Life's Essential 8 in Relation to Cardiovascular Disease and Mortality in Individuals With Diabetes.

Background: Evidence regarding the potential health effects of Life's Essential 8 (LE8) score among individuals with type 2 diabetes (T2D) is limited. Objectives: The purpose of this study was to examine the associations of LE8 score with risk of cardiovascular disease (CVD) and mortality among individuals with T2D. Methods: We prospectively followed 19,915 Chinese participants with T2D at baseline or diagnosed during follow-up (Kailuan Study: 2006-2020), who were free of CVD at diagnosis of diabetes. Diet, lifestyle, and health conditions were repeatedly assessed every 2 years. The LE8 score (range 0-100), was calculated based on 8 components: diet quality, physical activity, smoking status, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. We used time-varying cox models to model the associations. Results: During a median follow-up of 11.5 years in participants with T2D, there were 3,295 incident CVD cases and 3,123 deaths. Higher LE8 score was associated with lower risk of CVD incidence and total mortality among participants with diabetes. The multivariate-adjusted HRs for the highest quintile of LE8 score compared with the lowest quintile were 0.56 (95% CI: 0.53-0.59) for CVD, 0.57 (95% CI: 0.53-0.62) for heart disease, 0.53 (95% CI: 0.49-0.57) for stroke, and 0.73 (95% CI: 0.69-0.78) for total mortality (all P trend <0.001). Furthermore, compared with participants with stable or decreased LE8 score after diabetes diagnosis, those with increased LE8 score had 17% to 42% lower risk of CVD, heart disease, stroke, and mortality. Conclusions: A higher LE8 score was associated with a substantially lower risk of CVD incidence and total mortality among adults with T2D.

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.

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.

Sugar-sweetened or artificially-sweetened beverage consumption, physical activity, and risk of cardiovascular disease in adults: a prospective cohort study.

BACKGROUND: Whether physical activity could mitigate the adverse impacts of sugar-sweetened beverages (SSBs) or artificially sweetened beverages (ASBs) on incident cardiovascular disease (CVD) remains uncertain. OBJECTIVES: This study aimed to examine the independent and joint associations between SSB or ASB consumption and physical activity and risk of CVD, defined as fatal and nonfatal coronary artery disease and stroke, in adults from 2 United States-based prospective cohort studies. METHODS: Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% CIs between SSB or ASB intake and physical activity with incident CVD among 65,730 females in the Nurses' Health Study (1980-2016) and 39,418 males in the Health Professional's Follow-up Study (1986-2016), who were free from chronic diseases at baseline. SSBs and ASBs were assessed every 4-y and physical activity biannually. RESULTS: A total of 13,269 CVD events were ascertained during 3,001,213 person-years of follow-up. Compared with those who never/rarely consumed SSBs or ASBs, the HR for CVD for participants consuming ≥2 servings/d was 1.21 (95% CI: 1.12, 1.32; P-trend < 0.001) for SSBs and 1.03 (95% CI: 0.97, 1.09; P-trend = 0.06) for those consuming ≥2 servings/d of ASBs. The HR for CVD per 1 serving increment of SSB per day was 1.18 (95% CI: 1.10, 1.26) and 1.12 (95% CI: 1.04, 1.20) for participants meeting and not meeting physical activity guidelines (≥7.5 compared with <7.5 MET h/wk), respectively. Compared with participants who met physical activity guidelines and never/rarely consumed SSBs, the HR for CVD was 1.47 (95% CI: 1.37, 1.57) for participants not meeting physical activity guidelines and consuming ≥2 servings/wk of SSBs. No significant associations were observed for ASB when stratified by physical activity. CONCLUSIONS: Higher SSB intake was associated with CVD risk regardless of physical activity levels. These results support current recommendations to limit the intake of SSBs even for physically active individuals.

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.

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.

Impact of Blueberry Consumption on the Human Fecal Bileacidome: A Pilot Study of Bile Acid Modulation by Freeze-Dried Blueberry.

