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Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease
Author(s) -
Nsaibia M. J.,
Mahmut A.,
Boulanger M.C.,
Arsenault B. J.,
Bouchareb R.,
Simard S.,
Witztum J. L.,
Clavel M.A.,
Pibarot P.,
Bossé Y.,
Tsimikas S.,
Mathieu P.
Publication year - 2016
Publication title -
journal of internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.625
H-Index - 160
eISSN - 1365-2796
pISSN - 0954-6820
DOI - 10.1111/joim.12519
Subject(s) - autotaxin , medicine , lipoprotein(a) , apolipoprotein b , cardiology , coronary artery disease , lipoprotein , stenosis , endocrinology , diabetes mellitus , cholesterol , receptor , lysophosphatidic acid
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 (Ox PL ‐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 Ox PL ‐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 Ox PL ‐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 Ox PL ‐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 Ox PL ‐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 .