Daniel Gaudet

Université de Montréal, Montréal, Quebec, Canada

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Publications (335)1825.13 Total impact

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    ABSTRACT: Background Familial chylomicronemia syndrome (FCS) is a rare lipid disease caused by complete lipoprotein lipase (LPL) deficiency resulting in fasting chylomicronemia and severe hypertriglyceridemia. Inhibition of diacylglycerol acyltransferase 1 (DGAT1), which mediates chylomicron triglyceride (TG) synthesis, is an attractive strategy to reduce TG levels in FCS. In this study we assessed the safety, tolerability and TG-lowering efficacy of the DGAT1 inhibitor pradigastat in patients with FCS. Methods Six FCS patients were enrolled in an open-label clinical study. Following a 1-week very low fat diet run-in period patients underwent baseline lipid assessments, including a low fat meal tolerance test. Patients then underwent three consecutive 21 day treatment periods (pradigastat at 20, 40 & 10 mg, respectively). Treatment periods were separated by washout periods of ≥4 weeks. Fasting TG levels were assessed weekly through the treatment periods. Postprandial TGs, ApoB48 and lipoprotein lipid content were also monitored. Results Following once daily oral dosing, steady-state exposure was reached by Day 14. There was an approximately dose proportional increase in pradigastat exposure at studied doses. Pradigastat was associated with a 41% (20 mg) and 70% (40 mg) reduction in fasting triglyceride over 21 days of treatment. The reduction in fasting TG was almost entirely accounted for by a reduction in chylomicron TG. Pradigastat treatment also led to substantial reductions in postprandial TG as well as apo48 (both fasting and postprandial). Pradigastat was safe and well tolerated, with only mild, transient gastrointestinal adverse events. Conclusion The novel DGAT1 inhibitor pradigastat substantially reduces plasma TG levels in FCS patients, and may be a promising new treatment for this orphan disease. Trial registration ClinicalTrials.gov identifier NCT01146522.
    Lipids in Health and Disease 12/2015; 14(1). DOI:10.1186/s12944-015-0006-5 · 2.31 Impact Factor
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    ABSTRACT: Despite current standard-of-care, many patients at high cardiovascular disease (CVD) risk still have elevated low-density lipoprotein cholesterol (LDL-C). Alirocumab is a fully human monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9). To compare LDL-C-lowering efficacy of adding alirocumab vs other common lipid-lowering strategies. Design, Patients, Interventions: Patients (n=355) with CVD and LDL-C levels ≥70 mg/dL, or CVD risk factors and LDL-C ≥100 mg/dL, on baseline atorvastatin 20 or 40 mg, were randomized to: (1) add-on alirocumab 75 mg every 2 weeks (Q2W) subcutaneously; (2) add-on ezetimibe 10 mg/day; (3) double atorvastatin dose; (4) for atorvastatin 40 mg regimen only, switch to rosuvastatin 40 mg. For patients not achieving protocol-defined LDL-C goals, alirocumab dose was increased (blinded) at week 12 to 150 mg Q2W. Primary endpoint was % change in calculated LDL-C from baseline to 24 weeks (intent-to-treat). Among atorvastatin 20 and 40 mg regimens respectively, add-on alirocumab reduced LDL-C levels by 44.1% and 54.0% (p<0.001 vs all comparators); add-on ezetimibe, 20.5% and 22.6%; doubling of atorvastatin dose, 5.0% and 4.8%; and switching atorvastatin 40 mg to rosuvastatin 40 mg, 21.4%. Most alirocumab-treated patients (87.2% and 84.6%) achieved their LDL-C goals. Most alirocumab-treated patients (86%) maintained their 75 mg Q2W regimen. Treatment-emergent adverse events occurred in 65.4% of alirocumab patients, vs 64.4% ezetimibe and 63.8% double atorvastatin/switch to rosuvastatin (data pooled). Adding alirocumab to atorvastatin provided significantly greater LDL-C reductions vs adding ezetimibe, doubling atorvastatin dose, or switching to rosuvastatin, and enabled greater LDL-C goal achievement.
