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Role of fibre and fruit in the Mediterranean diet to protect against myocardial infarction: a case–control study in Spain


Objective: To assess the association between a first acute myocardial infarction and the consumption of fibre and fruit.

Design: Hospital-based case–control study with incident cases. A validated semi-quantitative food frequency questionnaire (136 items) was used to assess food intake.

Setting: Three third-level university hospitals in Pamplona (Spain).

Subjects: Cases were subjects aged under 80, newly diagnosed with acute myocardial infarction. Each case patient (n=171) was matched to a control subject of the same gender and age (5 y bands) admitted to the same hospital.

Results: An inverse association was apparent for the three upper quintiles of fibre intake. After adjustment for non-dietary and dietary confounders, an inverse linear trend was clearly significant, showing the highest relative reduction of risk (86%) for the fifth quintile (OR=0.14, 95% confidence interval: 0.03–0.67). An inverse association was also apparent for fruit intake, but not for vegetables or legumes.

Conclusions: Our data suggest that a substantial part of the postulated benefits of the Mediterranean diet on coronary risk might be attributed to a high intake of fibre and fruit.

Sponsorship: Partially funded by the National Department of Health (FIS 01/0619) and Navarre Regional Government (Project 24/99) and by another grant from Banco Santander-Central-Hispano.


The Mediterranean diet has been postulated many times as a healthful and palatable alternative to reduce cardiovascular risk (Kris-Etherton et al, 2001; Willett et al, 1995). Nevertheless, it is difficult to understand why epidemiologic studies about the nutritional determinants of coronary heart disease (CHD) have seldom been carried out in Mediterranean countries. A Mediterranean dietary pattern is uncommon in US and northern European populations, where, although increasing, olive consumption is still low, and the main source of monounsaturated fatty acids (MUFA) is red meat; the main source of ethanol intake is beer and liquors, instead of wine; and the main sources of some micronutrients are vitamin supplements instead of natural fresh fruit and vegetables. Conversely, the Spanish population is known to have a very high intake of fibre and fresh fruit. In the more recent available comparable data of food consumption in six European countries (Greece, Ireland, Luxembourg, Norway, Spain and UK participating in the DAFNE-II Project), Spain was the member state with the highest availability of fruit (307 g/person/day), the highest availability of legumes (18 g/person/day) and was second only to Greece in availability of fresh vegetables (155 g/person/day; Trichopoulou & Breslin, 1998; Naska et al, 2000).

The sharp contrast in dietary habits between northern Europe (or US) and Spain provides an exceptional opportunity to assess the aspects of the Mediterranean diet that may be protective. This opportunity exists because some associations may be apparent if some of the effects associated with the intake of a particular nutrient are manifested only at the higher levels or the lower levels of intake that exist in other populations, comparatively with the intakes in the countries where most research in nutritional epidemiology has been conducted. An analytical epidemiological study in a country with a high dietary fruit and fibre intake, such as Spain (Serra-Majem et al, 1995; Beer-Borst et al, 2000; De Irala-Estévez et al, 2000, Naska et al, 2000) can be the ideal setting to discern the different roles of fibre, fruit and vegetables in the genesis of CHD, and more specifically, of non-fatal acute myocardial infarction (AMI).

The aims of our study were to estimate the quantitative dose—response relationships between several dietary exposures typical of the Mediterranean diet and the risk of CHD. Specifically, we assessed the potential protective role of total fibre intake, and also of some food items with high fibre content (fruit, vegetables, legumes and cereals) on the risk of a first non-fatal AMI.


A hospital-based matched case–control study was conducted in Pamplona (Spain). Cases were male or female subjects, aged under 80, with first AMI (International Classification of Disease (ICD) code 410) who were admitted to one of the three third-level university hospitals of Pamplona during the periods October 1999 to June 2000 or October 2000 to February 2001. The criteria (WHO MONICA Project, 1990) for definitive AMI of the MONICA project were required for a patient to be included as case (two or more ECGs showing definitive changes; ECGs showing probable changes plus abnormal cardiac enzymes; or typical symptoms plus abnormal enzymes). Exclusion criteria were: a previous history of angina pectoris; a previous diagnosis of CHD; or other prior diagnosis of major cardiovascular disease. We identified 180 eligible cases. Nine of them refused to participate (participation=95%).

