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Background/objectives: We studied the ecologic relationships of food groups, macronutrients, eating patterns, and an a priori food pattern score (Mediterranean Adequacy Index: MAI) with long-term CHD mortality rates in the Seven Countries Study., Subjects/methods: Sixteen cohorts (12,763 men aged 40-59 years) were enrolled in the 1960s in seven countries (US, Finland, The Netherlands, Italy, Greece, former Yugoslavia: Croatia/Serbia, Japan). Dietary surveys were carried out at baseline and only in a subsample of each cohort. The average food consumption of each cohort was chemically analyzed for individual fatty acids and carbohydrates., Results: Ecologic correlations of diet were computed across cohorts for 50-year CHD mortality rates; 97% of men had died in cohorts with 50-year follow-up. CHD death rates ranged 6.7-fold among cohorts. At baseline, hard fat was greatest in northern Europe, olive oil in Greece, meat in the US, sweet products in northern Europe and the US, and fish in Japan. The MAI was high in Mediterranean and Japanese cohorts. The 50-year CHD mortality rates of the cohorts were closely positively ecologically correlated (r = 0.68-0.92) with average consumption of hard fat, sweet products, animal foods, saturated fat, and sucrose, but not with naturally occurring sugars. Vegetable foods, starch, and the a priori pattern MAI were inversely correlated (r = -0.59 to -0.91) with CHD mortality rates., Conclusions: Long-term CHD mortality rates had statistically significant ecologic correlations with several aspects of diet consumed in the 1960s, the traditional Mediterranean and Japanese patterns being rich in vegetable foods, and low in sweet products and animal foods.

The incidence of chronic diseases such as cardiovascular diseases is lower in Mediterranean Southern Europe than Northern Europe. This may be due to a lower level of oxidative stress and a higher antioxidant status in people living around the Mediterranean Sea. Oxidative stress may influence the rate of shortening of telomeres, the nucleoprotein structures at the ends of chromosomes. We compared leukocyte telomere length (LTL) in elderly men from Northern and Southern Europe and investigated the possible relationship between LTL and indicators of oxidative stress and antioxidant status. We examined 143 elderly Dutch men (mean age 83.9 years) and 109 Greek elderly men (mean age 84.6 years) and found that the Greek men had significantly longer telomeres (geometric mean 4.95 kbp, 95% confidence interval (CI): 4.71-5.23 kbp) compared to the men from the Netherlands (4.76 kbp, 95% CI: 4.55-4.98 kbp; P=0.001). Age was inversely associated with LTL (β=-0.10, P=0.31 in Cretan men and β=-0.19, P=0.02 in Dutch men). In all men LTL was not related to indicators of oxidative stress and plasma antioxidants. However, the endogenous antioxidants serum albumin (β=0.18, P=0.007) and uric acid (β=0.13, P=0.045) were positively associated with LTL. The age-adjusted difference between Crete and Zutphen was reduced by 25% after adjustment for serum albumin and uric acid. We conclude that Greek elderly men have significantly longer LTL compared to Dutch counterparts. The endogenous antioxidants albumin and uric acid were positively associated with longer telomeres., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Telomeres, repetitive DNA sequences that promote chromosomal stability, have been related to different measures of mental well-being and self-rated health, but mainly in women during adulthood. We aimed to investigate whether accelerated telomere shortening is associated with poor mental well-being and poor self-rated health in community-dwelling elderly men. Leukocyte telomere length was measured using quantitative PCR in two different samples of 203 elderly men (mean age 78 years) from the Netherlands in 1993, and 123 elderly men (mean age 84 years) from Greece in 2000. We also obtained follow-up data in 2000 from 144 Dutch subjects, of whom 75 had paired telomere length data in 1993 and 2000. Mental well-being was conceptualized as dispositional optimism, depressive symptoms, cognitive functioning, and loneliness. Linear regression analyses were used to study the association between telomere length, measures of mental well being, and self-rated health, while adjusting for potential confounders. In cross-sectional analyses, leukocyte telomere length was not associated with measures of mental well-being and self-rated health, neither in the Netherlands nor in Greece. Also, the rate of leukocyte telomere shortening (mean decrease: 0.28 kbp over 7 years) in the 75 Dutch participants with longitudinal data was not associated with changes in different measures of mental well-being and self-rated health. Thus, our results provide no support for a relationship between leukocyte telomere length and mental well-being in elderly community-dwelling men.

