Mediterranean diet and perceived stress have long been associated with the likelihood of having an acute coronary syndrome (ACS). The aim of this study was to evaluate whether the Mediterranean diet and other eating behaviors mediate and/or moderate the unfavorable impact of perceived stress on the likelihood of having a non-fatal ACS.
This is a case–control study with individuals matched by age and sex. A total of 250 consecutive patients (60±11 years, 78% men) with a first ACS and 250 population-based, control subjects (60±8.6 years, 77.6% men) were enrolled. Perceived stress levels were evaluated with the Perceived Stress Scale (PSS-14; range 0–14), and adherence to the Mediterranean diet was assessed by the MedDietScore (range 0–55). Stress eating, eating heavy meals and eating alone were also evaluated.
For each unit increase in the PSS-14, the likelihood of having an ACS increased by 14% (95% confidence interval (CI)=1.10, 1.18). Stratified analysis by Mediterranean diet adherence level revealed a similar association of PSS-14 with ACS likelihood between the low-to-moderate and moderate-to-high adherence groups (that is, odds ratio (OR)=1.15, 95% CI=1.09, 1.21 and OR=1.13, 95% CI=1.07, 1.80, respectively). Stress eating and eating alone were positively associated with the likelihood of having an ACS (OR=1.31, 95% CI=0.97, 1.77 and OR=1.36, 95% CI=1.08, 1.69, respectively). Eating heavy meals was not associated with ACS (OR=1.08, 95% CI=0.82, 1.41); no mediating or moderating effect of these behaviors on perceived stress ACS was observed.
The highly significant impact of perceived stress on ACS likelihood was not mediated or moderated by the level of adherence to the Mediterranean diet or other eating behaviors, underlying the strong effect of this psychological disorder on ACS.
Psychological stress, especially when chronic, is considered to result in permanent physiological, emotional and behavioral adaptations that are involved in physical disorder.1,2 For instance, stress has been linked to the pathogenesis of depression, some types of cancers, as well as infectious, autoimmune and cardiovascular disease (CVD).1 Importantly, stress is a very well-known CVD risk factor and has been associated with increased coronary heart disease incidence and prevalence.3 In research, several types of stress have been associated with CVD pathogenesis and incidence (that is, work stress, marital stress), indicating that stress is not always measured in the same way.4,5 To better facilitate the comprehension of stress effects on health and disease irrespective of stress origin (that is, life events, work), a unique measure of stress may be needed that takes into account most of the relative stress parameters (that is, personality characteristics such as hostility, optimism) and evaluates the overall stress load in life. Perceived stress presents a global and comprehensive stress construct that refers to the transactional process between the individual and the environment.6 Interestingly, perceived stress was independently associated with an increased likelihood of having an acute coronary syndrome (ACS) incidence among other subcategories of coronary heart disease, and in most studies, such a relationship emerged as causal.7,8 The underlying mechanisms that explain the association between perceived stress and an unfavorable cardiac profile are not completely understood. Stress has long been linked to the pathogenesis of the metabolic syndrome and the likelihood of having an ACS. It originally promotes insulin resistance and glucose intolerance, as well as adiposity, and is followed by hemodynamic, inflammatory and pro-thrombotic responses, as well as autonomic dysfunction and neuroendocrine activation, and has been strongly associated especially with the establishment of hypertension, hypercholesterolemia and central obesity; cortisol secretion seems to have a central role in this path.9, 10, 11
Healthy dietary habits have been associated with better health outcomes and greater life expectancy.12 Dietary habits are better evaluated by identifying ‘dietary patterns’, as the analysis of single nutrients evades considerable interactions between components of a diet.13 For instance, the Mediterranean dietary pattern presents a model of healthy eating, and its contribution to a favorable health status and a better quality of life has been widely demonstrated.14,15 In particular, the Mediterranean dietary pattern is associated with better mental health status and a reduction of overall mortality, mortality from cancer and CVD.14 The Mediterranean diet is mainly characterized by the consumption of cereals, olive oil, fresh or dried fruits and vegetables, a moderate amount of fish, dairy and meat, many condiments and spices, as well as wine or infusions.15 Furthermore, and according to the recent