A control subject of the same age (5 y bands), gender and admitted in the same hospital was matched to each case. Eligible controls were patients admitted to wards of Surgery, Trauma or Urology of the same hospital during the same month that matched cases for diseases believed to be unrelated to diet. The exclusion criteria were the same as those used for cases. We selected controls using a variety of diagnoses to have the advantage of diluting the potential biasing effects of including a specific diagnostic group that might be related to the main exposures (Rothman & Greenland, 1998). The most frequent diagnoses were injury (21.1%), osteoarthritis (12.9%) and benign prostatic hyperplasia (7.6%). Eight eligible controls refused to participate (participation=96%) and each of them was replaced by other patients of similar characteristics for matching variables.

Most cases (166/171) were interviewed in the cardiology ward once they had been discharged from the coronary unit. Three of them were interviewed in the Coronary Care Unit and two of them were interviewed at their homes after discharge from the hospital. The average time from AMI onset to study interview was 7 days (range 2–60 days). All control subjects were interviewed in hospital wards, except one who was interviewed at home. Informed consent was obtained both from patients and control subjects. The project was approved by the Institutional Review Board of the Medical School.

Interviews were conducted in a standard way with the same questionnaire for patients (cases) and control subjects. Four physicians belonging to the research team (EFJ, EML, MP, CB) interviewed the participants. The same physician who interviewed a case patient also interviewed the respective matched control. The physician approached the patients, invited them to participate, requesting their informed consent, and provided them with the self-administered questionnaire. Five cases did not personally answer the questionnaire, and we used the answers given by a relative. We used the same procedure for matched controls.

A semi-quantitative food-frequency questionnaire (118 food items) previously validated in Spain (Martin-Moreno et al, 1993) and slightly expanded for this study (136 items plus vitamin supplements) was used to assess dietary exposures. For each food item, a commonly used portion size was specified, and participants were asked how often they had consumed that unit on average over the previous year. Emphasis was added to ensure that the answers were related to long-term dietary exposures and not to recent changes in diet. Nine options for frequency of consumption were offered. A dietician updated the nutrient databank using the latest available information included in the food composition tables for Spain. Total energy-adjusted intakes were computed using the residuals method (Willett & Stampfer, 1998).

We calculated for each participant an activity metabolic equivalent (MET) index to quantify his/her volume and intensity of leisure-time physical activity. We assessed the participation and time spent in a typical week in each of the following activities: walking, jogging, running, athletics, cycling, swimming, racquet sports, soccer, team-sports other than soccer, dancing, aerobics, hill-walking, climbing, gardening, skiing, skating, fishing, martial arts and water sports. We assigned a multiple of resting metabolic rate (MET score) to each of these activities using previously published guidelines to quantify the average intensity of physical activities (Ainsworth et al, 1993). To appraise both the amount and relative intensity of physical exercise during a week for each participant, the MET index of each activity was multiplied by the weekly time spent in each activity obtaining a value of overall weekly MET-hours.

After each participant completed the self-administered part of the questionnaire, the physician clarified any questions the patient may have had in completing it, and subsequently conducted a face-to-face interview about major coronary risk factors (smoking, diabetes, high blood pressure, high blood cholesterol, recent weight changes) and family history of cardiovascular disease. The physician took systolic and fifth-phase diastolic blood pressure readings and measured weight and height according to a standardised protocol, with the subject barefoot and dressed in light clothing. For each participant we calculated the body mass index (BMI) as the weight in kilograms divided by the squared height in metres (kg/m2).

Quintiles of fibre intake defined according to the distribution among controls were compared regarding several potential confounding variables. For this comparison we merged the three intermediate quintiles (quintile 2 to quintile 4) in a single category.

