Meat Science 108 (2015) 32–36
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Meat Science journal homepage: www.elsevier.com/locate/meatsci
Review
Red meat consumption and ischemic heart disease. A systematic literature review Giuseppe Lippi a, Camilla Mattiuzzi b, Fabian Sanchis Gomar c,⁎ a b c
Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy Service of Clinical Governance, General Hospital of Trento, Trento, Italy Research Institute of Hospital 12 de Octubre (“i+12”), Madrid, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 20 March 2015 Received in revised form 17 May 2015 Accepted 19 May 2015 Available online 22 May 2015
Several lines of evidence attest that diet may strongly influence the cardiovascular risk. We performed an electronic search in Medline (with PubMed interface), Scopus and ISI Web of Science, to identify epidemiological studies on the association between red meat intake and the overall risk of ischemic heart disease (IHD). Eleven studies (8 prospective and 3 case–control) were finally selected for this systematic literature review. Although a larger intake of red meat was found to be a significant risk factor for IHD in four studies (2 prospective and 2 case–control), no significant association was found in five other trials (4 prospective and 1 case–control). We suggest that future diet recommendations for prevention of cardiovascular disease should take into account that the current literature data does not support the existence of a clear relationship between large intake of red meat and increased risk of myocardial ischemia. © 2015 Elsevier Ltd. All rights reserved.
Keywords: Diet Fatty acid Cholesterol Cardiovascular disease Mortality
Contents 1. Introduction . 2. Methods . . . 3. Results . . . 4. Discussion . . Conflicts of interests References . . . .
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1. Introduction Several lines of evidence now attest that diet may strongly influence the cardiovascular risk (Parikh et al., 2005). Among the various nutrients, meat plays a substantial role in human's diet, since it is an important source of proteins, essential amino acids, vitamins, minerals and other micronutrients (Lafarga & Hayes, 2014), despite the fact that fat and fatty acid composition of red meat may be involved in enhancing the risk of cardiovascular disease (CVD) (McAfee et al., 2010). Conventionally, the term “red” is used to define a type of meat characterized by a red hue and which does not turn to white when cooked. The global market of red meat is as high as 184 million tonnes per year, thus largely exceeding that of poultry (109 million tonnes per year) and ovine products ⁎ Corresponding author at: Research Institute of Hospital 12 de Octubre (‘i+12’), Avda. de Córdoba s/n, 28041 Madrid, Spain. E-mail address: [email protected] (F.S. Gomar).
http://dx.doi.org/10.1016/j.meatsci.2015.05.019 0309-1740/© 2015 Elsevier Ltd. All rights reserved.
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(14 million tonnes per year) (Food Agriculture & Organization of the United Nations, 2014). Such a large consumption of red meat, especially in high-income countries, has recently emerged as a public health care concern due to the potential association between red meat consumption and a number of human disorders, including diabetes and cancer (Walker, Rhubart-Berg, McKenzie, Kelling, & Lawrence, 2005). As regards CVD, the American Heart Association (AHA) has released specific recommendations aimed to reduce the risk of developing cardiovascular disorders, including statements that consumption of lean meats should be preferred over that of fat meat, the intake of processed meats high in saturated fat and sodium should be limited, and meat should be preferably consumed after grilling, baking or broiling (Lichtenstein et al., 2006). However, whether or not red met intake would represent a risk factor for CVD remains a matter of debate. A recent prospective cohort analyses including 11,116 subjects aged 18–75 years old and followed up for an average period of 6.6 years (Chen et al., 2013) concluded that a diet enriched in animal proteins may slightly increase the risk of heart
G. Lippi et al. / Meat Science 108 (2015) 32–36
