural myonecrosis, it is not surprising that more potent antiplatelet agents, such as the thienopyridines and the iv glycoprotein IIb IIIa receptor inhibitors, and more potent inhibitors of thrombin reduce the frequency of this...
Chlamydia Pneumoniae
C. pneumoniae was isolated in 1986 3 . It was found to be responsible for a variety of respiratory illnesses including 10 of cases of community-acquired pneumonia. Like the more familiar Chlamydia trachomatis, C. pneumoniae is an obligate intracellular pathogen with a unique life cycle Fig. 1 4 . Generally, C. pneumoniae enters the body through a respiratory route and exists outside of cells in a spore form called the elementary body. Once inside the host cell it makes use ofthe cell's own...
hsCRP Metabolic Syndrome and Type 2 Diabetes Mellitus
Another reason for clinical interest in adding hsCRP to current risk algorithms derives from the fact that inflammation may play a key role in processes associated with metabolic syndrome, a condition that confers increased cardiovascular risk 72 . hsCRP levels are correlated positively with components of metabolic syndrome commonly measured in Fig. 8. Cardiovascular event-free survival according to baseline level of hsCRP among individuals with metabolic syndrome. Adapted from ref. 75. Fig. 8....
hsCRP and Subclinical Atherosclerosis
In contrast to the consistent findings on the relationship between hsCRP and incident cardiovascular events, evidence for an association between hsCRP and measures of subclinical atherosclerosis has been mixed. Among 3173 persons in the Framingham Offspring Study, a comparison of the top vs bottom quartile of hsCRP measured 4 yr prior to carotid ultrasonography yielded an age-adjusted RR of carotid stenosis 25 of 3.90 95 CI 2.44-6.44 in women and 1.62 95 CI 1.12-2.36 in men 87 . After factoring...
electrical cardioversion
Conflicting reports have been published regarding the release of cardiac troponin following electrical cardioversion 19-23 . The majority of studies report minor increases in both cTnT and cTnl following direct-current cardioversion in patients presenting with atrial or ventricular fibrillation. Release of cardiac troponin occurs within 3-6 h after cardioversion, with blood concentrations declining to baseline within 24 h. In general, lt 50 of patients show an increase, with the percentage...
Evangelos Giannitsis MD and Hugo A Katus MD
Confirmation of Diagnosis of Acute Myocardial Infarction Monitoring Efficiency of Reperfusion Therapy The diagnosis and immediate initiation of reperfusion therapy in patients with acute ST-elevation myocardial infarction STEMI are based on results of the standard 12-lead electrocardiogram. Because the appearance of cardiac markers of myocardial injury in the blood is delayed relative to the onset of symptom, cardiac markers are neither helpful for early diagnosis nor should their results be...