Subject matter experts discuss their company’s offerings
BY: KURT WOOCK
Testing products continue to assist with the diagnosis or assessment of various cardiovascular conditions. With more precise tools, including new means to analyze the data, patients can receive the treatment they need sooner and with higher accuracy. Representatives from Abbott, Atherotech Diagnostics Lab, BG Medicine, LipoScience, Randox Laboratories, and Siemens Healthcare Diagnostics discuss the latest advancements in this arena with CLP.
CLP: WHAT IS THE NAME OF YOUR COMPANY’S CARDIOVASCULAR TESTING PRODUCT, WHAT TYPE OF TEST IS IT, AND WHAT DOES IT MEASURE?
Agim Beshiri, MD, medical director, Abbott, Abbott Park, Ill: The ARCHITECT STAT High Sensitive Troponin-I Assay is a blood test that allows doctors to evaluate whether or not patients are having a heart attack within 2 to 4 hours. This faster evaluation could allow doctors to reduce the time to diagnosis and treatment by several hours when compared to standard troponin tests. The preferred biomarker used to identify suspected heart attacks is cardiac troponin, a protein found in the heart muscle, because it can detect injury to the heart. Abbott’s ARCHITECT STAT High Sensitive Troponin-I (hsTnI) Assay can measure very low levels of cardiac troponin I. [The new assay runs on Abbott’s fully automated ARCHITECT family of analyzers and is available in CE-marked countries, pending country registration.]
The ARCHITECT Galectin-3 assay, a test for assessing the prognosis of patients diagnosed with chronic heart failure (HF), may help doctors identify patients at highest risk for a worse prognosis, including rehospitalization and death, allowing them to tailor the level of care to individual patient needs. While the progress of HF is different for each patient, several studies demonstrate that HF patients with higher levels of a protein called galectin-3 present are more likely to have worse outcomes, including rehospitalization and death.
[The ARCHITECT Galectin-3 test is available in several European countries. The test was developed in partnership with BG Medicine Inc to run on Abbott’s ARCHITECT immunochemistry platform. Abbott expects to submit a 510(k) clearance application for the assay some time this year, and anticipates introducing the assay in the United States next year.]
Atherotech Diagnostics Lab, Birmingham, Ala:Michael Cobble, MD, chief medical officer, Atherotech Diagnostics Lab is the leading clinical reference laboratory specializing in cardiometabolic testing and disease management solutions. Atherotech’s proprietary and comprehensive VAP Lipid Panel Plus, or Vertical Auto Profile, uses vertical density gradient ultracentrifugation to accurately identify cardiovascular disease risk through direct measurement of lipids.
The problem with the basic lipid panel commonly used is it misses true cardiovascular disease risk. In fact, recent studies show significant misclassification of nearly 60% of patients with LDL targets under 70 and triglycerides between 150 and 400. The VAP Lipid Panel Plus provides clinicians with the necessary comprehensive and accurate lipid measurement and risk identification to enable personalized effective treatment and improved outcomes.
BG Medicine, Waltham, Mass: Currently, we have two diagnostics products; the BGM Galectin-3 test for use in patients with chronic heart failure is available in the United States, where it has been cleared by the FDA, and in Europe; and our CardioSCORE test for the prediction of risk for major cardiovascular events will launch in Europe in 2013.Eric Bouvier, PharmD, president and CEO,
The BGM Galectin-3 test is an enzyme immunoassay that measures Galectin-3 protein levels in the blood. Galectin-3 is secreted by activated macrophages and modulates several physiological and pathological processes that contribute to heart failure, including fibrosis and inflammation.
The CardioSCORE test is a multianalyte blood-based test to identify patients at elevated risks for atherothrombotic cardiovascular disease, commonly known as vulnerable plaque. This test is designed to improve detection of risk prediction for major cardiovascular events, such as heart attack and stroke. The CardioSCORE test is designed to be additive to traditional risk-factor assessments, such as the Framingham Risk Score and European SCORE.
