Primary PCI

Usually the success of reperfusion after primary PCI is easily visualized on coronary angiography. However, a substantial proportion of patients deemed to have successful reperfusion have persistent compromise of myocardial blood flow owing to microvascular obstruction (15,16). Several methods may be used for identification of microvascular obstruction, including myocardial contrast echocardiography, ST-segment resolution, magnetic resonance tomography (MRT), intracoronary Doppler flow...

Introduction

The use of highly sensitive and nearly totally specific measurements of cardiac troponin I (cTnl) and cardiac troponin T (cTnT) has revolutionized the ability to detect cardiac injury. These proteins, which participate in a regulation of the myosin-actin interaction, have been known for many years (1). In the late 1970s, Cummins and Perry (2) developed the first serum-based assay predicated on polyclonal antibodies. Subsequently, while exploring the possibility of increased specificity with...

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....

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...

Years of Follow

Cardiovascular event-free survival according to baseline levels ofhsCRP and LDL-C. (Reproduced from ref. 12.) terms of either population-based quintiles or simple cut points. The latter approach, in which hsCRP levels < 1, 1-3, and > 3 mg L represent lower-, moderate-, and higher-risk groups, provides comparable predictive utility to that of the former approach and has greater clinical appeal. The largest ofthe US studies is the Women's Health Study, an 8-yr follow-up of27,939...

Timing of Measurement

The baseline measurements ofBNP and NT-proBNP in the aforementioned studies were performed between 9.5 h and 4 d after enrollment. Recent data suggest that even earlier measurements may be of value. A substudy of the Fast Assessment in Thoracic Pain study evaluated NT-proBNP in patients with NSTEMI and unstable angina (50). NT-proBNP levels were drawn on admission in 755 patients, who were subsequently followed for 40 mo. NT-proBNP levels correlated with future risk ofmortality independent...

Joseph B Muhlestein MD

Introduction Chlamydia pneumoniae Helicobacter pylori Mycoplasma pneumoniae Cytomegalovirus Other Herpesviruses Human Immunodeficiency Virus Influenza Virus Total Pathogen Burden as an Aggregate Serological Risk Factor Clinical Use of Infectious Markers for Risk Stratification Not Yet Ready for Prime Time Conclusion References Chronic infection has been found to be significantly associated with the development of atherosclerosis and the clinical complications of unstable angina, myocardial...

Contemporary Cardiology

Cannon, md, editor-in-chief Annemarie m. Armani, md, executive editor Essential Echocardiography A Practical Handbook With DVD, edited by Scott D. Solomon, md, 2006 Preventive Cardiology Insights Into the Prevention and Treatment of Cardiovascular Disease, Second Edition, edited by JoAnne Micale Foody, md, 2006 The Art and Science of Cardiac Physical Examination With Heart Sounds and Pulse Wave Forms on CD, by Narasimhan Ranganathan, md, Vahe Sivaciyan, md, and Franklin B....

Clinical Applications of apoB see also Incorporating Lipoprotein Number Into Treatment of Lipoprotein Disorders

ApoB has gained support as a risk marker from several recent analyses that have directly compared apoB to LDL-C (34,35). Grundy outlined the advantages and disadvantages of non-HDL-C and apoB and concluded that apoB is a reasonable alternative to non-HDL-C and proposed practical cutoffs (Table 2) (28). Updated prevention guidelines from the Canadian Cardiovascular Society (CCS) (4) and Canadian Diabetes Association (41) have also introduced apoB as an alternative to LDL-C. The CCS notes that...

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...

Prediction ofClinical Recurrence After Percutaneous Coronary Intervention

The concept of clinical recurrence is of particular interest when considering patients undergoing percutaneous coronary intervention (PCI), whether for management of ACS or in patients undergoing elective PCI. In the current era of continued frequent use of bare-metal stents in some regions of the world, clinical restenosis after PCI in patients with ACS is expected in approx 20 of patients. Evidence provided by some studies suggests that the recurrence of clinical events after PCI is confined...

Marc S Sabatine MD MPH

Establishing Genetic Determinants of Complex Diseases For classic Mendelian genetic diseases, a single gene is responsible. A rare mutation in that gene causes a dramatic change in protein concentration or function that is both necessary and sufficient to cause the disease, and environmental factors play a small or nonexistent role. Examples in cardiology include familial hypercholesterolemia, familial hypertrophic cardiomyopathy, Marfan syndrome, and congenital long QT syndrome. By contrast,...

What explains the hierarchy of utility of inflammatory biomarkers

Among the growing menu of inflammatory biomarkers described in the literature, CRP has received the most focus and appears to furnish the most consistent relationship to clinical end points. Why should CRP, a distal indicator of inflammation, appear so potent as a risk predictor The answer depends on a combination of fundamental and serendipitous features. Indeed, the acute-phase proteins PAI-1 and fibrinogen play direct roles in thrombus accumulation and might logically link more tightly to...

Proposed Application Of Bnp In

At the present time, adequate data do not exist to define the proper role of BNP and NT-proBNP in stratifying patients to more aggressive interventional therapy, and the clinician must consider plasma levels of these peptides in the context of other biomarkers and clinical factors before assigning a patient to a proper level of care. More research is needed to identify appropriate pharmacological and interventional strategies for high-risk patients with ACS and elevated levels of BNP or...

