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Boston Heart Enables Healthcare Providers to Better Identify Near-Term Risk of Heart Attack or Stroke with Launch of an Important Inflammation Marker, Myeloperoxidase (MPO)

Boston Heart Diagnostics Corporation, a pioneer in integrating next-generation diagnostics into personalized nutrition and lifestyle programs for patients with or at risk for heart disease, recently announced the commercial launch of an FDA-cleared MPO (myeloperoxidase) test, a key biomarker for inflammation. Studies show that MPO levels are useful predictors of near-term (one to six months) risk of heart attack or stroke.

Study: Aspirin Ineffective in 20 Percent of Heart Disease Patients

A major new study conducted in Ireland found that 20 percent of patients with established heart disease were not adequately protected by aspirin. Corgenix Medical Corporation, developers of the AspirinWorks® Test for aspirin effect, said the study adds more evidence to the importance of accurately measuring aspirin response by measuring levels of the biomarker thromboxane.

Biomarker Predicts Heart Attack Risk Based on Response to Aspirin Therapy

Aspirin has been widely used for more than 50 years as a common, inexpensive blood thinner for patients with heart disease and stroke, but doctors have little understanding of how it works and why some people benefit and others don’t.

Now researchers at Duke Medicine have solved some of the mysteries related to the use of this century-old drug, and developed a blood-based test of gene activity that has been shown to accurately identify who will respond to the therapy.

The new gene expression profile not only measures the effectiveness of aspirin, but also serves as a strong predictor of patients who are at risk for heart attack, according to a study appearing July 3, 2013, in the online edition of the Journal of the American College of Cardiology.

“We recognized the concept of aspirin resistance among a population of patients who have cardiac events or stroke,” said senior author Geoffrey S. Ginsburg, M.D., PhD, director of genomic medicine at Duke’s Institute for Genome Sciences & Policy and executive director of the Center for Personalized Medicine. “We give the same dose to all patients, but maybe some patients need a larger dose of aspirin, or maybe they need to try a different therapy entirely. We need better tools to monitor patients and adjust their care accordingly, and the findings from our study move us in that direction.”

The Duke researchers enlisted three groups of participants – two of healthy volunteers and one comprised of patients with heart disease seen in outpatient cardiology practices.

The healthy volunteers were given a dosage of 325 mg of aspirin daily for up to a month; the heart disease patients had been prescribed a low dose of aspirin as part of their treatment. Blood was then analyzed for the impact of aspirin on RNA expression and the function of platelets, which are the blood cells involved in clotting.

The RNA microarray profiling after aspirin administration revealed a set of 60 co-expressed genes that the researchers call the “aspirin response signature,” which consistently correlated with an insufficient platelet response to aspirin therapy among the healthy subjects as well as the heart disease patients.

The researchers also examined the aspirin response signature in another group of patients who had undergone cardiac catheterizations. They found the signature was also effective in identifying those patients who eventually suffered a heart attack or died.

“The aspirin response signature can determine who is at risk for heart attack and death,” said Deepak Voora, M.D., assistant professor of medicine at Duke and lead author of the study. “There is something about the biology of platelets that determines how well we respond to aspirin and we can now capture that with a genomic signature in blood.”

Ginsburg said the research is progressing to recreate the findings in other populations, and to develop a standardized testing system that could one day move the analysis into daily practice.

“Nearly 60 million people take aspirin regularly to reduce their chances of heart attack and death, but it doesn’t work for everyone,” said Rochelle Long, Ph.D., of the National Institutes of Health’s National Institute of General Medical Sciences, which partly supported the study. “By monitoring gene activity patterns these investigators uncovered a ‘signature’ linked to inadequate responsiveness. This work may eventually lead to a simple blood test to identify those who do not benefit from aspirin, enabling them to seek other therapeutic options.”

In addition to Ginsburg and Voora, study authors include Derek Cyr; Joseph Lucas; Jen-Tsan Chi; Jennifer Dungan; Timothy A. McCaffrey; Richard Katz; L. Kristin Newby; William E. Kraus; Richard C. Becker; and Thomas L. Ortel.

The study received funding from the Duke Institute for Genome Sciences & Policy; the National Institutes of Health (T32HL007101 to DV); the National Center for Research Resources (UL1RR024128); the National Institutes of General Medical Sciences (RC1GM091083); the Centers for Disease Control and Prevention (5U01DD000014); and the David H. Murdock Research Institute.