Cholesterol-derived bile acids (BAs) affect numerous physiological functions such as glucose homeostasis, lipid metabolism and absorption, intestinal inflammation and immunity, as well as intestinal microbiota diversity. Diet influences the composition of the BA pool. In the present study, we analyzed the impact of a dietary supplementation with a freeze-dried blueberry powder (BBP) on the fecal BA pool composition. The diet of 11 men and 13 women at risk of metabolic syndrome was supplemented with 50 g/day of BBP for 8 weeks, and feces were harvested before (pre) and after (post) BBP consumption. BAs were profiled using liquid chromatography coupled with tandem mass spectrometry. No significant changes in total BAs were detected when comparing pre- vs. post-BBP consumption samples. However, post-BBP consumption samples exhibited significant accumulations of glycine-conjugated BAs (p = 0.04), glycochenodeoxycholic (p = 0.01), and glycoursodeoxycholic (p = 0.01) acids, as well as a significant reduction (p = 0.03) in the secondary BA levels compared with pre-BBP feces. In conclusion, the fecal bileacidome is significantly altered after the consumption of BBP for 8 weeks. While additional studies are needed to fully understand the underlying mechanisms and physiological implications of these changes, our data suggest that the consumption of blueberries can modulate toxic BA elimination.

Healthy Lifestyle Score Including Sleep Duration and Cardiovascular Disease Risk.

INTRODUCTION: Although insufficient or prolonged sleep duration is associated with cardiovascular disease, sleep duration is not included in most lifestyle scores. This study evaluates the relationship between a lifestyle score, including sleep duration and cardiovascular disease risk. METHODS: A prospective analysis among 67,250 women in the Nurses' Health Study and 29,114 men in Health Professionals Follow-up Study (1986-2016) was conducted in 2021. Lifestyle factors were updated every 2-4 years using self-reported questionnaires. The traditional lifestyle score was defined as not smoking, having a normal BMI, being physically active (≥30 minutes/day of moderate physical activity), eating a healthy diet, and drinking alcohol in moderation. Low-risk sleep duration, defined as sleeping ≥6 to <8 hours/day, was included as an additional component in the updated lifestyle score. Cox proportional hazard regression models were used to estimate cardiovascular disease risk. The likelihood-ratio test and C-statistics were used to compare both scores. RESULTS: A total of 11,710 incident cardiovascular disease cases during follow-up were documented. The multivariable-adjusted hazard ratios comparing 6 with 0 low-risk factors in the healthy lifestyle score including sleep duration were 0.17 (95% CI=0.12, 0.23) for cardiovascular disease, 0.14 (95% CI=0.10, 0.21) for coronary heart disease, and 0.20 (95% CI=0.12, 0.33) for stroke. Approximately 66% (95% CI=56%, 75%) of cardiovascular disease, 67% (95% CI=54%, 77%) of coronary heart disease, and 62% (95% CI=42%, 76%) of stroke cases were attributable to poor adherence to a healthy lifestyle including sleep. Adding sleep duration to the score slightly increased the C-statistics from 0.64 (95% CI=0.63, 0.64) to 0.65 (95% CI=0.64, 0.65) (p<0.001). CONCLUSIONS: Adopting a healthy lifestyle including sleep recommendations could substantially reduce the risk of cardiovascular disease in U.S. adults.

Influence of the LDL-Receptor Genotype on Statin Response in Heterozygous Familial Hypercholesterolemia: Insights From the Canadian FH Registry.