disease mortality, especially among smokers (hazard ratio [HR], 1.20; 1.00–1.45). Interestingly, in another recent prospective study, including 448,568 subjects aged 35–69 years who were followed up for a median period of 12.7 years (Rohrmann et al., 2013), no association was found between larger consumption of total red meat and all-cause death (HR, 1.02; 95% CI, 0.98–1.06). Nevertheless, when the analysis was limited to subjects who died for CVD, a marginally significant association was found with total red meat intake (HR, 1.09; 95% CI, 1.00–1.18), especially with larger intake of processed meat (HR, 1.30; 95% CI, 1.17–1.45). At variance with this evidence, Whiteman et al. followed up for 9 years 10,522 subjects aged 35–64 years (5593 women and 4929 men) (Whiteman, Muir, Jones, Murphy, & Key, 1999), and found an inverse association between intake of fresh or frozen meat and mortality for CVD (relative risk [RR]; 0.71; 95% CI. 0.55–0.92). The controversial evidence on red meat intake and cardiovascular mortality persuaded us to carry out a systematic literature review in order to establish whether or not red meat intake represents an additional risk factor for ischemic heart disease (IHD). 2. Methods We performed an electronic search in Medline (with PubMed interface), Scopus and ISI Web of Science using the keywords “red” AND “meat” AND “coronary artery disease” OR “coronary heart disease” OR “acute coronary syndrome” OR “ischemic heart disease” OR “myocardial infarction” in “Title/Abstract/Keywords” and with no language or date restriction, to identify epidemiological studies on the association between red meat intake and the overall risk of IHD (i.e., fatal and non-fatal cases). The documents that could be identified were systematically reviewed by two authors (G.L. and C.M.) and the references were also hand-searched to identify other pertinent items. 3. Results A total number of 53 documents could be identified after elimination of replicates among the three scientific databases and 3 additional studies could be detected from the relative references. Forty five items were excluded after accurate reading of title, abstract or full text (see Fig. 1). Therefore, 11 studies (8 prospective and 3 case–control)
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were finally selected for this systematic literature review (Table 1) (Ascherio, Willett, Rimm, Giovannucci, & Stampfer, 1994; Bernstein et al., 2010; Burke et al., 2007; Hu et al., 1999; Kabagambe, Baylin, Siles, & Campos, 2003; Kontogianni, Panagiotakos, Pitsavos, Chrysohoou, & Stefanadis, 2008; Nagao, Iso, Yamagishi, Date, & Tamakoshi, 2012; Oliveira, Lopes, & Rodriguez-Artalejo, 2010; Qi, van Dam, Rexrode, & Hu, 2007; Takata et al., 2013; Whiteman et al., 1999). Inter-rater agreement was 96% (kappa statistics, 0.90; p b 0.001). The different types of meat and the diagnostic criteria for IHD used in the single studies are provided in Table 2. The first study that investigated the relationship between IHD and red meat consumption was published by Ascherio et al. (1994). The authors conducted a large prospective study, including 44,933 men with no previous history of CVD, who were followed up for 4 years. A total number of 844 incident cases of coronary artery disease (CAD) (249 nonfatal myocardial infarctions, 137 coronary disease fatalities and 458 bypass operations or angioplasties) were recorded on follow-up (rate of incident CAD: 1.9%). A slightly higher but non-significant risk of CAD was found in men consuming red meat (prevalently beef) ≥ 4 times per week compared to those reporting intake of ≤ 1 per month (RR, 1.38; 95% CI, 0.77–2.29). Interestingly, a slight but non-significant risk of CAD was also observed in subjects in the highest quintile of beef, chicken, liver and other processed meat consumption (RR, 1.18; 95% CI, 0.78–1.80). In a following prospective study, 80,082 women were followed up for 14 years (Hu et al., 1999). A total number of 939 incident cases of major CAD events were recorded during follow-up (rate of incident CAD: 1.2%). In the fully-adjusted multivariate model, no association was found between larger consumption of red meat and higher risk of CAD (RR of increment of 1 serving per day, 1.09; 95% CI, 0.91–1.30; p = 0.35 for trend). Whiteman et al. (1999) performed a prospective study including 10,522 subjects, who were followed up for 9 years. Overall, 144,939 incident cases of IHD were recorded during follow-up (rate of incident IHD: 1.4%). An inverse association was found between intake of fresh or frozen red meat and mortality for IHD (RR, 0.55; 95% CI, 0.31–0.99). Kabagambe et al. (2003) performed a case–control study, including 485 survivors of a first acute myocardial infarction (AMI) who were matched for age, gender and area of residence with 508 healthy
Fig. 1. Description of the search methodology.