LipoScience Inc, Raleigh, NC: LipoScience Inc is pioneering a new field of personalized diagnostics based on nuclear magnetic resonance (NMR) technology. Its first proprietary diagnostic test, the NMR LipoProfile test, measures the number of low density lipoprotein particles (LDL-P) in a blood sample and provides physicians and their patients with actionable information to personalize management of risk for heart disease. To date, more than nine million NMR LipoProfile tests have been ordered.Robert Honigberg, MD, chief medical officer,
Siemens Healthcare Diagnostics, Tarrytown, NY: Siemens Healthcare Diagnostics offers multiple solutions for high-sensitivity troponin I testing. Our high-sensitivity Troponin I assay runs on several core laboratory testing platforms, including ADVIA Centaur systems, Dimension Vista systems, and Dimension EXL systems. It is also available for the point of care on the Stratus CS Acute Care Diagnostic System. For the Stratus CS system, cTnI can be used as an aid in the diagnosis of AMI (acute myocardial infarction).Tania Buchmelter, senior global marketing manager, cardiac and ISD assays,
Cardiac troponin I is released into circulation in response to myocardial infarction. Troponins are recognized as preferred biomarkers for myocardial damage.
Siemens also offers a choice in natriuretic peptide (BNP and NT-proBNP) testing across multiple instrument platforms, including our ADVIA Centaur Systems, Dimension Integrated Systems, and Stratus CS Acute Care Diagnostic System.
Natriuretic peptides (NPs) are markers of hemodynamic stress on the heart, denoting the neurohumoral activation of the myocardium. BNP and NT-proBNP are produced in a 1:1 ratio when the left ventricle is stretched due to hemodynamic pressure. Elevated levels of either of these peptides are associated with heart failure, and both are equally useful as an aid in the diagnosis of congestive heart failure (CHF).
Randox Laboratories, Kearneysville, WVa: H-FABP (Heart-type Fatty Acid Binding Protein) is a biomarker of myocardial ischemia, detectable as early as 30 minutes from chest pain onset, and facilitates the earlier management of patients with suspected ACS, alongside troponin.Mary Jo Kurth, MD, business development manager, The Randox H-FABP test is a laboratory-based clinical chemistry assay, which can be easily used on a wide range of commercial biochemistry analyzers.
CLP: IN WHICH CATEGORIES OF CARDIOVASCULAR TESTING DOES YOUR COMPANY’S PRODUCT FIT?
Cobble/Atherotech: Cardiometabolic, lipids, vascular inflammation.
Beshiri/Abbott: The cTnI values are used as an aid in the diagnosis of myocardial infarction (MI) and to aid in the assessment of 30-day and 90?day prognosis relative to all-cause mortality and major adverse cardiac events (MACE) consisting of myocardial infarction, revascularization, and cardiac death in patients who present with symptoms suggestive of acute coronary syndrome (ACS).
The ARCHITECT Galectin-3 assay may be used in conjunction with clinical evaluation as an aid in assessing the prognosis of patients diagnosed with chronic heart failure.
Bouvier/BG Medicine: The BGM Galectin-3 test plays a clinical role in stratifying risk in patients diagnosed with chronic heart failure, making it a valuable and cost-effective tool for reducing unplanned hospital readmissions. Having additive information, which accurately identifies those at highest risk, allows clinicians to immediately direct intervention strategies and allocate precious resources most appropriately.
The CardioSCORE test helps improve the practice of cardiovascular risk prediction. In a clinical study evaluating nearly 7,000 asymptomatic adults, the CardioSCORE test, when used in conjunction with the Framingham Risk Score, identified approximately 56% of individuals who subsequently had a primary cardiovascular event in the next 3 years, compared to only 25% identified using the Framingham Risk Score alone. This is critically important, given that more than 70% of serious cardiovascular events occur in adults deemed not to be at high risk.
Honigberg/LipoScience: The NMR LipoProfile test is appropriate within patient populations being managed with lipid-lowering therapy, intensive lifestyle changes, or those with known cardiovascular disease (CVD), coronary heart disease risk equivalents such as diabetes, or risk factors that define metabolic syndrome. Measuring LDL-P allows physicians to manage an individual patient’s risk for CVD and personalize or adjust pharmacotherapy accordingly. LDL-cholesterol, which simply measures the amount of cholesterol within particles rather than the number of particles driving atherogenic plaque buildup, often underestimates CVD risk in higher-risk patients with signs of insulin resistance.
Kurth/Randox: Acute diagnostics—H-FABP is focused on the earlier management of myocardial infarction (MI), which is part of the acute coronary syndrome (ACS) spectrum.
Buchmelter/Siemens: Approximately 1.5 million myocardial infarction (MI) cases occur annually in the US. All suspected MI cases can be life-threatening, because if a coronary artery is blocked, the heart muscle loses critical blood flow and begins to die after 30 to 60 minutes. During this “golden hour” of a heart attack, it is often said that “time is muscle.” Every minute of delay in treatment after that hour means more heart muscle will die.
