Plasma metabolomic and proteomic profiling correlates with coronary plaque characteristic in older coronary heart disease patients

Coronary heart disease (CHD) is a lipid-driven inflammatory disease increasing in individuals. Lipoprotein(a) (Lp[a]) has an interdependence with systemic metabolism and inflammation to increase the risk of CHD. Our study aims to examine the coronary lesion and plaque characteristic in older CHD patients with elevated Lp(a) level by using untargeted metabolomics and proteomics assay. We included 285 consecutive individuals ≥ 65 years who took coronary artery CT scanning, collected blood samples and underwent percutaneous coronary angiography. After restricted exclusion, the enrolled age-matched individuals were randomly divided into two separated cohorts. For the testing cohort, plasma samples of 40 controls and 45 CHD patients were conducted with untargeted metabolomics and proteomics. Another validation cohort including 64 controls and 60 CHD patients was used to verify the link between differential plasma mediators and coronary stenosis and plaque characteristics. Compared with an averaged Lp(a) level of 98.9 nmol/L in controls with age ≥ 65 years, mean level of Lp(a) up to 188.4 nmol/L in age-matched CHD patients. The metabolome analyses revealed that differential plasma metabolites would be involved in the pathophysiological regulation of fatty acid transport, fatty-acid-CoA ligase and lipid transport related to lipid plaque progress. We found that plasma levels of β-Muricholic acid, 23-Nordeoxycholic acid, Docosahexaenoic acid, 7-Ketodeoxycholic acid, LPC (18:0) and LPA 16:1 were significantly altered in CHD group. Then proteomics assays showed positive immune response indicating by enhanced interleukin-18 (IL-18), immunoglobulin lambda joining 3 (IGLJ3) and immunoglobulin heavy variable 3 (IGHV3) levels in CHD patients compared to controls. Among these, β-muricholic acid, 23-nordeoxycholic acid, LPA 16:1 and IL-18 were correlated with coronary stenosis severity. Moreover, the levels of β-muricholic acid, IL-18 and IGLJ3 were associated with low-density noncalcified plaque burden in older CHD patients. We also observed plasma levels of β-muricholic acid, 23-nordeoxycholic acid, 7-Ketodeoxycholic acid and IL-18 altered in older CHD patients with chronic total occlusion (CTO) lesion. Our study demonstrated an altered profiling of plasma metabolites and proteins, and their correlation with coronary stenosis severity and plaque burden in older CHD individuals with elevated Lp(a) level, which may provide potential biomarkers in older CHD patients. Plasma metabolome and proteomics profiling was totally different in older CHD patients. Altered lipid-driven plasma metabolites and proteins were associated with coronary stenosis and plaque burden. Differential metabolites and proteins exhibited potential values linked to coronary stenosis severity and CTO lesion.