Adherence to the Mediterranean Diet in Relation to Acute Coronary Syndrome or Stroke Nonfatal Events

A Comparative Analysis of a Case/Case-Control Study

Christina-Maria Kastorini, MSc; Haralampos J. Milionis, MD, PhD; Aggeliki Ioannidi, MSc; Kallirroi Kalantzi, MD; Vassilios Nikolaou, MD; Konstantinos N. Vemmos, MD; John A. Goudevenos, MD, PhD; Demosthenes B. Panagiotakos, PhD


Am Heart J. 2011;162(4):717-724. 

In This Article


Results of the present work support the beneficial effect of the Mediterranean dietary pattern regarding the presence not only of an ACS but also of an ischemic stroke event. It is of interest that the effect of this diet on stroke outcome was at least similar to that on ACS. This is one of the few studies that have examined the relationship between adherence to the Mediterranean diet and stroke and, to the best of our knowledge, one of the first studies attempting to perform a comparative analysis regarding the role of this traditional diet on the development of ACS or stroke. Despite the limitations this study may carry due to the retrospective design of the study, the results were robust and multiadjusted for various potential confounders, revealing an important, nonpharmacologic, public health message for the prevention of stroke.

Since the Seven Countries Study[5] in the 1970s and the randomized clinical trial Lyon Heart Study[25] in the 1990s, many studies have supported the beneficial effect of the Mediterranean diet on the development of CVD and, particularly, CHD.[6] The CARDIO2000 study, a case-control study with 848 patients with ACS and 1,078 age- and sex-matched control subjects, showed that a 10-unit increase of the MedDietScore was associated with a roughly 30% lower likelihood of having an ACS.[26] Trichopoulou et al[27] showed that adherence to the Mediterranean dietary pattern was associated with a 33% (95% CI 0.47–0.94) lower mortality from CHD. In addition, recent results of the large-scale, multinational INTERHEART study, including 27,098 participants from 52 countries, highlighted the important role of unhealthy dietary habits as a risk factor for myocardial infarction. Most importantly, the population attributable risk of an unhealthy diet was approximately 27% in men and 26% in women;[28] suggesting that most CHD evens could have been avoided by adopting a healthier dietary pattern. In the present work, the estimated attributable risk for the lowest tertile of adherence to the Mediterranean pattern was 40% for ACS.

Despite the plethora of studies as regards Mediterranean diet and CHD, few studies have examined the role of the diet on the development of stroke. The Nurses' Health Study, a prospective cohort study of 74,886 female participants, showed that adherence to this pattern exerts a protective effect regarding the development of stroke (relative risk of highest compared with lowest quintile: 0.87, 95% CI 0.73–1.02).[13] Furthermore, a recent case-control study of only 48 patients with stroke and 47 age- and sex-matched controls reported that adherence to the Mediterranean diet was associated with a 91% lower likelihood of ischemic stroke (95% CI 0.02–0.40).[14] In addition, results of the INTERSTROKE case-control study suggested that unhealthy dietary habits were associated with a 34% higher likelihood of ischemic stroke (95% CI 1.09–1.65, highest vs lowest tertile), whereas the population attributable risk was 17.3% (95% CI 9.4–29.6).[29] In the present work, similar to the 2 aforementioned studies, it was observed that a greater adherence to the Mediterranean diet was associated with a lower likelihood of having an ischemic stroke event, whereas the estimated attributable risk for the lowest tertile of adherence to the Mediterranean pattern was 37%.

It is widely known that oxidative stress and chronic inflammation play a crucial role for the development of atherosclerosis, influencing endothelial and vascular function. Not surprisingly, the protective role of the Mediterranean dietary pattern regarding CVD has been mainly attributed to the antioxidant and anti-inflammatory properties of this pattern. The basic components of this diet—olive oil, red wine, fruits and vegetables, and fish—are foods rich in vitamins, antioxidants, polyphenols, phytochemicals, and omega-3 fatty acids. Results of epidemiologic studies and clinical trials have shown that subjects following closer the Mediterranean diet had a higher total antioxidant capacity[11] and lower inflammatory and coagulation markers: C-reactive protein, interleukin-6, homocysteine, white blood cell, and fibrinogen levels.[12,30] Furthermore, latest studies have shown the beneficial role of this diet on endothelial function.[30] In particular, adherence to the Mediterranean diet has been associated not only with a reduction in endothelial damage and dysfunction but also with improvement in the degenerative activity of the endothelium.[31]

