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


Design and Sampling Procedure

A multicenter, case-control study, with individual (1-for-1) matching by age (within ±3 years) and sex, was conducted.[15] From October 2009 to December 2010, 500 of the 615 consecutive patients with a first ACS event (n = 250; 209 acute myocardial infarction, 41 unstable angina) or ischemic stroke (n = 250) and without any suspicion of previous CVD who entered in the cardiology and pathology clinics or the emergency units of 3 major general hospitals in Greece agreed to participate (participation rate 81%). For the patients with stroke who were unable to communicate (speech disorders, aphasia, memory problems), the information was obtained by a valid surrogate respondent (first-degree relative living in the same home with the patient and being aware of the participant's dietary habits and medical history). Patients with chronic neoplasmatic disease or chronic inflammatory disease, as well as individuals with recent changes in their dietary habits, were not enrolled in the study. Five hundred control subjects (250 matched 1-for-1 with patients with ACS and another 250 matched 1-for-1 with patients with stroke) were selected concurrently with the patients (to eliminate residual confounding) on a volunteer, population basis and from the same region of the patients. Controls were without any clinical symptoms or suspicions of CVD in their medical history, as this was assessed by a physician.

Based on a priori statistical power analysis, a sample size of 500 patients (250 ACS, 250 stroke) and 500 age- and sex-matched healthy subjects was adequate to evaluate 2-sided odds ratios equal to 1.20, achieving statistical power greater than 0.80 at .05 probability level (P value). However, to achieve more robust estimates of the effect-sized measures, bootstrap resampling method was also applied (see details in the "Statistical analysis" section).


The study was approved by the Ethics Committee of Cardiology Clinic, University of Ioannina Medical School, and was carried out in accordance to the Declaration of Helsinki (1989) of the World Medical Association. Before the collection of any information, participants (or valid surrogate respondents) were informed about the aims and procedures of the study and provided their written signed consent.

Diagnosis of ACS or Stroke

Regarding the patients with ACS, clinical symptoms were evaluated at hospital entry, and a 12-lead electrocardiogram was performed. Evidence of myocardial cell death was assessed with blood tests and measurement of the levels of troponin I and the MB fraction of total creatinine phosphokinase (according to the Universal Definition of Myocardial Infarction [Joint European Society of Cardiology/American College of Cardiology Foundation/American Heart Association/World Heart Federation Task Force]);[16] unstable angina was defined by the occurrence of 1 or more angina episodes, at rest, within the preceding 48 hours, corresponding to class III of the Braunwald classification.[17]Ischemic strokes were defined through symptoms of neurologic dysfunction of acute onset of any severity, consistent with focal brain ischemia and imaging/laboratory confirmation of an acute vascular ischemic pathology.[18]

Dietary Assessment and Evaluation of Mediterranean Diet

Dietary habits of the past year were assessed through a 90-item, validated semiquantitative food frequency questionnaire (FFQ) that has been previously described.[15] In brief, the validation of the FFQ was performed using, as a reference method, a 3-day food record; both tools were administered in 136 subjects (40 ± 14 years, 59 men) over the same time span, in 2010. Moderate-to-good validity was observed as regards all food groups and beverages studied (Kendall τ coefficients varied between 0.22 and 0.56, Ps < .05).[15] Level of adherence to the Mediterranean diet was evaluated using an 11-item, large-scale, composite index, the MedDietScore.[19] The score was calculated for each participant based on the information retrieved through the FFQ. For the consumption of foods presumed to be part of the Mediterranean pattern (ie, those suggested on a daily basis or >4 servings/week, such as nonrefined cereals, fruits, vegetables, legumes, olive oil, fish, and potatoes), lower scores were assigned when participants reported no, rare, or moderate consumption, whereas higher scores were assigned when the consumption was according to the rationale of the Mediterranean pattern. For the consumption of foods presumed not to be part of the Mediterranean pattern (ie, consumption of meat and meat products, poultry, and full-fat dairy products), scores were assigned on a reverse scale. For alcohol, score 5 was assigned for consumption of less than 3 wineglasses per day; score 0, for consumption of more than 7 wineglasses per day; and scores from 4 to 1, for consumption of 3, 4 to 5, 6, and 7 or 0 wineglasses per day, respectively. The theoretical range of the MedDietScore was between 0 and 55. Higher values of this diet score indicate greater adherence to the Mediterranean diet, whereas no specific thresholds have been proposed. The validation properties of the MedDietScore have been presented elsewhere in the literature.[19]

Sociodemographic, Clinical, Anthropometric, and Lifestyle Characteristics

Sociodemographic variables recorded were age and sex (for the matching procedure), educational level measured by years of school, and financial status evaluated indirectly using an index measuring how satisfied the participant was from his/her income (ie, from value 1, which means not at all satisfied, to value 9, which means very satisfied). Current smokers were defined as those who smoked at least 1 cigarette/day; former smokers, as those who had stopped smoking more than 1 year previously; and the rest of the participants, as noncurrent smokers. Physical activity was assessed using the International Physical Activity Questionnaire index,[20] which has been validated for the Greek population.[21] According to their physical activity levels, participants were classified as inactive or physically active (moderate or health-enhancing physical activity). Body mass index (BMI) was calculated as weight (in kilograms) divided by standing height (in meters squared);[22]overweight and obesity were defined as BMI 25.0 to 29.9 and >29.9 kg/m,[2] respectively.

In all participants, detailed medical history was recorded, including family history of CVD, as well as personal and family history of hypertension, hypercholesterolemia, hypertriglyceridemia, and diabetes. Patients whose average blood pressure levels were ≥140/90 mm Hg or were under antihypertensive medication were classified as having hypertension. Hypercholesterolemia was defined as total serum cholesterol levels >200 mg/dL or the use of lipid-lowering agents, and diabetes mellitus was defined as fasting blood glucose >126 mg/dL or the use of antidiabetic medication. A previously translated and validated version of the Zung Depression Rating Scale (ZUNG-DRS; range 20–80) was used for the assessment of depressive symptoms.[23,24]

Statistical Analysis

Normally distributed continuous variables (age, BMI, education years, ZUNG-DRS and MedDietScore) are presented as mean values ± SD and categorical variables (sex, smoking habits, medical history, BMI categories, physical activity, financial status, MedDietScore categories, and ZUNG-DRS categories) as frequencies. Associations between categorical variables were tested by the calculation of the χ[2] test. Comparisons of mean values of normally distributed continuous variables by clinical outcome were performed using the Student t test. Correlations between continuous variables were evaluated using the Pearson r or Spearman ρ coefficients. Normality of the variables was tested using P-P plots. Estimations of the relative odds of having ACS or stroke according to the level of adherence to the Mediterranean diet and other covariates were performed through conditional logistic regression analysis; results are presented as odds ratios and the corresponding 95% CIs. Hosmer-Lemeshow statistic was calculated to evaluate a model's goodness of fit. Comparisons between the effect size measures (ie, odds ratios) of the 2 logistic models (the one for ACS and the other for stroke) were based on the Wald test (ie, log(odds ratio)/Var(log odds ratio), the higher the better). The robustness of the estimated odds ratios was evaluated using bootstrap resampling method of 1,000 data sets. A bias of the estimate less than 0.01 was considered adequate for the performance of the calculated odds ratio. All reported P values were based on 2-sided hypotheses. SPSS 18.0 software (SPSS Inc, Chicago, IL) was used for all the statistical calculations.

The authors are solely responsible for the design and conduct of this study, data analyses, drafting and editing of the paper, and its final contents. No extramural funding was used to support this work.


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