Genetic variation and risk of myocardial infarction

Testing for 11 specific genetic variations in hundreds of people with no history of heart disease provided information that led to revision of their estimated risk of myocardial infarction, say Mayo Clinic researchers, in a study presented at the American Heart Association's Scientific Sessions in Chicago last November.

"The method we have been using for decades to predict risk of coronary artery disease is not ideal; many people thought to be at low risk experience myocardial infarction," says the study's lead researcher, Iftikhar Kullo, M.D., a cardiologist at Mayo Clinic in Rochester, Minn.

The Mayo researchers are part of the eMERGE trial, funded by the National Human Genome Research Institute (NHGRI), to study human genetic variation and common human disorders, using electronic medical records. Mayo Clinic's role is to discover genetic variants that can help identify people at risk of vascular disease.

The 10-year probability of infarction is commonly estimated on the basis of the Framingham Risk Score (FRS), which uses conventional risk factors such as a patient's age, sex, lipid profile, blood pressure, and diabetes and smoking status.

Mayo Clinic researchers looked at medical records of 1,262 people who had no history of heart disease. Using information from their medical records, the researchers estimated the FRS for these individuals. Then, using blood samples, the researchers tested for the presence of 11 gene variants, known as single nucleotide polymorphisms (SNPs), which have been validated as potential risk factors for coronary disease in a number of genome-wide association studies.

Using the genetic markers alone, the researchers estimated the risk of myocardial infarction, and then modified the 10-year probability using the FRS groupings. This modification resulted in reclassification of 386 patients, about one-third of the participants.

Dr. Kullo acknowledges that these findings need to be replicated and validated in prospective studies before they are used in patient care; if genetic scores are validated, those likely to benefit most are individuals at intermediate risk. "Cardiologists are most uncertain of therapy in patients who fall into this group," he says.