BACKGROUND: Whether low-density lipoprotein (LDL) receptor (LDLR) residual activity influences the LDL-lowering effect of statins in heterozygous familial hypercholesterolemia (HeFH) remains unclear. The objective of this study was to investigate the relationship between the LDLR genotype and statin-induced LDL cholesterol (LDL-C) reductions in HeFH. METHODS: A total of 615 individuals with HeFH (receptor-defective [RD] genotype: n = 226; receptor-negative [RN] genotype: n = 389) from 7 lipid clinics across Canada who initiated statin monotherapy were included in this retrospective longitudinal study. Statin-induced reductions in LDL-C among individuals with RD and RN genotypes were compared with the use of linear models. RESULTS: There were 334 women and 281 men with a mean untreated LDL-C concentrations of 6.97 ± 1.65 mmol/L. Untreated and on-statin LDL-C levels where higher among patients with an RN genotype: untreated: RN 7.24 (95% confidence interval [CI] 6.98-7.50) mmol/L vs RD 6.70 (95% CI 6.41-6.98) mmol/L (P = 0.0002); on-statin: RN 4.50 (95% CI 4.31-4.70) vs RD 4.05 (95% CI 3.84-4.26) mmol/L (P = 0.0004). After adjustments for age, sex, smoking status, untreated LDL-C concentrations, statin type and dose, as well as the clinic where the patients were treated, the LDL-C-lowering effect of statins was significantly weaker for individuals with an RN mutation than for individuals with an RD mutation: RN: -31.1% (95% CI -34.7% to -27.4) vs RD -36.5% (95% CI -40.4% to -32.6%); P < 0.0001. The LDLR genotype was the strongest nonmodifiable independent correlate of statin-induced LDL-C reductions (R2 = 2.3%; P = 0.0001). CONCLUSION: The LDLR genotype is significantly associated with statin-induced reductions in LDL-C concentrations in HeFH.

Association of ultra-processed food consumption with colorectal cancer risk among men and women: results from three prospective US cohort studies.

OBJECTIVE: To examine the association between consumption of ultra-processed foods and risk of colorectal cancer among men and women from three large prospective cohorts. DESIGN: Prospective cohort study with dietary intake assessed every four years using food frequency questionnaires. SETTING: Three large US cohorts. PARTICIPANTS: Men (n= 46 341) from the Health Professionals Follow-up Study (1986-2014) and women (n=159 907) from the Nurses' Health Study (1986-2014; n=67 425) and the Nurses' Health Study II (1991-2015; n=92 482) with valid dietary intake measurement and no cancer diagnosis at baseline. MAIN OUTCOME MEASURE: Association between ultra-processed food consumption and risk of colorectal cancer, estimated using time varying Cox proportional hazards regression models adjusted for potential confounding factors. RESULTS: 3216 cases of colorectal cancer (men, n=1294; women, n=1922) were documented during the 24-28 years of follow-up. Compared with those in the lowest fifth of ultra-processed food consumption, men in the highest fifth of consumption had a 29% higher risk of developing colorectal cancer (hazard ratio for highest versus lowest fifth 1.29, 95% confidence interval 1.08 to 1.53; P for trend=0.01), and the positive association was limited to distal colon cancer (72% increased risk; hazard ratio 1.72, 1.24 to 2.37; P for trend<0.001). These associations remained significant after further adjustment for body mass index or indicators of nutritional quality of the diet (that is, western dietary pattern or dietary quality score). No association was observed between overall ultra-processed food consumption and risk of colorectal cancer among women. Among subgroups of ultra-processed foods, higher consumption of meat/poultry/seafood based ready-to-eat products (hazard ratio for highest versus lowest fifth 1.44, 1.20 to 1.73; P for trend<0.001) and sugar sweetened beverages (1.21, 1.01 to 1.44; P for trend=0.013) among men and ready-to-eat/heat mixed dishes among women (1.17, 1.01 to 1.36; P for trend=0.02) was associated with increased risk of colorectal cancer; yogurt and dairy based desserts were negatively associated with the risk of colorectal cancer among women (hazard ratio 0.83, 0.71 to 0.97; P for trend=0.002). CONCLUSIONS: In the three large prospective cohorts, high consumption of total ultra-processed foods in men and certain subgroups of ultra-processed foods in men and women was associated with an increased risk of colorectal cancer. Further studies are needed to better understand the potential attributes of ultra-processed foods that contribute to colorectal carcinogenesis.

Association of the odd-chain fatty acid content in lipid groups with type 2 diabetes risk: A targeted analysis of lipidomics data in the EPIC-Potsdam cohort.