A stepwise multiple regression analysis was used to assess the proportion of variability in total dietary fibre intake explained by each of the major sources of fibre (vegetables, fruit, cereals and legumes).

The association of fibre intake with myocardial infarction was calculated with conditional logistic regression modelling using matched data of 171 case–control pairs, thus controlling for gender, age, hospital and interviewer. Firstly, we introduced quintiles of total fibre (adjusted for total energy intake) as the independent variable using four indicator variables, one for each of the four upper quintiles (first quintile as the reference). Then, we also adjusted for several potential confounders introducing them as independent terms in conditional logistic multivariable models. Firstly, we introduced non-dietary confounders. In a second step we also added major dietary confounders (percentage of energy from ethanol, percentage of energy from saturated fat, and from unsaturated trans-fatty acids, folic acid intake, energy-adjusted glycemic load, energy-adjusted olive oil intake).

We also used the same procedures to estimate the quantitative dose–response relationships between each group of food items with a high fibre content (fruit, vegetables, legumes, cereals) and AMI. All variables estimating food items or nutrient intakes were adjusted for total energy, using the residuals method (Willett & Stampfer, 1998).

Quadratic terms for some confounders (BMI, METs-h/week) were used to account for non-linear relationships. We selected confounders by taking into account previous published literature about coronary risk factors and avoided the reliance on P-values or stepwise approaches. Tests for trend were done using the median of each quintile as a continuous variable. Reported P-values are two-tailed; values <0.05 were considered significant.


Mean age of patients with AMI and control subjects was 61.7 and 61.4 y, respectively. Eighty-one percent of participants were male. Most participants belonged to primary (44%) or less than primary (28%) educational level. The distribution of major socio-demographic characteristics and cardiovascular risk factors of cases and controls is shown in Table 1.

Table 1 Characteristics of case and control participants

The median (percentile 25–75) energy-adjusted intake of fibre was 29.4 g/day (23.9–36.4 g/day). Major sources of fibre intake were fibre from vegetables (median, 10.1; percentile 25–75, 7.3–13.6 g/day), fibre from fruit (5.0, 3.1–8.5 g/day), fibre from cereals (4.8, 3.6–7.7 g/day) and fibre from legumes (3.7, 2.7–4.7 g/day).

Table 2 shows the distribution of potential confounding variables among control subjects. Control subjects with the highest fibre intake were less likely to have a white collar job or to be married. They were more likely to have a history of high-blood cholesterol or a diagnosis of diabetes, but less likely to be current smokers. BMI, glycemic load and folic acid intake were positively associated with fibre intake, whereas leisure-time physical activity (METS-h/week), olive oil consumption, alcohol intake and saturated fat intake were inversely associated with fibre intake.

Table 2 Distribution of potential confounding variables across quintiles of energy-adjusted dietary total fibre intake among control subjects (n=171)

As expected, the consumption of fibre-rich products increased across quintiles of fibre intake. Nevertheless, this trend was not so clear with cereals consumption. In a stepwise multiple regression analysis, fibre from vegetables explained most of the variability (61%) in total fibre intake. The second variable selected by the stepwise procedure was fibre from fruit, which together with fibre from vegetables explained 80% of the variability in fibre intake.

An inverse association with AMI was apparent for the three upper quintiles of fibre intake (Table 3). When we only took into account gender, age and hospital using matched analysis to adjust for confounding, the three upper quintiles (Q3–Q5) of fibre intake exhibited virtually the same odds ratio (OR; equivalent to a 60–54% relative reduction in risk) with respect to the first quintile. This pattern suggested that a threshold effect instead of a linear trend existed. After adjustment for non-dietary and dietary confounders, an inverse linear trend was significant, showing the highest relative reduction of risk (86%) for the fifth quintile (OR=0.14, 95% confidence interval 0.03–0.67 in the fully adjusted model). Nevertheless, in spite of the statistical significance of the test for trend (P=0.01), the magnitude of the ORs was substantially similar for the three upper quintiles (Q3–Q5) and the dose–response could also be compatible with an L-shaped pattern.