definition given by UNESCO, the Mediterranean diet constitutes a set of skills, knowledge, practices and traditions ranging from the landscape to the table, including the crops, harvesting, fishing, conservation, processing, preparation and, particularly, consumption of food.16 The cardioprotective role of the Mediterranean dietary pattern has been vastly documented.15, 16, 17, 18 Unhealthy dietary patterns (that is, usual consumption of saturated fat) are frequently considered as a behavioral outcome of negative affective dispositions (that is, depression, stress).19,20 Perceived stress has been associated with the adoption of dietary patterns that diverge from the Mediterranean healthy one in some studies as well,21,22 contributing in a way to the pathogenesis of CVD. Indicatively, perceived stress was associated with lower fruit and vegetable intake and higher intake of salty snacks and sweets, whereas cortisol, a hypothesized mediator of stress-related food intake in this study, has been associated with higher intake of saturated fat as well.22 On the other hand, healthy eating may mitigate the adverse impact of negative affective dispositions on cardiac system.23, 24, 25 However, similar research regarding stress does not appear to have matured yet. Interestingly, in a randomized crossover study, the meal content (that is, three meals that differed in type and amount of fat) had no differentiating effect on cardiovascular reactivity to mental stress.26
Also, whether healthy eating mediates and/or moderates the adverse effect of perceived stress on cardiovascular integrity has not been well studied and appreciated yet.
Thus, the aim of the current work was to evaluate the potential mediating or moderating effect of adherence to a healthy diet (Mediterranean diet), as well as stressful eating behaviors (that is, eating alone, eating under stress, eating heavy meals), on the association between perceived stress and ACS development.
Materials and methods
This is a case–control study with individual (one-to-one) matching by age (within±3 years) and sex and in accordance with a larger epidemiological protocol that has been previously established.27
The study was approved by the Ethics Committee of the University Hospital of Thessaly (Larissa) and was carried out in accordance with the Declaration of Helsinki (1989) of the World Medical Association. Before the collection of any information, participants were informed about the aims and procedures of the study and provided their signed consent.
From August 2010 to September 2012, 250 patients who presented with a first ACS event (n=250), without any suspicion of previous CVD, in the cardiology and pathology clinics or the emergency units of two major General Hospitals in Greece agreed to participate (the participation rate was 75%) in our study. Regarding the ACS patients, 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.28 Two hundred and fifty control subjects, age–sex matched one-by-one with ACS patients, were selected concurrently with the patients on a volunteer population basis and from the same region as that of the patients. Controls were without any clinical symptoms or suspicions of CVD in their medical history, as this was assessed by a physician. Controls had no relationship with the patients and were recruited in non-hospital settings. Subjects with chronic neoplastic disease or chronic inflammatory disease, as well as individuals with recent changes in their dietary habits, were not enrolled in the study.
On the basis of a priori statistical power analysis, a sample size of 250 patients (250 ACS) and 250 age- and sex-matched healthy subjects was adequate to evaluate two-sided odds ratios (ORs) equal to 1.20, achieving statistical power >0.80 at 0.05 probability level (P-value).
Socio-demographic, clinical, anthropometric and lifestyle characteristics
Age and sex of the participants were recorded and enabled the matching procedure. Smokers were defined as those who smoked at least one cigarette per day, and the rest were defined as nonsmokers. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ) index validated for the Greek population;29,30 three categories were derived on the basis of the calculated metabolic equivalent via the IPAQ, that is, inactive, moderately active and physically active. Weight and height were measured using the standard procedures by the study's investigators; body mass index was calculated as weight (in kg) divided by standing height (in m2). Obesity was defined as having a body mass index>29.9 kg/m2.
In all participants, a detailed medical history was recorded, including family history of CVD as well as personal history of hypertension, hypercholesterolemia and diabetes. Patients whose average blood pressure levels were ⩾140/90 mm Hg or who 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.