SCD40L as a Marker for Platelet Activation

Plaque rupture induces platelet activation through the liberation of collagen, thrombin, and adenosine 5'-diphosphate (ADP) (Fig. 6). Platelet activation results in an increased surface expression of CD40L, which subsequently is cleaved from the membrane surface. The released sCD40L can activate CD40 on endothelial cells and thereby induce a proinflammatory cascade in the vessel wall. Moreover, sCD40L can activate CD40, which is also expressed on inflammatory cells such as monocytes and...

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...

D

CI, confidence interval D, death NSTEACS, non-ST-elevation ACSs RA, refractory angina UA, unstable angina UR, urgent revascularization. CI, confidence interval D, death NSTEACS, non-ST-elevation ACSs RA, refractory angina UA, unstable angina UR, urgent revascularization. CRP > 3 mg L CRP < 3 mg L Fig. 1. Incremental prognostic value of CRP in addition to troponin T for prediction of major adverse coronary events at 6 mo in patients with ACSs. The highest risk is confined to patients with...

Screening in Higher Risk Populations

Using traditional cut points, Silver and Pisano (50) found a high incidence of elevated levels of BNP in an unselected at-risk population in a community-based setting. Along with other emerging evidence, this observation suggests that BNP may serve as a viable screening tool to detect patients progressing from stage A to stage B in the natural history of heart failure (Fig. 1). In the Hillingdon Heart Failure Study, one-third of patients referred with a new diagnosis ofheart failure to a...

Association With Outcomes

A meta-analysis of 18 prospective studies included more than 4000 subjects free of ASCVD at baseline comparing those in the highest tertile of Lp(a) to the lowest tertile, the risk ratio for incident events was 1.7 (95 confidence interval CI 1.4-1.9) (50). This result was confirmed in a large prospective analysis that followed more than 9000 subjects for 5 yr and found a risk ratio of1.56 for fatal and nonfatal MI and angina (95 CI 1.10-2.21) when comparing the highest quartile of Lp(a) to the...

Other Conditions That Increase Natriuretic Peptides

Concentrations of BNP and NT-proBNP may be elevated in settings other than acute heart failure. Such increases do not represent analytic false positives but may cause false positive clinical diagnostic results, if other etiologies for abnormal BNP results are not considered. Disease processes other than heart failure (e.g., renal and thyroid function) have been shown to influence the concentration of natriuretic peptides (37). As an example, hyperthyroidism increases and hypothyroidism...

Recommendations Regarding Use of BNP for Screening

At this time, there is insufficient evidence to support BNP testing for screening asymptomatic, low-risk populations for LV systolic dysfunction. There may be some role for BNP to screen high-risk subgroups such as patients with prior myocardial infarction, patients with diabetes, or those with an extended history of uncontrolled hypertension. However, echocardiography is likely to remain the primary method of assessing LV function in this setting. Figure 11 depicts one possible algorithm for...

Ventricular Dysfunction as a Stimulus for BNP Release

Increased BNP synthesis and secretion may be owing to increased wall stress from ischemia-induced ventricular dysfunction. BNP levels positively correlate with hemodynamic parameters that reflect ventricular dysfunction, including LVEDP, and negatively correlate with left ventricular ejection fraction (LVEF) (31). A retrospective study reported that 30 of patients who develop heart failure after MI have preserved LVSF and are thought to have diastolic dysfunction (32). Since neurohormonal...

References

Dyslipidemia and other risk factors for coronary artery disease. In Braunwald E, ed. Heart Disease A Textbook of Cardiovascular Medicine, 5th ed. WB Saunders, Philadelphia, 1997, pp. 1126-1160. 2. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation 1998 97(18) 1837-1847. 3. Grayston IT, Kuo C-C, Campbell LA, Wang S-P. Chlamydia pneumoniae sp. Nov. for Chlamydia sp strain...

Acute coronary syndrome an inflammatory disease

Because acute coronary syndromes (ACSs) are heterogeneous with respect to their pathogenesis, it may be anticipated that they are also varied with respect to their risk and appropriate treatment (1,2). The growing evidence that atherosclerosis is an inflammatory From Contemporary Cardiology Cardiovascular Biomarkers Pathophysiology and Disease Management Edited by David A. Morrow Humana Press Inc., Totowa, NJ disease and that inflammation plays a pivotal role in the complex processes that are...

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...

Mechanisms Predictors of Elevated Troponin Levels After PCI

The pathophysiological mechanism for elevated cardiac troponin levels after PCI is unclear. Potential mechanisms include myocardial necrosis or ischemia from prolonged balloon inflations, transient abrupt closure, distal embolization, and side-branch occlusion. In two series of patients undergoing PCI, elevated postprocedural levels of troponin correlated closely with long balloon-inflation times (13,14). Katoh et al. (15) studied 16 patients undergoing PCI with measurements of coronary sinus...

Statins

The ability of statins to lower hsCRP was first described for pravastatin using data from the CARE trial (94,101). Subsequent confirmatory work has shown the effect of statins on hsCRP to be an important class effect. A meta-analysis of the effects of statins on nonlipid serum markers specifically CRP, fibrinogen, homocysteine, LDL-C oxidation, tissue plasminogen activator, plasminogen activator inhibitor, and platelet aggregation concluded that, of these, only CRP appears to be influenced by...

Influence ofAge and Gender

Several noncardiac factors may influence the circulating levels of natriuretic peptides and potentially confound the relation to indices of cardiac function. Age has been shown to be an important determinant of circulating natriuretic peptide levels (216-218). Both increased release and decreased clearance may contribute to elevated circulating levels of BNP and NT-proBNP in advanced age, but the exact mechanisms remain to be elucidated. Subclinical reduction in renal function, increased LV...

