Relationship of some risk factors with typical and atypical manifestations of coronary heart disease.

BACKGROUND: This analysis explores whether 'typical' clinical manifestations of coronary heart disease (CHD) such as myocardial infarction and sudden death, relate to major cardiovascular risk factors in the same way as the 'atypical' manifestations, e.g. heart failure and chronic arrhythmias. PATIENTS AND METHODS: Sixteen cohorts of men aged 40-59 in seven countries were examined, risk factors measured (age, systolic blood pressure, serum cholesterol and smoking habits) and 25-year mortality data collected in a systematic way. Cohorts were located in the US (n = 1), Finland (n = 2), the Netherlands (n = 1), Italy (n = 3), former Yugoslavia (n = 5), Greece (n = 2) and Japan (n = 2), with a total of 12,763 individuals. Ecological analysis based on regression equations and correlation among cohorts, and individual analyses based on proportional hazard models in pools of cohorts were conducted with typical and atypical CHD deaths as dependent variables. RESULTS: The ecological analysis suggests a significant relationship of populational mean levels of serum cholesterol and of systolic blood pressure to age-adjusted death rates from typical CHD manifestations. The relationships for atypical CHD deaths were not statistically significant. In the ecological approach with multivariate analysis, none of the risk factors showed relevant associations with event rates, except serum cholesterol and typical CHD deaths. The ecological relationship of serum cholesterol to atypical CHD death rates was negative but not significant. On average, mean age at death was statistically higher among atypical CHD than typical CHD patients (70.2 vs. 65.8 years). In the individual multivariate analysis conducted on pools of countries, the relationship of risk factors with typical CHD deaths was direct and significant for age, systolic blood pressure, and smoking habits in Northern Europe and America and Southern Europe, but only for systolic blood pressure and smoking habits in Japan, whereas for atypical CHD, the predictive factors were age, systolic blood pressure and cigarette smoking in Northern Europe and America and Southern Europe, but only age in Japan. CONCLUSIONS: The usual relationship of blood pressure and smoking habits and the differential relationship of serum cholesterol with atypical CHD (negative or absent) versus typical CHD (direct and significant) could be explained by 'two different diseases' or by a mix of poorly classified conditions among the atypical cases.

Comparative total mortality in 25 years in Italian and Greek middle aged rural men.

STUDY OBJECTIVE: Mortality over 25 years has been low in the Italian and very low in the Greek cohorts of the Seven Countries Study; factors responsible for this particularity were studied in detail. PARTICIPANTS AND SETTINGS: 1712 Italian and 1215 Greek men, aged 40-59 years, cohorts of the Seven Countries Study, representing over 95% of the populations in designated rural areas. DESIGN: Entry (1960-61) data included age, systolic blood pressure (SBP), smoking habits, total serum cholesterol, body mass index (BMI), arm circumference, vital capacity (VC), and forced expiratory volume in 3/4 seconds (FEV); the same data were obtained 10 years later. Multivariate Cox analysis was performed with all causes death in 25 years as end point. MAIN RESULTS: Italian men had higher entry levels of SBP, arm circumference, BMI, and VC; Greek men had higher cholesterol levels, smoking habits, and FEV. Mortality of Italian men was higher throughout; at 25 years cumulative mortality was 48.3% and 35.3% respectively. Coronary heart disease and stroke mortality increased fivefold in Italy and 10-fold in Greece between years 10 and 25. The only risk factor with a significantly higher contribution to mortality in Italian men was cholesterol. However, differences in entry SBP (higher in Italy) and FEV (higher in Greece) accounted for, according to the Lee method, 75% of the differential mortality between the two populations. At 10 years increases in SBP, cholesterol, BMI, and decreases in smoking habits, VC, FEV, and arm circumference had occurred (deltas). SBP increased more and FEV and VC decreased more in Italy than in Greece. Deltas, fed stepwise in the original model for the prediction of 10 to 25 years mortality, were significant for SBP, smoking, arm circumference, and VC in Greece, and for SBP and VC in Italy. CONCLUSION: Higher mortality in Italian men is related to stronger positive effects of entry SBP and weaker negative (protective) effects of FEV; in addition 10 year increases in SBP are higher and 10 year decreases in FEV are larger in Italy. Unaccounted factors, however, related to, for example, differences in the diet, may also have contributed to the differential mortality of these two Mediterranean populations.

