Fluid-based assays and precision medicine of cardiovascular diseases: the 'hope' for Pandora's box?

J Clin Pathol. 2019 Dec;72(12):785-799. doi: 10.1136/jclinpath-2019-206178. Epub 2019 Oct 14.

Abstract

Progresses in liquid-based assays may provide novel useful non-invasive indicators of cardiovascular (CV) diseases. By analysing circulating cells or their products in blood, saliva and urine samples, we can investigate molecular changes present at specific time points in each patient allowing sequential monitoring of disease evolution. For example, an increased number of circulating endothelial cells may be a diagnostic biomarker for diabetic nephropathy and heart failure with preserved ejection fraction. The assessment of circulating cell-free DNA (cfDNA) levels may be useful to predict severity of acute myocardial infarction, as well as diagnose heart graft rejection. Remarkably, circulating epigenetic biomarkers, including DNA methylation, histone modifications and non-coding RNAs are key pathogenic determinants of CV diseases representing putative useful biomarkers and drug targets. For example, the unmethylated FAM101A gene may specifically trace cfDNA derived from cardiomyocyte death providing a powerful diagnostic biomarker of apoptosis during ischaemia. Moreover, changes in plasma levels of circulating miR-92 may predict acute coronary syndrome onset in patients with diabetes. Now, network medicine provides a framework to analyse a huge amount of big data by describing a CV disease as a result of a chain of molecular perturbations rather than a single defect (reductionism). We outline advantages and challenges of liquid biopsy with respect to traditional tissue biopsy and summarise the main completed and ongoing clinical trials in CV diseases. Furthermore, we discuss the importance of combining fluid-based assays, big data and network medicine to improve precision medicine and personalised therapy in this field.

Keywords: biomarkers; cardiovascular diseases; imaging; liquid biopsy; network medicine; omics platforms; personalized therapy.

Publication types

  • Review

MeSH terms

  • Biomarkers / metabolism
  • Body Fluids / metabolism*
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / metabolism
  • Cell-Free Nucleic Acids / blood
  • Clinical Decision-Making
  • Humans
  • Liquid Biopsy
  • Molecular Diagnostic Techniques*
  • Patient Selection
  • Precision Medicine*
  • Predictive Value of Tests
  • Prognosis
  • Reproducibility of Results

Substances

  • Biomarkers
  • Cell-Free Nucleic Acids