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Background: The association between alcohol consumption and coronary heart disease (CHD) has been widely studied. Most of these studies have concluded that moderate alcohol intake reduces the risk of CHD. There are numerous discussions regarding whether this association is causal or biased. The objective of this paper is to analyse the association between alcohol intake and CHD risk in the Spanish cohort of the European Prospective Investigation into Cancer (EPIC). Methods: Participants from the EPIC Spanish cohort were included (15 630 men and 25 808 women). The median follow-up period was 10 years. Ethanol intake was calculated using a validated dietary history questionnaire. Participants with a definite CHD event were considered cases. A Cox regression model adjusted for relevant co-variables and stratified by age was produced. Separate models were carried out for men and women. Results: The crude CHD incidence rate was 300.6/100 000 person-years for men and 47.9/100 000 person-years for women. Moderate, high and very high consumption was associated with a reduced risk of CHD in men: hazard ratio 0.90 (95% CI 0.56 to 1.44) for former drinkers, 0.65 (95% CI 0.41 to 1.04) for low, 0.49 (95% CI 0.32 to 0.76) for moderate, 0.46 (95% CI 0.30 to 0.71) for high and 0.50 (95% CI 0.29 to 0.85) for very high consumers. A negative association was found in women, with p values above 0.05 in all categories. Conclusions: Alcohol intake in men aged 29-69 years was associated with a more than 30% lower CHD incidence. This study is based on a large prospective cohort study and is free of the abstainer error. [ABSTRACT FROM AUTHOR]

Objective:To assess the intake of glucosinolates and cruciferous vegetables among Spanish adults.Design:Cross-sectional analysis of a prospective cohort study.Setting:The Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC).Subjects:We analysed data from 40 684 men and women aged 35–64 years from the EPIC-Spain cohort. The usual diet was assessed by means of the dietary history method, and glucosinolate intake was calculated using a published food composition database.Results:The average intake of cruciferous vegetables was 11.3 g/day, accounting for about 5% of total vegetable consumption, whereas the daily intake of total glucosinolates was 6.5 mg, among which 35% were of indole type. The absolute intake of glucosinolates was in average higher in men than in women (6.8 vs 6.2 mg/day), whereas glucosinolate density per energy unit was higher in women's diet (3.4 vs 2.7 mg/4200 kJ). Northern regions consumed in average 36% more glucosinolates than Southern regions (7.3 vs 5.4 mg/day). There was a positive association of glucosinolate intake with body mass index, physical activity, educational level and an inverse relationship with alcohol consumption.Conclusions:Contrary to the pattern seen for total vegetable intake, our estimate of consumption of cruciferous vegetables, and hence of glucosinolates, is relatively low within Europe, which in turn is lower than in North America and several Asian populations.European Journal of Clinical Nutrition (2008) 62, 324–331; doi:10.1038/sj.ejcn.1602750; published online 4 April 2007 [ABSTRACT FROM AUTHOR]

Background: Although prostate cancer has recently registered increasing incidence and decreasing mortality in Spain, no analysis has yet been made of these two indicators to ascertain the magnitude of and reasons for these trends. [ABSTRACT FROM PUBLISHER]

Background: National indicators of cancer burden are essential information for cancer surveillance and health planning, so that in countries with partial registration coverage and geographically variable risk patterns, such as Spain, this is even more relevant. This article provides estimates of cancer incidence in Spain for all cancers combined, with the single exception of non-melanoma skin cancer, and for major cancer sites over the period 1981–2006, with projections up to 2012. [ABSTRACT FROM PUBLISHER]

Background: Cardiovascular disease, particularly ischemic heart disease (IHD), is the leading cause of mortality worldwide. Bisphenol A (BPA) is considered an endocrine disruptor and obesogen, present in numerous products of daily use. The aim of this study was to assess the potential association of serum BPA concentrations and the risk of incident IHD in a sub-cohort of the Spanish European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: We designed a case-cohort study within the EPIC-Spain cohort. The population consisted of 4636 participants from 4 EPIC-Spain centers (946 IHD cases and 3690 sub-cohort participants). BPA exposure was assessed by means of chemical analyses of serum samples collected at recruitment. Follow-up was performed by linking with national and regional databases and reviewing patients' clinical records. Cox Proportional Hazards Models were used for the statistical analyses., Results: Median follow-up time was 16 years and 70% of the participants showed detectable BPA values (>0.2 ng/ml). Geometric mean (GM) values of cases and sub-cohort were 1.22 ng/ml vs 1.19 ng/ml respectively (p = 0.90). Cox regression models showed no significant association of BPA serum levels and IHD, acute myocardial infarction or angina pectoris risk., Conclusions: We evidenced a similar percentage of detection of BPA among cases and sub-cohort participants from our population, and no clear association with IHD risk was observed. However, further investigation is needed to understand the influence of BPA on IHD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Objective: To determinate the role of lifestyle factors, recent diet, menstrual factors, and reproductive history in age at natural menopause in adult Spanish women., Methods: In total, 12 562 pre-menopausal women were available for analysis from the EPIC-Spain sub-cohort. Women were recruited between 1992 and 1996 in five regions of Spain (Asturias, Granada, Murcia, Navarra, and San Sebastian) and, for these analyses, were followed for 3 years. Questionnaires on diet, lifestyle, anthropometric measurements, and reproductive and exogenous hormones history were collected at baseline. Menopause status was updated at a median of 3 years of follow-up., Results: After a median of 3 years of follow-up 1166 women became postmenopausal. An earlier age at menopause was observed in current smokers (HR: 1.29; 95%CI 1.08-1.55) and in non-users of oral contraceptives (HR: 1.32; 95%CI 1.01-1.57). A later age at menopause was observed in women with irregular menses (HR: 0.71; 95%CI 0.56-0.91) and in women with a higher number of pregnancies (HR: 0.74; 95%CI 0.56-0.94)., Conclusions: Our results confirm that women who smoked had an earlier age at natural menopause, while use of oral contraceptives, higher number of pregnancies, and irregularity of menses were associated with a prolonged reproductive lifespan. No associations were observed for dietary habits assessed after the age of 40 years., (© 2018 Wiley Periodicals, Inc.)

