Physicians' Academy for Cardiovascular Education

High level of ApoCIII-Lp(a) complexes together with high Lp(a) or OxPL predicts rapid progression of aortic stenosis

ApoCIII-Lp(a) complexes in conjunction with Lp(a)-OxPL predict rapid progression of aortic stenosis

Literature - Capoulade R, Torzewski M, Mayr M et al. - Heart 2020, doi:10.1136/heartjnl-2019-315840

Introduction and methods

Risk factors for aortic stenosis (AS) include age, hypertension, metabolic syndrome and elevated LDL-c levels [1]. Modest increases in LDL-c have, however, not shown difference in progression rate of AS of need for aortic valve replacement (AVR) in patients with AS [2].

Elevated lipoprotein(a) [Lp(a)] levels in individuals with SNPs in the LPA gene are associated with aortic valve calcification and AS [3-5]. Also, oxidized phospholipids (OxPL), which are associated with apoB-100 and Lp(a), are associated with AS, as potential causal mediators [6-8]. Autotaxin (ATX) mass and activity generates pro-calcifying lysophosphatidic acid from breakdown products of OxPL. ATX has also been suggested to be associated with AS [7,9,10]. High levels of ApoC-III are associated with high levels of triglycerides, and high triglycerides levels are observed in individuals with metabolic syndrome. Perhaps measures like Lp(a), OxPL, ATX and ApoC-III can predict the progression of AS, as others are suboptimal.

Assays to measure complexes of ApoC-III on Lp(a) [ApoCIII-Lp(a)] [11] were applied in samples of patients in the AS Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) trial to examine the role of ApoCIII-Lp(a) in the progression of AS and need for AVR. In addition, ATX mass on Lp(a)[ATX-Lp(a)] and apoB [ATX-apoB] were measured by high-throughput ELISAs.

Outcomes in this study were assessed in 218 patients of the ASTRONOMER trial. Primary outcome of this study was progression rate of AS measured by echocardiography as annualized changes in peak aortic jet velocity (Vpeak). Secondary outcome was clinical events, a composite of AVR or cardiac death. Also, presence of ApoCIII was measured in surgically explanted aortic valves (of 68 patients). Median follow-up of this echocardiographic study was 3.5 years (2.9-4.5).

Main results


This study using samples from patients in the ASTRONOMER trial showed that ApoCIII is present on Lp(a) and in aortic valves. Highest levels of ApoCIII-Lp(a) complexes and highest levels of Lp(a) or highest levels of ApoCIIII-Lp(a) complexes and highest levels of OxPL are predictors of patients with rapid progression of AS. Highest levels of ApoCIII-Lp(a) complexes and highest levels of Lp(a) are a predictor of patients with highest risk of AS-related clinical events. These markers can be used to identify patients with fastest rate of AS progression and stratify risk in patients with AS.


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