Denis Talbot

A randomized, crossover, head-to-head comparison of eicosapentaenoic acid and docosahexaenoic acid supplementation to reduce inflammation markers in men and women: the Comparing EPA to DHA (ComparED) Study

BACKGROUND To date, most studies on the anti-inflammatory effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in humans have used a mixture of the 2 fatty acids in various forms and proportions. OBJECTIVES We compared the effects of EPA supplementation with those of DHA supplementation (re-esterified triacylglycerol; 90% pure) on inflammation markers (primary outcome) and blood lipids (secondary outcome) in men and women at risk of cardiovascular disease. DESIGN In a double-blind, randomized, crossover, controlled study, healthy men (n = 48) and women (n = 106) with abdominal obesity and low-grade systemic inflammation consumed 3 g/d of the following supplements for periods of 10 wk: 1) EPA (2.7 g/d), 2) DHA (2.7 g/d), and 3) corn oil as a control with each supplementation separated by a 9-wk washout period. Primary analyses assessed the difference in cardiometabolic outcomes between EPA and DHA. RESULTS Supplementation with DHA compared with supplementation with EPA led to a greater reduction in interleukin-18 (IL-18) (-7.0% ± 2.8% compared with -0.5% ± 3.0%, respectively; P = 0.01) and a greater increase in adiponectin (3.1% ± 1.6% compared with -1.2% ± 1.7%, respectively; P < 0.001). Between DHA and EPA, changes in CRP (-7.9% ± 5.0% compared with -1.8% ± 6.5%, respectively; P = 0.25), IL-6 (-12.0% ± 7.0% compared with -13.4% ± 7.0%, respectively; P = 0.86), and tumor necrosis factor-α (-14.8% ± 5.1% compared with -7.6% ± 10.2%, respectively; P = 0.63) were NS. DHA compared with EPA led to more pronounced reductions in triglycerides (-13.3% ± 2.3% compared with -11.9% ± 2.2%, respectively; P = 0.005) and the cholesterol:HDL-cholesterol ratio (-2.5% ± 1.3% compared with 0.3% ± 1.1%, respectively; P = 0.006) and greater increases in HDL cholesterol (7.6% ± 1.4% compared with -0.7% ± 1.1%, respectively; P < 0.0001) and LDL cholesterol (6.9% ± 1.8% compared with 2.2% ± 1.6%, respectively; P = 0.04). The increase in LDL-cholesterol concentrations for DHA compared with EPA was significant in men but not in women (P-treatment × sex interaction = 0.046). CONCLUSIONS DHA is more effective than EPA in modulating specific markers of inflammation as well as blood lipids. Additional studies are needed to determine the effect of a long-term DHA supplementation per se on cardiovascular disease risk. This trial was registered at clinicaltrials.gov as NCT01810003.

Comparison of the impact of SFAs from cheese and butter on cardiometabolic risk factors: a randomized controlled trial