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G. Lippi et al. / Meat Science 108 (2015) 32–36
Table 1 Description of prospective and case–control studies investigating the association between red meat intake and ischemic heart disease. Authors
Setting
Study design Study population
Ascherio et al. (1994)
USA
Prospective
44,933 men aged 40 Incident CAD to 75 followed up for (rate: 1.9%) 4 years
Hu et al. (1999)
USA
Prospective
80,082 women aged 34–59 years followed up for 14 years
Incident coronary heart disease (rate: 1.2%)
Whiteman et al. (1999)
USA
Prospective
10,522 subjects aged 35–64 years followed up for 9 years
Kabagambe et al. (2003)
Costa-Rica Case–control 485 patients with acute myocardial infarction and 508 matched healthy controls
Incident ischemic heart disease mortality (rate: 1.4%) Prevalence of acute myocardial infarction
Burke et al. (2007)
Australia
Prospective
514 subjects followed Incident coronary up for 14 years heart disease (rate: 25%)
Qi et al. (2007)
USA
Prospective
6161 women with diagnosis of type 2 diabetes at 30 years of age, followed up for 20 years
Kontogianni Greece et al. (2008)
Case–control 848 patients with acute coronary syndrome and 1078 matched healthy controls Case–control 820 patients with acute myocardial infarction and 2196 matched healthy controls
Oliveira et al. (2010)
Portugal
Bernstein et al. (2010)
USA
Prospective
84,136 women aged 30 to 55 years followed up for 26 years
Nagao et al. (2012)
Japan
Prospective
51,683 subjects followed up for 18.4 years
Takata et al. China (2013)
Prospective
136,424 subjects aged 40 to 70 years followed up for 5.5–11.2 years
Endpoint
Incident coronary heart disease (rate: 8.9%)
Prevalence of acute coronary syndrome
Adjustment
Results
Age, body mass, smoking habits, alcohol consumption, hypertension, diabetes, hypercholesterolemia, family history of CAD, profession, total energy, vitamin E, total iron, heme iron Age, body mass, cigarette smoking, menopausal status, history of CAD, vitamin E supplement use, alcohol consumption, hypertension, aspirin use vigorous exercise Age, sex, smoking habits
No significant higher risk of CAD with larger red meat consumption (RR, 1.38; 95% CI, 0.77–2.29)
Significant lower risk of mortality for ischemic heart disease with larger fresh or frozen red meat consumption (RR, 0.55; 95% CI, 0.31–0.99) Age, sex, smoking habits, alcohol intake, No significant higher risk of acute diabetes, hypertension, history of CAD, myocardial infarction with larger intake waist-to-hip ratio, physical activity, of red meat and pork (OR, 1.69; 95% CI, socioeconomic status, years living at current 0.93–3.06) residence since age 18, and intake of dietary fiber, total energy, and trans-fat Age, sex, total cholesterol, mean arterial Higher risk of coronary heart disease pressure and waist girth with larger intake of processed red meat (HR, 2.21; 95% CI, 1.05–4.63), but not with fresh red meat (data not reported) Age, body mass, smoking habits, alcohol No significant higher risk of coronary consumption, physical activity, aspirin use, heart disease with larger total red meat consumption (RR, 1.36; 95% CI, 0.97–1.91) diabetes duration, hypertension, hypercholesterolemia, postmenopausal hormone use, family history of CAD, cereal fiber, glycemic load, polyunsaturated fat-to-saturated fat ratio, trans fat, multivitamin use vitamin C Body mass, smoking, physical activity, Higher risk of acute coronary syndrome educational status, history of CAD, with larger intake of total red meat (OR, hypertension, hypercholesterolemia, 1.52; 95% CI, 1.47–1.58) diabetes and special medications
Prevalence of acute Age, sex, education, total energy intake, myocardial infarction intakes of fruit, refined cereals and white meat, smoking status, regular physical activity, history of CAD, body mass, menopause and hormone replacement therapy Incident coronary Age, time period, total energy, cereal fiber, heart disease alcohol consumption, trans fat, body mass, (rate: 3.8%) cigarette smoking, menopausal status, history of early CAD, multivitamin use, vitamin E supplement, aspirin, physical exercise Incident ischemic Age, body mass, alcohol intake, mental heart disease stress, walking time, sports participation, mortality education, hypertension, diabetes, total (rate: 1.0%) energy and energy-adjusted food intakes Incident ischemic heart disease mortality (rate: 0.4%)
No significant higher risk of CAD with larger red meat consumption (RR, 1.09; 95% CI, 0.91–1.30)
Higher risk of acute myocardial infarction with larger intake of red meat and pork (OR, 1.74; 95% CI, 1.43–2.12)
Higher risk of coronary heart disease with larger intake of total red meat (RR, 1.29; 95% CI, 1.12–1.49), but not with larger intake of beef (RR, 1.08; 95% CI, 0.92–1.27)
No significant higher risk of ischemic heart disease with larger total red meat consumption in men (HR, 0.70; 95% CI, 0.47–1.04) and women (HR, 1.23; 95% CI, 0.82–1.85) Age, total caloric intake, income, occupation, Higher risk of mortality for ischemic heart education, comorbidity index, physical disease with larger intake of total red activity, vegetable intake, fruit intake, fish meat in men (1.54; 95% CI, 1.02–2.32) but intake, smoking habits and alcohol not in women (HR, 1.28; 95% CI, consumption 0.84–1.96)
HR, hazard ratio; OR, odds ratio; RR, relative risk.
