349 study participants were followed up for 199
726 person years, during which period 1075 deaths occurred. Table 1 shows the distribution of study participants without a medically documented history of major chronic diseases at enrolment. By design, the Greek EPIC cohort contains more women than men. The sampled age groups contain relatively few people with university level education. As is well known for the Greek population in general, a high proportion of people were overweight or obese and a high proportion of men were ever smokers. Almost half of men and a substantial fraction of women were consumers of a moderate amount of alcoholic beverages; few men and very few women were high consumers.
Table 1 Distribution of study participants without cancer, coronary heart disease, or diabetes mellitus at enrolment, by sex and baseline sociodemographic, somatometric, lifestyle, and medical characteristics. Values are numbers (percentages)
Table 2 shows medians and interquartile ranges of the daily intakes (by sex) of food groups that are characteristics of the traditional Mediterranean diet because they are consumed either in relatively high or in relatively low amounts. The high consumption of vegetables, legumes, fruits, and monounsaturated lipids (mostly olive oil) is evident.
Table 2 Daily intakes (g/day) of indicated dietary variables by sex. Values are median (interquartile range)
Table 3 shows associations, derived from Cox regression, of the nine components of the Mediterranean diet with mortality, assessed through mutually adjusted ratios contrasting high with low consumption (except for ethanol) and controlled for potential confounders as indicated in the footnote. All components of the Mediterranean diet score have been simultaneously introduced in this model, allowing assessment of the relative impact of each component. Compared with moderate intake of ethanol, both low and high intakes were associated with excess mortality to a statistically significant degree. Among the presumed beneficial components of the Mediterranean diet score, high consumption of all but fish and seafood was inversely associated with mortality, although none of these associations was statistically significant. For fish and seafood, the mortality ratio for consumption above or equal to the median compared with consumption below the median was 1.078 (95% confidence interval 0.950 to 1.224; P=0.243). With respect to meat and meat products and dairy products, as expected we found positive associations, which for meat and meat products approached statistical significance (P=0.06). Because ethanol was introduced in the Mediterranean diet score as a binary variable (moderate intake versus other), we also calculated the corresponding mortality ratio, which is 0.810 (0.706 to 0.931).
Table 3 Mutually adjusted mortality ratios associated with intake of components of Mediterranean diet
After a mean follow-up of 8.5 years, 652 deaths from any cause had occurred among 12
694 participants with Mediterranean diet scores 0-4 and 423 among 10
655 participants with scores 5 or more. Table 4 shows the mortality ratio associated with a two unit increment in the Mediterranean diet score, as well as how this ratio changes with alternate exclusion of each of the nine components of the score. Because of the construction of the score (in which one unit is assigned when a beneficial component is consumed in high quantities, ethanol is consumed in moderate quantities, or a non-beneficial component is consumed in low quantities), the benefit is expected to decrease (and the mortality ratio is expected to increase towards the null value of 1) after the alternate exclusion from the score of each of the nine components. Table 4 also shows the percentage reduction in the apparent effect of the Mediterranean diet score. Thus, when vegetables are excluded from the score the mortality ratio, properly adjusted for the change from a 10 point to a nine point scale, increases from 0.864 to 0.886—that is, the beneficial effect of the Mediterranean diet score is reduced from 1−0.864=0.136 to 1−0.886=0.114 or by 16.2%. In the construction of the Mediterranean diet score, fish and seafood are expected to have an inverse (beneficial) association, but in this particular dataset the association turned out to be non-significantly positive (table 33
). For this reason, we did not calculate the mortality ratio corresponding to the exclusion of fish and seafood from the Mediterranean diet score in table 4.
Table 4 Mortality ratios associated with two unit increment* in Mediterranean diet score (MDS) and after alternate subtraction of each of its dietary components
Table 5 shows changes in the mortality ratios associated with a two unit increment in the Mediterranean diet score (properly adjusted for the sequential change in scale), after successive removal of each of its components, ranked according to the magnitude of effect in the model in which the nine components were mutually adjusted (table 3). Again, we did not consider fish and seafood in this analysis (except as a possible confounding variable). As expected, the mortality ratio gradually approaches the null value of 1 after removal firstly of ethanol, then of meat and meat products, then of vegetables, then of fruits and nuts, then of the lipid ratio, and finally of legumes. Change in the order of removal did not noticeably affect the pattern shown in table 5.
Table 5 Mortality ratios associated with two unit increment in Mediterranean diet score after successive removal of each of its components
We also examined the consequences of the joint presence of any two by two combinations of the nine components of the Mediterranean diet score, excluding combinations of fish and seafood with the rest of the components because of the unexpected (probably owing to chance) positive association of this food group with mortality. Of the 28 possible two by two combinations, we found clear additive or super-additive associations of the joint presence of any two components in 13 instances (in none of these instances was there a statistically significant interaction in the multiplicative scale implicit in the Cox regression). Moderate ethanol consumption, high lipid ratio, and low intake of meat and meat products were each present five times in the 26 (2×13) possible entries, whereas high intakes of vegetable, fruits, and legumes were each represented three times (the remaining two entries were once for low intake of dairy products and once for high cereal intake). In conjunction with the results in table 5, we interpret these findings as suggesting that moderate ethanol intake, low intake of meat and meat products, high lipid ratio, and high intake of plant foods are driving the association of high Mediterranean diet score with low mortality.