Background: Controversies persist concerning the association between intake of dietary saturated fatty acids (SFAs) and cardiovascular disease risk.Objective: We compared the impact of consuming equal amounts of SFAs from cheese and butter on cardiometabolic risk factors.Design: In a multicenter, crossover, randomized controlled trial, 92 men and women with abdominal obesity and relatively low HDL-cholesterol concentrations were assigned to sequences of 5 predetermined isoenergetic diets of 4 wk each separated by 4-wk washouts: 2 diets rich in SFAs (12.4-12.6% of calories) from either cheese or butter; a monounsaturated fatty acid (MUFA)-rich diet (SFAs: 5.8%, MUFAs: 19.6%); a polyunsaturated fatty acid (PUFA)-rich diet (SFAs: 5.8%, PUFAs: 11.5%); and a low-fat, high-carbohydrate diet (fat: 25%, SFAs: 5.8%).Results: Serum HDL-cholesterol concentrations were similar after the cheese and butter diets but were significantly higher than after the carbohydrate diet (+3.8% and +4.7%, respectively; P < 0.05 for both). LDL-cholesterol concentrations after the cheese diet were lower than after the butter diet (-3.3%, P < 0.05) but were higher than after the carbohydrate (+2.6%), MUFA (+5.3%), and PUFA (+12.3%) diets (P < 0.05 for all). LDL-cholesterol concentrations after the butter diet also increased significantly (from +6.1% to +16.2%, P < 0.05) compared with the carbohydrate, MUFA, and PUFA diets. The LDL-cholesterol response to treatment was significantly modified by baseline values (P-interaction = 0.02), with the increase in LDL cholesterol being significantly greater with butter than with cheese only among individuals with high baseline LDL-cholesterol concentrations. There was no significant difference between all diets on inflammation markers, blood pressure, and insulin-glucose homeostasis.Conclusions: The results of our study suggest that the consumption of SFAs from cheese and butter has similar effects on HDL cholesterol but differentially modifies LDL-cholesterol concentrations compared with the effects of carbohydrates, MUFAs, and PUFAs, particularly in individuals with high LDL cholesterol. In contrast, SFAs from either cheese or butter have no significant effects on several other nonlipid cardiometabolic risk factors. This trial was registered at clinicaltrials.gov as NCT02106208.

A cautionary note concerning the use of stabilized weights in marginal structural models

Marginal structural models are commonly used to estimate the causal effect of a time-varying treatment in presence of time-dependent confounding. When fitting an MSM to data, the analyst must specify both the structural model for the outcome and the treatment models for the inverse-probability-of-treatment weights. The use of stabilized weights is recommended because they are generally less variable than the standard weights. In this paper, we are concerned with the use of the common stabilized weights when the structural model is specified to only consider partial treatment history, such as the current or most recent treatments. We present various examples of settings where these stabilized weights yield biased inferences while the standard weights do not. These issues are first investigated on the basis of simulated data and subsequently exemplified using data from the Honolulu Heart Program. Unlike common stabilized weights, we find that basic stabilized weights offer some protection against bias in structural models designed to estimate current or most recent treatment effects.

Chronic exposure to adverse psychosocial work factors and high psychological distress among white-collar workers: A 5-year prospective study

OBJECTIVES Prospective studies which evaluated whether the effects of chronic exposure to psychosocial work factors on mental health persisted over time are scarce. For the first time, this study evaluated: 1) the effect of chronic exposure to effort-reward imbalance over 5years on the prevalence of high psychological distress among men and women, and 2) the persistence of this effect over time. METHODS Overall, 1747 white-collar workers from three public organizations participated in a prospective study. Psychological distress and effort-reward imbalance were measured using validated questionnaires at baseline, and at 3- and 5-year follow-ups. Prevalence ratios (PRs) of high psychological distress were estimated using log-binomial regression according to baseline and repeated exposure. RESULTS Compared to unexposed workers, those with repeated exposure to effort-reward imbalance had a higher prevalence of high psychological distress. Workers exposed only at some time-points also had a higher prevalence. The deleterious effect of repeated exposure observed at the 3-year follow-up persisted at the 5-year follow-up among women (PR=2.48 95% confidence interval (CI) 1.97-3.11) and men (PR=1.91 95% CI 1.20-3.04). These effects were greater than those found using a single baseline measurement. CONCLUSION The current study supported a deleterious effect of repeated exposure to effort-reward imbalance on psychological distress, and a lack of adaptation to these effects over time among men and women. Since psychological distress may later lead to severe mental problems, current results highlight the need to consider exposure to these adverse work factors in primary and secondary preventions aimed at reducing mental health problems at work.