Table 3 Odds ratios (OR) and 95% confidence intervals of a first myocardial infarction according to quintiles of energy-adjusted total fibre intake

When we assessed the quantitative dose–response relationships between fibre-rich food items and AMI, we found inverse associations for overall fruit, vegetables and legumes in almost all quintiles. However, after adjustment for non-dietary confounders, the inverse association was only apparent for fruit intake. Although there was no linear trend across the five quintiles of fruit consumption (Table 4), when the three upper fruit quintiles were merged, a strong and statistically significant inverse association between fruit consumption and AMI was found (OR=0.25, 95% confidence interval 0.08–0.74). On the other hand, we found higher risk with higher intake of cereals. Moreover, the linear trend test was statistically significant for the direct association between the group of cereals and AMI risk when non-dietary confounders were taken into account (Table 4). However, the statistical significance was lost when we also adjusted for dietary confounders.

Table 4 Odds ratios (OR) and 95% confidence intervals of a first myocardial infarction according to quintiles of fruit consumption, consumption of vegetables, consumption of cereals and consumption of legumes. All nutrients and food items were analyzed after they were adjusted for total energy intake (residuals method)


In this hospital-based case–control study assessing the risk of a first non-fatal AMI in a Mediterranean population with a very high fibre intake and exposed to a very high consumption of fruit, we found strong inverse associations of both dietary fibre intake and fruit consumption with the risk of AMI. A linear trend was apparent for fibre intake whereas an uniform pattern of risk reduction beyond the second quintile (>250 g/day) was observed for fruit intake, suggesting that a threshold effect may exist, ie suboptimal consumption of fruit was associated with a substantially increased risk.

There is enough evidence supported by ample epidemiologic data indicating that the intake of dietary fibre is inversely associated to risk for coronary artery disease (Pietinen et al, 1996; Law & Morris, 1998; Kushi et al, 1999; Wolk et al, 1999; Todd et al, 1999). However, the epidemiological evidence about the protective role of fibre intake against CHD obtained in Mediterranean countries is sparse. The degree of between-subjects variability in the intake of a particular nutrient or food item in the population under study is a strong determinant of the ability of a study to detect an association between that nutrient and CHD. The higher the level of consumption of a food item, the higher is its between-subjects variability. It is possible that the high between-subjects variability in the levels of fibre and fruit intake in our sample may have allowed us to show more clearly the protection provided by very high intakes of dietary fibre. In this context, an analytical design in Mediterranean areas where fibre intake is substantially higher than in northern Europe or USA can be very helpful to extrapolate the potential benefits to other countries (Kouris-Blazos et al, 1999; Kris-Etherton et al, 2001). However, no previous epidemiological study from Mediterranean areas was included in the meta-analysis by Law and Morris (1998) or in the review by Kushi et al (1999). Moreover, the best designed studies conducted in Mediterranean areas were negative (Tzounou et al, 1993) or did not specifically assess the protective role for dietary fibre (Fortes et al, 2000; Trichopoulou et al, 1995).

Populations in Mediterranean countries where traditional diets consisted largely of foods of plant origin exhibit low rates of ischaemic heart disease and long life expectancies. However, international comparisons and ecological studies have customarily been the main basis for attributing such large benefits to a Mediterranean dietary pattern (Kushi et al, 1995). Our study adds some evidence at the individual level to support the protective role of two of the main elements of the traditional Mediterranean diet.