    The Journal of Clinical Endocrinology and Metabolism 06/2015; DOI:10.1210/jc.2015-1520 · 6.31 Impact Factor
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    ABSTRACT: Background and objectives • Homozygous familial hypercholesterolemia (HoFH) is a rare genetic condition characterized by markedly elevated low-density lipoprotein cholesterol (LDL-C) levels, inadequate response to conventional drug therapy and premature-onset cardiovascular disease.1 • HoFH is most commonly caused by the occurrence of two LDL–receptor (LDL-R) gene (LDLR) mutations but can also be caused by mutations in other genes which directly or indirectly affect the LDL-C/LDL-R pathway, including the genes encoding apolipoprotein B (APOB) and proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDL-receptor adapter protein 1 (LDLRAP1) (Figure 1).1 • The genotype and clinical phenotype of HoFH patients varies, and depending on the type of mutations, patients can present with untreated LDL-C levels as low as 4.4 mmol/L.1, 2 • To further explore the variability of HoFH, we examined the phenotype, genotype and baseline-treated LDL-C levels in a cohort of patients with genetically confirmed HoFH enrolled in a clinical trial.
    ISA 2015 - 17th International Symposium on Atherosclerosis, Netherlands, Amsterdam; 05/2015
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    ABSTRACT: (EN): The invention relates to traceable metallic products, methods of uses and methods of making same. The metallic products may be made traceable for integrity purposes, identification purposes, counterfeit avoidance and the like. The invention also relates to metallic supports for nanostorage of various compounds and samples. (FR): L'invention concerne des produits métalliques traçables, des procédés d'utilisation et des procédés de fabrication de ceuxci. Ces produits métalliques peuvent être rendus traçables à des fins d'intégrité, d'identification, de lutte contre la contrefaçon et analogue. L'invention concerne également des supports métalliques pour le nanostockage de divers composés et échantillons.
    Ref. No: WO/2015/054778, Year: 04/2015
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    ABSTRACT: Objective: Hypertension and osteoporosis are age-related health risks differentially expressed in men and women. Here we have analysed their prevalence in a randomly selected cross-sectional cohort [CARTaGENE (CaG) of Quebec, Canada and explored their existing relationships along with height, arterial stiffness and bone fractures. Methods: The principal cohort CaG included 20 007 individuals of age 40–70 years. Participants were subjected to an extensive phenotyping and a questionnaire of medical history and habits. Results: We determined the differences in height of participants and their relation to hypertension status and sex in this cohort and validated it in two other cohorts (The Canadian Heart Health Study and a family cohort from the Saguenay Lac Saint-Jean, a region of Quebec). In all three cohorts, we found that at younger age individuals with hypertension are taller than normotensive individuals, but they have a shorter stature at an older age compared with normotensive individuals. In CaG, we observed that hypertension, low bone mineral density (BMD) and arterial stiffness are strongly associated with height when adjusted for antihypertensive medications (P < 0.0001). Fractures are the net outcome of low BMD, and a significant association is observed (odds ratio = 2.34, confidence interval = 2.12–2.57); this relation was stronger in hypertensive individuals compared with normotensive individuals particularly in younger hypertensive individuals. In addition, we observed that increased arterial stiffness was significantly correlated with a low BMD in both men and women at all ages. Conclusion: Shorter stature in elderly, low BMD and fractures correlated with increased arterial stiffness and hypertension. We propose that hypertension and osteoporosis share components of accelerated aging.
