Cardiovascular disease prevention in heterozygous familial hypercholesterolemia: how important is a healthy diet in the era of long-lasting cholesterol-lowering drug therapies?

PURPOSE OF REVIEW: This review aims to provide an in-depth perspective on the importance of diet for cardiovascular disease (CVD) prevention in heterozygous familial hypercholesterolemia (HeFH). RECENT FINDINGS: Even though data on diet and CVD prevention in HeFH are limited, the currently available evidence supports its cholesterol-lowering effect and its favorable association with CVD risk on the long-term. However, qualitative evidence from individuals with HeFH suggests that there is a common perception that diet is useless compared to medication, and this misconception serves as a barrier to healthy eating. On the other hand, evidence also suggests that individuals with HeFH are at higher risk of eating disorders compared with unaffected individuals. Family history of premature death and the chronic nature of the disease would be in cause. SUMMARY: Emphasizing a healthy diet needs to remain at the foundation of CVD prevention in HeFH. Evidence are limited but supportive of the cholesterol-lowering and cardioprotective potential effects of diet. Engaging in conversations about healthy dieting with individuals in HeFH is likely to help prevent misconceptions about diet. Additionally, it could help reduce the risk of eating disorders, which, altogether, is likely to improve overall CVD prevention.

Household Food Insecurity and Changes in BMI Z-Score in a Pediatric Obesity Management Clinic.

BACKGROUND: Multicomponent lifestyle interventions are fundamental in pediatric obesity management. However, whether household food insecurity influences the efficacy of such interventions remains undocumented. OBJECTIVES: The objective was to compare changes in BMI z-score (BMIz) among children whose family received lifestyle counseling at a pediatric obesity management clinic in Montréal (Canada) according to their household food security status. METHODS: This is a retrospective, longitudinal analysis of medical records of children (2-17 y) with overweight or obesity who received lifestyle counseling at a pediatric obesity management clinic. The number of visits at the clinic and the duration of the follow-up were individualized. Household food security status was assessed using the Health Canada's Household Food Security Survey Module at the first visit at the clinic. BMIz was calculated and updated at each visit. A reduction of ≥0.25 in BMIz between the last and the first visit at the clinic was considered clinically meaningful. Statistical significance was considered at P < 0.05. RESULTS: Among the 214 children included in the study, 83 (38.8%) lived in a food insecure household. In multivariable-adjusted analyses, differences in BMIz between the last and the first appointment tended to be smaller among children who lived in a food insecure household than those in children living in a food secure household [ΔBMIzfood insecurity = -0.432 (95% CI: -0.672, -0.193) compared with ΔBMIzfood security = -0.556 (95% CI: -0.792, -0.319; P = 0.14)]. Differences were most notable in the first 6 mo of follow-up. The OR of achieving a clinically significant reduction in BMIz over follow-up associated with household food insecurity, compared with household food security, was 0.57 (95% CI: 0.31, 1.05; P = 0.07). CONCLUSIONS: In this sample of children followed up at a pediatric obesity clinic, those who lived in a food insecure household experienced smaller BMIz reductions than those who lived in a food secure household.

Relationship between lifestyle habits and cardiovascular risk factors in familial hypercholesterolemia.

BACKGROUND AND AIM: Little is known about the cardioprotective potential of a healthy lifestyle in familial hypercholesterolemia (FH). The objective of this study was to evaluate the relationship between lifestyle and cardiovascular risk factors in adults with FH. METHODS AND RESULTS: This cross-sectional study leveraged data from the CARTaGENE Quebec population-based cohort (Canada). Participants with FH were identified using the validated Simplified Canadian Definition for FH. A healthy lifestyle score (HLS), ranging from 0 to 5, was calculated per adherence to 5 lifestyle habits: 1) not smoking; 2) being physically active (≥150 min/week of moderate or vigorous physical activity); 3) eating a healthy diet (Alternate Healthy Eating Index ≥50%); 4) having a light to moderate alcohol consumption (men: 1-30 g/day; women: 1-15 g/day); and 5) sleeping 7-8 h/day. Among the 122 included individuals (women, n = 78; men, n = 44; mean age ± SD: 57.3 ± 6.7 years), 92 (75.4%) had a HLS ≤3/5, while only 5 (4.1%) had a HLS of 5/5. After adjustments for sex, age, body mass index, and lipid-lowering medication use, we found no evidence of an association between the HLS and concentrations of LDL-cholesterol (ß = 0.04, 95% CI = -0.08, 0.15 mmol/L; P = 0.54). However, the HLS was favorably associated with HbA1c levels (ß = -0.07, 95% CI = -0.13, -0.01%; P = 0.02), and statistical trends suggested favorable associations with HDL-cholesterol (ß = 0.06, 95% CI = -0.02, 0.14 mmol/L; P = 0.06) and waist circumference (ß = -2.22, 95% CI = -4.62, 0.17 cm; P = 0.07). CONCLUSION: This study suggests that a healthy lifestyle is favorably associated with CVD risk factors in adults with FH.

Food insecurity in households of children receiving care at a paediatric obesity management clinic in Montreal: Overall prevalence and changes associated with the COVID-19 pandemic.

