Publications by authors named "Patrick Couture"

211 Publications

A combination of single nucleotide polymorphisms is associated with the interindividual variability in the blood lipid response to dietary fatty acid consumption in a randomized clinical trial.

Am J Clin Nutr 2021 Apr 19. Epub 2021 Apr 19.

C2VN, Aix Marseille Univ, INRAE, INSERM, Marseille, France.

Background: Blood lipid concentrations display high interindividual variability in response to dietary interventions, partly due to genetic factors. Existing studies have focused on single nucleotide polymorphisms (SNPs) analyzed individually, which only explain a limited fraction of the variability of these complex phenotypes.

Objective: We aimed to identify combinations of SNPs associated with the variability in LDL cholesterol and triglyceride (TG) concentration changes following 5 dietary interventions.

Design: In a multicenter randomized crossover trial, 92 participants with elevated waist circumference and low HDL cholesterol concentrations consumed 5 isoenergetic diets for 4 wk: a diet rich in saturated fatty acids (SFAs) from cheese, SFA from butter, monounsaturated fatty acids (MUFAs), n-6 polyunsaturated fatty acids (PUFAs), and a diet higher in carbohydrates (CHO). The association between 22 candidate SNPs in genes involved in lipid and bile acid metabolism and transport and changes in LDL cholesterol and TG concentrations was assessed with univariate statistics followed by partial least squares regression.

Results: Endpoint LDL cholesterol concentrations were significantly different (cheese: 3.18 ± 0.04, butter: 3.31 ± 0.04, MUFA: 3.00 ± 0.04, PUFA: 2.81 ± 0.04, CHO: 3.11 ± 0.04 mmol/L; P < 0.001) while endpoint TG concentrations were not (P = 0.117). Both displayed consistently elevated interindividual variability following the dietary interventions (CVs of 34.5 ± 2.2% and 55.8 ± 1.8%, respectively). Among the 22 candidate SNPs, only ABCA1-rs2066714 and apolipoprotein E (APOE) isoforms exhibited consistent significant effects, namely on LDL cholesterol concentrations. However, several SNPs were significantly associated with changes in LDL cholesterol and TG concentrations in a diet-specific fashion. Generated multivariate models explained from 16.0 to 33.6% of the interindividual variability in LDL cholesterol concentration changes and from 17.5 to 32.0% of that in TG concentration changes.

Conclusions: We report combinations of SNPs associated with a significant part of the variability in LDL cholesterol and TG concentrations following dietary interventions differing in their fatty acid profiles.
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http://dx.doi.org/10.1093/ajcn/nqab064DOI Listing
April 2021

Polymorphisms in the stearoyl-CoA desaturase gene modify blood glucose response to dietary oils varying in MUFA content in adults with obesity.

Br J Nutr 2021 Apr 8:1-10. Epub 2021 Apr 8.

Richardson Center for Functional Foods and Nutraceuticals, University of Manitoba, Winnipeg, MB, Canada.

Diets varying in SFA and MUFA content can impact glycaemic control; however, whether underlying differences in genetic make-up can influence blood glucose responses to these dietary fatty acids is unknown. We examined the impact of dietary oils varying in SFA/MUFA content on changes in blood glucose levels (primary outcome) and whether these changes were modified by variants in the stearoyl-CoA desaturase (SCD) gene (secondary outcome). Obese men and women participating in the randomised, crossover, isoenergetic, controlled-feeding Canola Oil Multicenter Intervention Trial II consumed three dietary oils for 6 weeks, with washout periods of ˜6 weeks between each treatment. Diets studied included a high SFA/low MUFA Control oil (36·6 % SFA/28·2 % MUFA), a conventional canola oil (6·2 % SFA/63·1 % MUFA) and a high-oleic acid canola oil (5·8 % SFA/74·7 % MUFA). No differences in fasting blood glucose were observed following the consumption of the dietary oils. However, when stratified by SCD genotypes, significant SNP-by-treatment interactions on blood glucose response were found with additive models for rs1502593 (P = 0·01), rs3071 (P = 0·02) and rs522951 (P = 0·03). The interaction for rs3071 remained significant (P = 0·005) when analysed with a recessive model, where individuals carrying the CC genotype showed an increase (0·14 (sem 0·09) mmol/l) in blood glucose levels with the Control oil diet, but reductions in blood glucose with both MUFA oil diets. Individuals carrying the AA and AC genotypes experienced reductions in blood glucose in response to all three oils. These findings identify a potential new target for personalised nutrition approaches aimed at improving glycaemic control.
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http://dx.doi.org/10.1017/S0007114521001264DOI Listing
April 2021

2021 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult.

Can J Cardiol 2021 Mar 26. Epub 2021 Mar 26.

McGill University Health Centre, Montréal, Québec, Canada.

The 2021 guidelines primary panel selected clinically relevant questions and produced updated recommendations, on the basis of important new findings emerging since the 2016 guidelines. In subjects with clinical atherosclerosis, abdominal aortic aneurysm, most subjects with diabetes or chronic kidney disease, and those with low-density lipoprotein cholesterol (LDL-C) ≥5 mmol/L, statin therapy continues to be recommended. We have introduced the concept of lipid/lipoprotein treatment thresholds for intensifying lipid-lowering therapy with non-statin agents, and have identified the secondary prevention patients who have been shown to derive the largest benefit from intensification of therapy with these agents. For all other patients, we emphasize risk assessment linked to lipid/lipoprotein evaluation to optimize clinical decision-making. Lipoprotein(a) measurement is now recommended once in a patient's lifetime, as part of initial lipid screening to assess cardiovascular risk. For any patient with triglycerides ˃1.5 mmol/L, either non-high-density lipoprotein cholesterol or apolipoprotein-B are the preferred lipid parameter for screening, rather than LDL-C. We provide updated recommendations regarding the role of coronary artery calcium scoring as a clinical decision tool to aid the decision to initiate statin therapy. There are new recommendations on the preventative care of women with hypertensive disorders of pregnancy. Health behaviour modification, including regular exercise and a heart-healthy diet, remain the cornerstone of cardiovascular disease prevention. These guidelines are intended to provide a platform for meaningful conversation and shared-decision making between patient and care provider, so that individual decisions can be made for risk screening, assessment, and treatment.
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http://dx.doi.org/10.1016/j.cjca.2021.03.016DOI Listing
March 2021

Impact of Diet on Plasma Lipids in Individuals with Heterozygous Familial Hypercholesterolemia: A Systematic Review of Randomized Controlled Nutritional Studies.

Nutrients 2021 Jan 15;13(1). Epub 2021 Jan 15.