    Journal of Hypertension 04/2015; 33(4):727-735. DOI:10.1097/HJH.0000000000000475 · 4.22 Impact Factor
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    ABSTRACT: Objective Lomitapide (a microsomal triglyceride transfer protein inhibitor) is an adjunctive treatment for homozygous familial hypercholesterolaemia (HoFH), a rare genetic condition characterised by elevated low-density lipoprotein-cholesterol (LDL-C), and premature, severe, accelerated atherosclerosis. Standard of care for HoFH includes lipid-lowering drugs and lipoprotein apheresis. We conducted a post-hoc analysis using data from a pivotal Phase 3 study to assess whether concomitant apheresis affected the lipid-lowering efficacy of lomitapide Methods Existing lipid-lowering therapy, including apheresis, was to remain stable from Week –6 to Week 26. Lomitapide dose was escalated on the basis of individual safety/tolerability from 5 mg to a maximum of 60 mg a day. The primary endpoint was mean percent change in LDL-C from baseline to Week 26 (efficacy phase), after which patients remained on lomitapide through Week 78 for safety assessment and further evaluation of efficacy. During this latter period, apheresis could be adjusted. We analysed the potential impact of apheresis on LDL-C reductions in patients receiving lomitapide Results Of the 29 patients that entered the efficacy phase, 18 (62%) were receiving apheresis at baseline. Twenty-three patients (13 receiving apheresis) completed the Week-26 evaluation. Of the six patients who discontinued in the first 26 weeks, five were receiving apheresis. There were no significant differences in percent change from baseline of LDL-C at Week 26 in patients treated (–48%) and not treated (–55%) with apheresis (p=0.545). Lp(a) levels did not change in either group Conclusion The LDL-C lowering efficacy of lomitapide is independent of lipoprotein apheresis
    Atherosclerosis 03/2015; 240(2). DOI:10.1016/j.atherosclerosis.2015.03.014 · 3.97 Impact Factor
  • Journal of the American College of Cardiology 03/2015; 65(10):A1370. DOI:10.1016/S0735-1097(15)61370-5 · 15.34 Impact Factor
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    ABSTRACT: To assess whether DNA methylation is associated with coronary artery disease (CAD). An epigenome-wide analysis has been performed on leucocytes from familial hypercholesterolemic (FH) men with (n = 6) or without CAD (n = 6). The results were replicated in an extended sample of FH men (n = 61) and in non-FH men (n = 100) for two of the top differentially methylated loci. FH men with CAD had significantly more hypomethylated and hypermethylated loci and showed less DNA methylation level variability compared with men without CAD (p < 0.001). Moreover, COL14A1 and MMP9 DNA methylation levels were associated with CAD, age of onset of CAD or CAD risk factors. These results suggest that epigenome-wide changes are associated with CAD occurrence in men.
    Epigenomics 02/2015; 7(1):17-34. DOI:10.2217/epi.14.64 · 5.22 Impact Factor
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    ABSTRACT: Patients with homozygous familial hypercholesterolemia (HoFH) are at extremely elevated risk for early cardiovascular disease because of exposure to elevated low-density lipoprotein cholesterol (LDL-C) plasma levels from birth. Lowering LDL-C by statin therapy is the cornerstone for cardiovascular disease prevention, but the residual risk in HoFH remains high, emphasizing the need for additional therapies. In the present study, we evaluated the effect of serial infusions with CER-001, a recombinant human apolipoprotein A-I (apoA-I)-containing high-density lipoprotein-mimetic particle, on carotid artery wall dimensions in patients with HoFH. Twenty-three patients (mean age 39.4 ± 13.5 years, mean LDL-C 214.2 ± 81.5 mg/dL) with genetically confirmed homozygosity or compound heterozygosity for LDLR, APOB, PCSK9, or LDLRAP1 mutations received 12 biweekly infusions with CER-001 (8 mg/kg). Before and 1 hour after the first infusion, lipid values were measured. Magnetic resonance imaging (3-T magnetic resonance imaging) scans of the carotid arteries were acquired at baseline and after 24 weeks to assess changes in artery wall dimensions. After CER-001 infusion, apoA-I increased from 114.8 ± 20.7 mg/dL to 129.3 ± 23.0 mg/dL. After 24 weeks, mean vessel wall area (primary end point) decreased from 17.23 to 16.75 mm(2) (P = .008). A trend toward reduction of mean vessel wall thickness was observed (0.75 mm at baseline and 0.74 mm at follow-up, P = .0835). In HoFH, 12 biweekly infusions with an apoA-I-containing high-density lipoprotein-mimetic particle resulted in a significant reduction in carotid mean vessel wall area, implying that CER-001 may reverse atherogenic changes in the arterial wall on top of maximal low-density lipoprotein-lowering therapy. This finding supports further clinical evaluation of apoA-I-containing particles in patients with HoFH. Copyright © 2015 Mosby, Inc. All rights reserved.