Objectives: Food insecurity and paediatric obesity are two major public health issues in Canada that may have been exacerbated by the COVID-19 pandemic. We assessed food insecurity and its correlates among households of children receiving care at a paediatric obesity management clinic in Montreal. We also assessed whether the prevalence of food insecurity among households of children who received care during the COVID-19 pandemic differed from those who received care before it. Methods: This is a retrospective, cross-sectional analysis of medical records of children (2 to 17 years) who received care at a paediatric obesity management clinic in Montreal (Maison de santé prévention - Approche 180 [MSP-180]). Children's household food security status was assessed using Health Canada's Household Food Security Survey Module. Results: Among the 253 children included in the study, 102 (40.3%) lived in households with moderate (n=89; 35.2%) or severe food insecurity (n=13; 5.1%). Food insecurity was more prevalent in households of children who were first- or second-generation immigrants compared with those who were third generation or more (48.3% versus 30.1%; P=0.03). Prevalence of food insecurity among households of children who received care during the COVID-19 pandemic was 5.5% higher than among those who received care before the pandemic, but the difference was not statistically significant (39.6% versus 45.1%; P=0.65). Conclusions: Forty per cent of children treated at this paediatric obesity clinic lived in a food insecure household. This prevalence may have increased during the first year of the COVID-19 pandemic, but statistical power was insufficient to confirm it.

Walnut Consumption, Plasma Metabolomics, and Risk of Type 2 Diabetes and Cardiovascular Disease.

BACKGROUND: Walnut consumption is associated with lower risk of type 2 diabetes (T2D) and cardiovascular disease (CVD). However, it is unknown whether plasma metabolites related to walnut consumption are also associated with lower risk of cardiometabolic diseases. OBJECTIVES: The study aimed to identify plasma metabolites associated with walnut consumption and evaluate the prospective associations between the identified profile and risk of T2D and CVD. METHODS: The discovery population included 1833 participants at high cardiovascular risk from the PREvención con DIeta MEDiterránea (PREDIMED) study with available metabolomics data at baseline. The study population included 57% women (baseline mean BMI (in kg/m2): 29.9; mean age: 67 y). A total of 1522 participants also had available metabolomics data at year 1 and were used as the internal validation population. Plasma metabolomics analyses were performed using LC-MS. Cross-sectional associations between 385 known metabolites and walnut consumption were assessed using elastic net continuous regression analysis. A 10-cross-validation (CV) procedure was used, and Pearson correlation coefficients were assessed between metabolite weighted models and self-reported walnut consumption in each pair of training-validation data sets within the discovery population. We further estimated the prospective associations between the identified metabolite profile and incident T2D and CVD using multivariable Cox regression models. RESULTS: A total of 19 metabolites were significantly associated with walnut consumption, including lipids, purines, acylcarnitines, and amino acids. Ten-CV Pearson correlation coefficients between self-reported walnut consumption and the plasma metabolite profile were 0.16 (95% CI: 0.11, 0.20) in the discovery population and 0.15 (95% CI: 0.10, 0.20) in the validation population. The metabolite profile was inversely associated with T2D incidence (HR per 1 SD: 0.83; 95% CI: 0.71, 0.97; P = 0.02). For CVD incidence, the HR per 1-SD was 0.71 (95% CI: 0.60, 0.85; P < 0.001). CONCLUSIONS: A metabolite profile including 19 metabolites was associated with walnut consumption and with a lower risk of incident T2D and CVD in a Mediterranean population at high cardiovascular risk.

Changes in Eating Behaviours Throughout Pregnancy: Associations with Gestational Weight Gain and Pre-pregnancy Body Mass Index.

OBJECTIVE: Most pregnant women gain weight above recommended levels, and this weight gain affects mothers' and children's health. Factors influencing gestational weight gain (GWG) are numerous and include eating behaviours. The objective of this study was to evaluate the association between eating behaviours and GWG while considering pre-pregnancy body mass index (BMI). METHODS: Fifty-three (n = 53) women were recruited at 9.4 ± 0.6 gestational weeks. At each trimester, they completed the Three-Factor Eating Questionnaire, which evaluates disinhibition, dietary restraint, and susceptibility to hunger. Using a weight gain curve, trimester-specific GWG was calculated with interpolated weights. Total GWG was calculated as the difference between maternal weight before delivery and self-reported pre-pregnancy weight (Canadian Task Force Classification II-2). RESULTS: Women were aged 31.5 ± 3.5, and 81.1% had a university degree. The proportion of women who gained weight within recommendations was 21%, 28%, and 26%, at each trimester, respectively, and 38% for total pregnancy. Overall, dietary restraint score was lower in the third trimester in comparison with the first (6.1 ± 4.1 vs. 7.2 ± 4.6; P = 0.049), whereas no difference was observed for disinhibition or susceptibility to hunger. Our data suggest that variations in eating behaviours throughout pregnancy were similar among women who exhibited total GWG below, within, or above recommendations (Ptrim × GWG = NS) (NS: not significant; trim: trimester). Similar observations were reported when women were compared according to their pre-pregnancy BMI (Ptrim × BMI = NS). CONCLUSION: Maintaining high levels of restraint may be challenging considering the increase in hunger, which could explain the decrease observed in dietary restraint scores. Changes in eating behaviours were not associated with total GWG or pre-pregnancy BMI.

Plasma PCSK9 correlates with apoB-48-containing triglyceride-rich lipoprotein production in men with insulin resistance.