Novel risk factors and cardiovascular risk prediction

Identifying asymptomatic individuals at high risk of developing a first cardiovascular disease (CVD) event is a critical issue in primary prevention. Although the use of global From Contemporary Cardiology Cardiovascular Biomarkers Pathophysiology and Disease Management Edited by David A. Morrow Humana Press Inc., Totowa, NJ LDL-C slCAM-1 SAA Apo B TC HDL-C hsCRP Relative Risk of Future Cardiovascular Events Fig. 1. Head-to-head comparison ofvarious biomarkers in cardiovascular risk prediction....

Actions of LPL

The physiological action of LPL consists of the hydrolysis of the triacylglycerol component of triglycerides and VLDL, resulting in the production of chylomicron remnants, and in the case of VLDL, resulting in the production of smaller, intermediate-density lipoproteins (IDLs) (119). During a further hydrolysis of IDL by the enzyme, LDL is formed, providing cells with the cholesterol needed to build up cellular membranes. Thus, the efficient lipolysis of triglyceride-rich lipoproteins, with...

Mass Spectrometry

Although 2D-PAGE capabilities continue to advance, the field has increasingly turned to direct mass spectrometric analysis of complex mixtures (Fig. 3), a significant break- through that has enabled many ofthe accomplishments ofproteomics analysis. The experimental origins of modern MS date back more than 100 yr, when J. J. Thomson noted that the parabolic trajectory exhibited by ions moving through electric fields was proportional to their mass-to-charge (m z) values. The first instrument, a...

Plasma Proteomics in Cardiovascular Disease

The plasma proteome is unique in that it does not represent a particular cellular genome but, instead, reflects the collective expression of all cellular genomes. It has thus far been poorly characterized. Twenty-two of the most abundant proteins, including albumin and the immunoglobulins, comprise 99 ofthe plasma proteome mass. Many of the biologically interesting molecules relevant to cardiovascular disease (CVD) are low-abundance proteins. For example, cardiac markers such as troponin are...

Ldl Particle Number

No doubt, the ATP-III strategy emphasizing metabolic syndrome and following non-HDL-C will detect many individuals who warrant aggressive preventive efforts. However, the objective to better identify at-risk patients has prompted new discussion on how to measure lipoproteins (28,34,42,43). The ideal measure of dyslipidemia might be to estimate the number of lipoprotein particles, because LDL-C does not distinguish small, dense LDL, and particle number may actually correlate more closely with...

Frequency and Pathobiology of Troponin Elevation in Sepsis

Numerous reports have established that both cTnl and cTnT are biomarkers of myocardial injury in sepsis and septic shock or other systemic immune response syndromes (SIRSs), such as pancreatitis (27-32). Septic patients presenting to tertiary, urgent, and intensive care settings without documented heart disease have abnormal troponin results in a substantial proportion (31-85 ) of cases. In a representative study among adult patients (n 46) with septic shock, levels of cTnI ( 0.4 Mg L Stratus...

CRP as a Marker of Widespread Inflammation

One of the limitations of CRP as a marker of cardiovascular disease activity is that CRP represents a sensitive but nonspecific marker. It is not specific to vascular or plaque inflammation and, therefore, correlating this protein with CVD is difficult. The more recent and continuously evolving knowledge regarding the pathobiology of ACS suggests a complex and possibly systemic involvement of the endothelium, blood cells, and proteins. The reasons for adverse prognosis in patients with elevated...

Inflammatory Biomarkers and Clinical Utility

Some have argued that assessment of inflammatory biomarkers is superfluous because of the lack of evidence-based interventions that would be predicated on them. Moreover, some oppose the measurement of inflammatory biomarkers on the grounds that if they revealed higher risk in patients already receiving maximal medical therapy, those results would not change management. A more optimistic position would argue that residual risk indicated by inflammatory biomarkers in an optimally managed patient...

Detection of myocardial ischemia

The ECG has long been the standard for the detection of ischemia. This capitalizes on the fact that ischemic myocardium repolarizes differently than normal myocardium, seen as changes in the ST-complex. Ischemic myocardium also does not contract normally because energy production and utilization are altered. Thus, the effects of ischemia can be observed by examining myocardial function through a number of imaging modalities. Finally, ischemia interferes with a myriad of biochemical processes...

Estrogen Receptor

Epidemiological studies have demonstrated that, compared with men, premenopausal women are relatively protected from the development of CVD. This difference has been attributed to estrogen and its effects on atherosclerosis, thrombosis, and inflammation. The relationship, though, is not straightforward, because several clinical trials have shown hormone therapy to be associated with an increased incidence of MI and stroke (87,88). However, the relevance of estrogen and its receptors extends to...

Managing Potential False Test Results

False positive test results should be suspected in the setting of elevated BNP or NT-proBNP values that do not exhibit variation consistent with the clinical picture or the serial kinetics. Similarly to that for troponin, serial testing can be very valuable in discerning false test results. Analytic false positives resulting from poor sample handling will resolve with proper technique. Clinicians should consult with their laboratory if heterophilic antibodies or autoantibodies are suspected,...