BACKGROUND: Plasma odd-chain saturated fatty acids (OCFA) are inversely associated with type 2 diabetes (T2D) risk and may serve as biomarkers for dairy fat intake. Their distribution across different lipid classes and consequences for diabetes risk remain unknown. AIM: To investigate the prospective associations of OCFA-containing lipid species with T2D risk and their dietary determinants. METHODS: Within the European Prospective Investigation into Cancer and Nutrition-Potsdam study (n = 27,548), we applied a nested case-cohort design (subcohort: n = 1,248; T2D cases: n = 820; median follow-up 6.5 years). OCFA-containing lipids included triacylglycerols, free fatty acids (FFA), cholesteryl esters (CE), phosphatidylcholines, phosphatidylethanolamines, lysophosphatidylcholines, lysophosphatidylethanolamines, monoacylglycerols, and diacylglycerols. We estimated lipid class-specific associations between OCFA-containing lipids and T2D in sex-stratified Cox proportional-hazards models. We investigated correlations between lipids and dietary intakes derived from food-frequency questionnaires. RESULTS: We observed heterogeneous integration of OCFA in different lipid classes: triacylglycerols, FFA, CE, and phosphatidylcholines contributed most to the total OCFA-plasma abundance. The relative concentration of OCFA was particularly high in monoacylglycerols, and the contribution of C15:0 versus C17:0 to the total OCFA-abundance differed across lipid classes. In women, several OCFA-containing phospholipids were inversely associated with T2D risk [phosphatidylcholine(C15:0), HR Q5 vs Q1: 0.56, 95% CI 0.32-0.97; phosphatidylcholine(C17:0), HR per SD: 0.59, 95% CI 0.48-0.71; lysophosphatidylcholine(C17:0), HR Q5 vs Q1: 0.42, 95% CI 0.23-0.76]. In men, we did not detect statistically significant inverse associations in phospholipids, and lysophosphatidylcholine(C15:0) was associated with higher T2D risk (HR Q5 vs. Q1: 1.96, 95% CI 1.06-3.63). Besides, CE(C17:0), monoacylglycerols(C15:0), and diacylglycerols(C15:0) were inversely associated with T2D risk; FFA(C17:0) was positively associated with T2D risk in women. Consumption of fat-rich dairy and fiber-rich foods were positively and red meat inversely correlated to OCFA-containing lipid plasma levels. CONCLUSIONS: OCFA-containing lipids are linked to T2D risk in a lipid class and sex-specific manner, and they are correlated with several foods.

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

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, n = 3; phytosterols, n = 7; guar gum, n = 1; policosanol, n = 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, n = 6, omega-3, n = 1; guar gum, n = 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; p = 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.

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

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, P < 0.0001), family history of premature cardiovascular disease (OR: 3.88, 95% CI: 1.71, 8.81, P = 0.001), male sex (OR: 3.40, 95% CI: 1.49, 7.78, P = 0.004), statin use (OR: 15.5, 95% CI: 1.89, 126, P = 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, P = 0.01), ever smoking (OR: 3.06, 95% CI: 1.20, 7.81, P = 0.02), receptor-negative genotype (OR: 3.17, 95% CI: 1.16, 8.66, P = 0.02), lipoprotein(a) year-score (OR per 1 standard deviation of log-transformed year-score: 1.53, 95% CI: 0.99, 2.36, P = 0.05). CONCLUSIONS: In individuals with HeFH, age, family history of premature cardiovascular disease, sex, statin use, diet quality, smoking status, the LDLR genotype, and lipoprotein(a) concentrations were independently associated with CAC prevalence and severity.