The inverse relation of average population blood pressure and stroke mortality rates in the seven countries study: a paradox.

This study attempts to explain the unexpected finding of an inverse population (ecological) relationship between mean systolic blood pressure levels and stroke death rates in 25 years follow-up of the Seven Countries Study, a cross-cultural study of cardiovascular disease. Sixteen cohorts of all men aged 40-59 in seven countries (one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Croatia (former Yugoslavia), three in Serbia (former Yugoslavia), two in Greece, two in Japan) were surveyed from 1958 to 1964. Risk factors and personal characteristics were measured and follow-up for vital status and cause of death was then carried out over 25 years. Analyses were based on comparisons of mean levels of risk factors and death rates within and among the 16 cohorts. Mean entry population levels of systolic blood pressure among the cohorts were strongly and inversely related with their 25-year stroke death rates (R -0.55; CI -0.81 and -0.06; p = 0.0276). Within cohorts in contrast, the individual relation of blood pressure and stroke was strongly positive and significant in 14 of the 16 cohorts. Mean population levels of serum cholesterol were inversely and strongly related to stroke death rates (R -0.79; CI -0.92 and -0.46; p = 0.0003), while the partial correlation coefficient of systolic blood pressure, computed in models including serum cholesterol, became small and not significant (-0.05; CI -0.55 and +0.48; p = 0.8537). Age at death for stroke (average 68.9 +/- 7.1 years) was significantly higher than age at dath from myocardial infarction and sudden death (average 65.8 +/- 7.8 years) suggesting a competition effect between the conditions. Multivariate models including population average systolic blood pressure and serum cholesterol provided no added explanation for the lack of direct and significant relationship of population blood pressure with stroke death rates. They were based on these variables: age at stroke death, age at myocardial infarction death or and sudden death, death rates from myocardial infarction and sudden death, the interaction term of systolic blood pressure with serum cholesterol and the multivariate coefficients for systolic blood pressure from Cox models run in individuals. Similar findings were obtained using diastolic instead of systolic blood pressure and excluding the Japanese cohorts. The paradox of the inverse ecologic relation of population blood pressure and stroke mortality and a direct relation for individual is only partly explained by the cofounding effect of population mean serum cholesterol levels. An effect of low cholesterol levels on excess stroke mortality cannot be excluded. A major limitation of the study was our inability to segregate thrombotic from heamorrhagic strokes.

The relation of chronic diseases to all-cause mortality risk--the Seven Countries Study.

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.

Changes in population cholesterol levels and coronary heart disease deaths in seven countries.

BACKGROUND: Are trends in coronary heart disease deaths based on risk factor changes? OBJECTIVE: To study the relationship between trends in coronary deaths and changes in blood cholesterol in the Seven Countries Study. MATERIAL AND METHODS: Sixteen cohorts of men aged 40-59 years from seven countries (U.S.A., Finland, the Netherlands, Italy, Croatia (former Yugoslavia), Serbia (former Yugoslavia), Greece, Japan) were units for the analyses of serum cholesterol measured at entry and after 5 and 10 years, and for mortality over 25 years. RESULTS: In the populations, the ecological relationship of mean serum cholesterol at entry to late coronary heart disease death rates during the 10- to 25-year follow-up was weak, with an R-square of 0.31. Cholesterol measurements made at year 10, and an indicator of cholesterol change during the first 10 years, increased the association (R-square, 0.49). A negative and significant interaction was shown between baseline population cholesterol levels and their 10-year change. As an indicator of acceleration in mortality, cholesterol change over 10 years was also positively correlated (partial R-square 0.44) with the ratio of 25-year to 5-year deaths. CONCLUSIONS: In the Seven Countries Study, late coronary heart disease death rates are largely "explained' by changes in blood cholesterol levels during the early phases of the study, mainly due to increases in lower cholesterol levels among some cohorts.

Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes.

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.

Comparison of multivariate predictive power of major risk factors for coronary heart diseases in different countries: results from eight nations of the Seven Countries Study, 25-year follow-up.

