Role of Polyunsaturated Fat in Modifying Cardiovascular Risk Associated With Family History of Cardiovascular Disease: Pooled De Novo Results From 15 Observational Studies.

BACKGROUND: It is unknown whether dietary intake of polyunsaturated fatty acids (PUFA) modifies the cardiovascular disease (CVD) risk associated with a family history of CVD. We assessed interactions between biomarkers of low PUFA intake and a family history in relation to long-term CVD risk in a large consortium. METHODS: Blood and tissue PUFA data from 40 885 CVD-free adults were assessed. PUFA levels ≤25th percentile were considered to reflect low intake of linoleic, alpha-linolenic, and eicosapentaenoic/docosahexaenoic acids (EPA/DHA). Family history was defined as having ≥1 first-degree relative who experienced a CVD event. Relative risks with 95% CI of CVD were estimated using Cox regression and meta-analyzed. Interactions were assessed by analyzing product terms and calculating relative excess risk due to interaction. RESULTS: After multivariable adjustments, a significant interaction between low EPA/DHA and family history was observed (product term pooled RR, 1.09 [95% CI, 1.02-1.16]; P=0.01). The pooled relative risk of CVD associated with the combined exposure to low EPA/DHA, and family history was 1.41 (95% CI, 1.30-1.54), whereas it was 1.25 (95% CI, 1.16-1.33) for family history alone and 1.06 (95% CI, 0.98-1.14) for EPA/DHA alone, compared with those with neither exposure. The relative excess risk due to interaction results indicated no interactions. CONCLUSIONS: A significant interaction between biomarkers of low EPA/DHA intake, but not the other PUFA, and a family history was observed. This novel finding might suggest a need to emphasize the benefit of consuming oily fish for individuals with a family history of CVD.

Omega-3 Blood Levels and Stroke Risk: A Pooled and Harmonized Analysis of 183 291 Participants From 29 Prospective Studies.

BACKGROUND: The effect of marine omega-3 PUFAs on risk of stroke remains unclear. METHODS: We investigated the associations between circulating and tissue omega-3 PUFA levels and incident stroke (total, ischemic, and hemorrhagic) in 29 international prospective cohorts. Each site conducted a de novo individual-level analysis using a prespecified analytical protocol with defined exposures, covariates, analytical methods, and outcomes; the harmonized data from the studies were then centrally pooled. Multivariable-adjusted HRs and 95% CIs across omega-3 PUFA quintiles were computed for each stroke outcome. RESULTS: Among 183 291 study participants, there were 10 561 total strokes, 8220 ischemic strokes, and 1142 hemorrhagic strokes recorded over a median of 14.3 years follow-up. For eicosapentaenoic acid, comparing quintile 5 (Q5, highest) with quintile 1 (Q1, lowest), total stroke incidence was 17% lower (HR, 0.83 [CI, 0.76-0.91]; P<0.0001), and ischemic stroke was 18% lower (HR, 0.82 [CI, 0.74-0.91]; P<0.0001). For docosahexaenoic acid, comparing Q5 with Q1, there was a 12% lower incidence of total stroke (HR, 0.88 [CI, 0.81-0.96]; P=0.0001) and a 14% lower incidence of ischemic stroke (HR, 0.86 [CI, 0.78-0.95]; P=0.0001). Neither eicosapentaenoic acid nor docosahexaenoic acid was associated with a risk for hemorrhagic stroke. These associations were not modified by either baseline history of AF or prevalent CVD. CONCLUSIONS: Higher omega-3 PUFA levels are associated with lower risks of total and ischemic stroke but have no association with hemorrhagic stroke.

Dietary and genetic determinants of non-alcoholic fatty liver disease in coronary heart disease patients.

