Guillem Pera

Modified Mediterranean diet and survival: EPIC-elderly prospective cohort study.

Abstract Objective To examine whether adherence to the modified Mediterranean diet, in which unsaturates were substituted for monounsaturates, is associated with longer life expectancy among elderly Europeans. Design Multicentre, prospective cohort study. Setting Nine European countries (Denmark, France, Germany, Greece, Italy, the Netherlands, Spain, Sweden, United Kingdom). Participants 74 607 men and women, aged 60 or more, without coronary heart disease, stroke, or cancer at enrolment and with complete information about dietary intake and potentially confounding variables. Main outcome measures Extent of adherence to a modified Mediterranean diet using a scoring system on a 10 point scale, and death from any cause by time of occurrence, modelled through Cox regression. Results An increase in the modified Mediterranean diet score was associated with lower overall mortality, a two unit increment corresponding to a statistically significant reduction of 8% (95% confidence interval 3% to 12%). No statistically significant evidence of heterogeneity was found among countries in the association of the score with overall mortality even though the association was stronger in Greece and Spain. When dietary exposures were calibrated across countries, the reduction in mortality was 7% (1% to 12%). Conclusion The Mediterranean diet, modified so as to apply across Europe, was associated with increased survival among older people.

Body size and breast cancer risk: Findings from the European prospective investigation into cancer and nutrition (EPIC)

The evidence for anthropometric factors influencing breast cancer risk is accumulating, but uncertainties remain concerning the role of fat distribution and potential effect modifiers. We used data from 73,542 premenopausal and 103,344 postmenopausal women from 9 European countries, taking part in the EPIC study. RRs from Cox regression models were calculated, using measured height, weight, BMI and waist and hip circumferences; categorized by cohort‐wide quintiles; and expressed as continuous variables, adjusted for study center, age and other risk factors. During 4.7 years of follow‐up, 1,879 incident invasive breast cancers were identified. In postmenopausal women, current HRT modified the body size–breast cancer association. Among nonusers, weight, BMI and hip circumference were positively associated with breast cancer risk (all ptrend ≤ 0.002); obese women (BMI > 30) had a 31% excess risk compared to women with BMI < 25. Among HRT users, body measures were inversely but nonsignificantly associated with breast cancer. Excess breast cancer risk with HRT was particularly evident among lean women. Pooled RRs per height increment of 5 cm were 1.05 (95% CI 1.00–1.16) in premenopausal and 1.10 (95% CI 1.05–1.16) in postmenopausal women. Among premenopausal women, hip circumference was the only other measure significantly related to breast cancer (ptrend = 0.03), after accounting for BMI. In postmenopausal women not taking exogenous hormones, general obesity is a significant predictor of breast cancer, while abdominal fat assessed as waist–hip ratio or waist circumference was not related to excess risk when adjusted for BMI. Among premenopausal women, weight and BMI showed nonsignificant inverse associations with breast cancer.

Fruit and vegetable intake and the risk of stomach and oesophagus adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST).

It is considered that fruit and vegetable (F&V) protect against oesophagus and gastric cancer (GC). However, 2 recent meta‐analyses suggest that the strength of association on GC seems to be weaker for vegetables than for fruit and weaker in cohort than in case‐control studies. No evidence exists from cohort studies about adenocarcinoma of oesophagus (ACO). In 521,457 men and women participating in the EPIC cohort in 10 European countries, information of diet and lifestyle was collected at baseline. After an average of 6.5 years of follow‐up, a total of 330 GC and 65 ACO, confirmed and classified by a panel of pathologists, was used for the analysis. We examined the relation between F&V intake and GC and ACO. A calibration study in a sub‐sample was used to control diet measurement errors. In a sub‐sample of cases and a random sample of controls, antibodies against Helicobacter pylori (Hp) were measured and interactions with F&V were examined in a nested case‐control study. We observed no association with total vegetable intake or specific groups of vegetables and GC risk, except for the intestinal type, where a negative association is possible regarding total vegetable (calibrated HR 0.66; 95% CI 0.35–1.22 per 100 g increase) and onion and garlic intake (calibrated HR 0.70; 95% CI 0.38–1.29 per 10 g increase). No evidence of association between fresh fruit intake and GC risk was observed. We found a negative but non significant association between citrus fruit intake and the cardia site (calibrated HR 0.77; 95% CI 0.47–1.22 per 100 g increase) while no association was observed with the non‐cardia site. Regarding ACO, we found a non significant negative association for vegetable intake and for citrus intake (calibrated HRs 0.72; 95% CI 0.32–1.64 and 0.77; 95% CI 0.46–1.28 per 100 and 50 g increase, respectively). It seems that Hp infection does not modify the effect of F&V intake. Our study supports a possible protective role of vegetable intake in the intestinal type of GC and the ACO. Citrus fruit consumption may have a role in the protection against cardia GC and ACO.

