Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease

Abstract

Background

Studies have shown that lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, is causally related to calcific aortic valve stenosis (CAVS). Recently, we found that Lp(a) mediates the development of CAVS through autotaxin (ATX).

Objective

To determine the predictive value of circulating ATX mass and activity for CAVS.

Methods

We performed a case-control study in 300 patients with coronary artery disease (CAD). Patients with CAVS plus CAD (cases, n = 150) were age- and gender-matched (1 : 1) to patients with CAD without aortic valve disease (controls, n = 150). ATX mass and enzymatic activity and levels of Lp(a) and oxidized phospholipids on apolipoprotein B-100 (OxPL-apoB) were determined in fasting plasma samples.

Results

Compared to patients with CAD alone, ATX mass (P < 0.0001), ATX activity (P = 0.05), Lp(a) (P = 0.003) and OxPL-apoB (P < 0.0001) levels were elevated in those with CAVS. After adjustment, we found that ATX mass (OR 1.06, 95% CI 1.03–1.10 per 10 ng mL⁻¹, P = 0.001) and ATX activity (OR 1.57, 95% CI 1.14–2.17 per 10 RFU min⁻¹, P = 0.005) were independently associated with CAVS. ATX activity interacted with Lp(a) (P = 0.004) and OxPL-apoB (P = 0.001) on CAVS risk. After adjustment, compared to patients with low ATX activity (dichotomized at the median value) and low Lp(a) (<50 mg dL⁻¹) or OxPL-apoB (<2.02 nmol L⁻¹, median) levels (referent), patients with both higher ATX activity (≥84 RFU min⁻¹) and Lp(a) (≥50 mg dL⁻¹) (OR 3.46, 95% CI 1.40–8.58, P = 0.007) or OxPL-apoB (≥2.02 nmol L⁻¹, median) (OR 5.48, 95% CI 2.45–12.27, P < 0.0001) had an elevated risk of CAVS.

Conclusion

Autotaxin is a novel and independent predictor of CAVS in patients with CAD.

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