PURPOSE: A healthy diet reduces the risk of non-alcoholic fatty liver disease (NAFLD) in the general population, especially in individuals who are genetically predisposed to NAFLD. Little is known in patients who suffered from a myocardial infarction (MI). We examined the interaction between diet quality and genetic predisposition in relation to NAFLD in post-MI patients. METHODS: We included 3437 post-MI patients from the Alpha Omega Cohort. Diet quality was assessed with adherence to the Dutch Healthy Diet index 2015 (DHD15-index). A weighted genetic risk score (GRS) for NAFLD was computed using 39 genetic variants. NAFLD prevalence was predicted using the Fatty Liver Index. Prevalence ratios (PR) with 95% confidence intervals of DHD15-index and GRS in relation to NAFLD were obtained with multivariable Cox proportional hazards models. The interaction between DHD15-index and GRS in relation to NAFLD was assessed on an additive and multiplicative scale. RESULTS: Patients had a mean age of 69 (± 5.5) years, 77% was male and 20% had diabetes. The DHD15-index ranged from 28 to 120 with a mean of 73. Patients with higher diet quality were less likely to suffer from NAFLD, with a PR of 0.76 (0.62, 0.92) for the upper vs lower quintile of DHD15-index. No association between the GRS and NAFLD prevalence was found (PR of 0.92 [0.76, 1.11]). No statistically significant interaction between the DHD15-index and GRS was observed. CONCLUSION: In Dutch post-MI patients, adherence to the Dutch dietary guidelines was associated with a lower prevalence of NAFLD, as assessed by the FLI. This association was present regardless of genetic predisposition in this older aged cohort.

Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients.

PURPOSE: We examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD). METHODS: We analysed 2169 patients from the Alpha Omega Cohort (aged 60-80 years, 81% male). Dietary intake was assessed at baseline (2002-2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS. RESULTS: The average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and - 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS. CONCLUSION: The DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.

Dietary atherogenicity and thrombogenicity indexes predicting cardiovascular mortality: 50-year follow-up of the Seven Countries Study.

BACKGROUND AND AIM: To study the relationships of an Atherogenicity Index (ATI) and a Thrombogenicity Index (THI), with 50-year mortality from coronary heart disease (CHD), other heart diseases of uncertain etiology (HDUE) and cerebrovascular disease or stroke (STR), in 16 international cohorts of middle-aged men. METHODS AND RESULTS: Foods from a dietary survey in subsamples of men in each cohort of the Seven Countries Study (SCS) were chemically analyzed for several types of fatty acids that were converted into ATI and THI identifying each of 16 cohorts. Ecological correlations of the ATI and THI were calculated with the three fatal CVD conditions and with all-cause mortality at 25 and 50 years. Correlation coefficients (Rs) were positive and highly significant between ATI and THI versus CHD mortality, with levels ranging from 0.79 to 0.97, depending on the duration of follow-up and the choice of 10 or of 16 cohorts. This was not the case for HDUE and STR mortality for which Rs were variable and not significant. A strong direct association was also found with all-causes deaths at 25 and 50-years. ATI and THI were also directly related with dietary saturated fat and cholesterol levels and inversely with the Mediterranean Adequacy Index (a score identifying the Mediterranean diet). CONCLUSION: These findings indicate that CHD has a different relationship with dietary lipids intake than HDUE and STR. This suggests that HDUE and STR have different underlying pathways or are different diseases.

The Beverage Quality Index and risk of cardiometabolic outcomes after a myocardial infarction: A prospective analysis in the Alpha Omega Cohort.

BACKGROUND AND AIMS: Individual beverages have varying associations with cardiometabolic outcomes, but little is known about overall beverage quality and cardiometabolic risk after myocardial infarction (MI). We created the Beverage Quality Index (BQI) to assess beverage quality and examined its association with cardiometabolic outcomes after MI. METHODS AND RESULTS: We included 4365 Dutch post-MI patients from the Alpha Omega Cohort, aged 60-80 years. Diet was assessed at baseline (2002-2006) with a 203-item FFQ. The BQI included eight components (coffee, tea, milk, juices, sugar-sweetened beverages, alcohol, added sugar to coffee and tea, and energy from beverages), and ranged from 0 to 80. Multivariable Cox models were used to estimate HRs for the BQI in relation to incident diabetes mellitus (DM), major adverse cardiovascular events (MACE), recurrent cardiovascular disease (CVD) and fatal CVD over 3.4 y of follow-up, with follow-up for fatal CVD extended through 2018 (12.4 y). The average BQI was 50.0 ± 12.5. During 3.4 y of follow-up, we identified 186 incident cases of DM, 601 of MACE, 310 of recurrent CVD and 140 of fatal CVD. In multivariable models, a higher BQI (T3 vs. T1) was associated with lower risk of MACE [HR: 0.73 (0.59-0.90)], and recurrent CVD [HR: 0.67 (0.50-0.91)], but not with DM or CVD mortality. After 12.4 y of follow-up, 903 CVD deaths occurred. A significant inverse association with CVD mortality during long-term follow-up was found [HR: 0.81 (0.68-0.96)]. CONCLUSION: Overall beverage intake quality, as assessed by the BQI, may represent an important target for the prevention of recurrent CVD.