    American heart journal 01/2015; 169(5). DOI:10.1016/j.ahj.2015.01.008 · 4.56 Impact Factor
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    ABSTRACT: Adolescents who exhibit exaggerated blood pressure (BP) reactivity to physical and mental challenges are at increased risk of developing hypertension in adulthood. BP at rest and in response to challenges is higher in males than females, beginning in early adolescence. CYP17A1 is one of the well-established gene loci of adult hypertension. Here, we investigated whether this gene locus is associated with elevated BP at rest and in response to physical (active standing) and mental (math stress) challenges in adolescence. We studied 496 male and 532 female adolescents (age 12-18 years) who were recruited from a genetic founder population. Our results showed that the variant of CYP17A1 rs10786718 was associated with enhanced BP reactivity to the mental but not physical challenge and in males but not females. In males, BP increase in response to math stress was higher in major versus minor allele homozygotes by 7.6 mm Hg (P = 8.3 × 10(-6)). Resting BP was not associated with the CYP17A1 variant in either sex. These results suggest that, in adolescent males but not females, CYP17A1 enhances BP reactivity to mental stress. Whether this effect contributes to the higher prevalence of hypertension in males than females later in life remains to be determined.
    01/2015; 2015:734586. DOI:10.1155/2015/734586
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    ABSTRACT: Objectives: Homozygous familial hypercholesterolemia (HoFH) is a rare genetic disease characterized by markedly elevated LDL-C levels, limited response to conventional lipid-lowering therapies, and high risk of premature CVD. Severe atherosclerosis, believed related to LDL-C levels, may be evident by the second decade of life. Clinicians have traditionally identified HoFH based upon LDL-C levels: untreated >500mg/dL or treated ≥300mg/dL. Recent studies suggest that the clinical presentation of HoFH may be more variable. We examined baseline treated LDL-C levels in a cohort of patients with genetically confirmed HoFH to assess the relevance of traditional identification. Methods: Baseline characteristics of 29 HoFH patients from a multinational Phase 3 study were collected. All subjects were ≥18 years and met the diagnosis of HoFH based on: untreated TC >500 mg/dL and both parents with documented untreated TC >250mg/dL; documented genetic mutations of genes known to affect LDLR functionality; or skin fibroblast LDLR activity <20% normal. Results: All patients had confirmed mutations in both alleles of LDLR (n=28) or LDLRAP1 (n=1) gene. Age ranged from 18-55 years; 93% of patients had a history of CVD, 35% had undergone CABG, and 10% each had undergone coronary angioplasty, aortic valve replacement, or mitral valve replacement/repair. Patients were receiving statins (93%; 76% with ezetimibe) and apheresis (62%). Treated LDL-C levels ranged from 152-564mg/dL; 38% had LDL-C <300mg/dL and 14% <200mg/dL (Table). There was no difference between levels of subjects receiving apheresis treatment or not. Conclusion: Contrary to conventional viewpoints, and consistent with recent studies, this cohort of patients provides further evidence of the heterogeneity of treated LDL-C values in genetically defined HoFH patients. Diagnosis of HoFH should not be excluded based on treated levels <300 mg/dL, but must also include other supportive clinical or genetic evidence.
    The 2nd World Congress of Clinical Lipidology, Vienna, Austria; 12/2014
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    ABSTRACT: The familial chylomicronemia syndrome is a genetic disorder characterized by severe hypertriglyceridemia and recurrent pancreatitis due to a deficiency in lipoprotein lipase (LPL). Currently, there are no effective therapies except for extreme restriction in the consumption of dietary fat. Apolipoprotein C-III (APOC3) is known to inhibit LPL, although there is also evidence that APOC3 increases the level of plasma triglycerides through an LPL-independent mechanism. We administered an inhibitor of APOC3 messenger RNA (mRNA), called ISIS 304801, to treat three patients with the familial chylomicronemia syndrome and triglyceride levels ranging from 1406 to 2083 mg per deciliter (15.9 to 23.5 mmol per liter). After 13 weeks of study-drug administration, plasma APOC3 levels were reduced by 71 to 90% and triglyceride levels by 56 to 86%. During the study, all patients had a triglyceride level of less than 500 mg per deciliter (5.7 mmol per liter) with treatment. These data support the role of APOC3 as a key regulator of LPL-independent pathways of triglyceride metabolism.