To optimize patient outcomes, early detection, risk stratification, and placing patients on the correct clinical treatment pathway is critical. The development of more sensitive and specific serological biomarkers allows detection of ever-smaller amounts of myocardial infarction. In this regard, high-sensitivity troponin assays are improving the diagnostic accuracy and rapid detection of MI.
Blood levels of BNP and NT-proBNP are proportional to the severity of cardiac dysfunction, and can be used for various applications, including CHF diagnosis. Siemens’ BNP and NT-proBNP assays are sensitive and specific markers for cardiac function. Testing for blood levels of either marker can be used as an aid in heart failure assessment. Natriuretic peptides can be used for diagnosing clinical problems associated with left ventricular dysfunction.
CLP: HOW DOES THE TEST HELP WITH DIAGNOSIS, RISK STRATIFICATION, ASSESSING THE PATIENT’S PROGNOSIS, AND/OR WITH THE TREATMENT/MANAGEMENT OF PATIENTS?
Cobble/Atherotech: The basic cholesterol test leaves millions at risk due to miscalculation of LDL levels, according to a major study published in the Journal of the American College of Cardiology. The study compared the accuracy of calculated LDL measurement in the traditional basic lipid panel to directly measured LDL in the VAP Lipid Panel Plus. The basic lipid panel is most inaccurate when accuracy is most crucial in patients with LDL cholesterol levels in the high-risk treatment range and elevated triglycerides. The VAP Lipid Panel Plus is the only comprehensive lipid panel that directly measures LDL, the primary target of therapy in cholesterol testing for CVD risk assessment.
Bouvier/BG: The BGM Galectin-3 test is used as an aid in assessing the prognosis of chronic heart failure in patients who suffer from an inherently progressive form of the disease due to Galectin-3 mediated fibrosis and adverse cardiac remodeling.
The CardioSCORE test provides a numerical score and is used as an aid in the assessment of near-term risk prediction for heart attack, ischemic stroke, unstable angina, coronary revascularization, and death in asymptomatic individuals (men 55 to 80 years of age and women 60 to 80 years of age). The score is based on an algorithm that is derived from seven biomarkers and is independent of traditional risk factors such as cholesterol, smoking, age, and weight.
Beshiri/Abbott: Because Abbott’s hsTnI test can measure very low levels of cardiac troponin, it may more precisely confirm or exclude a heart attack much sooner and with higher accuracy compared to contemporary tests. The ARCHITECT Galectin-3 test may help doctors know which patients are at increased risk of hospital readmission—independent of other variables—providing physicians with important information to help them reach different decisions about treatment, which may benefit patient care.
Honigberg/LipoScience: LDL particle number (LDL-P) measured by NMR has been shown to have significant and independent associations with cardiovascular disease events regardless of LDL-C levels. If a person has a high number of LDL particles in the blood, they need proactive and individualized management to lower LDL-P. The American College of Cardiology and American Diabetes Association issued a consensus statement in 2008 acknowledging that “even with adequate cholesterol lowering, many patients on statin therapy have significant CVD risk” and “many studies show that particle number is a better discriminator of risk than cholesterol.”
In 2011, the National Lipid Association convened a panel of experts and published a consensus statement that evaluates the use of selected biomarkers for the following patient types; low risk, intermediate risk (5% to 20% 10-year CHD event risk), CHD or CHD equivalent, family history and recurrent events, in clinical practice as either tools to improve risk assessment or as markers to adjust therapy once a decision to treat had been made. “It was suggested that intensification of therapy would be a reasonable consideration when residually elevated LDL-P concentration is present. To adjudicate response to therapy, LDL-P targets were proposed as an optional therapeutic goal.”
Kurth/Randox: H-FABP measured in combination with troponin I or T or high-sensitivity troponin, can be used in the diagnosis of MI. A recent study by Dr Rick Body demonstrated that H-FABP measured in combination with high-sensitivity troponin T and ECG on presentation of chest pain patients to the emergency department resulted in a sensitivity of 99.1% and a NPV of 99.7%. This could have enabled AMI to be excluded in 48.8% of patients (Body et al, 2012).
In addition, an independent economic analysis demonstrated that savings of $516 per presenting patient were achievable (Body et al, 2012).
