Olive oil consumption and risk of non-fatal myocardial infarction in Italy

Michaela Bertuzzia, Alessandra Tavania, Eva Negria and Carlo La Vecchiaa,b

a Istituto di Ricerche Farmacologiche ‘Mario Negri’, Milano, Italy.
b Istituto di Statistica Medica e Biometria, Università degli Studi di Milano, Milano, Italy.

Sir—In a hospital-based case-control study conducted in Spain on 171 cases, Fernandez-Jarne et al.1 reported an inverse association between olive oil consumption and the risk of non-fatal acute myocardial infarction (AMI); the multivariate odds ratio (OR) was 0.18 for patients in the upper quintile of consumption, having a median intake of 54 g/day.

The issue is, however, still open to discussion. An inverse association between olive oil and coronary heart disease (CHD) has long been suggested on the basis of the lower incidence and mortality for the disease in Mediterranean countries.2 Moreover, olive oil intake has been related to a favourable coronary risk factor profile.3,4 However, an Italian case-control study,5 based on 287 women with non-fatal AMI, found an OR of 1.1 in the highest tertile of oil intake compared to the lowest one, and a Greek one,6 based on 329 patients with CHD, found no association of the disease with monounsaturated fat intake.

To provide further information on the issue, we analysed the relation between olive oil consumption and the risk of non-fatal AMI in a case-control study carried out in the greater Milan area, northern Italy, between 1995 and 1999.7 This study was based on a validated food frequency questionnaire (FFQ),8,9 including more detailed information than the previous Italian one, as well as data on physical activity and other risk factors for CHD. Cases were 507 patients (378 men, 129 women; median age 61, range 25–79 years) with non-fatal AMI, admitted to a network of general hospitals in the area. Controls were 478 patients, (297 men, 181 women; median age 59, range 25–79 years) from the same geographical areas, admitted to the same hospitals for a wide spectrum of acute conditions unrelated to known or potential AMI risk factors (34% traumas, 30% non-traumatic orthopaedic disorders, 14% acute surgical conditions, 22% miscellaneous other illnesses). Interviews were conducted in hospital using a structured questionnaire including information on socio-demographic factors, anthropometric variables, smoking, alcohol, a problem-oriented medical history, physical activity, and history of AMI in relatives. Information on diet referred to the previous 2 years and was based on an FFQ, including 78 foods or food groups, and additional questions to assess the type of fat for seasoning and cooking (olive oil, specific seed oils, butter, and margarine), a subjective score on the amount used, and habits of eating or leaving on the plate the seasoning or sauce; these questions, frequency of consumption and portion size were used to estimate the intake of lipids.10 The OR and the corresponding 95% CI, for subsequent quintiles of olive oil intake were derived using unconditional multiple logistic regression,11 including terms for age, sex, and selected confounding factors.

Compared to the lowest quintile of intake the multivariate OR for the subsequent quintiles were 0.90, 1.01, 0.86 and 1.48 (95% CI: 0.86–2.55) with no trend in risk with consumption (Table 1Go). Further adjustment for total vegetable intake did not materially modify the risk estimates. The FFQ was satisfactorily valid and reproducible,8,9,12 and the mean amount of olive oil consumed among patients was relatively high, being 35.6 g/day in the whole population and 74.2 g/day in the highest quintile of consumption. Cases and controls were interviewed in the same hospitals and came from the same geographical area, participation was almost complete, and patients admitted for chronic conditions or diseases related to known or potential risk factors for AMI were excluded from controls. It is unlikely that recall of olive oil intake was systematically different on the basis of the disease status, since the possibility of a relation between it and AMI was unknown to most subjects.


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Table 1 Distribution of 507 acute myocardial infarction (AMI) and 478 controls, and corresponding odds ratios (OR) with 95% CI, according to olive oil intake. Milan, Italy, 1995–1999
 
Thus, these data, based on a larger dataset than previously available studies and on a detailed and validated FFQ, do not support the existence of a strong relation between olive oil and risk of AMI.

Acknowledgments

Partly supported by ‘Ministero della Salute’ (Contract n. 177, RF 2001).

References

1 Fernández-Jarne E, Martínez-Losa E, Prado-Santamaría, Brugarolas-Brufau C, Serrano-Martínez M, Martínez-González MA. Risk of first non-fatal myocardial infarction negatively associated with olive oil consumption: a case-control study in Spain. Int J Epidemiol 2002;31:474–80.[Abstract/Free Full Text]

2 Menotti A, Keys A, Aravanis C et al. Seven Countries Study. First 20-year mortality data in 12 cohorts of six countries. Ann Med 1989;21:175–79.[ISI][Medline]

3 Trevisan M, Krogh V, Freudenheim J et al. Consumption of olive oil, butter, and vegetable oils and coronary heart disease risk factors. The Research Group ATS-RF2 of the Italian National Research Council. JAMA 1990;263:688–92.[Abstract]

4 Mensink RP, Katan MB. Effect of monounsaturated fatty acids versus complex carbohydrates on high-density lipoproteins in healthy men and women. Lancet 1987;i:122–25.

5 Gramenzi A, Gentile A, Fasoli M, Negri E, Parazzini F, La Vecchia C. Association between certain foods and risk of acute myocardial infarction in women. BMJ 1990;300:771–73.[ISI][Medline]

6 Tzonou A, Kalandidi A, Trichopoulou A et al. Diet and coronary heart disease: a case-control study in Athens, Greece. Epidemiology 1993;4:511–16.[ISI][Medline]

7 Tavani A, Pelucchi C, Negri E, Bertuzzi M, La Vecchia C. n-3 Polyunsaturated fatty acids, fish, and nonfatal acute myocardial infarction. Circulation 2001;104:2269–72.[Abstract/Free Full Text]

8 Franceschi S, Negri E, Salvini S et al. Reproducibility of an Italian food frequency questionnaire for cancer studies: results for specific food items. Eur J Cancer 1993;29A:2298–305.

