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J Am Coll Cardiol. 2015 Sep 15;66(11):1236-1246. doi: 10.1016/j.jacc.2015.07.020.

Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis.

Author information

1
Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.
2
Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
3
Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California.
4
Department of Medicine, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.
5
Department of Medicine (Cardiology), McMaster University, Hamilton, Ontario, Canada.
6
Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.
7
Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada. Electronic address: philippe.pibarot@med.ulaval.ca.
8
Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.

Abstract

BACKGROUND:

Elevated lipoprotein(a) (Lp[a]) is associated with aortic stenosis (AS). Oxidized phospholipids (OxPL) are key mediators of calcification in valvular cells and are carried by Lp(a).

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).

KEYWORDS:

Doppler echocardiography; aortic valve replacement; lipoprotein; peak aortic jet velocity

PMID:
26361154
DOI:
10.1016/j.jacc.2015.07.020
[Indexed for MEDLINE]
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