Evaluation of the Quebec Healthy Enterprise Standard: Effect on Adverse Psychosocial Work Factors and Psychological Distress

Adverse psychosocial work factors are recognized as a significant source of psychological distress, resulting in a considerable socioeconomic burden. The impact of occupational health standards that aim to reduce these adverse work factors, such as the Quebec Healthy Enterprise Standard (QHES), is of great interest for public health. The aim of this study was to evaluate, for the first time, the effect of QHES interventions targeting adverse psychosocial work factors on the prevalence of these factors and of psychological distress among ten Quebec organizations. These outcomes were assessed by questionnaire using validated instruments before (T1, n = 2849) and 2–3 years following (T2, n = 2560) QHES implementation. Beneficial effects of interventions were observed for two adverse psychosocial work factors: low rewards (ratio of prevalence ratios (PRs) = 0.77, 95% CI = 0.66–0.91) and low social support at work (ratio of PRs = 0.89, 95% CI = 0.77–1.03). Moreover, beneficial effects of interventions were also observed on the prevalence of high psychological distress (ratio of PRs = 0.86, 95% CI = 0.75–0.998). Psychosocial interventions implemented in the context of this standard improved the psychosocial work environment and had beneficial effects on workers’ mental health.

Effects of climate and fine particulate matter on hospitalizations and deaths for heart failure in elderly: A population-based cohort study.

BACKGROUND There are limited data on the effects of climate and air pollutant exposure on heart failure (HF) within taking into account individual and contextual variables. OBJECTIVES We measured the lag effects of temperature, relative humidity, atmospheric pressure and fine particulate matter (PM2.5) on hospitalizations and deaths for HF in elderly diagnosed with this disease on a 10-year period in the province of Quebec, Canada. METHODS Our population-based cohort study included 112,793 elderly diagnosed with HF between 2001 and 2011. Time dependent Cox regression models approximated with pooled logistic regressions were used to evaluate the 3- and 7-day lag effects of daily temperature, relative humidity, atmospheric pressure and PM2.5 exposure on HF morbidity and mortality controlling for several individual and contextual covariates. RESULTS Overall, 18,309 elderly were hospitalized and 4297 died for the main cause of HF. We observed an increased risk of hospitalizations and deaths for HF with a decrease in the average temperature of the 3 and 7days before the event. An increase in atmospheric pressure in the previous 7days was also associated with a higher risk of having a HF negative outcome, but no effect was observed in the 3-day lag model. No association was found with relative humidity and with PM2.5 regardless of the lag period. CONCLUSIONS Lag effects of temperature and other meteorological parameters on HF events were limited but present. Nonetheless, preventive measures should be issued for elderly diagnosed with HF considering the burden and the expensive costs associated with the management of this disease.

Importance of the lipid-related pathways in the association between statins, mortality, and cardiovascular disease risk: The Multi-Ethnic Study of Atherosclerosis.

Estimating how much of the impact of statins on coronary heart diseases (CHD), cardiovascular disease (CVD), and mortality risk is attributable to their effect on low‐density lipoprotein cholesterol (LDL), high‐density lipoprotein cholesterol (HDL), and triglycerides.

Impact of the addition of new vaccines in the early childhood schedule on vaccine coverage by 24 months of age from 2006 to 2016 in Quebec, Canada

CONTEXT Between 2004 and 2016, in the province of Quebec (Canada), 4 new antigens were added in the early childhood vaccine schedule from birth to 18 months, increasing the number of injections or doses needed from 7 to 12. These additions may have decreased the proportion of children who had received all recommended vaccines. OBJECTIVES To assess the impact of the introduction of new vaccines to the childhood schedule on the 24-month vaccine coverage from 2006 to 2016 and identify factors associated with incomplete vaccination status by 24 months of age. METHODS We used the data from six cross-sectional vaccine coverage surveys conducted every two years which included a total of 3515 children aged 2 years old and randomly selected from the Quebec public health insurance database. Factors associated with an incomplete vaccine status by 24 months were identified with multivariable logistic regression. RESULTS Despite the addition of 4 new vaccine antigens since 2004, the vaccine coverage remained high from 2006 (82.4%) through 2016 (88.3%) for vaccines present in the schedule since 2006. In 2016, vaccine coverage was 78.2% for all vaccines included in the schedule. The vaccine coverage of new vaccines increases rapidly within 2 years of their introduction. For both new and older vaccines, incomplete vaccine status by 24 months of age is associated with a delay of 30 days or more in receiving the vaccines scheduled at 2 and 12 months of age. CONCLUSIONS Increasing to 12 the number of doses in the recommended schedule has slightly reduced the vaccine coverage by 24 months of age and the vaccine coverage of vaccines already in the schedule remained stable over the years. Future additions to the vaccine schedule may not be similarly accepted by the population and this will require continuing the monitoring of vaccine coverage.