9 Decarli A, Franceschi S, Ferraroni M et al. Validation of a food-frequency questionnaire to assess dietary intakes in cancer studies in Italy. Results for specific nutrients. Ann Epidemiol 1996;6:110–18.[CrossRef][ISI][Medline]

10 Braga C, La Vecchia C, Franceschi S et al. Olive oil, other seasoning fats, and the risk of colorectal carcinoma. Cancer 1998;82:448–53.[CrossRef][ISI][Medline]

11 Breslow NE, Day NE. Statistical Methods in Cancer Research. Vol. I. The Analysis of Case-control Studies. Lyon: IARC Sci Publ 1980;32.

12 Franceschi S, Barbone F, Negri E et al. Reproducibility of an Italian food frequency questionnaire for cancer studies. Results for specific nutrients. Ann Epidemiol 1995;5:69–75.[CrossRef][Medline]


 

Author’s response

Elena Fernández Jarne, Manuel Serrano-Martinez and Miguel A Martínez González

We have read with interest the letter by Bertuzzi et al. We agree that the role of olive oil in coronary heart disease (CHD) is open to discussion. In fact, in our conclusions we stated that further observational studies and trials are needed.1 In the introduction to our published article we acknowledged that ‘a case-control study in Italian women (287 cases/649 controls) reported no significant benefit for oil consumption (odds ratio = 0.7 for the second tertile and 1.1 for the third)2 and another case-control study in Greece did not find any significant protection from monounsaturated fatty acids (MUFA) intake’.3 The present letter by Bertuzzi et al. provides additional data showing no association in a different case-control study conducted in Italy. Interestingly, the study conducted by Bertuzzi et al. specifically assessed olive oil intake, and not only total oil or MUFA. All studies used hospitalized controls. In all studies the percentage of participation was almost complete. However, important differences exist among them. Table 1Go shows the main differences in the design of the four Mediterranean case-control studies. We acknowledge that we had a smaller sample size; but we used a matched design, thus increasing the efficiency of our study. A detailed examination of Table 1Go may give some clues about the sources of disagreement.


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Table 1 Mediterranean case-control studies of olive oil and coronary heart disease (CHD)
 
In first place, the exposure was not specifically olive oil in the two earlier studies. Although olive oil is usually the main source of MUFA in traditional Mediterranean diets, mechanistic reasons provide a stronger biological plausibility for a protection derived from olive oil than from all MUFA.4,5 However, discrepancy still persists between the results of Bertuzzi and our results.

A second important source of heterogeneity lies in the case definition and the eligibility criteria. In our case-control study, a previous history of angina pectoris, a previous diagnosis of CHD or other prior diagnosis of major cardiovascular disease were exclusion criteria. As Bertuzzi et al. report in their letter ‘an inverse association between olive oil and CHD has long been suggested’. This suggestion has been in large part also transferred to the general public, especially in Mediterranean countries, and it is likely that somebody who knows or suspects that he/she has had some previous manifestation of CHD may be motivated to increase the consumption of olive oil. This would lead to a bias with potential to underestimate the protection afforded by olive oil. Therefore, in the design of our study we took special care to avoid the inclusion of cases who had a previous history of cardiovascular disease. Trained physicians examined each potential participant to exclude such cases. This bias could explain why our study is the only one to detect the protective role of olive oil, because other studies did not take into account this important exclusion.

We observed that the protective role of olive oil was more clearly apparent when we adjusted the estimates for total energy intake using the residuals method. A shorter food frequency questionnaire or the use of foreign tables for food composition would introduce misclassification in total energy intake and this may interfere with the procedures of adjustment for total energy. Misclassification, which is pervasive in nutritional epidemiology, is a very likely explanation for finding no association when this association in fact exists.

The Italian studies were conducted in a network of hospitals. A related caveat is the heterogeneity among centres. In our study, conducted in three hospitals, the hospital was one of the matching variables and we adjusted the estimates for hospital using conditional logistic regression.

In summary, strong mechanistic reasons are available to support the benefit derived from olive oil consumption,4,5 and some reasons might still explain the discrepant findings in the available case-control studies. More importantly, further prospective studies and trials conducted in Mediterranean countries are needed to more clearly elucidate this association.

References

1 Fernández-Jarne E, Martínez-Losa E, Prado-Santamaria M, Brugarolas-Brufau C, Serrano-Martínez M, Martínez-González MA. Risk of first not-fatal myocardial infarction negatively associated with olive oil consumption: a case-control study in Spain. Int J Epidemiol 2002;31:474–80.[Abstract/Free Full Text]

2 Gramenzi A, Gentile A, Fasoli M, Negri E, Parazzini F, La Vecchia C. Association between certain foods and risk of acute myocardial infarction in women. BMJ 1990;300:771–73.[ISI][Medline]

3 Tzonou a, Kalandidi A, Trichopoulou A et al. Diet and coronary heart disease: A case-control study in Athens, Greece. Epidemiology 1993;4:511–16.[ISI][Medline]

4 Pérez-Jimenez F, López-Miranda J, Mata P. Protective effect of dietary monounsaturated fat on arteriosclerosis: beyond cholesterol. Atherosclerosis 2002;163:385–98.[CrossRef][ISI][Medline]

5 Fito M, Covas MI, Lamuela-Raventós RM et al. Protective effect of olive oil and its phenolic compounds against low density lipoprotein oxidation. Lipids 200;35:633–38.[ISI][Medline]