Long-term secondary prevention of cardiovascular disease with a Mediterranean diet and a low-fat diet (CORDIOPREV): a randomised controlled trial.

BACKGROUND: Mediterranean and low-fat diets are effective in the primary prevention of cardiovascular disease. We did a long-term randomised trial to compare the effects of these two diets in secondary prevention of cardiovascular disease. METHODS: The CORDIOPREV study was a single-centre, randomised clinical trial done at the Reina Sofia University Hospital in Córdoba, Spain. Patients with established coronary heart disease (aged 20-75 years) were randomly assigned in a 1:1 ratio by the Andalusian School of Public Health to receive a Mediterranean diet or a low-fat diet intervention, with a follow-up of 7 years. Clinical investigators (physicians, investigators, and clinical endpoint committee members) were masked to treatment assignment; participants were not. A team of dietitians did the dietary interventions. The primary outcome (assessed by intention to treat) was a composite of major cardiovascular events, including myocardial infarction, revascularisation, ischaemic stroke, peripheral artery disease, and cardiovascular death. This study is registered with ClinicalTrials.gov, NCT00924937. FINDINGS: From Oct 1, 2009, to Feb 28, 2012, a total of 1002 patients were enrolled, 500 (49·9%) in the low-fat diet group and 502 (50·1%) in the Mediterranean diet group. The mean age was 59·5 years (SD 8·7) and 827 (82·5%) of 1002 patients were men. The primary endpoint occurred in 198 participants: 87 in the Mediterranean diet group and 111 in the low-fat group (crude rate per 1000 person-years: 28·1 [95% CI 27·9-28·3] in the Mediterranean diet group vs 37·7 [37·5-37·9] in the low-fat group, log-rank p=0·039). Multivariable-adjusted hazard ratios (HRs) of the different models ranged from 0·719 (95% CI 0·541-0·957) to 0·753 (0·568-0·998) in favour of the Mediterranean diet. These effects were more evident in men, with primary endpoints occurring in 67 (16·2%) of 414 men in the Mediterranean diet group versus 94 (22·8%) of 413 men in the low-fat diet group (multiadjusted HR 0·669 [95% CI 0·489-0·915], log-rank p=0·013), than in 175 women for whom no difference was found between groups. INTERPRETATION: In secondary prevention, the Mediterranean diet was superior to the low-fat diet in preventing major cardiovascular events. Our results are relevant to clinical practice, supporting the use of the Mediterranean diet in secondary prevention. FUNDING: Fundacion Patrimonio Comunal Olivarero; Fundacion Centro para la Excelencia en Investigacion sobre Aceite de Oliva y Salud; local, regional, and national Spanish Governments; European Union.

Frying oils with high natural or added antioxidants content, which protect against postprandial oxidative stress, also protect against DNA oxidation damage.

PURPOSE: Using sunflower oil as frying oil increases postprandial oxidative stress, which is considered the main endogenous source of DNA oxidative damage. We aimed to test whether the protective effect of virgin olive oil and oil models with added antioxidants against postprandial oxidative stress may also protect against DNA oxidative damage. METHODS: Twenty obese people received four breakfasts following a randomized crossover design consisting of different oils [virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)], which were subjected to 20 heating cycles. RESULTS: We observed the postprandial increase in the mRNA levels of p53, OGG1, POLB, and GADD45b after the intake of the breakfast prepared with SFO and SOX, and an increase in the expression of MDM2, APEX1, and XPC after the intake of the breakfast prepared with SFO, whereas no significant changes at the postprandial state were observed after the intake of the other breakfasts (all p values <0.05). We observed lower 8-OHdG postprandial levels after the intake of the breakfast prepared with VOO and SOP than after the intake of the breakfast prepared with SFO and SOX (all p values <0.05). CONCLUSIONS: Our results support the beneficial effect on DNA oxidation damage of virgin olive oil and the oil models with added antioxidants, as compared to the detrimental use of sunflower oil, which induces p53-dependent DNA repair pathway activation.

CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (the CORDIOPREV study): Rationale, methods, and baseline characteristics: A clinical trial comparing the efficacy of a Mediterranean diet rich in olive oil versus a low-fat diet on cardiovascular disease in coronary patients.

