Caffeinated coffee consumption and risk of atrial fibrillation in two Spanish cohorts.

AIMS: The association between caffeinated coffee consumption and atrial fibrillation remains unclear. Recent studies suggest an inverse association only between a moderate caffeinated coffee consumption and atrial fibrillation, but others have reported no association. The aim of our study was to prospectively assess the association between caffeinated coffee consumption and atrial fibrillation in two Spanish cohorts, one of adults from a general population and another of elderly participants at high cardiovascular risk. METHODS AND RESULTS: We included 18,983 and 6479 participants from the 'Seguimiento Universidad de Navarra' (SUN) and 'Prevención con Dieta Mediterránea' (PREDIMED) cohorts, respectively. Participants were classified according to their caffeinated coffee consumption in three groups: ≤3 cups/month, 1-7 cups/week, and >1 cup/day. We identified 97 atrial fibrillation cases after a median follow-up of 10.3 years (interquartile range 6.5-13.5), in the SUN cohort and 250 cases after 4.4 years median follow-up (interquartile range 2.8-5.8) in the PREDIMED study. No significant associations were observed in the SUN cohort although a J-shaped association was suggested. A significant inverse association between the intermediate category of caffeinated coffee consumption (1-7 cups/week) and atrial fibrillation was observed in PREDIMED participants with a multivariable-adjusted hazard ratio = 0.53 (95% confidence interval 0.36-0.79) when compared with participants who did not consume caffeinated coffee or did it only occasionally. No association was found for higher levels of caffeinated coffee consumption (>1 cup per day), hazard ratio = 0.79 (95% confidence interval 0.49-1.28). In the meta-analysis of both PREDIMED and SUN studies, the hazard ratio for intermediate consumption of caffeinated coffee was 0.60 (95% confidence interval 0.44-0.82) without evidence of heterogeneity. Similar findings were found for the association between caffeine intake and atrial fibrillation risk. CONCLUSION: Intermediate levels of caffeinated coffee consumption (1-7 cups/week) were associated with a reduction in atrial fibrillation risk in two prospective Mediterranean cohorts.

Effects of total dietary polyphenols on plasma nitric oxide and blood pressure in a high cardiovascular risk cohort. The PREDIMED randomized trial.

BACKGROUND AND AIM: Hypertension is one of the main cardiovascular risk factors in the elderly. The aims of this work were to evaluate if a one-year intervention with two Mediterranean diets (Med-diet) could decrease blood pressure (BP) due to a high polyphenol consumption, and if the decrease in BP was mediated by plasma nitric oxide (NO) production. METHODS AND RESULTS: An intervention substudy of 200 participants at high cardiovascular risk was carried out within the PREDIMED trial. They were randomly assigned to a low-fat control diet or to two Med-diets, one supplemented with extra virgin olive oil (Med-EVOO) and the other with nuts (Med-nuts). Anthropometrics and clinical parameters were measured at baseline and after one year of intervention, as well as BP, plasma NO and total polyphenol excretion (TPE) in urine samples. Systolic and diastolic BP decreased significantly after a one-year dietary intervention with Med-EVOO and Med-nuts. These changes were associated with a significant increase in TPE and plasma NO. Additionally, a significant positive correlation was observed between changes in urinary TPE, a biomarker of TP intake, and in plasma NO (Beta = 4.84; 95% CI: 0.57-9.10). CONCLUSIONS: TPE in spot urine sample was positively correlated with plasma NO in Med-diets supplemented with either EVOO or nuts. The statistically significant increases in plasma NO were associated with a reduction in systolic and diastolic BP levels, adding to the growing evidence that polyphenols might protect the cardiovascular system by improving the endothelial function and enhancing endothelial synthesis of NO.

Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study.

BACKGROUND AND AIMS: Epidemiologic and biological evidence supports an inverse association between polyphenol consumption and the risk of cardiovascular disease (CVD). However, no previous studies have prospectively evaluated the relationship between polyphenol intake and the incidence of CVD in such a comprehensive way. The aim was to evaluate the association between intakes of total polyphenol and polyphenol subgroups, and the risk of major cardiovascular events (myocardial infarction, stroke or death from cardiovascular causes) in the PREDIMED study. METHODS AND RESULTS: The present work is an observational study within the PREDIMED trial. Over an average of 4.3 years of follow-up, there were 273 confirmed cases of CVD among the 7172 participants (96.3%) who completed a validated 137-item food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the Phenol-Explorer database on polyphenol content of each reported food. After multivariate adjustment, a 46% reduction in risk of CVD risk was observed comparing Q5 vs. Q1 of total polyphenol intake (HR = 0.54; 95% confidence interval [CI] = 0.33-0.91; P-trend = 0.04). The polyphenols with the strongest inverse associations were flavanols (HR = 0.40; CI 0.23-0.72; P-trend = 0.003), lignans (HR = 0.51; CI 0.30-0.86; P-trend = 0.007), and hydroxybenzoic acids (HR = 0.47; CI 0.26-0.86; P-trend 0.02). CONCLUSION: Greater intake of polyphenols, especially from lignans, flavanols, and hydroxybenzoic acids, was associated with decreased CVD risk. Clinical trials are needed to confirm this effect and establish accurate dietary recommendations.

