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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.
J Intern Med. 2016 11; 280(5):509-517.JI

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.

Authors+Show Affiliations

Laboratory of Cardiovascular Pathobiology Quebec Heart and Lung Institute/Research Center, Department of Surgery, Quebec, Canada.Laboratory of Cardiovascular Pathobiology Quebec Heart and Lung Institute/Research Center, Department of Surgery, Quebec, Canada.Laboratory of Cardiovascular Pathobiology Quebec Heart and Lung Institute/Research Center, Department of Surgery, Quebec, Canada.Department of Medicine, Laval University, Quebec, Canada.Laboratory of Cardiovascular Pathobiology Quebec Heart and Lung Institute/Research Center, Department of Surgery, Quebec, Canada.Statistical Consulting Service Unit at the Quebec Heart and Lung Institute/Research Center, Laval University, Quebec, Canada.University of California San Diego, La Jolla, CA, USA.Department of Medicine, Laval University, Quebec, Canada.Department of Medicine, Laval University, Quebec, Canada.Department of Molecular Medicine, Laval University, Quebec, Canada.University of California San Diego, La Jolla, CA, USA.Laboratory of Cardiovascular Pathobiology Quebec Heart and Lung Institute/Research Center, Department of Surgery, Quebec, Canada. patrick.mathieu@chg.ulaval.ca.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

27237700

Citation

Nsaibia, M J., et al. "Autotaxin Interacts With Lipoprotein(a) and Oxidized Phospholipids in Predicting the Risk of Calcific Aortic Valve Stenosis in Patients With Coronary Artery Disease." Journal of Internal Medicine, vol. 280, no. 5, 2016, pp. 509-517.
Nsaibia MJ, Mahmut A, Boulanger MC, et al. Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease. J Intern Med. 2016;280(5):509-517.
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. (2016). Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease. Journal of Internal Medicine, 280(5), 509-517. https://doi.org/10.1111/joim.12519
Nsaibia MJ, et al. Autotaxin Interacts With Lipoprotein(a) and Oxidized Phospholipids in Predicting the Risk of Calcific Aortic Valve Stenosis in Patients With Coronary Artery Disease. J Intern Med. 2016;280(5):509-517. PubMed PMID: 27237700.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease. AU - Nsaibia,M J, AU - Mahmut,A, AU - Boulanger,M-C, AU - Arsenault,B J, AU - Bouchareb,R, AU - Simard,S, AU - Witztum,J L, AU - Clavel,M-A, AU - Pibarot,P, AU - Bossé,Y, AU - Tsimikas,S, AU - Mathieu,P, Y1 - 2016/05/30/ PY - 2016/10/21/pubmed PY - 2017/6/15/medline PY - 2016/5/31/entrez KW - autotaxin KW - calcific aortic valve disease KW - calcific aortic valve stenosis KW - lipoprotein(a) KW - oxidized phospholipids SP - 509 EP - 517 JF - Journal of internal medicine JO - J Intern Med VL - 280 IS - 5 N2 - 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. SN - 1365-2796 UR - https://www.unboundmedicine.com/medline/citation/27237700/Autotaxin_interacts_with_lipoprotein_a__and_oxidized_phospholipids_in_predicting_the_risk_of_calcific_aortic_valve_stenosis_in_patients_with_coronary_artery_disease_ L2 - https://doi.org/10.1111/joim.12519 DB - PRIME DP - Unbound Medicine ER -