Smoking and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Smoking has recently been recognised as causally associated with the development of gastric cancer (GC). However, evidence on the effect by sex, duration and intensity of smoking, anatomic subsite and cessation of smoking is limited. Our objective was to assess the relation between tobacco use and GC incidence in the European Prospective Investigation into Cancer and Nutrition (EPIC). We studied data from 521,468 individuals recruited from 10 European countries taking part in the EPIC study. Participants completed lifestyle questionnaires that included questions on lifetime consumption of tobacco and diet in 1991–1998. Participants were followed until September 2002, and during that period 305 cases of stomach cancer were identified. After exclusions, 274 were eligible for the analysis, using the Cox proportional hazard model. After adjustment for educational level, consumption of fresh fruit, vegetables and preserved meat, alcohol intake and body mass index (BMI), there was a significant association between cigarette smoking and gastric cancer risk: the hazard ratio (HR) for ever smokers was 1.45 (95% confidence interval [CI] = 1.08–1.94). The HR of current cigarette smoking was 1.73 (95% CI = 1.06–2.83) in males and 1.87 (95% CI = 1.12–3.12) in females. Hazard ratios increased with intensity and duration of cigarette smoked. A significant decrease of risk was observed after 10 years of quitting smoking. A preliminary analysis of 121 cases with identified anatomic site showed that current cigarette smokers had a higher HR of GC in the cardia (HR = 4.10) than in the distal part of the stomach (HR = 1.94). In this cohort, 17.6 % (95% CI = 10.5–29.5 %) of GC cases may be attributable to smoking. Findings from this large study support the causal relation between smoking and gastric cancer in this European population. Stomach cancer should be added to the burden of diseases caused by smoking.

Endogenous sex hormones and endometrial cancer risk in women in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Epidemiological data show that reproductive and hormonal factors are involved in the etiology of endometrial cancer, but there is little data on the association with endogenous sex hormone levels. We analyzed the association between prediagnostic serum concentrations of sex steroids and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition using a nested case–control design of 247 incident endometrial cancer cases and 481 controls, matched on center, menopausal status, age, variables relating to blood collection, and, for premenopausal women, phase of menstrual cycle. Using conditional regression analysis, endometrial cancer risk among postmenopausal women was positively associated with increasing levels of total testosterone, free testosterone, estrone, total estradiol, and free estradiol. The odds ratios (ORs) for the highest versus lowest tertile were 2.66 (95% confidence interval (CI) 1.50–4.72; P=0.002 for a continuous linear trend) for estrone, 2.07 (95% CI 1.20–3.60; P=0.001) for estradiol, and 1.66 (95% CI 0.98–2.82; P=0.001) for free estradiol. For total and free testosterone, ORs for the highest versus lowest tertile were 1.44 (95% CI 0.88–2.36; P=0.05) and 2.05 (95% CI 1.23–3.42; P=0.005) respectively. Androstenedione and dehydroepiandrosterone sulfate were not associated with risk. Sex hormone-binding globulin was significantly inversely associated with risk (OR for the highest versus lowest tertile was 0.57, 95% CI 0.34–0.95; P=0.004). In premenopausal women, serum sex hormone concentrations were not clearly associated with endometrial cancer risk, but numbers were too small to draw firm conclusions. In conclusion, relatively high blood concentrations of estrogens and free testosterone are associated with an increased endometrial cancer risk in postmenopausal women.

Incidence and consequences of falls among elderly people living in the community.

