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Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial.
JAMA Cardiol. 2018 12 01; 3(12):1212-1217.JC

Abstract

Importance

Several studies have reported an association of levels of lipoprotein(a) (Lp[a]) and the content of oxidized phospholipids on apolipoprotein B (OxPL-apoB) and apolipoprotein(a) (OxPL-apo[a]) with faster calcific aortic valve stenosis (CAVS) progression. However, whether this association is threshold or linear remains unclear.

Objective

To determine whether the plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) have a linear association with a faster rate of CAVS progression.

Design, Setting, and Participants

This secondary analysis of a randomized clinical trial tested the association of baseline plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) with the rate of CAVS progression. Participants were included from the ASTRONOMER (Effects of Rosuvastatin on Aortic Stenosis Progression) trial, a multicenter study conducted in 23 Canadian sites designed to test the effect of statin therapy (median follow-up, 3.5 years [interquartile range, 2.9-4.5 years]). Patients with mild to moderate CAVS defined by peak aortic jet velocity ranging from 2.5 to 4.0 m/s were recruited; those with peak aortic jet velocity of less than 2.5 m/s or with an indication for statin therapy were excluded. Data were collected from January 1, 2002, through December 31, 2005, and underwent ad hoc analysis from April 1 through September 1, 2018.

Interventions

After the randomization process, patients were followed up by means of echocardiography for 3 to 5 years.

Main Outcomes and Measures

Progression rate of CAVS as assessed by annualized progression of peak aortic jet velocity.

Results

In this cohort of 220 patients (60.0% male; mean [SD] age, 58 [13] years), a linear association was found between plasma levels of Lp(a) (odds ratio [OR] per 10-mg/dL increase, 1.10; 95% CI, 1.03-1.19; P = .006), OxPL-apoB (OR per 1-nM increase, 1.06; 95% CI, 1.01-1.12; P = .02), and OxPL-apo(a) (OR per 10-nM increase, 1.16; 95% CI, 1.05-1.27; P = .002) and faster CAVS progression, which is marked in younger patients (OR for Lp[a] level per 10-mg/dL increase, 1.19 [95% CI, 1.07-1.33; P = .002]; OR for OxPL-apoB level per 1-nM increase, 1.06 [95% CI, 1.02-1.17; P = .01]; and OR for OxPL-apo[a] level per 10-nM increase, 1.26 [95% CI, 1.10-1.45; P = .001]) and remained statistically significant after comprehensive multivariable adjustment (β coefficient, ≥ 0.25; SE, ≤ 0.004 [P ≤ .005]; OR, ≥1.10 [P ≤ .007]).

Conclusions and Relevance

This study demonstrates that the association of Lp(a) levels and its content in OxPL with faster CAVS progression is linear, reinforcing the concept that Lp(a) levels should be measured in patients with mild to moderate CAVS to enhance management and risk stratification.

Trial Registration

ClinicalTrials.gov Identifier: NCT00800800.

Authors+Show Affiliations

Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec City, Québec, Canada. L'institut du thorax, Institut National de la Santé et de la Recherche Medicale, Centre National de la Recherche Scientifique, Centre Hospitalier Universitaire Nantes, University of Nantes, Nantes, France.Vascular Medicine Program, University of California, San Diego, La Jolla.Ottawa Heart Institute, University of Ottawa, Ottawa, Ontario, Canada.Institut Universitaire de Cardiologie et de Pneumologie de Québec, Laval University, Québec City, Québec, Canada.Vascular Medicine Program, University of California, San Diego, La Jolla.