Studies have shown that depression relates to biomarkers of both short-term and long-term polyunsaturated fatty acid intake. However, it is not known which of these two biomarkers is more closely related to depression. The aim of this study was to examine the relationship of depression with both adipose tissue and serum phospholipid polyunsaturated fatty acids and to assess the importance of each of these two biomarkers in relating to depression. This is a cross-sectional study of healthy adults from the island of Crete. Subjects were examined by the Preventive Medicine and Nutrition Clinic of the University of Crete. Subjects were 394 healthy adults (175 males, 219 females) aged 18-60. The sample consisted of farmers from a number of rural communities of Crete. Fatty acids were determined by gas chromatography in adipose tissue and serum phospholipids. Information about depression was obtained through the Beck Depression Inventory (BDI) and Zung Self-rating Depression Scale (ZSRDS). Adipose tissue alpha-linolenic acid (ALA) (C18:3n-3) was inversely correlated to BDI (r=-0.17, p<0.02). Multiple linear regression analysis taking into account the possible confounding effect of age, gender, body mass index (BMI), smoking and educational level did not confirm this association. The other polyunsaturated fatty acids in adipose tissue were not related to depression. Serum phospholipid polyunsaturated fatty acids did not correlate with depression. This study did not show that the polyunsaturated fatty acids in the adipose tissue are better predictors of depression than those in serum phospholipids.

Background: Oxidative stress may accelerate ageing and increase the risk of chronic diseases, such as coronary heart disease (CHD). We assessed differences in oxidative stress, and iron and antioxidant status between elderly men living in Mediterranean southern Europe (Crete, Greece) and northern Europe (Zutphen, The Netherlands)., Design: A cross-sectional study using data from two cohorts of the Seven Countries Study., Methods: Non-fasting blood samples were drawn in 2000 from 105 men from Crete and 139 men from Zutphen, all aged 79 years or over. All assays were performed in the same laboratory., Results: After multiple adjustments, serum levels of the markers of oxidative stress were lower in Cretan men than in men from Zutphen, as indicated by lower mean levels of hydroperoxides (33.2 versus 57.3 micromol/l; P=0.005) and gamma-glutamyltransferase (20.3 versus 26.1 U/l; P=0.003). The most pronounced difference in iron status was a twofold lower mean serum ferritin level in Cretan men (69.8 microg/l) compared with men from Zutphen (134.2 microg/l; P<0.0001). Men from Crete had consistently higher plasma levels of major plasma antioxidants than the Zutphen men, including a nearly fourfold higher mean level of lycopene (15.3 versus 4.1 microg/100 ml; P<0.0001)., Conclusion: Elderly men from Crete had consistently lower levels of the indicators of oxidative stress and iron status and higher concentrations of major antioxidants than men from Zutphen. These differences may contribute to the lower rate of CHD and total mortality that has been observed in this cohort of Cretan men.

Background: Hypertension is a dominant characteristic in the prediction of cardiovascular diseases (CVDs). We aimed to evaluate the association of blood pressure measurements with CVD mortality among different populations of the world., Methods: A total of 12 763 men, aged 40 to 59 years, from 7 countries (United States, Japan, Italy, Greece, former Yugoslavia, Finland, and the Netherlands) were surveyed from 1958 to 1964. Follow-up for vital status and causes of death was carried out over 25 years., Results: All baseline blood pressure measurements were the best predictors of CVD mortality, compared with age, physical activity, total serum cholesterol level, body mass index or height, and smoking. Moreover, pulse pressure and diastolic and systolic blood pressures were the best predictors for CVD death, followed by mean and mid blood pressures. The age-adjusted hazard ratio per 10-mm Hg increase in pulse pressure varied among cohorts from 1.19 in the United States (P = .04) to 1.29 in southern Europe (P = .01). Differences among cohorts were not significant. In the pooled cohorts, pulse pressure measurements were also a significant predictor for coronary heart disease (hazard ratio per 10-mm Hg increase, 1.15; P = .04) as well as stroke death (hazard ratio per 10-mm Hg increase, 1.32; P = .01)., Conclusions: Pulse pressure followed by diastolic and systolic blood pressures were the best predictors for CVD mortality among other blood pressures, as well as age, physical activity, total serum cholesterol level, anthropometric indexes, and smoking habits. No significant differences were observed among the different populations studied.

