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

Abstract

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.

Clinical Impact and Prognostic Role of Triglyceride to High-Density Lipoprotein Cholesterol Ratio in Patients With Chronic Coronary Syndromes at Very High Risk: Insights From the START Study

“…Several studies have reported that the combination of high TG and low HDL-C level was a predictor of cardiovascular disease independent of LDL-C level ( 1 – 4 , 15 ). Moreover, combining the two lipid measures into one as the ratio of TG to HDL-C has been proved to be a reliable indicator for metabolic syndrome, insulin resistance, with direct implications in endothelial damage and atherosclerosis ( 5 , 6 , 16 , 17 ). Reference values for TG/HDL-C ratio and its association with cardiometabolic diseases in a mixed adult population were also recently identified ( 18 ).…”

Low HDL cholesterol and the eNOS Glu298Asp polymorphism are associated with inducible myocardial ischemia in patients with suspected stable coronary artery disease

“…The efficiency of this mechanism is not only related with the abundance of HDL-C particles but also with their functionality. For example, there is recent evidence that high levels of TG rich lipoproteins cause not only a decrease in HDL lipoproteins, due to enhanced catabolism, but also some structural changes [24]. The alteration of HDL composition is able to decrease the anti-atherosclerotic properties of these particles involving not only their contribution to the reverse cholesterol transport but also their antiinflammatory actions [25].…”

The Essence of Lipoproteins in Cardiovascular Health and Diseases Treated by Photodynamic Therapy

“…There have also been analyses of HDL and LDL lipidomes in coronary artery disease (CAD) and also in acute coronary syndrome (ACS) [50,51]. Currently, studies in the field of plasma lipidomics are being discussed more and more due to the fact that several pieces of evidence are emerging that indicate an association between certain types of plasma lipids, atherosclerosis, and adverse clinical events [28][29][30][31][32][33][34][35][36]. To date, there are only a few studies described that address the relationship between biologically active lipids, closely linked to their lipoprotein carriers, and cardiovascular disease [37].…”