Comparative effect of two Mediterranean diets versus a low-fat diet on glycaemic control in individuals with type 2 diabetes.

BACKGROUND/OBJECTIVES: Although benefits have been attributed to the Mediterranean diet, its effect on glycaemic control has not been totally elucidated. The aim of this work was to compare the effect of two Mediterranean diets versus a low-fat diet on several parameters and indices related to glycaemic control in type 2 diabetic subjects. SUBJECTS/METHODS: A multicentric parallel trial was conducted on 191 participants (77 men and 114 women) of the PREDIMED study in order to compare three dietary interventions: two Mediterranean diets supplemented with virgin olive oil (n=67; body mass index (BMI)=29.4±2.9) or mixed nuts (n=74; BMI=30.1±3.1) and a low-fat diet (n=50; BMI=29.8±2.8). There were no drop-outs. Changes in body weight and waist circumference were determined. Insulin resistance was measured by HOMA-IR index, adiponectin/leptin and adiponectin/HOMA-R ratios after 1 year of follow-up. RESULTS: Increased values of adiponectin/leptin ratio (P=0.043, P=0.001 and P<0.001 for low-fat, olive oil and nut diets, respectively) and adiponectin/HOMA-IR ratio (P=0.061, P=0.027 and P=0.069 for low-fat, olive oil and nut diets, respectively) and decreased values of waist circumference (P=0.003, P=0.001 and P=0.001 for low-fat, olive oil and nut diets, respectively) were observed in the three groups. In both Mediterranean diet groups, but not in the low-fat diet group, this was associated with a significant reduction in body weight (P=0.347, P=0.003 and P=0.021 for low-fat, olive oil and nut diets, respectively). CONCLUSIONS: Mediterranean diets supplemented with virgin olive oil or nuts reduced total body weight and improved glucose metabolism to the same extent as the usually recommended low-fat diet.

"Towards an even healthier Mediterranean diet".

Dietary guidelines to promote good health are usually based on foods, nutrients, and dietary patterns predictive of chronic disease risk in epidemiologic studies. However, sound nutritional recommendations for cardiovascular prevention should be based on the results of large randomized clinical trials with "hard" end-points as the main outcome. Such evidence has been obtained for the Mediterranean diet from the PREDIMED (Prevención con Dieta Mediterránea) trial and the Lyon Heart Study. The traditional Mediterranean diet was that found in olive growing areas of Crete, Greece, and Southern Italy in the late 1950s. Their major characteristics include: a) a high consumption of cereals, legumes, nuts, vegetables, and fruits; b) a relatively high-fat consumption, mostly provided by olive oil; c) moderate to high fish consumption; d) poultry and dairy products consumed in moderate to small amounts; e) low consumption of red meats, and meat products; and f) moderate alcohol intake, usually in the form of red wine. However, these protective effects of the traditional Mediterranean diet may be even greater if we upgrade the health effects of this dietary pattern changing the common olive oil used for extra-virgin olive oil, increasing the consumption of nuts, fatty fish and whole grain cereals, reducing sodium intake, and maintaining a moderate consumption of wine with meals.

Mediterranean diet and non enzymatic antioxidant capacity in the PREDIMED study: evidence for a mechanism of antioxidant tuning.

