Personne : Simard, Sébastien
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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
2020-05-30, Simard, Sébastien, Bouchareb, Rihab, Arsenault, Benoit, Boulanger, Marie-Chloé, Bossé, Yohan, Mahmut, Ablajan, Witztum, Joseph L., Pibarot, Philippe, Clavel, Marie-Annick, Nsaibia, Mohamed Jalloul, Mathieu, Patrick, Tsimikas, Sotirios
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.
Temporal relationship between dysfunctional beliefs, self-efficacy and panic apprehension in the treatment of panic disorder with agoraphobia
2006-12-08, Simard, Sébastien, Vallières, Annie, Ivers, Hans, Gauthier, Janel G., Nouwen, Arie, Bouchard, Stéphane, Fournier, Thomas
The aim of this study is to assess if changes in dysfunctional beliefs and self-efficacy precede changes in panic apprehension in the treatment of panic disorder with agoraphobia. Subjects participated in a larger study comparing the effectiveness of cognitive restructuring and exposure. Four variables were measured: (a) the strength of each subject's main belief toward the consequence of a panic attack; (b) perceived self-efficacy to control a panic attack in the presence of panicogenic body sensations; (c) perceived self-efficacy to control a panic attack in the presence of panicogenic thoughts; and (d) the level of panic apprehension of a panic attack. Variables were recorded daily on a “0” to “100” scale using category partitioning. Multivariate time series analysis and “causality testing” showed that, for all participants, cognitive changes preceded changes in the level of panic apprehension. Important individual differences were observed in the contribution of each variable to the prediction of change in panic apprehension. Changes in apprehension were preceded by changes in belief in three cases, by changes in self-efficacy in six cases, and by changes in both belief and self-efficacy in the remaining three cases. This pattern was observed in participants in the exposure condition as well as those in the cognitive restructuring condition. These results provide more empirical support to the hypothesis that cognitive changes precede improvement. They also underlie the importance of individual differences in the process of change. Finally, this study does not support the hypothesis that exposure and cognitive restructuring operate through different mechanisms, namely a behavioral one and a cognitive one.