Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proinflammatory participant in atherosclerosis and a potential biomarker for coronary heart disease. The effects of low-density lipoprotein (LDL) apheresis on Lp-PLA(2) levels were evaluated in 8 patients with cardiovascular disease. Each patient received 5 LDL apheresis treatments over a 3-month period. The mean direct LDL cholesterol level reduction was 60% (252 to 100 mg/dl). LDL apheresis acutely reduced Lp-PLA(2) by 21.4%. Over the course of treatment, Lp-PLA(2) levels were reduced by 29%. Chronic LDL apheresis significantly reduces Lp-PLA(2) independent of LDL cholesterol, which may be a potential mechanism by which LDL apheresis diminishes coronary heart disease risk.