Centre Nutrition, Santé et Société (NUTRISS), Institut Sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Background: Conclusive data on the effectiveness of dietary interventions in heterozygous familial hypercholesterolemia (HeFH) management are unavailable. Whether this is due to a true lack of effects or biases in intervention designs remains unsettled. We systematically assessed the impact on LDL-C of published dietary randomized controlled trials (RCTs) conducted among individuals with HeFH in relation to their design and risk of bias.

Methods: We systematically searched PubMed, Web of Science, and Embase in November 2020 to identify RCTs that assessed the impact of: (1) food-based interventions; (2) dietary counseling interventions; or (3) dietary supplements on LDL-C in individuals with HeFH. We evaluated the risk of bias of each study using the Cochrane Risk of Bias 2 method.

Results: A total of 19 RCTs comprising 837 individuals with HeFH were included. Of those, five were food-based interventions, three were dietary counseling interventions and 12 were dietary supplement-based interventions (omega-3, = 3; phytosterols, = 7; guar gum, = 1; policosanol, = 1). One study qualified both as a food-based intervention and as a dietary supplement intervention due to its factorial design. A significant reduction in LDL-C levels was reported in 10 RCTs, including eight dietary supplement interventions (phytosterols, = 6, omega-3, = 1; guar gum, = 1), one food-based intervention and one dietary counseling intervention. A total of 13 studies were judged to have some methodological biases in a way that substantially lowers confidence in the results. Studies at low risk of biases were more likely to report significant reductions in LDL-C concentrations, compared with studies at risk of bias (chi-square statistic: 5.49; = 0.02).

Conclusion: This systemic review shows that the apparent lack of effectiveness of diet manipulation in modulating plasma levels of LDL-C among individuals with HeFH is likely due to biases in study designs, rather than a true lack of effects. The likelihood of reporting significant reductions in LDL-C was associated with the concurrent risk of bias.
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http://dx.doi.org/10.3390/nu13010235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7829745PMC
January 2021

Sex May Modulate the Effects of Combined Polyphenol Extract and L-citrulline Supplementation on Ambulatory Blood Pressure in Adults with Prehypertension: A Randomized Controlled Trial.

Nutrients 2021 Jan 27;13(2). Epub 2021 Jan 27.

Centre Nutrition, Santé et Société (NUTRISS), Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Increased blood pressure (BP), vascular dysfunction and inflammation are involved in the etiology of cardiovascular disease (CVD). Although several dietary components such as polyphenols and L-citrulline may help to control BP, their combined impact on ambulatory BP in individuals at risk of CVD remains unknown. The objective of this research was to investigate the short-term impact of supplementation with a combination of polyphenol extract and L-citrulline on ambulatory BP, endothelial function and inflammation. In a randomized double-blind parallel trial, 73 men and women with prehypertension were supplemented with a placebo (cellulose, = 34, Plac) or 548 mg/day of polyphenols and 2 g/day of L-citrulline ( = 35, Suppl) for 6 weeks. The primary outcome of this study was the difference between groups in 24-h ambulatory diastolic BP (DBP) at week six. Secondary outcomes were a difference between groups at week six in ambulatory systolic BP (SBP), casual BP, serum lipids and high-sensitivity C-reactive protein (hs-CRP) concentrations and skin advanced glycation end products (AGEs). Potential interaction of treatment with sex was examined. Suppl had no impact on mean ambulatory SBP and DBP ( > 0.10 vs. placebo). Daytime and 24-h SBP were reduced with Suppl in women ( ≤ 0.01), but not in men ( ≥ 0.27). A non-significant reduction in AGEs was observed after Suppl compared to Plac among all participants ( = 0.07) and there was no difference in the concentrations of blood lipids ( > 0.20) or CRP ( = 0.36) between treatments at week six. Therefore, supplementation with polyphenol extract and L-citrulline for 6 weeks has no impact on ambulatory BP, blood lipids and CRP in adults with prehypertension. However, the polyphenol extract/L-citrulline supplement may reduce ambulatory SBP in women, but not in men. These preliminary results need further research efforts towards further documenting this sex-dependent BP response to supplementation with polyphenols and L-citrulline.
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http://dx.doi.org/10.3390/nu13020399DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912201PMC
January 2021

Correlates of Coronary Artery Calcification Prevalence and Severity in Patients With Heterozygous Familial Hypercholesterolemia.

CJC Open 2021 Jan 16;3(1):62-70. Epub 2020 Sep 16.

Nutrition, health and society (NUTRISS) Research Center, Institute on Nutrition and Functional Foods (INAF), Laval University, Québec, Québec, Canada.

Background: Determinants of coronary artery calcification (CAC) prevalence and severity in heterozygous familial hypercholesterolemia (HeFH) remain understudied. The objective of this cross-sectional study was to investigate correlates of CAC in patients with HeFH.

Methods: A CAC score was calculated by a noncontrast computed tomography scan in women (n = 68) and men (n = 78) with genetically defined HeFH. We classified CAC prevalence and severity using 3 categories: CAC score = 0 Agatston Unit (AU), CAC score = 1-100 AU, and CAC score > 100 AU. Information on potential correlates of CAC including familial and personal health history, cardiovascular risk factors, lipid-lowering medication, and lifestyle habits was collected.

Results: A total of 95 patients had prevalent CAC. Independent correlates of CAC prevalence and severity included age (odds ratio [OR] per 10 years: 5.06, 95% confidence interval [CI]: 3.19, 7.93, < 0.0001), family history of premature cardiovascular disease (OR: 3.88, 95% CI: 1.71, 8.81,  = 0.001), male sex (OR: 3.40, 95% CI: 1.49, 7.78,  = 0.004), statin use (OR: 15.5, 95% CI: 1.89, 126,  = 0.01), diet quality assessed with the Alternative Healthy Eating Index score (OR per 1 standard deviation: 0.59, 95% CI: 0.39, 0.90,  = 0.01), ever smoking (OR: 3.06, 95% CI: 1.20, 7.81,  = 0.02), receptor-negative genotype (OR: 3.17, 95% CI: 1.16, 8.66,  = 0.02), lipoprotein(a) year-score (OR per 1 standard deviation of log-transformed year-score: 1.53, 95% CI: 0.99, 2.36,  = 0.05).

Conclusions: In individuals with HeFH, age, family history of premature cardiovascular disease, sex, statin use, diet quality, smoking status, the genotype, and lipoprotein(a) concentrations were independently associated with CAC prevalence and severity.
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http://dx.doi.org/10.1016/j.cjco.2020.09.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801218PMC
January 2021

Effects of Daily Raspberry Consumption on Immune-Metabolic Health in Subjects at Risk of Metabolic Syndrome: A Randomized Controlled Trial.