BACKGROUND AND AIMS: The intake of antioxidant-rich foods may increase the blood levels of non enzymatic antioxidant capacity (NEAC). NEAC takes into account all antioxidants from food and synergistic effects between them. We examined the effect of a 1-year intervention with Mediterranean diet on plasma NEAC and assessed whether it was related to baseline NEAC levels. METHODS AND RESULTS: Five hundred sixty-four participants at high cardiovascular risk were randomly selected from the PREDIMED (Prevención con DIeta MEDiterránea) Study, a large 3-arm randomized clinical trial. Blood NEAC levels were measured at baseline and after 1-year of dietary intervention with 1) a Mediterranean diet supplemented with virgin olive oil (MED + VOO); 2) a Mediterranean diet supplemented with nuts (MED + nuts), or 3) a control low-fat diet. Plasma NEAC was analyzed using FRAP (ferric reducing antioxidant potential) and TRAP (total radical-trapping antioxidant parameter) assays. Plasma FRAP levels increased after 1-year of intervention with MED + VOO [72.0 µmol/L (95% CI, 34.2-109.9)] and MED + nuts [48.9 µmol/L (24.3-73.5)], but not after the control low-fat diet [13.9 µmol/L (-11.9 to 39.8)]. Participants in the lowest quartile of plasma FRAP at baseline significantly increased their levels after any intervention, while those in the highest quartile decreased. Similar results occurred with TRAP levels. CONCLUSIONS: This study shows that a 1-year of MED diet intervention increases plasma TAC level in subjects at high risk for cardiovascular disease. Moreover, the effectiveness of dietary supplementation with antioxidants may be related to baseline levels of plasma NEAC.

Dietary intake and major food sources of polyphenols in a Spanish population at high cardiovascular risk: the PREDIMED study.

BACKGROUND AND AIMS: Epidemiological data have shown an inverse association between the consumption of polyphenol-rich foods and the risk of cardiovascular disease or overall mortality. A comprehensive estimation of individual polyphenol intake in nutritional cohorts is needed to gain a better understanding of this association. The aim of this study was to estimate the quantitative intake of polyphenols and the major dietary sources in the PREDIMED (PREvención con DIeta MEDiterránea) cohort using individual food consumption records. METHODS AND RESULTS: The PREDIMED study is a large, parallel-group, multicentre, randomised, controlled 5-year feeding trial aimed at assessing the effects of the Mediterranean diet on the primary prevention of cardiovascular disease. A total of 7200 participants, aged 55-80 years, completed a validated 1-year food frequency questionnaire (FFQ) at baseline. Polyphenol consumption was calculated by matching food consumption data from the FFQ with the recently developed Phenol-Explorer database on polyphenol content in foods. The mean total polyphenol intake was 820 ± 323 mg day⁻¹ (443 ± 218 mg day⁻¹ of flavonoids and 304 ± 156 mg day⁻¹ of phenolic acids). Hydroxycinnamic acids were the phenolic group with the highest consumption and 5-caffeoylquinic acid was the most abundantly ingested individual polyphenol. The consumption of olives and olive oil was a differentiating factor in the phenolic profile of this Spanish population compared with other countries. CONCLUSION: In Mediterranean countries, such as Spain, the main dietary source of polyphenols is coffee and fruits, but the most important differentiating factor with respect to other countries is the consumption of polyphenols from olives and olive oil.

Total polyphenol excretion and blood pressure in subjects at high cardiovascular risk.

BACKGROUND AND AIMS: Dietary factors are critical for the prevention and treatment of hypertension, but data on the effects of specific nutrients on blood pressure (BP) are scarce. The aim of this study was to assess the relationship between total polyphenol excretion (TPE) in urine, as an objective measurement of total polyphenol intake and BP in an elderly population at high cardiovascular risk. METHODS AND RESULTS: Cross-sectional substudy of 589 high-risk participants entering in the PREDIMED trial. BP was measured and TPE was determined in urine by Folin-Ciocalteu assay. A significant positive association was observed between TPE in urine and daily intake of fruit and vegetables (F&V), coffee or wine after adjusting for potential confounders. The intake of 100 g of F&V (Beta=0.150;P<0.001) had a greater contribution to TPE than 100 mL of coffee (Beta=0.141;P=0.001), and the latter two foods contributed more than the consumption of 100 mL of wine (Beta=0.120;P=0.019). An inverse association was observed between urinary TPE and the prevalence of hypertension. Participants in the highest quartile of urinary TPE had a reduced prevalence of hypertension compared to those in the lowest quartile (Odds Ratio=0.64; 95% confidence interval 0.45 to 0.92; P=0.015). Systolic and diastolic BP were inversely associated with urinary TPE after adjustment for potential confounders (P=0.024 and P=0.003, respectively). CONCLUSIONS: Polyphenol intake, assessed via TPE in urine, was negatively associated with BP levels and prevalence of hypertension in an elderly Mediterranean population at high cardiovascular risk. Participants with the highest intake of polyphenol-rich foods showed the lowest BP measurements.

Olive oil and health: summary of the II international conference on olive oil and health consensus report, Jaén and Córdoba (Spain) 2008.