Background and Aims: Time trends in major cardiovascular risk factors are described in cohorts of middle-aged men followed for 35 years in 9 European cohorts of Finland, The Netherlands, Italy, Serbia and Greece., Methods: Men aged 40 to 59 years at entry in the early 1960s were repeatedly re-examined 3 to 5 times over the last 35 years. Systolic blood pressure, serum cholesterol, body weight and body mass index were considered for analysis, including study of aging (35 years of follow-up) and of generation effects (10 years for men aged 50-59 in the period 1960-1970 and separately 10 years for men aged 75-84 years in the period 1985-1995)., Results: For the aging effect, average systolic blood pressure increased approximately 15 mmHg over 25 years maintaining a steady state thereafter, the largest increases being found in Serbia and Greece. Average serum cholesterol varied between approximately 4.5 in Serbia and 6.5 mmo/L in Finland in about 1960. Twenty-five years later, the average level was about 6 mmol/L in all five countries and decreased slightly thereafter. Average body weight and body mass index increased in all countries for 25 years and levelled off thereafter. For the generation effect, average systolic blood pressure decreased in all countries, with the exception of men aged 50-59 in Serbia and men aged 75-84 in The Netherlands. Average serum cholesterol uniformly increased in men aged 50-59 for the younger age-class and slightly decreased in men aged 75-84. Average body weight and body mass index increased systematically in all countries and in both age groups., Conclusions: Major changes were the great increases in average systolic blood pressure and serum cholesterol level in Serbia and in systolic blood pressure level in Greece between 1960 and 1985, and the large decrease in average serum cholesterol in Finland between 1970 and 1995. Average body weight and body mass index showed universal increases in both middle-aged and older men after 1960.

Background: In 1960, all male inhabitants of a series of villages in rural Crete, born between 1900 and 1919, were invited to participate in the Seven Countries Study. Analysis of 25-year mortality data from the 16 cohorts of participants indicated that the cohort from Crete had the lowest age-standardised all-cause and coronary heart disease death rates., Methods: At baseline, 686 Cretan men (98% of those invited) participated in health examinations. Mortality data were collected over 40 years. Time-fixed and updated covariate survival analysis techniques were applied to assess eight cardiovascular disease risk factors as long-term predictors of all-cause and cardiovascular disease mortality., Results: The median survival time was 32 years. All-cause and cardiovascular mortality rates were 26 and 11 per 1000 person-years, respectively. Age (relative risk 1.11, 95% CI 1.09-1.13), diastolic blood pressure (relative risk 1.02, 95% CI 1.01-1.03), and smoking (relative risk 1.37, 95% CI 1.14-1.64) were positively associated and forced expiratory volume (relative risk 0.50, 95% CI 0.36-0.68) was negatively associated with all-cause mortality. Age (relative risk 1.13, 95% CI 1.09-1.16), diastolic blood pressure (relative risk 1.01, 95% CI 1.001-1.03), and forced expiratory volume (relative risk 0.53, 95% CI 0.32-0.89) were independent predictors of cardiovascular mortality. Serum cholesterol concentration and body mass index were not independently associated with death risk., Conclusions: The Cretan cohort displays favourable 40-year survival. Even so, long-term predictors of the hazard of both all-cause and cardiovascular disease mortality are present.