BACKGROUND AND OBJECTIVES To evaluate the incidence of falls according to socio-demographic and health factors, and to determine their physical, psychological and social consequences. SUBJETS AND METHOD: Population-based prospective study, which included a representative cohort of 448 elderly community-dwellers, aged 65 or more living in the city of Mataró (Spain). We made a baseline evaluation, which was repeated after a one-year follow up, consisting of a standardized questionnaire on socio-demographic characteristics, physical activity, tests of physical and cognitive function, history of falls during the previous year, the Falls Efficacy Scale, and associated chronic conditions. Follow-up interviews at intervals of one month over 12 months, consisting of a standardized questionnaire aimed at detecting and describing any fall occurred during the previous month. RESULTS 25.1% (95% CI, 18.8-31.4) of males and 37.0% (95% CI, 31.2-42.8) of females fell. Multiple falls were observed in 3.8% of men and 10.9% of women. 203 falls were reported, providing a crude incidence rate of 30.9 falls per 100 men-years (95% CI, 23.3-41.0) and 56.5 falls per 100 women-years (95% CI, 46.5-68.8). A positive association with falls was found with age, reduced physical and cognitive function, associated chronic conditions and previous falls. 71.1% of falls had physical consequences, with 7.7% of fractures, and 21.7% needed medical aid. 64.4% of fallers feared of falling again. CONCLUSIONS Our study shows a pattern of high incidence of falls among the elderly living in the Spanish non-institutionalized community. Our data confirm that adverse consequences derived from the falls are frequent and often severe, which makes falls one of the major problems of elderly people.

The Peripheral Arterial disease study (PERART/ARTPER): prevalence and risk factors in the general population

BackgroundThe early diagnosis of atherosclerotic disease is essential for developing preventive strategies in populations at high risk and acting when the disease is still asymptomatic. A low ankle-arm index is a good marker of vascular events and may be diminished without presenting symptomatology (silent peripheral arterial disease). The aim of the study is to know the prevalence and associated risk factors of peripheral arterial disease in the general population.MethodsWe performed a cross-sectional, multicentre, population-based study in 3786 individuals >49 years, randomly selected in 28 primary care centres in Barcelona (Spain). Peripheral arterial disease was evaluated using the ankle-arm index. Values < 0.9 were considered as peripheral arterial disease.ResultsThe prevalence (95% confidence interval) of peripheral arterial disease was 7.6% (6.7-8.4), (males 10.2% (9.2-11.2), females 5.3% (4.6-6.0); p < 0.001).Multivariate analysis showed the following risk factors: male sex [odds ratio (OR) 1.62; 95% confidence interval 1.01-2.59]; age OR 2.00 per 10 years (1.64-2.44); inability to perform physical activity [OR 1.77 (1.17-2.68) for mild limitation to OR 7.08 (2.61-19.16) for breathless performing any activity]; smoking [OR 2.19 (1.34-3.58) for former smokers and OR 3.83 (2.23-6.58) for current smokers]; hypertension OR 1.85 (1.29-2.65); diabetes OR 2.01 (1.42-2.83); previous cardiovascular disease OR 2.19 (1.52-3.15); hypercholesterolemia OR 1.55 (1.11-2.18); hypertriglyceridemia OR 1.55 (1.10-2.19). Body mass index ≥25 Kg/m2 OR 0.57 (0.38-0.87) and walking >7 hours/week OR 0.67 (0.49-0.94) were found as protector factors.ConclusionsThe prevalence of peripheral arterial disease is low, higher in males and increases with age in both sexes. In addition to previously described risk factors we found a protector effect in physical exercise and overweight.

Prevalence and factors associated with the presence of nonalcoholic fatty liver disease in an adult population in Spain.

