Linear Association Between Plasma Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression

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Lipoprotein(a) levels should be measured in mild to moderate calcific aortic valve stenosis to improve patient risk stratification.
Lipoprotein(a) levels should be measured in mild to moderate calcific aortic valve stenosis to improve patient risk stratification.

Plasma levels of lipoprotein(a) (Lp[a]), oxidized phospholipids on apolipoprotein B (OxPL-apoB), and apolipoprotein(a) (OxPL-apo[a]) may predict progression of mild to moderate calcific aortic valve stenosis (CAVS), according to a study published in JAMA Cardiology.

Patients with mild to moderate CAVS who participated in the multicenter Canadian ASTRONOMER (Effects of Rosuvastatin on Aortic Stenosis Progression, ClinicalTrials.gov identifier: NCT00800800) trial and who had a median follow-up of 3.5 years were enrolled (N=220).

Study participants enrolled had a peak aortic jet velocity between 2.5 and 4.0 m/second. Investigators from the ASTRONOMER trial randomly assigned patients to either 40 mg rosuvastatin calcium (n=112) or placebo (n=108) and followed them for 3 5 years.

The researchers measured levels of OxPL-apoB, OxPL-apo(a), and Lp(a), and CAVS severity with Vpeak Doppler echocardiographic index. In addition, annualized progression of peak aortic jet velocity was used to evaluate the progression rate of CAVS.

The investigators found significant linear associations between faster CAVS progression and 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).

Younger patients had the most noticeable associations between Lp[a] (OR for Lp[a] level per 10-mg/dL increase, 1.19; 95% CI, 1.07-1.33; P =.002), OxPL-apoB (OR for OxPL-apoB level per 1-nM increase, 1.06; 95% CI, 1.02-1.17; P =.01), and OxPL-apo[a] (OR for OxPL-apo[a] level per 10-nM increase, 1.26; 95% CI, 1.10-1.45; P =.001) plasma levels and faster CAVS progression.

Statistical significance remained stable for Lp(a) (P =.001), OxPL-apoB (P =.007), and OxPL-apo(a) (P =.001) in the multivariable analysis.

Patients were relatively young (mean age, 58 years) and had only mild to moderate AS, which may limit the study's generalizability to older patients with severe AS.

"By documenting the linear association of lipoprotein(a) and its content of oxidized phospholipids with faster progression of calcific aortic stenosis," the researchers wrote, "this study has pathophysiological and clinical implications for these patients."

Reference

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 [published online November 21, 2018]. JAMA Cardiol. doi: 10.1001/jamacardio.2018.3798

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