Abstract 321: Cardiometabolic Recovery Kinetics Post Apheresis in a Model of Accelerated Atherothrombosis

Background: Atherothrombotic disease is a chronic, smoldering multifaceted process of inflammatory, lipid, and oxidative insult. Familial hypercholesterolemia (FH) serves as a model of accelerated disease in which these pathways may be better characterized. Methods: Eight FH patients were assessed before and after LDL apheresis at multiple time points for levels of: Non-esterified fatty acids (NEFA), lipoprotein-associated phospholipase A2 mass (PLAC), thiobarbituric acid reactive substances (TBARS), C-reactive protein (CRP), triglycerides (TG), insulin, and glucose. Results: Mean pre- and post-apheresis plasma levels were: 2.76 and 1.05 for CRP, 16.64 and 7.11 for insulin, 98.7 and 81.1 for glucose, 156 and 110 for TG, 177 and 97 for PLAC, and 0.5 and 0.72 for NEFA (p < 0.10, all). Plasma glucose, insulin, and TG levels showed concurrent post-prandial peaks at 12 and 36 hours post-apheresis (Fig 1). NEFA peaked during fasting states at 24 and 48 hours post-apheresis (Fig 1). Maximum mean % gain was: 33.7%[(1.98-1.05)/2.76] for CRP from 6 to 12 hours, followed by 24.1%[(0.48-0.35)/0.54] for TBARS and 15.2%[(123.2-96.29)/177.12] for PLAC from 12 to 24 hours. Conclusion: Our data show that LDL apheresis significantly decreases inflammatory, metabolic and oxidative burden in FH patients. Peaks in glucose, insulin and TG were within normal range arguing against post-prandial dysmetabolism in FH patients. NEFA increased with apheresis and fasting, suggestive of hormone-sensitive lipase upregulation. The temporal progression of recovery shows a predominant inflammatory process acutely, followed by high oxidative stress as a result of PLAC preponderance.