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In this clinical trial involving patients who had had an MI, supplementation with low doses of n−3 fatty acids in margarine did not have a significant effect on the risk of subsequent cardiovascular events. A meta-analysis of randomized trials involving patients with cardiac disease showed that supplementation with the marine n−3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduced the rate of death from coronary heart disease by 20%. 1 Mozaffarian and Rimm concluded from their meta-analysis of cohort studies and clinical trials that a daily intake of 250 mg of EPA and DHA reduced the risk of fatal coronary heart disease by 36%. 2 There was no additional benefit from higher intakes. There is less evidence for a protective effect of the plant-derived n−3 fatty acid alpha-linolenic acid (ALA). A meta-analysis of five . . .

At a workshop to update the science linking saturated fatty acid (SAFA) consumption with the risk of coronary heart disease (CHD) and ischemic stroke, invited participants presented data on the consumption and bioavailability of SAFA and their functions in the body and food technology. Epidemiological methods and outcomes were related to the association between SAFA consumption and disease events and mortality. Participants reviewed the effects of SAFA on CHD, causal risk factors, and surrogate risk markers. Higher intakes of SAFA were not associated with higher risks of CHD or stroke apparently, but studies did not take macronutrient replacement into account. Replacing SAFA by cis-polyunsaturated fatty acids was associated with significant CHD risk reduction, which was confirmed by randomized controlled trials. SAFA reduction had little direct effect on stroke risk. Cohort studies suggest that the food matrix and source of SAFA have important health effects.

PurposeEpidemiological findings indicate that higher adherence to a healthy diet may lower cardiovascular disease (CVD) risk. The present study aimed to investigate whether adherence to a healthy diet, assessed by the Healthy Diet Indicator (HDI), Dietary Approaches to Stop Hypertension (DASH) score, and Alternative Healthy Eating Index 2010 (AHEI-2010), was associated with CVD incidence and risk markers.MethodsIncluded in the present analyses were data from 1867 middle-aged men, aged 56.7 ± 4.5 years at baseline, recruited into the Caerphilly Prospective Study. Adherence to a healthy diet was examined in relation to CVD, coronary heart disease (CHD), and stroke incidence (Cox regression), and risk markers (linear regression) with adjustment for relevant confounders.ResultsThe DASH score was inversely associated with CVD [hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.66, 0.99], and stroke (HR 0.61; 95% CI 0.42, 0.88) incidence, but not with CHD after an average of 16.6 year follow-up, and with diastolic blood pressure, after 12 year follow-up. The AHEI-2010 was inversely associated with stroke (HR 0.66; 95% CI 0.42, 0.88) incidence, aortic pulse wave velocity, and C-reactive protein. The HDI was not associated with any single outcome.ConclusionsHigher DASH and AHEI-2010 scores were associated with lower CVD and stroke risk, and favourable cardiovascular health outcomes, suggesting that encouraging middle-aged men to comply with the dietary recommendations for a healthy diet may have important implications for future vascular disease and population health.

Accumulating evidence shows that NAFLD might play a role in the etiology and progression of CVD, but little is known on the association of NAFLD and CVD mortality in patients with a history of a myocardial infarction (MI). Therefore, we studied the relationship of Fatty Liver Index (FLI), as indicator for non-alcoholic fatty liver disease (NAFLD), with 12-year risk of cardiovascular disease (CVD) and all-cause mortality in post-MI patients. We included 4165 Dutch patients from the Alpha Omega Cohort aged 60–80 years who had an MI ≤10 years prior to study enrolment. NAFLD was defined as FLI ≥60. Patients were followed for cause-specific mortality from enrolment (2002–2006) through December 2018. Hazard ratios for CVD and all-cause mortality were obtained by multivariable Cox regression using FLI <30 (indicating absence of NAFLD) as the reference. Baseline FLI as a continuous measure was studied with mortality using restricted cubic splines analyses. The median (IQR) FLI was 68 (48–84). Sixty percent of the patients had FLI ≥60, who were more likely to be male and more often had diabetes, high blood pressure, and high serum cholesterol levels. During 12 years of follow-up, 2042 deaths occurred of which 846 from CVD. Patients with NAFLD were at increased risk of CVD mortality (HR: 1.55 [1.19, 2.03]) and all-cause mortality (HR: 1.21 [1.03; 1.41]) compared to patients without NAFLD. Results remained consistent after excluding patients with obesity and diabetes. To conclude, the adverse association of FLI with CVD mortality was stronger in female than in male patients with conventional cut-off points. FLI ≥60, indicating NAFLD, was a predictor for CVD and all-cause mortality in post-MI patients, independent of other cardiometabolic risk factors. However, cut-off points might differ between male and female patients for predicting CVD mortality.