controls. A slightly but not significantly higher intake of meat and pork was reported for cases than for controls (1.44 versus 1.14 servings/day; p N 0.05). When study participants were classified according to quintiles of dietary intake, those in the highest quintile of red meat and pork ingestion exhibited a higher risk of AMI compared to those in the lower quintiles (odds ratio [OR] of the highest versus the lowest quintile, 1.69; 95% CI, 0.93–3.06; p = 0.02 for trend). Burke et al. (2007) performed a small prospective study including 514 subjects, who were followed up for 14 years. A total number of 130 CAD events were recorded on follow-up (incidence rate of CAD: 25%). A larger intake of processed red meat (i.e., N 4 serves/month) was found to be significantly associated with increased risk of CAD
(HR, 2.21; 95% CI, 1.05–4.63), whereas no higher risk was observed in subjects consuming fresh red meat (data not reported). Qi et al. (2007) designed a prospective study including 6161 women reporting a diagnosis of type 2 diabetes at 30 years of age, and who were followed up for 20 years. Overall, 550 incident cases of CAD (259 nonfatal myocardial infarctions, 153 coronary heart deaths and 138 bypass operations or angioplasties) were recorded during follow-up (incidence rate of CAD: 8.9%). In the fully-adjusted multivariate analysis, larger intake of total red meat was not found to be significantly associated with incident CAD (RR, 1.36; 95% CI, 0.97–1.91). Kontogianni et al. (2008) performed a case–control study including 848 patients with acute coronary syndrome (ACS) (no demographical
G. Lippi et al. / Meat Science 108 (2015) 32–36 Table 2 Definition of endpoints and type of red meat investigated in the different studies. Authors
Definition of endpoints
Ascherio et al. (1994)
Fatal coronary disease (including Beef sudden death), nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty Nonfatal myocardial infarction or Total red meat (beef, pork, or fatal coronary disease lamb as a main dish; beef as a sandwich or mixed dish; hamburger; hot dog; processed meat; bacon) Mortality from acute myocardial Total red meat (fresh or frozen infarction; chronic ischemic red meat, excluding pies, burgers heart disease and sausages) Survivors of a first acute Total red meat (beef and pork myocardial infarction products)
Hu et al. (1999)
Whiteman et al. (1999) Kabagambe et al. (2003) Burke et al. (2007)
Acute myocardial infarction, other acute and subacute forms of ischemic heart disease, old myocardial infarction, angina pectoris, other forms of chronic ischemic heart disease Fatal and nonfatal myocardial Qi et al. (2007) infarction, coronary revascularization (coronary bypass surgery or coronary angioplasty) Kontogianni First event of acute myocardial et al. infarction, first event of unstable (2008) angina corresponding to class III of Braunwald classification Oliveira Newly admitted cases of acute et al. myocardial infarction (2010) Bernstein Fatal and non-fatal acute et al. myocardial infarction (2010) Nagao et al. Ischemic heart disease (2012) (ICD-10 codes 120–125) Takata et al. Ischemic heart disease (2013) (ICD-9 codes 410–414)
Type of red meat investigated
Processed red meat (i.e., bacon, canned meat, salami, other sausage); fresh red meat (beef, lamb or mutton, mince)
Total red meat (beef, pork, or lamb as a main dish; beef as a sandwich or mixed dish; hamburger; hot dog; processed meat; and bacon) Total red meat (any type)
Total red meat (beef, pork, and pork products including smoked ham, bacon and sausages) Total red meat; beef (main dish); bacon; hot dog; hamburger; Total red meat (beef, pork, poultry, liver and processed meat) Total red meat (beef, lamb, pork, pig, cow, sheep, and organ meat including heart, brain, liver, tongue, tripe and intestine)
data reported) and 1078 matched healthy controls. Overall, larger consumption of total red meat was found to be associated with an increased risk of ACS (OR, 1.52; 95% CI, 1.47–1.58). Oliveira et al. (2010) performed another case–control study including 820 patients with AMI and 2196 matched healthy controls from the same geographical area. In the fully adjusted multivariate analysis, higher consumption of red meat and pork (i.e., ≥ median) was found to be significantly associated with an increased risk of AMI (OR, 1.74; 95% CI, 1.43–2.12). Bernstein et al. (2010) conducted another large prospective study, including 84,136 women who participated to the Nurses' Health Study and were followed up for 26 years. A total number of 3162 CAD events (2210 incident nonfatal infarctions and 952 deaths from CAD) were recorded during follow-up (rate of incident CAD: 3.8%). In the fully adjusted risk model, women in the highest quintile of total red meat intake exhibited a higher risk of CAD than those in the lowest quintile of intake (RR, 1.29; 95% CI, 1.12–1.49). Each increment of 1 serving of total red meat per day was also associated with a 16% (95% CI, 9–23%) higher risk of CAD. In sub-analysis of red meat types, the association with CAD was found to be significant for larger consumption of processed meat (RR, 1.20; 95% CI, 1.03–1.40), bacon (RR, 1.41; 95% CI, 1.12–1.76) and hamburger (RR, 1.42; 95% CI, 1.10–1.84), but not for larger intake of beef as the main dish (RR, 1.08; 95% CI, 0.92–1.27).