Coronary heart disease (CHD) represents a major global health burden. However, despite the well-known influence that dietary habits exert over the progression of this disease, there are no well-established and scientifically sound dietary approaches to prevent the onset of clinical outcomes in secondary prevention. The objective of the CORonary Diet Intervention with Olive oil and cardiovascular PREVention study (CORDIOPREV study, clinical trials number NCT00924937) is to compare the ability of a Mediterranean diet rich in virgin olive oil versus a low-fat diet to influence the composite incidence of cardiovascular events after 7 years in subjects with documented CHD at baseline. For this purpose, we enrolled 1,002 coronary patients from Spain. Baseline assessment (2009-2012) included detailed interviews and measurements to assess dietary, social, and biological variables. Results of baseline characteristics: The CORDIOPREV study in Spain describes a population with a high body mass index (37.2% overweight and 56.3% obesity) and with a median of low-density lipoprotein cholesterol of 88.5 mg/dL (70.6% of the patients having <100 mg/dL and 20.3% patients <70 mg/dL). A total of 9.6% of the participants were active smokers, and 64.4% were former smokers. Metabolic syndrome was present in 58% of this population. To sum up, we describe here the rationale, methods, and baseline characteristics of the CORDIOPREV study, which will test for the first time the efficacy of a Mediterranean diet rich in extra virgin olive oil as compared with a low-fat diet on the incidence of CHD recurrence in a long-term follow-up study.

The influence of olive oil on human health: not a question of fat alone.

Olive oil is the most representative food in the traditional Mediterranean diet and its most important source of MUFA. The healthy benefits of MUFA-rich diets on plasma cholesterol levels, were the first to generate interest in this dietary model. In addition to the benefits conferred by its lipids, olive oil has other biological effects, some of them also related to MUFA. However, most recent studies have shown that there are a number of properties that depend on, or are potentiated by, the consumption of olive oil, such as virgin olive oil, that is rich in microcomponents. This foodstuff, thanks to its double set of benefits, thus tends to produce a better lipid profile and a less prothrombotic environment, promoting antioxidant and anti-inflammatory effects, with a greater endothelial protective capacity. In view of these effects, it would appear that when olive oil is the basic source of dietary alimentary fat it has a major antiatherogenic capacity, which is not shared to the same extent by other oils that are rich in oleic acid but lack its characteristic micronutrients.

Effect of frying oils on the postprandial endoplasmic reticulum stress in obese people.

The addition of antioxidants to frying oil reduces postprandial oxidative stress and the inflammatory response. ER stress may trigger both inflammation and oxidative stress processes. We aimed to determine the biological effects of the intake of four models of frying oils on postprandial ER stress in peripheral blood mononuclear cells. Twenty obese people received four breakfasts following a randomized crossover design, consisting of muffins made with different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixture of seed oils (SFO/canola oil) with either dimethylpolysiloxane (SOD) or natural antioxidants from olives (SOP) added), which were previously subjected to 20 heating cycles. ER stress was assessed by measuring the mRNA levels of sXBP1, BiP, CRT, and CNX in peripheral blood mononuclear cells. Our study showed that the intake of the muffins made with SFO induced the postprandial increase of the mRNA levels of the ER stress-sensor sXBP1, and the ER stress related chaperones BiP and CRT (all p-values <0.05). The harmful effects associated with the use of SFO as frying oil, in terms of inflammatory response and postprandial oxidative stress, may be partially mediated by the induction of postprandial ER stress.

The antioxidants in oils heated at frying temperature, whether natural or added, could protect against postprandial oxidative stress in obese people.

We have investigated the effects of the intake of oils heated at frying temperature in order to find an oil model for deep-frying that prevents postprandial oxidative stress. Twenty obese people received four breakfasts following a randomised crossover design consisting of different oils (virgin olive oil (VOO), sunflower oil (SFO), and a mixed seed oil (SFO/canola oil) with added dimethylpolysiloxane (SOX) or natural antioxidants from olives (SOP)), which were subjected to 20 heating cycles. The intake of SFO-breakfast reduced plasma GSH levels and the GSH/GSSG ratio, increased protein carbonyl levels, and induced a higher gene expression of the different NADPH-oxidase subunits, Nrf2-Keap1 activation, gene expression of the antioxidant enzymes in peripheral blood mononuclear cells and antioxidant plasma activities than the intake of the breakfasts prepared with VOO, SOP and SOX. Oils with phenolic compounds, whether natural (VOO) or artificially added (SOP), or with artificial antioxidant (SOX), could reduce postprandial oxidative stress compared with sunflower oil.

NOS3 Glu298Asp polymorphism interacts with virgin olive oil phenols to determine the postprandial endothelial function in patients with the metabolic syndrome.