Both CHD and ischemic stroke share many common risk factors[28,29] but also important dissimilarities in the development and phenotypic expression of atherosclerotic plaques in coronary and cerebral arteries, possibly due to differences in genetic characteristics, anatomy, or different response of coronary and cerebral arteries to risk factors.[32] The presented results suggest that adherence to Mediterranean diet exerts a stronger effect regarding the development of stroke. It is possible that the antioxidant and anti-inflammatory benefits of the Mediterranean dietary pattern could have an apparent effect in cerebral and carotid arteries. In fact, a study by Shai et al[33] has shown significant regression of carotid atherosclerosis, for participants following a low-fat Mediterranean diet or a low-carbohydrate diet.

At this point, it should be noted that although the Mediterranean diet is believed to be followed closely only in countries surrounding the upper Mediterranean basin, population-based studies performed in northern Europe, United States, Chile, or Australia, suggest that the adoption of this type of diet can exert its beneficial effects globally.[13,34,35] In addition, globalization and improved transportations have contributed to the consumption of Mediterranean products worldwide. Nevertheless, it should be noted that there are still cultural, religion, and geoclimatologic aspects as regards dietary habits that will be difficult to overcome to spread this dietary pattern around the world.[36] Moreover, it could be speculated that the comparison of this diet with a control but less healthy, dietary pattern adopted elsewhere might provide more prominent results against ACS or stroke risk.

The holistic approach of dietary pattern, instead of food-specific, analysis applied here to evaluate the research hypotheses is now considered a very promising scientific area in dietary assessment and encouraged by several investigators in the field of nutritional epidemiology. Compared with the traditional food-specific analyses, dietary pattern analyses have considerable advantages regarding both concept and design; first of all, people do not eat isolated nutrients but consume a variety of foods and complex meals, whereas several methodological limitations, such as high levels of intercorrelation and synergistic effect of foods, are better controlled.[37,38]

Strengths and Limitations

In the present work, the existing knowledge regarding adherence to the Mediterranean diet and the development of stroke was expanded; moreover, the effect size measures were even better to that of the role of diet on ACS. These findings state a new hypothesis as regards the role of diet in the primary prevention of both heart disease and stroke and may suggest common pathophysiologic mechanisms for the aforementioned outcomes. However, there are some limitations due to the retrospective, observational design of the study, such as the selection and the recall bias and the lack of causal interpretations. To minimize the selection bias, only cases with a first event were enrolled, and to minimize recall bias, accurate and detailed data from all participants during the first 3 days of hospitalization were obtained. Nevertheless, a controlled clinical trial would be more effective in assessing causal relationships, and it is suggested as a future work. For the dietary evaluation, an FFQ was administered; although these tools may carry measurement error and be less accurate (especially in energy and nutrients assessment) as compared with a diary, an effort was made to reduce these errors and inaccuracies of dietary reporting with its application by trained dietitians through face-to-face interviews. Moreover, although the FFQ used here has shown good validation properties, the information used was based only on food groups and level of adherence to a specific pattern. Overestimation/underestimation in reporting may also exist, especially in the measurement of diet (eg, people with a disease usually tend to overreport unhealthier dietary habits to provide a reason for their condition, or healthy individuals usually report healthier dietary habits when interviewed by specialists), smoking habits, and the onset of CVD risk factors (eg, the best available information is the date of first diagnosis, whereas the initiation of the condition and the burden of damage it may cause to the cardiovascular system remains unknown). However, an effort was given to retrieve accurate information from the participants' medical records, as well as their relatives. Residual confounding and the omitted variables, for example, direct financial status and other social parameters (due to lack of accuracy), separate information for medication (not combined with the health condition), and presence of stress (due to the collinearity with depression status), may have influenced the effect size measures. Regarding the patients with stroke, self-reported information was obtained from 76% of the sample, whereas for 60 patients (24%) unable to answer to the interviewer due to their condition, data were collected from a valid surrogate respondent. Moreover, the patients with coronary disease and stroke who died at hospital entry or the following day were not included in the study (survivor bias); thus, the results should be generalized only to CVD survivors. Finally, the inclusion of patients and controls from only 2 regions may limit the generalization of the findings to the whole country; nevertheless, it should be noted that Athens metropolitan area and Ioannina city in western Greece represent most of the Greek urban and rural population.


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