A specific plasma lipid signature associated with high triglycerides and low HDL cholesterol identifies residual CAD risk in patients with chronic coronary syndrome

Background and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/ HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS). Methods: TG/HDL-C ratio was calculated in 193 patients (57.8 +/- 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 +/- 1.17 years), including clinical, lipidomics and coronary CTA assessments. Results: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (<1.391), IIQ (1.392-2.000), IIIQ (2.001-3.286), and IVQ (>= 3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up. Conclusions: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments.

Automated summary

This study found that in patients with chronic coronary syndrome, a high TG/HDL-C ratio is associated with a specific pattern of altered lipids and higher coronary CTA risk score. These results suggest the presence of a specific lipidomic signature in stable CCS patients, indicating potential molecular pathways of residual CAD risk not addressed by current optimal medical treatments.