    New England Journal of Medicine 12/2014; 371(23):2200-6. DOI:10.1056/NEJMoa1400284 · 54.42 Impact Factor
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    ABSTRACT: Familial hypercholesterolemia (FH) is the most common genetic disorder causing premature cardiovascular disease and death. Heterozygous FH conservatively affects approximately 1:500 Canadians, and the more serious homozygous form affects approximately 1:1,000,000 Canadians, although these numbers might be underestimated. Of approximately 83,500 Canadians estimated to have FH, most are undiagnosed, which represents a simultaneous public health deficit and opportunity, because early treatment of heterozygous FH can normalize life expectancy. Diagnostic algorithms for FH incorporate increased plasma low-density lipoprotein cholesterol, pathognomonic clinical features, and family history of early cardiovascular disease and hyperlipidemia. DNA-based detection of causative mutations in FH-related genes can help with diagnosis. Maximizing diagnosis and treatment of FH in Canada will involve a multipronged approach, including: (1) increasing awareness of FH among health care providers and patients; (2) creating a national registry for FH individuals; (3) setting standards for screening, including cascade screening in affected families; (4) ensuring availability of standard-of-care therapies, in particular optimization of plasma low-density lipoprotein cholesterol levels and timely access to future validated therapies; (5) promoting patient-based support and advocacy groups; and (6) forming alliances with international colleagues, resources, and initiatives that focus on FH. This document aims to raise awareness of FH nationally, and to mobilize knowledge translation, patient support, and availability of treatment and health care resources for this underrecognized, but important medical condition. Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
    The Canadian journal of cardiology 12/2014; 30(12):1471-81. DOI:10.1016/j.cjca.2014.09.028 · 3.94 Impact Factor
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    ABSTRACT: This paper provides an overview of the Saguenay Youth Study (SYS) and its parental arm. The overarching goal of this effort is to develop trans-generational models of developmental cascades contributing to the emergence of common chronic disorders, such as depression, addictions, dementia and cardio-metabolic diseases. Over the past 10 years, we have acquired detailed brain and cardio-metabolic phenotypes, and genome-wide genotypes, in 1029 adolescents recruited in a population with a known genetic founder effect. At present, we are extending this dataset to acquire comparable phenotypes and genotypes in the biological parents of these individuals. After providing conceptual background for this work (transactions across time, systems and organs), we describe briefly the tools employed in the adolescent arm of this cohort and highlight some of the initial accomplishments. We then outline in detail the phenotyping protocol used to acquire comparable data in the parents.
    Developmental Cognitive Neuroscience 10/2014; 11. DOI:10.1016/j.dcn.2014.10.003 · 3.71 Impact Factor
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    ABSTRACT: Prenatal exposure to maternal cigarette smoking (prenatal smoke exposure) had been associated with altered DNA methylation (DNAm) at birth.