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More recently, Nagao et al. (2012) performed a prospective cohort study including 51,683 subjects, who were followed up for a median period of 18.4 years. A total number of 537 deaths for CAD were recorded during follow-up (incidence rate of CAD mortality: 1.0%). A larger consumption of total red meat was not found to be significantly associated with mortality for CAD in women (HR, 1.23; 95% CI, 0.82–1.85), whereas a trend towards a negative association was found in men (HR, 0.70; 95% CI, 0.47–1.04; p = 0.038 for trend). Finally, Takata et al. (2013) performed another large populationbased prospective cohort study including 136,424 subjects, who were followed up for median period of 11.2 years (women) and 5.5 years (men). Although no association between larger intake of total red meat and death for IHD was found in the female cohort (HR, 1.28; 95% CI, 0.84–1.96), men consuming larger intake of total red meat exhibited a significantly increased risk of mortality for IHD (HR, 1.54; 95% CI, 1.02–2.32). 4. Discussion The relationship between red meat intake and cardiovascular mortality remains controversial (McAfee et al., 2010), thus making the public health care concerns that larger intake of red meat would substantially increase the burden of cardiovascular disorders mostly unfounded. Overall, the evidence of the current scientific literature seemingly attests that no definitive conclusions can be drawn about the putative relationship between red meat intake and both fatal and non-fatal IHD. Although a larger intake of red meat was found to be a significant risk factor for myocardial ischemia in four studies (2 prospective and 2 case–control), no significant association was found in five other trials (4 prospective and 1 case–control) (Table 1). Moreover, in the study of Burke et al. (2007) a significant association with risk of IHD was found with larger intake of processed red meat (i.e., bacon, canned meat, salami other sausage), but not with fresh red meat (beef, lamb or mutton, mince). Similar evidence was reported by Bernstein et al. (2010), showing that the risk of coronary heart disease was higher in subjects consuming larger amounts of total red meat but not in those with higher intake of beef. It is also noteworthy that a negative association between total red meat intake and IHD was reported in one prospective study (Whiteman et al., 1999), whereas a similar trend was observed in the male cohort men in the prospective study of Nagao et al. (2012). Additional evidence that limiting red meat is unnecessarily restrictive and may also carry adverse health consequences has been recently brought. Interestingly, a recent study including 1152 subjects (635 women and 517 men) failed to find a significant association between red or processed meat intake and serum cholesterol level or blood pressure (Wagemakers, Prynne, Stephen, & Wadsworth, 2009). A very modest association could only be observed between red or processed meat intake and waist circumference in men (p = 0.04) but not in women (p N 0.05). The lean red meat contains a very modest amount of saturated fat and its consumption within an appropriate diet was shown to be effective to lower low density lipoprotein (LDL) cholesterol (Binnie, Barlow, Johnson, & Harrison, 2014; Li, Siriamornpun, Wahlqvist, Mann, & Sinclair, 2005). These finding was confirmed by a recent meta-analysis of eight randomized, controlled clinical trials (Maki et al., 2012), which showed that fasting lipid level profile was not significantly modified with beef consumption compared to poultry or fish intake. It was also demonstrated that lean red meat intake is not effective to induce a prothrombotic state, due to the lack of any interaction with both primary and secondary hemostasis (Li et al., 2005). Overall, total red meat consumption appears to be globally modest in developed countries and in line with current recommendations (Binnie et al., 2014). It is now clearly established that intake of total red meat is associated with the generation of a vast array of carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and saturated fatty acids, which would ultimately