Coffee consumption and risk of kidney function decline in a Dutch population-based cohort.

BACKGROUND AND AIMS: Whether coffee consumption is associated with changes in estimated glomerular filtration rate (eGFR) is unknown. We investigated the relationship between coffee consumption and annual eGFR change in a large Dutch population-based study. METHODS AND RESULTS: This study was performed in 78,346 participants without chronic kidney disease (CKD) in the population-based Lifelines Cohort Study. Coffee consumption was assessed at baseline using food frequency questionnaires. Outcomes were annual eGFR change and a composite kidney outcome (defined as eGFR <60 mL/min per 1.73 m2 or >20 % eGFR decline). Multivariable linear and logistic regression analyses were used to evaluate the associations of coffee consumption (categories and cups/day) with kidney outcomes. Overall, 90 % of the participants drank coffee daily and 36 % drank >2-4 cups/day. Unadjusted mean ± SD annual eGFR change ranged from -2.86 ± 2.96 (for non-coffee drinkers) to -2.35 ± 2.62 (for participants consuming >6 cups/day) mL/min per 1.73 m2. During 3.6 ± 0.9 years follow-up, 11.1 % of participants reached the composite kidney outcome. As compared to non-coffee drinkers, higher coffee consumption was associated with less annual eGFR decline in multivariable models (ß [95 % CIs] ranged from 0.15 [0.07, 0.22] for >0-2 cups/day to 0.29 [0.20, 0.38] for >6 cups/day, P-trend <0.001). Consumption of one more cup of coffee per day was associated with a 3 % lower risk of the composite kidney outcome (OR [95%CI], 0.97 [0.96, 0.99]). The inverse association was more pronounced in a subgroup of individuals with diabetes. CONCLUSION: Coffee consumption was inversely associated with annual eGFR change and CKD risk in a large Dutch population-based cohort.

The healthy beverage index is not associated with insulin resistance, prediabetes and type 2 diabetes risk in the Rotterdam Study.

PURPOSE: Whether beverage quality affects changes in glycaemic traits and type 2 diabetes (T2D) risk is unknown. We examined associations of a previously developed Healthy Beverage Index (HBI) with insulin resistance, and risk of prediabetes and T2D. METHODS: We included 6769 participants (59% female, 62.0 ± 7.8 years) from the Rotterdam Study cohort free of diabetes at baseline. Diet was assessed using food-frequency questionnaires at baseline. The HBI included 10 components (energy from beverages, meeting fluid requirements, water, coffee and tea, low-fat milk, diet drinks, juices, alcohol, full-fat milk, and sugar-sweetened beverages), with a total score ranging from 0 to 100. A higher score represents a healthier beverage pattern. Data on study outcomes were available from 1993 to 2015. Multivariable linear mixed models and Cox proportional-hazards regression models were used to examine associations of the HBI (per 10 points increment) with two measurements of HOMA-IR (a proxy for insulin resistance), and risk of prediabetes and T2D. RESULTS: During follow-up, we documented 1139 prediabetes and 784 T2D cases. Mean ± SD of the HBI was 66.8 ± 14.4. Higher HBI score was not associated with HOMA-IR (ß: 0.003; 95% CI - 0.007, 0.014), or with risk of prediabetes (HR: 1.01; 95% CI 0.97, 1.06), or T2D (HR: 1.01; 95% CI 0.96, 1.07). CONCLUSION: Our findings suggest no major role for overall beverage intake quality assessed with the HBI in insulin resistance, prediabetes and T2D incidence. The HBI may not be an adequate tool to assess beverage intake quality in our population.

Association of sweetened beverages consumption with all-cause mortality risk among Dutch adults: the Lifelines Cohort Study (the SWEET project).