Aims: The purpose was to study the association of a single serum cholesterol measurement with early and late coronary and other cardiovascular deaths during 35 years of follow-up in samples of men aged 40-59 years in five European countries., Methods and Results: A single serum total cholesterol measurement was considered in samples from Finland (N = 1563), the Netherlands (N = 811), Italy (N = 1642), Serbia (N = 1537) and Greece (N = 1158) (total = 6711). Seven partitioned proportional hazards models were solved, one for each of seven independent 5-year blocks, to predict coronary, stroke, cardiovascular disease and all-cause mortality risk. Partitioned hazard scores were cumulated. The resulting curves showed a relatively constant strength in risk for coronary deaths as a function of baseline serum cholesterol levels, although a strong relationship during the first 10-year period was followed by a weaker relationship later on. The pooled estimates for the five countries gave a relative risk for 1 mmol/l of serum cholesterol (95% confidence intervals) of 1.44 (1.23-1.68) for the first period; 1.52 (1.31-1.76) for the second period; and 1.16 (1.02-1.32) for the third period; 1.18 (1.05-1.32) for the forth period; 1.17 (1.05-1.31) for the fifth period; 1.22 (1.10-1.35) for the sixth period; 1.18 (1.05-1.32) for the seventh 5-year period of follow-up. No significant relationship were found between serum cholesterol and stroke and all-cause mortality, while intermediate findings were obtained for cardiovascular diseases., Conclusion: A single serum cholesterol measurement in middle aged-men maintains a strong relationship with the occurrence of coronary heart disease (CHD) deaths during 35 years of follow-up.

This analysis aims at describing all-cause mortality and their determinants in 16 cohorts of middle-aged men of eight nations. A total of 12,763 men aged 40-59 years were enrolled in the late 1950s and early 1960s in 16 cohorts located in the USA, Finland, The Netherlands, Italy, Croatia, Serbia, Greece and Japan. The highest death rates were found in Slavonia-Croatia, due to high rates of infectious diseases and violence (death rate of 610 per 1000), and in East Finland due to high rates from coronary heart disease (death rate of 597 per 1000). The lowest death rates were found in a highly educated group in Belgrade, Serbia (death rate 295 per 1000) and in Crete, Greece (death rate 314 per 1000). The ecological analysis showed no significant relationship between mean risk factor levels and all-cause death rates except for the direct association with systolic blood pressure during the first 15 years follow-up. Individual multivariate analysis on eight national pools showed that age, systolic blood pressure, and smoking habits are direct, significant, and universal long-term predictors of all-cause mortality. Serum cholesterol, physical activity and body mass index were so only in some areas. Multivariate coefficients were similar across nations. Pooled hazards ratios were 1.55 for a difference of 5 years of age (CI: 1.51-1.59); 1.23 for 10 cigarettes smoked per day (CI: 1.20-1.26); 0.91 for one unit (based on three grades) of physical activity score (CI: 0.87-0.95); 1.04 for 1 mmol/l of serum cholesterol (CI: 1.02-1.07); and 0.93 for three units of body mass index (CI: 0.91-0.96). In conclusion some cardiovascular risk factors predict long-term risk of all-cause mortality in different cultures.

Objective: A systematic reanalysis of 10 year coronary heart disease incidence data from the northern and the southern European cohorts of the seven countries study, to contribute indirectly to the production of a European coronary risk chart., Design and Setting: Men aged 40-59 years at entry were studied in three northern European cohorts based in Finland and Netherlands (n = 2213); and in 10 southern European cohorts based in Italy, former Yugoslavia, and Greece (n = 5897). Multiple logistic models for the prediction of coronary deaths, coronary incidence (hard criteria), and coronary incidence (any criterion) were solved for the two geographical groups and their pool. Risk factors fed into the models were age, systolic blood pressure, serum total cholesterol, and cigarette smoking., Results: 10 year coronary heart disease mortality and incidence were higher in northern than in southern Europe, with ratios around 2.65. Ratios among the three coronary heart disease manifestations were identical in the two cultural groupings. Coefficients of the multiple logistic models were similar and not significantly different between the two groupings. When applying the coefficients back to the same or the opposite population, the relative risk was large and similar in the different cultures. Relative risk was larger for more severe coronary heart disease manifestations. The absolute risk was overestimated when applying the northern European model to southern European populations and vice versa, with ratios of about 1.5 and 0.5, respectively. Coronary risk charts created to reproduce the shape of those incorporated in recent European guidelines confirmed the excess of absolute risk in the northern compared with the southern European cohorts, all else being equal., Conclusions: In theory, a more appropriate European coronary risk chart could be produced by adopting coefficients to correct for different background incidence rates in different cultures. Other coefficients could appropriately be used to transform mortality risk into incidence risk.

