01 - ATRIAL FIBRILLATION IS ASSOCIATED WITH ALTERATIONS IN HDL FUNCTION, METABOLISM AND PARTICLE NUMBER

Aim: Increased morbidity and mortality in atrial fibrillation (AF) are related to the pro-fibrotic, pro-thrombotic and pro-inflammatory processes that underpin the disease. High-density lipoproteins (HDL) have anti-inflammatory, anti-oxidative, and anti-thrombotic properties. Functional impairment of HDL may, therefore, associate with AF initiation or progression. We studied indices of HDL quality and quantity of apolipoprotein (apo) B-depleted serum of AF patients and healthy control, including HDL particle number, HDL-cholesterol, apolipoprotein (apo) A-I levels, serum amyloid A (SAA) content, HDL cholesterol efflux capacity and paraoxonase activity. Methods and Results: Serum samples were collected from AF patients (n=91) before catheter ablation and from age and sex-matched control subjects (n= 54). HDL cholesterol efflux capacity was assessed in a validated assay using [3H]-cholesterol labeled J774 macrophages. Lecithin-cholesterol acyltransferase (LCAT) and paraoxonase activities were assessed using fluorometric assays, apolipoproteins were determined by ELISA, HDL particle number was assessed by nuclear magnetic resonance spectroscopy. HDL cholesterol efflux capacity, HDL particle number, apoA-I levels, and LCAT activity were markedly reduced in AF patients when compared to healthy individuals, whereas HDL-associated paraoxonase activity and SAA content were not altered. Notably, cholesterol efflux capacity, HDL particle number, apoA-I levels as well as LCAT activity recovered following the restoration of sinus rhythm (all p<0.001).Conclusions: We identified marked alterations in HDL function, HDL maturation and HDL particle number in AF patients. Assessing HDL particle number and function in AF may be used as a surrogate marker of AF onset and progression and may help to identify patients at high risk.