BACKGROUND: It was hypothesized that among eight national groups of men aged 40-59 years enrolled in the Seven Countries Study, the multivariate coefficients of major risk factors predicting coronary heart disease mortality over 25 years would be relatively similar. MATERIALS AND METHODS: Sixteen cohorts were located in eight nations and pooled, comprising one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Croatia (former Yugoslavia), three in Serbia (Yugoslavia), two in Greece and two in Japan, for a total of over 12000 subjects at entry. Coronary heart disease (CHD) mortality was defined as fatal myocardial infarction or sudden coronary death, and proportional hazard models were solved, for each country, with age, serum cholesterol level, systolic blood pressure and cigarette consumption as covariates. RESULTS: The relationships between risk factors and CHD mortality were statistically significant for all risk factors and for all countries, except for age in Croatia and Japan, cholesterol in Croatia and Japan, systolic blood pressure in Serbia and Greece, and cigarette-smoking in the Netherlands, Croatia, Serbia and Greece. When comparing all pairs of coefficients (28 comparisons for each factor) significant differences were found on four occasions for age, on six occasions for cholesterol, on no occasion for blood pressure and on four occasions for cigarette-smoking. Other tests suggested a substantial homogeneity among multivariate coefficients. Estimates for pooled coefficients were: age, in years, 0.0570 (95% confidence limits 0.0465 and 0.0673); relative risk for 5 years 1.33 (95% confidence limits 1.26 and 1.40); serum cholesterol level in mg/dl, 0.0057 (95% confidence limits 0.0045 and 0.0069); relative risk for 40 mg/dl 1.31 (95% confidence limits 1.20 and 1.31); systolic blood pressure in mmHg, 0.0160, (95% confidence limits 0.0134 and 0.0185), relative risk for 20 mmHg 1.38 (95% confidence limits 1.31 and 1.45); cigarettes per day, 0.0220 (95% confidence limits 0.0170 and 0.0272); relative risk for 10 cigarettes per day 1.25 (95% confidence limits 1.18 and 1.31). CONCLUSIONS: Great similarities were found in the multivariate coefficients of major coronary risk factors to CHD risk derived from population samples varying in CHD frequency.

Serum total cholesterol and long-term coronary heart disease mortality in different cultures. Twenty-five-year follow-up of the seven countries study.

OBJECTIVE: To compare the relationship between serum total cholesterol and long-term mortality from coronary heart disease (CHD) in different cultures. DESIGN: Total cholesterol was measured at baseline (1958 through 1964) and at 5- and 10-year follow-up in 12,467 men aged 40 through 59 years in 16 cohorts located in seven countries: five European countries, the United States, and Japan. To increase statistical power six cohorts were formed, based on similarities in culture and cholesterol changes during the first 10 years of follow-up. MAIN OUTCOME MEASURES: Relative risks (RRs), estimated with Cox proportional hazards (survival) analysis, for 25-year CHD mortality for cholesterol quartiles and per 0.50-mmol/L (20-mg/dL) cholesterol increase. Adjustment was made for age, smoking, and systolic blood pressure. RESULTS: The age-standardized CHD mortality rates in the six cohorts ranged from 3% to 20%. The RRs for the highest compared with the lowest cholesterol quartile ranged from 1.5 to 2.3, except for Japan's RR of 1.1. For a cholesterol level of around 5.45 mmol/L (210 mg/dL), CHD mortality rates varied from 4% to 5% in Japan and Mediterranean Southern Europe to about 15% in Northern Europe. However, the relative increase in CHD mortality due to a given cholesterol increase was similar in all cultures except Japan. Using a linear approximation, a 0.50-mmol/L (20-mg/dL) increase in total cholesterol corresponded to an increase in CHD mortality risk of 12%, which became an increase in mortality risk of 17% when adjusted for regression dilution bias. CONCLUSION: Across cultures, cholesterol is linearly related to CHD mortality, and the relative increase in CHD mortality rates with a given cholesterol increase is the same. The large difference in absolute CHD mortality rates at a given cholesterol level, however, indicates that other factors, such as diet, that are typical for cultures with a low CHD risk are also important with respect to primary prevention.

Average intake of anti-oxidant (pro)vitamins and subsequent cancer mortality in the 16 cohorts of the Seven Countries Study.

