This study showed that a Mediterranean style diet was inversely associated with total CVD and more strongly so with fatal CVD. Inverse associations were also observed for composite CVD, myocardial infarction, stroke and pulmonary embolism. The MDS was not related to incident angina pectoris, transient ischemic attack and peripheral arterial disease. Alternate exclusion of components of the MDS showed that alcohol contributed most to the inverse association between MDS and CVD.
In the present study, a MDS of 7–9 was associated with a 56% lower incidence of fatal CVD compared to a MDS of 0–2, with a 16% lower incidence of total CVD and a 35% lower incidence of composite CVD. Comparison of our results with those of other investigations is hampered by differences in definition of Mediterranean style diet and of CVD endpoints. In previous studies, the MDS varied in definition of the components. Also, adherence to a Mediterranean style diet was categorized in various ways, ranging from two, to five categories of adherence. 
The definition of CVD also varied among studies, with various combinations of ICD codes and inclusion of fatal or nonfatal CVD events. Taken together, results of previous studies showed that high compared to low adherence to a Mediterranean style diet was associated with a 20 
to 40% 
lower incidence of fatal CVD and a 20 
to 25% 
lower incidence of composite CVD. These results are in line with those in the present study.
The association of the MDS with fatal CVD was stronger than with total CVD. A stronger association with fatal CVD may be due to the probabilistic linkage of the non-fatal Hospital Discharge data causing more misclassification than for fatal events. This may have resulted in weaker associations for nonfatal CVD. Furthermore, our results showed that adding ‘softer’ endpoints such as transient ischemic attack, angina pectoris and peripheral arterial disease to the composite of ‘hard’ endpoints reduced the strength of the associations considerably. Therefore, in discussing the strength of associations with different CVD endpoints, the definition of the latter is of utmost importance.
For the highest compared to the lowest MDS category we observed a 30% lower incidence of myocardial infarction and for each two unit increment a 14% lower incidence. This was in line with a recent cohort study in 2568 men and women in the United States by Gardener et al. who observed a 39% lower incidence of myocardial infarction for the highest compared to the lowest MDS category, and for each 1 unit increment a 6% lower incidence, though these associations were non-significant due to the small sample size. 
Our results are also consistent with those observed in other cohort studies, in which high compared to low adherence to a Mediterranean style diet was associated with a 30–40% lower incidence of coronary heart disease 
, although coronary hart disease incidence was defined differently in the various studies.
The inverse association between the MDS and stroke incidence in the present study (highest compared to lowest category HR: 0.70 (0.47–1.05) and for a two unit increment HR: 0.88 (0.78–1.00)) is in agreement with the results Fung et al. obtained in the Nurses Health Study 
. They observed a 13% lower incidence of stroke for those in the highest compared to the lowest quintile of adherence to a Mediterranean style diet. 
The results of the cohort studies published so far, including ours (results not shown), showed similar results for ischemic and hemorrhagic stroke 
We observed that the MDS was inversely associated with the incidence of pulmonary embolism. This association was stronger for men than for women. Diet is hypothesized to affect venous thromboembolism, and thereby pulmonary embolism, by altering levels of haemostatic and fibrinolytic factors. 
To our knowledge other studies did not investigate diet in relation to pulmonary embolism before. However, we could compare our results with those of three large cohort studies investigating the relation of diet with venous thromboembolism. The results of these studies were inconsistent. 
Therefore, our results for pulmonary embolism need confirmation by other prospective cohort studies.
In the present study, the MDS was not statistically significantly related to incident angina pectoris, transient ischemic attack and peripheral arterial disease. To our knowledge these associations have not been investigated earlier. These three diseases are ‘softer’ endpoints than e.g. myocardial infarction and stroke. This may have resulted in more misclassification 
which may have diluted the associations of the MDS with these endpoints.
The associations of the MDS with fatal CVD, incident CVD, composite CVD, and myocardial infarction attenuated most when excluding alcohol from the MDS. Excluding fish and seafood or the fatty acid ratio attenuated the association with pulmonary embolism most. No previous study on the MDS in relation to CVD assessed the effect of alternately excluding components of the MDS. Trichopoulou et al. observed for the association between MDS and all-cause mortality also most attenuation after excluding alcohol consumption from the MDS. 
Previous studies on a Mediterranean style diet assessing the contribution of its individual components to CVD incidence showed inconsistent results with respect to which component was strongest associated to CVD 
We studied the adherence to a Mediterranean style diet in a Dutch population. The Dutch diet is characterized by a low consumption of plant foods and fish and by a high consumption of animal foods compared to the traditional Mediterranean diet. 
However, similar associations of a Mediterranean style diet with CVD were observed in Mediterranean, Northern European and in American populations. 
This implies that, at different levels of adherence, a Mediterranean style diet is beneficial in relation to cardiovascular health. Furthermore, our associations were robust since in sensitivity analyses, including only whole grain cereals in the component ‘cereals’, or only moderate to high fat meat products and dairy products in the components ‘meat products’ and ‘dairy products’, hardly changed the results (results not shown). Also additionally adjusting the components of the MDS for energy intake (density method) or exclusion of cases in the first two years of follow-up hardly changed our results (results not shown).
Some limitations of our study need to be addressed. Dietary intake was self-reported using a validated food-frequency questionnaire (FFQ). This questionnaire had a good reproducibility, although the validity of vegetable (Spearman correlation coefficients: 0.38 for men and 0.31 for women) and fish (0.32 for men and 0.37 for women) consumption is of concern. 
In addition, diet was assessed only once and may have changed during follow-up, resulting in non-differential misclassification that may have attenuated the observed associations. Furthermore, our study is a prospective cohort study in which adherence to MDS was not randomized. Therefore, residual confounding cannot be ruled out. With regard to the cardiocascular follow-up, ‘hard’ endpoints, like myocardial infarction or stroke, are easier to diagnose than ‘softer’ endpoints like angina pectoris, transient ischemic attack or peripheral arterial disease. Also, ‘hard’ endpoints are more likely to be treated in the hospital than ‘softer’ ones, and thus monitored in the Hospital Discharge Registries 
. In a validation study comparing the Hospital Discharge data to that of a cardiology information system, sensitivity was considerably larger for acute myocardial infarction (84%) than for unstable angina pectoris (53%) 
. Therefore, misclassification is likely smaller for the ‘hard’ events, which may have resulted in stronger associations.
The present study also has advantages. EPIC-NL is a large prospective cohort study, especially designed to study associations between diet and chronic diseases, and included both men and women from the general population, with a broad age range and a long follow-up period. Because of the detailed cardiovascular follow-up data and the large sample size, we were able to investigate associations of a Mediterranean style diet with specific CVD.
In conclusion, the present study showed that better adherence to a Mediterranean style diet was more strongly associated with fatal CVD than with total CVD. Disease specific associations were strongest for incident myocardial infarction, stroke and pulmonary embolism.