A microbiota pattern associated with cardiovascular events in secondary prevention: the CORDIOPREV study

Background and aims: Preventing new cardiovascular events in patients with established cardiovascular disease (CVD) is a daunting task for clinicians. Intestinal microbiota may help identify patients at risk, thus improving the strategies of secondary prevention. The aim of this study was to evaluate the baseline differences between the gut microbiota from coronary heart disease (CHD) patients suffering new major adverse cardiovascular events (MACEs) in the following 7 years, compared with CHD patients who did not undergo new MACE in this period, and to build a score associated with the risk of suffering new MACE. Methods: Within the framework of the CORDIOPREV study, a clinical trial that involved 1002 patients with CHD, intestinal microbiota was examined in patients with available faecal samples (n = 679, 132 MACE), through 16S metagenomics on the Illumina MiSeq and Quiime2 software. Lipopolysaccharide (LPS) was measured using limulus amoebocyte lysate test. Results: Random survival forest identified 10 bacterial taxa with a higher predictive power for MACE incidence. Receiver operating characteristic curves yielded an area under the curve of 65.2% (59.1%-71.3%) in the training set and 68.6% (59.3%-77.9%) in the validation set. The intestinal microbiota risk score was associated with a MACE incidence hazard ratio of 2.01 (95% confidence interval 1.37-3.22). Lipopolysaccharide analysis showed a greater LPS post-prandial fold change in the MACE group (P = .005). Conclusions: These results reinforce the relationship between intestinal microbiota and CVD and suggest that a microbiota profile is associated with MACE in CHD patients, in addition to higher endotoxaemia.