Mitochondrial DNA Copy Number Can Help Determine Cardiovascular Disease Risk

Mitochondrial DNA Copy Number Can Help Determine Cardiovascular Disease Risk

Researchers have found that mitochondrial DNA copy number may be useful as an independent predictor of cardiovascular disease.

The study titled, “Association of Mitochondrial DNA Copy Number With Cardiovascular Disease,” was published in JAMA Cardiology.

Mitochondrial DNA copy number, which refers to the amount of DNA in the mitochondria, is an indirect biomarker of mitochondrial function as it represents the number of mitochondria present per cell. Mitochondrial dysfunction develops as part of the normal aging process and, therefore, may be associated with atherosclerotic CVD (cardiovascular disease). Early detection of patients at risk for CVD is important as it can allow patients to start statin therapy, which can help prevent a cardiac event.

Researchers at Johns Hopkins University set out to determine whether mitochondrial DNA copy number that is measured in circulating white blood cells could predict the development of CVD and improve classification of patients at risk.

Researchers conducted a prospective, population-based cohort analysis that included 21,870 patients from three different studies: the Cardiovascular Health Study (CHS), Atherosclerosis Risk in Communities Study (ARIC), and the Multiethnic Study of Atherosclerosis (MESA). Data from March 10, 2014 to Jan. 29, 2017 were analyzed for this study. Researchers looked for patients who developed incident CVD, which is defined as the first incident myocardial infarction or death due to coronary heart disease and stroke.

Researchers evaluated each patient’s individual mitochondrial DNA copy number as compared to DNA levels found in the cell’s nucleus and then used the difference as a risk factor for the Heart Risk Calculator, which also takes into account cholesterol, blood pressure, family history, smoking habits, and other lifestyle factors. This calculator is able to predict the risk for a cardiac event in 10 years.

Researchers discovered that the lower the mitochondrial DNA copy number, the higher the risk for cardiovascular disease.

Furthermore, adding the mitochondrial DNA copy numbers to this Heart Risk Calculator significantly improved risk classification for patients. It improved both sensitivity and specificity for the 2013 American College of Cardiology/American Heart Association recommendations on initiating statin therapy for the primary prevention of ASCVD.

Upon using the Heart Risk Calculator and including the mitochondrial DNA copy number data, researchers were able to determine six people who would otherwise not have been recommended under the current calculation who suffered from near-fatal cardiac events.

Mitochondrial DNA copy number also allowed researchers to flag 139 patients as not having a risk for CVD that would have been otherwise prescribed statin according to current guidelines. These patients never had any cardiac events, indicating that this extra factor can help improve recognition of patients that are truly at risk for developing CVD and will avoid statin therapy in patients who are not at risk.

“This is important, because though statins are great drugs and they clearly lower the risk of heart disease, there are side effects and costs associated with taking them, including muscle pain, liver damage, and neurological effects,” Dr. Dan Arking, associate professor of medicine at JHU School of Medicine, said in a press release.

While these data are very promising, further studies are needed before mitochondrial DNA copy number can be introduced into a calculator for prediction of CVD, researchers said.

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