In 2007, Stanford cardiologist Tim Assimes, MD, PhD, started along an investigative path to discover the root genetic causes of coronary artery disease (CAD).
Ten years later, he says, that journey is well under way but far from over.
Coronary artery disease is the process by which plaque builds up in heart vessels over a span of several decades, eventually leading to chest pain that may require angioplasty or bypass surgery. CAD also causes heart attacks, which can lead to heart failure and death. It is the leading cause of death worldwide.
Over the last decade, Assimes has been a key collaborator in numerous genome-wide-association studies, or GWAS, involving international consortiums of scientists working together to identify the multiple regions of the human genome associated with CAD. In a study appearing today in Nature Genetics, Assimes and one such consortium pinpointed 15 newly identified genomic regions associated with heart disease -- bringing the total number to 73.
"We are driven to conduct these large-scale population genetic studies for two reasons," Assimes told me. The first is to better understand the pathophysiology of CAD with the hope that this knowledge will lead the development of new therapeutic agents such as medications that would slow down or stop the formation of plaque in heart vessels, he said. The second is to use a patient's genetic profile associated with CAD to better understand whether they will develop CAD over the long term.
For this particular study, which is detailed in a Penn Medicine press release, researchers genotyped more than 56,00 participants using a targeted gene array devised from earlier GWA studies and then performed a meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 participants with coronary artery disease and 162,544 controls. The team found about two thirds of the regions of the genome associated with CAD have no obvious connection to established risk factors of heart disease such as obesity, diabetes, high bad cholesterol, and high blood pressure.
"The regions discovered in this study are interesting because many point to biological processes active in the vessel wall," Assimes said. "It's now becoming quite clear that cells in the vessel wall are very actively involved in plaque formation."
The new discoveries also take yet another incremental step forward toward the second goal of providing physicians with another tool in their arsenal to help predict who is most at risk of heart disease.
"We are adding 15 more variables to the equation that determines your risk of having a heart attack," Assimes said. "The majority of patients with coronary artery disease do not have one or two extremely bad gene variants that are driving their risk. By far, the most common reason for someone to be genetically predisposed to heart attacks is because they have inherited many variants each with a slight effect on the risk of disease."
Previously: Don't think of heart disease as inevitable, Stanford expert says, Cholesterol testing recommended for all says Stanford cardiologist and Assessing the challenges and opportunities when bringing whole genome sequencing to the bedside
Image by Lisa Yont