Johns Hopkins researchers report that mitochondrial DNA copy number is a novel and distinct biomarker that is able to predict the risk of heart attacks and sudden cardiac deaths a decade or more before they happen.
In two studies, one on cardiovascular disease published in JAMA Cardiology yesterday and the other focused on sudden cardiac death and published in the European Heart Journal in June, it was shown that including the mitochondrial DNA copy number improved the accuracy of currently used clinical measures for a patient's risk of a deadly cardiac event.
"We believe the mitochondrial DNA copy number is a novel risk factor for cardiovascular disease, in addition to known predictors like LDL, total cholesterol and blood pressure, and it adds sensitivity and specificity to whether or not you should be taking a statin," says Dan Arking, Ph.D., associate professor of medicine at the McKusick-Nathans Institute of Genetic Medicine.
To study the role of the mitochondrial DNA copy number as an effective predictor of cardiovascular disease, Arking and his team collected genetic data from 21,870 participants. The researchers measured the mitochondrial DNA levels relative to nuclear DNA levels, and then added that value as a risk factor to the American College of Cardiology/American Heart Association's Heart Risk Calculator.
At the end of the study, Arking and his team accurately predicted that six people who would not have been recommended treatment under the standard calculation went on to have a life-threatening cardiac event and 139 people who would have been recommended treatment did not have any cardiac events.
"Essentially, our study told us that you can probably safely take 139 people off of the drug who would have been prescribed it and that six people who weren't recommended the drug should really be on it," says Arking.
In addition to improving the predictive value of the Heart Risk Calculator, the second study adds evidence that the mitochondrial DNA copy number also appears to be predictive of sudden cardiac death.
Using similar methods as in the JAMA study, Arking and his team measured the mitochondrial DNA copy number of 11,093 participants. They found that over the course of 20.4 years, 361 participants suffered sudden cardiac death. After adjusting for other risk factors, the researchers determined that participants with relatively low mitochondrial DNA copy numbers were at the highest risk for sudden cardiac death.