Assessment of perceived stress
Perceived Stress was assessed using the Perceived Stress Scale (PSS-14), which is a 14-item self-reported questionnaire that evaluates the degree to which individuals appraise their lives as unpredictable, uncontrollable or overloaded.6 The 14 items were rated from 0 to 4 according to the frequency of feelings experienced by the participant (that is, never, almost never, sometimes, often, almost always). Total theoretical range of the score is 0–56. Higher values of the PSS-14 score indicated greater perceived stress. The scale has been validated into Greek by two independent groups and has been found reliable and accurate for use.31,32
Dietary habits were assessed through a 90-item, validated semiquantitative food-frequency questionnaire that has been previously described27 and validated.33 Level of adherence to the Mediterranean diet was evaluated using an 11-item large-scale, composite index, the MedDietScore.34 In brief, for the consumption of foods deemed to be part of the Mediterranean pattern (that is, those consumed on a daily basis or at more than four servings per week, such as non-refined 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 assumed not to be part of the Mediterranean pattern (that is, 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<3 wineglasses per day, score 0 for consumption of >7 wineglasses per day and scores from 4 to 1 for consumption of 3, 4–5, 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. The validation properties of the MedDietScore have been presented elsewhere in the literature.34 Further, participants who reported drinking coffee and tea weekly or daily were classified as coffee and tea drinkers, respectively, and the rest as coffee and tea nondrinkers. Participants who reported eating sweets ⩾3–5 times/week were classified as sweet-eaters and the rest eating sweets ⩽1–2 times/week were classified as sweet non-eaters.
Assessment of eating behaviors
To examine whether certain eating behaviors mediate and/or moderate the effect of perceived stress on the likelihood of developing ACS, participants were asked: (a) how often (rarely, 1–2 times per week, 3–5 times per week, daily) they consume food under stress conditions (before the participant has time to relax), (b) how often (less than once in 3 months, 1–4 times per month, 2–4 times per week, almost every day) they consume a more heavy meal that makes them feel full, and (c) how frequently they eat alone (rarely, sometimes a week, a meal per day, all meals). Stress-eaters were considered those who reported eating while being stressed 3–5 times/week or daily and the rest as non-stress eaters. Heavy-meal eaters were considered as those who reported eating a heavy meal 2–4 times a week or almost every day. Participants who reported having a meal per day or all meals alone were coded as alone-eaters.
Normally distributed continuous variables (age, body mass index, PSS-14 and MedDietScore) were presented as mean values±s.d. and categorical variables (sex, smoking, medical history, obesity status, physical activity level, stress eating, eating heavy meals and eating alone) as frequencies. Normality of the variables was tested using P-P plots. Associations between categorical variables were tested by the calculation of the chi-square test. Comparisons of mean values of normally distributed continuous variables by the outcomes were performed using the Student’s t-test. Correlations between continuous variables were evaluated using the Pearson’s r or Spearman ρ coefficients. Conditional logistic regression analysis was applied to evaluate the association of PSS-14 and various participant’s characteristics on the likelihood of having ACS; results are presented as OR and their corresponding 95% confidence intervals (CIs). The Hosmer–Lemeshow statistic was calculated to evaluate the model’s goodness-of-fit. To test for the potential mediating role of adherence to the Mediterranean diet, stress eating, heavy meal consumption and eating alone on the relationship between perceived stress and ACS, the following approach, as suggested by Baron and Kenny, was applied:35 first, the independent association between PSS-14 and MedDietScore on ACS was evaluated, then the association between PSS-14 and ACS was evaluated without and with the presence of MedDietScore in the model (Table 2). A change in b-coefficients of PSS-14 in the two nested models was evaluated using the Z-test, where a case of significant change suggests a mediating effect of diet on the relationship between perceived stress and ACS. To test for the potential moderating role of Mediterranean diet and eating behaviors, the interaction between Mediterranean diet, eating behaviors and PSS-14 was evaluated, including the PSS-14 and MedDietScore variables in the model; when significant, stratification analysis was applied (Table 3). All reported P-values were based on two-sided hypotheses. SPSS 18.0 software (SPSS Inc., Chicago, IL, USA) was used for all the statistical calculations.
