Lipoprotein-Associated Phospholipase A2 Loss-of-Function Variant and Risk of Vascular Diseases in 90,000 Chinese Adults

Lipoprotein-associated phospholipase A2 (Lp-PLA2) produces the proinflammatory mediators lysophosphatidylcholine and oxidized free fatty acids through hydrolysis of oxidized phospholipids carried on low-density lipoproteins in atherosclerotic plaques. Although increased Lp-PLA2 activity has been associated with higher risks of occlusive vascular diseases, recent phase III trials of the Lp-PLA2 inhibitor darapladib, which reduces Lp-PLA2 activity by ∼60%, failed to establish a protective role of darapladib for prevention of major vascular events in patients with stable coronary heart disease (CHD) or acute coronary syndrome 1, 2.