ObjectivesTo assess the longitudinal evidence of the relationships between sleep disturbances (of quantity and quality) and dyslipidaemia in the general population and to quantify such relationships.SettingSystematic review and meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.MethodsWe performed a systematic search of PubMed and Embase (up to 9 September 2017), complemented with manual searches, of prospective population studies describing the association between sleep duration and quality and the incidence of dyslipidaemias. Relative risks (95% CIs) were extracted and pooled using a random effects model. Subgroup analyses by lipid type were performed. Heterogeneity and publication bias were also assessed. Quality was assessed with Downs and Black score.ParticipantsStudies were included if they were prospective, had measured sleep quantity and/or quality at baseline and either incident cases of dyslipidaemia or changes in blood lipid fractions assessed prospectively.Primary outcome measuresRisk of of dyslipidaemia and changes in lipid fractions. Dyslipidaemia was defined as unfavorable lipid profile, such as high total cholesterol, triglycerides, low-density lipoprotein cholesterol or low high-density lipoprotein cholesterol.ResultsEleven studies were identified (seven using sleep duration, three sleep quality and one both). There was heterogeneity in the sleep quality aspects and types of lipids assessed. Classification of sleep duration (per hour/groups) also varied widely. In the pooled analysis of sleep duration (6 studies, 16 samples; 59945 participants; follow-up 2.6–10 years), short sleep was associated with a risk of 1.01 (95% CI 0.93 to 1.10) of developing dyslipidaemia, with moderate heterogeneity (I2=56%, P=0.003) and publication bias (P=0.035). Long sleep was associated with a risk of 0.98 (95% CI 0.87 to 1.10) for dyslipidaemia, with heterogeneity (I2=63%, P<0.001) and no significant publication bias (P=0.248).ConclusionThe present analysis was unable to find supportive evidence of a significant relationship between sleep duration and the development of dyslipidaemia. However, heterogeneity and small number of studies limit the interpretation.PROSPERO registration numberCRD42016045242.

Cocoa consumption has beneficial cardiometabolic effects, but underlying mechanisms remain unclear. Epicatechin, the cocoa major monomeric flavan-3-ol, is considered to contribute to these cardio-protective effects. We investigated effects of pure epicatechin supplementation on gene expression profiles of immune cells in humans. In a double blind, placebo-controlled cross-over trial, 32 (pre)hypertensive subjects aged 30 to 80, received two 4-week interventions, i.e. epicatechin (100mg/day) or placebo with a 4-week wash-out between interventions. Gene expression profiles of peripheral blood mononuclear cells were determined before and after both interventions. Epicatechin regulated 1180 genes, of which 234 differed from placebo. Epicatechin upregulated gene sets involved in transcription and tubulin folding and downregulated gene sets involved in inflammation, PPAR signalling and adipogenesis. Several negatively enriched genes within these gene sets were involved in insulin signalling. Most inhibited upstream regulators within the epicatechin intervention were cytokines or involved in inflammation. No upstream regulators were identified compared to placebo. Epicatechin, a cocoa flavan-3-ol, reduces gene expression involved in inflammation, PPAR-signalling and adipogenesis in immune cells. Effects were mild but our findings increase our understanding and provide new leads on how epicatechin rich products like cocoa may affect immune cells and exert cardiometabolic protective effects.

Body adiposity is known to affect mortality risk in patients with coronary artery disease (CAD). We examined associations of body mass index (BMI) and waist circumference (WC) with long term mortality in Dutch CAD patients, and potential and effect modification of these associations by lifestyle and health determinants. 10,370 CAD patients (mean age ∼65 y; 20% female; >80% on cardiovascular drugs) from the prospective Alpha Omega Cohort and Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease study were included. Cox models were used to estimate categorical and continuous associations (using restricted cubic splines) of measured BMI and WC with all-cause and cardiovascular mortality risk, adjusting for age, sex, smoking, alcohol, physical activity and educational level. Analyses were repeated in subgroups of lifestyle factors (smoking, physical activity, diet quality), education and health determinants (diabetes, self-rated health). During ∼10 years of follow-up (91,947 person-years), 3,553 deaths occurred, including 1,620 from cardiovascular disease. U-shaped relationships were found for BMI and mortality risk, with the lowest risk for overweight patients (BMI ∼27 kg/m2). For obesity (BMI ≥30), the HR for all-cause mortality was 1.31 (95% CI: 1.11, 1.41) in male patients and 1.10 (95% CI: 0.92, 1.30) in female patients, compared to BMI 25-30 kg/m2. WC was also non-linearly associated with mortality, and HRs were 1.18 (95%CI:1.06, 1.30) in males and 1.31 (95%CI:1.05, 1.64) in females for the highest vs. middle category of WC. Results for cardiovascular mortality were mostly in line with the results for all-cause mortality. U-shaped associations were found in most subgroups, associations were moderately modified by physical activity, smoking and educational level. CAD patients with obesity and a large WC were at increased risk of long-term CVD and all-cause mortality, while mildly overweight patients had the lowest risk. These associations were consistent across subgroups of patients with different lifestyles and health status.

