High-Sensitivity Assays for Troponin in Patients with Cardiac Disease !

Troponin is a widely used biomarker in patients with cardiac disease. The use of troponin is well established in patients with suspected acute myocardial infarction (AMI), but troponin measurement is also used in other acute and nonacute settings. In patients with suspected AMI, early decision-making is crucial to allow rapid treatment and further diagnostic evaluation. Current guidelines recommend serial measurements of troponin with a cut-off concentration at the 99th percentile to triage patients in the emergency department.

Newer, high-sensitivity assays for troponin enable the detection of distinctly lower concentrations. Using these assays and very low cut-off concentrations, several rapid diagnostic strategies have been reported to improve diagnosis in acute cardiac care. Furthermore, noncoronary and non-acute applications of troponin assays — for example as a biomarker in patients with heart failure, pulmonary embolism, or stable coronary artery disease — are on the horizon and might improve individual risk stratification.

In this Review, we provide an overview on the development of high-sensitivity assays for troponin, and their application in patients with cardiac disease.

Pathophysiological background of troponin and troponin release

in different settings. A schematic overview of myocardial structure

related to troponin (inset), as well as the plasma troponin concentrations 

in different clinical settings (young and healthy, elderly or chronic diseases,

myocardial injury, and myocardial infarction).

Read more: High-Sensitivity Assays for Troponin in Patients with Cardiac Disease !

Source: NatureReviewsCadiology

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Lowering LDL Cholesterol: When Numbers are Not Enough

Clinicians worldwide continue to be challenged by cholesterol management for their patients; specifically, whether to attempt low-density lipoprotein (LDL-C) reduction to previously described targets, or to specific percent reductions (e.g., ≥ 50% or < 50%) based on an individual's risk assessment as advocated by the US Guidelines. Indeed, Canadian and European Guidelines suggest using both strategies. Data addressing whether the high-intensity statin strategy (to achieve ≥ 50% LDL-C reduction) correlates with improved cardiovascular outcomes is limited.

In addition, it is known that LDL-C reduction to the same strength of statin can vary widely in the population4 resulting in a significant number of patients who may continue to be at increased, potentially modifiable risk, for future events. Recently, the Treating to New Targets (TNT) investigators reported in their known coronary artery disease patient population that visit-to-visit variability in LDL-C levels correlated with increased cardiovascular risk, suggesting yet another possible contributor to residual risk, reportedly independent of LDL-C levels.

Read more: Lowering LDL Cholesterol: When Numbers are Not Enough

Source: acc

Cardiovascular Disease Diagnostics and Testing

Current and emerging cardiac markers signal improved testing for better patient outcomes

Cardiovascular diseases continue to be the leading cause of death in the United States, responsible for nearly 800,000 deaths annually—or about one in every three deaths. Heart disease is the leading cause of death for both men and women, claiming the lives of about 610,000 Americans each year.1Coronary artery disease is the most common type of heart disease, killing more than 370,000 people annually.

In addition, about 5.1 million people in the United States have heart failure.2About half of the people who develop heart failure die within 5 years of diagnosis. In 2009, one out of every nine deaths included heart failure as a contributing cause. Heart failure costs the nation an estimated $32 billion each year.

In light of such dire statistics, it’s no wonder that achieving speedy diagnosis of acute myocardial infarction (AMI)—heart attack—remains a significant concern in emergency departments throughout the nation. Early triage of patients to rule-in or rule-out AMI is challenging. For many years, testing for the presence of the regulatory proteins troponin I or troponin T—both released into the bloodstream when the heart muscle has been damaged—has been the gold standard for diagnosing AMI. But recent reports have indicated that the latest generation of high-sensitivity troponin tests can increase diagnostic efficiency and improve early diagnosis of myocardial infarction.

Read more: Cardiovascular Disease Diagnostics and Testing

Alere’s troponin I test is a cartridge-based high-sensitivity immunoassay.