Intestinal triglyceride (TG)-rich lipoproteins (TRLs) are important in the pathogenesis of atherosclerosis in insulin resistance (IR). We investigated the association of plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentrations with apoB-48-containing TRL metabolism in 148 men displaying various degrees of IR by measuring in vivo kinetics of TRL apoB-48 during a constant-fed state after a primed-constant infusion of L-[5,5,5-D3]leucine. Plasma PCSK9 concentrations positively correlated with TRL apoB-48 pool size (r = 0.31, P = 0.0002) and production rate (r = 0.24, P = 0.008) but not the fractional catabolic rate (r = -0.04, P = 0.6). Backward stepwise multiple linear regression analysis identified PCSK9 concentrations as a positive predictor of TRL apoB-48 production rate (standard ß = +0.20, P = 0.007) independent of BMI, age, T2D/metformin use, dietary fat intake during the kinetic study, and fasting concentrations of TGs, insulin, glucose, LDL cholesterol, or C-reactive protein. We also assessed intestinal expression of key genes involved in chylomicron processing from duodenal samples of 71 men. Expression of PCSK9 and HMG-CoAR genes was positively associated (r = 0.43, P = 0.002). These results support PCSK9 association with intestinal secretion and plasma overaccumulation of TRL apoB-48 in men with IR.

Differential associations between plasma concentrations of insulin and glucose and intestinal expression of key genes involved in chylomicron metabolism.

The mechanisms underlying the oversecretion of apolipoprotein (apo)B-48-containing triglyceride-rich lipoproteins (TRL) in insulin-resistance (IR) states in humans remain to be fully understood. The objective of this study was to evaluate the association between the plasma levels of insulin and glucose and the intestinal expression of key genes involved in chylomicron metabolism in a large sample of nondiabetic men displaying various degrees of IR. Duodenal biopsies were obtained by gastroduodenoscopy in 127 men free of intestinal disease. Gene expression was measured using quantitative PCR in duodenal samples. Plasma insulin and glucose concentrations were measured in the fasting state. Postprandial TRL apoB-48 kinetics were measured using a primed-constant infusion of l-[5,5,5-D3]leucine for 12 h in a subgroup of 75 subjects maintained in a constant fed state. Plasma insulin levels were negatively associated with intestinal expression of ACS1 (standard ß = -0.20, P = 0.007), DGAT1 (ß = -0.18, P = 0.001), DGAT2 (ß = -0.20, P = 0.02), and MTP (ß = -0.27, P = 0.0005), whereas glucose levels were positively associated with MTP expression (ß = 0.15, P = 0.04) independent of age, BMI, waist circumference, dietary intake, and duodenal expression of SREBP1c. Insulin levels, but not glucose concentrations, were positively correlated with postprandial TRL apoB-48 production rate ( r = 0.24, P = 0.04) and pool size ( r = 0.27, P = 0.03). In conclusion, plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism. These results suggest that alterations in intestinal lipoprotein metabolism associated with IR may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency. NEW & NOTEWORTHY We demonstrate that plasma insulin and glucose levels are differentially associated with the expression of key genes involved in chylomicron metabolism in men. For instance, intestinal expression of MTP is negatively associated with plasma insulin concentrations and positively associated with plasma glucose concentrations. Alterations in intestinal lipoprotein metabolism associated with insulin resistance may be regulated by plasma levels of both insulin and glucose concurrently and are therefore likely modified by the onset of insulin insufficiency.

Impact of lipoprotein apheresis with dextran-sulfate adsorption on the expression of genes involved in cardiovascular health in the blood of patients with homozygous familial hypercholesterolemia.

Lipoprotein apheresis (LA) with dextran sulfate adsorption (DSA) is a reliable method to decrease LDL-cholesterol (C) concentrations in patients with homozygous familial hypercholesterolemia (HoFH). The objective of the present study was to investigate the impact of LA with DSA on the mRNA expression of genes associated with cardiovascular health in the whole blood of HoFH patients. Blood samples were collected before and after LA treatment with DSA in 9 HoFH patients. Microarray analyses were performed to measure the whole blood expression of >30 000 annotated genes pre- and post-LA. Concomitant reductions in LDL-C (median -73.8%, range: -55.9 to -82.0, P = .0001) and lipoprotein (a) concentrations (median -74.1%, range -65.6 to -84.1, P = .003) were induced with LA treatment. LA with DSA did not impact the whole blood mRNA expression of most key genes involved in cardiovascular health, including those associated with cholesterol, fatty acid and lipoprotein metabolism. However, LA with DSA significantly upregulated the whole blood expression of early growth response protein (EGR)1 (1.94-fold, P = .02), EGR3 (1.56-fold, P = .0008) and B-cell lymphoma 3-encoded protein (BCL3; 1.25-fold, P = .03). In conclusion, this study demonstrated that a single LA treatment with DSA has very limited impact on the whole blood expression of a broad spectrum of genes associated with cardiovascular health. Our results suggest that contact between blood cells and the primary membrane or extracorporeal circulation could upregulate the expression of EGR1, EGR3, BCL3, and MMP9 in blood cells.

The elevation of plasma concentrations of apoB-48-containing lipoproteins in familial hypercholesterolemia is independent of PCSK9 levels.