Richard L Dunbar MD and Daniel J Rader MD

Heterogeneity of Atherogenic Lipoproteins What Marker of Atherogenic Lipoproteins Is Optimal for Clinical Practice Incorporating Lipoprotein Number Into Treatment of Lipoprotein Disorders Conclusion Appendix Case Study References In the past several decades, multiple landmark clinical trials have proven that certain lipoprotein abnormalities not only predict but also provoke atherosclerotic cardiovascular disease. Yet, there is a growing concern that traditional measures of atherogenic...

Tissue Factor

Tissue factor is a small transmembrane glycoprotein synthesized in subendothelial smooth muscle cells and monocytes and is also found circulating in procoagulant micro- particles. The presence of tissue factor in the circulation initiates the coagulation cascade. Tissue factor is also produced in circulating monocytes and is involved in the patho-biology of atherothrombosis and several inflammatory disorders, such as systemic lupus erythematosus (54,55). The tissue factor gene is found on...

PAPPA as a Marker for Plaque Stability

The progression and destabilization of atheromatous plaques involve major changes in the structure ofthe arterial wall. Matrix metalloproteinases (MMPs) are potential indicators of arterial inflammation, and by degrading extracellular matrix, they contribute to the fragility of the lipid-rich, atherosclerotic plaque and finally to its rupture. PAPP-A is a high-molecular-weight, zinc-binding MMPs enzyme that is measured during pregnancy in maternal blood for the fetal diagnosis of Down syndrome....

Thrombomodulin

Thrombomodulin is an integral membrane-bound receptor found on the surface of ECs that binds thrombin, accelerates thrombin-mediated protein C activation, and contributes to factor Va and factor Villa neutralization. Genetic studies have identified two polymorphisms that may have potential clinical implications. A mutation at Ala455Val is reported to be associated with the occurrence of MI (65) and has been specifically associated with increased risk among African Americans (66). A mutation...

Use Of Bnp For Inpatient Management Of Heart Failure

There are approx 1 million admissions annually to US hospitals for heart failure. Patients admitted to the hospital with decompensated heart failure often have improvement in symptoms with the various treatment modalities available. However, readmission after hospitalization for heart failure is surprisingly common, estimated at 44 at 6 mo within the Medicare population, and challenging to predict (56). Considering that hospitalization is the principal contributor to the cost of patient care...

Effects of Urocortin

Because of its similarity to CRF, the first studies on urocortin focused on its possible effects in the stress response through the hypothalamic-pituitary-adrenal axis. However, studies of receptor affinities and subtype distributions revealed that although CRF and urocortin both bind to two receptors (CRF-R1 and CRF-R2) corticotropin-releasing factor has 10 times greater affinity for CRF-R1 and urocortin has 40 times greater affinity for CRF-R2. In addition, CRF-R2 is further subtyped into...

A B C D E G H

Imprecision vs analyte concentration profiles for cTnI. A AIA21 B, C Access and Access 2 D Stratus CS E Centaur F Immulite G Dimension H ACS 180 I Immuno 1 J ECi K Liaison L Opus Plus M Vidas N AxSym O Alpha Dx. (Reproduced from ref. 28, with permission from the American Association for Clinical Chemistry.)

MPO as a Marker for Oxidative Stress

The results of the combined use ofPlGF and sCD40L for risk stratification of patients with acute chest pain and troponin T levels < 0.01 pg L with respect to death or nonfatal AMI during 30 d of follow-up (n 531) are shown. Fig. 10. Neutrophil activation is indicated by the change in the MPO index in blood from the aorta and great cardiac vein. In patients with unstable angina, but not in patients with stable angina, a decrease in MPO content was observed in...

Impact of Antioxidant Therapy

Because lipoprotein oxidation is thought to play a major role in atherogenesis, it could be expected that intervention with antioxidants would be protective against atherosclerotic disease. Although antioxidant studies in four different animal models of atherosclerosis (rabbit, mouse, hamster, and monkey) mainly showed positive results (67,82), several large-scale, double-blind, placebo-controlled trials evaluating the effects of different antioxidant compounds on cardiovascular outcome were...

Graded Exercise Electrocardiography

Exercise ECG testing is a common noninvasive diagnostic test used in the ED for low-to moderate-risk chest pain patients. It is easy to perform (49,50) and relatively safe after eliminating the possibility ofrest myocardial ischemia by serial 12-lead ECGs or myocardial necrosis by serial cardiac biomarkers (51). Compared with other noninvasive cardiac imaging, exercise ECG testing is relatively inexpensive (52). A meta-analysis of protocols including exercise ECG reported a sensitivity of 68...

Mhc

Importance of inflammatory balance in patients with ACS. The cumulative incidence of death or nonfatal MI at 6 mo of follow-up by baseline levels of hsCRP and IL-10, respectively, is shown. Diagnostic threshold levels were 3.5 ng L for IL-10 and 10 mg L for CRP (n 547). MHC, major histocompatibility complex TCR, T-cell receptor GITR, glucocorticoid-induced tumor necrosis factor receptor. acute ischemic event caused by plaque instability. In addition, the beneficial effect of elevated...

Thrombin

Thrombin is a pivotal enzyme in both protective hemostasis and pathological thrombosis with several discrete functions that include platelet activation EC activation monocyte tissue factor expression conversion of fibrinogen into fibrin activation of factors V, VIII, and XIII and, finally, binding to the regulatory molecules antithrombin and thrombomodulin. The most widely studied genetic mutation of thrombin production is the prothrombin 20210G A polymorphism. Although clearly linked to venous...