Furthermore, H-FABP can be used in the risk stratification of ACS patients. Prognostically, H-FABP measured 12 to 24 hours after patient admission, can identify troponin negative ACS patients who are at long-term risk of death (Kilcullen et al, 2007). H-FABP identifies a very high-risk group of patients who warrant further investigation and possible intervention. Conversely, some ACS patients undergo angiography based on a false-positive troponin level. The addition of H-FABP to troponin measurement could avoid unnecessary investigations caused by false positives (Kilcullen et al 2007).
Buchmelter/Siemens: Siemens’ high-sensitivity troponin assay helps improve the diagnostic accuracy and rapid detection of MI, which, in turn, facilitates earlier detection of myocardial injury, enabling more rapid diagnosis and faster initiation of appropriate therapy.
In patients with acute coronary syndromes (ACS), our natriuretic peptide assays can be used in conjunction with other known risk factors to predict survival as well as the likelihood of future heart failure. In their guidelines, the European Society of Cardiology Task Force for the Diagnosis and Treatment of Chronic Heart Failure recommends that natriuretic peptides, including NT-proBNP, may be most useful clinically as a rule-out test due to consistent and very high negative predictive values.
CLP: DOES YOUR COMPANY’S PRODUCT DETECT CARDIOVASCULAR RISK IN PATIENTS BEFORE THEY HAVE HEART FAILURE, AND/OR DETERMINE RISKS FOR RECURRING HEART DISEASE?
Cobble/Atherotech: Yes, clinical trials have repeatedly demonstrated that VAP technology adds value beyond the basic lipid panel in both primary and secondary prevention populations. Because of its ability to uncover hidden risk, the VAP Lipid Panel Plus helps clinicians take steps to prevent heart disease before it manifests as a cardiovascular event and reduces the likelihood of a recurrent heart attack or stroke in patients with existing heart disease—using targeted treatment and lifestyle changes.
Bouvier/BG: Equipping clinicians with validated diagnostics that enable them to better stratify patients according to their risk, for example, recurring hospital admissions, and to predict near-term cardiovascular events in otherwise asymptomatic adults, is the crux of BG Medicine’s mission.
When used in conjunction with clinical evaluation, the BGM Galectin-3 test can improve the prediction of unexpected heart failure readmissions independent of other common heart failure risk factors. And the CardioSCORE test can identify elevated risk for cardiovascular events including stroke and heart attack with significantly higher accuracy than conventional available assessments. We believe that having access to this additional risk information allows clinicians to personalize their management strategies and positively influence long-term patient outcomes.
Honigberg/LipoScience: Yes, the NMR LipoProfile test allows physicians to manage patients who may have residual risk due to an elevated LDL-P. The management of residual risk using LDL-P as an LDL goal can be used for either primary prevention, which is in the setting before heart disease clinically presents, or for secondary prevention, which is after heart disease is clinically diagnosed with a focus to either preventing a first event or recurrent event. Therefore, the test is used to detect residual cardiovascular risk and guide the management of therapy considerably before the manifestation of heart failure.
Beshiri/Abbott: A concern for patients who have experienced symptoms of a heart attack or who suffered from an actual attack is that they are at a higher risk for experiencing a second cardiac event or heart attack within a few weeks or months. Abbott’s High Sensitive Troponin-I Assay also enables doctors to determine if patients are at risk to suffer from cardiovascular events 30 days and 90 days later.
Kurth/Randox: Prognostically, H-FABP measured 12 to 24 hours after patient admission, can identify troponin negative ACS patients who are at long-term risk of death (Kilcullen et al, 2007). H-FABP identifies a very high-risk group of patients who warrant further investigation and possible intervention. Furthermore, it has been shown in a 6-year follow-up of this cohort of individuals that patients who were troponin negative but H-FABP positive were at an increased risk of mortality after 6 years (Pearson et al, 2010). Increased H-FABP concentrations demonstrated increased risk of death or MI (Viswanathan et al, 2010).
Similar results in a study where H-FABP was measured in combination with high-sensitivity Troponin T in chest pain patients on presentation at the emergency department were demonstrated. In terms of prognostic value, H-FABP and hs-troponin again gave independent predictive value. Patients that were positive for both H-FABP and hs-Troponin T had particularly bad prognosis. Interestingly, H-FABP positive patients that were hs-Troponin T negative did fairly badly too, whereas H-FABP negative and hs-Troponin T negative patients had a pretty good overall prognosis (unpublished results).