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

30476957

Citation

Capoulade, Romain, et al. "Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial." JAMA Cardiology, vol. 3, no. 12, 2018, pp. 1212-1217.
Capoulade R, Yeang C, Chan KL, et al. Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2018;3(12):1212-1217.
Capoulade, R., Yeang, C., Chan, K. L., Pibarot, P., & Tsimikas, S. (2018). Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiology, 3(12), 1212-1217. https://doi.org/10.1001/jamacardio.2018.3798
Capoulade R, et al. Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial. JAMA Cardiol. 2018 12 1;3(12):1212-1217. PubMed PMID: 30476957.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Mild to Moderate Aortic Valve Stenosis Progression With Higher Lipoprotein(a) and Oxidized Phospholipid Levels: Secondary Analysis of a Randomized Clinical Trial. AU - Capoulade,Romain, AU - Yeang,Calvin, AU - Chan,Kwan L, AU - Pibarot,Philippe, AU - Tsimikas,Sotirios, PY - 2018/11/27/pubmed PY - 2019/10/8/medline PY - 2018/11/27/entrez SP - 1212 EP - 1217 JF - JAMA cardiology JO - JAMA Cardiol VL - 3 IS - 12 N2 - Importance: Several studies have reported an association of levels of lipoprotein(a) (Lp[a]) and the content of oxidized phospholipids on apolipoprotein B (OxPL-apoB) and apolipoprotein(a) (OxPL-apo[a]) with faster calcific aortic valve stenosis (CAVS) progression. However, whether this association is threshold or linear remains unclear. Objective: To determine whether the plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) have a linear association with a faster rate of CAVS progression. Design, Setting, and Participants: This secondary analysis of a randomized clinical trial tested the association of baseline plasma levels of Lp(a), OxPL-apoB, and OxPL-apo(a) with the rate of CAVS progression. Participants were included from the ASTRONOMER (Effects of Rosuvastatin on Aortic Stenosis Progression) trial, a multicenter study conducted in 23 Canadian sites designed to test the effect of statin therapy (median follow-up, 3.5 years [interquartile range, 2.9-4.5 years]). Patients with mild to moderate CAVS defined by peak aortic jet velocity ranging from 2.5 to 4.0 m/s were recruited; those with peak aortic jet velocity of less than 2.5 m/s or with an indication for statin therapy were excluded. Data were collected from January 1, 2002, through December 31, 2005, and underwent ad hoc analysis from April 1 through September 1, 2018. Interventions: After the randomization process, patients were followed up by means of echocardiography for 3 to 5 years. Main Outcomes and Measures: Progression rate of CAVS as assessed by annualized progression of peak aortic jet velocity. Results: In this cohort of 220 patients (60.0% male; mean [SD] age, 58 [13] years), a linear association was found between plasma levels of Lp(a) (odds ratio [OR] per 10-mg/dL increase, 1.10; 95% CI, 1.03-1.19; P = .006), OxPL-apoB (OR per 1-nM increase, 1.06; 95% CI, 1.01-1.12; P = .02), and OxPL-apo(a) (OR per 10-nM increase, 1.16; 95% CI, 1.05-1.27; P = .002) and faster CAVS progression, which is marked in younger patients (OR for Lp[a] level per 10-mg/dL increase, 1.19 [95% CI, 1.07-1.33; P = .002]; OR for OxPL-apoB level per 1-nM increase, 1.06 [95% CI, 1.02-1.17; P = .01]; and OR for OxPL-apo[a] level per 10-nM increase, 1.26 [95% CI, 1.10-1.45; P = .001]) and remained statistically significant after comprehensive multivariable adjustment (β coefficient, ≥ 0.25; SE, ≤ 0.004 [P ≤ .005]; OR, ≥1.10 [P ≤ .007]). Conclusions and Relevance: This study demonstrates that the association of Lp(a) levels and its content in OxPL with faster CAVS progression is linear, reinforcing the concept that Lp(a) levels should be measured in patients with mild to moderate CAVS to enhance management and risk stratification. Trial Registration: ClinicalTrials.gov Identifier: NCT00800800. SN - 2380-6591 UR - https://www.unboundmedicine.com/medline/citation/30476957/Association_of_Mild_to_Moderate_Aortic_Valve_Stenosis_Progression_With_Higher_Lipoprotein_a__and_Oxidized_Phospholipid_Levels:_Secondary_Analysis_of_a_Randomized_Clinical_Trial_ L2 - https://jamanetwork.com/journals/jamacardiology/fullarticle/10.1001/jamacardio.2018.3798 DB - PRIME DP - Unbound Medicine ER -