Valvular Heart Disease

Aortic stenosis is associated with LV hypertrophy and LV relaxation abnormalities and may, in some cases, eventually progress to LV systolic dysfunction. The progression of aortic stenosis is routinely monitored by serial Doppler echocardiographic examinations, permitting noninvasive estimates ofthe transvalvular gradient and aortic valve orifice area. The relation among natriuretic peptide plasma levels, disease severity, and symptoms has been examined in patients with aortic stenosis...

Discussion

At baseline, RC had optimal cholesterol levels, few major risk factors, and a reassuring Framingham score. Yet he had an ominous family history, impaired fasting glucose, and a low HDL-C. The low HDL-C was the only lipid abnormality that suggested he had atherogenic dyslipidemia, but prediabetes is also an important clue. Although the standard labs hinted at subtle abnormalities, the apoB and NMR findings revealed substantial lipoprotein abnormalities that were not reflected in his LDL-C...

James Rider MD and Leslie Miller MD

Detection of Cardiac Troponin in CHF Combined Measurement of Troponin and Natriuretic Peptides Cardiac troponin I (cTnl) and cardiac troponin T (cTnT) are highly specific and sensitive biomarkers of necrosis. Although they are used primarily for the diagnosis of acute coronary syndromes, their application to the field of congestive heart failure (CHF) has now received significant interest. cTnl and cTnT provide valuable clinical information not available through other diagnostic methods and...

Endstage renal disease

Cardiac disease is the major cause ofdeath in patients with ESRD, accounting for approx 45 of all deaths (80). In dialysis patients, about 20 of cardiac deaths are attributed to AMI. MI is a catastrophic clinical event in ESRD patients, with a 2-yr mortality of 73 . Increased cardiac death rates in ESRD patients occur more frequently on Mondays and Tuesdays (20 ) compared with other days of the week (14 ) (81). One challenge confronting the nephrology community is the exploration of more...

Cd41pe

Identification and quantification of monocyte-platelet aggregates using whole-blood flow cytometry. (A) Monocytes are identified based on light-scatter properties and differential cell-surface expression of the lipopolysaccharide receptor (CD14). (B) The monocytes are then analyzed for expression of platelet-specific antigens, in this case GPIIb (CD41). Expression of platelet-specific antigens on monocytes above isotype control represents monocyte-platelet aggregation. Monocyte-platelet...

Aspirin and Other Antiplatelet Agents

The ability of antiplatelet therapy to prevent future cardiovascular events appears to vary by hsCRP level. In the Physicians' Health Study, a large primary prevention trial, the reduction in risk of future MI associated with assignment to aspirin (325 mg on alternate days) was 56 (p 0.02) among participants with baseline hsCRP levels in the highest quartile and declined with hsCRP levels such that a reduction of only 14 (p 0.80) was observed among those in the lowest quartile, suggesting that...

FollowUp Visit

RC returns a year later without new complaints and reports no changes in his health. He brings additional laboratory test results conducted when he participated as a health volunteer in a research study. His cholesterol levels are comparable with the previous values, but the additional test results include an apoB of135 mg dL (optimal < 90 mg dL) and, by NMR technique, an LDL particle number of2204 nmol L (optimal < 1100). His LDL is predominately the small, dense variety. His Lp(a) is 6 mg...

Human Immunodeficiency Virus

Some evidence has also linked human immunodeficiency virus (HIV) with atherosclerosis. Constans et al. (82) showed that, although no clinically relevant atherosclerotic lesions were found, plaques occurred more often in patients with HIV than in control subjects. During postmortem examination of eight HIV-seropositive male patients, major atherosclerosis in coronary arteries was present in the absence of an associated cardiovascular risk factor (83). Investigators have postulated that viral...

Influenza Virus

Although most studies examining an association between infection and atherosclerosis have been conducted to elucidate the association of infection with the development of atherosclerosis, a few studies have targeted the triggering of ACSs by infections. One prospective study (84) and several retrospective studies have suggested that acute respiratory infection might trigger MI (85-87). A possible relationship between influenza and MI was first suggested after epidemics of influenza struck...

Does High BNP Always Mean High Filling Pressure

Because a major stimulus for the release of BNP is increased wall tension, BNP levels might be expected to correlate with elevated LV filling pressures. However, in the clinical setting there are circumstances in which a high level of BNP is not associated with high left heart filling pressures. These situations include right-sided failure secondary to advanced pulmonary disease, PE, or primary pulmonary hypertension acute or chronic renal failure and rapid lowering of the wedge pressure with...

The clinical problem

For patients presenting with chest pain or other symptoms suggestive of NSTEACS, there is a broad spectrum of diagnoses, including chest pain of noncardiac causes, unstable angina, and myocardial infarction (MI) of varying size, with diverse prognoses and appropriate treatments. These patients must be considered to have an ACS until proven otherwise. Of those admitted to the hospital, < 10 will have STEMI, approx 50 will have a NSTEACS, and the remaining approx 40 will have diagnoses other...

Problems With Clinical Application ofLDLC Approximation

As the understanding of lipoprotein disorders has advanced, it has become more apparent that the LDL-C approximation has important clinical limitations (Table 1) (15). The LDL-C approximation has been extended from a small study of a highly selected population to estimate risk and govern the therapy of millions of patients around the globe. The assumptions regarding TG VLDL-C and its value have not held up to scrutiny (16-18). Subsequent studies have shown that the LDL-C does not compare well...

