Genetic Evidence That Lipoprotein(a) Associates With Atherosclerotic Stenosis Rather Than Venous Thrombosis
Objective—The aim of the present study was to determine whether lipoprotein(a) [Lp(a)], considered a causal risk factor for cardiovascular disease, primarily promotes thrombosis or atherosclerosis.
Methods and Results—Using a Mendelian randomization study design, we measured plasma Lp(a) and genetically elevated Lp(a) levels through the LPA kringle IV type 2 repeat genotype in 41 231 individuals. We included 2 general population studies of both venous thrombosis and combined thrombosis and atherosclerosis in coronary arteries (=myocardial infarction), and 3 case–control studies of atherosclerotic stenosis. Neither Lp(a) tertiles nor LPA kringle IV type 2 tertiles associated with the risk of venous thrombosis in general population studies (trend: P=0.12–0.76), but did each associate with risk of coronary, carotid, and femoral atherosclerotic stenosis in case–control studies (trend: P<0.001 to 0.04). Lp(a) and LPA kringle IV type 2 tertiles also associated with the risk of myocardial infarction in general population studies (trend: P<0.001 to 0.003). For doubling of Lp(a) levels, instrumental variable estimates of hazard/odds ratios were 1.02 (95% CI 0.90–1.15) and 1.04 (0.93–1.16) for venous thrombosis in the 2 general population studies, 1.12 (1.01–1.25), 1.17 (1.05–1.32), and 1.16 (1.01–1.35), respectively, for coronary, carotid, and femoral atherosclerotic stenosis in case–control studies, and 1.21 (1.10–1.33) and 1.17 (1.05–1.29) for myocardial infarction in general population studies.
Conclusion—This supports that Lp(a) primarily promotes atherosclerotic stenosis rather than venous thrombosis.
- Received December 16, 2011.
- Accepted April 5, 2012.
- © 2012 American Heart Association, Inc.