The recent debate concerning the possibilities – and the ethics – for personalizing medical treatment along racial/ethnic lines blinked brighter on the hi-tech radar last month with the report by deCode (Reykjavik, Iceland) that its scientists have discovered a gene variant they say confers increased risk of heart attack, moderately in those of European descent, but most particularly in African-Americans. The link between the variant of the gene encoding the leukotriene A4 hydrolase (LTA4H) and increased risk of heart attack, first made in Iceland, was confirmed in studies of three cohorts in the U.S. – Atlanta, Cleveland and Philadelphia.

The debate concerning the targeting of therapies to African-Americans was brought to the fore in June with the FDA’s approval of the drug Bidil from NitroMed (Lexington, Massachusetts) for marketing specificially to this group. The approval was based on company research indicating African-Americans responded to the drug, though initial clinical trials had shown no significant efficacy in the general population.

The researchers found that in Icelanders and in Americans of European origin, the at-risk version of the gene is “quite common,” the company said, and confers a moderate increase in risk of heart disease. However, the variant, which occurs much less frequently in African-Americans, more than triples that group’s risk of heart attack, raising it by as much as 250%, the company said.

A paper on the findings by a deCode-led team of scientists was published in the online edition of Nature Genetics and will appear in the January print edition.

“This is an important discovery with immediate relevance to improving health,” said Kari Stefansson, CEO of deCode and senior author on the study “It confirms the importance of the leukotriene pathway in mediating susceptibility to heart attack and provides a means of directing new medicine to those at particularly elevated risk.”

The company said it is preparing a Phase III clinical trial of a compound called DG301, which is aimed at reducing the risk of heart attack by correcting the biological perturbation caused by the gene variants it has discovered, he said.

“By weaving these findings into the design of our Phase III trial, we may be able to swiftly translate this discovery into benefit for patients,” Stefansson said. “At the same time, we are looking at how to make available to African-Americans a diagnostic test for the at-risk variant. This could be used to help people at risk to work with their doctors to develop prevention strategies aimed at minimizing the likelihood of suffering a heart attack.”

The company said the study builds upon its previously published work linking variants of the gene encoding the five lipoxygenase activating protein (FLAP) to increased risk of heart attack. The at-risk variants of the FLAP gene appear to contribute to the risk of heart attack by upregulating the production of leukotriene B4 (LTB4). Higher production of LTB4, an important modulator of inflammatory response, may increase the propensity of atherosclerotic plaques to rupture, the event directly preceding most heart attacks.”

The LTA4H enzyme acts downstream in the leukotriene pathway from FLAP, and is directly involved in the synthesis of LTB4. At its medicinal chemistry group in Chicago, the company has developed an inhibitor of LTA4H.

To search for variants in the LTA4H gene that might confer risk of heart attack, the deCode team analyzed a set of single-base variations, or SNPs (single nucleotide polymorphisms) in the gene encoding the LTA4H in more than 2,000 patients and controls in Iceland. The haplotype, or version of the gene, defined by those markers and referred to as HapK, was found to correlate with a 40% greater risk of heart attack in Icelandic patients with a history of other cardiovascular disease such as stroke or peripheral artery disease.

To study the significance of this variant in the U.S., HapK was analyzed in more than 3,000 persons in study cohorts at the Cleveland Clinic, Emory University (Atlanta), and the University of Pennsylvania (Philadelphia).

Overall, among participants self-identified as being of European ancestry, 27% of control subjects carried one or more copies of HapK, compared to 31% of heart attack patients, corresponding to a 16% increase in risk. Among participants self-identified as African-American, HapK was carried by 6% of controls and 20% of patients, representing a more than 250% increase in risk.

The authors note that the higher relative risk conferred by HapK in African- Americans is likely due to interaction between HapK and other genetic or environmental risk factors for heart attack which are not yet well understood. An analysis of the prevalence of HapK and other genetic markers in Icelanders, Nigerian Yorubans and in the U.S. study cohorts points to the likelihood that its occurrence in African-Americans is due to European admixture.

The company said that, if so, HapK would be relatively new in the African-American population, reducing time for the evolution of other genetic factors that might mitigate the risk conferred by HapK, as may have occurred in European populations in which HapK has been present long enough to have become very common.

SIR backs Senate push on AAA screening

The Society of Interventional Radiology (SIR; Fairfax, Virginia) last month voiced its support of the Senate’s efforts to increase the early detection of abdominal aortic aneurysms (AAA). A newly passed amendment would institute a one-time ultrasound screening for AAAs through Medicare, as well as establish a national education and information campaign.