Association ofLpPLA2 With Cardiovascular Risk

Prospective Nested Case-Control Studies Initial evidence for an association of Lp-PLA2 with cardiovascular risk came from the West of Scotland Coronary Prevention Study (WOSCOPS), a large primary prevention trial of men at high risk that was primarily initiated to evaluate the effect of pravastatin therapy on reduction of CHD (26). Of6595 middle-aged men with hypercholesterolemia and no preexisting CHD, 580 with subsequent coronary events (nonfatal myocardial infarction MI , CHD death, or...

Clearance Of Natriuretic Peptides Mechanisms of Natriuretic Peptide Clearance

Clearance of natriuretic peptides from the circulation involves two main pathways (1) NPR-C-mediated endocytosis followed by lysosomal degradation and (2) enzymatic degradation independent of the clearance receptor by the enzyme neutral endopeptidase (NEP) (99,100). NEP is a zinc metallopeptidase widely distributed on the surface of endothelial cells, vascular smooth muscle cells (VSMCs), cardiac myocytes, and fibroblasts (101). The lungs, liver, and kidneys are the most important organs for...

Abcdefgh

Concentration of BNP in patients with pulmonary disease. COPD, chronic obstructive pulmonary disease. of increase is typically less than that for patients with dyspnea from heart failure (Fig. 6). In a substudy of the Breathing Not Properly Multinational Study (25), among 417 sub-j ects with a history of asthma or chronic obstructive pulmonary disease without prior heart failure, 21 were newly discovered to have heart failure. Only 37 of these new cases were identified by physicians in...

Association of LPL With Cardiovascular Risk

Epidemiological evidence on the potential role of LPL in CHD remains scarce and controversial. The association between LPL activity and mass and the presence of CAD were studied in a large cohort of patients with CAD participating in the Regression Growth Evaluation Statin Study (124). Patients with the lowest LPL activity reported more severe angina pectoris according to New York Heart Association classification, compared with patients in the highest quartile ofthe LPL distribution. The...

Implications lor Therapy

Despite strong evidence for the prognostic value ofthe newer markers, such as BNP and CRP, their integration into clinical practice has not become widespread. The primary determinant ofthis pace ofintegration has been the absence of guidance regarding the appropriate therapeutic response. Although therapies that mitigate the risk of an elevated level of troponin in patients with suspected ACS are well defined, to date there is not a consistent base of evidence to guide treatment in response to...

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,...

An Integrated Approach to Risk Assessment

In addition to measurements of troponin, the clinical history and the standard 12-lead ECG constitute the basis for accurate assessment of risk. A thoughtful interpretation of the patient's symptoms is essential for appropriate diagnosis and risk statification. Previous manifestations of ischemic heart disease and comorbidities, such as CHF, diabetes mellitus, or renal dysfunction, are associated with an increased risk of new cardiac events independent oftroponin. The standard 12-lead ECG is an...

Antihyperglycemic Agents

Given the interrelationship among inflammation, metabolic syndrome, and diabetes, it is not surprising that antihyperglycemic agents such as metformin and thiazolidinedione have been shown to lower hsCRP levels. In a 26-wk trial among patients with type 2 diabetes, rosiglitazone therapy reduced hsCRP levels and other inflammatory markers (118). Changes in hsCRP level were uncorrelated with changes in glycemic control, as measured by hemoglobin A1c (r 0.06) and fasting glucose level (r 0.06) and...

Urotensin Expression in Hypertension and Heart Failure

A high density of urotensin receptors is found in the smooth muscle layer of coronary arteries and LV myocytes (69). Urotensin is approx 50 times more potent than ET-1 in contracting human coronary, mammary, and radial arteries in responding tissue however, some samples fail to respond to urotensin but are reactive toward ET-1 (69). These results demonstrate binding of urotensin to the urotensin receptor in the human vasculature. Urotensin gene expression is abundant in the human kidney and...

Info

Future markers of myocardial necrosis Accurate recognition of myocardial necrosis is important for achieving an accurate diagnosis but, more important, for assessing risk and directing appropriate therapy that improves clinical outcome. Most investigators agree that future efforts in diagnostics and therapeutics should focus on that phase of myocardial ischemia during which injury is reversible so that myocardial salvage can be maximized. Multimarker strategies using established and new...

Bertil Lindahl MD PhD FESC

Definition of Non-ST-Elevation Acute Coronary Syndrome Mechanisms Underlying Prognostic Relationship of Troponin in ACS Practical Issues Conclusion References The clinical history, standard 12-lead electrocardiogram (ECG), and markers of myocardial necrosis constitute the basis for diagnosis and accurate risk assessment in patients with suspected of a non-ST-elevation acute coronary syndrome (NSTEACS). Cardiac troponin T and cardiac troponin I are ideal biochemical markers for the detection of...

Assays for BNP

Synthesis and secretion of BNP and proBNP. aa, amino acid MM, molecular mass. Fig. 3. Synthesis and secretion of BNP and proBNP. aa, amino acid MM, molecular mass. Antibody Characteristics of BNP Assays Cleared by the Food and Drug Administration Antibody Characteristics of BNP Assays Cleared by the Food and Drug Administration Bayer Shionogi Biosite Beckman Abbott Murine MAb vs ring structure Murine MAb vs ring structurea Murine MAb vs ring structurea Murine MAb vs C-terminus Murine...

Druginduced myocardial damage

Increases in cardiac troponin have been described in (1) patients treated with certain types of antineoplastic agents, (2) patients presenting to hospitals following alcohol and drug abuse, and (3) patients with therapeutic drug-induced cardiac toxicity. The release of cardiac troponin into the circulation following therapy with antineoplastic agents has been well documented (71-74). Both acute (within hours) and chronic (days to weeks) myocardial toxicity manifested by ischemia, arrhythmias,...

