Author + information
- Received October 2, 2012
- Revision received November 26, 2012
- Accepted December 11, 2012
- Published online March 19, 2013.
- Pia R. Kamstrup, MD, PhD⁎,†,
- Anne Tybjærg-Hansen, MD, DMSc†,‡,§∥ and
- Børge G. Nordestgaard, MD, DMSc⁎,†,§∥,⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Børge G. Nordestgaard, Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev Ringvej 75, DK-2730 Herlev, Denmark
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.
The study was supported by the Danish Heart Foundation, The Danish Council for Independent Research–Medical Sciences, IMK Almene Fund, and Johan and Lise Boserup’s Fund. The study sponsors had no role in the conduct of the study; in the collection, management, analysis, or interpretation of data; or in the preparation, review, or approval of the manuscript. Dr. Kamstrup has received lecture honoraria from Fresenius Medical Care. Dr. Nordestgaard has received consultancy fees/lecture honoraria from AstraZeneca, Pfizer, Merck, Karo Bio, Abbott, sanofi-aventis, Regeneron, Boehringer-Ingelheim, and Omthera. Dr. Tybjærg-Hansen reported that she has no relationships relevant to the contents of this paper to disclose.
- Received October 2, 2012.
- Revision received November 26, 2012.
- Accepted December 11, 2012.
- American College of Cardiology Foundation