Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population.

Abstract

OBJECTIVES:

The purpose of this study was to determine whether elevated lipoprotein(a) levels and corresponding LPA risk genotypes (rs10455872, rs3798220, kringle IV type 2 repeat polymorphism) prospectively associate with increased risk of aortic valve stenosis (AVS).

BACKGROUND:

The etiologic basis of AVS is unclear. Recent data implicate an LPA genetic variant (rs10455872), associated with Lp(a) levels, in calcific AVS.

METHODS:

We combined data from 2 prospective general population studies, the Copenhagen City Heart Study (1991 to 2011; n = 10,803) and the Copenhagen General Population Study (2003 to 2011; n = 66,877), following up 77,680 Danish participants for as long as 20 years, during which time 454 were diagnosed with AVS. We conducted observational and genetic instrumental variable analyses in a Mendelian randomization study design.

RESULTS:

Elevated Lp(a) levels were associated with multivariable adjusted hazard ratios for AVS of 1.2 (95% confidence interval [CI]: 0.8 to 1.7) for 22nd to 66th percentile levels (5 to 19 mg/dl), 1.6 (95% CI: 1.1 to 2.4) for 67th to 89th percentile levels (20 to 64 mg/dl), 2.0 (95% CI: 1.2 to 3.4) for 90th to 95th percentile levels (65 to 90 mg/dl), and 2.9 (95% CI: 1.8 to 4.9) for levels greater than 95th percentile (>90 mg/dl), versus levels less than the 22nd percentile (<5 mg/dl; trend, p < 0.001). Lp(a) levels were elevated among carriers of rs10455872 and rs3798220 minor alleles, and of low number of KIV-2 repeats (trend, all p < 0.001). Combining all genotypes, instrumental variable analysis yielded a genetic relative risk for AVS of 1.6 (95% CI: 1.2 to 2.1) for a 10-fold Lp(a) increase, comparable to the observational hazard ratio of 1.4 (95% CI: 1.2 to 1.7) for a 10-fold increase in Lp(a) plasma levels.

CONCLUSIONS:

Elevated Lp(a) levels and corresponding genotypes were associated with increased risk of AVS in the general population, with levels >90 mg/dl predicting a threefold increased risk.

• Authors: Pia R Kamstrup, Anne Tybjærg-Hansen, Børge G Nordestgaard
• Journal: Journal of the American College of Cardiology (J Am Coll Cardiol) Vol. 63 Issue 5 Pg. 470-7 (Feb 11 2014) ISSN: 1558-3597 [Electronic] United States
• PMID: 24161338 (Publication Type: Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Lipoprotein(a)

Topics

• Aged
• Aortic Valve Stenosis (blood, epidemiology, etiology)
• Biomarkers (blood)
• Denmark (epidemiology)
• Female
• Humans
• Hyperlipoproteinemias (blood, complications, epidemiology)
• Incidence
• Lipoprotein(a) (blood)
• Male
• Middle Aged
• Population Surveillance
• Prevalence
• Prospective Studies
• Risk Assessment (methods)
• Risk Factors
• Severity of Illness Index