BACKGROUND: Previous studies have reported high plasma concentrations of both intestinal apolipoprotein (apo) B-48-containing lipoproteins and PCSK9 in subjects with familial hypercholesterolemia (FH). However, the extent to which LDL receptor deficiency and PCSK9 levels influence plasma apoB-48 concentrations in humans remains to be fully characterized. The objective of the study was to assess the independent association between FH, PCSK9 concentrations and plasma apoB-48 levels in a large cohort of genetically defined FH heterozygotes (HeFH) and homozygotes (HoFH). METHODS: A total of 118 HeFH, 6 HoFH, and 117 controls were included in the study. Plasma PCSK9 and apoB-48 concentrations were measured in the fasting state. RESULTS: Plasma PCSK9 and apoB-48 levels were higher in FH subjects compared with controls (PCSK9: HoFH: 642.6 ± 246.9 vs. HeFH: 324.9 ± 119.8 vs. CONTROLS: 194.5 ± 65.9 ng/mL, P < 0.0001; apoB-48: HoFH: 14.71 ± 4.36 vs. HeFH: 6.55 ± 4.24 vs. CONTROLS: 3.03 ± 2.07 µg/mL; P < 0.0001). There were no correlations between apoB-48 and PCSK9 plasma levels in both controls (ρ = 0.06, P = 0.5) and HeFH subjects (ρ = 0.07, P = 0.4). Multiple linear regression analysis showed that the FH status was the only independent factor associated with apoB-48 levels, contributing to 28.7% of the variance (P < 0.0001). CONCLUSIONS: These data indicate that the elevation in plasma apoB-48 levels associated with FH is independent of PCSK9 levels. TRIAL REGISTRATION: NCT02225340 .

Ezetimibe increases intestinal expression of the LDL receptor gene in dyslipidaemic men with insulin resistance.

AIM: To gain further insight into intestinal cholesterol homeostasis in dyslipidaemic men with insulin resistance (IR) by examining the impact of treatment with ezetimibe on the expression of key genes involved in cholesterol synthesis and LDL receptor (R)-mediated uptake of lipoproteins. METHODS: A total of 25 men with dyslipidaemia and IR were recruited to participate in this double-blind, randomized, crossover, placebo-controlled trial. Participants received 10 mg/day ezetimibe or placebo for periods of 12 weeks each. Intestinal gene expression was measured by quantitative PCR in duodenal biopsy samples collected by gastroduodenoscopy at the end of each treatment. RESULTS: A total of 20 participants completed the protocol. Treatment with ezetimibe significantly increased intestinal LDLR (+16.2%; P = .01), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoAR; +14.0%; P = .04) and acetyl-Coenzyme A acetyltransferase 2 (ACAT-2) mRNA expression (+12.5%; P = .03). Changes in sterol regulatory element-binding transcription factor 2 (SREBP-2) expression were significantly correlated with changes in HMG-CoAR (r = 0.55; P < .05), ACAT-2 (r = 0.69; P < .001) and proprotein convertase substilisin/kexin type 9 (PCSK9) expression (r = 0.45; P < .05). CONCLUSIONS: These results show that inhibition of intestinal cholesterol absorption by ezetimibe increases expression of the LDLR gene, supporting the concept that increased LDL clearance with ezetimibe treatment occurs not only in the liver but also in the small intestine.

Comparison of two low-density lipoprotein apheresis systems in patients with homozygous familial hypercholesterolemia.

Low-density lipoprotein (LDL) apheresis (LA) is a reliable method to decrease LDL-C concentrations and remains the gold standard therapy in homozygous familial hypercholesterolemia (HoFH). The objective of this study was to compare the efficacy of two LA systems [heparin-induced extracorporeal LDL precipitation (HELP) vs. dextran sulfate adsorption (DS) on the reduction of lipids, inflammatory markers, and adhesion molecules in a sample of genetically defined HoFH subjects (n = 9)]. Fasting blood samples were collected before and after LA. All subjects served as their own control and were first treated with the HELP system then with DS in this single sequence study. Compared with HELP, DS led to significantly greater reductions in total cholesterol (-63.3% vs. -59.9%; P = 0.05), LDL-C (-70.5% vs. -63.0%; P = 0.02), CRP (-75.3% vs. -48.8%; P < 0.0001), and TNF-α (-23.7% vs. +14.7%; P = 0.003). Reductions in the plasma levels of PCSK9 (-45.3% vs. -63.4%; P = 0.31), lipoprotein (a) (-70.6% vs. -65.0%; P = 0.30), E-selectin (-16.6% vs. -18.3%; P = 0.65), ICAM-1 (-4.0 vs. 5.6%; P = 0.56), and VCAM-1 (8.3% vs. -1.8%; P = 0.08) were not different between the two systems. For the same volume of filtered plasma (3,000 mL), however, HELP led to greater reductions in plasma apoB (-63.1% vs. -58.3%; P = 0.04), HDL-C (-20.6% vs. -6.5%; P = 0.003), and PCSK9 (-63.4% vs. -28.5%; P = 0.02) levels. These results suggest that both LA systems are effective in reducing plasma lipids and inflammatory markers in HoFH. Compared with HELP, greater reductions in lipid levels and inflammatory markers were achieved with DS, most likely because this method allows for a larger plasma volume to be filtered. J. Clin. Apheresis 31:359-367, 2016. © 2015 Wiley Periodicals, Inc.

Impact of milk consumption on cardiometabolic risk in postmenopausal women with abdominal obesity.