Background: Brain cancer incidence rates in Spain are below the European's average. However, there are two regions in the north of the country, Navarre and the Basque Country, ranked among the European regions with the highest incidence rates for both males and females. Our objective here was two-fold. Firstly, to describe the temporal evolution of the geographical pattern of brain cancer incidence in Navarre and the Basque Country, and secondly, to look for specific high risk areas (municipalities) within these two regions in the study period (1986-2008)., Methods: A mixed Poisson model with two levels of spatial effects is used. The model also included two levels of spatial effects (municipalities and local health areas). Model fitting was carried out using penalized quasi-likelihood. High risk regions were detected using upper one-sided confidence intervals., Results: Results revealed a group of high risk areas surrounding Pamplona, the capital city of Navarre, and a few municipalities with significant high risks in the northern part of the region, specifically in the border between Navarre and the Basque Country (Gipuzkoa). The global temporal trend was found to be increasing. Differences were also observed among specific risk evolutions in certain municipalities., Conclusions: Brain cancer incidence in Navarre and the Basque Country (Spain) is still increasing with time. The number of high risk areas within those two regions is also increasing. Our study highlights the need of continuous surveillance of this cancer in the areas of high risk. However, due to the low percentage of cases explained by the known risk factors, primary prevention should be applied as a general recommendation in these populations.

Background and Aims: The evidence about the benefits of omega-3 fatty acid intake on coronary heart disease (CHD) is not consistent. We thus aimed to assess the relation between dietary intake of total omega-3 fatty acids (from plant and marine foods) and marine polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the risk of CHD in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods and Results: The analysis included 41,091 men and women aged 20-69 years, recruited from 1992 to 1996 and followed-up until December 2004. Omega-3 fatty acid intake was estimated from a validated dietary questionnaire. Only participants with definite incident CHD event were considered as cases. Cox regression models were used to assess the association between the intake of total omega-3 fatty acids, EPA or DHA and CHD. A total of 609 participants (79% men) had a definite CHD event. Mean intakes of total omega-3 fatty acids, EPA and DHA were very similar in the cases and in the cohort, both in men and women. In the multivariate adjusted model, omega-3 fatty acids, EPA and DHA were not related to incident CHD in either men or women. The hazard ratios (HR) for omega-3 were 1.23 in men (95% CI 0.94-15.9, p = 0.20); and 0.77 in women (95% CI 0.46-1.30, p = 0.76)., Conclusion: In the Spanish EPIC cohort, with a relatively high intake of fish, no association was found between EPA, DHA and total omega-3 fatty acid intake and risk of CHD., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Objective: Social position has yet to be established as a risk factor of coronary heart disease (CHD). Our aim was to investigate an individual life-course social position gradient link with CHD incidence in the EPIC-Spain cohort., Methods: 41,066 participants, mostly 30-65 years old, and free of cardiovascular disease at baseline (1992-1996) were followed up for a mean of 10.4 years. A combined score of paternal occupation in childhood and own adult education was used to assess individual life-course risk accumulation. Hazard ratios of CHD were estimated using Cox models, stratifying by centre, and age, and adjusting for cardiovascular risk factors., Results: 583 participants (80 % men) developed a definite CHD event. Paternal occupational class IV was associated with CHD in all models in men. The educational gradient remained significant after adjusting for diet and physical activity (p = 0.01). All adjusted risk of incident CHD rose by 23 % (95 % CI 6-42 %) per category increase of life-course social position score in men. No significant associations were found in women., Conclusions: Individual life-course social position gradient was adversely related to incident CHD in Spanish men.

Background and Purpose: Large-scale prospective epidemiological data testing the association between physical activity (PA) and cerebrovascular diseases (CVDs) are scarce, particularly in Europe. The objective was to assess the risk of CVD according to PA levels in adults., Methods: We included a total of 13 576 men and 19 416 women aged 29 to 69 years and participating in the European Prospective Investigation into Cancer and Nutrition cohort in Spain, recruited between 1992 and 1996 and followed-up until 2006 to ascertain incident CVD events. The validated European Prospective Investigation into Cancer and Nutrition PA questionnaire was used to assess metabolic equivalent × hours per week dedicated to different types of PA. Hazard ratios of CVD by PA levels were estimated using multivariate Cox regression. Extensive baseline data collected on diet, lifestyle habits, medical history, and anthropometry were available to adjust for., Results: A total of 210 transient ischemic attacks and 442 stroke cases (80% ischemic, 10% hemorrhagic, 7% subarachnoid hemorrhage, and 3% mixed or unspecified) were registered after 12.3 years of mean follow-up. Recreational activity was inversely associated with risk of CVD in women but not in men. Women walking for ≥3.5 hours per week were at lower risk of stroke than those who did not engage in regular walking. No significant associations were found for other leisure time activities or vigorous PA with CVD in either sex., Conclusions: Recreational PA of moderate intensity was inversely associated with stroke incidence in women, whereas PA showed no effect on CVD risk in men. Increasing time dedicated to activities such as walking would be expected to help to reduce the stroke burden in women.

