Genetics
Extreme Lp(a) or its gene variants correctly reclassify up to 23% of heart attack risk predictions, a Danish study of 8720 people (J Am Coll Cardiol 2013)
Original title: Extreme lipoprotein(a) levels and improved cardiovascular risk prediction
This study by Kamstrup, Tybjaerg-Hansen and Nordestgaard tested whether extreme Lp(a) levels or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction, following 8,720 Danish participants from 1991-1994 through 2011, during which 730 MI and 1,683 CHD events occurred. Among individuals with Lp(a) at or above the 80th percentile (47 mg/dL or higher), 23% of MI events and 12% of CHD events were correctly reclassified (both P<0.001), with no incorrect reclassification of events, yielding overall net reclassification indices of +16% for MI and +3% for CHD. Similar improvements were seen for LPA kringle IV-2 repeat count at or below the 21st percentile (+12% for MI, +4% for CHD), rs3798220 carrier status (+15% for MI, +10% for CHD), and rs10455872 carrier status (+16% for MI, +2% for CHD), with even greater improvement among those at intermediate (10-19.9%) baseline risk. The findings show extreme Lp(a) levels or corresponding LPA risk genotypes substantially improve MI and CHD risk prediction.
Original abstract
Objectives: The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors.
Background: Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene.
Methods: We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk.
Results: For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD 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% confidence interval: 8% to 24%) and +3% (-1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (-14% to 44%) and +10% (-10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (-1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further.
Conclusions: Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction.
Summary written by lp-a.org from the published abstract; figures as published. Page updated 18 August 2026. Methods.