Citing a threefold increase in the occurrence of AAAs over the past 30 years, and more than 15,000 deaths per year attributed to AAAs that rupture, SIR said it has been working with congressional leaders to ensure that patients receive access to screenings that could save their life.

The organization commended Sen. Rick Santorum (R-Pennsylvania), who sponsored the amendment to Senate Bill 1932, along with co-sponsors Jim Bunning (R-Kentucky), Christopher Dodd (D-Connecticut), Joseph Lieberman (D-Connecticut), John Rockefeller (D-West Virginia), Craig Thomas (R-Wyoming) and George Voinovich (R-Ohio).

“Once an abdominal aortic aneurysm has ruptured, the chances of survival are low, with 80% to 90% of all ruptured aneurysms resulting in death. These deaths can be avoided if an aneurysm is detected and treated before it ruptures,” said interventional radiologist George Fueredi, MD, who chairs SIR’s Government Affairs & Health Care Policy Committee.

He added: “This bill ensures those patients at highest risk, those over 65, can receive AAA screening which can lead to early treatment and ultimately prevent death.”

Besides SIR, other organizations participating in the National Aneurysm Alliance include the Society of Vascular Surgery, American College of Surgeons, American Society of Echocardiography, American Vascular Association, Aneurysm Outreach, National Electrical Manufacturers Association, Society of Diagnostic Medical Sonography and Society for Vascular Ultrasound.

Med-tech firms Boston Scientific, Cook, Gore, Johnson & Johnson, Medical Media Systems, Medtronic, Philips, Siemens and SonoSite also are part of the alliance.

Sleep apnea increases stroke risk

An observational study of more than 1,000 patients at the Yale Center for Sleep Medicine (New Haven, Connecticut) found that obstructive sleep apnea “significantly increases” the risk of stroke or death from any cause, and that the risk is linked to sleep apnea severity. The researchers found the increased risk to be independent of other factors, including hypertension.

Participants were over age 50 without a history of heart attack or stroke at the start of the study, and they were followed for an average of nearly 3-1/2 years.

“Obstructive Sleep Apnea as a Risk Factor for Stroke and Death,” and an accompanying editorial, “Sleep-A New Cardiovascular Frontier,” by NHLBI grantee Virend K. Somers, MD, PhD, was published in the Nov. 10 issue of the New England Journal of Medicine.

The study was supported by the National Heart, Lung and Blood Institute of the National Institutes of Health (both Bethesda, Maryland) and the Veterans Affairs Health Services Research and Development Service.

Praise for Remote Monitoring Act

The Advanced Medical Technology Association (AdvaMed; Washington) last month hailed the introduction of the Remote Monitoring Access Act of 2005 (S. 2022), saying the bill “will allow seniors living in rural and underserved communities to have access the necessary medical care to treat diabetes, heart failure, cardiac arrhythmia and other chronic diseases.”

AdvaMed President Stephen Ubl said the act “encourages the use of remote monitoring technologies that can be used to track patient information, such as heart rate and blood glucose levels, in real time. These devices can help improve the quality of patient care and reduce costs by enabling doctors to closely monitor patients with chronic diseases outside of the office setting.”

Ubl praised Sens. Norm Coleman (R-Minnesota) and Jeff Bingaman (D-New Mexico) for introducing the bill, saying the Remote Monitoring Access Act of 2005 and Coleman’s Critical Access to Health Information Technology Act “work together to give providers the resources they need to provide the best care to patients.”

He said, “Remote monitoring is innovation that is worth its weight in gold because it saves lives and money by enabling earlier disease detection, reduced hospitalizations and less-expensive care. It overcomes geographic boundaries to enable physicians to keep people healthy and to cure disease [and] is part of the future of healthcare.”

10 hospitals in cardiac care program

Ten hospitals nationwide have been selected to participate in Expecting Success: Excellence in Cardiac Care, a new national program that will focus on a wide range of cardiovascular care interventions that are delivered in both inpatient and outpatient settings. The program’s four key goals are:

• To develop effective, replicable quality-improvement strategies, models and resources.
• To encourage the spread of those strategies and models to clinical areas outside of cardiac care.
• To share relevant lessons with healthcare providers and policymakers nationwide.
• To improve cardiovascular care for African-Americans and Hispanics.

Funded by the Robert Wood Johnson Foundation (Princeton, New Jersey) and coordinated by the George Washington University Medical Center (Washington) School of Public Health and Health Services, the Ex-pecting Success program is aimed to develop and test potential solutions to well-documented racial and ethnic disparities in healthcare delivery.