PURPOSE: Examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) consumption and all-cause mortality in Dutch adults. METHODS: Data of 118,707 adults participating (mean age = 45 years; 60% was women) the Lifelines Cohort Study were prospectively analyzed. Dietary intake was assessed using a validated food-frequency questionnaire. Participants' vital status was followed-up until February 2022 via the National Personal Records Database. Associations between beverages of interest and all-cause mortality risk were investigated using restricted cubic spline and Cox proportional hazard regression analyses, including substitution analyses. Models were adjusted for demographics, lifestyle, and other dietary factors. RESULTS: During follow-up (median = 9.8 years), a total of 2852 (2.4%) deaths were documented. Median (IQR) of SSB, LNCB, and FJ consumption were 0.1 (0.0-0.6), 0.1 (0.0-0.6), and 0.2 (0.0-0.6) serving/day, respectively. Dose-response analyses showed linear associations between SSB, LNCB, and FJ consumption and mortality risk. For each additional serving of SSB and LNCB, HRs of all-cause mortality risk were 1.09 (95% CI 1.03-1.16) and 1.06 (95% CI 1.00-1.11). Replacing SSB with LNCB showed a nonsignificant association with a lower mortality risk, particularly in women (HR 0.91, 95% CI 0.81-1.01). Finally, an inverse association between FJ and all-cause mortality was observed at moderate consumption with HR of 0.87 (95% CI 0.79-0.95) for > 0-2 servings/week and HR of 0.89 (95% CI 0.81-0.98) for > 2-< 7 servings/week when compared to no consumption. CONCLUSIONS: Our study showed adverse associations between SSB consumption and all-cause mortality. Replacing SSB with LNCB might be associated with lower mortality risk, particularly in women. Moderate intake of FJ was associated with lower all-cause mortality risk.

Sugar and low/no-calorie-sweetened beverage consumption and associations with body weight and waist circumference changes in five European cohort studies: the SWEET project.

PURPOSE: Results of prospective studies investigating associations between low/no-calorie sweeteners (LNCS) and body weight-related outcomes are inconclusive. We conducted dose-response and theoretical replacement individual patient data meta-analyses using harmonised prospective data to evaluate associations between sugar-sweetened beverage (SSB) consumption, low/no-calorie sweetened beverage (LNCB) consumption, and changes in body weight and waist circumference. METHODS: Individual participant data were obtained from five European studies, i.e., Lifelines Cohort Study, NQplus study, Alpha Omega Cohort, Predimed-Plus study, and Feel4diabetes study, including 82,719 adults aged 18-89 with follow-up between 1 and 9 years. Consumption of SSB and LNCB was assessed using food-frequency questionnaires. Multiple regression analyses adjusting for major confounders and including substitution models were conducted to quantify associations in individual cohorts; random-effects meta-analyses were performed to pool individual estimates. RESULTS: Overall, pooled results showed weak adverse associations between SSB consumption and changes in body weight (+ 0.02 kg/y, 95%CI 0.00; 0.04) and waist circumference (+ 0.03 cm/y, 95%CI 0.01; 0.05). LNCB consumption was associated with higher weight gain (+ 0.06 kg/y, 95%CI 0.04; 0.08) but not with waist circumference. No clear associations were observed for any theoretical replacements, i.e., LNCB or water for SSB or water for LNCB. CONCLUSION: In conclusion, this analysis of five European studies found a weak positive association between SSB consumption and weight and waist change, whilst LNCB consumption was associated with weight change only. Theoretical substitutions did not show any clear association. Thus, the benefit of LNCBs as an alternative to SSBs remains unclear.

Use of benzodiazepine and Z-drugs and mortality in older adults after myocardial infarction.

BACKGROUND: The adverse cardiovascular effects of benzodiazepines and Z-drugs (jointly referred as BZDRs) have been of concern. Yet, little is known about the use of BZDRs in relation to mortality risk among older adults with myocardial infarction history (post-MI). METHODS: This study is a secondary analysis of the Alpha Omega Cohort study, comprising post-MI patients aged 40-60 years. Self-reported information on the use of BZDRs, including types and dose, was collected at baseline. Four categories of mortality were examined, namely all-cause mortality, cardiovascular (CVD) mortality, cancer mortality, and non-CVD/non-cancer mortality. Associations between BZDRs use, by types and doses, and mortality were estimated with Cox regression models, adjusted for demographic and classic cardiovascular risk factors. RESULTS: A total of 433 (8.9%) out of 4837 (21.8% females) patients reported BZDRs use at baseline. During a median follow-up of 12.4 years, 2287 deaths were documented, of which 825 (36.1%) were due to CVD. BZDRs use was related to a statistically significantly higher risk of all-cause and CVD mortality; adjusted hazard ratios [95% CI] were (1.31 [1.41, 1.52]) and (1.43 [1.14, 1.81]), respectively. These relationships were dose-dependent-patients using BZDRs on an as-needed basis had similar risks compared to the non-uses, whereas patients with a daily use schedule and increasing doses had higher risks (p-value for trend: <0.001). CONCLUSION: BZDRs use was independently associated with a higher risk of all-cause and cardiovascular mortality in older post-MI patients, and there was evidence for a dose-dependent relationship. CLINICAL TRIAL REGISTRATION: NCT00127452 (www. CLINICALTRIALS: gov).