CONTEXTE: Les déterminants de la prévalence et de la sévérité de la calcification des artères coronaires (CAC) dans l'hypercholestérolémie familiale hétérozygote (HFHe) demeurent peu étudiés. L'objectif de cette étude transversale était d'identifier les corrélats de la CAC chez des patients atteints d'HFHe. MÉTHODOLOGIE: Un score calcique coronarien (SCC) a été calculé par un examen de tomodensitométrie sans contraste chez des femmes (n = 68) et des hommes (n = 78) avec HFHe génétiquement définie. Nous avons classé la prévalence et la gravité de la CAC en trois catégories : SCC = 0 unité d'Agatston (UA), SCC = 1 à 100 UA et SCC > 100 UA. Des renseignements ont été recueillis sur des corrélats potentiels de la CAC, dont les antécédents médicaux familiaux et personnels, les facteurs de risque cardiovasculaire, les médicaments hypolipidémiants et les habitudes de vie. RÉSULTATS: Au total, 95 patients présentaient une CAC. Les corrélats indépendants de la prévalence et de la gravité de la CAC comprenaient l'âge (rapport de cotes [RC] par tranche de 10 ans : 5,06; intervalle de confiance [IC] à 95 % : 3,19 à 7,93; p < 0,0001), des antécédents familiaux de maladie cardiovasculaire précoce (RC : 3,88; IC à 95 % : 1,71 à 8,81; p = 0,001), le sexe masculin (RC : 3,40; IC à 95 % : 1,49 à 7,78; p = 0,004), l'emploi de statines (RC : 15,5; IC à 95 % : 1,89 à 126; p = 0,01), la qualité du régime alimentaire évaluée selon le score AHEI (Alternative Healthy Eating Index) (RC par écart-type : 0,59; IC à 95 % : 0,39 à 0,90; p = 0,01), le tabagisme (RC : 3,06; IC à 95 % : 1,20 à 7,81; p = 0,02), le génotype récepteur-négatif (RC : 3,17; IC à 95 % : 1,16 à 8,66; p = 0,02) et le score lipoprotéine(a)-année (RC par écart-type du score-année transformé en logarithme : 1,53; IC à 95 % : 0,99 à 2,36; p = 0,05). CONCLUSIONS: Chez les personnes atteintes d'HFHe, l'âge, les antécédents familiaux de maladie cardiovasculaire précoce, le sexe, l'emploi de statines, la qualité du régime alimentaire, le statut de tabagisme, le génotype du LDLR et les concentrations de lipoprotéine(a) ont été associés de façon indépendante à la prévalence et à la gravité de la CAC.

Changes in Plant-Based Diet Indices and Subsequent Risk of Type 2 Diabetes in Women and Men: Three U.S. Prospective Cohorts.

OBJECTIVE: We evaluated the associations between changes in plant-based diets and subsequent risk of type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 76,530 women in the Nurses' Health Study (NHS) (1986-2012), 81,569 women in NHS II (1991-2017), and 34,468 men in the Health Professionals Follow-up Study (1986-2016). Adherence to plant-based diets was assessed every 4 years with the overall plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI). We used multivariable Cox proportional hazards models to estimate hazard ratios (HRs). We pooled results of the three cohorts using meta-analysis. RESULTS: We documented 12,627 cases of type 2 diabetes during 2,955,350 person-years of follow-up. After adjustment for initial BMI and initial and 4-year changes in alcohol intake, smoking, physical activity, and other factors, compared with participants whose indices remained relatively stable (±3%), participants with the largest decrease (>10%) in PDI and hPDI over 4 years had a 12-23% higher diabetes risk in the subsequent 4 years (pooled HR, PDI 1.12 [95% CI 1.05, 1.20], hPDI 1.23 [1.16, 1.31]). Each 10% increment in PDI and hPDI over 4 years was associated with a 7-9% lower risk (PDI 0.93 [0.91, 0.95], hPDI 0.91 [0.87, 0.95]). Changes in uPDI were not associated with diabetes risk. Weight changes accounted for 6.0-35.6% of the associations between changes in PDI and hPDI and diabetes risk. CONCLUSIONS: Improving adherence to overall and healthful plant-based diets was associated with a lower risk of type 2 diabetes, whereas decreased adherence to such diets was associated with a higher risk.

Egg consumption and risk of type 2 diabetes: findings from 3 large US cohort studies of men and women and a systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. OBJECTIVES: We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. METHODS: We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. RESULTS: During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. CONCLUSIONS: Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.

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

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 UHPLC­MS 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.

Egg consumption and risk of cardiovascular disease: three large prospective US cohort studies, systematic review, and updated meta-analysis.

