Abstract 14273: Extreme Lipoprotein(a) Levels, Corresponding LPA Risk Genotypes, and Improved Myocardial Infarction and Coronary Heart Disease Risk Prediction
Background Elevated lipoprotein(a) levels cause myocardial infarction and coronary heart disease. Levels are primarily determined by variation in the LPA gene. We tested the hypothesis that extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (associated with small lipoprotein(a) isoforms and elevated levels) improve myocardial infarction and coronary heart disease risk prediction beyond conventional risk factors.
Methods We followed 8720 Danish general population participants (the Copenhagen City Heart Study), from 1991-1994 through 2011 without losses to follow-up. During this period, 730 and 1683 first-time myocardial infarctions and coronary heart disease events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels (top 20%) and/or corresponding LPA risk genotypes (kringle-IV type 2 (KIV-2) repeat polymorphism (bottom 20%) and rs3798220 (2% carriers) and rs10455872 (13% carriers) SNPs), we calculated net reclassification indices from <10% to 10-19.9% to ≥20% absolute 10-year coronary heart disease risk.
Results For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dL), 23% (p<0.001) of myocardial infarction events and 12% (p<0.001) of coronary heart disease events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16%(95%CI:9%-24%) and +3%(-1%-8%) for myocardial infarction and coronary heart disease. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12%(5%-19%) and +4%(0%-8%), for rs3798220 carrier status +15%(-14%-44%) and +10%(-10%-30%), and for rs10455872 carrier status +16%(6%-26%) and +2%(-1%-6%). Combining extreme lipoprotein(a) levels and corresponding LPA risk genotypes improved risk prediction for myocardial infarction.
Conclusion Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved myocardial infarction and coronary heart disease risk prediction.
- © 2012 by American Heart Association, Inc.