Background/aims The prevalence of nonalcoholic fatty liver disease (NAFLD) is unknown in Spain. The purpose of detecting NAFLD patients is to determine the associated factors and prevent its evolution to more severe forms. The aim of this study is to determine the prevalence and factors associated with NAFLD. Methods This is a multicentre, cross-sectional, populational study. Individuals between 15 and 85 years of age were randomly selected from 25 primary healthcare centres in the province of Barcelona, Spain. Clinical histories were reviewed, and anamnesis, physical examination, blood analysis and hepatic echography were performed. Individuals with an alcohol intake greater than 30 g/day in men and greater than 20 g/day in women or with known liver disease were excluded. Results Seven hundred and sixty-six individuals with a mean age of 53±14 years (range 17–83, 42.2% men) were included in the study. One hundred and ninety-eight individuals presented NAFLD with echographic criteria (prevalence 25.8, 33.4% men and 20.3% women P<0.001). On multivariate analysis, the following were associated with NAFLD: male sex [odds ratio (OR): 2.34, 95% confidence interval (95% CI): 1.57–3.49], age (OR: 1.04 per year, 95% CI: 1.02–1.05), metabolic syndrome (OR: 2.19, 95% CI: 1.29–3.72), insulin resistance (OR: 6.00, 95% CI: 3.43–10.5) and alanine aminotransferase (OR: 4.21, 95% CI: 2.23–7.95). Of the individuals who consumed alcohol, 29.4% consumed alcohol within the inclusion criteria, with a mean of 9.17±6.75 standard beverage units per week. Moderate alcohol intake was not related to NAFLD, although a possible protector effect was found with the quantity consumed among the drinkers who did not consume excessive amounts of alcohol (OR: 0.93 per standard beverage units, 95% CI: 0.88–0.98). Conclusion NAFLD prevalence in our population is very high. Male sex, age, metabolic syndrome, insulin resistance and alanine aminotransferase are the factors associated with NAFLD. Furthermore, studies should be carried out with respect to the controversial effect of alcohol on NAFLD.

The evaluation of the diet/disease relation in the EPIC study: considerations for the calibration and the disease models

BACKGROUND International multicentre studies on diet and cancer are relatively new in epidemiological research. They offer a series of challenging methodological issues for the evaluation of the association between dietary exposure and disease outcomes, which can both be quite heterogeneous across different geographical regions. This requires considerable work to standardize dietary measurements at the food and the nutrient levels. METHODS Within the European Prospective Investigation into Cancer and Nutrition (EPIC), a calibration study was set up to express individual dietary intakes according to the same reference scale. A linear regression calibration model was used to correct the association between diet and disease for measurement errors in dietary exposures. In the present work, we describe an approach for analysing the EPIC data, using as an example the evaluation of the association between fish intake and colorectal cancer incidence. RESULTS Sex- and country-specific attenuation factors ranged from 0.083 to 0.784, with values overall higher for men compared with women. Hazard ratio estimates of colorectal cancer for a 10 g/day increase in fish intake were 0.97 [95% confidence interval (CI): 0.95-0.99] and 0.93 (0.88-0.98), before and after calibration, respectively. CONCLUSIONS In a multicentre study, the diet/disease association can be evaluated by exploiting the whole variability of intake over the entire study. Calibration may reduce between-centre heterogeneity in the diet-disease relationship caused by differential impact of measurement errors across cohorts.

CagA+ Helicobacter pylori infection and gastric cancer risk in the EPIC-EURGAST study

Helicobacter pylori (H. pylori), atrophic gastritis, dietary and life‐style factors have been associated with gastric cancer (GC). These factors have been evaluated in a large case–control study nested in the European Prospective Investigation into Cancer and Nutrition carried out in 9 countries, including the Mediterranean area. Participants, enrolled in 1992–1998, provided life‐style and dietary information and a blood sample (360,000; mean follow‐up: 6.1 years). For 233 GC cases diagnosed after enrolment and their 910 controls individually‐matched by center, gender, age and blood donation date H. pylori antibodies (antilysate and antiCagA) and plasma Pepsinogen A (PGA) were measured by ELISA methods. Severe chronic atrophic gastritis (SCAG) was defined as PGA circulating levels <22 μg/l. Overall, in a conditional logistic regression analysis adjusted for education, smoke, weight and consumption of total vegetables, fruit, red and preserved meat, H. pylori seropositivity was associated with GC risk. Subjects showing only antibodies anti‐H. pylori lysate, however, were not at increased risk, while those with antiCagA antibodies had a 3.4‐fold increased risk. Overall, the odds ratio associated with SCAG was 3.3 (95% CI 2.2–5.2). According to site, the risk of noncardia GC associated with CagA seropositivity showed a further increase (OR 6.5; 95% CI 3.3–12.6); on the other hand, a ten‐fold increased risk of cardia GC was associated with SCAG (OR 11.0; 95% CI 3.0–40.9). These results support the causal relationship between H. pylori CagA+ strains infection, and GC in these European populations even after taking into account dietary habits. This association was limited to distal GC, while serologically defined SCAG was strongly associated with cardia GC, thus suggesting a divergent risk pattern for these 2 sites.