OBJECTIVE: To evaluate the association between egg intake and cardiovascular disease risk among women and men in the United States, and to conduct a meta-analysis of prospective cohort studies. DESIGN: Prospective cohort study, and a systematic review and meta-analysis of prospective cohort studies. SETTING: Nurses' Health Study (NHS, 1980-2012), NHS II (1991-2013), Health Professionals' Follow-Up Study (HPFS, 1986-2012). PARTICIPANTS: Cohort analyses included 83 349 women from NHS, 90 214 women from NHS II, and 42 055 men from HPFS who were free of cardiovascular disease, type 2 diabetes, and cancer at baseline. MAIN OUTCOME MEASURES: Incident cardiovascular disease, which included non-fatal myocardial infarction, fatal coronary heart disease, and stroke. RESULTS: Over up to 32 years of follow-up (>5.54 million person years), 14 806 participants with incident cardiovascular disease were identified in the three cohorts. Participants with a higher egg intake had a higher body mass index, were less likely to be treated with statins, and consumed more red meats. Most people consumed between one and less than five eggs per week. In the pooled multivariable analysis, consumption of at least one egg per day was not associated with incident cardiovascular disease risk after adjustment for updated lifestyle and dietary factors associated with egg intake (hazard ratio for at least one egg per day v less than one egg per month 0.93, 95% confidence interval 0.82 to 1.05). In the updated meta-analysis of prospective cohort studies (33 risk estimates, 1 720 108 participants, 139 195 cardiovascular disease events), an increase of one egg per day was not associated with cardiovascular disease risk (pooled relative risk 0.98, 95% confidence interval 0.93 to 1.03, I2=62.3%). Results were similar for coronary heart disease (21 risk estimates, 1 411 261 participants, 59 713 coronary heart disease events; 0.96, 0.91 to 1.03, I2=38.2%), and stroke (22 risk estimates, 1 059 315 participants, 53 617 stroke events; 0.99, 0.91 to 1.07, I2=71.5%). In analyses stratified by geographical location (P for interaction=0.07), no association was found between egg consumption and cardiovascular disease risk among US cohorts (1.01, 0.96 to 1.06, I2=30.8%) or European cohorts (1.05, 0.92 to 1.19, I2=64.7%), but an inverse association was seen in Asian cohorts (0.92, 0.85 to 0.99, I2=44.8%). CONCLUSIONS: Results from the three cohorts and from the updated meta-analysis show that moderate egg consumption (up to one egg per day) is not associated with cardiovascular disease risk overall, and is associated with potentially lower cardiovascular disease risk in Asian populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019129650.

High serum triglyceride concentrations in patients with homozygous familial hypercholesterolemia attenuate the efficacy of lipoprotein apheresis by dextran sulfate adsorption.

BACKGROUND AND AIMS: Maximizing the acute reduction of LDL-cholesterol (C) and lipoprotein (a) (Lp(a)) concentrations in patients with homozygous familial hypercholesterolemia (HoFH) is the main goal of lipoprotein apheresis (LA). The objective of this study was to examine how the pre-LA serum TG concentrations influence the efficacy of LA to acutely reduce LDL-C and Lp(a) concentrations in HoFH patients. METHODS: Data from 1761 LA treatments of HoFH patients (n = 10) and compound heterozygous patients (n = 5) collected between 2008 and 2016 were analyzed. These data included the pre- and post-LA concentrations of LDL-C, TGs and Lp(a); volume of filtered plasma; type of LA system used (dextran sulfate adsorption (DSA) or heparin-induced extracorporeal LDL precipitation (HELP)); and interval between treatments. RESULTS: A significant association between the pre-LA TG concentrations and acute LA-induced reduction in LDL-C, modified by the type of LA system used, was observed (ppre-LA TG quartile*LA system = .04). Using the DSA system, the acute reduction of the LDL-C concentrations was attenuated by 3.9% when the pre-LA TG concentrations were >2.09 mmol/L vs. ≤0.93 mmol/L (highest vs. lowest quartiles: -59.4% vs. -63.3%, p = .007). Using the HELP system, no significant difference was observed in the reduction of LDL-C between the highest and the lowest quartiles of serum TGs (-65.8% vs. -66.4%, p = .9). No association was observed between pre-LA TG concentrations and acute LA-induced decrease in Lp(a) (p = .2). CONCLUSIONS: The efficacy of LA is inversely associated with pre-LA TG concentrations in HoFH patients who used the DSA system instead of the HELP system.

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.