Study: Aspirin Exposure Reveals Novel Genes Associated with Platelet Function and Cardiovascular Events

Source: Duke Medicine

Two Biomarkers Predict Increased Risk for “Silent” Strokes

Two biomarkers widely being investigated as predictors of heart and vascular disease appear to indicate risk for “silent” strokes and other causes of mild brain damage that present no symptoms, report researchers from The Methodist Hospital and several other institutions in an upcoming issue of Stroke (now online).

The researchers found high blood levels of troponin T and NT-proBNP were associated with as much as 3 and 3.5 times the amount of damaged brain tissue, respectively. The findings are part of the large-scale Atherosclerosis Risk in Communities (ARIC) study, funded by the National Heart, Lung, and Blood Institute.

“The concept of prevention is expanding,” said principal investigator Christie Ballantyne, M.D., director of the Center for Cardiovascular Disease Prevention at The Methodist Hospital. “It’s not good enough to simply do a few tests and try to assess risk for heart attack. What we need to do is assess the risk for heart attack, stroke, heart failure and also asymptomatic disease so we can start preventive efforts earlier. Waiting to correct problems until after a symptomatic stroke may be too late.”

One possible outcome is that patients determined to be in high-risk groups could be started on anti-stroke medications sooner.

In another ARIC paper published two months ago in Stroke, Ballantyne and coauthors reported a strong association between blood levels of troponin T and NT-proBNP and more severe instances of stroke, called symptomatic stroke. The current study looked at the two biomarkers and “subclinical,” asymptomatic events in the brain that are usually caused by a lack of blood flow.

“Taken together, these two papers show the biomarkers are effective at identifying people who are likely to have mild brain disease and stroke well before damage is done,” said Ballantyne, who also is a Baylor College of Medicine professor. “This hopefully will give doctors more time to help patients take corrective steps to protect their brains.”

For the subclinical brain disease study, researchers gleaned data from about 1,100 patient volunteers who agreed to have blood drawn and two MRI scans eleven years apart to look for silent brain infarcts and also white matter lesions (WMLs) caused by chronic inflammation.

Statistical analysis showed a strong relationship between high NTproBNP and the likelihood of brain infarcts and WMLs. Study participants with the highest levels of NT-proBNP had as much as 3.5 times the number of brain infarcts as participants with low NT-proBNP levels, and more WMLs. Those with the highest levels of troponin T had as much as 3.0 times the number of brain infarcts and more WMLs.

The protein troponin T is part of the troponin complex and its presence is often used to diagnose recent heart attacks. NT-proBNP is an inactive peptide fragment left over from the production of brain natiuretic peptide (BNP), a small neuropeptide hormone that has been shown to have value in diagnosing recent and ongoing congestive heart failure.

“The highly sensitive troponin T test we used is not approved for general clinical use in the US yet, but the NT-proBNP test is just now starting to be used more widely beyond making a diagnosis for heart failure,” Ballantyne said.

The Center for Cardiovascular Disease Prevention is part of the Methodist DeBakey Heart & Vascular Center.

Also contributing to this study were Razvan Dadu, Salim Virani, Vijay Nambi, and Ron Hoogeveen (Baylor College of Medicine and Methodist Center for Cardiovascular Disease Prevention), Myriam Fornage and Eric Boerwinkle (University of Texas Health Sciences Center at Houston), Alvaro Alonso (University of Minnesota School of Public Health), Rebecca Gottesman (Johns Hopkins School of Medicine), and Thomas Mosley (University of Mississippi Medical Center). It was funded with grants from NHLBI and NIH, while Roche Applied Science helped fund the development of diagnostic technology.

Stroke is published by the American Heart Association and American Stroke Association.

Source: Cardiovascular Biomarkers and Subclinical Brain Disease in the Atherosclerosis Risk in Communities Study.

Source: Troponin T, N-terminal pro-B-type natriuretic peptide, and incidence of stroke: the atherosclerosis risk in communities study.

Source: The Methodist Hospital System

Decades of Improving Cholesterol Levels Abruptly Ended in 2008, PLOS ONE Study Finds

Decades of declines in LDL cholesterol blood levels, a key marker of death risk from heart disease, abruptly ended in 2008, and may have stalled since, according to a multi-year, national study published recently in PLOS ONE.

The study, by researchers at Quest Diagnostics (NYSE: DGX), examined low-density lipoprotein, or LDL, blood-serum cholesterol test results of nearly 105 million individual adult Americans of both genders in all 50 states and the District of Columbia from 2001-2011. The study is the largest of LDL cholesterol levels in an American population, and the first large-scale analysis to include data from recent years 2009-2011.