Plasma fatty acids and kidney function decline in post-myocardial infarction patients of the Alpha Omega Cohort.

BACKGROUND AND AIMS: Age-related kidney function decline is accelerated in patients with coronary heart disease (CHD). CHD and chronic kidney disease may share common etiologies. We examined plasma fatty acids (FAs) as novel biomarkers of kidney function decline after myocardial infarction (MI). METHODS AND RESULTS: The analysis included 2329 Dutch post-MI patients aged 60-80y (Alpha Omega Cohort) most receiving state-of-the-art medications. Plasma FAs (% total FAs) in cholesteryl esters were assessed at baseline (2002-2006), and ∼40 months change in creatinine-cystatin C based glomerular filtration rate was estimated (eGFR, in ml/min per 1.73 m2). Beta coefficients for annual eGFR change in relation to plasma linoleic acid (LA; 50.1% of total FAs in CE), omega-3 FAs (EPA + DHA; 1.7%), odd-chain FAs (C15:0 and C17:0; 0.2%), and C14:0 (0.7%) were obtained from linear regression analyses adjusted for age, sex, smoking, and alcohol intake. Mean baseline eGFR ±SD was 78.5 ± 18.7, which declined by 4.7 ± 13.1 during follow-up, or 1.4 ± 3.9 per year. The annual decline in eGFR was less in patients with higher plasma LA (adjusted beta: 0.40 for LA >47 vs ≤ 47%, 95% CI: 0.01; 0.78; p = 0.046). Associations of plasma LA with annual eGFR decline were stronger in 437 patients with diabetes (1.21, 0.24; 2.19) and in 402 patients with CKD (eGFR<60; 0.90, -0.09; 1.89). Weaker, non-significant associations with kidney function decline were observed for the other plasma FAs. CONCLUSION: Higher plasma LA may be a good predictor of less kidney function decline after MI, particularly in patients with diabetes. The Alpha Omega Cohort is registered with clinicaltrials.gov, NCT03192410.

The Mediterranean diet from past to future: Key concepts from the second "Ancel Keys" International Seminar.

The year 2020 celebrated the tenth anniversary of the recognition of the Mediterranean Diet as Intangible Cultural Heritage of Humanity by the UNESCO Intergovernmental Committee. This event represented a milestone in the history of nutrition, as the Mediterranean diet was the first traditional food practice to receive such award. Since then, a lot has been discussed not only on the beneficial aspects of the Mediterranean diet, but also on its complex role as a lifestyle model that includes a set of skills, knowledge and intercultural dialogue. This process ended up with the recognition in 2019 of Mediterranean diet as a possibly universal model of healthy diet from the EAT-Lancet Commission. These concepts were widely debated at the 2019 "Ancel Keys" International Seminar, held in Ascea (Italy) (for more information see: www.mediterraneandietseminar.org) with the aim to stimulate interest and awareness of a young group of participants on the current problems inherent to the effective implementation of the Mediterranean diet. The present article collects the contributions of several lecturers at the Seminar on key issues such as methodological and experimental approach, sustainability, molecular aspects in disease prevention, future exploitation, without neglecting a historical view of the Seven Countries Study. From the Seminar conclusions emerged a still vibrant and modern role of Mediterranean diet. The years to come will see national and international efforts to reduce the barriers that limit adherence to Mediterranean diet in order to plan for multi-factorial and targeted interventions that would guide our populations to a sustainable healthy living.

Metabolic syndrome-related dietary pattern and risk of mortality in kidney transplant recipients.