This ecologic study aimed to investigate whether differences in population mortality from lung, stomach and colorectal cancer among the 16 cohorts of the Seven Countries Study could be explained by differences in the average intake of anti-oxidant (pro)vitamins. In the 1960s, detailed dietary information was collected in small sub-samples of the cohorts by the dietary record method. In 1987, food-equivalent composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified after 25 years of follow-up. The average intake of vitamin C was strongly inversely related to the 25-year stomach-cancer mortality (r = -0.66, p = 0.01), also after adjustment for smoking and intake of salt or nitrate. The average intake of alpha-carotene, beta-carotene, and alpha-tocopherol were not independently related to mortality from lung, stomach or colorectal cancer, nor was vitamin C related to lung and colorectal cancer.

Dietary saturated and trans fatty acids and cholesterol and 25-year mortality from coronary heart disease: the Seven Countries Study.

BACKGROUND: In the Seven Countries Study associations between intake of individual fatty acids and dietary cholesterol were studied in relation to serum cholesterol and 25-year mortality from coronary heart disease. All analyses concern only intercohort comparisons. METHODS: In the baseline surveys carried out between 1958 and 1964, risk factors for coronary heart disease were measured among 12,763 middle-aged men constituting 16 cohorts in seven countries. In 1987 and 1988 equivalent food composites representing the average food intake of each cohort at baseline were collected locally and analyzed in a central laboratory. The vital status of all participants was verified at regular intervals during 25 years of follow-up. RESULTS: Of the individual saturated fatty acids, the average population intake of lauric and myristic acid was most strongly related to the average serum cholesterol level (r > 0.8, P < 0.001). Strong positive associations were observed between 25-year death rates from coronary heart disease and average intake of the four major saturated fatty acids, lauric, myristic, palmitic, and stearic acid (r > 0.8, P < 0.001); the trans fatty acid elaidic acid (r = 0.78, P < 0.001); and dietary cholesterol (r = 0.55, P < 0.05). CONCLUSIONS: Interpreted in the light of experimental and clinical studies, the results of these cross-cultural analyses suggest that dietary saturated and trans fatty acids and dietary cholesterol are important determinants of differences in population rates of coronary heart disease death.

Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study.

OBJECTIVE: To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. DESIGN: Cross-cultural correlation study. SETTING/PARTICIPANTS: Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. MAIN OUTCOME MEASURES: Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. RESULTS: Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. CONCLUSIONS: Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.

Long-term prediction of coronary heart disease mortality in two rural Greek populations.

In 1960-61 two pooled Greek rural populations totalling 1215 men aged 40-59 years were followed-up for 25 years. A Cox model analysis of fatal coronary events over 15 years showed that serum cholesterol in men aged 40-59 years, cholesterol in men aged 45-64 years, and systolic blood pressure in men aged 50-69 played a predictive role. The coefficient of age became more significant with advancing age and that of cigarette smoking only at 25 years follow-up. The coefficient of cholesterol decreased stepwise and became negative for men aged 50-69; body mass index was without effect in any follow-up of these cohorts. Systolic blood pressure and serum cholesterol increased in these populations by 5.4 mmHg and 23.5 mg.dl-1 (0.61 mmol.l-1), respectively between the years 0 and 10, whereas cigarette consumption decreased minimally. These changes were used to test the predictability of coronary events occurring between years 10 and 25 of follow-up when added to the model containing the factors at entry. Of these changes only systolic blood pressure significantly increased the predictability of coronary deaths. It is concluded that even minor alterations in systolic blood pressure above or below the entry levels can be associated with marked modifications in coronary mortality above or below those occurring naturally in the 15 years after the changes occurred.

Inter-cohort differences in coronary heart disease mortality in the 25-year follow-up of the seven countries study.