Source: clpmag

Troponins as cardiac injury markers

Cardiac injury occurs when there is disruption of normal cardiac myocyte membrane integrity. This results in the loss into the extracellular space (including blood) of intracellular constituents including detectable levels of a variety of biologically active cytosolic and structural proteins, referred to as biomarkers, such as troponin, creatine kinase, myoglobin, heart-type fatty acid binding protein, and lactate dehydrogenase. Injury is usually considered irreversible (cell death), but definitive proof that cell death is an inevitable consequence of the process is not available. 

When a sufficient number of myocytes have died (myocyte necrosis) or lost function, acute clinical disease is apparent. Ischemia, with or without infarction, consequent to an imbalance between the supply and demand of oxygen (and nutrients) is the most common cause of cardiac injury. Other causes include trauma, toxins, and viral infection.

The biochemical characteristics and utility of troponins, the diagnosis of cardiac injury, and acute myocardial infarction (MI) in particular will be reviewed here. The other biomarkers of cardiac injury and disease states, other than an acute MI, in which elevation of biomarkers are seen are discussed separately.

Read more: Troponins as cardiac injury markers

Source: sciencsnutshell

Troponin I and Brain Natriuretic Peptide Antibodies as new Generation of Cardiac Markers.

HyTest specialists have been involved in cardiac troponin I (cTnI) studies for more than 15 years. Currently many well characterised antibodies directed to different regions of the cTnI molecule are available. Many of these antibodies are used in commercial assays. The company has determined antibody pairs and combinations useful for the development of high sensitivity cTnI assays, and also validated pairs suitable for lateral flow assays. A new generation of cTnI antibodies is currently under development.

Work with brain natriuretic peptides is ongoing, and BNP, proBNP and NT-proBNP antibodies and antigens are available. In addition a new type of BNP/proBNP immunoassay, the "single epitope" sandwich assay, has been developed, which differs from the conventional format of sandwich immunoassays. In the single epitope sandwich assay, the capture antibody recognises the antigen (BNP or proBNP), whereas the detection antibody is specific to the complex of capture antibody and antigen. The single epitope sandwich approach has great advantages compared with conventional assays, especially in the case of unstable antigen detection. HyTest holds the intellectual property rights for this invention.

Read more:
Troponin I and Brain Natriuretic Peptide Antibodies as new Generation of Cardiac Markers.

Source: cli-online, bpac, stmd

Clinical Considerations for High-Sensitivity Cardiac Troponin Assays.

Cardiac troponins (cTn) have been available for nearly 2 decades in clinical laboratories and are now considered the gold standard for biochemical detection of myocardial infarction (MI). Furthermore, multiple organizations have endorsed the biomarkers’ use in both clinical and analytical guidelines. Today, the universal definition of MI includes the typical rise and/or fall of cTn with at least one value above the 99th percentile of a healthy reference population accompanied by at least one of the following clinical factors: presence of ischemic symptoms; electrocardiographic changes; or imaging evidence of loss of viable myocardium or a new wall motion abnormality.

However, a growing body of evidence now suggests that very low cTn values are clinically important. Investigators have found that patients who have cTn elevations considered normal, but near the 99th percentile, have worse prognoses and require more aggressive clinical management. These findings have prompted the search for newer techniques to enhance precision and enable measurements of cTn at or even below the 99th percentile cutoff.

Recently, researchers and commercial manufacturers have developed several high-sensitivity assays for cardiac troponin (hs-cTn) that are expected to be available soon for routine clinical use in the U.S. Understanding their analytical and clinical performance will be extremely important because under the current MI definition, a significant proportion of the general population would have evidence of myocardial injury. In this article, we will review the basic analytical and clinical characteristics of hs-cTn assays that are important for laboratory professionals to understand and describe how best to help clinicians employ these powerful assays.

Read more:
Clinical Considerations for High-Sensitivity Cardiac Troponin Assays.

Source: aacc, shutterstock