BACKGROUND AND AIMS: Presence of the metabolic syndrome (MetS) importantly contributes to excess mortality in kidney transplant recipients (KTRs). However, it is unclear which dietary factors drive the adverse role of MetS in KTRs. We aimed to define a dietary pattern that maximally explained the variation in MetS components, and to investigate the association between this MetS-related dietary pattern (MetS-DP) and all-cause mortality in KTRs. METHODS AND RESULTS: We included 429 adult KTRs who had a functioning graft ⩾1 year. A MetS-DP was constructed using habitual dietary intake derived from a 177-item food frequency questionnaire. We used reduced rank regression (RRR), and defined the six components of MetS (waist circumference, systolic blood pressure, diastolic blood pressure, serum triglycerides, HbA1c, and HDL cholesterol) as response variables and 48 food groups as predictor variables. We evaluated the association between the MetS-DP and all-cause mortality using multivariable Cox regression analysis. The MetS-DP was characterized by high intakes of processed meat and desserts, and low intakes of vegetables, tea, rice, fruits, milk, and meat substitutes. During a mean follow-up of 5.3 ± 1.2 years, 63 KTRs (14.7%) died. Compared to the lowest tertile of the Mets-DP score, those with the greatest adherence had a more than 3-fold higher risk of all-cause mortality (hazard ratio [HR] = 3.63; 95% confidence interval [CI], 1.70-7.74, P < 0.001), independent of potential confounders. CONCLUSIONS: We identified a MetS-related dietary pattern which was independently associated with all-cause mortality in KTRs. The association between this dietary pattern and all-cause mortality was mediated by MetS. Clinical trial reg. no. NCT02811835.

Improving health and carbon footprints of European diets using a benchmarking approach.

OBJECTIVE: This study aimed to identify diets with improved nutrient quality and environmental impact within the boundaries of dietary practices. DESIGN: We used Data Envelopment Analysis to benchmark diets for improved adherence to food-based dietary guidelines (FBDG). We then optimised these diets for dietary preferences, nutrient quality and environmental impact. Diets were evaluated using the Nutrient Rich Diet score (NRD15.3), diet-related greenhouse gas emission (GHGE) and a diet similarity index that quantified the proportion of food intake that remained similar as compared with the observed diet. SETTING: National dietary surveys of four European countries (Denmark, Czech Republic, Italy and France). SUBJECTS: Approximately 6500 adults, aged 18-64 years. RESULTS: When dietary preferences were prioritised, NRD15·3 was ~6 % higher, GHGE was ~4 % lower and ~85 % of food intake remained similar. This diet had higher amounts of fruit, vegetables and whole grains than the observed diet. When nutrient quality was prioritised, NRD15·3 was ~16 % higher, GHGE was ~3 % lower and ~72 % of food intake remained similar. This diet had higher amounts of legumes and fish and lower amounts of sweetened and alcoholic beverages. Finally, when environmental impact was prioritised, NRD15·3 was ~9 % higher, GHGE was ~21 % lower and ~73 % of food intake remained similar. In this diet, red and processed meat partly shifted to either eggs, poultry, fish or dairy. CONCLUSIONS: Benchmark modelling can generate diets with improved adherence to FBDG within the boundaries of dietary practices, but fully maximising health and minimising GHGE cannot be achieved simultaneously.

Biomarkers of Dietary Omega-6 Fatty Acids and Incident Cardiovascular Disease and Mortality.

BACKGROUND: Global dietary recommendations for and cardiovascular effects of linoleic acid, the major dietary omega-6 fatty acid, and its major metabolite, arachidonic acid, remain controversial. To address this uncertainty and inform international recommendations, we evaluated how in vivo circulating and tissue levels of linoleic acid (LA) and arachidonic acid (AA) relate to incident cardiovascular disease (CVD) across multiple international studies. METHODS: We performed harmonized, de novo, individual-level analyses in a global consortium of 30 prospective observational studies from 13 countries. Multivariable-adjusted associations of circulating and adipose tissue LA and AA biomarkers with incident total CVD and subtypes (coronary heart disease, ischemic stroke, cardiovascular mortality) were investigated according to a prespecified analytic plan. Levels of LA and AA, measured as the percentage of total fatty acids, were evaluated linearly according to their interquintile range (ie, the range between the midpoint of the first and fifth quintiles), and categorically by quintiles. Study-specific results were pooled using inverse-variance-weighted meta-analysis. Heterogeneity was explored by age, sex, race, diabetes mellitus, statin use, aspirin use, omega-3 levels, and fatty acid desaturase 1 genotype (when available). RESULTS: In 30 prospective studies with medians of follow-up ranging 2.5 to 31.9 years, 15 198 incident cardiovascular events occurred among 68 659 participants. Higher levels of LA were significantly associated with lower risks of total CVD, cardiovascular mortality, and ischemic stroke, with hazard ratios per interquintile range of 0.93 (95% CI, 0.88-0.99), 0.78 (0.70-0.85), and 0.88 (0.79-0.98), respectively, and nonsignificantly with lower coronary heart disease risk (0.94; 0.88-1.00). Relationships were similar for LA evaluated across quintiles. AA levels were not associated with higher risk of cardiovascular outcomes; in a comparison of extreme quintiles, higher levels were associated with lower risk of total CVD (0.92; 0.86-0.99). No consistent heterogeneity by population subgroups was identified in the observed relationships. CONCLUSIONS: In pooled global analyses, higher in vivo circulating and tissue levels of LA and possibly AA were associated with lower risk of major cardiovascular events. These results support a favorable role for LA in CVD prevention.