Nutrients 2020 Dec 17;12(12). Epub 2020 Dec 17.

Centre Nutrition, Santé et Société (NUTRISS) and Institut sur la Nutrition et les Aliments Fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Consumption of red raspberries has been reported to exert acute beneficial effects on postprandial glycemia, insulinemia, triglyceridemia, and cytokine levels in metabolically disturbed subjects. In a two-arm parallel-group, randomized, controlled trial, 59 subjects with overweight or abdominal obesity and with slight hyperinsulinemia or hypertriglyceridemia were randomized to consume 280 g/day of frozen raspberries or to maintain their usual diet for 8 weeks. Primary analyses measured metabolic differences between the groups. Secondary analyses performed with omics tools in the intervention group assessed blood gene expression and plasma metabolomic changes following the raspberry supplementation. The intervention did not significantly affect plasma insulin, glucose, inflammatory marker concentrations, nor blood pressure. Following the supplementation, 43 genes were differentially expressed, and several functional pathways were enriched, a major portion of which were involved in the regulation of cytotoxicity, immune cell trafficking, protein signal transduction, and interleukin production. In addition, 10 serum metabolites were found significantly altered, among which β-alanine, trimethylamine N-oxide, and bioactive lipids. Although the supplementation had no meaningful metabolic effects, these results highlight the impact of a diet rich in raspberry on the immune function and phospholipid metabolism, thus providing novel insights into potential immune-metabolic pathways influenced by regular raspberry consumption.
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http://dx.doi.org/10.3390/nu12123858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7767072PMC
December 2020

Diet Quality, Saturated Fat and Metabolic Syndrome.

Nutrients 2020 Oct 22;12(11). Epub 2020 Oct 22.

Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, QC G1V 0A6, Canada.

Indices reflecting overall diet quality are used globally in research to predict the risk of various diseases and metabolic disorders such as metabolic syndrome (MetS). Such indices are built to measure adherence to current dietary guidelines or to best assess the diet-disease relationship. Although mostly food-based, dietary guidelines often include recommendations to limit saturated fatty acid (SFA) intake in order to prevent cardiovascular diseases. However, not all diet quality indices consider SFA in their definition of diet quality. Additionally, the relationship between SFA consumption and the development of MetS remains unclear. The purpose of this short review was to explore the association between MetS and various diet quality indices and dietary patterns, with a focus on how SFA contributes to these associations.
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http://dx.doi.org/10.3390/nu12113232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7690379PMC
October 2020

Interaction of Autotaxin With Lipoprotein(a) in Patients With Calcific Aortic Valve Stenosis.

JACC Basic Transl Sci 2020 Sep 26;5(9):888-897. Epub 2020 Aug 26.

Centre de Recherche de l'Institut Universitaire de Cardiologie et de Pneumologie de Québec, Quebec, Canada.

Our objectives were to determine whether autotaxin (ATX) is transported by lipoprotein(a) [Lp(a)] in human plasma and if could be used as a biomarker of calcific aortic valve stenosis (CAVS). We first found that ATX activity was higher in Lp(a) compared to low-density lipoprotein fractions in isolated fractions of 10 healthy participants. We developed a specific assay to measure ATX-Lp(a) in 88 patients with CAVS and 144 controls without CAVS. In a multivariable model corrected for CAVS risk factors, ATX-Lp(a) was associated with CAVS (p = 0.003). We concluded that ATX is preferentially transported by Lp(a) and might represent a novel biomarker for CAVS.
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http://dx.doi.org/10.1016/j.jacbts.2020.06.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524777PMC
September 2020

Lomitapide for treatment of homozygous familial hypercholesterolemia: The Québec experience.

Atherosclerosis 2020 10 5;310:54-63. Epub 2020 Aug 5.

Research Institute of the McGill University Health Centre, Montreal, Québec, Canada. Electronic address:

Background And Aims: Homozygous familial hypercholesterolemia (HoFH) is an orphan disease, most often caused by bi-allelic mutations of the LDLR gene. Patients with HoFH have elevated LDL-C levels >13 mmol/L, tendinous xanthomata and severe, premature atherosclerotic cardiovascular disease (ASCVD). Untreated, most HoFH patients die of ASCVD in youth. New therapeutic modalities include lomitapide, an inhibitor of microsomal triglyceride transfer protein that lowers hepatic LDL-C production. We have recently identified 79 Canadian patients with HoFH. Here, we describe our experience with lomitapide in the province of Quebec, a geographic area known to have a high prevalence of HoFH.

Methods: This is a retrospective case series of 12 HoFH patients followed at three lipidology centers in the province of Quebec.

Results: Mean age of the patients was 44 ± 18 years; age at time of HoFH diagnosis ranged from 2 to 59 years. All patients were on a statin and ezetimibe 10 mg/day and five patients were treated with LDL apheresis. Treatment with lomitapide reduced LDL-C levels by 38% (intention-to-treat). Intolerable gastrointestinal side effects were observed in 3/12 patients and were the main reason for treatment discontinuation. Three patients tolerated lomitapide at doses ranging between 5 and 30 mg/day without major side effects. Downwards drug titration was necessary in the 6 remaining patients because of gastrointestinal side effects (n = 5) and elevated liver enzymes (n = 1), and 2 of them finally discontinued treatment.

Conclusions: Lomitapide may be used to further decrease LDL-C in HoFH patients; gastrointestinal side effects and hepatic toxicity may limit adherence.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.028DOI Listing
October 2020

Genetic risk prediction of the plasma triglyceride response to independent supplementations with eicosapentaenoic and docosahexaenoic acids: the ComparED Study.

Genes Nutr 2020 Jun 15;15(1):10. Epub 2020 Jun 15.

Centre Nutrition, Santé et Société-Institut sur la nutrition et les aliments fonctionnels (Institute of Nutrition and Functional Foods (INAF)), Université Laval, 2440 Hochelaga Blvd., Quebec City, Quebec, Canada.

Background: We previously built a genetic risk score (GRS) highly predictive of the plasma triglyceride (TG) response to an omega-3 fatty acid (n-3 FA) supplementation from marine sources. The objective of the present study was to test the potential of this GRS to predict the plasma TG responsiveness to supplementation with either eicosapentaenoic (EPA) or docosahexaenoic (DHA) acids in the Comparing EPA to DHA (ComparED) Study.

