Advanced lipoprotein, glycoprotein and lipidomic profiles in hyperalphalipoproteinemia with and without atherosclerotic cardiovascular disease: a case–control study

Despite the well-established protective role of HDL-cholesterol against atherosclerotic cardiovascular disease (ASCVD), several studies have observed a higher incidence of ASCVD in individuals with elevated HDL-cholesterol concentrations. This condition, known as hyperalphalipoproteinemia, appears to modify HDL composition, potentially resulting in a loss of its anti-atherogenic properties and, in some cases, a pro-atherogenic effect. This study aimed to assess advanced lipoprotein, lipidomic and inflammatory biomarker profiles using nuclear magnetic resonance (NMR) spectroscopy in patients diagnosed with hyperalphalipoproteinemia who have suffered a cardiovascular event. A case-control study was conducted on a cohort of patients diagnosed with hyperalphalipoproteinemia and ASCVD (n = 29) and a control group of individuals with hyperalphalipoproteinemia but without ASCVD (n = 41). A conventional lipid profile and an advanced lipoprotein, lipidomic and inflammatory biomarker profiles were performed using NMR spectroscopy. Patients with hyperalphalipoproteinemia and ASCVD showed higher concentrations of VLDL particles (particularly small VLDL), HDL particles (particularly small HDL) and higher triglyceride content in both lipoproteins, although serum concentrations of HDL-cholesterol and triglycerides were comparable within groups. Furthermore, ASCVD group presented an altered lipidomic profile, characterised by decreased concentrations of lysophosphatidylcholine, and increased concentrations of saturated fatty acids. In addition, these patients exhibited elevated concentrations of amyloid A protein in both serum and isolated HDL3 fraction. Patients with hyperalphalipoproteinemia and ASCVD showed a lipoprotein and lipidomic profile with metabolic, structural, and compositional alterations consistent with a more atherogenic pattern. This profile could not be detected by a conventional lipid profile.