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DNA particles may signal CV risk in patients with chest pain
Elevated levels of DNA particles, including markers of cell death and formation of neutrophil extracellular traps, may help physicians predict CV risk and identify CAD in patients with chest discomfort, according to study results.
“The more the ongoing cell death, which is normal with inflammation, the more DNA enters the circulation and more plaque builds up,” study researcher Julian I. Borissoff, MD, PhD, a postdoctoral fellow at Boston Children’s Hospital and Harvard Medical School, said in a press release. “Cells get damaged, and the products released from the damaged cells can cause even more damage and inflammatory responses.”
Borissoff and colleagues examined a prospective, observational, cross-sectional cohort of 282 patients aged 34 to 83 years with chest pain and suspected CAD. The researchers used coronary CT angiography (CCTA) to assess the severity, extent and phenotype of coronary atherosclerosis. Blood samples also were collected and underwent DNA analysis. The occurrence of major adverse cardiac events, including revascularization more than 60 days after CCTA with PCI or CABG, ACS and cardiac mortality, served as the composite endpoint.
Results revealed significantly elevated plasma double-stranded DNA, nucleosomes and myeloperoxidase (MPO)-DNA complexes in patients with severe coronary atherosclerosis or with extreme coronary artery calcification. After adjustment for confounding factors, data from a multinomial regression analysis showed that high plasma nucleosome levels were independently associated with an increased risk for severe coronary stenosis (OR=2.14; 95% CI, 1.26-3.63). The researchers also found that neutrophil extracellular trap markers, including MPO-DNA complexes, served as independent predictors of the number of atherosclerotic coronary vessels and the occurrence of major adverse cardiac events.
These data may be clinically meaningful in helping physicians predict CV risk using these biomarkers, according to the researchers.
“If those markers are proven to be effective — specific and sensitive — they may improve medical care in terms of identifying patients at risk sooner, and so the patients may go on treatment sooner,” Borissoff said.
The researchers said larger and longer studies are required to understand the role of neutrophil extracellular traps in the development of atherosclerosis and atherothrombosis.
Disclosure: The researchers report no relevant financial disclosures.
Perspective
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This is a small but interesting study based upon what we believe to be a pathogenic mechanism in the progression of atherosclerosis and endothelial damage. There are types of cells that actually create damage and release various forms of DNA that can be measured in the bloodstream, so conceptually, testing for these substances in the bloodstream makes sense. It is intuitive that, if the burden of atherosclerosis is high, these byproducts of atherosclerosis should be more easily detected and should be at higher concentrations in the bloodstream. The notion that this would predict events does need to be tested in a larger cohort of patients. It’s easy to understand why there would be an association between the amount of atherosclerosis and the levels of circulating double-stranded DNA and MPO complex, but it’s less clear that that in and of themselves these bloodstream DNA markers would predict adverse events, such as MI or sudden cardiac death.
If evaluated in a larger cohort of patients, these findings could have significant clinical impact. We are constantly trying to find robust biomarkers that will tell us who is at risk and how high is that risk for complications of CHD. These complications can include HF, MI or sudden cardiac death. It would be great if we had better tools to predict those events. One could also conceive of using these substances as a marker of clinically significant atherosclerosis when evaluating patients with chest pain or other symptoms worrisome for cardiac disease. Those are two areas where we can do better, and this is potentially a test that will allow us to do better. However, it does need to be evaluated more extensively.
Before being used on a larger scale, we would also have to figure out a way to actually make the test as easy as possible for screening and as resistant to external factors that might influence the measurements of these substances in the blood. For example, in the study, there was no correction for the number of white blood cells in the bloodstream, and one would anticipate that perhaps that might influence the outcomes of the test. Essentially, making the test robust and reproducible are key to ensuring that potential confounders are addressed, and that is going to be important before the test even gets used in larger cohorts.