Abstract 17097: Lipoprotein(a) Genetic Variants Associated With Risk of Atherothrombotic Disease in 14,465 Participants From the Heart Protection Study
Background: Increased plasma levels of Lp(a) lipoprotein have been associated with coronary heart disease (CHD), stroke and other vascular diseases in observational studies. Genetic studies have identified two single nucleotide polymorphisms (SNPs) at the LPA locus (rs3798220 and rs10455872) that were strongly and independently related both to Lp(a) lipoprotein levels and to CHD risk, but their relevance for the risks of stroke and other vascular diseases is uncertain.
Methods and Results: These two LPA SNPs were examined together as an LPA genotype score for associations with different vascular outcomes in the Heart Protection Study of 40 mg simvastatin daily versus placebo in 14,465 people at high-risk of vascular disease. The LPA score was examined in 12,236 participants with prevalent vascular disease at enrolment (9277 CHD cases, 1326 ischemic stroke cases with no history of CHD, and 2011 with peripheral vascular disease with no history of CHD) and compared with 3687 controls with no history of vascular disease (2229 from HPS and 1458 from another UK population). The LPA score was also examined in 3251 participants who had incident major vascular events during study follow-up (2106 CHD events, 507 ischemic strokes, and 707 peripheral vascular disease events) and 11,207 who did not. For prevalent disease, the LPA score was strongly associated with CHD (Odds Ratio [OR] per variant allele 1.19; 95% confidence interval [CI] 1.08-1.30) and peripheral vascular disease (OR 1.18; 95% CI 1.04-1.34]), but was unrelated to ischemic stroke (OR 1.03; 95% CI 0.89-1.20). For incident disease, the LPA score was also similarly strongly associated with CHD (Hazard Ratio [HR] 1.18; 95% CI 1.07-1.29) and peripheral vascular disease (HR 1.24; 95% CI 1.06-1.45), but not with ischemic stroke (HR 0.86; 95%CI: 0.69-1.06).
Conclusions: The comparable strength of associations of LPA variants with CHD and peripheral vascular disease but not with ischemic stroke, and the consistency of effects for both prevalent and incident comparisons, suggest that Lp(a) may have an effect on atherothrombotic vascular disease that is only relevant at specific sites.
- © 2010 by American Heart Association, Inc.