“Our study suggests that significant improvements in heart disease risk through declines in LDL cholesterol blood levels over the past several decades came to an unexpected and sudden end in 2008,” said investigator Robert Superko, M.D., medical director, cardiovascular disease, Quest Diagnostics. “The unprecedented scale of our data set should spur additional research to identify the cause or causes in order to prevent a possible reversal in years of gains in cardiovascular health in the U.S. population.”

The study found a net 13% decline in the annual mean LDL cholesterol level of the study population over the 11-year period. Between 2001 and 2008, the average age-adjusted mean LDL levels declined from about 120 mg/dL to 104.7 mg/dL, but plateaued at that level for the remainder of the study period. LDL levels of 100 mg/dL or lower are considered optimal by the American Heart Association. By 2011, about 46% of patients had achieved LDL levels lower than 100 mg/dL, while 6% of patients had LDL levels in the high-risk category of 160 mg/dL or higher.

Blood cholesterol levels are the primary biomarker for cardiovascular disease, which accounts for one in every three deaths in America. High levels of LDL (“bad”) cholesterol can cause arterial clogging, increasing the risk of stroke and heart disease. Treatments typically include lifestyle modification and therapy with lipid-lowering medications such as statins. Every 10 mg/dL decline in LDL is associated with an approximately 5-13% decline in major vascular disease events, such as strokes and mortality.

Prior research, including results of three National Health and Nutrition Examination Surveys (NHANES) of nearly 40,000 patients for the years 1988 to 2010, demonstrated that LDL levels have declined in the United States while the use of lipid-lowering medications has increased.

The Quest Diagnostics Health Trends study, “Blood Cholesterol Trends 2001-2011 in the United States: Analysis of 105 Million Patient Records,” was published online May 10, 2013 in the peer-reviewed, open-access journal PLOS ONE.

Theories for the LDL Plateau

The observational study in PLOS ONE did not identify a cause for the trends in LDL cholesterol blood levels, although investigators suggested several hypotheses.

“It is possible that the economic recession that began at about the same time LDL values plateaued in our study played a role. Patients dealing with financial constraints may have been less inclined to visit their physician or use their medications at full dose, limiting access to and effectiveness of treatment. Individuals may also have experienced changes in stress levels, diet, sleep and other behaviors, due to the poor economy, which in turn may have adversely impacted lipids,” said Harvey W. Kaufman, M.D., senior medical director, Quest Diagnostics.

The investigators also theorized that statins users in the study may have reached the maximum therapeutic-threshold level or that increases in obesity prevalence or other co-morbid factors during the 11 years of the study period contributed to the LDL plateau.

“These speculative, but plausible theories deserve additional research so the cause of the trend seen in our data can be addressed and hopefully reversed,” said Dr. Kaufman.

Gender Differences

The investigators also found differences in LDL cholesterol declines by gender. The decline in annual age-adjusted mean LDL cholesterol blood levels was slightly greater among men than women, with an average 13.4% decline for men compared to a decline of 12.5% for women.

“Though the differences are not statistically significant, they may reflect meaningful differences in the prescription rate and effectiveness of lipid-lowering interventions, including statins and lifestyles, between genders,” wrote investigators in the study. They also theorize that the differences may be due in part to “under-appreciation of heart disease risk in women,” given female-specific AHA guidelines and risk-classification algorithms for women were introduced only in 1999 and 2007, respectively.

Greater Vigilance Required

“Like other Quest Diagnostics Health Trends reports, our goal is to provide insights, based on diagnostic data, to enhance public health and patient management and, fundamentally, create a healthier world,” said Dr. Kaufman.

“We believe this new study will encourage additional population research to inform public health efforts. But we also believe the study should prompt individual patients to be vigilant about practicing healthy behaviors and lipid-lowering treatment plans. Our hope is physicians and patients will have more productive conversations about the importance of LDL control to cardiovascular health as a result of this study,” said Dr. Kaufman.

The study’s strengths include its size, national representation, longitudinal analysis and incorporation of data up through 2011. It also includes its separation of data into distinct years, as opposed to other large-scale studies, such as NHANES, which group findings into multiple years. The study represents patients under medical care and not the general American population and did not include results of clinical records, such as medical history and medications, to assess contributing factors to the results. The study examined test results of patients tested by Quest Diagnostics. Data was de-identified prior to analysis and the Western Institutional Review Board exempted the study from review.

Study: Blood Cholesterol Trends 2001–2011 in the United States: Analysis of 105 Million Patient Records

Source: Quest Diagnostics