Sixteen cohorts of men aged 40-59 years at entry were examined with the measurement of some risk factors and then followed-up for mortality and causes of death for 25 years. These cohorts were located in the USA (1 cohort), Finland (2), the Netherlands (1), Italy (3), the former Yugoslavia (5), Greece (2), and Japan (2), and included a total of 12,763 subjects. Large differences in age-adjusted coronary heart disease (CHD) death rates were found, with extremes of 45 per 1000 in 25 years in Tanushimaru, Japan, to 288 per 1000 in 25 years in East Finland. In general, higher rates were found in the US and Northern European cohorts as compared to the Southern European and Japanese cohorts. However, during the last 10 years of follow-up large increases of CHD death rates were found in some Yugoslavian areas. Out of 5 measured entry characteristics treated as age-adjusted levels (serum cholesterol, systolic blood pressure, cigarette smoking, body mass index and physical activity at work), only serum cholesterol was significant in explaining cohort differences in CHD death rates. Over 50% of the variance in CHD death rates in 25 years was accounted for by the difference in mean serum cholesterol. This association tended to decline with increasing length of follow-up, but this was due to the great changes in mean serum cholesterol in the two Yugoslavian cohorts of Velika Krsna and Zrenjanin. When these two cohorts were excluded the association increased with time. Changes in mean serum cholesterol between year 0 and 10 helped in explaining differences in CHD death rates from year 10 onward. It can be concluded that this study suggests that mean serum cholesterol is the major risk factor in explaining cross-cultural differences in CHD.

Serum cholesteryl ester fatty acids and their relation with serum lipids in elderly men in Crete and The Netherlands.

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)

Twenty-year stroke mortality and prediction in twelve cohorts of the Seven Countries Study.

Twelve cohorts of men aged 40-59 for a total of 8287 individuals in six countries (Finland, the Netherlands, Italy, Yugoslavia, Greece and Japan) were examined in the late 1950s or early 1960s for the measurement of some risk factors and then followed up for mortality and causes of death through 20 years. Large differences in 20-year death rates from stroke were recorded among cohorts, with the highest levels in the pool of the Yugoslavia (67 per 1000) and Japanese cohorts (62 per 1000) and the lowest in the Dutch cohort (22 per 1000). The simple linear correlation (among cohorts) of stroke mortality on mean levels at entry of some factors showed inverse significant coefficients for systolic (-0.63) diastolic (-0.51) and mean blood pressure (-0.72), and for serum cholesterol (-0.72), whereas no significant coefficients were found for mean body mass index, mean cigarette consumption and mean physical activity. The Cox model solved for six national pools of cohorts showed that only age and mean blood pressure carry significant positive coefficients, whereas all the other available factors (cigarette consumption, serum cholesterol, body mass index, physical activity) did not approach significant levels except the negative coefficients of smoking habits in Greece.

Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries.

Out of the original 16 cohorts in the Seven Countries Study on Cardiovascular Diseases, 12 population samples in six countries have reached the 20 year follow-up deadline. Data on mortality became fully available for a total of 8287 men aged 40-59 at entry examination (two cohorts in Finland, one in the Netherlands, three in Italy, two in Yugoslavia, two in Greece, and two in Japan). Death rates from CHD as well as from all causes follow the traditional falling north to south trend (18 fold between the extremes for CHD; 2.7 fold for total mortality). The differences in all causes mortality are, however, largely accounted for by the variation in CHD mortality. The mean entry levels of serum cholesterol and representative levels of the consumption of saturated fats, mono-unsaturated fats, poly-unsaturated fats and carbohydrates explain a large proportion of inter-cohort difference in CHD mortality (81% for saturated fats). By applying the proportional hazards model to the pools of national cohorts, with CHD deaths as end-point and five risk factors as covariates, only age and mean blood pressure are universally significant predictors of fatal events. Cholesterol, smoking habits, body mass index and physical activity play some part but not in all the pools. Age and mean blood pressure are also the only universal risk factors for all causes of death.

Food consumption patterns in the 1960s in seven countries.

At the end of the 1950s the Seven Countries Study was designed to investigate the relations between diet and cardiovascular diseases. Sixteen cohorts were selected in Finland, Greece, Italy, Japan, The Netherlands, United States, and Yugoslavia. During the 1960s food consumption data were collected from random samples of these cohorts by use of the record method. In Finland the intake of milk, potatoes, edible fats, and sugar products was very high. A similar but lower intake pattern was observed in The Netherlands. Fruit, meat, and pastry consumption was high in the United States; cereal and alcoholic drink consumption was high in Italy; and bread consumption high in Yugoslavians except for those in Belgrade. In Greece the intake of olive oil and fruit was high and the Japanese cohorts were characterized by a high consumption of fish, rice, and soy products. These differences in food consumption patterns have lessened during the past 25 y.

