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Cited by 417Cardiac Valve Diseases and TreatmentsAtherosclerosis and Cardiovascular DiseasesLipoproteins and Cardiovascular Health

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

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Capoulade, Romain, Chan, Kwan L., Yeang, Calvin, Mathieu, Patrick, Bossé, Yohan, Dumesnil, Jean G., Tam, James W., Teo, Koon K. +7 more·2015·Journal of the American College of Cardiology
DOI 10.1016/j.jacc.2015.07.020
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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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  • Clinical factors associated with faster stenosis progression include older age, female sex, severity of stenosis, degree of aortic valve calcification at diagnosis, smoking, hypertension, obesity, metabolic syndrome, secondary hyperparathyroidism, renal failure, elevated circulating Lp(a), and increased Lp-PLA2 activity.

    “The clinical factors associated with faster stenosis progression include older age, female sex, severity of the stenosis and degree of aortic valve calcification at diagnosis, smoking, hypertension, obesity, metabolic syndrome, secondary hyperparathyroidism, renal failure elevated circulating levels of Lp(a), and increased activity of Lp-PLA2 (also called lipoprotein–associated phospholipase A2)51”

    From Calcific aortic stenosis (2016) · cites this paper as [51]

    The Conclusions (page not supplied) report that elevated Lp(a) is associated with faster aortic stenosis progression, and the passage on Lp-PLA2 (indexed under Abstract; page not supplied) reports an association between its plasma level and faster progression in patients with mild stenosis. The paper does not establish the full list as factors associated with faster progression: it uses age, sex, hypertension, smoking, metabolic syndrome, baseline severity, calcification and creatinine as adjustment variables, rather than reporting each as a predictor. It also does not establish increased Lp-PLA2 activity specifically as a predictor. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Elevated plasma Lp(a) (>50 mg/dL; upper normal <30 mg/dL) is associated with twofold faster stenosis progression.

    “In particular, the presence of elevated plasma Lp(a) (>50 mg per dL; the upper normal limit is <30 mg per dL)) is associated with a twofold faster stenosis progression51.”

    From Calcific aortic stenosis (2016) · cites this paper as [51]

    The progression results (page unavailable) associate the top Lp(a) tertile (>58.5 mg/dL) with faster stenosis progression, but the measured rates were 0.26 versus 0.17 m/s/year—not twofold faster. The paper’s approximately twofold figure refers instead to the odds of being a rapid progressor. Our copy does not establish <30 mg/dL as an upper normal limit. (LLM, conf=0.91)

    Experimental — accuracy not yet measured

  • Circulating lipoprotein(a) and oxidized phospholipid levels are independently associated with faster progression of calcific aortic stenosis.

    “In addition, Capoulade and colleagues showed that circulating Lp(a) and Ox-PL levels were independently associated with faster progression of calcific AS51.”

    From Calcific aortic stenosis (2016) · cites this paper as [51]

  • Prior studies have linked ApoB to the onset and accelerated progression of CAVD.

    “prior studies have linked ApoB to the onset and accelerated progression of CAVD [38,39].”

    From Identifying novel drug targets for calcific aortic valve disease through Mendelian randomization (2025) · cites this paper as [38]

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Research works printed but not linked: 2

  1. [19]19. Mahmut A, Boulanger MC, El Husseini D, et al. Elevated expression of Lp-PLA2 in calcific aortic valve disease: implication for valve mineralization. J Am Coll Cardiol 2014;63:460-9.
  2. [42]42. Carabello BA, Paulus WJ. Aortic stenosis. Lancet 2009;373:956-66.

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Authors
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.
Affiliations
  • Institut universitaire de cardiologie et de pneumologie de Québec (CA)
  • Ottawa Heart Institute (CA)
  • University of California San Diego (US)
  • St. Boniface Hospital (CA)
  • McMaster University (CA)
Corresponding author
Tsimikas, Sotirios
ORCID
Venue
Journal of the American College of Cardiology
Publisher
Elsevier BV
Published
2015-09
Volume
66
Issue
11
Pages
1236-1246
ISSN
0735-1097 (ISSN-L)
DOI
10.1016/j.jacc.2015.07.020
OpenAlex
W1609565130
Cited by
417
References
45
Citations by year
2026: 26 · 2025: 49 · 2024: 37 · 2023: 37 · 2022: 52 · 2021: 30 · 2020: 40 · 2019: 47 · 2018: 26 · 2017: 38 · 2016: 32 · 2015: 3
FWCI
24.02
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of the American College of Cardiology (publishedVersion)
  • PubMed (publishedVersion)
  • Corpus Université Laval (Université Laval) (submittedVersion)
Funders
  • Abbott Laboratories
  • Eli Lilly and Company
  • Pfizer
  • AstraZeneca
  • GlaxoSmithKline
  • Sanofi
  • National Institutes of Health (HL055798, HL088093)
  • University of California, San Diego
  • Pfizer Canada
  • Eli Lilly Canada
  • Canadian Institutes of Health Research (MOP# 114997, MOP-245048, 114997, 245048)
  • National Heart, Lung, and Blood Institute (HL-055798, HL093767, R01HL093767, HL119828, P01HL055798, R01HL119828, HL-088093, P01HL088093)
Topics
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Valve Diseases and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Keywords
aortic stenosis, calcific aortic stenosis, lipoprotein(a), oxidized phospholipids, apolipoprotein B-100, disease progression, aortic jet velocity, aortic valve replacement, cardiovascular mortality, valve calcification, Lp(a)-lowering therapy
MeSH terms
Adult, Aged, Aortic Valve, Aortic Valve Stenosis, Calcinosis, Death, Female, Humans, Male, Middle Aged, Oxidation-Reduction, Phospholipids, Ultrasonography, Biomarkers, Lipoprotein(a), Disease Progression

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