Background: Information on the validity of self-reported cases of stroke and acute myocardial infarction (AMI) is varied. The aim of this study was to assess the validity and agreement of self-reported prevalent cases of stroke and AMI in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)., Methods: At recruitment, 1992-1996, and in the follow-up (3 years after recruitment), each participant in the Spanish EPIC cohort (15,630 men and 25,808 women) was asked if a doctor had ever said that they had had a stroke or AMI, and the results were compared with information available in medical records. Validity of self-reported prevalent cases of stroke and AMI was examined by calculating sensitivity, specificity, positive predictive values and κ statistics., Results: The sensitivity of self-reported prevalent cases of stroke was 81.3% and that for AMI was 97.7%. The positive predictive value was 22.2% and 60.7% for stroke and AMI, respectively, whereas specificity was very high (>99%) for both diseases. The agreement between self-report questionnaire results and medical records was substantial (κ=0.75) for AMI but not for stroke (κ=0.35)., Conclusion: Self-reported information on stroke and AMI included in the EPIC questionnaire is a valid instrument for the assessment of AMI disease but should be used with caution in stroke.

Olive oil is well known for its cardioprotective properties; however, epidemiological data showing that olive oil consumption reduces incident CHD events are still limited. Therefore, we studied the association between olive oil and CHD in the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort study. The analysis included 40 142 participants (38 % male), free of CHD events at baseline, recruited from five EPIC-Spain centres from 1992 to 1996 and followed up until 2004. Baseline dietary and lifestyle information was collected using interview-administered questionnaires. Cox proportional regression models were used to assess the relationship between validated incident CHD events and olive oil intake (energy-adjusted quartiles and each 10 g/d per 8368 kJ (2000 kcal) increment), while adjusting for potential confounders. During a 10·4-year follow-up, 587 (79 % male) CHD events were recorded. Olive oil intake was negatively associated with CHD risk after excluding dietary mis-reporters (hazard ratio (HR) 0·93; 95 % CI 0·87, 1·00 for each 10 g/d per 8368 kJ (2000 kcal) and HR 0·78; 95 % CI 0·59, 1·03 for upper v. lower quartile). The inverse association between olive oil intake (per 10 g/d per 8368 kJ (2000 kcal)) and CHD was more pronounced in never smokers (11 % reduced CHD risk (P = 0·048)), in never/low alcohol drinkers (25 % reduced CHD risk (P < 0·001)) and in virgin olive oil consumers (14 % reduced CHD risk (P = 0·072)). In conclusion, olive oil consumption was related to a reduced risk of incident CHD events. This emphasises the need to conserve the traditional culinary use of olive oil within the Mediterranean diet to reduce the CHD burden.

Background: An epidemiologic survey showed in 1992 iodine deficiency and endemic goiter in schoolchildren from the Basque Country., Objectives: (1) To determine the percentage of homes of schoolchildren where iodized salt (IS) is used; (2) to assess iodine nutrition status in schoolchildren and to compare the data collected to those available from previous epidemiological studies., Design and Methods: A cross-sectional study in 720 randomly selected schoolchildren. Urinary iodine concentration (UIC) was measured using high-performance liquid chromatography(HPLC) with electrochemical detection., Results: IS was used at 53.0% of the homes (95% confidence interval [CI], 49.2-56.7%). Median UIC has increased by 226%, from 65 μg/L in 1992 to 147 μg/L (percentile [P], P(25), 99 μg/L; P(75), 233 μg/L) today. Both schoolchildren consuming IS and those using unfortified salt at their homes had UICs corresponding to adequate iodine intakes (165 and 132 μg/L respectively). UICs experienced great seasonal fluctuations, being 55% higher during the November-February period than in June-September period (191 μg/L vs 123 μg/L; p<0.001), Conclusions: Schoolchildren from the Basque Country have normalized their iodine nutrition status. The strong seasonal pattern of UICs suggests that consumption of milk and iodine-rich dairy products coming from cows feed iodized fodder is one of the most significant factors involved in the increase in iodine intake since 1992., (Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.)

Introduction: The aim of this study is to analyse the evolution of the survival of patients diagnosed with prostate cancer during the period 1995-2003., Material and Methods: This is a population survival study of incident cases of prostate cancer in four Spanish areas: Basque Country, Girona, Murcia and Navarra. We calculated the relative survival (RS) at 5 years and its 95% confidence intervals using a cohort analysis and adjusted for age. To assess the trend in survival between the periods (1995-1999 and 2000-2003) a Poisson regression model was used, adjusting for age, region and period, obtaining the relative risk of death., Results: The number of patients diagnosed during the 1995- 1999 period was 6493 and 8331 in the period 2000-03. The RS at 5 years adjusted for age increased significantly, from 75.3% (95% CI 73.3-77.2) in the period 1995-99 to 85% (95% CI 83.4-86.4) in the period 2000-03., Conclusion: In Spain the survival of patients with prostate cancer has increased significantly from 1999 to 2003, probably due to the advancement in diagnosis produced by the opportunistic screening of prostate-specific antigen (PSA). Differences in the dissemination and use of the PSA level could explain the observed geographic differences in the increase of survival. It would be necessary to carry out studies to quantify the produced overdiagnosis by screening with PSA in prostate cancer.