Our findings are based on a case–control design and several threats to validity must be considered. In the first place, an alternative explanation to attributing a causal protection to fibre and fruit is that participation of control subjects may be selective, including preferentially as controls those who have a healthier diet. Our very high rate of participation among controls (96%) makes this potential bias unlikely in our study. Secondly, misclassification of exposure is a major issue in nutritional epidemiology. If the experience of suffering a myocardial infarction were a stimulus for case subjects to better recall or overestimate their intake of a particular nutrient, a biased assessment of the effect of that nutrient due to differential misclassification would be expected. Nevertheless, this bias would be more likely to occur with widely known harmful exposures such as saturated fat intake or consumption of red-meat, but it is not so likely to happen with protective factors and even less likely with nutrients not so strongly perceived to be positively or negatively associated with risk by the general public. The previously shown validity of the food-frequency questionnaire (Martin-Moreno et al, 1993) provides additional reassurance about appropriate classification of exposure. Only very seldom, has the information about nutritional exposures in case–control studies of diet and infarction been collected by trained physicians who assisted the participants in completing the food-frequency questionnaire and were available to solve the possible doubts of participants and were likely to be perceived by the patients as more reliable than other possible interviewers. In addition, we matched the interviewers of cases and controls. The physicians conducted the interviews with matched controls as soon as possible after conducting the interview with the respective case. In addition, all interviewers met every 2 weeks with the rest of the research team to keep homogenous criteria in the procedures for performing the interview and administering the questionnaires.

A third caveat is that participants may have increased their intake of fibre or fruit because they perceived themselves to be at elevated risk of myocardial infarction. This possibility is consistent with the higher proportion of diabetics and of individuals with high cholesterol levels we have found in the highest level of fibre intake among controls. This tendency would lead to confounding. The statistical adjustment we have performed to take into account known coronary risk factors may have controlled, at least partially, this bias. In addition, the likely direction of this bias is toward an underestimation of the magnitude of the true protective effect of fibre and fruit. Therefore, had residual confounding occurred, the inverse association with myocardial infarction risk for fibre and fruit would be even more important than that reported here. We adjusted our estimates for a wide array of dietary and non-dietary coronary risk factors that may act as potential confounders. For example, a unique characteristic of our study among other previously published case–control designs is that the glycaemic index was calculated and we controlled for it in the analyses. This adjustment has not been used in earlier studies, because it is a very recently identified risk factor (Liu et al, 2000a).

In spite of all these procedures to ensure a high-quality design, unknown risk factors inversely associated with higher consumption of fruit or higher fibre intake could alternatively explain the reduction in the risk of myocardial infarction. Nevertheless, this unknown factors would need to have an incredibly strong association with both exposure and disease to explain such a high magnitude as that observed for the inverse association with myocardial infarction.

Although the available evidence in Mediterranean countries is sparse, a recent case–control study (100 cases and 198 unmatched controls) conducted in Portugal found, consistently with our results, a relative risk of 0.3 (95% Cl 0.1–0.9) for the fourth quartile of fibre intake (Lopes et al, 1998). Our findings, together with this Portuguese study (Lopes et al, 1998) may help to explain the advantages of the Mediterranean diet and the lower mortality by CHD in Mediterranean populations. Although the nutritional factors associated with primary and secondary prevention of CHD need not to be the same, our results are also consistent with a randomised trial conducted in France (De Lorgeril et al, 1999), which showed a strong protection associated with an experimental Mediterranean diet on the risk of death and re-infarction among survivors of a first AMI. Nevertheless, as the major element of the assigned diet in the Lyon study was an experimental canola oil-based margarine and the diet simultaneously included a high intake of alpha-linolenic acid, fruit and vegetables, it was not possible to attribute its benefit to fibre, fruit or any other single factor. Moreover, some methodological concerns have been raised on the Lyon Trial raising the need to corroborate its findings (Kris-Etherton et al, 2001).

