Is the association of increased lipoprotein(a) and oxidized phospholipid levels with a faster rate of calcific aortic valve stenosis progression a linear or a threshold association?
In a secondary analysis of the ASTRONOMER trial following up a cohort of 220 patients with mild to moderate aortic stenosis, a significant linear association was found between plasma levels of lipoprotein(a) and oxidized phospholipids on apolipoprotein B and apolipoprotein(a) and a faster rate of aortic stenosis progression.
By documenting the linear association of lipoprotein(a) and its content of oxidized phospholipids with faster progression of calcific aortic stenosis, this study has pathophysiological and clinical implications for these patients.
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.
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.
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.
In this cohort of 220 patients (60.0% male; mean [SD] age, 58  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.
ClinicalTrials.gov Identifier: NCT00800800
Capoulade R, Yeang C, Chan KL, Pibarot P, Tsimikas S. 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. doi:https://doi.org/10.1001/jamacardio.2018.3798
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