Intro: Integrative analysis of extracellular microRNA (miRNA) and metabolomics is a novel approach to identifying molecular pathways underlying cardiovascular health (CVH). Levels of miRNAs are linked to cardiovascular disease (CVD), while cardiometabolic risk factors are known to alter activity of select metabolic pathways. We identified miRNAs and metabolites underlying CVH in a cohort of Black adults through an integrative analysis of extracellular miRNA levels, metabolite concentrations and clinical factors associated with CVH.Methods: The MECA cohort consisted of 371 Black adults (age 53+10, 38.5% male) without known CVD. CVH was determined by Life’s Simple 7 (LS7) score, calculated from blood pressure, fasting glucose, cholesterol, BMI, exercise, diet, and smoking. Metabolite concentrations in plasma was assessed by high-resolution metabolomics profiling, and expression of miRs-122-5p, -150-5p, and -30c-5p was assessed by RT-qPCR. Metabolome wide association study (MWAS) identified metabolites associated with LS7. Association of miRNA levels with CVH clinical domains was assessed using Spearman correlation. Integrative analysis of select miRNAs, metabolites, and CVH clinical domains was performed using the program xMWAS.Results: Expression of 30 metabolites was associated with improved CVH (FDR<0.2) where glutamine was higher (p=0.005), and glutamate was lower (p<0.001). Integrative analysis showed association between miR-122-5p, glutamine and fasting glucose. miR-122-5p expression independently correlated with fasting glucose (p=0.03) and glutamine/glutamate is known to be associated with glucose metabolism. In silico and in vitro analyses revealed glutamine synthetase as a potential target of miR-122-5p (Fig).Conclusions: We demonstrate novel associations between glutamine, miR-122-5p and fasting glucose in CVH, suggesting that select metabolites and miRNAs are markers of CVH and maybe potential therapeutic targets.