Methods: The ComparED Study is a double-blind, controlled, crossover trial, with participants randomized to three supplemented phases of 10 weeks each: (1) 2.7 g/day of DHA, (2) 2.7 g/day of EPA, and (3) 3 g/day of corn oil (control), separated by 9-week washouts. The 31 SNPs used to build the previous GRS were genotyped in 122 participants of the ComparED Study using TaqMan technology. The GRS for each participant was computed by summing the number of rare alleles. Ordinal and binary logistic models, adjusted for age, sex, and body mass index, were used to calculate the ability of the GRS to predict TG responsiveness.

Results: The GRS predicted TG responsiveness to EPA supplementation (p = 0.006), and a trend was observed for DHA supplementation (p = 0.08). The exclusion of participants with neutral TG responsiveness clarified the association patterns and the predictive capability of the GRS (EPA, p = 0.0003, DHA p = 0.01).

Conclusion: Results of the present study suggest that the constructed GRS is a good predictor of the plasma TG response to supplementation with either DHA or EPA.

Trial Registration: ClinicalTrials.gov, NCT01810003. The study protocol was registered on March 4, 2013.
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http://dx.doi.org/10.1186/s12263-020-00669-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7294612PMC
June 2020

Plasma biomarkers of small intestine adaptations in obesity-related metabolic alterations.

Diabetol Metab Syndr 2020 9;12:31. Epub 2020 Apr 9.

1École de nutrition, Faculté des sciences de l'agriculture et de l'alimentation, Université Laval, 2440, boulevard Hochelaga, Québec, QC G1V 0A6 Canada.

Background: Evidence suggests that pathophysiological conditions such as obesity and type 2 diabetes (T2D) are associated with morphologic and metabolic alterations in the small intestinal mucosa. Exploring these alterations generally requires invasive methods, limiting data acquisition to subjects with enteropathies or undergoing bariatric surgery. We aimed to evaluate small intestine epithelial cell homeostasis in a cohort of men covering a wide range of adiposity and glucose homoeostasis statuses.

Methods: Plasma levels of citrulline, a biomarker of enterocyte mass, and I-FABP, a biomarker of enterocyte death, were measured by UHPLC‑MS and ELISA in 154 nondiabetic men and 67 men with a T2D diagnosis.

Results: Plasma citrulline was significantly reduced in men with insulin resistance and T2D compared to insulin sensitive men. Decreased citrulline levels were, however, not observed in men with uncontrolled metabolic parameters during T2D. Plasma I-FABP was significantly higher in men with T2D, especially in presence of uncontrolled glycemic and lipid profile parameters. Integration of both parameters, which estimate enterocyte turnover, was associated with glucose homeostasis as well as with T2D diagnosis. Differences in biomarkers levels were independent of age and BMI and glucose filtration rates.

Conclusions: Our study supports a decreased functional enterocyte mass and an increased enterocyte death rate in presence of metabolic alterations but emphasizes that epithelial cell homeostasis is especially altered in presence of severe insulin resistance and T2D. The marked changes in small intestine cellularity observed in obesity and diabetes are thus suggested to be part of gut dysfunctions, mainly at an advanced stage of the disease.
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http://dx.doi.org/10.1186/s13098-020-00530-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7144049PMC
April 2020

Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography.

CJC Open 2019 May 12;1(3):131-140. Epub 2019 Apr 12.

Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Québec, Canada.

Background: Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification.

Methods: We recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Québec City, Canada. In a second group of individuals with high (≥75 nmol/L, n = 27) or low (<75 nmol/L, n = 28) Lp(a) levels, 18F-sodium fluoride positron emission tomography/computed tomography was performed to determine the difference in mean tissue-to-background ratio (TBR) of the aortic valve.

Results: Patients with CAVS had 62.0% higher Lp(a) (median = 28.7, interquartile range [8.2-116.6] vs 10.9 [3.6-28.8] nmol/L, 0.0001), 50% higher OxPL-apolipoprotein-B (2.2 [1.3-6.0] vs 1.1 [0.7-2.6] nmol/L, 0.0001), and 69.9% higher OxPL-apolipoprotein(a) (7.3 [1.8-28.4] vs 2.2 [0.8-8.4] nmol/L, 0.0001) levels compared with individuals without CAVS (all 0.0001). Individuals without CAVS but elevated Lp(a) had 40% higher mean TBR compared with individuals with low Lp(a) levels (mean TBR = 1.25 ± 0.23 vs 1.15 ± 0.11,  = 0.02).

Conclusions: Elevated Lp(a) and OxPL levels are associated with prevalent CAVS in patients studied in an echocardiography laboratory setting. In individuals with elevated Lp(a), evidence of aortic valve microcalcification by 18F-sodium fluoride positron emission tomography/computed tomography is present before the development of clinically manifested CAVS.
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http://dx.doi.org/10.1016/j.cjco.2019.03.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063623PMC
May 2019

Omega-3 fatty acids: new insights into the impact of eicosapentaenoic and docosahexaenoic acids on lipid and lipoprotein metabolism.

Curr Opin Lipidol 2020 02;31(1):38-39

Centre Nutrition, santé et société (NUTRISS), Institut sur la nutrition et les aliments fonctionnels (INAF), Université Laval, Québec, Canada.

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http://dx.doi.org/10.1097/MOL.0000000000000660DOI Listing
February 2020

Prevention of Potential Adverse Metabolic Effects of a Supplementation with Omega-3 Fatty Acids Using a Genetic Score Approach.

Lifestyle Genom 2020 28;13(1):32-42. Epub 2019 Nov 28.

Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, Québec, Canada,

Introduction: The consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) has been reported to have beneficial health effects, notably, by reducing plasma triglyceride levels. Nonetheless, a concomitant decrease in insulin sensitivity has also been observed, but is highly variable among subjects. Herein, we aimed to determine the importance of the genetic background in the interindividual variability of the insulin sensitivity response following an n-3 PUFA supplementation.

Methods: A total of 210 participants completed a 6-week n-3 PUFA supplementation with 5 g/day of fish oil (providing 1.9-2.2 g of eicosapentaenoic acid + 1.1 g of docosahexaenoic acid). Insulin resistance was estimated by the homeostatic model assessment (HOMA-IR), and participants were further classified as high-risk or low-risk depending on their HOMA-IR change following the n-3 PUFA supplementation, as compared to pre-supplementation values. Genome-wide genotyping data were obtained for 138 participants using HumanOmni-5-Quad BeadChips containing 4,301,331 single nucleotide polymorphisms. A genome-wide association analysis (GWAS) was carried out between high-risk and low-risk participants. The population study was split into training (60%) and testing (40%) datasets to assess the predictive accuracy of a genetic risk score (GRS) constructed by summing the number of risk alleles.