Table 1 describes the demographic, lifestyle, psychological and behavioral characteristics in both ACS patients and controls. Patients reported significantly lower levels of adherence to the Mediterranean diet principles compared with controls (29.5±4.5 vs 31.8±4, P<0.001). Levels of PSS-14 also differed significantly between patients and controls, with patients reporting 49% higher score compared with the control participants (29.6±8.2 vs 19.8±7.8, P<0.001). The prevalence of clinical characteristics (that is, obesity, hypertension, hypercholesterolemia and diabetes mellitus) as well as lifestyle variables (that is, smoking, physical activity) also differed significantly between the two groups. Moreover, patients reported eating more frequently heavy meals while being stressed, as well as eating while being alone (Table 1).
Focusing on perceived stress, it was observed that the PSS-14 score was lower in males as compared with females (24±9 vs 26±9, P=0.04) and was inversely associated with participant’s age (ρ=−0.10, P=0.05). Furthermore, PSS-14 was inversely correlated with MedDietScore (ρ=−0.219, P<0.001), whereas it was positively associated with the history of hypertension (P<0.001), hypercholesterolemia (P<0.001), diabetes mellitus (P<0.001) and smoking habits (P<0.001). Regarding eating behaviors, PSS-14 was positively associated with eating while stressed (P<0.001), eating alone (P<0.001) and eating heavy meals (P<0.001).
Perceived stress, ACS and the potential mediating role of dietary habits and behaviors
However, the aforementioned relationships between perceived stress, Mediterranean dietary pattern adoption and likelihood of having ACS may be prone to bias, especially due to the observational design of the study. Thus, a multi-adjusted analysis using nested models was performed (Table 2). It revealed that PSS-14 was significantly associated with the likelihood of ACS even after adjusting for related clinical variables (model 1) and lifestyle characteristics (model 2); particularly, a one-unit increase in PSS-14 score was associated with 14% higher likelihood of ACS, after various adjustments were made (model 2). Further, in order to examine the potential mediating role of the Mediterranean dietary pattern on perceived stress–ACS relationship, MedDietScore was included. As it can be seen, no changes in the effect size measures of PSS-14 were evident when MedDietScore was included in the analysis (model 3), suggesting lack of any mediating effect of diet on the relationship between perceived stress and ACS. It should be noted that Mediterranean diet was highly associated with ACS; moderate-to-high adherence to the MedDietScore led to a 43% lower likelihood of having an ACS (model 3). Furthermore, no significant changes in effect size measures of PSS-14 on ACS were observed when stress-eating behavior, eating alone or heavy meal consumption were also entered (one variable each time due to colinearity) in the model 3; suggesting also lack of mediation of eating behaviors on the effect of perceived stress on ACS (data not shown).
Of note, the inclusion of body mass index in the multivariate analysis was also tested (model 1), but no significant association regarding ACS incidence was found.
Perceived stress, ACS and the potential moderating role of dietary habits and behaviors
In order to examine the potential moderating role of the Mediterranean diet regarding the impact of perceived stress on the likelihood of ACS, the analysis was stratified by level of adherence to this pattern. ORs of PSS-14 between participants with low-to-moderate and those with moderate-to-high adherence were approximately equal (P=0.80), suggesting lack of moderating effect of this healthy dietary pattern on ACS (P for interaction=0.99) (Table 3).
Further analyses were focused on the effect of specific, stress-related eating behaviors. After the same adjustments as in model 3 were made, stress eating was positively associated with the likelihood of having an ACS (OR=1.31, 95% CI 0.97, 1.77); similarly, eating alone was significantly associated with the likelihood of having an ACS (OR=1.36, 95% CI=1.08, 1.69), whereas eating heavy meals was not associated with ACS likelihood (OR=1.08, 95% CI=0.82, 1.41). However, no significant interactions with eating heavy meals, stress eating, eating alone and PSS-14 were observed (all P-values>0.10), suggesting lack of moderation.
