Observational cohort studies and a secondary prevention trial have shown inverse associations between adherence to the Mediterranean diet and cardiovascular risk. In a multicenter trial in Spain, we assigned 7447 participants (55 to 80 years of age, 57% women) who were at high cardiovascular risk, but with no cardiovascular disease at enrollment, to one of three diets: a Mediterranean diet supplemented with extra-virgin olive oil, a Mediterranean diet supplemented with mixed nuts, or a control diet (advice to reduce dietary fat). Participants received quarterly educational sessions and, depending on group assignment, free provision of extra-virgin olive oil, mixed nuts, or small nonfood gifts. The primary end point was a major cardiovascular event (myocardial infarction, stroke, or death from cardiovascular causes). After a median follow-up of 4.8 years, the trial was stopped on the basis of a prespecified interim analysis. In 2013, we reported the results for the primary end point in the Journal. We subsequently identified protocol deviations, including enrollment of household members without randomization, assignment to a study group without randomization of some participants at 1 of 11 study sites, and apparent inconsistent use of randomization tables at another site. We have withdrawn our previously published report and now report revised effect estimates based on analyses that do not rely exclusively on the assumption that all the participants were randomly assigned. A primary end-point event occurred in 288 participants; there were 96 events in the group assigned to a Mediterranean diet with extra-virgin olive oil (3.8%), 83 in the group assigned to a Mediterranean diet with nuts (3.4%), and 109 in the control group (4.4%). In the intention-to-treat analysis including all the participants and adjusting for baseline characteristics and propensity scores, the hazard ratio was 0.69 (95% confidence interval [CI], 0.53 to 0.91) for a Mediterranean diet with extra-virgin olive oil and 0.72 (95% CI, 0.54 to 0.95) for a Mediterranean diet with nuts, as compared with the control diet. Results were similar after the omission of 1588 participants whose study-group assignments were known or suspected to have departed from the protocol. In this study involving persons at high cardiovascular risk, the incidence of major cardiovascular events was lower among those assigned to a Mediterranean diet supplemented with extra-virgin olive oil or nuts than among those assigned to a reduced-fat diet. (Funded by Instituto de Salud Carlos III, Spanish Ministry of Health, and others; Current Controlled Trials number, ISRCTN35739639.)

The Mediterranean diet (MedDiet), abundant in minimally processed plant-based foods, rich in monounsaturated fat from olive oil, but lower in saturated fat, meats, and dairy products, seems an ideal nutritional model for cardiovascular health. Methodological aspects of Mediterranean intervention trials, limitations in the quality of some meta-analyses, and other issues may have raised recent controversies. It remains unclear whether such limitations are important enough as to attenuate the postulated cardiovascular benefits of the MedDiet. We aimed to critically review current evidence on the role of the MedDiet in cardiovascular health. We systematically searched observational prospective cohorts and randomized controlled trials which explicitly reported to assess the effect of the MedDiet on hard cardiovascular end points. We critically assessed all the original cohorts and randomized controlled trials included in the 5 most comprehensive meta-analyses published between 2014 and 2018 and additional prospective studies not included in these meta-analyses, totaling 45 reports of prospective studies (including 4 randomized controlled trials and 32 independent observational cohorts). We addressed the existing controversies on methodology and other issues. Some departures from individual randomization in a subsample of the landmark Spanish trial (PREDIMED [Prevención con Dieta Mediterránea]) did not represent any clinically meaningful attenuation in the strength of its findings and the results of PREDIMED were robust in a wide range of sensitivity analyses. The criteria for causality were met and potential sources of controversies did not represent any reason to compromise the main findings of the available observational studies and randomized controlled trials. The available evidence is large, strong, and consistent. Better conformity with the traditional MedDiet is associated with better cardiovascular health outcomes, including clinically meaningful reductions in rates of coronary heart disease, ischemic stroke, and total cardiovascular disease.

Background: Ultraprocessed food consumption has increased in the past decade. Evidence suggests a positive association between ultraprocessed food con

Some available evidence suggests that high consumption of ultra-processed foods (UPFs) is associated with a higher risk of obesity. Collectively, this association and the nutritional characteristics of UPFs suggest that UPFs might also be associated with hypertension. We prospectively evaluated the relationship between UPF consumption and the risk of hypertension in a prospective Spanish cohort, the Seguimiento Universidad de Navarra project. We included 14,790 Spanish adult university graduates who were initially free of hypertension at baseline who were followed for a mean of 9.1 years (SD, 3.9 years; total person-years: 134,784). UPF (industrial formulations of chemical compounds which, beyond substances of common culinary use such as salt, sugar, oils, and fats, include substances also derived from foods but not used in culinary preparations) consumption was assessed using a validated semi-quantitative 136-item food-frequency questionnaire. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for hypertension incidence. During follow-up, 1,702 incident cases of hypertension were identified. Participants in the highest tertile of UPF consumption had a higher risk of developing hypertension (adjusted HR, 1.21; 95% CI, 1.06, 1.37; P for trend = 0.004) than those in the lowest tertile after adjusting for potential confounders. In this large prospective cohort of Spanish middle-aged adult university graduates, a positive association between UPF consumption and hypertension risk was observed. Additional longitudinal studies are needed to confirm our results.

Background: Dietary fat quality and fat replacement are more important for cardiovascular disease (CVD) prevention than is total dietary fat intake.Ob