BACKGROUND: The impact of dairy intake on cardiometabolic risk factors associated with metabolic syndrome (MetS) needs further research. OBJECTIVE: To investigate the impact of milk consumption on a wide array of cardiometabolic risk factors associated with MetS (blood lipids, cholesterol homeostasis, glucose homeostasis, systemic inflammation, blood pressure, endothelial function) in postmenopausal women with abdominal obesity. METHODS: In this randomized, crossover study, 27 women with abdominal obesity consumed two 6-week diets based on the National Cholesterol Education Program (NCEP), one with 3.2 servings/d of 2% fat milk per 2000 kcal (MILK) and one without milk or other dairy (NCEP). The macronutrient composition of both diets was comparable (55% carbohydrates, 15% proteins, 30% fat and 10% saturated fat). RESULTS: The MILK diet had no significant effect on LDL-C, triglycerides, LDL size, CRP and cell adhesion molecule concentrations and on indicators of insulin sensitivity. The MILK diet reduced HDL-C, adiponectin, endothelin and fasting glucose levels as well blood pressure (all P ≤ 0.01), but those changes were comparable to those seen with the NCEP milk-free diet (all between-diet P ≥ 0.07). Finally, the MILK diet was associated with lower VLDL apolipoprotein B fractional catabolic rate (-13.4%; P = 0.04) and plasma sterol concentrations (-12.0%; P = 0.04) compared with the control NCEP milk-free diet. CONCLUSIONS: These data suggest that short-term consumption of low fat milk in the context of a prudent NCEP diet has no favorable nor deleterious effect on cardiometabolic risk factors associated with MetS in postmenopausal women with abdominal obesity.

Impact of dairy consumption on essential hypertension: a clinical study.

BACKGROUND: Several studies have presented evidence suggesting that dairy consumption has beneficial effects on blood pressure (BP) in healthy subjects; however, only a few studies have examined this possibility in patients with established essential hypertension using ambulatory blood pressure monitoring. The objective of this study was to investigate how consuming dairy products impacts mean daytime systolic and diastolic BP in men and women with mild to moderate essential hypertension. METHODS: Eighty-nine men and women with systolic BP ≥ 135 mm Hg and ≤ 160 mm Hg and diastolic BP ≤ 110 mm Hg were enrolled in this single-blind, randomized, cross-over, controlled study. Participants had to incorporate three daily servings of dairy products or control products equivalent in macronutrients and sodium during four-week treatment phases. Twenty-four hour ambulatory BP and endothelial function were assessed at screening and at the end of each dietary phase. RESULTS: The consumption of three daily servings of dairy products led to a significant reduction in mean daytime ambulatory systolic BP (-2 mm Hg; P = 0.05) in men compared with readings after the control phase. In women, dairy consumption had no effect on ambulatory systolic BP. Moreover, endothelial function was significantly improved by dairy consumption in the whole cohort. CONCLUSION: These data indicate that the consumption of three daily servings of dairy products have beneficial effects on daytime systolic ambulatory BP compared to a heart-healthy, dairy-free, diet in men with mild to moderate essential hypertension. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov as NCT01776216.

Relationship Between Diet Quality and Antihypertensive Medication Intensity Among Adults With Metabolic Syndrome-Associated High Blood Pressure.

Background: Management of high blood pressure (BP), a key feature of the metabolic syndrome (MetS), relies on diet and medication. Whether these modalities are used as complements has never been evaluated in real-world settings. This study assessed the relationship between diet quality and antihypertensive medication intensity among adults with MetS-associated high BP. Methods: This cross-sectional study included 915 adults with MetS-associated high BP from the CARTaGENE cohort (Québec, Canada), of whom 677 reported using BP-lowering medication. Antihypertensive medication intensity was graded per the number of BP-lowering classes used simultaneously. Diet quality was assessed using the Dietary Approach to Stop Hypertension (DASH) score. Results: No evidence of a relationship between antihypertensive medication intensity and diet quality was found (ß for each additional antihypertensive = -0.05; 95% CI, -0.35; 0.26 DASH score points). However, among men aged < 50 years and women aged < 60 years, the DASH score was inversely associated with medication intensity (ß = -0.72; 95% CI, -1.24, -0.19), whereas this relationship tended to be positive among older participants (ß = 0.32; 95% CI, -0.05, 0.69). Among participants with low Framingham risk score, the DASH score was inversely associated with medication intensity (ß = -0.70; 95% CI, -1.31, -0.09), but no evidence of an association was found among individuals at moderate (ß = 0.00; 95% CI, -0.45, 0.45) or high (ß = 0.30, 95% CI, -0.24, 0.84) risk. Conclusions: In this cohort of adults with MetS-associated high BP, there was an overall lack of complementarity between diet quality and BP-lowering medication, especially among younger individuals and those with a lower risk for cardiovascular disease for whom diet quality was inversely associated with intensity of medication.