However, some interesting interactions were observed between eating habits and behaviors. Specifically, eating heavy meals was associated with a higher likelihood of having an ACS in non-alone eaters as compared with alone-eaters (OR for non-alone eaters 6.97, 95% CI=2.60, 18.64 and OR for alone-eaters 4.30, 95% CI=1.61, 11.46, P for interaction<0.001). The protective association of the Mediterranean diet was significant only in the non-alone eaters and was associated with a 72.8% lower likelihood of having a non-fatal ACS (OR=0.37, 95% CI=0.15, 0.92; P for interaction<0.001). Stress eating was positively associated with the likelihood of having an ACS only in the alone-eaters group (OR=5.12, 95% CI=1.83, 14.28; P for interaction<0.001).
In the present work, it was revealed that perceived stress has a highly significant, independent role on ACS development, whereas it was confirmed by the observation from several other studies that the Mediterranean diet was associated with a lower likelihood of having an ACS. However, no mediating or moderating role of Mediterranean diet on the relationship between perceived stress and ACS was verified. Furthermore, in the present work, the independent and the mediating/ moderating impact of specific eating behaviors on ACS was examined as well. Eating while being stressed and eating alone were independently associated with a greater likelihood of having an ACS, but, again, no mediation or moderation on the relationship between perceived stress and ACS was evident. The retrospective nature of the study does not allow the identification of causality; however, the aforementioned findings are of major importance as they constitute evidence for further research to elucidate the independent role, from dietary habits and behaviors, of perceived stress in CVD incidence.
It is believed that perceived stress may serve as one piece in the bigger picture of advancing mental health issues, such as depression or anxiety disorder. Indeed, stress is closely related to depression and anxiety. In particular, such disorders consist of more prominent psychological manifestations as a result of chronic perception of a stressful life, whereas perceived stress may serve as a more unique and global alternative, which applies to all individuals in life periods when depression and/or anxiety may or may not exist or are preparing to manifest.36 Thus, in this work, the nature of perceived stress as a CVD risk factor may not have permitted the extraction of a clear mediating and/or moderating role of the Mediterranean diet. Interestingly, except from a few previous studies that have addressed only the interaction between the Mediterranean dietary pattern and certain affective dispositions, there are no similar findings to compare.24
Apart from dietary habits, eating behaviors and their relation to CVD pathogenesis have recently gained interesting attention.37 Indeed, current findings suggest that behaviors such as eating while being stressed, eating with or without company or eating heavy meals may present novel CVD predictors as well. In fact, stress eating has been linked to increased visceral adiposity and the metabolic syndrome.38,39 Actually, eating while stressed appears to be linked to a non-homeostatic manner of eating that is characterized by overeating and over-indulgence of easily available foods and the energy consumed mostly ends up being stored mostly as fat, promoting in this way visceral adiposity and CVD pathogenesis.38, 39, 40, 41 On the other hand, eating heavy meals per se, either stressed or not, presents another eating behavior that seems to disrupt the body’s biochemical environment. In fact, large meals promote endothelial dysfunction.42,43 Undoubtedly, further research is needed to better clarify the proportion of responsibility attributable to such eating behaviors regarding CVD pathogenesis and incidence. Thus, besides the demonstrated, well-known cardioprotective role of the Mediterranean diet mainly due to its antioxidant and anti-inflammatory properties,14 the proposed adverse effect of several eating behaviors poses certain considerations regarding the biochemical conditions under which food is processed in the body. In other words, consuming a diet very closely placed to the Mediterranean one is certainly of great importance regarding CVD prevention, but the way this otherwise beneficial dietary pattern is consumed appears crucially important as well. Furthermore, when such eating behaviors are identified, the importance of conforming to the Mediterranean dietary principles shall be further emphasized.
