Circulating cell-free DNA and its association with cardiovascular disease: what we know and future perspectives

Purpose of review The aim of this review is to explore a possible link between cell-free DNA (cfDNA) and cardiovascular disease (CVD), which may hold valuable potential for future diagnostics. Recent findings cfDNA has become topic of high interest across several medical fields. cfDNA is used as a diagnostic biomarker in cancer, prenatal care, and transplantation. In addition, cfDNA may play an unrecognized role in biological processes that are involved in or underlying various disease states, for example, inflammation. Elevated levels of cfDNA are associated with various elements of CVD, cardio-metabolic risk factors, and autoimmune diseases. Mitochondrial cfDNA and neutrophil extracellular traps may play distinct roles. Total circulating cfDNA may reflect the unspecific accumulation of stressors and the organism's susceptibility and resilience to such stressors. As such, cfDNA, in a stressful situation, may provide predictive value for future development of CVD. We suggest exploring such possibility through a large-scale prospective cohort study of pregnant women. Summary There is no doubt that cfDNA is a valuable biomarker. For CVD, its potential is indicated but less explored. New studies may identify cfDNA as a valuable circulating cardiovascular risk marker to help improve risk stratification.