Prospective cohort studies have shown that high fruit and vegetable consumption is inversely associated with coronary heart disease (CHD). Whether food processing affects this association is unknown. Therefore, we quantified the association of fruit and vegetable consumption with 10-year CHD incidence in a population-based study in the Netherlands and the effect of processing on these associations. Prospective population-based cohort study, including 20,069 men and women aged 20 to 65 years, enrolled between 1993 and 1997 and free of cardiovascular disease at baseline. Diet was assessed using a validated 178-item food frequency questionnaire. Hazard ratios (HR) were calculated for CHD incidence using multivariable Cox proportional hazards models. During a mean follow-up time of 10.5y, 245 incident cases of CHD were documented, which comprised 211 non-fatal acute myocardial infarctions and 34 fatal CHD events. The risk of CHD incidence was 34% lower for participants with a high intake of total fruit and vegetables (>475 g/d; HR: 0.66; 95% CI: 0.45-0.99) compared to participants with a low total fruit and vegetable consumption (≤241 g/d). Intake of raw fruit and vegetables (>262 g/d vs ≤92 g/d; HR: 0.70; 95% CI: 0.47-1.04) as well as processed fruit and vegetables (>234 g/d vs ≤113 g/d; HR: 0.79; 95% CI: 0.54-1.16) were inversely related with CHD incidence. Higher consumption of fruit and vegetables, whether consumed raw or processed, may protect against CHD incidence.

Background Individual beverages have shown divergent associations with type 2 diabetes. Whether overall beverage quality affects diabetes risk is unknown. Therefore, we estimated the association of a previously developed Beverage Quality Index (BQI) with the incidence of diabetes in Mexican women. Methods We included 77,484 female participants from the Mexican Teachers’ Cohort without diabetes at baseline (2006–2008). At baseline, diet was assessed using a 140-item food-frequency questionnaire. The BQI included seven components (coffee, milk, juices, sugar-sweetened beverages [SSBs], alcohol, sugar added to beverages, and energy from beverages), with a total theoretical score ranging from 0 to 70. A higher score represents a healthier beverage intake pattern. Data on diabetes incidence were available through 2018 from self-reports or cross-linkage with administrative data. We used multivariable Cox proportional-hazard models adjusted for potential confounders. Results Participants’ mean (SD) baseline age was 45.9 (7.2) years, and BQI score was 37.3 (8.6), ranging from 9.8 to 69.3. During a median follow-up of 7.6 years, 4521 participants developed diabetes. After multivariable adjustment, when comparing extreme categories (≥55 vs. <25), a higher BQI was suggestively associated with lower diabetes incidence (HR: 0.87; 95% CI: 0.71, 1.06), although the estimate was imprecise. Restricted cubic spline analysis showed no association between the BQI and diabetes incidence (p-nonlinearity = 0.20). Conclusions In a cohort of Mexican women, the BQI for overall beverage quality showed no consistent association with diabetes incidence. Further research on beverage quality indices for Mexican populations, including those with high SSB intake, is warranted.

Chronic kidney disease (CKD) is highly prevalent among older post-myocardial infarction (MI) patients. It is not known whether CKD is an independent risk factor for mortality in older post-MI patients with optimal cardiovascular drug-treatment. Therefore, we studied the relation between kidney function and all-cause and specific mortality among older post-MI patients, without severe heart failure, who are treated with state-of-the-art pharmacotherapy. From 2002-2006, 4,561 Dutch post-MI patients were enrolled and followed until death or January 2012. We estimated Glomerular Filtration Rate (eGFR) with cystatin C (cysC) and creatinine (cr) using the CKD-EPI equations and analyzed the relation with any and major causes of death using Cox models and restricted cubic splines. Mean (SD) for age was 69 years (5.6), 79% were men, 17% smoked, 21% had diabetes, 90% used antihypertensive drugs, 98% used antithrombotic drugs and 85% used statins. Patients were divided into four categories of baseline eGFRcysC: ≥90 (33%; reference), 60-89 (47%), 30-59 (18%), and <30 (2%) ml/min/1.73m2. Median follow-up was 6.4 years. During follow-up, 873 (19%) patients died: 370 (42%) from cardiovascular causes, 309 (35%) from cancer, and 194 (22%) from other causes. After adjustment for age, sex and classic cardiovascular risk factor, hazard ratios (95%-confidence intervals) for any death according to the four eGFRcysC categories were: 1 (reference), 1.4 (1.1-1.7), 2.9 (2.3-3.6) and 4.4 (3.0-6.4). The hazard ratios of all-cause and cause-specific mortality increased linearly below kidney functions of 80 ml/min/1.73 m2. Weaker results were obtained for eGFRcr. To conclude, we found in optimal cardiovascular drug-treated post-MI patients an inverse graded relation between kidney function and mortality for both cardiovascular as well as non-cardiovascular causes. Risk of mortality increased linearly below kidney function of about 80 ml/min/1.73 m2.