Results: Following the n-3 PUFA supplementation, 32 participants had increased HOMA-IR as compared to initial values and were classified as high risk (23.2%), whereas remaining subjects were classified as low risk (n = 106, 76.8%). A total of 8 loci had frequency differences between high-risk and low-risk participants at a suggestive GWAS association threshold (p value <1 × 10-5). After applying 10-fold cross validation, the GRS showed a significant association with the risk of increased HOMA-IR in the testing dataset (OR = 3.16 [95% CI, 1.85-7.14]), with a predictive accuracy of 0.85, and explained 40% of variation in HOMA-IR change.

Conclusions: These results suggest that the genetic background has a relevant role in the interindividual variability observed in the insulin sensitivity response following an n-3 PUFA supplementation. Subjects being at risk of insulin sensitivity lowering following an n-3 PUFA supplementation may be identified using genetic-based precision nutrition approaches.
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http://dx.doi.org/10.1159/000504022DOI Listing
November 2019

Effects of regular-fat and low-fat dairy consumption on daytime ambulatory blood pressure and other cardiometabolic risk factors: a randomized controlled feeding trial.

Am J Clin Nutr 2020 01;111(1):42-51

Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.

Background: The extent to which dairy products and their fat content influence cardiovascular health remains uncertain.

Objective: This study aimed to assess how consumption of low-fat milk and regular-fat cheese enriched in γ-aminobutyric acid (GABA) influences daytime ambulatory blood pressure (BP) and other cardiometabolic risk factors.

Methods: In this crossover controlled feeding study, 55 healthy men and women with high-normal daytime BP were randomly assigned to sequences of three 6-wk isoenergetic diets, each comprising 1) no dairy (control diet), 2) 3 daily servings of 1% fat milk, and 3) 1 daily serving of 31% fat cheddar cheese naturally enriched in GABA. Total proteins, carbohydrates, and fats were matched across all 3 diets. The additional 2% of energy from SFAs in the cheese diet was replaced by n-6 PUFAs in the other diets.

Results: Comparison of postdiet ambulatory systolic BP revealed no difference (P = 0.34), which was also the case for ambulatory diastolic BP (P = 0.45). The cheese diet increased serum LDL-cholesterol concentrations compared with the control and milk diets (+5.8%, P = 0.006 and +7.0%, P = 0.0008, respectively) and increased LDL particle size compared with the milk diet (P = 0.02). HDL-cholesterol concentrations after the milk diet were lower than after the control diet (-4.1%; P = 0.009). The milk and cheese diets increased triglycerides compared with the control diet (+9.9%, P = 0.01 and +10.5%, P = 0.007, respectively). There was no significant difference between all diets for C-reactive protein concentrations and markers of glucose/insulin homeostasis.

Conclusions: These results suggest that short-term consumption of dairy products, whether low or regular in fat, has no overall effect on daytime ambulatory BP compared with a dairy-free diet. Other cardiometabolic risk factors may be differently modified according to the fat content of the dairy product. This trial was registered at clinicaltrials.gov as NCT02763930.
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http://dx.doi.org/10.1093/ajcn/nqz251DOI Listing
January 2020

The Lifelong Burden of Homozygous Familial Hypercholesterolemia.

Can J Cardiol 2019 10 13;35(10):1419.e1-1419.e4. Epub 2019 Jun 13.

Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada. Electronic address:

Homozygous familial hypercholesterolemia is caused by mutations in the low-density lipoprotein receptor gene. It is diagnosed in children or youth who present with extensive tendinous and cutaneous xanthomas and extreme elevation of low-density lipoprotein cholesterol. Untreated, premature coronary artery disease develops in the teenage years or earlier and survival to ages older than 30 years is rare. Herein we describe the clinical course of a patient with homozygous familial hypercholesterolemia treated according to the standards of care and experimental approaches. Despite aggressive therapies, atherosclerosis in all vascular beds progressed, leading to the patient's demise at age 59 years, highlighting the importance of early diagnosis and appropriate follow-up.
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http://dx.doi.org/10.1016/j.cjca.2019.06.009DOI Listing
October 2019

Common Variants in Lipid Metabolism-Related Genes Associate with Fat Mass Changes in Response to Dietary Monounsaturated Fatty Acids in Adults with Abdominal Obesity.

J Nutr 2019 10;149(10):1749-1756

Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, Manitoba, Canada.

Background: Different fatty acids (FAs) can vary in their obesogenic effect, and genetic makeup can contribute to fat deposition in response to dietary FA composition. However, the antiobesogenic effects of the interactions between dietary MUFAs and genetics have scarcely been tested in intervention studies.

Objective: We evaluated the overall (primary outcome) and genetically modulated (secondary outcome) response in body weight and fat mass to different levels of MUFA consumption.

Methods: In the Canola Oil Multicenter Intervention Trial II, a randomized, crossover, isocaloric, controlled-feeding multicenter trial, 44 men and 71 women with a mean age of 44 y and an increased waist circumference (men ∼108 cm and women ∼102 cm) consumed each of 3 oils for 6 wk, separated by four 12-wk washout periods. Oils included 2 high-MUFA oils-conventional canola and high-oleic canola (<7% SFAs, >65% MUFAs)-and 1 low-MUFA/high-SFA oil blend (40.2% SFAs, 22.0% MUFAs). Body fat was measured using DXA. Five candidate single-nucleotide polymorphisms (SNPs) were genotyped using qualitative PCR. Data were analyzed using a repeated measures mixed model.

Results: No significant differences were observed in adiposity measures following the consumption of either high-MUFA diet compared with the low-MUFA/high-SFA treatment. However, when stratified by genotype, 3 SNPs within lipoprotein lipase (LPL), adiponectin, and apoE genes influenced, separately, fat mass changes in response to treatment (n = 101). Mainly, the LPL rs13702-CC genotype was associated with lower visceral fat (high-MUFA: -216.2 ± 58.6 g; low-MUFA: 17.2 ± 81.1 g; P = 0.017) and android fat mass (high-MUFA: -267.3 ± 76.4 g; low-MUFA: -21.7 ± 102.2 g; P = 0.037) following average consumption of the 2 high-MUFA diets.

Conclusions: Common variants in LPL, adiponectin, and apoE genes modulated body fat mass response to dietary MUFAs in an isocaloric diet in adults with abdominal obesity. These findings might eventually help in developing personalized dietary recommendations for weight control. The trial was registered at clinicaltrials.gov as NCT02029833 (https://www.clinicaltrials.gov/ct2/show/NCT02029833?cond=NCT02029833&rank=1).
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http://dx.doi.org/10.1093/jn/nxz136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443768PMC
October 2019

Preliminary Evaluation of Gamification in Residency Training.

