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Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis.
J Am Coll Cardiol. 2015 Sep 15; 66(11):1236-1246.JACC

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).

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Authors+Show Affiliations

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Department of Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.

Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Department of Medicine, St. Boniface General Hospital, Winnipeg, Manitoba, Canada.

Department of Medicine (Cardiology), McMaster University, Hamilton, Ontario, Canada.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California.

Division of Endocrinology and Metabolism, Department of Medicine, University of California San Diego, La Jolla, California.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

Department of Medicine (Cardiology), Institut Universitaire de Cardiologie et de Pneumologie de Québec/Québec Heart and Lung Institute, Laval University, Québec City, Québec, Canada.

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.

Division of Cardiovascular Diseases, Department of Medicine, University of California San Diego, La Jolla, California. Electronic address: stsimikas@ucsd.edu.

MeSH

AdultAgedAortic ValveAortic Valve StenosisBiomarkersCalcinosisDeathDisease ProgressionFemaleHumansLipoprotein(a)MaleMiddle AgedOxidation-ReductionPhospholipidsUltrasonography

Pub Type(s)

Journal Article

Multicenter Study

Randomized Controlled Trial

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26361154

Clinical Trial Links

Clinical trial which this article describes

Lp(a) and Aortic Valve Calcification

Metabolic Determinants of the Progression of Aortic Stenosis

Citation

Capoulade, Romain, et al. "Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis." Journal of the American College of Cardiology, vol. 66, no. 11, 2015, pp. 1236-1246.

Capoulade R, Chan KL, Yeang C, et al. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. J Am Coll Cardiol. 2015;66(11):1236-1246.

Capoulade, R., Chan, K. L., Yeang, C., Mathieu, P., Bossé, Y., Dumesnil, J. G., Tam, J. W., Teo, K. K., Mahmut, A., Yang, X., Witztum, J. L., Arsenault, B. J., Després, J. P., Pibarot, P., & Tsimikas, S. (2015). Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. Journal of the American College of Cardiology, 66(11), 1236-1246. https://doi.org/10.1016/j.jacc.2015.07.020

Capoulade R, et al. Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. J Am Coll Cardiol. 2015 Sep 15;66(11):1236-1246. PubMed PMID: 26361154.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Oxidized Phospholipids, Lipoprotein(a), and Progression of Calcific Aortic Valve Stenosis. AU - Capoulade,Romain, AU - Chan,Kwan L, AU - Yeang,Calvin, AU - Mathieu,Patrick, AU - Bossé,Yohan, AU - Dumesnil,Jean G, AU - Tam,James W, AU - Teo,Koon K, AU - Mahmut,Ablajan, AU - Yang,Xiaohong, AU - Witztum,Joseph L, AU - Arsenault,Benoit J, AU - Després,Jean-Pierre, AU - Pibarot,Philippe, AU - Tsimikas,Sotirios, PY - 2015/04/01/received PY - 2015/06/30/revised PY - 2015/07/02/accepted PY - 2015/9/12/entrez PY - 2015/9/12/pubmed PY - 2015/12/15/medline KW - Doppler echocardiography KW - aortic valve replacement KW - lipoprotein KW - peak aortic jet velocity SP - 1236 EP - 1246 JF - Journal of the American College of Cardiology JO - J Am Coll Cardiol VL - 66 IS - 11 N2 - 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). SN - 1558-3597 UR - https://www.unboundmedicine.com/medline/citation/26361154/Oxidized_Phospholipids_Lipoprotein_a__and_Progression_of_Calcific_Aortic_Valve_Stenosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0735-1097(15)04465-4 DB - PRIME DP - Unbound Medicine ER -