BACKGROUND: Glu298Asp polymorphism of the endothelial nitric oxide synthase (eNOS) gene (NOS3) has been characterized as a risk factor of hypertension and coronary artery disease. Previous studies suggest that the higher risk observed in T allele carriers is due to endothelial dysfunction associated with a lower eNOS activity and that acute consumption of phenol-rich olive oil ameliorates postprandial endothelial dysfunction by reducing oxidative stress and increasing nitric oxide bioavailability. Nevertheless, how these facts may interact in a population with altered endothelial function such as metabolic syndrome patients remains unknown. OBJECTIVE: The objective of the study was to evaluate whether the presence of NOS3 Glu298Asp polymorphism interacts with the phenol content of virgin olive oil (VOO) to influence postprandial endothelial function. DESIGN: Fifty-seven subjects with metabolic syndrome received three breakfasts based on VOO with different phenolic content. Baseline, incremental area under the curve, peak, and maximum parameters of postocclusive skin reactive hyperemia (PORH) were evaluated by laser Doppler, and the nitrate/nitrite [NO((x))] and eNOS concentrations were obtained during fasting and postprandially. RESULTS: A gene-diet interaction was found on maximum PORH and NO((x)) (P = 0.039 and P = 0.043, respectively). TT subjects showed lower values of eNOS, NO((x)), and maximum PORH as compared with GG and GT subjects, especially in the postprandial measurements (all P < 0.05). However, most of these differences were attenuated when high-phenol VOO was consumed. CONCLUSION: In a population with a compromised endothelial function, concentrations of phenols in dietary VOO interact with NOS3 Glu298Asp to ameliorate the endothelial dysfunction associated to the TT genotype.

Olive oil and haemostasis: a review on its healthy effects.

UNLABELLED: Interest in the Mediterranean diet (MD) has grown worldwide. Despite the high complexity of its nutrients composition, olive oil emerges as its principal food, since it provides the higher percentage of energy and a lot of bioactive compounds. OBJECTIVE: In this review, we will discuss the benefits of diets enriched in virgin olive oil, whose effects are probably due not only to its oleic acid content but also to its other potentially health-promoting components. METHODS: Traditionally, the benefits of MD were linked to its effect on lipoprotein metabolism, but today we realise that there exists a whole sheaf of other benefits, including the components of haemostasis: platelet function, thrombogenesis and fibrinolysis. RESULTS: A diet enriched in virgin olive oil can reduce the sensitivity of platelets to aggregation, decreasing von Willebrand and thromboxane B2 plasma levels. Moreover, a particular interest has aroused about its capacity to decrease fasting factor VII plasma levels and to avoid or modulate its postprandial activation. In addition, tissue factor expression in mononuclear cells could be reduced with the chronic intake of virgin olive oil, and finally, studies performed in different experimental situation have shown that it could also increase fibrinolytic activity, reducing plasma concentration of plasma activator inhibitor type-1 (PAI-1). CONCLUSION: The MD is an alimentary model with a high content of monounsaturated fats that is capable of inducing a wide range of biological effects on the cardiovascular system. The application of modern focuses of study will dilucidate in the future the biological and clinical interest of these findings.

Aceite de oliva y prevención cardiovascular: más que una grasa / Olive oil and cardiovascular prevention: more than just fat

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Tratamiento de la hipercolesterolemia: los nuevos ensayos con estatinas. ¿Se deben revisar las guías de tratamiento? / Treatment of hypercholesterolemia: new trials with statins. Should guidelines be revised?

En el año 2001, el National Cholesterol Education Program-Adult Treatment Panel-III (NCEP ATP III) publicó su tercer informe para la detección, evaluación y tratamiento de la hipercolesterolemia. Desde entonces se han publicado varios estudios relacionados con nuevas estrategias de tratamiento. Algunos de ellos, centrados en los valores de colesterol unido a lipoproteínas de baja densidad (cLDL), han dado resultados que obligan a replantear los objetivos determinados hasta ahora. Y es que los resultados sugieren que la terapia hipolipemiante debería ser más intensa y buscar mayores reducciones del cLDL. En general, las nuevas orientaciones afectan a los subgrupos de alto riesgo, lo que ha motivado que se planteen valores de cLDL tan bajos que hasta hace poco eran inimaginables. No obstante, aún hay bastantes incertidumbres que deberán resolverse en los próximos años, incluido el valor inferior de cLDL que se debe conseguir para una prevención más efectiva (AU)

In 2001, the National Cholesterol Education Program published its third expert-panel report on the detection, evaluation, and treatment of hypercholesterolemia in adults (Adult Treatment Panel III). Since then, many new studies of the best way to achieve LDL cholesterol targets have been completed. These indicate that a more aggressive approach to LDL cholesterol therapy should be taken and that modification of previous treatment guidelines should be considered. In particular, new approaches are especially important for high-risk patients, who need to achieve extremely low LDL cholesterol levels. The present paper contains a review of these recent trials and an assessment of their implications for managing the cholesterol level (AU)