J Am Coll Radiol 2019 Sep 30;16(9 Pt A):1201-1205. Epub 2019 Apr 30.

Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee. Electronic address:

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http://dx.doi.org/10.1016/j.jacr.2019.02.040DOI Listing
September 2019

Comparing the serum TAG response to high-dose supplementation of either DHA or EPA among individuals with increased cardiovascular risk: the ComparED study.

Br J Nutr 2019 06 11;121(11):1223-1234. Epub 2019 Mar 11.

Institut sur la nutrition et les aliments fonctionnels (INAF), Pavillon des Services,Université Laval,Québec,Canada.

Studies have shown that the reduction in serum TAG concentrations with long-chain n-3 fatty acid supplementation is highly variable among individuals. The objectives of the present study were to compare the proportions of individuals whose TAG concentrations lowered after high-dose DHA and EPA, and to identify the predictors of response to both modalities. In a double-blind, controlled, crossover study, 154 men and women were randomised to three supplemented phases of 10 weeks each: (1) 2·7 g/d of DHA, (2) 2·7 g/d of EPA and (3) 3 g/d of maize oil, separated by 9-week washouts. As secondary analyses, the mean intra-individual variation in TAG was calculated using the standard deviation from the mean of four off-treatment samples. The response remained within the intra-individual variation (±0·25 mmol/l) in 47 and 57 % of participants after DHA and EPA, respectively. Although there was a greater proportion of participants with a reduction >0·25 mmol/l after DHA than after EPA (45 υ. 32 %; P 0·25 mmol/l after both DHA and EPA had higher non-HDL-cholesterol, TAG and insulin concentrations compared with other responders at baseline (all P < 0·05). In conclusion, supplementation with 2·7 g/d DHA or EPA had no meaningful effect on TAG concentrations in a large proportion of individuals with normal mean TAG concentrations at baseline. Although DHA lowered TAG in a greater proportion of individuals compared with EPA, the magnitude of TAG lowering among them was similar.
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http://dx.doi.org/10.1017/S0007114519000552DOI Listing
June 2019

Diets Enriched with Conventional or High-Oleic Acid Canola Oils Lower Atherogenic Lipids and Lipoproteins Compared to a Diet with a Western Fatty Acid Profile in Adults with Central Adiposity.

J Nutr 2019 03;149(3):471-478

Departments of Food and Human Nutritional Sciences, Winnipeg, MB, Canada.

Background: Novel oils high in monounsaturated fatty acids (MUFAs) and low in saturated fatty acids (SFAs) are an alternative to partially hydrogenated oils high in trans-unsaturated fatty acids. There is widespread use of high-MUFA oils across the food industry; however, limited knowledge of their cardiovascular impact exists.

Objectives: We investigated the effects of diets containing canola oil, high-oleic acid canola oil (HOCO), and a control oil blend (diet formulated to emulate a Western fat profile) on lipids, lipoproteins, and apolipoproteins (apos), as secondary outcomes of the trial.

Methods: In a multi-center, double-blind, randomized, 3-period crossover, controlled feeding trial, men (n = 44) and women (n = 75) with a mean age of 44 y, mean body mass index (BMI; in kg/m2) of 31.7, and an increased waist circumference plus ≥1 metabolic syndrome criteria consumed prepared, weight-maintenance diets containing canola oil [17.5% MUFAs, 9.2% polyunsaturated fatty acids (PUFAs), 6.6% SFAs], HOCO (19.1% MUFAs, 7.0% PUFAs, 6.4% SFAs), or control oil (10.5% MUFAs, 10.0% PUFAs, 12.3% SFAs) for 6 wk with ≥4-wk washouts. Fasting serum lipids were assessed at baseline and 6 wk. Diet effects were examined using a repeated measures mixed model.

Results: Compared with the control, canola and HOCO diets resulted in lower endpoint total cholesterol (TC; -4.2% and -3.4%; P < 0.0001), LDL cholesterol (-6.6% and -5.6%; P < 0.0001), apoB (-3.7% and -3.4%; P = 0.002), and non-HDL cholesterol (-4.5% and -4.0%; P = 0.001), with no differences between canola diets. The TC:HDL cholesterol and apoB:apoA1 ratios were lower after the HOCO diet than after the control diet (-3.7% and -3.4%, respectively). There were no diet effects on triglyceride, HDL cholesterol, or apoA1 concentrations.

Conclusions: HOCO, with increased MUFAs at the expense of decreased PUFAs, elicited beneficial effects on lipids and lipoproteins comparable to conventional canola oil and consistent with reduced cardiovascular disease risk in adults with central adiposity. This trial was registered at www.clinicaltrials.gov as NCT02029833.
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http://dx.doi.org/10.1093/jn/nxy307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398388PMC
March 2019

Fine mapping of genome-wide association study signals to identify genetic markers of the plasma triglyceride response to an omega-3 fatty acid supplementation.

Am J Clin Nutr 2019 01;109(1):176-185

Institute of Nutrition and Functional Foods, Laval University, Quebec City, Quebec, Canada.

Background: Using a genome-wide association study (GWAS) approach, our group previously computed a genetic risk score (GRS) from single nucleotide polymorphisms (SNPs) of 10 loci that affect the plasma triglyceride (TG) response to an omega-3 (n-3) fatty acid (FA) supplementation.

Objectives: The objective was to compute a novel and more refined GRS using fine mapping to include a large number of genetic variants.

Methods: A total of 208 participants of the Fatty Acid Sensor (FAS) Study received 5 g fish oil/d, containing 1.9-2.2 g eicosapentaenoic acid and 1.1 g docosahexanoic acid, for 6 wk. Plasma TG concentrations were measured before and after supplementation. Dense genotyping and genotype imputation were used to refine mapping around GWAS hits. A GRS was computed by summing the number of at-risk alleles of tagging SNPs. Analyses were replicated in samples of the FINGEN study.

Results: A total of 31 tagging SNPs associated with the TG response were used for GRS calculation in the FAS study. In a general linear model adjusted for age, sex, and body mass index, the GRS explained 49.73% of TG response variance (P < 0.0001). Nonresponders to the n-3 FA supplementation had a higher GRS than did responders. In the FINGEN replication study, the GRS explained 3.67% of TG response variance (P = 0.0006).