    Environmental Health Perspectives 10/2014; DOI:10.1289/ehp.1408614 · 7.03 Impact Factor
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    ABSTRACT: Background Heterozygous familial hypercholesterolaemia is characterised by low cellular uptake of LDL cholesterol, increased plasma LDL cholesterol concentrations, and premature cardiovascular disease. Despite intensive statin therapy, with or without ezetimibe, many patients are unable to achieve recommended target levels of LDL cholesterol. We investigated the effect of PCSK9 inhibition with evolocumab (AMG 145) on LDL cholesterol in patients with this disorder. Methods This multicentre, randomised, double-blind, placebo-controlled trial was undertaken at 39 sites (most of which were specialised lipid clinics, mainly attached to academic institutions) in Australia, Asia, Europe, New Zealand, North America, and South Africa between Feb 7 and Dec 19, 2013. 331 eligible patients (18–80 years of age), who met clinical criteria for heterozygous familial hypercholesterolaemia and were on stable lipid-lowering therapy for at least 4 weeks, with a fasting LDL cholesterol concentration of 2·6 mmol/L or higher, were randomly allocated in a 2:2:1:1 ratio to receive subcutaneous evolocumab 140 mg every 2 weeks, evolocumab 420 mg monthly, or subcutaneous placebo every 2 weeks or monthly for 12 weeks. Randomisation was computer generated by the study sponsor, implemented by a computerised voice interactive system, and stratified by LDL cholesterol concentration at screening (higher or lower than 4·1 mmol/L) and by baseline ezetimibe use (yes/no). Patients, study personnel, investigators, and Amgen study staff were masked to treatment assignments within dosing frequency groups. The coprimary endpoints were percentage change from baseline in LDL cholesterol at week 12 and at the mean of weeks 10 and 12, analysed by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01763918. Findings Of 415 screened patients, 331 were eligible and were randomly assigned to the four treatment groups: evolocumab 140 mg every 2 weeks (n=111), evolocumab 420 mg monthly (n=110), placebo every 2 weeks (n=55), or placebo monthly (n=55). 329 patients received at least one dose of study drug. Compared with placebo, evolocumab at both dosing schedules led to a significant reduction in mean LDL cholesterol at week 12 (every-2-weeks dose: 59·2% reduction [95% CI 53·4–65·1], monthly dose: 61·3% reduction [53·6–69·0]; both p<0·0001) and at the mean of weeks 10 and 12 (60·2% reduction [95% CI 54·5–65·8] and 65·6% reduction [59·8–71·3]; both p<0·0001). Evolocumab was well tolerated, with rates of adverse events similar to placebo. The most common adverse events occurring more frequently in the evolocumab-treated patients than in the placebo groups were nasopharyngitis (in 19 patients [9%] vs five [5%] in the placebo group) and muscle-related adverse events (ten patients [5%] vs 1 [1%]). Interpretation In patients with heterozygous familial hypercholesterolaemia, evolocumab administered either 140 mg every 2 weeks or 420 mg monthly was well tolerated and yielded similar and rapid 60% reductions in LDL cholesterol compared with placebo. Funding Amgen Inc.
    The Lancet 10/2014; 385(9965). DOI:10.1016/S0140-6736(14)61399-4 · 45.22 Impact Factor
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    ABSTRACT: Lipoprotein(a) [Lp(a)] is an independent risk factor for cardiovascular disease, with limited treatment options. This analysis evaluated the effect of a monoclonal antibody to proprotein convertase subtilisin/kexin 9 (PCSK9), alirocumab 150 mg every 2 weeks (Q2W), on Lp(a) levels in pooled data from 3 double-blind, randomized, placebo-controlled phase 2 studies of 8 or 12 weeks duration conducted in patients with hypercholesterolemia on background lipid-lowering therapy (NCT01266876, NCT01288469, NCT01288443). Data were available for 102/108 patients who received alirocumab 150 mg Q2W and 74/77 patients who received placebo. Alirocumab resulted in a significant reduction in Lp(a) from baseline compared with placebo (–30.3% versus –0.3%, p <0.0001). Median percentage Lp(a) reductions in the alirocumab group were of a similar magnitude across a range of baseline Lp(a) levels, resulting in greater absolute reductions in Lp(a) in patients with higher baseline levels. Regression analysis indicated that less than 5% of the variance in the reduction of Lp(a) was explained by the effect of alirocumab on low-density lipoprotein cholesterol (LDL-C). In conclusion, pooled data from 3 phase 2 trials demonstrate substantive reduction in Lp(a) with alirocumab 150 mg Q2W, including patients with baseline Lp(a) >50 mg/dl. Reductions in Lp(a) only weakly correlated with the magnitude of LDL-C lowering.