Introduction: La prise en charge de la pression artérielle (PA) élevée, l'une des caractéristiques principales du syndrome métabolique (SMet), repose sur une saine alimentation et l'usage de médicaments hypotenseurs. Il n'a jamais été évalué si ces modalités étaient utilisées de façon complémentaire en contexte réel. La présente étude portait sur la relation entre la qualité de l'alimentation et la médication antihypertensive au sein d'adultes ayant une PA élevée associée au SMet. Méthodes: Cette étude transversale regroupait 915 adultes de la cohorte CARTaGENE (Québec, Canada) ayant une PA élevée associée au SMet, dont 677 ont rapporté prendre des médicaments abaissant la PA. L'intensité de la médication antihypertensive a été évaluée par le nombre de classes de médicaments abaissant la PA utilisées simultanément. La qualité du régime alimentaire a été évaluée à l'aide du score Dietary Approache to Stop Hypertension (DASH). Résultats: Aucune évidence d'une relation entre l'intensité des médicaments antihypertenseurs et la qualité de l'alimentation n'a été observée (ß pour chaque antihypertenseur supplémentaire = ­0,05 ; intervalle de confiance [IC] à 95 %, ­0,35 ; 0,26 point au score DASH). Toutefois, chez les hommes âgés < 50 ans et chez les femmes âgées < 60 ans, le score DASH était inversement associé à l'intensité des médicaments (ß = ­0,72 ; IC à 95 %, ­1,24, ­0,19), alors que cette relation avait tendance à être positive chez les participants plus âgés (ß = 0,32 ; IC à 95 %, ­0,05, 0,69). Chez les participants qui avaient un score de risque de Framingham faible, le score DASH était inversement associé à l'intensité des médicaments (ß = ­0,70 ; IC à 95 %, ­1,31, ­0,09), mais aucune évidence d'une association n'a été observée chez les individus qui avaient un risque modéré (ß = 0,00 ; IC à 95 %, ­0,45, 0,45) ou élevé (ß = 0,30, IC à 95 %, ­0,24, 0,84). Conclusions: Au sein de cette cohorte d'adultes qui avaient une PA élevée associée au SMet, aucune évidence de complémentarité entre la qualité de l'alimentation et l'intensité de la médication antihypertensive n'a été observée, particulièrement chez les individus plus jeunes et chez ceux exposés à un risque plus faible de maladies cardiovasculaires pour qui la qualité du régime alimentaire était inversement associée à l'intensité des médicaments.

Relationship between COVID-19 pandemic-related experienced stress and lifestyle habits among university students from Québec, Canada.

Whether COVID-19-related experienced stress influenced lifestyle habits remains to be thoroughly evaluated among university students. This study examined the relationship between COVID-19-related experienced stress and subsequent lifestyle habits among undergraduate students. This cross-sectional study included 708 undergraduate students from Université Laval (Québec, Canada) participating in the Expériences Pandémiques (ExPan) cohort. Data on COVID-19-related experienced stress and lifestyle were self-reported using a questionnaire completed between February and April of 2022. A stress index (SI) was computed by summing scores associated with 31 situational statements related to the pandemic (e.g., not being able to see friends, dealing with job loss). A healthy lifestyle score (HLS) ranging from zero to seven was calculated based on seven lifestyle habits: moderate-to-vigorous physical activity, sleep quality, fruit and vegetable intake, tobacco and electronic cigarette use, alcohol consumption, cannabis use, and hard or sedative-hypnotic drugs use. In multivariable-adjusted models, a negative association between the SI and the HLS was found (ß10% increment SI = -0.23, 95% CI = -0.30, -0.16 HLS point; P < 0.0001). The SI was also negatively associated with sleep quality, and fruit and vegetable consumption, while being positively associated with at-risk alcohol consumption, cannabis use, and hard or sedative-hypnotic drug use. Subgroup analyses suggested a negative relationship between the SI and HLS among participants who did not receive academic accommodations (e.g., additional time for evaluations, personal notetaker), but not those who received such accommodations. This study suggests that COVID-19-related experienced stress was negatively associated with healthy lifestyle habits in this cohort of undergraduate students.

Relationship Between Diet Quality and Statin Use Among Adults With Metabolic Syndrome From the CARTaGENE Cohort.

Background: In metabolic syndrome (MetS), cardiovascular disease (CVD) risk reduction relies on the complementary use of diet and lipid-lowering medication. Evidence suggests that initiating such medication may impede diet quality. The objective of this study was to evaluate the relationship between diet quality and statin use among adults with MetS and free of CVD from the Province of Québec. Methods: This cross-sectional study included 2481 adults with MetS (40-69 years of age) from the CARTaGENE Québec population-based cohort, of whom 463 self-reported using statin monotherapy. Diet was assessed using the Canadian Dietary History Questionnaire II, a food- frequency questionnaire, and diet quality was assessed using the Alternative Healthy Eating Index (AHEI). Results: In multivariable-adjusted linear regression models, statin users had lower AHEI (%) compared with nonusers (users: 40.0; 95% confidence interval [CI], 38.9, 41.2 vs nonusers: 41.2; 95% CI, 40.4, 42.0; P = 0.03] because of a lower consumption of vegetables and whole grains. Stratified interaction analyses showed that the lower diet quality among statin users was mostly prevalent among men aged ≥ 50 years and women aged ≥ 60 years, among individuals with annual household incomes of < $50,000 and persons who self-reported history of high blood pressure. Conclusions: In this cohort of adults with MetS from Quebéc, the use of statin monotherapy in primary prevention of CVD was associated with a slightly lower diet quality. These data suggest suboptimal complementarity between diet quality and use of cholesterol-lowering medication in primary prevention of CVD in MetS.

