Genetics
Lp(a) genetically drives atherosclerotic narrowing but not venous blood clots, a Mendelian randomisation study of 41,231 people (Arterioscler Thromb Vasc Biol 2012)
Original title: Genetic evidence that lipoprotein(a) associates with atherosclerotic stenosis rather than venous thrombosis
This Mendelian randomisation study by Kamstrup, Tybjaerg-Hansen and Nordestgaard measured plasma and genetically elevated Lp(a) (via LPA kringle IV type 2 repeat genotype) in 41,231 individuals across 2 general population studies of venous thrombosis and myocardial infarction, and 3 case-control studies of atherosclerotic stenosis, to test whether Lp(a) primarily promotes thrombosis or atherosclerosis. Neither Lp(a) nor LPA kringle IV type 2 tertiles were associated with venous thrombosis risk (trend P=0.12-0.76), but both were associated with coronary, carotid, and femoral atherosclerotic stenosis (trend P<0.001 to 0.04) and myocardial infarction (trend P<0.001 to 0.003). For a doubling of Lp(a), instrumental variable hazard/odds ratios were 1.02 and 1.04 for venous thrombosis in the two population studies, 1.12, 1.17, and 1.16 for coronary, carotid, and femoral stenosis, and 1.21 and 1.17 for myocardial infarction. The findings show Lp(a) primarily promotes atherosclerotic stenosis rather than venous thrombosis.
Original abstract
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 41231 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.
Conclusions: This supports that Lp(a) primarily promotes atherosclerotic stenosis rather than venous thrombosis.
geneticsrisk predictionthrombosis
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.