A graphical perspective of marginal structural models: An application for the estimation of the effect of physical activity on blood pressure:

Estimating causal effects requires important prior subject-matter knowledge and, sometimes, sophisticated statistical tools. The latter is especially true when targeting the causal effect of a time-varying exposure in a longitudinal study. Marginal structural models are a relatively new class of causal models that effectively deal with the estimation of the effects of time-varying exposures. Marginal structural models have traditionally been embedded in the counterfactual framework to causal inference. In this paper, we use the causal graph framework to enhance the implementation of marginal structural models. We illustrate our approach using data from a prospective cohort study, the Honolulu Heart Program. These data consist of 8006 men at baseline. To illustrate our approach, we focused on the estimation of the causal effect of physical activity on blood pressure, which were measured at three time points. First, a causal graph is built to encompass prior knowledge. This graph is then validated and improved utilizing structural equation models. We estimated the aforementioned causal effect using marginal structural models for repeated measures and guided the implementation of the models with the causal graph. By employing the causal graph framework, we also show the validity of fitting conditional marginal structural models for repeated measures in the context implied by our data.

Saturated Fats from Butter but Not from Cheese Increase HDL-Mediated Cholesterol Efflux Capacity from J774 Macrophages in Men and Women with Abdominal Obesity

Abstract Background Recent evidence suggests that the association between dietary saturated fatty acids (SFAs) and coronary artery disease risk varies according to food sources. How SFAs from butter and cheese influence HDL-mediated cholesterol efflux capacity (CEC), a key process in reverse cholesterol transport, is currently unknown. Objective In a predefined secondary analysis of a previously published trial, we have examined how diets rich in SFAs from either cheese or butter influence HDL-mediated CEC, compared with diets rich in either monounsaturated fatty acids (MUFAs) or polyunsaturated fatty acids (PUFAs). Methods In a randomized crossover controlled consumption trial, 46 men and women with abdominal obesity consumed 5 isocaloric diets, each for 4 wk. Two diets were rich in SFAs either from cheese (CHEESE) or butter (BUTTER) [12.4–12.6% of energy (%E) as SFAs, 32%E as fat, 52%E as carbohydrates]. In 2 other diets, SFAs (5.8%E) were replaced with either MUFAs from refined olive oil (MUFA) or PUFAs from corn oil (PUFA). Finally, a lower fat and carbohydrate diet was used as a control (5.8%E as SFAs, 25.0%E as fat, 59%E as carbohydrates; CHO). Post-diet HDL-mediated CEC was determined ex vivo using radiolabelled J774 macrophages incubated with apolipoprotein B–depleted serum from the participants. Results Mean (±SD) age was 41.4 ± 14.2 y, and waist circumference was 107.6 ± 11.5 cm in men and 94.3 ± 12.4 cm in women. BUTTER and MUFA increased HDL-mediated CEC compared with CHEESE (+4.3%, P = 0.026 and +4.7%, P = 0.031, respectively). Exploring the significant diet × sex interaction (P = 0.044) revealed that the increase in HDL-mediated CEC after BUTTER compared with CHEESE was significant among men (+6.0%, P = 0.047) but not women (+2.9%, P = 0.19), whereas the increase after MUFA compared with CHEESE was significant among women (+9.1%, P = 0.008) but not men (–0.6%, P = 0.99). Conclusion These results provide evidence of a food matrix effect modulating the impact of dairy SFAs on HDL-mediated CEC with potential sex-related differences that deserve further investigation. This trial was registered at clinicaltrials.gov as NCT02106208.