Abstract | BACKGROUND: OBJECTIVES: This study sought to determine whether Lp(a) and OxPL are associated with hemodynamic progression of AS and AS-related events. METHODS:
OxPL on apolipoprotein B-100 ( OxPL- apoB), which reflects the biological activity of Lp(a), and Lp(a) levels were measured in 220 patients with mild-to-moderate AS. The primary endpoint was the progression rate of AS, measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up. RESULTS: AS progression was faster in patients in the top tertiles of Lp(a) (peak aortic jet velocity: +0.26 ± 0.26 vs. +0.17 ± 0.21 m/s/year; p = 0.005) and OxPL- apoB (+0.26 ± 0.26 m/s/year vs. +0.17 ± 0.21 m/s/year; p = 0.01). After multivariable adjustment, elevated Lp(a) or OxPL- apoB levels remained independent predictors of faster AS progression. After adjustment for age, sex, and baseline AS severity, patients in the top tertile of Lp(a) or OxPL- apoB had increased risk of aortic valve replacement and cardiac death. CONCLUSIONS: Elevated Lp(a) and OxPL- apoB levels are associated with faster AS progression and need for aortic valve replacement. These findings support the hypothesis that Lp(a) mediates AS progression through its associated OxPL and provide a rationale for randomized trials of Lp(a)-lowering and OxPL- apoB-lowering therapies in AS. ( Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin [ASTRONOMER]; NCT00800800).
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Authors | Romain Capoulade, Kwan L Chan, Calvin Yeang, Patrick Mathieu, Yohan Bossé, Jean G Dumesnil, James W Tam, Koon K Teo, Ablajan Mahmut, Xiaohong Yang, Joseph L Witztum, Benoit J Arsenault, Jean-Pierre Després, Philippe Pibarot, Sotirios Tsimikas |
Journal | Journal of the American College of Cardiology
(J Am Coll Cardiol)
Vol. 66
Issue 11
Pg. 1236-1246
(Sep 15 2015)
ISSN: 1558-3597 [Electronic] United States |
PMID | 26361154
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Biomarkers
- Lipoprotein(a)
- Phospholipids
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Topics |
- Adult
- Aged
- Aortic Valve
(diagnostic imaging, pathology)
- Aortic Valve Stenosis
(blood, diagnostic imaging, mortality)
- Biomarkers
(blood)
- Calcinosis
(blood, diagnostic imaging, mortality)
- Death
- Disease Progression
- Female
- Humans
- Lipoprotein(a)
(blood)
- Male
- Middle Aged
- Oxidation-Reduction
- Phospholipids
(blood)
- Ultrasonography
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