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G. Lippi et al. / Meat Science 108 (2015) 32–36
promote the development of certain types of cancer, especially colorectal malignancies (Abid, Cross, & Sinha, 2014). Nevertheless, the epidemiological data that we have reviewed in this article does not support the existence of clear relationship between total red meat consumption and IHD. Some conclusions can be made. First, due to the large heterogeneity of the criteria used for diagnosing IHD and for defining red meat (Table 2), large prospective trials with standardized criteria are needed to clearly establish the relationship between IHD and different types of red or processed meat. Importantly, this latter aspect is an insurmountable drawback for meta-analyzing data in this systematic literature review, since it may be essentially misleading to arbitrarily pool the effects of different types of red or processed meat across the various studies, as clearly shown in Table 2. Then, future diet recommendations for prevention of CVD should take into account that the current literature data does not support the existence of an unquestionable relationship between large intake of red meat and the risk of myocardial ischemia. Conflicts of interests The authors declare that no conflict of interest exists. References Abid, Z., Cross, A. J., & Sinha, R. (2014). Meat, dairy, and cancer. The American Journal of Clinical Nutrition, 100(Suppl. 1), 386S–393S. http://dx.doi.org/10.3945/ajcn.113. 071597 (ajcn.113.071597). Ascherio, A., Willett, W. C., Rimm, E. B., Giovannucci, E. L., & Stampfer, M. J. (1994). Dietary iron intake and risk of coronary disease among men. Circulation, 89(3), 969–974. Bernstein, A. M., Sun, Q., Hu, F. B., Stampfer, M. J., Manson, J. E., & Willett, W. C. (2010). Major dietary protein sources and risk of coronary heart disease in women. Circulation, 122(9), 876–883. http://dx.doi.org/10.1161/CIRCULATIONAHA.109. 915165 (CIRCULATIONAHA.109.915165). Binnie, M. A., Barlow, K., Johnson, V., & Harrison, C. (2014). Red meats: Time for a paradigm shift in dietary advice. Meat Science, 98(3), 445–451. http://dx.doi.org/10. 1016/j.meatsci.2014.06.024 S0309-1740(14)00192-2. Burke, V., Zhao, Y., Lee, A. H., Hunter, E., Spargo, R. M., & Gracey, M. (2007). Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines. Preventive Medicine, 44(2), 135–142. http://dx.doi.org/10.1016/j.ypmed.2006.09.008 (S0091-7435(06)00378-1). Chen, Y., McClintock, T. R., Segers, S., Parvez, F., Islam, T., & Ahmed, A. (2013). Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh. International Journal of Cardiology, 167(4), 1495–1501. http://dx.doi. org/10.1016/j.ijcard.2012.04.041 (S0167-5273(12)00462-7). Food Agriculture and Organization of the United Nations (2014). FAO world food outlook Retrieved Accessed: March, 10, 2015, from http://www.fao.org/ag/againfo/themes/ en/meat/home.html. Hu, F. B., Stampfer, M. J., Manson, J. E., Ascherio, A., Colditz, G. A., & Speizer, F. E. (1999). Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. The American Journal of Clinical Nutrition, 70(6), 1001–1008.