Contexte: Dans le syndrome métabolique, la réduction du risque de maladie cardiovasculaire repose sur la complémentarité entre une saine alimentation et l'utilisation d'hypolipidémiants. Des évidences suggèrent que l'initiation d'un traitement médicamenteux hypolipémiant influencerait négativement la qualité de l'alimentation. Cette étude avait pour objectif de déterminer la relation entre la qualité de l'alimentation et l'utilisation de statines chez des adultes avec un syndrome métabolique, mais sans maladie cardiovasculaire, au Québec. Méthodologie: Cette étude transversale comptait 2481 adultes avec un syndrome métabolique (âgés de 40 à 69 ans) provenant de la cohorte CARTaGENE, représentative de la population du Québec, dont 463 sujets ayant autodéclaré qu'ils prenaient une statine en monothérapie. L'alimentation des sujets a été évaluée à l'aide du Canadian Dietary History Questionnaire II, un questionnaire de fréquence alimentaire, et la qualité de l'alimentation a été évaluée à l'aide de l'Alternative Healthy Eating Index (AHEI). Résultats: Dans des modèles de régression linéaire multivariée, les utilisateurs de statines ont présenté un indice AHEI (%) plus faible en comparaison aux non-utilisateurs (utilisateurs : 40,0; intervalle de confiance [IC] à 95 % : 38,9-41,2 vs non-utilisateurs : 41,2; IC à 95 % : 40,4-42,0; p = 0,03), en raison d'une plus faible consommation de légumes et de grains entiers. Selon des analyses d'interaction stratifiées, la plus faible qualité nutritionnelle chez les utilisateurs de statines était particulièrement prévalente chez les hommes de ≥ 50 ans et les femmes de ≥ 60 ans, chez les personnes dont le revenu annuel du ménage était < 50 000 dollars et chez les personnes ayant autodéclaré des antécédents d'hypertension. Conclusions: Dans cette cohorte d'adultes du Québec avec un syndrome métabolique, l'utilisation de statines en monothérapie dans la prévention des maladies cardiovasculaires était associée à une alimentation dont la qualité était légèrement plus faible. Ces données suggèrent une complémentarité sous-optimale entre la qualité de l'alimentation et l'utilisation d'hypocholestérolémiants en prévention des maladies cardiovasculaires chez les personnes avec un syndrome métabolique.

Relationship Between Diet Quality and Glucose-Lowering Medication Intensity Among Adults With Type 2 Diabetes: Results From the CARTaGENE Cohort.

Background: In real-world settings, whether diet and medication are used as complements for glycemic management in type 2 diabetes (T2D) remains unclear. This study assessed the relationship between diet quality and intensity of glucose-lowering medication among adults with T2D. Methods: This cross-sectional study included 352 adults with T2D from the CARTaGENE Québec population-based cohort. Diet quality was assessed using the Healthful Plant-Based Diet Index (hPDI). Glucose-lowering medication intensity was graded according to self-reported information on the type and number of drugs: no medication; oral monotherapy; oral polytherapy; and insulin with and without oral medication. In the subsample of 239 individuals who reported the medication dosages, intensity was also graded using the Medication Effect Score (MES). Results: In multivariable-adjusted models, we found no evidence of a relationship between the hPDI and medication intensity, assessed using the categorical approach (Pbetween-group = 0.25) or the MES (P = 0.43). However, the hPDI was inversely associated with the MES among men < 50 years of age and women < 60 years (ß1-point MES = -2.24 [95% confidence interval, -4.46, -0.02] hPDI points), but not among older individuals (ß = -0.03 [-1.28, 1.21] hPDI points). Evidence of a nonsignificant inverse relationship between the hPDI and HbA1c was observed (ß10-point hPDI = -0.23% [-0.63, 0.17]), whereas a positive and significant association between the MES and hemoglobin (Hb)A1c was found (ß1-point MES = 0.30% [0.10, 0.51]). Conclusions: In this cohort of adults with T2D, there was an overall lack of complementarity between diet quality and intensity of glucose-lowering medication. The issue was particularly important among younger adults for whom diet quality was inversely associated with intensity of medication.

Introduction: Il n'a jamais été étudié, en contexte réel, si la qualité de l'alimentation et la médication sont utilisées de façon complémentaire dans la gestion de la glycémie chez des personnes avec le diabète de type 2 (DT2). La présente a évalué la relation entre la qualité de l'alimentation et l'intensité de la médication hypoglycémiante chez des adultes avec DT2. Méthodes: Cette étude transversale portait sur 352 adultes avec DT2 participant à la cohorte populationnelle québécoise CARTaGENE. Nous avons évalué la qualité du régime à l'aide du Healthful Plant-based Diet Index (hPDI, soit l'indice d'un régime alimentaire à base de plantes). Nous avons évalué l'intensité des médicaments hypoglycémiants à partir des renseignements fournis sur le type et le nombre de médicaments : aucun médicament, monothérapie orale, polythérapie orale, insuline avec ou sans médicaments par voie orale. Dans le sous-échantillon de 239 individus qui ont mentionné les posologies de médicaments, nous avons aussi évalué l'intensité au moyen du Medication Effect Score (MES). Résultats: Dans les modèles multivariés, nous n'avons observé aucune évidence de relation entre le hPDI et l'intensité des médicaments au moyen de l'approche catégorielle (Pentre les groupes = 0,25) ou du MES (P = 0,43). Toutefois, le hPDI était inversement associé au MES chez les hommes < 50 ans et chez les femmes < 60 ans (ßMES 1 point = ­2,24 [intervalle de confiance à 95 %, ­4,46, ­0,02] points hPDI), mais non chez les personnes plus âgées (ß = ­0,03 [­1,28, 1,21] point hPDI). Nous avons observé une relation inverse non significative entre le hPDI et l'hémoglobine (Hb)A1c (ßhPDI 10 points = ­0,23 % [­0,63, 0,17]) et une association positive et significative entre le MES et l'HbA1c (ßMES 1 point = 0,30 % [0,10, 0,51]). Conclusions: Au sein de cette cohorte d'adultes avec DT2, nous avons constaté une absence globale de complémentarité entre la qualité de l'alimentation et l'intensité des médicaments hypoglycémiants. Cet enjeu était d'autant plus important chez les personnes plus jeunes pour lesquels la qualité du régime était inversement associée à l'intensité des médicaments.

