Metabolomics and cardiovascular risk in patients with heart failure: a systematic review and meta-analysis

Abstract

The association of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis, to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Five independent cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1560 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two cohorts, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95%CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting and sharing.