Kabagambe, E. K., Baylin, A., Siles, X., & Campos, H. (2003). Individual saturated fatty acids and nonfatal acute myocardial infarction in Costa Rica. European Journal of Clinical Nutrition, 57(11), 1447–1457. http://dx.doi.org/10.1038/sj.ejcn.16017091601709 (pii). Kontogianni, M. D., Panagiotakos, D. B., Pitsavos, C., Chrysohoou, C., & Stefanadis, C. (2008). Relationship between meat intake and the development of acute coronary syndromes: the CARDIO2000 case–control study. European Journal of Clinical Nutrition, 62(2), 171–177. http://dx.doi.org/10.1038/sj.ejcn.1602713 (1602713 [pii]). Lafarga, T., & Hayes, M. (2014). Bioactive peptides from meat muscle and by-products: Generation, functionality and application as functional ingredients. Meat Science, 98(2), 227–239. http://dx.doi.org/10.1016/j.meatsci.2014.05.036 (S0309-1740(14)00167-3). Li, D., Siriamornpun, S., Wahlqvist, M. L., Mann, N. J., & Sinclair, A. J. (2005). Lean meat and heart health. Asia Pacific Journal of Clinical Nutrition, 14(2), 113–119. Lichtenstein, A. H., Appel, L. J., Brands, M., Carnethon, M., Daniels, S., & Franch, H. A. (2006). Diet and lifestyle recommendations revision 2006: A scientific statement from the American Heart Association Nutrition Committee. Circulation, 114(1), 82–96. http://dx.doi.org/10.1161/CIRCULATIONAHA.106.176158 (CIRCULATIONAHA. 106.176158). Maki, K. C., Van Elswyk, M. E., Alexander, D. D., Rains, T. M., Sohn, E. L., & McNeill, S. (2012). A meta-analysis of randomized controlled trials that compare the lipid effects of beef versus poultry and/or fish consumption. Journal of Clinical Lipidology, 6(4), 352–361. http://dx.doi.org/10.1016/j.jacl.2012.01.001 (S1933-2874(12)00015-3). McAfee, A. J., McSorley, E. M., Cuskelly, G. J., Moss, B. W., Wallace, J. M., & Bonham, M. P. (2010). Red meat consumption: An overview of the risks and benefits. Meat Science, 84(1), 1–13. http://dx.doi.org/10.1016/j.meatsci.2009.08.029 (S03091740(09)00251-4). Nagao, M., Iso, H., Yamagishi, K., Date, C., & Tamakoshi, A. (2012). Meat consumption in relation to mortality from cardiovascular disease among Japanese men and women. European Journal of Clinical Nutrition, 66(6), 687–693. http://dx.doi.org/10.1038/ ejcn.2012.6 (ejcn20126). Oliveira, A., Lopes, C., & Rodriguez-Artalejo, F. (2010). Adherence to the Southern European Atlantic Diet and occurrence of nonfatal acute myocardial infarction. The American Journal of Clinical Nutrition, 92(1), 211–217. http://dx.doi.org/10.3945/ ajcn.2009.29075 (ajcn.2009.29075). Parikh, P., McDaniel, M. C., Ashen, M. D., Miller, J. I., Sorrentino, M., & Chan, V. (2005). Diets and cardiovascular disease: An evidence-based assessment. Journal of the American College of Cardiology, 45(9), 1379–1387. http://dx.doi.org/10.1016/j.jacc. 2004.11.068 (S0735-1097(05)00367-0). Qi, L., van Dam, R. M., Rexrode, K., & Hu, F. B. (2007). Heme iron from diet as a risk factor for coronary heart disease in women with type 2 diabetes. Diabetes Care, 30(1), 101–106. http://dx.doi.org/10.2337/dc06-1686 (30/1/101). Rohrmann, S., Overvad, K., Bueno-de-Mesquita, H. B., Jakobsen, M. U., Egeberg, R., & Tjonneland, A. (2013). Meat consumption and mortality—Results from the European Prospective Investigation into Cancer and Nutrition. BMC Medicine, 11, 63. http://dx.doi.org/10.1186/1741-7015-11-63 (1741-7015-11-63). Takata, Y., Shu, X. O., Gao, Y. T., Li, H., Zhang, X., & Gao, J. (2013). Red meat and poultry intakes and risk of total and cause-specific mortality: Results from cohort studies of Chinese adults in Shanghai. PLoS ONE, 8(2), e56963. http://dx.doi.org/10.1371/ journal.pone (0056963PONE-D-12-32559 [pii]). Wagemakers, J. J., Prynne, C. J., Stephen, A. M., & Wadsworth, M. E. (2009). Consumption of red or processed meat does not predict risk factors for coronary heart disease; results from a cohort of British adults in 1989 and 1999. European Journal of Clinical Nutrition, 63(3), 303–311. http://dx.doi.org/10.1038/sj.ejcn.1602954 (1602954). Walker, P., Rhubart-Berg, P., McKenzie, S., Kelling, K., & Lawrence, R. S. (2005). Public health implications of meat production and consumption. Public Health Nutrition, 8(4), 348–356 (S1368980005000492 [pii]). Whiteman, D., Muir, J., Jones, L., Murphy, M., & Key, T. (1999). Dietary questions as determinants of mortality: The OXCHECK experience. Public Health Nutrition, 2(4), 477–487 (S136898009900066X [pii]).