Plant foods are generally considered to be beneficial for health. A higher consumption of fruits, and to a lesser extent vegetables, is consistently associated with a lower risk of stomach cancer. Results on the association between stomach cancer and grain consumption are less clear. We associated plant food consumption with 25-year stomach cancer mortality at population level in the Seven Countries Study. Around 1960, > 12,000 men aged 40-59 years from 7 countries and 16 cohorts were enrolled. In each cohort, dietary information was collected in small random samples. Crude and adjusted associations were calculated for a change of 10% of mean intake. Results differed for the plant foods studied: an inverse association was observed for fruits (adjusted rate ratio = 0.96, 95% confidence interval = 0.91-0.99), a positive relation for refined grains (adjusted rate ratio = 1.07, 95% confidence interval = 1.03-1.12), and no association for total plant foods, vegetables, whole grains, and potatoes. A high intake of refined grains was correlated with a low consumption of fruits. In conclusion, high intake of refined grains may increase stomach cancer risk. However, because adjustment could only be limited in this study, high intake of refined grains may just reflect the deleterious effect of a diet low in fruits or other characteristics associated with low fruit consumption.

Objective: To investigate whether average intake of antioxidants, fruits, vegetables and fish may help to explain international differences in chronic obstructive pulmonary disease (COPD) mortality., Design: Ecological analysis using information on baseline diet and the 25-year COPD mortality rate in the 16 cohorts of the Seven Countries Study., Setting: Population-based cohorts., Subjects: Men aged 40-59 years at baseline., Methods: Dietary information was collected at baseline in small random samples of each cohort. In 1987 the reported foods were bought locally and analysed chemically. After 25 years of follow-up the underlying cause of death of those who died was established centrally. COPD mortality rate ratios were calculated, for a change equivalent to 10% of the overall mean consumption of a dietary factor., Results: We observed independent inverse associations between 25-year COPD mortality and baseline consumption of fruits (rate ratio 0.49; 95% confidence interval 0.36-0.67) and fish (rate ratio, 0.97; 95% confidence interval 0.93-1.00), after adjustment for potential confounders. COPD mortality showed no statistically significant association with intake of antioxidants or vegetables. Fruit and fish consumption together explained about 67% of the variance in the COPD mortality rates of the cohorts., Conclusions: Fruit and fish consumption may partly explain population differences in COPD mortality. This is in accordance with suggestions for a relationship between fruit and fish consumption and COPD observed in studies in individuals.

The relation of chronic conditions on all-cause mortality in population samples was studied based on observations from the Seven Countries Study. The objective of this work was to study the risk of death during a 15-year follow-up of middle-aged men in relation to six chronic diseases. Fifteen cohorts of men aged 50-69, totalling 8122 subjects, were examined around 1970 in seven countries: Finland, The Netherlands, Italy, Croatia (former Yugoslavia), Serbia (former Yugoslavia), Greece and Japan. Clinical diagnoses findings were made for coronary heart disease (CHD), 'other heart diseases' (OTH), peripheral arterial disease (PAD), stroke (STR), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DIAB). All-cause mortality was assessed in the subsequent 15 years. Death rates and relative risks were estimated from crude data, and in proportional hazards models after adjustment for age, systolic blood pressure and serum cholesterol level, cigarette smoking and body mass index. Large regional differences were found in the prevalence of the six conditions. Weak relations were found between population prevalence of each disease and population death rates for that disease. Among cohorts the relative risk of death in 15 years from any cause, adjusted for other risk factors, showed little variation among countries. Pooled relative risks, adjusted by the inverse of variance (with 95% CI) were: for CHD, 1.81 (1.60-2.06); for OTH, 1.47 (1.28-1.69); for PAD, 1.64 (1.39-1.93); for STR, 1.56 (1.23-1.98); for COPD, 1.67 (1.48-1.88); and for DIAB, 1.75 (1.43-2.15). The smallest variability of prognosis among countries was found for CHD, OTH and DIAB; the largest for PAD, STR and COPD. Despite simple clinical diagnostic procedures and large differences in prevalence, the relation of established prevalent conditions to subsequent all-cause mortality is relatively uniform among countries and across these conditions, with a relative risk of dying in 15 years usually ranging between 1.5 and 2.0.