Buchmelter/Siemens: Siemens also offers a choice in natriuretic peptide (BNP and NT-proBNP) testing across multiple instrument platforms, including our ADVIA Centaur Systems, Dimension Integrated Systems, and Stratus CS Acute Care Diagnostic System. (Refer to answer to questions 1 and 3.)
CLP: HOW IS THIS TEST IMPROVING THE DIAGNOSTIC ACCURACY AND RAPID DETECTION OF CARDIOVASCULAR DISEASE?
Cobble/Atherotech: Atherotech’s VAP Lipid Panel Plus, now with LDL particle, is the most accurate and comprehensive lipid profile available. VAP technology is based on the gold standard of density gradient ultracentrifugation and utilizes direct measurement of LDL to identify cholesterol, triglyceride, and genetic lipid disorders. Results are accurate in nonfasting patients. The VAP Lipid Panel Plus reveals residual cardiometabolic risk as recommended in the NCEP ATP III, ADA/ACC Joint Consensus and AACE guidelines. It is the most comprehensive cardiovascular risk assessment tool on the market that personalizes risk assessment, targets treatment, and improves patient health outcomes.
Beshiri/Abbott: The ARCHITECT STAT High Sensitive Troponin-I Assay helps doctors evaluate whether or not patients are having a heart attack within 2 to 4 hours. This faster evaluation could allow doctors to reduce the time to diagnosis and treatment by several hours when compared to standard troponin tests.Abbott’s High Sensitive Troponin-I Assay also enables doctors to determine if patients are at risk to suffer from cardiovascular events 30 days and 90 days later.
Heart failure patients with higher levels of a protein called galectin-3 present are more likely to have worse outcomes, including rehospitalization and death. The new ARCHITECT Galectin-3 test is a helpful tool to aid physicians in their care of these critically ill patients.
Bouvier/BG: In general, the rate at which cardiovascular disease manifests and progresses is different from patient to patient, and there is often little correlation between disease and traditional risk factors.
I can’t stress enough the importance of rapid detection and accurate diagnosis. We are making this happen in two distinct settings—helping to identify the asymptomatic patient who is actually at risk, and helping to identify the heart failure patient who is most likely to progress rapidly.
It is for these reasons that our continued focus at BG Medicine is on developing novel cardiovascular tests that address significant unmet medical needs. Incorporating the BGM Galectin-3 test, and our CardioSCORE test, into the clinician’s toolkit provides significant added information that is used to more effectively stratify patients according to progression risk and severity, ultimately toward improving patient outcomes and reducing health care costs.
Honigberg/LipoScience: Heart disease is the leading cause of death for both men and women, according to the Centers for Disease Control and Prevention. LDL is a well-established risk factor and important management goal for the prevention and control of heart disease. The peer-reviewed clinical literature has demonstrated that LDL cholesterol testing may not be enough to optimally manage an individual’s risk for cardiovascular disease. For example, the American Heart Association’s “Get with the Guidelines” study showed that 72.1% of patients without CHD hospitalized for an acute coronary event had LDL cholesterol levels at or below their cholesterol goal (less than 130 mg/dL).
The published findings that demonstrate that LDL-P is a better discriminator of cardiovascular risk than is LDL-C, particularly in patients with metabolic syndrome and diabetes, suggests an important benefit to using NMR testing in addition to the reference test in these patients.
Kurth/Randox: H-FABP measured in combination with high-sensitivity troponin and ECG can be used to diagnose and risk-stratify chest pain patients who arrive at the emergency department at the time of presentation.
If H-FABP, high sensitivity troponin, and ECG are all negative, this provides sensitivity for AMI of 99.1% and a NPV of 99.7% and could have enabled AMI to be excluded in 48.8% of patients (Body et al, 2012). Furthermore, patients who are high sensitivity troponin negative but H-FABP positive are at risk of an event in the future and warrant further investigation (Kilcullen et al, 2007).
Buchmelter/Siemens: Siemens’ BNP and NT-proBNP testing solutions are used for the diagnosis of CHF, a life-threatening chronic condition affecting approximately 4.8 million Americans. Changes in NT-proBNP concentration can be used to evaluate the success of treatment in patients with left ventricular dysfunction. There are indications that NT-proBNP, due to its functions, is suitable for use in assessing vascular remodeling, and therefore contributes to the establishment of individualized rehabilitation procedures. These assays help support fast, accurate diagnoses, and reduced time to initiation of appropriate therapy. This may enable better patient care and reduced hospital costs.
Kurt Woock is associate editor for CLP.