Risk factors for coronary heart disease in middle-aged men in Crete in 1982.

Risk factors for coronary heart disease were studied in healthy middle-aged Cretan men in order to compare them with the middle-aged men of a previous generation studied in 1960 as the Cretan cohort of the Seven Countries Study (1960). In the present cohort mean values for total cholesterol were 5.48 mmol/L, for HDL-cholesterol 1.26 mmol/L, for triglycerides 1.41 mmol/L, for systolic blood pressure 128 mmHg, and for diastolic blood pressure 77 mmHg. Serum cholesterol was higher and blood pressure slightly lower than the values observed in 1960. However, it is uncertain whether these changes were real or caused by changes in methodology. The mean body mass index has increased from 22.6 in 1960 to 26.9 kg/m2 in 1982, due to an increase in fatness. The percentage of smokers had increased from 57.4% to 74.1%. Upon multiple regression analysis the body mass index, the subscapular to triceps skinfold ratio and smoking were negatively and independently related with HDL-cholesterol. Body mass index correlated positively with serum triglycerides. Although the incidence of coronary heart disease is still low in Crete, it is concluded that there is nothing in the risk profile of these middle-aged men to suggest that they are at a low risk for coronary heart disease.

Serum lipids, apoproteins and nutrient intake in rural Cretan boys consuming high-olive-oil diets.

A high intake of olive oil has produced high levels of high-density and low levels of low-density lipoprotein cholesterol in short-term dietary trials. To investigate long-term effects of olive oil we have studied the diet and serum lipids of boys in Crete, where a high olive oil consumption is the norm. Seventy-six healthy rural Cretan boys aged 7-9 years were studied. The diet was assessed by a 2-day dietary recall. Blood was collected according to a standardized protocol and sera were analyzed in a rigidly standardized laboratory. The mean daily intake of energy was 11.0 MJ (2629 kcal). The intake of fat (45.0% of energy) and oleic acid (27.2% of energy) was high, and that of saturated fat low (10.0% of energy), reflecting a high consumption of olive oil. The high consumption of olive oil was confirmed by a high proportion of oleic-acid (27.1%) in serum cholesteryl fatty acids. Mean concentration of serum total cholesterol was 4.42 mmol l-1 (171 mg dl-1), of HDL-cholesterol 1.40 mmol l-1 (54 mg dl-1), of serum triglycerides 0.59 mmol l-1 (52 mg dl-1), of apo-AI 1210 mg l-1 and of LDL apo-B 798 mg l-1. The body mass index of the Cretan boys (18.2 kg m-2) was on average 2 kg m-2 higher than that of boys from other countries. Contrary to our expectation, the Cretan boys did not show a more favourable serum lipoprotein pattern than boys from more westernized countries studied previously using the same protocol. Our hypothesis that a typical, olive-oil-rich Cretan diet causes a relatively high HDL- to total cholesterol ratio is not supported by the present findings.

The diet and 15-year death rate in the seven countries study.

In 15 cohorts of the Seven Countries Study, comprising 11,579 men aged 40-59 years and "healthy" at entry, 2,288 died in 15 years. Death rates differed among cohorts. Differences in mean age, blood pressure, serum cholesterol, and smoking habits "explained" 46% of variance in death rate from all causes, 80% from coronary heart disease, 35% from cancer, and 45% from stroke. Death rate differences were unrelated to cohort differences in mean relative body weight, fatness, and physical activity. The cohorts differed in average diets. Death rates were related positively to average percentage of dietary energy from saturated fatty acids, negatively to dietary energy percentage from monounsaturated fatty acids, and were unrelated to dietary energy percentage from polyunsaturated fatty acids, proteins, carbohydrates, and alcohol. All death rates were negatively related to the ratio of monounsaturated to saturated fatty acids. Inclusion of that ratio with age, blood pressure, serum cholesterol, and smoking habits as independent variables accounted for 85% of variance in rates of deaths from all causes, 96% coronary heart disease, 55% cancer, and 66% stroke. Oleic acid accounted for almost all differences in monounsaturates among cohorts. All-cause and coronary heart disease death rates were low in cohorts with olive oil as the main fat. Causal relationships are not claimed but consideration of characteristics of populations as well as of individuals within populations is urged in evaluating risks.