    The American Journal of Cardiology 09/2014; 114(5). DOI:10.1016/j.amjcard.2014.05.060 · 3.43 Impact Factor
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    ABSTRACT: Background: Preference for fatty foods is a risk factor for obesity. It is a complex behaviour that involves the brain reward system and is regulated by genetic and environmental factors, such as the opioid receptor mu-1 gene (OPRM1) and prenatal exposure to maternal ciga-rette smoking (PEMCS). We examined whether OPRM1 and PEMCS interact in influencing fat intake and whether exposure-associated epigenetic modifications of OPRM1 may mediate this gene-environment interaction. Methods: We studied adolescents from a French Canadian genetic founder population, half of whom were exposed prenatally to maternal cigarette smoking. Fat intake was assessed with a 24-hour food recall in the form of a structured interview conducted by a trained nutritionist. The OPRM1 variant rs2281617 was genotyped for the whole sample with the Illumina Human610-Quad and HumanOmniExpress BeadChips. Methylation of blood DNA was assessed at 21 CpGs across OPRM1 in a subset of the sample using the Illumina HumanMethylation450 BeadChip. Results: We included 956 adolescents in our study. In the whole sample, OPRM1 (T carrier in rs2281617) was associated with lower fat intake (-1.6%, p = 0.017), and PEMCS was associated with higher fat intake (+ 1.6%, p = 0.005). OPRM1 and PEMCS interacted with each other (p = 0.003); the "protective" (fat intake-lowering) allele of OPRM1 was associated with lower fat intake in nonexposed (-3.2%, p < 0.001) but not in exposed individuals (+0.8%, p = 0.42). Further, PEMCS was associated with lower DNA methylation across multiple CpGs across OPRM1 in exposed versus nonexposed individuals (p = 0.031). Limitations: A limitation of our study was its cross-sectional design. Conclusion: Our study suggests that PEMCS may interact with OPRM1 in increasing fat preference. Silencing of the protective OPRM1 allele in exposed adolescents might be related to epigenetic modification of this gene.
    Journal of psychiatry & neuroscience: JPN 08/2014; 39(4):130263. DOI:10.1503/jpn.130263 · 7.49 Impact Factor

Publication Stats

7k Citations
1,825.13 Total Impact Points


  • 2002–2015
    • Université de Montréal
      • • Department of Medicine
      • • Center for Mathematical Research
      Montréal, Quebec, Canada
    • Medical College of Wisconsin
      Milwaukee, Wisconsin, United States
  • 2014
    • AVACO AG, Switzerland
      Basel-Landschaft, Switzerland
    • Centre hospitalier affilié universitaire de Québec (CHA)
      Quebec City, Quebec, Canada
  • 2013
    • Hamilton Health Sciences
      Hamilton, Ontario, Canada
  • 2012–2013
    • Université de Sherbrooke
      • Department of Biochemistry
      Шербрук, Quebec, Canada
  • 2007–2013
    • Université du Québec à Montréal
      Montréal, Quebec, Canada
  • 1997–2013
    • University of Québec in Chicoutimi
      Saguenay, Quebec, Canada
  • 1995–2012
    • Centre hospitalier de l'Université de Montréal (CHUM)
      • Département Médecine dentaire
      Montréal, Quebec, Canada
  • 2006–2009
    • University of Nottingham
      • Brain and Body Centre
      Nottingham, ENG, United Kingdom
    • Massachusetts General Hospital
      • Center for Human Genetic Research
      Boston, MA, United States
    • Institute of Heart Sciences
      Valladolid, Castille and León, Spain
  • 2004–2007
    • University of Helsinki
      • Department of Oral Medicine
      Helsinki, Uusimaa, Finland
  • 2003–2007
    • University of Toronto
      • Department of Laboratory Medicine and Pathobiology
      Toronto, Ontario, Canada
    • Children's Hospital of Eastern Ontario
      Ottawa, Ontario, Canada
  • 2005
    • New York State
      New York City, New York, United States
  • 1997–2005
    • Laval University
      • • Department of Food and Nutrition Sciences
      • • Institute of Nutraceuticals and Functional Foods (INAF)
      • • Department of Medicine
      Quebec City, Quebec, Canada
  • 2002–2004
    • Philadelphia ZOO
      Filadelfia, Pennsylvania, United States
  • 2000
    • University of Texas at San Antonio
      San Antonio, Texas, United States
    • McGill University Health Centre
      Montréal, Quebec, Canada