Data expands the clinical utility of deCODE tests for heart attack, atrial fibrillation and stroke



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Several presentations by deCODE genetics scientists and independent researchers at the American Heart Association Scientific Sessions 2008 being held at the New Orleans Convention Center from November 8 to12 are expected to expand upon the clinical utility of evaluating individual risk of heart attack, or atrial fibrillation and stroke, respectively, by measuring the genetic markers that are the basis of the deCODE MI and deCODE AF tests.

These tests measure single-letter variations in the human genome (SNPs) on chromosomes 9p21 and 4q25 that deCODE has linked to increased risk of these cardiovascular conditions, enabling a better understanding of individual risk. As this information is independent of other conventional risk factors, these tests provide doctors in the clinic with a new tool for improving screening, prevention and treatment.

Important avenues for expanding the clinical utility of the deCODE tests to be discussed at the AHA meeting are summarized below. To assist those interested in learning more about deCODE’s tests while onsite at AHA or to follow proceedings on the AHA Web site, www.americanheart.org , deCODE would like to note below the titles, time, date and locations listed. The full abstracts and contents of these talks are strictly embargoed for public dissemination until their time of presentation, as noted per AHA guidelines.

Myocardial infarction and 9p21 risk variants:

Several presentations focus on the 9p21 genetic risk markers for myocardial infarction (MI) that deCODE first reported in 2007 and which form the basis of the deCODE MI test for assessing individual risk as an aid in clinical practice. Individuals who have the at-risk versions of the SNPs detected by this test are 1.6- to 2-fold more likely to develop MI than are those with lowest risk genotypes, or at 1.3- to 1.5-fold higher risk than the general population. This level of risk is comparable to the risk due to highest quintile LDL cholesterol and is as common, with about 25 percent of the general population carrying the high-risk markers.

In the Sunday morning session, deCODE will review the latest findings on these 9p21 variants in MI and other cardiovascular conditions for which these SNPs are risk factors, including abdominal aortic aneurysm and intracranial aneurysm. The session will also summarize the results of a UK clinical study showing that the accuracy of MI risk prediction is increased by measuring these 9p21 variants in addition to conventional risk factors. In two Tuesday sessions, Christie M. Ballantyne, M.D., and his colleagues from Baylor College of Medicine will discuss the clinical utility of measuring the 9p21 markers in addition to conventional risk factors for MI in the context of the ARIC study.

The 4q25 variants and risk of atrial fibrillation and stroke

In 2007, deCODE discovered two SNPs on chromosome 4q25 that double the risk of atrial fibrillation (AF), and launched its deCODE AF test to detect these variants. Given that AF is underdiagnosed, one principal purpose of this test is to enable the identification of people at higher risk and to monitor them more intensively and to put those who exhibit AF on appropriate medication.

At this year’s AHA, deCODE and independent groups will present data from studies that expand the understanding of how deCODE AF can contribute to better clinical practice. deCODE’s original discovery of the 4q25 SNPs was replicated and validated in several European and U.S. case-control cohorts. Since then, the company has published findings that the SNPs in deCODE AF also confer risk of ischemic stroke, with highest risk for cardioembolic stroke. At AHA the company will discuss the implications of linking these markers not only with risk of AF, but also to risk of stroke and non-cardiogenic stroke. One implication is that AF appears to cause an even larger proportion of stroke than originally thought. This strengthens the case for going beyond standard cardiac monitoring, for hospitalized and discharged patients who have suffered stroke or transient ischemic attack (TIA), and for the prescription of warfarin, rather than Plavix or aspirin, for those with AF. deCODE will also present data on the utility of deCODE AF for detecting recurrent AF.

Researchers from Cleveland Clinic have conducted their own study of the link between the 4q25 markers and AF, and will look at correlations between these variants and mRNA expression profiles of the nearby PITX2 gene, which is expressed in atrial cardiac muscle. Groups from Brigham and Women’s Hospital and Vanderbilt University examine the utility of testing for these variants to predict likelihood of developing AF after cardiac surgery, a complication that is associated with increased morbidity and mortality. Determining which patients may most benefit from prevention therapy with anti-arrhythmic medications is important because these drugs have side effects that make them unsuitable for use in all patients.

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