Interleukin10 as a Marker ofInflammatory Balance

Inflammatory balance may also play an important role in patients with ACS (57,58). Interleukin (IL)-10 is secreted by activated monocytes macrophages and lymphocytes (59). It has multifaceted anti-inflammatory properties including inhibition of the proto-typic proinflammatory transcription factor nuclear factor-kB leading to suppressed cytokine production (60), inhibition of matrix-degrading metalloproteinases (61), reduction of tissue factor expression (62), inhibition of apoptosis of...

Plasminogen Activator Inhibitor1Tissue Type Plasminogen Activator

The endogenous fibrinolytic system is under meticulous control of clot-dissolving enzymes such as t-PA and inhibitors of these enzymes, such as PAI-1. This system represents the most studied of the anticoagulant systems regarding future cardiovascular risk. PAI-1 is produced in the human vascular endothelial cell, the liver, and adipose tissue (68). PAI-1 is a serine protease that binds and irreversibly inhibits tPA from cleaving fibrin. Several genetic polymorphisms of PAI-1 have been...

Other Herpesviruses

Although CMV has the most information regarding its potential role in the development and progression of coronary atherosclerosis, a variety of other viruses have also been implicated. Herpes simplex virus (HSV) has been associated with atherosclerosis in a variety of ways. In vitro studies of HSV-1 and HSV-2 have demonstrated the presence of similar potentially proatherogenic mechanisms similar to those found with CMV. Specifically, HSV infection leads to lipid accumulation in vascular cells,...

Actions of Adiponectin

The mechanisms whereby adiponectin exerts its physiological actions are not entirely clear. Apart from its role as an insulin-sensitizing agent, and its implication in metabolic disorders, adiponectin might also be involved in the regulation of inflammatory processes that contribute to atherosclerosis. Because adiponectin and TNF-a are both secreted by adipose tissue, a direct link between these two markers seems conceivable. Indeed, TNF-a has been suggested to be a strong inhibitor of the...

Traditional Cardiac Biomarkers Used in the Ed Ckmb Isoenzyme

CK-MB is predominantly found in the myocardium and is the most specific of the three CK isoenzymes for the detection of myocardial necrosis. Elevation of CK-MB occurs 4-6 h after the onset of myocardial necrosis and can remain for 24-48 h (10). The initial sensitivity of CK-MB for the detection of AMI has been reported to be 23-57 (11,12). Obtaining additional CK-MB measurements incrementally improves the sensitivity repeat testing at 3 h after initial presentation improves the sensitivity to...

Atherosclerosis no longer a bland lipidstorage disease

Only a few decades ago the prevailing postulate regarding the pathogenesis of atherosclerosis predicated a proliferation of smooth muscle cells (SMCs) leading to a fibrous stenotic lesion that surrounded a necrotic core of deposited cholesterol and cholesteryl esters (1). A combination of observations on experimental atherosclerosis and study of human atherosclerotic lesions has added to this traditional model of atherogenesis by encompassing inflammatory processes. Early after initiation of a...

Matthew D Linden PhD andMark I Furman MD

Molecular Basis of Monocyte-Platelet Interaction Monocyte-Platelet Aggregates as a Marker of CAD Laboratory Detection of Monocyte-Platelet Aggregation Pathophysiology of Monocyte-Platelet Aggregates in CAD Conclusion References Platelets are a central cellular interface of the thrombotic and inflammatory processes of coronary atherosclerosis and modulate this interface by binding to leukocytes and altering their function. In addition, platelet activation formation of leukocyte-platelet...

Comorbidity and Special Issues That Influence Interpretation of BNP

The Breathing Not Properly Multinational Study and other observational studies have demonstrated a correlation between estimated glomerular filtration rate (eGFR) and BNP in patients with and without heart failure (22). Findings from this study indicated that the concentration of BNP should not be interpreted in isolation but should be integrated with other findings in the diagnostic evaluation. Chronic kidney disease influences the optimal threshold for BNP in the diagnosis of heart failure....

Association ofoxLDL With Cardiovascular Risk

To date, a number of cross-sectional studies have examined the involvement of oxidative modification of LDL in subjects with clinical evidence of CVD. Clinical studies (72, 73) have demonstrated that patients with both stable CHD and acute coronary syndrome (ACS) have elevated plasma levels of oxLDL compared with apparently healthy control subjects. A positive association between oxLDL and severity of ACS was found by Ehara et al. (74), who reported that oxLDL concentrations were significantly...

Clinical Role for Troponin Testing in Sepsis

At present, data supporting any clinical application of troponin for prognostic assessment in SIRSs are limited, and, more important, no specific therapeutic strategies that might modify the risk of patients with SIRS have been identified. Application of aggressive antithrombotic, antiplatelet, and invasive therapies effective for patients presenting with ACS and elevated troponin are not supported by clinical data in this setting and may expose patients with sepsis to additional, unacceptable...

Clinical Use Of Infectious Markers For Risk Stratification Not Yet Ready For Prime Time

Although a significant number of infectious markers are available and are linked by epidemiological evidence to atherosclerotic CVD, the evidence does not yet rise to the level required to justify routine use during clinical risk stratification of individual patients. Limitations of the available body of information arise from several perspectives. First, the infection and atherosclerosis hypothesis remains just that, a hypothesis. A direct cause-and-effect relationship has not yet been proven...