Background: geographic differences described in the prognosis of cancer patients in the Basque Country have been attributed to a different incidence in tumours with different lethality. Therefore, cancer relative survival adjusted by case-mix was included to estimate cancer survival by provinces and health regions, using data from 1995 to 2004., Methods: a total of 93 585 cases of malignant tumours were identified from a population-based cancer registry. The five-year relative survival (RS) was calculated using Ederer´s method. The five-year relative excess risk (RER) of death was estimated with a generalised linear model, standardized by age and adjusted for sex, date of diagnosis and case-mix., Results: the five-year RS increased from period 1995-1999 to 2000-2004, this latter, with values ranging by health regions between 46-58% and 57-65% in men and women, respectively. There was an excess risk of death in Bizkaia (RER=1.06, CI95%: 1.03-1.09), this same effect being identified in almost all the health regions in the province. In contrast, in Gipuzkoa province, differences were only statistically significant in the Gipuzkoa and Tolosa health regions (RER=1.07; CI95%: 1.02-1.13 and RER=0.91; CI95%: 0.84-0.98, respectively), and even these disappeared after adjusting for potential confounders., Conclusions: cancer patients of Bizkaia, except for the Uribe health region, presented a worse prognosis.

Objective: To estimate the incidence and 28-day and 5-year survival rates after a first acute myocardial infarction (AMI) in relation to socioeconomic status in the Basque Country (Spain) between 1999 and 2000., Methods: Data from a population-based registry of AMI were used. The study included 3,619 patients to calculate age-standardized incidence by the direct method and 2,003 patients (out-of-hospital deaths were excluded) to calculate observed and relative survival using the Kaplan-Meier and Hakulinen methods, respectively. Socioeconomic status was quantified using a deprivation index ecologically assigned to each patient according to the census tract of residence at diagnosis of AMI and was categorized into quintiles., Results: Among men, the risk of AMI was higher in the lowest socioeconomic group than in the highest socioeconomic group (RR=1.17; 95%CI: 1.02-1.34). In men, a higher risk of death was observed in the middle (Q3; HR=1.60; 95%CI: 1.02-2.51) and low (Q5; HR=1.65; 95%CI: 1.02-2.69) quintiles compared with the least deprived group for age-adjusted survival during the acute phase. In the fully adjusted model, this effect was attenuated and no significant differences were observed in long-term survival. Among women, no significant differences were observed either in incidence or in short- and long-term survival., Conclusions: Socioeconomic inequalities were only observed in men in incidence and in survival during the acute phase after an AMI., (Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.)

Epidemiological studies show that adherence to a Mediterranean diet (MD) increases longevity; however, few studies are restricted to Mediterranean populations or explore the effect of a MD pattern that directly incorporates olive oil. Therefore the relationship between adherence to the MD and mortality was studied within the the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Spain). The EPIC-Spain analysis included 40 622 participants (37·7 % males) aged 29-69 years who were recruited from five Spanish regions in 1992-1996. During a mean follow-up of 13·4 years, 1855 deaths were documented: 913 from cancer, 399 from CVD, 425 from other causes and 118 from unknown causes of death. Risk of all-cause and cause-specific mortality was assessed according to the level of adherence to a relative MD (rMED) score, measured using an 18-unit scale incorporating nine selected dietary components. A high compared with a low rMED score was associated with a significant reduction in mortality from all causes (hazard ratio (HR) 0·79; 95 % CI 0·69, 0·91), from CVD (HR 0·66; 95 % CI 0·49, 0·89), but not from overall cancer (HR 0·92; 95 % CI 0·75, 1·12). A 2-unit increase in rMED score was associated with a 6 % (P < 0·001) decreased risk of all-cause mortality. A high olive oil intake and moderate alcohol consumption contributed most to this association. In this Spanish cohort, following an olive oil-rich MD was related to a significant reduction in all-cause mortality, and reduced the risk of mortality from CVD. These results support the important role that the MD pattern has on reducing mortality in Mediterranean countries.

The association is still not clear between the common APOE polymorphism and coronary heart disease (CHD) risk, nor its modulation by diet. Thus, our aim was to study the association between the APOE genotypes and incident CHD and how dietary fat and alcohol consumption modify these effects. We performed a nested case-control study in the Spanish European Prospective Investigation into Cancer and Nutrition cohort. Healthy men and women (41,440, 30-69 years) were followed up over a 10-year period, with the incident CHD cases being identified. We analyzed 534 incident CHD cases and 1123 controls. APOE, dietary intake and plasma lipids were determined at baseline. The APOE polymorphism was significantly associated with low-density lipoprotein cholesterol (LDL-C), and gene-alcohol interactions in determining LDL-C were detected. In the whole population, the E2 allele was significantly associated with a lower CHD risk than E3/E3 subjects [odds ratio (OR), 0.58; 95% confidence interval (CI), 0.38-0.89]. The E4 allele did not reach statistical significance vs. E3/E3 (OR, 1.17; 95% CI, 0.88-1.58). However, saturated fat intake modified the effect of the APOE polymorphism in determining CHD risk. When saturated fat intake was low (<10% of energy), no statistically significant association between the APOE polymorphism and CHD risk was observed (P=.682). However, with higher intake (≥10%), the polymorphism was significant (P=.005), and the differences between E2 and E4 carriers were magnified (OR for E4 vs. E2, 3.33; 95% CI, 1.61-6.90). Alcohol consumption also modified the effect of the APOE on CHD risk. In conclusion, in this Mediterranean population, the E2 allele is associated with lower CHD risk, and this association is modulated by saturated fat and alcohol consumption., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Introduction and Objectives: To determine 28-day and 5-year survival rates in patients who have experienced a first acute myocardial infarction and to identify prognostic factors for survival., Methods: This study involved 1,677 patients with a first acute myocardial infarction who were treated at a hospital in Guipuzcoa, Spain between 1997 and 2000., Results: Women were approximately 10 years older than men, presented more often with diabetes and hypertension, were in a less favorable clinical condition, and consumed fewer medical resources, but were less likely to smoke. Survival rates at 28 days and 5 years were higher in men over 60 years of age. In the period from 29 days to 5 years, the relative survival rate was higher in men from all age groups. Factors associated with short- and long-term survival varied between the sexes. Disease severity in the acute phase and, later on, age were associated with survival in both men and women, whereas the effect of other variables differed between the sexes., Conclusions: Myocardial infarction is a condition associated with high mortality in the acute phase. There is an interaction between sex and age that affects survival after an acute myocardial infarction. A number of factors are associated with poor short- and long-term prognoses in both sexes.

Phytosterol intake with natural foods, a measure of healthy dietary choices, increases plasma levels, but increased plasma phytosterols are believed to be a coronary heart disease (CHD) risk factor. To address this paradox, we evaluated baseline risk factors, phytosterol intake, and plasma noncholesterol sterol levels in participants of a case control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) Spanish cohort who developed CHD (n = 299) and matched controls (n = 584) who remained free of CHD after a 10 year follow-up. Sitosterol-to-cholesterol ratios increased across tertiles of phytosterol intake (P = 0.026). HDL-cholesterol level increased, and adiposity measures, cholesterol/HDL ratios, and levels of glucose, triglycerides, and lathosterol, a cholesterol synthesis marker, decreased across plasma sitosterol tertiles (P < 0.02; all). Compared with controls, cases had nonsignificantly lower median levels of phytosterol intake and plasma sitosterol. The multivariable-adjusted odds ratio for CHD across the lowest to highest plasma sitosterol tertile was 0.59 (95% confidence interval, 0.36-0.97). Associations were weaker for plasma campesterol. The apolipoprotein E genotype was unrelated to CHD risk or plasma phytosterols. The data suggest that plasma sitosterol levels are associated with a lower CHD risk while being markers of a lower cardiometabolic risk in the EPIC-Spain cohort, a population with a high phytosterol intake.

Background: The use of hospital discharge administrative data (HDAD) has been recommended for automating, improving, even substituting, population-based cancer registries. The frequency of false positive and false negative cases recommends local validation., Methods: The aim of this study was to detect newly diagnosed, false positive and false negative cases of cancer from hospital discharge claims, using four Spanish population-based cancer registries as the gold standard. Prostate cancer was used as a case study., Results: A total of 2286 incident cases of prostate cancer registered in 2000 were used for validation. In the most sensitive algorithm (that using five diagnostic codes), estimates for Sensitivity ranged from 14.5% (CI95% 10.3-19.6) to 45.7% (CI95% 41.4-50.1). In the most predictive algorithm (that using five diagnostic and five surgical codes) Positive Predictive Value estimates ranged from 55.9% (CI95% 42.4-68.8) to 74.3% (CI95% 67.0-80.6). The most frequent reason for false positive cases was the number of prevalent cases inadequately considered as newly diagnosed cancers, ranging from 61.1% to 82.3% of false positive cases. The most frequent reason for false negative cases was related to the number of cases not attended in hospital settings. In this case, figures ranged from 34.4% to 69.7% of false negative cases, in the most predictive algorithm., Conclusions: HDAD might be a helpful tool for cancer registries to reach their goals. The findings suggest that, for automating cancer registries, algorithms combining diagnoses and procedures are the best option. However, for cancer surveillance purposes, in those cancers like prostate cancer in which care is not only hospital-based, combining inpatient and outpatient information will be required.

No known cohort study has investigated whether the Mediterranean diet can reduce incident coronary heart disease (CHD) events in a Mediterranean population. This study examined the relation between Mediterranean diet adherence and risk of incident CHD events in the 5 Spanish centers of the European Prospective Investigation into Cancer and Nutrition. Analysis included 41,078 participants aged 29-69 years, recruited in 1992-1996 and followed up until December 2004 (mean follow-up:10.4 years). Confirmed incident fatal and nonfatal CHD events were analyzed according to Mediterranean diet adherence, measured by using an 18-unit relative Mediterranean diet score. A total of 609 participants (79% male) had a fatal or nonfatal confirmed acute myocardial infarction (n = 468) or unstable angina requiring revascularization (n = 141). After stratification by center and age and adjustment for recognized CHD risk factors, high compared with low relative Mediterranean diet score was associated with a significant reduction in CHD risk (hazard ratio = 0.60, 95% confidence interval: 0.47, 0.77). A 1-unit increase in relative Mediterranean diet score was associated with a 6% reduced risk of CHD (95% confidence interval: 0.91, 0.97), with similar risk reductions by sex. Mediterranean diet adherence was associated with a significantly reduced CHD risk in this Mediterranean country, supporting its role in primary prevention of CHD in healthy populations.

Background: Since the 1980s, Spain experienced two decades of sharply increasing breast cancer incidence. Declines in breast cancer incidence have recently been reported in many developed countries. We examined whether a similar downturn might have taken place in Spain in recent years., Methods: Cases of invasive female breast cancer were drawn from all population-based Spanish cancer registries that had at least 10 years of uninterrupted registration over the period 1980-2004. Overall and age-specific changes in incidence rates were evaluated using change-point Poisson models, which allow for accurate detection and estimation of trend changes. All statistical tests were two-sided., Results: A total of 80,453 incident cases of invasive breast cancer were identified. Overall age- and registry-adjusted incidence rates rose by 2.9% (95% confidence interval [CI] = 2.7% to 3.1%) annually during the 1980s and 1990s; there was a statistically significant change in this trend in 2001 (95% CI = 1998 to 2004; P value for the existence of a change point <.001), after which incidence declined annually by 3.0% (95% CI = 1.8% to 4.1%). This trend differed by age group: There was a steady increase in incidence for women younger than 45 years, an abrupt downturn in 2001 for women aged 45-64 years, and a gradual leveling off in 1995 for women aged 65 years or older. Separate analyses for registries that had at least 15 years of uninterrupted registration detected a statistically significant interruption of the previous upward trend in breast cancer incidence in provinces that had aggressive breast cancer screening programs and high screening participation rates, including Navarra (change point = 1991, P < .001), Granada (change point = 2002, P = .003), Bizkaia (change point = 1998, P < .001), Gipuzkoa (change point = 1998, P = .001), and Araba (change point = 1997, P = .002)., Conclusions: The recent downturn in breast cancer incidence among Spanish women older than 45 years is best explained by a period effect linked to screening saturation.

Objective: To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other., Methods: All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied., Results: Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease., Conclusions: Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.

Background: Polychlorinated biphenyls (PCBs) are persistent compounds that may pose an environmental hazard to humans, food being the main source of exposure for the general population., Objective: To measure the serum concentrations of the main PCBs in subjects from the general population in Spain, and to assess potential determinants of such concentrations., Methods: Serum was obtained from blood samples of 953 subjects aged 35-64 years, residents in five Spanish regions (three from the North and two from the South), randomly selected from the EPIC-Spain cohort. Blood collection took place during 1992-1996 and four PCB congeners (118, 138, 153 and 180) were determined by means of gas chromatography with electron-capture detection (GC-ECD)., Results: The concentration of total PCBs was 459 ng/g lipids (or 3.1 microg/l); the corresponding figures for PCB 153 were 186 ng/g lipids and 1.25 microg/l. Men had higher values than women, PCB levels increased with age, and serum concentration of PCBs was higher in northern regions. Body mass index (BMI) was inversely related to PCB concentrations, and fish intake was the dietary factor showing the greatest association with serum PCBs. The pattern described was similar for each congener separately., Conclusions: We found concentrations similar to those reported in European countries where blood collection was carried during the same period. Regional differences within Spain are not fully explained by anthropometric or dietary factors. The inverse association with BMI suggests that in the mid-1990s there was still ongoing or recent exposure to PCBs in Spain.

Background: In Gipuzkoa, screening for breast cancer was initiated in 1997 and in this paper we present breast cancer characteristics and survival for women diagnosed during the pre-screening period., Methods: All cases diagnosed during 1995-1996 were included and the tumour characteristics were analysed. One-, five- and ten-year observed and relative survival (RS) were estimated overall, as well as by age and tumour characteristics. Multiple regression models were used to evaluate the effect of tumour characteristics on ten-year RS., Results: Six hundred and twenty-two cases with a mean age of 60.7+/-15 years were included. The mean follow-up was 7.5 years (max. 10) with a mortality of 40.5%. Ductal carcinoma accounted for 78% of all cases; almost 50% had good or moderate differentiation and 28% were positive for both hormone receptors studied. Nearly 80% of cases were diagnosed in stage I or II and breast-conserving surgery was employed more often than mastectomy. Age-standardised RS was 77% (95% CI 72.1-82.3) and 68% (95% CI 60.4-74.6), five and ten years after diagnosis respectively. The relative excess risk of death was significantly different only for age, stage and degree of differentiation., Discussion: This study shows an increase in survival compared to previous studies in the region. This could be explained by advances in diagnosis and treatment, as demonstrated by younger age and earlier stage at diagnosis and by the therapy profiles. Age and stage were shown to be major predictors of survival in our study and adjustment for the other factors had only limited effects on the risk of death for these two variables.

Background: There is some evidence that Mediterranean diet reduces risk of ischemic heart disease, and this is to be investigated in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC). In this paper we present the incidence of acute myocardial infarction (AMI) in four EPIC Spanish cohorts., Method: Incidence cases were ascertained in EPIC cohort during the follow up period (from recruitment to the end of 2004), by means of self-report questionnaires, hospital morbidity and mortality registries, and population AMI registries. Analysis was restricted to aged 45 to 74. The present study included data from 13,704 women and 19,410 men, after excluding a priori participants with prevalent AMI. Age standardized incidence rate for each cohort was estimated and compared with the available population rates., Results: The Median duration of follow-up was 9.3 years, yielding a total of 297,704 person-years. 391 men and 99 women presented AMI in the four cohorts studied. Age standardized AMI rates in men of the EPIC cohorts go from the lowest 302 (CI: 268-335) per 100.000 person-year of Gipuzkoa to the highest 330 (CI: 293-367) of Navarra. Women in Navarra presented the lowest AMI incidence with 60 (CI: 43-77) per 100,000 and the highest was observed in Murcia (114, CI: 91-137). The AMI incidence in all EPIC centres are close to the population incidence rates and in any case these are within the EPIC 95% CI., Conclusions: The comparison of incidence in EPIC with population rates shows very good agreement for acute myocardial infarction.

Objectives: To determine the cancer incidence in Gipuzkoa (Spain) from 1998 to 2002 and describe time trends since 1986., Methods: The annual incidence of cancer in Gipuzkoa from 1998 to 2002 was estimated as a rate per 100,000 inhabitants. Incidence trends for the period 1986-2002 were studied for all cancers and for the main cancer sites using Poisson regression and Joinpoint regression for prostate tumours., Results: On average, one in 3 men and one in 5 women would probably be diagnosed with cancer at some time during their life (0-74 years). Among men, prostate surpassed lung as the most frequent cancer site. Among women, breast cancer represented approximately 30% of all cases of cancer (excluding non-melanoma skin cancers). There was an annual increase in the incidence of cancer of 1.5% (95% CI, 1.1-1.8) in men and 0.9% (95% CI, 0.5-1.3) in women. The incidence of prostate cancer in men increased over the study period, and especially between 1996 and 1999, with an annual increase of 34.7% (95% CI, 5.9-71.5). The incidence of lung cancer in women presented an annual increase of 5.2% (95% CI, 3.4-7.1). In contrast, the incidence of stomach cancer decreased during the study period., Conclusions: Cancer incidence in Gipuzkoa increased during the study period. This increase was particularly marked in lung cancer and skin melanoma, for which preventive strategies are fundamental.

The objective of the study was to estimate the prevalence of overweight and obesity in children and adolescents in the Basque Country, Spain. It consisted of an analysis of baseline data of the Nutrition Survey, a cross-sectional study, carried out in 2004-2005. The study population comprised child and adolescent living in the Basque Country. The analysis was carried out in a representative random sample of 1178 people aged 4-18 years. Anthropometric examinations were undertaken by trained observers using standardized methods and included measurements of weight and height. Subjects were classified into different body mass index categories, according to the International Obesity Task Force guidelines. A 5.4% of the population studied was obese; 6% of males and 4.7% of females, the highest in the 11-14 age group in boys (7.2%) and in the 4-6 age group in girls (12.5%). Overweight (22.9%) was slightly higher in girls. The highest prevalence of excess weight (overweight+obesity) was observed in girls aged 4-6 years (38.4%), decreasing with age. Subjects in the 15-18 age group rated 16.6%. Boys evidenced a higher excess weight rate in the 11-14 (32.9%) and 7-10 (32%) age groups; the lowest rate was found in the 4-6 age group. Prevalence of obesity was higher in the less privileged socio-economic strata (6.9% vs. 5.2%), for both boys and girls. However, this trend was observed only in girls for overweight (25.9% vs. 21.8%). This study shows a high prevalence of obesity and overweight in the studied population and similar to other European countries and regions.

Background: Epidemiologic data suggest that persons with diets rich in fruit and vegetables are at a lower risk of several chronic diseases and mortality than are persons with diets poor in fruit and vegetables. Often, this effect is attributed to antioxidant micronutrients found in plant foods., Objective: We aimed to assess the relation of mortality to the consumption of fruit, vegetables, and other plant foods and to the dietary intake of vitamin C, vitamin E, and carotenoids., Design: The study was a prospective study in the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition. During 6.5 y of follow-up, 562 deaths occurred in 41 358 subjects aged 30-69 y. Proportional hazards regression analysis was used to assess the relation between dietary factors and total mortality., Results: After adjustment for age, sex, and several potential confounders, the hazard ratio for the highest versus the lowest quartile of consumption was 0.79 (95% CI: 0.62, 1.00; P for trend = 0.029) for fresh fruit, 0.72 (0.56, 0.91; P for trend = 0.006) for root vegetables, and 0.77 (0.60, 0.98; P for trend = 0.015) for fruiting vegetables (ie, vegetables that contain the "fruit" part of the plant, the seeds). The corresponding figures for antioxidant nutrients were 0.74 (0.58, 0.94; P for trend = 0.009) for vitamin C, 0.68 (0.53, 0.87; P for trend = 0.006) for provitamin A carotenoids, and 0.65 (0.51, 0.84; P for trend 0.001) for lycopene. The effect of vitamin C and provitamin A disappeared after adjustment for total antioxidant capacity in plant foods., Conclusions: A high intake of fresh fruit, root vegetables, and fruiting vegetables is associated with reduced mortality, probably as a result of their high content of vitamin C, provitamin A carotenoids, and lycopene. Antioxidant capacity could partly explain the effect of ascorbic acid and provitamin A but not the association with lycopene.

Objective: To conduct a comprehensive assessment of dietary intakes of nitrites and N-nitrosodimethylamine (NDMA)., Subjects and Setting: A study was conducted within the Spanish cohort of the European Prospective Investigation in Cancer and Nutrition (EPIC) to assess the intake and food sources of these compounds in Spanish adults. The study included 41,446 health volunteers, aged 29-69 years, from Northern and Southern regions. Usual food intake was estimated by in-person interviews using a computerised dietary questionnaire., Results: The estimated geometric mean was 0.994 mg day(-1) for nitrites and 0.114 microg day(-1) for NDMA. For both compounds a positive trend in consumption with increasing energy intake was observed. Dietary NDMA was related to age and sex after energy adjustment, while nitrite consumption increased with higher intakes of vitamin C (P < 0.001). The food groups that contributed most to intakes were meat products, cereals, vegetables and fruits for nitrites, and processed meat, beer, cheese and broiled fish for NDMA. Current and past smokers, who had high levels of NDMA from tobacco exposure, were also identified as the highest consumers of dietary NDMA. Furthermore, smokers had low intakes of vitamin C (an inhibitor of endogenous nitrosation)., Conclusions: Intake levels of NDMA and nitrites in a Mediterranean cohort are currently relatively lower than those previously reported, although processed meat, beer and cured cheese still are the most important contributors to NDMA intake.

Introduction: This study aims to assess the validity of self reported diagnoses of cancer by persons recruited for the Spanish EPIC (European prospective investigation into cancer and nutrition) cohort study and to identify variables associated with correctly reporting a diagnosis of cancer., Methods: 41 440 members of EPIC were asked at the time of recruitment whether they had been diagnosed with cancer and the year of diagnosis and site. The process of validating self reported diagnoses of cancer included comparison of the cohort database with the data from the population based cancer registries. Cancer diagnostic validity tests were calculated. The association between a correct report and certain sociodemographic, tumour related, or health related variables were analysed by logistic regression., Results: The overall sensitivity of self reported diagnoses of cancer is low (57.5%; 95% CI: 51.9 to 63.0), the highest values being shown by persons with a higher level of education or with a family history of cancer and the lowest values by smokers. Breast and thyroid cancers are those with the highest diagnostic validity and uterus, bladder, and colon-rectum those with the lowest. In both sexes the variables showing a significant association with a correct report of cancer are: higher education level, number of previous pathologies, invasive tumour, and, in women, a history of gynaecological surgery., Conclusions: The overall sensitivity of self reported diagnoses of cancer is comparatively low and it is not recommended in epidemiological studies for identifying tumours. However, self reported diagnoses might be highly valid for certain tumour sites, malignant behaviour, and average to high levels of education.

Purpose: We assessed changes in smoking behavior and its related factors among healthy adults from five regions in Spain., Methods: The smoking status at recruitment and after 3 years was compared in 14,288 men and 23,983 women aged 35 to 64 years. The pattern of smoking and several lifestyle factors were investigated as potential predictors of subsequent changes in smoking habits., Results: Among current smokers at baseline the age-adjusted rates of cessation per 1000 person-years were 57.4 for men and 43.2 for women. Among former smokers at baseline the relapse rates were 37.6 and 48.8 per 1000 person-years for men and women, respectively. The initiation rate per 1000 person-years among men who had never smoked was 12.5 and 2.7 for women. Higher amount currently smoked and longer time since quitting were strong predictors of lower rates of cessation and relapse, respectively, while age was associated with lower initiation rates in women. Increased alcohol consumption was related to low cessation and high relapse and initiation rates, mainly among men, while more educated women had higher cessation and initiation rates., Conclusions: The current pattern of changes in smoking behavior in Spanish populations aged 35 to 64 years results in rather small prevalence reduction. Additional efforts should be made to promote successful cessation and prevent initiation to reduce the tobacco burden in Spain.

Background: Study of the incidence and change the number of cases of tuberculosis within the Alava Medical Care Area from 1990-1993 and comparison with reported cases., Method: Active research of tuberculosis cases diagnosed in hospitals located in the Area. All cases reported to the Epidemiological Unit of the Alava Territorial Health Delegation via the System of Compulsory Declaration of Diseases (EDO) were also included., Results: 756 cases of tuberculosis were detected, representing an average incidence of 69.4 cases/100,0000 inhabitants. There was an increase from 57.3 in 1990 to 86.6 cases/100,000 inhabitants in 1993, in particular amongst people over the age of 80. People under the age of 20 not only showed the lowest rate (7.1 cases/100,000 inhabitants) but also remained stable over the period analysed. The greatest number of cases were males (71.3%) aged from 20-39 (48.9%). 22% of all cases were patients suffering from AIDS. The annual increase in the total number of patients was 23.3% as opposed to 12.3% of AIDS patients. A deficient level of declaration was observed over the 4 year period, gradually decreasing from 28.9% in 1991 to 16.9% in 1993., Conclusions: The incidence of cases of tuberculosis within the Alava Medical Care Area is extremely high, showing an increasing trend during the period not covered by EDOs, which should be confirmed by a study carried out over a longer period of time.