Conclusions: Fine mapping proved to be effective to refine the previous GRS. Carrying increasing numbers of at-risk alleles of 31 SNPs confers a higher risk of being nonresponsive to n-3 FAs. The genetic profile therefore appears to be an important determinant of the plasma TG response to an n-3 FA supplementation and could be used to target those most likely to gain clinical benefit. This trial was registered at http://www.clinicaltrials.gov as NCT01343342.
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http://dx.doi.org/10.1093/ajcn/nqy298DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6358031PMC
January 2019

Canadian Cardiovascular Society Position Statement on Familial Hypercholesterolemia: Update 2018.

Can J Cardiol 2018 12;34(12):1553-1563

Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montréal, Quebec, Canada; Department of Medicine, McGill University, Montréal, Quebec, Canada.

Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease. It affects 1 in 250 individuals worldwide, and of the approximately 145,000 Canadians estimated to have FH, most are undiagnosed. Herein, we provide an update of the 2014 Canadian Cardiovascular Society position statement on FH addressing the need for case identification, prompt recognition, and treatment with statins and ezetimibe, and cascade family screening. We provide a new Canadian definition for FH and tools for clinicians to make a diagnosis. The risk of atherosclerotic cardiovascular disease in patients with "definite" FH is 10- to 20-fold that of a normolipidemic individual and initiating treatment in youth or young adulthood can normalize life expectancy. Target levels for low-density lipoprotein cholesterol are proposed and are aligned with the Canadian Cardiovascular Society guidelines on dyslipidemia. Recommendation for the use of inhibitors of proprotein convertase kexin/subtilisin type 9 are made in patients who cannot achieve therapeutic low-density lipoprotein cholesterol targets on maximally tolerated statins and ezetimibe. The writing committee used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology in the preparation of the present document, which offers guidance for practical evaluation and management of patients with FH. This position statement also aims to raise awareness of FH nationally, and to mobilize patient support, promote knowledge translation, and availability of treatment and health care resources for this under-recognized, but important medical condition.
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http://dx.doi.org/10.1016/j.cjca.2018.09.005DOI Listing
December 2018

Correlates of the difference in plasma carotenoid concentrations between men and women.

Br J Nutr 2019 01 5;121(2):172-181. Epub 2018 Nov 5.

1Institute of Nutrition and Functional Food,Université Laval,Québec,CanadaG1V 0A6.

Health professionals consider the evaluation of eating habits to be challenging, given the potential biases of dietary questionnaires based on self-reported data. Circulating carotenoid concentrations are reliable biomarkers of dietary carotenoid intake and could be useful in the validation of dietary assessment tools. However, there is a sex difference in circulating carotenoids, with women displaying higher concentrations compared with men independent of intake. The aim of the present study was to identify the correlates of plasma carotenoid concentrations among men (n 155) and women (n 110) enrolled in six fully controlled dietary interventions with varying dietary carotenoid intakes. We looked at the associations of post-intervention fasting plasma carotenoid concentrations (α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene and zeaxanthin) with physical and metabolic characteristics. We found that increased body weight (r -0·47, P<0·0001) and waist circumference (r -0·46, P<0·0001) were associated with lower plasma total carotenoid concentrations, while elevated plasma LDL-cholesterol (r 0·49, P<0·0001) and HDL-cholesterol (r 0·50, P<0·0001) concentrations were correlated with higher total carotenoids in plasma. Women had significantly higher plasma total carotenoid concentrations compared with men, despite significantly lower dietary carotenoid intake. Adjustment of circulating carotenoid concentrations for plasma HDL-cholesterol eliminated sex difference in plasma carotenoid concentrations. Our results suggest that physical characteristics as well as plasma lipids are associated with circulating carotenoid concentrations and that these variables should be taken into account when using plasma carotenoids as biomarkers for food intake in men and women.
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http://dx.doi.org/10.1017/S0007114518003045DOI Listing
January 2019

The spectrum of type III hyperlipoproteinemia.

J Clin Lipidol 2018 Nov - Dec;12(6):1383-1389. Epub 2018 Sep 14.

Centre Hospitalier de l'Universite Laval, Quebec, Quebec, Canada.

Background: Type III hyperlipoproteinemia is a highly atherogenic dyslipoproteinemia characterized by hypercholesterolemia and hypertriglyceridemia due to markedly increased numbers of cholesterol-enriched chylomicron and very-low-density lipoprotein (VLDL) remnant lipoprotein particles. Type III can be distinguished from mixed hyperlipidemia based on a simple diagnostic algorithm, which involves total cholesterol, triglycerides, and apolipoprotein B (apoB). However, apoB is not measured routinely.

Objective: The objective of the present study was to determine if patients with type III could be distinguished from mixed hyperlipidemia based on lipoprotein lipids.

Methods: Classification was based first on total cholesterol and triglyceride and then on the apoB diagnostic algorithm using apoB plus total cholesterol plus triglycerides, and validated by sequential ultracentrifugation. Four hundred and forty normals, 637 patients with hypertriglyceridemia, and 714 with hypertriglyceridemia and hypercholesterolemia were studied. Plasma lipoproteins were separated by sequential ultracentrifugation and heparin-manganese precipitation. Cholesterol, triglyceride, and apoB were measured in plasma and isolated lipoprotein fractions.

Results: Of the 1351 patients with hypertriglyceridemia, 49 had type III hyperlipoproteinemia, as diagnosed by the apoB algorithm and validated by ultracentrifugation. Plasma triglycerides were higher in the type III subjects: 4.16 mmol/L (3.35-6.08, 25th-75th percentile), but there was considerable overlap with the hypertriglyceridemic subjects 2.65 mmol/L (1.91-4.20, 25th-75th percentile) and the combined hyperlipidemic subjects 3.02 mmol/L (2.07-5.32, 25th-75th percentile). Similarly, total cholesterol was 4.79 mmol/L (4.31-5.58, 25th-75th percentile) for type III vs 5.5 mmol/L (4.64-5.78, 25th-75th percentile) and 7.02 mmol/L (6.39-7.96, 25th-75th percentile), respectively. By contrast, as identified by the apoB algorithm, the VLDL-C/TG, VLDL-C/VLDL-TG, VLDL-C/VLDL apoB, and VLDL apoB/LDL apoB ratios were all higher in type III than in the other hypertriglyceridemic dyslipoproteinemias with the exception of type V as diagnosed by the apoB algorithm.

Conclusion: Cholesterol and triglycerides cannot reliably distinguish type III hyperlipoproteinemia from mixed hyperlipidemia. Adding apoB and applying the apoB algorithm makes reliable diagnosis possible and easy. However, unless apoB is introduced into routine clinical care, type III hyperlipoproteinemia will often not be recognized. Given the cardiovascular risk associated with type III and its responsiveness to treatment, this should not be acceptable.
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http://dx.doi.org/10.1016/j.jacl.2018.09.006DOI Listing
October 2019

Familial hypercholesterolemia in Canada: Initial results from the FH Canada national registry.