Issues Related to Imprecision

There was significant concern that the high imprecision at the low cutoff values suggested would result in frequent analytic false positives. Accordingly, it was recommended that the 99th percentile be measured with a coefficient of variation (CV) < 10 . This value, which initially led to complaints from the diagnostic industry, was predicated on several factors and is really a conservative estimate. Data to define the 10 CV were available at that time only through the diagnostic companies...

Monocyteplatelet Aggregates As A Marker Of

Patients with stable CAD have elevated P-selectin expressed on the platelet surface and both increased circulating monocyte-platelet aggregates and an increased propensity to form monocyte-platelet aggregates with platelet stimulation (7). This phenomenon reflects a process of ongoing platelet degranulation and an as yet poorly defined intracellular platelet environment that makes the platelets more responsive to agonist stimulation. The increase in monocyte-platelet aggregate formation may...

Robert L Jesse MD PhD

Framing the Clinical Need for Biomarkers of Ischemia Detection of Myocardial Ischemia The Quest for a Biochemical Marker of Myocardial Ischemia Clinical Challenges to the Development of Ischemia Markers Conclusion References Assessment ofthe patient with suspected acute coronary syndrome (ACS) has remained challenging despite the growing armamentarium of both diagnostic and prognostic tests. Inadvertent discharge of patients thought to be at low risk of ischemia but later found to have an ACS...

Diagnosis ofBlunt Cardiac Trauma

Concentrations of both cTnI and cTnT have been shown to be increased in trauma patients, especially following cardiac contusion (13-16). Blunt cardiac injury typically results from direct compression of the heart or decelerating forces delivered to the chest. Such cardiac injury may occur even after relatively low-energy trauma without other obvious injuries. In the large majority of patients with blunt chest trauma studied, small to moderate increases in cardiac troponin were found, implying...

Clinical challenges to the development of ischemia markers

Absence of a Gold Standard The single greatest impediment to the development of new markers for myocardial ischemia is the lack of a gold standard. Historically, the diagnosis of ischemia has been a clinical decision based on the history, physical examination, ECG, and aggregate of other tests performed and data acquired during the admission. It is fundamentally a clinical decision, and even in the absence of any hard end point or objective data such as elevated cardiac troponin or ECG changes,...

Flow Cytometry

Flow-cytometric measurement of platelet-surface glycoproteins in unfixed whole blood is a rapid, sensitive, and quantitative method that enables simultaneous analysis of multiple aspects of platelet biology to be conducted on large numbers of single platelets in a short time (29). It can be carried out in small samples of whole blood, and thrombocytopenic samples can be analyzed. It enables 100 of the platelet population to be studied, including giant platelets, platelet-derived microparticles,...

Differences in Regulation of ANP and BNP Synthesis

Although the main stimulus for synthesis and release appears to be the same for ANP and BNP, important aspects of the regulation and induction of peptide synthesis differ (Table 4). In experimental models, both atrial and ventricular BNP mRNA levels increase rapidly (< 1 h) following acute pressure overload, and these changes are paralleled by increased circulating BNP (66). Similarly, activation of the BNP gene in the cardiac ventricles occurs rapidly after experimental myocardial infarction...

Assessment of Mechanical Properties of Platelets

Because they are performed on anticoagulated blood, aggregation studies cannot be used to test platelets under conditions of maximal activation, and they are incapable of assessing the role of platelets in thrombin production (36). Assays capable of assessing platelet function during clotting and thus allowing measurement of the contribution of platelets to thrombin generation are available. Because platelets are monitored in the presence of thrombin, the test gages platelets under conditions...

Interfering Antibodies

Human antianimal (heterophilic) antibodies, rheumatoid factor, and autoantibodies in patients with autoimmune diseases are potential sources for false test results. Commercial assays include blocking agents to minimize these analytic interferences, but this method may not be effective in every situation. Exposure to animal antigens (e.g., close contact with animals or treatment with antibody fragments, such as abciximab) can give rise to human antianimal antibodies. The BNP and NT-proBNP assays...

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...

Monitoring IIbIIIa Receptor Antagonists

GpIIb IIIa antagonists prevent thrombus formation in proportion to their blockade of the approx 80,000 GpIIb IIIa receptors present on the platelet surface (41). The most widely used method to monitor GpIIb IIIa-receptor antagonists (RA) is turbidimetric aggrego-metry. Early studies found that inhibition of 50 of the GpIIb IIIa receptors was needed to detect significant inhibition of ADP-induced platelet aggregation, whereas blockade of 80 of the receptors completely abolished ADP-induced...

Using BNP Levels to Triage Patients Presenting With Acute Dyspnea

Measurement of BNP helps to make the diagnosis of heart failure in the ED and may also assist in triage decisions, such as in identifying those patients who should be admitted directly vs those who might be treated and then discharged. In The Rapid Emergency Department Heart Failure Outpatient Trial (20) in 464 patients presenting to the ED with complaints ofdifficulty breathing, BNP measurements were performed on arrival, and then every 3 h in the ED, at the time of hospital admission, and at...

And Paul M Ridker MD MPH

Novel Risk Factors and Cardiovascular Risk Prediction Pathophysiology of CRP hsCRP and Cardiovascular Risk Epidemiological and Clinical Data Practical Considerations Therapeutic Interventions Clinical Recommendations References High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy persons without a history of cardiovascular disease, as well as recurrent...