Dietary fibre has previously been shown to be inversely associated to the risk of coronary disease in many observational studies (Law & Morris, 1998; Kushi et al, 1999; Wolk et al, 1999). In some early studies the inverse relationship between fibre and CHD was entirely explained by cereal fibre (Rimm et al, 1996) or nuts (Fraser et al, 1992), rather than by fibre from fruits. In the Health Professionals Follow-up Study (Rimm et al, 1996) fibre from grain, vegetables and fruit sources each contributed to the lower risk of CHD, suggesting fibre per se may be beneficial, although fibre from cereal presented a stronger inverse association. It is not surprising to find the opposite trend for cereals in our study because in the Health Professionals Follow-up Study the intake of cold breakfast cereals was a major contributor to total dietary fibre intake, whereas the exposure to this food item was negligible in our population. Moreover, there is substantial epidemiologic evidence that whole grains are associated with decreased risk of coronary artery disease (Jacobs et al, 1998; Liu et al, 1999), but the main source of cereals in our population was white bread and almost no consumption of whole-grain bread was observed among the participants in our study. On the other hand, in Mediterranean countries, especially in Spain, fruit consumption is extremely high and accounts for a high proportion of fibre intake. It is interesting to compare the median of fruit consumption of our study (303 g/day) with the mean estimated for the average American (0.7 servings/day, approximately 100 g/day (Liu et al, 2000b)). In our study, the median number of servings/day of fruit among controls was 1.92.

The pattern of eating almost exclusively fruit as the dessert after the main meals may explain the high consumption observed in Spain and may have some interesting benefits, such as replacing alternative foods rich in saturated fat (ice-creams, cakes, cookies), easily maintaining a high level of fruit consumption and consequently a high level of intake of a variety of phytosterols, tocotrienols and antioxidant vitamins that may grant additional benefit. Moreover, interactions of the nutrients contained in fruits with other previously eaten nutrients may also offer further protection (Fraser, 1994). Although this sort of biologic interaction has been only shown in models of colon cancer (Rijnkels et al, 1997), other animal models lead us to think that they might exist also for lipid peroxidation, plaque development and coronary thrombosis (Singh et al, 1995).

The protective role of fruit in the Mediterranean diet is consistent with the results found for some fruits regarding overall survival in a small cohort of elderly Italians (Fortes et al, 2000). The threshold pattern (no linear trend but a very great magnitude of risk reduction beyond 250 g/day) is also consistent with the recently published findings of the Women's Health Study (Liu et al, 2000b) that reported a similar or even slightly lower relative risk for the third quintile (RR=0.58) of fruit consumption than for the fifth quintile (RR=0.66). As we have found in our data, these authors also reported a stronger protective effect for fruit than for vegetables (Liu et al, 2000b). Information about particular types of fruit which can offer a stronger protection would be very interesting because our results suggest that other factors different to fibre which are also present in these products could be partially responsible for the further protection against AMI offered by fruit.

The American Heart Association have very recently issued a scientific recommendation supporting that a Mediterranean-style diet demonstrates impressive effects on secondary prevention of coronary heart disease (Kris-Etherton et al, 2001). Our results are encouraging because they provide a further corroboration of the very high protection for the primary prevention of myocardial infarction which can be derived from a high fibre and fruit intake.


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We are specially indebted to Ms Carmen de la Fuente, our dietitian, who updated the food composition databank according to current Spanish food composition tables and worked in the calculation of nutrients taken into account as potential confounders in our analyses. We thank the following persons for technical assistance and support: Professor Jokin De Irala-Estévez, Professor J Alfredo Martínez, Dr Isabel Coma MD, Dr Almudena Sánchez-Villegas, Ms Jane Hoashi and Ms Estefanía Ruiz-Gaona. We thank the Cardiology Chairmen of the three hospitals that participated in this study: Hospital de Navarra (Dr Enrique de los Arcos, MD), Hospital Virgen del Camino (Dr Eugenio Torrano, MD), and University Clinic of Navarre (Dr Joaquin Barba, MD).

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Correspondence to MA Martínez-González.

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Martínez-González, M., Fernández-Jarne, E., Martínez-Losa, E. et al. Role of fibre and fruit in the Mediterranean diet to protect against myocardial infarction: a case–control study in Spain. Eur J Clin Nutr 56, 715–722 (2002).

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  • coronary heart disease
  • case–control studies
  • nutritional epidemiology
  • conditional logistic regression
  • plant foods

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