Atherosclerosis 2018 10;277:419-424

Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, QC, Canada; Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, QC, Canada. Electronic address:

Background And Aims: Familial hypercholesterolemia (FH) is under-diagnosed and under-treated in most of the world, including Canada. National registries play a key role in identifying patients with FH, understanding gaps in care, and advancing the science of FH to better treat these patients.

Methods: FH Canada has established a national registry across 19 academic sites acting as "hubs" in Canada to increase awareness and access to standard-of-care therapies.

Results: To-date, more than 3000 patients with FH have been entered into a secure, web-based database. Early outcomes of this initiative include a greater understanding of treatment gaps for patients with FH in Canada, the development of a new, simplified Canadian definition of FH, and tools to aid in the diagnosis of FH, including imputation of baseline levels of LDL cholesterol.

Conclusions: As the national registry expands in size and scope, further learning will emerge with ultimate benefit for the diagnosis and treatment of FH in Canada.
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http://dx.doi.org/10.1016/j.atherosclerosis.2018.05.040DOI Listing
October 2018

Comparing Interviewer-Administered and Web-Based Food Frequency Questionnaires to Predict Energy Requirements in Adults.

Nutrients 2018 Sep 12;10(9). Epub 2018 Sep 12.

Institute of Nutrition and Functional Foods (INAF), Laval University, Quebec City, QC G1V 0A6, Canada.

Traditional food frequency questionnaires (FFQs) are influenced by systematic error, but web-based FFQ (WEB-FFQs) may mitigate this source of error. The objective of this study was to compare the accuracy of interview-based and web-based FFQs to assess energy requirements (mERs). The mER was measured in a series of controlled feeding trials in which participants daily received all foods and caloric drinks to maintain stable body weight over 4 to 6 weeks. FFQs assessing dietary intakes and hence mean energy intake were either interviewer-administered by a registered dietitian (IA-FFQ, = 127; control method) or self-administered using a web-based platform (WEB-FFQ, = 200; test method), on a single occasion. Comparison between self-reported energy intake and mER revealed significant under-reporting with the IA-FFQ (-9.5%; 95% CI, -12.7 to -6.1) and with the WEB-FFQ (-11.0%; 95% CI, -15.4 to -6.4), but to a similar extent between FFQs ( = 0.62). However, a greater proportion of individuals were considered as accurate reporters of energy intake using the IA-FFQ compared with the WEB-FFQ (67.7% vs. 48.0%, respectively), while the prevalence of over-reporting was lower with the IA-FFQ than with the WEB-FFQ (6.3% vs. 17.5%, respectively). These results suggest less accurate prediction of true energy intake by a self-administered WEB-FFQ than with an IA-FFQ.
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http://dx.doi.org/10.3390/nu10091292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6165380PMC
September 2018

Simplified Canadian Definition for Familial Hypercholesterolemia.

Can J Cardiol 2018 09 19;34(9):1210-1214. Epub 2018 May 19.

Research Institute of the McGill University Health Centre, Royal Victoria Hospital, Montreal, Quebec, Canada; Department of Medicine, McGill University, Royal Victoria Hospital, Montreal, Quebec, Canada.

Familial hypercholesterolemia (FH) is an autosomal codominant lipoprotein disorder characterized by elevated low-density lipoprotein cholesterol (LDL-C) and high risk of premature atherosclerotic cardiovascular disease. Definitions for FH rely on complex algorithms that are on the basis of levels of total or LDL-C, clinical features, family history, and DNA analysis that are often difficult to obtain. We propose a novel simplified definition for FH. Definite FH includes: (1) elevated LDL-C (≥ 8.50 mmol/L); or (2) LDL-C ≥ 5.0 mmol/L (for age 40 years or older; ≥ 4.0 mmol/L if age younger than 18 years; and ≥ 4.5 mmol/L if age is between 18 and 39 years) when associated with at least 1 of: (1) tendon xanthomas; or (2) causal DNA mutation in the LDLR, APOB, or PCSK9 genes in the proband or first-degree relative. Probable FH is defined as subjects with an elevated LDL-C (≥ 5.0 mmol/L) and the presence of premature atherosclerotic cardiovascular disease in the patient or a first-degree relative or an elevated LDL-C in a first-degree relative. LDL-C cut points were determined from a large database comprising > 3.3 million subjects. To compare the proposed definition with currently used algorithms (ie, the Simon Broome Register and Dutch Lipid Clinic Network), we performed concordance analyses in 5987 individuals from Canada. The new FH definition showed very good agreement compared with the Simon Broome Register and Dutch Lipid Clinic Network criteria (κ = 0.969 and 0.966, respectively). In conclusion, the proposed FH definition has diagnostic performance comparable to existing criteria, but adapted to the Canadian population, and will facilitate the diagnosis of FH patients.
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http://dx.doi.org/10.1016/j.cjca.2018.05.015DOI Listing
September 2018

Assessing the impact of the diet on cardiometabolic outcomes: are multiple measurements post-intervention necessary?

Eur J Clin Nutr 2019 11 31;73(11):1546-1550. Epub 2018 Jul 31.

Institute of Nutrition and Functional Foods (INAF), Pavillon des Services, Laval University, Quebec City, Canada.

The purpose of this study was to examine how using the mean of two consecutive measurements vs. one measurement post-treatment influences the sample size required to detect changes in cardiometabolic risk factors in dietary studies. For a given statistical power, using the mean of two measurements taken on consecutive days post-treatment instead of a single measurement significantly reduces the sample size required to observe changes in triglyceride, total apolipoprotein B100, and C-reactive protein concentrations in the context of a supplementation study. In the context of a controlled-feeding study, this gain is seen only in the case of change in triglyceride concentrations.
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http://dx.doi.org/10.1038/s41430-018-0257-0DOI Listing
November 2019

Diets Low in Saturated Fat with Different Unsaturated Fatty Acid Profiles Similarly Increase Serum-Mediated Cholesterol Efflux from THP-1 Macrophages in a Population with or at Risk for Metabolic Syndrome: The Canola Oil Multicenter Intervention Trial.

J Nutr 2018 05;148(5):721-728

Departments of Nutritional Sciences, Veterinary and Biomedical Sciences, and Biobehavioral Health, The Pennsylvania State University, University Park, PA.

Background: Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear.

Objective: The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity.

Methods: The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure.

Results: The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively).

Conclusion: Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.
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http://dx.doi.org/10.1093/jn/nxy040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669947PMC
May 2018