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Stanford Researchers Aim to See if Patients are Helped by Genetic Tests

Article / Review by on September 13, 2011 – 9:02 pmNo Comments

Stanford Researchers Aim to See if Patients are Helped by Genetic Tests

Researchers at Stanford University Medical Center are conducting a clinical trial to determine whether giving patients genetic information about their risk of coronary artery disease will help motivate them to reduce that risk by changing their behavior.

Stanford Hospital & Clinics physicians will tell some of the patients recruited for the randomized trial whether they have any genetic markers for coronary artery disease, the leading cause of death in the United States. The researchers want to see whether these patients, armed with their genetic information, make positive changes to their lifestyle and eating habits, as well as adhere more faithfully to their prescribed drug regimens, compared with members of a control group.

Joshua Knowles, a cardiologist at Stanford Hospital & Clinics, is investigating whether showing patients information about their genetic risk of coronary artery disease helps motivate them to reduce that risk.
Joshua Knowles, a cardiologist at Stanford Hospital & Clinics, is investigating whether showing patients information about their genetic risk of coronary artery disease helps motivate them to reduce that risk.

“There’s a huge need to test this hypothesis,” said Joshua Knowles, MD, PhD, the lead investigator of the study, who is also a cardiologist at Stanford Hospital & Clinics and an instructor in cardiovascular medicine at Stanford University School of Medicine.

This is partly because the American Heart Association has concluded that, given the absence of data on how genetic testing actually affects patient outcomes, there is not enough information to advocate for such testing, Knowles said. And at least for the moment, genetic tests are no better at predicting someone’s risk of coronary disease than old-fashioned diagnostic methods, such as looking at family history and measuring things like age, weight, blood pressure, cholesterol levels and diabetes status, he added.

Coronary artery disease results from the accumulation of fat, cholesterol and other substances along walls of the coronary arteries, causing them to harden and narrow and increasing the likelihood of a heart attack. Roughly half a million people die because of the disease each year in the United States.

Researchers overseeing the clinical trial, which is set to last about a year, are interested in recruiting roughly 100 adult patients who are at medium to high risk for coronary disease. All patients who enroll in the trial will undergo testing for dozens of genetic markers unequivocally associated with increased susceptibility to the disease. However, only half of the participants, selected at random, will be given the results of their tests. (At the end of the trial, all participants will be given their genetic-test results.)

Participants will be expected to make three visits to Stanford Hospital during the trial. They will have their medical history evaluated and undergo a physical exam. They also will receive standard care, including laboratory tests for lipids and a calculation of their risk of the disease based on traditional prediction models. Therapy will be based on current clinical guidelines and may include recommendations related to diet, exercise and lifestyle, as well as prescribed medication.

The researchers will gauge whether patients who received genetic-test results experienced improved outcomes by looking for decreases in their bad cholesterol, blood pressure and weight, as well as whether their diet and clinical attendance improved.

A few European studies have found that patients saw improved outcomes after they were told about test results confirming a genetic predisposition for a particular disease. These findings raise the question of whether people react more to genetic information than to other criteria used in diagnoses. “It’s a concept called genetic exclusivity,” said Knowles. “It’s surprising and not necessarily intuitive.”

The clinical trial is currently supported by a seed grant from Spectrum, the Stanford Center for Clinical and Translational Education and Research, which is funded by a National Institutes of Health Clinical and Translational Science Award.  Inclusion/exclusion criteria for the trial can be found at http://clinicaltrials.gov/ct2/show/NCT01406808?term=knowles&rank=5 

For those interested in learning more about the trial or possibly enrolling, contact Aleksandra Pavlovic at (650) 736-1147 or apavlovi@stanford.edu 

Joshua Knowles, MD, PhD. Bio.
Joshua W. Knowles
Instructor
300 Pasteur Dr MC 5406
CV 158
Stanford, CA 94305
Tel Work (650) 723-1431
Fax (650) 725-2178 
Medicine – Cardiovascular Medicine

> Clinical Focus
Cardiology
Cardiovascular Medicine
Insulin Resistance

> Honors and Awards
1991-1993 Freshman and Sophomore Honors Program, UNC
1991-1995 Dean’s List, multiple semesters, UNC
1995 Graduated with Honors, double major in History and Biology, UNC
1996 John B. Graham Medical Student Research Society, UNC School of Medicine
2000 Invited oral abstract presentation and travel award for Keystone Meeting, Snowbird, Utah.
2000 Travel award for Conference on Arteriosclerosis, Thrombosis and Vascular Biology, Denver
2003-present Stanford Clinical Investigator Pathway
2005-2006 Stanford University School of Medicine Dean’s Fellowship
2006 The Future Leaders in CV Medical Research Program, Fellowship Award
2007 Invited oral presentation, Cold Spring Harbor Meeting: Clinical Cardiovascular Genomics
2007 Edwin Alderman Excellence Award for Clinical Research, Stanford Cardiovascular Medicine
2008 Edwin Alderman Excellence Award for Clinical Research, Stanford Cardiovascular Medicine
2009 Invited Participant, Workshop on the Genetics of Complex Disorders, Broad Institute

> Professional Education
Board Certification: Cardiovascular Medicine, American Board of Internal Medicine (2010) 
Medical Education:  University of North Carolina – Chapel Hill NC (2003) 
PhD:  University of North Carolina, Chapel Hill , Genetics and Molecular Biology (2001) 
Residency:  Stanford Hospital and Clinics CA (2005) 
Fellowship:  Stanford Hospital and Clinics CA (2010) 

> Current Research Interests
The overall theme of my work is to understand the genetic basis of complex cardiovascular diseases such as coronary disease and insulin resistance. Currently, I am involved in genome wide association (GWA) studies of coronary disease through the NIH-funded ADVANCE study and of insulin resistance through the international GENESIS-2 project. After using the GWA approach to discover and validate interesting candidate genes, I hope to explore the biology underlying these genes and pathways using cell culture and in vivo model systems. I also have a strong interest in developing tools to help translate newly emerging genetic data into clinical practice.

> Positions and Employment
2003-2005 Medical Internship and Residency, Internal Medicine, Stanford University
2005- Cardiovascular Medicine Fellow, Stanford University

About Stanford Hospital & Clinics
Stanford Hospital & Clinics is known worldwide for advanced treatment of complex disorders in areas such as cardiovascular care, cancer treatment, neurosciences, surgery, and organ transplants. It is currently ranked No. 17 on the U.S. News & World Report’s “America’s Best Hospitals” list and No. 1 in the San Jose Metropolitan area.  Stanford Hospital & Clinics is internationally recognized for translating medical breakthroughs into the care of patients.  The Stanford University Medical Center is comprised of three world renowned institutions: Stanford Hospital & Clinics, the Stanford University School of Medicine, the oldest medical school in the Western United States, and Lucile Packard Children’s Hospital, an adjacent pediatric teaching hospital providing general acute and tertiary care.

*  The above story is adapted from materials provided by Stanford University School of Medicine 

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