Olive oil (OO) is the most representative food of the traditional Mediterranean Diet (MedDiet). Increasing evidence suggests that monounsaturated fatty acids (MUFA) as a nutrient, OO as a food, and the MedDiet as a food pattern are associated with a decreased risk of cardiovascular disease, obesity, metabolic syndrome, type 2 diabetes and hypertension. A MedDiet rich in OO and OO per se has been shown to improve cardiovascular risk factors, such as lipid profiles, blood pressure, postprandial hyperlipidemia, endothelial dysfunction, oxidative stress, and antithrombotic profiles. Some of these beneficial effects can be attributed to the OO minor components. Therefore, the definition of the MedDiet should include OO. Phenolic compounds in OO have shown antioxidant and anti-inflammatory properties, prevent lipoperoxidation, induce favorable changes of lipid profile, improve endothelial function, and disclose antithrombotic properties. Observational studies from Mediterranean cohorts have suggested that dietary MUFA may be protective against age-related cognitive decline and Alzheimer's disease. Recent studies consistently support the concept that the OO-rich MedDiet is compatible with healthier aging and increased longevity. In countries where the population adheres to the MedDiet, such as Spain, Greece and Italy, and OO is the principal source of fat, rates of cancer incidence are lower than in northern European countries. Experimental and human cellular studies have provided new evidence on the potential protective effect of OO on cancer. Furthermore, results of case-control and cohort studies suggest that MUFA intake including OO is associated with a reduction in cancer risk (mainly breast, colorectal and prostate cancers).

A 3-year Mediterranean-style dietary intervention may modulate the association between adiponectin gene variants and body weight change.

PURPOSE: Adiponectin gene variations have been associated with obesity. There are few interventional studies analyzing this association. The aim of this study was to analyze the effects of a nutritional intervention with Mediterranean-style diet and three (-4034A/C, +45T/G, and +276 G/T) adiponectin gene variants on 3-year body weight changes in high cardiovascular risk patients. SUBJECTS AND METHODS: A total of 737 participants, aged 55-80 at high cardiovascular risk were assigned to a low-fat diet or to a Mediterranean-style diet (MD) groups, one with high intake of virgin olive oil (VOO) and the other with high intake of nuts. Anthropometric parameters were taken at baseline and after 3-year follow-up, and the genotyping of the -4034A/C, +45T/G, and +276 G/T polymorphisms was done. RESULTS: GG genotype of the +45T/G polymorphism was associated with 3-year higher body weight gain (B = 1.399; B = 0.043). TT genotype of the +276G/T polymorphism was linked to the highest 3-year body weight gain in men. Both Mediterranean diets appeared to reverse this effect (p for interaction = 0.053). CONCLUSION: Adiponectin gene variation appeared to be associated with 3-year body weight changes in a high cardiovascular risk population. This association may be modulated by a nutritional intervention with a Mediterranean-style diet.

A 3 years follow-up of a Mediterranean diet rich in virgin olive oil is associated with high plasma antioxidant capacity and reduced body weight gain.

BACKGROUND/OBJECTIVES: The aim of this study was to analyze the influence of a Mediterranean dietary pattern on plasma total antioxidant capacity (TAC) after 3 years of intervention and the associations with adiposity indexes in a randomized dietary trial (PREDIMED trial) with high cardiovascular risk patients. SUBJECTS/METHODS: 187 subjects were randomly selected from the PREDIMED-UNAV center after they completed 3-year intervention program. Participants were following a Mediterranean-style diet with high intake of virgin olive oil or high intake of nuts, or a conventional low-fat diet. Adiposity indexes were measured at baseline and at year 3. Plasma TAC was evaluated using a commercially available colorimetric assay kit. RESULTS: Plasma TAC in the control, olive oil and nuts groups was 2.01+/-0.15, 3.51+/-0.14 and 3.02+/-0.14 mM Trolox, respectively after adjusting for age and sex. The differences between the Mediterranean diet and control groups were statistically significant (P<0.001). Moreover higher levels of TAC were significantly associated with a reduction in body weight after 3 years of intervention among subjects allocated to the virgin olive oil group (B=-1.306; 95% CI=-2.439 to -0.173; P=0.025, after adjusting for age, sex and baseline body mass index). CONCLUSIONS: Mediterranean diet, especially rich in virgin olive oil, is associated with higher levels of plasma antioxidant capacity. Plasma TAC is related to a reduction in body weight after 3 years of intervention in a high cardiovascular risk population with a Mediterranean-style diet rich in virgin olive oil.

Components of the Mediterranean-type food pattern and serum inflammatory markers among patients at high risk for cardiovascular disease.