Association between density of food retailers and fitness centers and gestational diabetes mellitus in Eastern Massachusetts, USA: population-based study.

Background: Few studies have investigated the relationship between the food and physical activity environment and odds of gestational diabetes mellitus (GDM). This study quantifies the association between densities of several types of food establishments and fitness centers with the odds of having GDM. Methods: The density of supermarkets, fast-food restaurants, full-service restaurants, convenience stores and fitness centers at 500, 1000 and 1500 m (m) buffers was counted at residential addresses of 68,779 pregnant individuals from Eastern Massachusetts during 2000-2016. The 'healthy food index' assessed the relative availability of healthy (supermarkets) vs unhealthy (fast-food restaurants, convenience stores) food retailers. Multivariable logistic regression quantified the cross-sectional association between exposure variables and the odds of having GDM, adjusting for individual and area-level characteristics. Effect modification by area-level socioeconomic status (SES) was assessed. Findings: In fully adjusted models, pregnant individuals living in the highest density tertile of fast-food restaurants had higher GDM odds compared to those living in the lowest density tertile (500 m: odds ratio (OR):1.17 95% CI: [1.04, 1.31]; 1000 m: 1.33 95% CI: [1.15, 1.53]); 1500 m: 1.18 95% CI: [1.01, 1.38]). Greater residential density of supermarkets was associated with lower odds of GDM (1000 m: 0.86 95% CI: [0.74, 0.99]; 1500 m: 0.86 95% CI: [0.72, 1.01]). Similarly, living in the highest fitness center density tertile was associated with decreased GDM odds (500 m:0.87 95% CI: [0.76, 0.99]; 1500 m: 0.89 95% CI: [0.79, 1.01]). There was no evidence of effect modification by SES and no association found between the healthy food index and GDM odds. Interpretation: In Eastern Massachusetts, living near a greater density of fast-food establishments was associated with higher GDM odds. Greater residential access to supermarkets and fitness centers was associated with lower the odds of having GDM. Funding: NIH.

Substitution of dietary monounsaturated fatty acids from olive oil for saturated fatty acids from lard increases low-density lipoprotein apolipoprotein B-100 fractional catabolic rate in subjects with dyslipidemia associated with insulin resistance: a randomized controlled trial.

BACKGROUND: The substitution of monounsaturated acids (MUFAs) for saturated fatty acids (SFAs) is recommended for cardiovascular disease prevention but its impact on lipoprotein metabolism in subjects with dyslipidemia associated with insulin resistance (IR) remains largely unknown. OBJECTIVES: This study aimed to evaluate the impact of substituting MUFAs for SFAs on the in vivo kinetics of apolipoprotein (apo)B-containing lipoproteins and on the plasma lipidomic profile in adults with IR-induced dyslipidemia. METHODS: Males and females with dyslipidemia associated with IR (n = 18) were recruited for this crossover double-blind randomized controlled trial. Subjects consumed, in random order, a diet rich in SFAs (SFAs: 13.4%E; MUFAs: 14.4%E) and a diet rich in MUFAs (SFAs: 7.1%E; MUFAs: 20.7%E) in fully controlled feeding conditions for periods of 4 wk each, separated by a 4-wk washout. At the end of each diet, fasting plasma samples were taken together with measurements of the in vivo kinetics of apoB-containing lipoproteins. RESULTS: Substituting MUFAs for SFAs had no impact on triglyceride-rich lipoprotein apoB-48 fractional catabolic rate (FCR) (Δ = -8.9%, P = 0.4) and production rate (Δ = 0.0%, P = 0.9), although it decreased very low-density lipoprotein apoB-100 pool size (PS) (Δ = -22.5%; P = 0.01). This substitution also reduced low-density lipoprotein cholesterol (LDL-C) (Δ = -7.0%; P = 0.01), non-high-density lipoprotein cholesterol (Δ = -2.5%; P = 0.04), and LDL apoB-100 PS (Δ = -6.0%; P = 0.05). These differences were partially attributed to an increase in LDL apoB-100 FCR (Δ = +1.6%; P = 0.05). The MUFA diet showed reduced sphingolipid concentrations and elevated glycerophospholipid levels compared with the SFA diet. CONCLUSIONS: This study demonstrated that substituting dietary MUFAs for SFAs decreases LDL-C levels and LDL PS by increasing LDL apoB-100 FCR and results in an overall improved plasma lipidomic profile in individuals with IR-induced lipidemia. TRIAL REGISTRATION: This trial was registered as clinicaltrials.gov as NCT03872349.