Mitochondrial DNA copy number and trimethylamine levels in the blood: new insights on cardiovascular disease biomarkers

Among cardiovascular disease (CVD) biomarkers, the mitochondrial DNA copy number (mtDNAcn) is a promising candidate. A growing attention has been also dedicated to trimethylamine-N-oxide (TMAO), an oxidative derivative of the gut metabolite trimethylamine (TMA). With the aim to identify biomarkers predictive of CVD, we investigated TMA, TMAO and mtDNAcn in a population of 389 coronary artery disease (CAD) patients and 151 healthy controls, in association with established risk factors for CVD (gender, age, hypertension, smoking, diabetes, glomerular filtration rate (GFR)). MtDNAcn was significantly lower in CAD patients and in hypertensive subjects; it correlates with GFR and TMA, but not with TMAO. A biomarker including mtDNAcn, gender, and hypertension (but neither TMA nor TMAO) emerged as a good predictor of CAD. Our findings support the usage of mtDNAcn as a plastic biomarker to monitor the exposure to risk factors and the efficacy of preventive interventions for a personalized CAD risk reduction. Highlights- mtDNAcn measured in whole blood is associated to the cardiovascular health status in humans; - mtDNAcn is reduced in CAD and hypertension, and inversely correlates with GFR; - mtDNA, gender and hypertension together represent a good predictive biomarker for CAD; - TMA metabolism is different in healthy and CAD subjects; - TMA and TMAO are not good predictors of CAD.