Clinical Laboratory Strategies: August 30, 2007

Genetic Research on CVD: AHA Statement Calls for Better Coordination
By Deborah Levenson

Press reports continually announce discoveries linking particular genes to common disorders, including cardiovascular disease (CVD). A recent scientific statement from the American Heart Association (AHA) says the day when these discoveries will yield clinically useful CVD tools is within sight, and suggests ways to hasten it. This issue of Strategies examines the AHA recommendations.

Much has been made of genomics’ potential to revolutionize healthcare by tailoring interventions to individual patients’ genetic makeup, but discoveries thus far have improved care for relatively few people. Researchers know the path to CVD is a complex process involving several risk factors, and have shown involvement of several novel risk markers and mutations involved in the disease. But genetic testing for CVD “is not ready for prime time” in public health and clinical medicine, concludes a recent scientific statement from the American Heart Association’s Council on Epidemiology and Prevention, Stroke Council, and Functional Genomics and Translational Biology Interdisciplinary Working Group (Circulation 2007; 115: 2878-2901).

Translation of genetic findings into clinical strategies will be a reality in coming years, if research follows the proper path and the healthcare industry properly prepares to put findings to use, the statement maintains. “We now stand on the threshold of a new era in molecular genetics,” it says, explaining that once the proper research has been done, improvements in care will rapidly follow. The statement likens the current state of knowledge in the field of medical molecular genetics to when computers were large, bulky, slow, and uncommon outside of research settings.

Coordination Presents a Challenge

While the statement details several studies and discoveries of genes linked to myocardial infarction, atherosclerosis, hypertension, and familial forms of hypercholesterolemia, as well as a current research focus on the interaction between genes and environment and pharmacogentics, these efforts have been largely uncoordinated, noted the statement’s lead author, Donna K. Arnett, PhD, Chair and Professor in the Department of Epidemiology at University of Alabama at Birmingham’s School of Public Health, and expert in cardiovascular genetic epidemiology and pharmacogenetics. “The biggest problem with research is lack of cross-fertilization of scientific findings from different domains and systems, and an organized effort aimed at quickly translating findings from animal research to humans, and then moving them quickly into the clinic,” she explained. “Right now, if you make a discovery you often have to hunt down another lab working on that gene by yourself.”

Arnett envisions the day when research findings are regularly examined by what she called “dream teams” that would include experts in a variety of areas, including basic research, animal models, cellular processes, pharmacology, and statistics. Laboratorians would also be important members of these teams. “We need people who study markers and could help translate findings into screening tests,” she explained.

But until this kind of coordination becomes commonplace within and across institutions, exciting research findings aren’t affecting what most labs do and more importantly, improving clinical practice. “The best genetic test you can perform right now is usually a good family history. That’s the take-home point of the (AHA) statement, if you read between the lines,” commented laboratorian Greg Tsongalis, PhD, Director of Molecular Pathology at Dartmouth-Hitchcock Medical Center in Lebanon, N.H.

The Good Ole’ Family History

Given Tsongalis’s assessment, the fact that the statement’s very first recommendation does not involve research or testing makes sense. It urges clinicians to continue to use family history as a screening tool to identify both individuals and families who are susceptible to CVD. But the statement also calls for changes to the nation’s research infrastructure that would create incentives for researchers to form more multidisciplinary, collaborative research teams, to collect DNA and consent to use it in future studies, and to perform more translational research. Creations of more public-private partnerships would expedite translation of genetic findings to clinical and public health practice, the statement adds.

It also calls for research agendas that give priority to characterizing how genes and genetic variants are associated with CVD in individuals, communities, and populations. Specifically, agendas should prompt more evaluation of how behavioral and environmental factors interact with genetic variants to influence CVD risk and development of new technologies that assess risk and predict outcomes. More trials should assess gene-drug interactions their impact on drug development and other intervention strategies.


Another group of recommendations encourage healthcare professionals and institutions to prepare for the day when knowledge of gene-environment interaction and pharmacogenomics reaches patients. Of particular interest to labs is the call for more standards and laboratory oversight mechanisms for genetic testing facilities. While the statement doesn’t mention the Center for Medicare and Medicaid Services’ (CMS) recent announcement that it had abandoned plans to create a genetic specialty under CLIA, Arnett said this turn of events prompted the recommendation. “We rely on certified labs. But there’s skepticism regarding genetic tests. Without specific oversight, there’s a lack of assurance that a test is reproducible,” she explained.

Tsongalis isn’t bothered by the lack of a specialty, however. “If genetic labs are held to high standards just as other labs are, and everyone follows through, lack of a genetic specialty isn’t an issue,” he explained. Proper interpretation of test results worries him more. “The bigger concern should be what results of genetic tests mean for clinicians and creating guidelines for their use,” he advised.

Lab organizations have already responded to these concerns. Tsongalis pointed to a standard on molecular diagnostic methods for genetic diseases from the Clinical Laboratory Standards Institute and several guidelines on lab testing for specific disorders from the American College of Medical Genetics. But much like genetic research, creation of guidelines on genetic testing has been a piecemeal process. “People have been looking to the feds to take charge, but they have said they are not going to take that route. CMS has its own problems with resources and infrastructure,” he concluded.

Was this issue of Strategies of interest to you? Please help us improve by rating this article.

Page Access: