How the Seven Countries Study contributed to the definition and development of the Mediterranean diet concept: a 50-year journey.

The Seven Countries Study of Cardiovascular Diseases was started at the end of the 1950s and it continues to be run after >50 years. It enrolled, at entry, 16 population cohorts in eight nations of seven countries for a total of 12,763 middle-aged men. It was the prototype of epidemiological studies seeking cultural contrasts and the first to compare cardiovascular disease (CVD) rates related to diet differences. The study has shown that populations suffer widely different incidence and mortality rates from coronary heart disease (CHD) as well as from other CVDs and overall mortality. Higher rates were found in North America and northern Europe, and lower rates in southern Europe - Mediterranean countries - and Japan. These differences in CHD rates were strongly associated with different levels of saturated fat consumption and average serum cholesterol levels, with lowest rates in Greece and Japan where the total fat intake was very different. The cohorts were also different in dietary patterns defined by the ratio of calories derived from plant foods and fish on the one hand and calories derived from animal foods and sugar on the other. These findings pointed to the so-called Mediterranean diet, which is characterized by large values of that plant/animal ratio, a pattern associated with lower incidence and mortality from CHD and also with the lowest death rates and the greatest survival rates. More recent studies have refined these concepts and documented on a larger scale the virtues of these eating habits.

Lifestyle habits and mortality from all and specific causes of death: 40-year follow-up in the Italian Rural Areas of the Seven Countries Study.

OBJECTIVES: Three lifestyle factors were investigated in a population study to explore their relationships with a long-term mortality. MATERIAL AND METHODS: In a cohort of 1564 men aged 45-64 and examined in 1965 within the Italian Rural Areas of the Seven Countries Study, smoking habits, physical activity at work and eating habits (as derived from factor analysis) were determined. During the follow-up 693 men died in 20 years and 1441 in 40 years. RESULTS: In Cox proportional hazards models men smoking cigarettes (versus never smokers), those having a sedentary activity (versus the very active) and those following the Diet Score 1, indexing an unhealthy Diet (versus men with a Diet close to the healthy Mediterranean style) had highly significant hazards ratios (HR) in relations with 20- and 40-year mortality from all causes, coronary heart disease (CHD), cardiovascular disease (CVD) and cancer. HR for all causes in 40 years were 1.44 (95% confidence intervals, CI, 1.27 and 1.64) for smokers, 1.43 (CI 1.23 and 1.67) for sedentary people, and 1.31 (CI 1.15 and 1.50) for men with unhealthy diet. Larger HR were found for CHD, CVD and cancers deaths. Combination of 3 unhealthy risk factors versus their absence was associated with 4.8-year life loss in the 20-year follow-up and 10.7-year in the 40-year follow-up. CONCLUSIONS: Lifestyle behavior linked to physical activity and smoking and eating habits is strongly associated with mortality and survival in middle aged men during long-term follow-up.

The association of the Mediterranean Adequacy Index with fatal coronary events in an Italian middle-aged male population followed for 40 years.

BACKGROUND AND AIMS: The dietary habits defined as the Mediterranean diet have shown to be protective for coronary heart disease (CHD) and other morbid conditions. The present analysis aims to test the Mediterranean Adequacy Index (MAI), a dietary index derived from the Mediterranean habits, versus the occurrence of fatal CHD events in an Italian male population followed for 40 years. METHODS AND RESULTS: In 1965, at the time of the 5-year follow-up examination of the Italian Rural Areas of the Seven Countries Study, the diet was assessed by the dietary-history method in 1139 men aged 45-64 years, free from previous coronary events, in the rural communities of Crevalcore (Northern Italy) and Montegiorgio (Central Italy). MAI has been computed and its natural log (lnMAI) used for the analysis. Mortality data were collected and coded for the subsequent 40 years. The lnMAI was inversely associated with CHD mortality at 20 and 40 years when entered alone in the Cox proportional hazards model and when adjusted for age, cigarette smoking, systolic blood pressure, serum cholesterol, physical activity and body mass index. The hazard ratio for 1 unit of lnMAI (roughly corresponding to 2.7 units of MAI) was associated with a CHD mortality reduction of 26% in 20 years and 21% in 40 years of follow-up, when adjusted for the covariates. CONCLUSIONS: In an Italian middle-aged male population, MAI showed the protective effect of a healthy Mediterranean Diet pattern versus the occurrence of fatal CHD events at 20 and 40 years.

The role of HDL cholesterol in metabolic syndrome predicting cardiovascular events. The Gubbio population study.

BACKGROUND AND AIMS: Metabolic syndrome (MS) has recently been claimed to be an important new risk factor for the occurrence of coronary heart disease (CHD) and cardiovascular disease (CVD) events, although it is simply a combination of known risk factors used in a dichotomized fashion. The aims of this analysis were to explore the predictive role of MS for CHD and CVD events in a population study, in comparison with using the same factors in a continuous fashion, with special emphasis on HDL cholesterol. METHODS AND RESULTS: In the second examination of the Gubbio population study from central Italy, 2650 cardiovascular disease-free men and women, aged 35-74 years around 1990, were examined and followed-up for 12 years. The classic risk factors (sex, age, systolic blood pressure, serum cholesterol and smoking habits) were studied as predictors of CHD and CVD events, alone and with the contribution of other factors (HDL cholesterol, blood glucose, serum triglycerides and waist circumference) included in the so-called MS, based on several multivariate models. MS was also tested after adjustment for other risk factors. MS produced a predictive significant relative risk of 1.67 for CHD events and 1.82 for CVD events, but considering its single risk factors, the only ones contributing to prediction were HDL cholesterol and systolic blood pressure. Dedicated analyses showed that MS does not add anything to the power of prediction beyond the role of the single risk factors treated in a continuous fashion, while the best predictive power is obtained using classic risk factors (sex, age, smoking habits, total cholesterol, systolic blood pressure) with the addition of HDL cholesterol. CONCLUSIONS: The predictive power of MS is bound only to the presence of HDL cholesterol and blood pressure and does not add anything to using the same risk factor treated in a continuous fashion.

HDL cholesterol protects against cardiovascular disease in both genders, at all ages and at all levels of risk.

OBJECTIVE: We aimed to clarify some previous inconsistencies regarding the role of high density lipoprotein cholesterol (HDL-C) as a CVD protective factor. METHODS: The SCORE dataset contained data on HDL-C for 104,961 individuals (45% women) without pre-existing coronary heart disease (CHD). These were from 7 pooled European prospective studies. The effect of HDL-C, both in quintiles and as a continuous variable, on risk of CVD and CHD mortality was examined, using Cox proportional hazards model, adjusted for age, total cholesterol, systolic blood pressure, smoking, diabetes and body mass index and stratified by gender, age group, country and category of SCORE CVD risk. RESULTS: A strong, graded, independent, inverse relationship between HDL-C and both CVD and CHD mortality was demonstrated. Adjusted hazard ratios per 0.5mmol/l increase in HDL-C were 0.60 (0.51, 0.69) and 0.76 (0.70, 0.83) in women and men, respectively for the CVD mortality endpoint. The corresponding hazard ratios were 0.53 (0.42, 0.68) and 0.79 (0.64, 0.98) in elderly women and men, respectively. The relationship was significant in all SCORE CVD risk strata and age groups. CONCLUSIONS: This multivariable analysis, the largest of its kind to date, has confirmed the inverse, independent, strong and graded relationship between HDL-C and both CVD and CHD mortality. We have clarified previous suggestions that the relationship is stronger in women and that it applies in all age groups. This is the first prospective study to demonstrate the independent relationship specifically in healthy elderly women and to show that the relationship holds at all levels of total CVD risk.

Chromosome painting shows that skunks (Mephitidae, Carnivora) have highly rearranged karyotypes.

The karyotypic relationships of skunks (Mephitidae) with other major clades of carnivores are not yet established. Here, multi-directional chromosome painting was used to reveal the karyological relationships among skunks and between Mephitidae (skunks) and Procyonidae (raccoons). Representative species from three genera of Mephitidae (Mephitis mephitis, 2n = 50; Mephitis macroura, 2n = 50; Conepatus leuconotus, 2n = 46; Spilogale gracilis, 2n = 60) and one species of Procyonidae (Procyon lotor, 2n = 38) were studied. Chromosomal homology was mapped by hybridization of five sets of whole-chromosome paints derived from stone marten (Martes foina, 2n = 38), cat, skunks (M. mephitis; M. macroura) and human. The karyotype of the raccoon is highly conserved and identical to the hypothetical ancestral musteloid karyotype, suggesting that procyonids have a particular importance for establishing the karyological evolution within the caniforms. Ten fission events and five fusion events are necessary to generate the ancestral skunk karyotype from the ancestral carnivore karyotype. Our results show that Mephitidae joins Canidae and Ursidae as the third family of carnivores that are characterized by a high rate of karyotype evolution. Shared derived chromosomal fusion of stone marten chromosomes 6 and 14 phylogenetically links the American hog-nosed skunk and eastern spotted skunk.

Physical activity decreases the risk of stroke in middle-age men with left ventricular hypertrophy: 40-year follow-up (1961-2001) of the Seven Countries Study (the Corfu cohort).

Left ventricular hypertrophy (LVH) is a dominant characteristic of cardiovascular mortality. We investigated the interaction between physical activity and LVH on stroke mortality, based on a 40-year follow-up of the Corfu cohort from the Seven Countries Study. The population studied consisted of 529 rural men (40-59 years old) enrolled in the Study at 1961. LVH was electrographically confirmed according to Minnesota coding. Physical activity levels were assessed by self-reports of habitual, occupational and leisure-time activities. Cox proportional hazard models were used to evaluate exercise levels with respect to stroke mortality in people with and without LVH. During the follow-up, 461 (87%) died, and 74 (16%) of these deaths were due to stroke. LVH was present in 40 (7.5%) men. A total of 362 (68%) men were defined as physically active. Physical activity was associated with a lower risk of stroke (hazard ratio=0.65, P<0.05). On the other hand, LVH had 5.8-fold the risk of stroke (P<0.001) among sedentary and 4.5-fold the risk (P<0.001) among physically active men, after controlling for several potential confounders. However, moderate physical activity decreased the risk of stroke by 49% in men with LVH as compared to sedentary without LVH (hazard ratio=0.51, P<0.01), while hard exercise did not confer any significant reduction in stroke risk. We revealed the benefits from moderate physical activity on stroke mortality among men with LVH. Physicians and other health-care professionals should encourage patients with LVH to adopt a physically active lifestyle.

Mediterranean Adequacy Index: correlation with 25-year mortality from coronary heart disease in the Seven Countries Study.

BACKGROUND AND AIM: The Mediterranean Adequacy Index (MAI) is an overall indicator characterising a diet in comparison with a Reference Mediterranean Diet. We computed the MAI of random samples of men surveyed for their eating habits in the 16 cohorts of the Seven Countries Study, and found that it inversely correlated with the 25-year death rates from coronary heart disease in the 16 cohorts (R = -0.72; p = 0.001). The correlation coefficient was -0.84 (p < 0.001) when the MAI was converted into natural logarithms. CONCLUSIONS: These findings once again support the association between typical Mediterranean eating habits and protection against coronary heart disease.

Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project.

AIMS: The SCORE project was initiated to develop a risk scoring system for use in the clinical management of cardiovascular risk in European clinical practice. METHODS AND RESULTS: The project assembled a pool of datasets from 12 European cohort studies, mainly carried out in general population settings. There were 20,5178 persons (88,080 women and 11,7098 men) representing 2.7 million person years of follow-up. There were 7934 cardiovascular deaths, of which 5652 were deaths from coronary heart disease. Ten-year risk of fatal cardiovascular disease was calculated using a Weibull model in which age was used as a measure of exposure time to risk rather than as a risk factor. Separate estimation equations were calculated for coronary heart disease and for non-coronary cardiovascular disease. These were calculated for high-risk and low-risk regions of Europe. Two parallel estimation models were developed, one based on total cholesterol and the other on total cholesterol/HDL cholesterol ratio. The risk estimations are displayed graphically in simple risk charts. Predictive value of the risk charts was examined by applying them to persons aged 45-64; areas under ROC curves ranged from 0.71 to 0.84. CONCLUSIONS: The SCORE risk estimation system offers direct estimation of total fatal cardiovascular risk in a format suited to the constraints of clinical practice.

Twenty-five-year coronary mortality trends in the seven countries study using the accelerated failure time model.

The 'accelerated failure time model' (AFT) was tested in the 25-year experience of the Seven Countries Study, to describe the shape of hazard for coronary heart disease (CHD) mortality during long-term follow-up. Sixteen cohorts of men aged 40-59 at entry were enrolled in eight countries (USA, Finland, The Netherlands, Italy, Croatia, Serbia, Greece and Japan) for a total of 12,763 subjects. Risk factors were measured and CHD mortality data collected during 25 years. The AFT incorporating the Weibull survival distribution was applied to the pooled cohorts of each country, with CHD mortality as endpoint. Cumulative hazards and the annual hazard for CHD mortality were estimated during 25 years and compared among countries. The annual hazard for CHD in 25 years tended to reduce relatively or flatten out in the northern American and northern European countries, exponentially increased in Serbia and Japan, and increased moderately in the other countries of southern Europe. Positive correlations were found between the shape of the hazard curve and population mean risk factor changes (serum cholesterol and systolic blood pressure) observed during the first 10 years follow-up. The Japanese group was an outlier. The countries with the largest relative decline in the annual hazard function were the same where, during the same historical period, the largest decreases in official death rates from CHD were recorded and vice versa. The curve shape in the annual hazard for CHD mortality in different countries seems related to changes in mean levels of serum cholesterol and systolic blood pressure.

Coronary risk factors predicting early and late coronary deaths.

OBJECTIVE: To study the time related association of a single measurement of coronary risk factors with coronary heart disease (CHD) deaths occurring during a very long follow up period in a population sample of middle aged men. DESIGN, SETTING, AND METHODS: Age, systolic blood pressure, serum total cholesterol, physical activity at work, body mass index, and cigarette smoking were measured once in 1622 CHD-free men aged 40-59 belonging to the Italian rural cohorts of the seven countries study. During 35 years of follow up 214 men died from CHD (sudden death and definite myocardial infarction). Seven partitioned proportional hazards models were solved, one for each independent five year block of follow up, to predict the risk of CHD death. RESULTS: The seven, five year partitioned hazard functions were cumulated and smoothed for each risk factor. The resulting curves showed a regularly increasing time trend in risk for coronary deaths as a function of age, serum cholesterol, systolic blood pressure, and cigarette smoking and a regularly decreasing risk for physical activity. The curves fit straight lines, with large squared correlation coefficients ranging from 0.92-0.97. This suggests a relatively constant strength in the association of risk factor levels with events, which are predicted whatever the length of time after risk factors were measured. These findings were not altered by adding to the models risk factor changes preceding the quinquennium of death. CONCLUSION: A single measurement of some coronary risk factors in middle aged men maintains a regular and almost monotonic relation with the occurrence of CHD deaths during 35 years of follow up.

Diet and 20-year chronic obstructive pulmonary disease mortality in middle-aged men from three European countries.

OBJECTIVE: To investigate the relation of baseline antioxidant, fruit, vegetable and fish intake with 20 y chronic obstructive pulmonary disease (COPD) mortality in middle-aged men from three European countries. DESIGN: Prospective study (1970-1990). SETTING: Five population-based cohorts of middle-aged men from Finland, Italy and The Netherlands. SUBJECTS: A total of 2917 men aged 50-69 y at baseline. METHODS: Baseline information on diet was collected using the cross-check dietary history method. After 20 y of follow-up the underlying cause of death of those who died was established centrally. Survival analyses were performed using the Cox Proportional Hazards Model. RESULTS: After adjustment for age, smoking and country, we observed an inverse trend (P-trend <0.05) of 20 y COPD mortality across tertiles of fruit and vitamin E intake. No trend was observed for vegetables, fish, vitamin C and beta-carotene. When modelled continuously, a 100 g increase in fruit intake was associated with a 24% lower COPD mortality risk (RR=0.76, 95% CI=0.60-0.92). For vitamin E intake (per 5 mg) the RR was 0.77 (95% CI=0.55-1.06), after adjustment for age, smoking and country. Additional adjustment for body mass index, total energy intake and alcohol consumption reduced the RR to 0.86 (95% CI=0.69-1.07, P=0.12) for fruit and 0.93 (95% CI=0.65-1.33) for vitamin E. CONCLUSIONS: Our results suggest a protective effect of fruit and possibly vitamin E intake against COPD. No effect was observed for intake of vitamin C, beta-carotene, vegetables and fish.

Predicting cardiovascular risk in the elderly in different European countries.

AIMS: The objective of this study was to develop risk functions for coronary heart disease and cardiovascular disease mortality for elderly men in different European countries. METHODS AND RESULTS: The FINE Study is a prospective follow-up study of 2170 elderly men aged 65-84 years in Finland, Italy and The Netherlands. During 10 years of follow-up 289 men died from coronary heart disease and 545 men from cardiovascular disease. Risk functions were estimated using logistic regression analysis, in order to take competing causes of death into account. The results of the present study show that total cholesterol and smoking were the most important predictors of coronary heart disease mortality, and HDL cholesterol, systolic blood pressure and smoking of cardiovascular disease mortality. Left ventricular hypertrophy, being subject to coronary heart disease or cardiovascular disease in Finland and The Netherlands and use of antihypertensive medication in Italy, were also important predictors. For estimating the absolute risk of coronary heart disease and cardiovascular disease mortality in the elderly it is necessary to take into account the European country in which they live. CONCLUSION: Total and HDL cholesterol, systolic blood pressure and smoking remain important predictors of coronary heart disease and/or cardiovascular disease mortality in elderly men, but also left ventricular hypertrophy, being subject to coronary heart disease, use of antihypertensive medication and country are predictive of coronary heart disease and cardiovascular disease risk.

Serum uric acid for short-term prediction of cardiovascular disease incidence in the Gubbio population Study.

OBJECTIVE: The Gubbio Study is an Italian population study measuring risk factors for and incidence of major cardiovascular diseases. This analysis investigates the association of serum uric acid with the incidence of coronary and cardiovascular events. METHODS: A population sample of 2469 men and women aged 35-74 years, free from major cardiovascular diseases and in whom serum uric acid was measured in 1983 along with other standard risk factors, were followed up for 6 years and the incidence of coronary heart disease (CHD) and all cardiovascular atherosclerotic (CVD) events, both fatal and non-fatal, was computed. Proportional hazards models were used for the prediction of these events. RESULTS: In six years 61 CHD hard criteria, 109 CHD any criterion and 149 CVD events were recorded. Age-adjusted rates per 1000 of the 3 event categories were computed in sex-specific quintiles (Q) of serum uric acid with 428 +/- 76 (Q5) and 198 +/- 42 (Q1) micromol/l, respectively. Although higher rates were seen in Q5 as compared to Q1 for all three first event categories considered (relative risks 6.2, 3.6 and 3.7, respectively), a statistically significant trend was seen only for CVD all criteria (t = 3.63, p < 0.036). These trends were borderline significant for CHD any criterion (t = 2.92, p < 0.06) and not significant for CHD hard criteria (t = 2.23, p < 0.11). In multivariate models, adjusted for 8 other risk factors, serum uric acid showed a statistically significant contribution to predict CVD incidence [relative risk (RR) for 92 micromol/l difference of 1.24 with 95% confidence intervals (CI) 1.05-1.45], whereas the statistical contribution to predict CHD any criterion (RR = 1.19 with CI 0.98-1.45) and CHD hard criteria (RR = 1.20 with CI 0.93-1.55) was not significant. Diuretic treatment and blood urea, as further confounders, were positively and significantly related to event incidence (RR ranging from 1.21 to 2.00) but serum uric acid maintained its independent and statistically significant role in the prediction of CVD events (RR = 1.18 with CI 1.00-1.39). Presence of specific treatments to lower serum uric acid levels (in 1.13% of the population), tested as final confounders, was not statistically contributory. CONCLUSIONS: Increased serum uric acid levels are independently and significantly associated with risk of CVD events in the 6-year follow-up of the Gubbio Study. Longer follow-up is needed before the contributory role of serum uric acid can be properly assessed to explain CHD incidence.

Markers of insulin resistance and colorectal cancer mortality.

A link between insulin metabolism and colorectal cancer has been hypothesized, supported by a series of potential physiological mechanisms, and confirmed by a number of reports in experimental animals. However, the evidence in humans is limited and mostly indirect. The aim of the present report is to analyze whether individuals with a cluster of metabolic abnormalities associated with abnormalities in insulin metabolism experience higher mortality for colorectal cancer than those without this cluster of metabolic abnormalities. A total of 21,311 men and 15,991 women 20-69 years of age were followed-up for an average of 7 years as part of the Risk Factors and Life Expectancy Project, a pooling of a number of epidemiological studies conducted in Italy. Our analyses indicate that participants with high levels of blood glucose and a cluster of metabolic abnormalities linked to insulin resistance experienced a significant increased risk of colorectal cancer mortality compared with participants without the cluster. For the presence of the cluster of metabolic abnormalities, the calculated hazard ratios and 95% CIs were 2.96 (1.05-8.31) for men, 2.71 (0.59-12.50) for women, and 2.99 (1.27-7.01) when both sexes were combined. These associations were independent from the potential confounding effect of age, drinking of alcoholic beverages, and smoking. Our findings are supportive of the hypotheses that glucose metabolism hyperinsulinemia, insulin resistance, and metabolic abnormalities associated with it may play a significant role in the etiology of colorectal cancer.

Prevalence of morbidity and multimorbidity in elderly male populations and their impact on 10-year all-cause mortality: The FINE study (Finland, Italy, Netherlands, Elderly).

Older males are known to carry, more likely than younger people, one or more chronic diseases with an expected impact on mortality. This study was aimed at identifying the relationship of prevalent chronic diseases in elderly populations of different countries with all-cause mortality. Men aged 65-84 from defined areas were enrolled in Finland (N=716), the Netherlands (N=887) and Italy (N=682). They were survivors of cohorts studied for 25 years within the Seven Countries Study. Major chronic diseases were diagnosed at entry. Ten-year follow-up for mortality was completed. Entry prevalence of selected chronic diseases was higher in Finland (56%) than in Italy (51%) and the Netherlands (44%). Ten-year age-adjusted death rates from all causes were higher in Finland (565 per 1000) and lower in the Netherlands (478 per 1000) and Italy (445 per 1000). The absolute risk of death related to chronic disease was high in the three countries, but was higher in Finland than in the Netherlands and Italy. The most lethal condition was stroke, with 10-year death rates of 806 per 1000 in Finland and 707 and 729 per 1000 in the Netherlands and Italy, respectively. The relative risk of all-cause mortality for a set of seven chronic diseases (coronary heart disease, heart failure, claudicatio intermittens, cerebrovascular accidents, diabetes, COPD and cancer) adjusted by age, other diseases and cohort was less than two for each condition, except cerebrovascular accidents in the Netherlands (RR 2.20). In general, relative risk was higher in Finland, intermediate in the Netherlands and lower in Italy, where only cerebrovascular accidents, intermittent claudication, diabetes and the presence of any chronic condition had a significant relative risk. About one third of men had one chronic disease, and between 10% and 15% had two diseases. The coexistence of any two or three chronic conditions was associated with a relative risk of 2 or more in Finland and the Netherlands and less than 2 in Italy. In these elderly men prevalent morbidity and comorbidity was relatively common and it explained a large proportion of excess in all-cause mortality in 10 years of follow-up.

Impact of the Gubbio population study on community control of blood pressure and hypertension. Gubbio Study Research Group.

BACKGROUND: Awareness and treatment of hypertension have markedly increased in the last 30 years in most parts of the world, but a satisfactory control of blood pressure is still infrequent OBJECTIVES: To describe trends in community control of hypertension and blood pressure levels in the small town of Gubbio, Italy. METHODS: Large samples of the populations (aged 30-79 years) were examined 6 years apart for measurement of blood pressure, other cardiovascular risk factors and knowledge, attitude and practice towards control of hypertension. Data were available from a total of 1125 men and 1445 women with two examinations and 1566 men and 1658 women with at least one examination. Two different definitions of hypertension were used (old definition: systolic blood pressure (SBP) > or = 160 mmHg or diastolic blood pressure (DBP) > or = 95 mmHg or use of antihypertensive drugs; recent definition: SBP > or = 140 mmHg or DBP > or =90 mmHg or use of anti-hypertensive drugs). RESULTS: Awareness, treatment and control of hypertension increased from one survey to the other, whatever definition of hypertension was used. Control rose from 41 to 63% (old definition) and from 12 to 24% (recent definition). In a 6-year period, the average population SBP declined 2-8 mmHg and DBP declined 2-3 mmHg depending on type of analysis, against an expected rise of 9 mmHg for SBP and 2 mmHg for DBP. These trends are partly explained by a marked decline in alcohol consumption and by more common and intensive anti-hypertensive treatment, while change in body mass index, which showed a slight but systematic increase, cannot be considered as a contributor to this trend. CONCLUSIONS: An epidemiological study has motivated a population group and its medical profession towards a better control of hypertension.

Cohort analysis of fruit and vegetable consumption and lung cancer mortality in European men.

Our aim was to examine the relationship between fruit and vegetable consumption and lung cancer mortality in a cohort of European males. Around 1970, dietary intake of Finnish, Italian and Dutch middle-aged men was assessed using a cross-check dietary history. Complete baseline information was available for 3,108 men, of whom 1,578 were baseline smokers. We used Cox proportional hazard analyses to calculate risk estimates for the consumption in country-specific tertiles on lung cancer in smokers. During 25 years of follow-up, 149 lung cancer deaths occurred in the smokers. Fruit consumption was inversely associated with lung cancer mortality among smokers; compared with the lowest, adjusted RRs for the intermediate and highest tertiles were 0.56 (0.37-0.84) and 0.69 (0.46-1.02), p-trend 0.05. Only in the Dutch cohort was this association statistically significant [adjusted relative risks (RRs) 1.00, 0.33 (0.16-0.70) and 0.35 (0.16-0.74), p-trend 0.004]. In Finland lung cancer risk was lower with higher fruit intake but not significantly, whereas in Italy no association was observed. Stratifying on cigarette smoking intensity (non, light and heavy) revealed an inverse association in the heavy smokers only [adjusted RRs (95% confidence intervals [CI]) 1; 0.47 (0.26-0.84); 0.40 (0.20-0.78)). Vegetable consumption was not related to lung cancer risk in smokers. However, analyses stratified on cigarette smoking intensity gave some indication for a lower lung cancer risk with higher intake. In conclusion, in this prospective analysis among European smoking men, fruit intake was inversely related to lung cancer mortality. This association was confined to heavy cigarette smokers.