OBJECTIVE: To evaluate associations between components of the Mediterranean diet and circulating markers of inflammation in a large cohort of asymptomatic subjects at high risk for cardiovascular disease. SUBJECTS/METHODS: A total of 339 men and 433 women aged between 55 and 80 years at high cardiovascular risk because of presence of diabetes or at least three classical cardiovascular risk factors, food consumption was determined by a semi-quantitative food frequency questionnaire. Serum concentrations of high-sensitivity C-reactive protein (CRP) were measured by immunonephelometry and those of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) by enzyme-linked immunosorbent assay. RESULTS: After adjusting for age, gender, body mass index, diabetes, smoking, use of statins, non-steroidal antiinflammatory drugs and aspirin, a higher consumption of fruits and cereals was associated with lower concentrations of IL-6 (P for trend 0.005;both). Subjects with the highest consumption of nuts and virgin olive oil showed the lowest concentrations of VCAM-1, ICAM-1, IL-6 and CRP; albeit only for ICAM-1 was this difference statistically significant in the case of nuts (for trend 0.003) and for VCAM-1 in the case of virgin olive oil (P for trend 0.02). Participants with higher adherence to the Mediterranean-type diet did not show significantly lower concentrations of inflammatory markers (P<0.1 for VCAM-1 and ICAM-1). CONCLUSIONS: The consumption of some typical Mediterranean foods (fruits, cereals, virgin olive oil and nuts) was associated with lower serum concentrations of inflammatory markers especially those related to endothelial function, in subjects with high cardiovascular risk living in a Mediterranean country.

Mediterranean diet, antioxidants and cancer: the need for randomized trials.

In nutritional epidemiology the traditional approach has been to assess single nutrients or food items. Now, a growing interest exists in dietary patterns. The study of dietary patterns with a whole-diet approach represents a needed and complementary methodology. Among a priori defined patterns, the highly palatable traditional Mediterranean diet has many options to be the first choice in the dietary prevention of cancer. However, sound epidemiologic evidence about its ability to prevent the most frequent cancers is scarce. In conjunction with large and well-designed cohort studies, randomized trials using a whole-diet approach and not a simple antioxidant supplement are needed in Mediterranean countries.

Alcohol and heart muscle disease.

Ethanol consumption may induce acute and chronic effects on the myocardium. High-dose acute ethanol intake may induce a decrease in myocardial contraction and produce a variety of rhythm disturbances. These effects are more relevant in patients with underlying cardiomyopathy. Chronic ethanol intake may induce the development of a dilated cardiomyopathy, which is clinically and functionally similar to idiopathic dilated cardiomyopathy. Alcoholic cardiomyopathy is potentially reversible with abstinence. The prognosis depends on the persistence or abstinence of ethanol intake. There is a positive correlation between alcoholic cardiomyopathy and the presence of other ethanol-related diseases, such as skeletal myopathy and cirrhosis. In patients with a specific ethanol-related disease, the possible presence of other complications of alcoholism should be ruled out. Although there are several factors potentially implicated in the pathogenesis of alcohol-related myocardial damage, ethanol itself may induce direct myocardial lesions, which are dose-related and independent of nutrition, protein or ionic deficiencies. The most relevant pathogenic studies on alcoholic cardiomyopathy are based on the disruption of membrane permeability and ionic fluxes mediated by ethanol, inducing a decrease in the calcium transients through the sarcolemma and interfering with the excitation-contraction coupling of myocytes. Cell energy depletion or protein-turnover disruption may contribute to the deleterious effect of ethanol on the myocardium.

Prophylaxis of gastrointestinal tract bleeding with magaldrate in patients admitted to a general hospital ward.

A randomized, placebo-controlled trial was performed to assess the effect of magaldrate (800 mg every 4 h) in reducing the rate of upper gastrointestinal tract bleeding among 100 consecutive patients with severe diseases admitted to a general hospital ward. Upper gastrointestinal tract bleeding occurred in 11 of 48 placebo-treated patients and in only 1 of 52 magaldrate-treated patients (p less than 0.01). Endoscopic examination of these patients showed gastric ulcer (two cases), multiple gastric mucosa ulcerations (nine), and no lesions (one). In three patients who received placebo the hemorrhage was clinically relevant and required transfusion of two or more blood units. Patients with two or more risk factors showed a higher rate of gastrointestinal hemorrhage (p less than 0.05). Respiratory failure and treatment with a high dose of corticosteroids were associated with the highest incidence of bleeding (p less than 0.05 for both). The only adverse reaction associated with magaldrate was a mild and self-limiting diarrhea in two cases. We conclude that patients seriously ill admitted to a general hospital ward should be treated with a prophylactic agent against stress-induced ulcer bleeding. Magaldrate is an effective and safe antacid to prevent gastrointestinal tract bleeding in such patients.