When analyzing by stress-eating behaviors, no moderating effect on the relationship between perceived stress and likelihood of having an ACS was extracted. The latter underlines that perceived stress is highly associated with the likelihood of having an ACS, independently of eating behaviors, and implies that stress perception overcomes serious eating behaviors. It is of interest that the protective role of the Mediterranean diet disappeared in alone-eaters, a fact that may indicate that eating alone hinders the otherwise beneficial choice of eating according to this dietary prototype. Eating alone or with others consists of a certain circumstance in which food is consumed. It has been supported that individuals who manage mealtime structure and orchestrate family meals, a behavioral characteristic of competent eaters, have been characterized by greater adherence to the Mediterranean diet and a lower CVD risk.44 According to our analysis, when eating mostly with others (that is, family or friends), having a heavy meal appears as a more aggravating behavior regarding ACS likelihood compared with eating mostly by oneself. Furthermore, stress eating remained a significant predictor of the likelihood of having an ACS only in alone-eaters. Combining together, eating with others constitutes a moment of social exchange and communication, an affirmation and renewal of family, group or community identity,16 and this circumstance under which food is consumed may regulate a potential adverse effect of stress eating. Furthermore, it seems that individuals who mostly eat with others are characterized possibly by a more structured life than alone-eaters, the last being more prone to eating practices such as external eating or snacking that resemble the stress-eating motif.39 However, non-alone eaters appear to be more prone to the adverse effect of frequent heavy meals, and thus a greater emphasis on the highly protective Mediterranean diet is considered of great importance, given the much heavier impact of perceived stress found in this group as well.
The retrospective nature of the present study does not allow for causal inferences and predisposes to systematic selection and/or recall bias. To minimize selection bias, cases with a first ACS event only were enrolled. To minimize recall bias, accurate and detailed data from all participants during the first 3 days of hospitalization were obtained. Perceived stress was evaluated through a validated answer to the referent population’s questionnaire. However, although PSS-14 was used to evaluate levels of perceived stress in life before the event, data were obtained afterward, and this may lead to potential biases, although special attention was given to this issue while obtaining the data. In addition, measurements of psychological characteristics usually succumb to overreporting or underreporting and do not always resemble the accuracy of measuring specific psychological manifestations (that is, depression disorder subsets). Assessment of perceived stress in a hospital setting compared with a non-hospital setting presents a certain difference between patient and control group and cannot fit as matching criterion, although a special effort was made to neutralize any hospital or medical effect on the reported stress by the patients. Regarding dietary evaluation, an food-frequency questionnaire was administered and applied by trained dieticians through face-to-face interviews in an effort to reduce inaccuracies of dietary reporting. In addition, an effort was made to retrieve accurate information regarding patients' eating behaviors, participants’ medical records as well as of their relatives regarding the onset of CVD risk factors and smoking. Furthermore, data regarding financial and educational status were not obtained. Finally, the inclusion of patients and controls from only two regions may limit the generalization of the findings to the whole country. Nevertheless, it should be noted that Athens is the capital of Greece and Larissa is the metropolitan city in central Greece, and thus both represent a vast majority of the Greek urban and rural population.
The highly significant impact of perceived stress on ACS likelihood was not mediated or moderated by the level of adherence to the Mediterranean diet or other eating behaviors; underlying the strong effect of this psychological disorder on ACS. Greater adherence to the Mediterranean dietary principles, irrespective of an individual's perceived stressful experiences, deserves appropriate emphasis and may state another research hypothesis concerning the independent, of stressful behaviors, role of Mediterranean diet on CVD risk. Nevertheless, along with healthy eating, combined interventions under which behaviors such as eating while being stressed or eating heavy meals are prevented or ameliorated may well contribute to CVD prevention.
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We thank the field investigators of the study: Julia DeVita, Georgio Karayanni, Emmanuela Griva, Asimenia Kouroupi, Evaggelia Nanou, Konstantino Syriano, Dionysia Voutsa, and Nikolao Zaxaro.
The authors declare no conflict of interest.
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Katsarou, A., Triposkiadis, F., Skoularigis, J. et al. Evaluating the role of Mediterranean diet and eating behaviors on the likelihood of having a non-fatal acute coronary syndrome, under the context of stress perception: a case–control study. Eur J Clin Nutr 68, 1016–1021 (2014). https://doi.org/10.1038/ejcn.2014.74
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