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Levels of cf-DNA predict all-cause mortality

A recent study published in Scientific Reports has observed the role of circulating cell-free DNA (cf-DNA) as a viable marker of health.


Circulating cf-DNA in recent years has been shown to be a sensitive and useful marker of cellular death and tissue damage in a variety of pathologies. These include sepsis, trauma, cardiovascular diseases (CVDs) and cancer. These pathologies are characterised by elevated levels of cf-DNA in the blood, with higher levels associated with poorer outcomes. The use of cf-DNA has generated a lot of excitement as it offers a minimally invasive prognostic approach. Nonetheless, its characterisation as a marker for general health is in its infancy, particularly for its use in risk stratification.

Prediction of all-cause mortality

In this study, a team of researchers from Finland utilised the sample from the Finnish population-based Health 2000 Survey. This survey contains an extensive array of health indicators and a 15-year mortality follow-up (n= 1,257, 46–76 years of age).

From a set of 30 predefined variables that are associated with health and mortality, the team identified those which – independently of each other – predict all-cause mortality. These variables include blood biomarkers (levels of fasting glucose, adiponectin, TNF-alpha, IL-6, CRP and insulin), education level, health behaviours (eating fresh vegetables, smoking, alcohol consumption and frequency of intensive exercise), diseases (e.g. diabetes, cardiovascular diseases, respiratory diseases) and self-rated health. They also assessed whether cf-DNA adds predictive power on top of these other risk factors. In addition, they determined whether it holds equal predictive power in individuals with and without CVD.

The researchers found, using a multivariate model, that increases in cf-DNA levels were associated with increased mortality. When stratified for CVD status, the team found that cf-DNA predicted mortality equally well in individuals with and without CVD.

Overall, these results indicate that cf-DNA can be considered as a valuable biomarker that is independent of other risk factors and is sensitive enough to identify individuals at a higher mortality risk, irrespective of CVD status. Nevertheless, the authors emphasise that lack of standardisation of cf-DNA measurement methods impedes its clinical translation. Therefore, research into the validity and reproducibility of each method is required.

Image credit: Medical photo created by kjpargeter –

More on these topics

Biomarkers / Cardiovascular disease / cf-DNA