Fatty acids in the de novo lipogenesis pathway and incidence of type 2 diabetes: A pooled analysis of prospective cohort studies.

BACKGROUND: De novo lipogenesis (DNL) is the primary metabolic pathway synthesizing fatty acids from carbohydrates, protein, or alcohol. Our aim was to examine associations of in vivo levels of selected fatty acids (16:0, 16:1n7, 18:0, 18:1n9) in DNL with incidence of type 2 diabetes (T2D). METHODS AND FINDINGS: Seventeen cohorts from 12 countries (7 from Europe, 7 from the United States, 1 from Australia, 1 from Taiwan; baseline years = 1970-1973 to 2006-2010) conducted harmonized individual-level analyses of associations of DNL-related fatty acids with incident T2D. In total, we evaluated 65,225 participants (mean ages = 52.3-75.5 years; % women = 20.4%-62.3% in 12 cohorts recruiting both sexes) and 15,383 incident cases of T2D over the 9-year follow-up on average. Cohort-specific association of each of 16:0, 16:1n7, 18:0, and 18:1n9 with incident T2D was estimated, adjusted for demographic factors, socioeconomic characteristics, alcohol, smoking, physical activity, dyslipidemia, hypertension, menopausal status, and adiposity. Cohort-specific associations were meta-analyzed with an inverse-variance-weighted approach. Each of the 4 fatty acids positively related to incident T2D. Relative risks (RRs) per cohort-specific range between midpoints of the top and bottom quintiles of fatty acid concentrations were 1.53 (1.41-1.66; p < 0.001) for 16:0, 1.40 (1.33-1.48; p < 0.001) for 16:1n-7, 1.14 (1.05-1.22; p = 0.001) for 18:0, and 1.16 (1.07-1.25; p < 0.001) for 18:1n9. Heterogeneity was seen across cohorts (I2 = 51.1%-73.1% for each fatty acid) but not explained by lipid fractions and global geographical regions. Further adjusted for triglycerides (and 16:0 when appropriate) to evaluate associations independent of overall DNL, the associations remained significant for 16:0, 16:1n7, and 18:0 but were attenuated for 18:1n9 (RR = 1.03, 95% confidence interval (CI) = 0.94-1.13). These findings had limitations in potential reverse causation and residual confounding by imprecisely measured or unmeasured factors. CONCLUSIONS: Concentrations of fatty acids in the DNL were positively associated with T2D incidence. Our findings support further work to investigate a possible role of DNL and individual fatty acids in the development of T2D.

Dietary protein intake and kidney function decline after myocardial infarction: the Alpha Omega Cohort.

BACKGROUND: Post-myocardial infarction (MI) patients have a doubled rate of kidney function decline compared with the general population. We investigated the extent to which high intake of total, animal and plant protein are risk factors for accelerated kidney function decline in older stable post-MI patients. METHODS: We analysed 2255 post-MI patients (aged 60-80 years, 80% men) of the Alpha Omega Cohort. Dietary data were collected with a biomarker-validated 203-item food frequency questionnaire. At baseline and 41 months, we estimated glomerular filtration rate based on the Chronic Kidney Disease Epidemiology Collaboration equations for serum cystatin C [estimated glomerular filtration rate (eGFRcysC)] alone and both creatinine and cystatin C (eGFRcr-cysC). RESULTS: Mean [standard deviation (SD)] baseline eGFRcysC and eGFRcr-cysC were 82 (20) and 79 (19) mL/min/1.73 m2. Of all patients, 16% were current smokers and 19% had diabetes. Mean (SD) total protein intake was 71 (19) g/day, of which two-thirds was animal and one-third plant protein. After multivariable adjustment, including age, sex, total energy intake, smoking, diabetes, systolic blood pressure, renin-angiotensin system blocking drugs and fat intake, each incremental total daily protein intake of 0.1 g/kg ideal body weight was associated with an additional annual eGFRcysC decline of -0.12 (95% confidence interval -0.19 to -0.04) mL/min/1.73 m2, and was similar for animal and plant protein. Patients with a daily total protein intake of ≥1.20 compared with <0.80 g/kg ideal body weight had a 2-fold faster annual eGFRcysC decline of -1.60 versus -0.84 mL/min/1.73 m2. Taking eGFRcr-cysC as outcome showed similar results. Strong linear associations were confirmed by restricted cubic spline analyses. CONCLUSION: A higher protein intake was significantly associated with a more rapid kidney function decline in post-MI patients.