In the Seven Countries Study, which was started in 1958, the risk factors of coronary heart disease are studied in a large number of men. The study still runs and the results also provide insight in the relation between life style and health in elderly people.

Background and Purpose: This report explores the prediction of long-term stroke mortality in cohorts of the Seven Countries Study., Methods: Sixteen cohorts of men aged 40 to 59 years at entry were examined at years 0, 5, and 10, with mortality follow-up through 25 years., Results: Stroke death rates in 25 years were high in rural Serbia, Croatia, and Japan; intermediate in Italy, Greece, and urban Serbia; and low in Finland, the Netherlands, and the United States. Age and blood pressure were powerful predictors of 25-year stroke mortality in almost all cohorts and countries. Proportional hazards regression coefficients were .0232 increase in stroke death hazard per millimeter of mercury (t=14.60) for systolic blood pressure and .0409 (t=13.41) for diastolic blood pressure. Moderate blood pressure increases from low usual levels were associated with lower stroke mortality rates in years 10 to 25. Increases of blood pressure starting from high usual levels were associated with increased rates of stroke mortality. Systolic blood pressure was associated with stroke mortality at given levels of diastolic pressure, but diastolic blood pressure was not predictive of stroke mortality at given levels of systolic blood pressure., Conclusions: Associations of systolic and diastolic blood pressure with stroke mortality were similar in cultures with different stroke mortality rates. Increases in blood pressure were associated with subsequent excess stroke mortality only in those who started from high usual levels; this study finds lower stroke risk in those men whose blood pressure increased moderately from low usual levels. Diastolic blood pressure is not independently associated with stroke risk in these populations.

This study describes dietary fatty acid intake, as assessed from serum cholesteryl ester composition, and its relation to serum lipoprotein levels in 100 age-matched elderly men from Crete and Zutphen. All were survivors of the respective cohorts of the Seven Countries Study [Keys A (1980) Seven countries: a multivariate analysis of death and coronary heart disease. Cambridge, MA: Harvard University Press]. A significantly higher percentage of oleic acid and a significantly lower percentage of linoleic acid in the cholesteryl esters was observed in the Cretan compared with the Zutphen men. The mean serum total cholesterol levels of the elderly men in Crete and Zutphen were similar (5.98 and 5.92 mmol/l, respectively), but in the Cretans the HDL cholesterol level was significantly higher (1.28 vs 1.09 mmol/l). The percentage of smokers and the average body mass index did not differ between the Cretan and Zutphen men, but the percentage of severely overweight men was three times higher in the Cretan cohort. Among men in Zutphen the oleic acid content of the cholesteryl esters was positively associated with the HDL cholesterol level, independent of the effects of age, body mass index, cigarette smoking and alcohol intake. However, the difference in HDL cholesterol level between Zutphen and Crete could be explained to only a minor extent by differences in serum cholesteryl oleic acid, smoking, or obesity.(ABSTRACT TRUNCATED AT 250 WORDS)

Twelve cohorts of men aged 40-59 at entry, enrolled in six countries (Finland, The Netherlands, Italy, Yugoslavia, Greece and Japan), giving a total of 8,287 subjects, were examined for the measurement of cardiovascular risk factors and then followed-up for 20 years. Changes of systolic blood pressure (SBP) occurred over the first 10 years in 6,767 men and these values, computed by an integral-like procedure (Delta-SBP), were used as possible predictors of fatal events recorded in the second 10 years of follow-up. Men who had a relative increase of SBP in the first 10 years showed an excess risk of death as compared with those who had a relative decrease of SBP, after adjustment for age and entry levels of SBP. Such relative risks were greater than 1 in the cohorts pooled within each of the six countries, ranging from 1.07 to 1.79 for all causes of death and from 1.12 to 2.15 for atherosclerotic cardiovascular disease deaths (coronary, stroke and peripheral atherosclerotic disease). The Cox model was solved using the same two end-points as dependent variables and, as coviariates, six risk factors measured at entry examination (age, cigarettes smoked per day, body mass index, serum cholesterol, physical activity at work and systolic blood pressure). By adding Delta-SBP the predictive power of the models was significantly improved and the coefficients of Delta-SBP proved to be statistically significant.