Adherence to the Dutch dietary guidelines and 15-year incidence of heart failure in the EPIC-NL cohort.

PURPOSE: A healthy diet may contribute to the primary prevention of heart failure (HF), but evidence is still inconclusive. We aimed to study the association between adherence to the Dutch dietary guidelines and incidence of HF. METHODS: We studied 37,468 participants aged 20-70 years and free of HF at baseline from the EPIC-NL cohort. At baseline (1993-1997), data were collected on demographics, lifestyle, and presence of chronic diseases. Dietary intake was assessed using a 178-item validated food frequency questionnaire. Dietary intake data were used to calculate scores on the Dutch Healthy Diet 2015 Index (DHD15-index) measuring adherence to the Dutch dietary guidelines. The DHD15-index is based on the average daily intake of 14 food groups resulting in a total score ranging between 0 and 140, with higher scores indicating better adherence. HF morbidity and mortality during follow-up were ascertained through linkage with national registries. Cox proportional hazards analysis was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between DHD15 adherence and HF risk, adjusting for sociodemographic and lifestyle characteristics. RESULTS: The average score on the DHD15-index was 71 (SD = 15). During a median follow-up of 15.2 years (IQR 14.1-16.5), 674 HF events occurred. After adjustment for demographic and lifestyle characteristics, higher scores on the DHD15-index were associated with lower risk of HF (HRQ4vsQ1 0.73; 95% CI 0.58-0.93; Ptrend 0.001). CONCLUSION: In a large Dutch population of middle-aged adults, higher adherence to the Dutch dietary guidelines was associated with lower risk of HF.

Consumption of a diet high in dairy leads to higher 15:0 in cholesteryl esters of healthy people when compared to diets high in meat and grain.

BACKGROUND AND AIMS: A higher dairy product intake has been associated to higher blood concentrations of 15:0 (pentadecanoic acid), 17:0 (margaric acid), and 14:0 (myristic acid). This study investigates whether a diet high in dairy products influences cholesteryl ester fatty acid concentrations of these specific fatty acids (FA). METHODS AND RESULTS: In a randomized multiple cross-over study, 13 men and 17 women aged 22 ± 4 years with a BMI of 21.6 ± 2.2 kg/m2 received 3 isocaloric intervention diets (dairy, meat or grain) in random order. For this post-hoc analysis, FA in plasma cholesteryl esters were measured using gas chromatography. We performed a linear mixed model per centered log-ratio transformed FA, adjusting for period, and the interaction between diet and period. Consumed total fat intake per controlled intervention diet was 31.0 ± 0.9 en%/day (dairy), 31.5 ± 0.6 en%/day (meat), and 28.4 ± 1.2 en%/day (grain), respectively. The dairy diet led to higher relative concentrations of 15:0 when compared to diets high in meat and grain, (ß; 0.27, 95%CI: 0.18,0.37; p = 1.2 × 10-5, and ß: 0.15; 95%CI: 0.06,0.24; p = 1.2 × 10-2, respectively). The dairy diet also led to higher 14:0 when compared to the meat diet (ß: 0.34; 95%CI: 0.21,0.46; p = 6.0 × 10-5), but not when compared to the grain diet. 17:0 did not differ between diets. CONCLUSION: The plasma cholesteryl ester fraction after a diet high in dairy was characterized by higher 15:0 levels. Concentrations of 14:0 were only higher when comparing the FA profile after a diet high in dairy when compared to a diet high in meat. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01314040.