Contents lists available at ScienceDirect
Meat Science journal homepage: www.elsevier.com/locate/meatsci
Review
Red meat consumption and ischemic heart disease. A systematic literature review Giuseppe Lippi a, Camilla Mattiuzzi b, Fabian Sanchis Gomar c,⁎ a b c
Laboratory of Clinical Chemistry and Hematology, Academic Hospital of Parma, Parma, Italy Service of Clinical Governance, General Hospital of Trento, Trento, Italy Research Institute of Hospital 12 de Octubre (“i+12”), Madrid, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history: Received 20 March 2015 Received in revised form 17 May 2015 Accepted 19 May 2015 Available online 22 May 2015
Several lines of evidence attest that diet may strongly influence the cardiovascular risk. We performed an electronic search in Medline (with PubMed interface), Scopus and ISI Web of Science, to identify epidemiological studies on the association between red meat intake and the overall risk of ischemic heart disease (IHD). Eleven studies (8 prospective and 3 case–control) were finally selected for this systematic literature review. Although a larger intake of red meat was found to be a significant risk factor for IHD in four studies (2 prospective and 2 case–control), no significant association was found in five other trials (4 prospective and 1 case–control). We suggest that future diet recommendations for prevention of cardiovascular disease should take into account that the current literature data does not support the existence of a clear relationship between large intake of red meat and increased risk of myocardial ischemia. © 2015 Elsevier Ltd. All rights reserved.
Keywords: Diet Fatty acid Cholesterol Cardiovascular disease Mortality
Contents 1. Introduction . 2. Methods . . . 3. Results . . . 4. Discussion . . Conflicts of interests References . . . .
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1. Introduction Several lines of evidence now attest that diet may strongly influence the cardiovascular risk (Parikh et al., 2005). Among the various nutrients, meat plays a substantial role in human's diet, since it is an important source of proteins, essential amino acids, vitamins, minerals and other micronutrients (Lafarga & Hayes, 2014), despite the fact that fat and fatty acid composition of red meat may be involved in enhancing the risk of cardiovascular disease (CVD) (McAfee et al., 2010). Conventionally, the term “red” is used to define a type of meat characterized by a red hue and which does not turn to white when cooked. The global market of red meat is as high as 184 million tonnes per year, thus largely exceeding that of poultry (109 million tonnes per year) and ovine products ⁎ Corresponding author at: Research Institute of Hospital 12 de Octubre (‘i+12’), Avda. de Córdoba s/n, 28041 Madrid, Spain. E-mail address: [email protected] (F.S. Gomar).
http://dx.doi.org/10.1016/j.meatsci.2015.05.019 0309-1740/© 2015 Elsevier Ltd. All rights reserved.
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(14 million tonnes per year) (Food Agriculture & Organization of the United Nations, 2014). Such a large consumption of red meat, especially in high-income countries, has recently emerged as a public health care concern due to the potential association between red meat consumption and a number of human disorders, including diabetes and cancer (Walker, Rhubart-Berg, McKenzie, Kelling, & Lawrence, 2005). As regards CVD, the American Heart Association (AHA) has released specific recommendations aimed to reduce the risk of developing cardiovascular disorders, including statements that consumption of lean meats should be preferred over that of fat meat, the intake of processed meats high in saturated fat and sodium should be limited, and meat should be preferably consumed after grilling, baking or broiling (Lichtenstein et al., 2006). However, whether or not red met intake would represent a risk factor for CVD remains a matter of debate. A recent prospective cohort analyses including 11,116 subjects aged 18–75 years old and followed up for an average period of 6.6 years (Chen et al., 2013) concluded that a diet enriched in animal proteins may slightly increase the risk of heart
G. Lippi et al. / Meat Science 108 (2015) 32–36
disease mortality, especially among smokers (hazard ratio [HR], 1.20; 1.00–1.45). Interestingly, in another recent prospective study, including 448,568 subjects aged 35–69 years who were followed up for a median period of 12.7 years (Rohrmann et al., 2013), no association was found between larger consumption of total red meat and all-cause death (HR, 1.02; 95% CI, 0.98–1.06). Nevertheless, when the analysis was limited to subjects who died for CVD, a marginally significant association was found with total red meat intake (HR, 1.09; 95% CI, 1.00–1.18), especially with larger intake of processed meat (HR, 1.30; 95% CI, 1.17–1.45). At variance with this evidence, Whiteman et al. followed up for 9 years 10,522 subjects aged 35–64 years (5593 women and 4929 men) (Whiteman, Muir, Jones, Murphy, & Key, 1999), and found an inverse association between intake of fresh or frozen meat and mortality for CVD (relative risk [RR]; 0.71; 95% CI. 0.55–0.92). The controversial evidence on red meat intake and cardiovascular mortality persuaded us to carry out a systematic literature review in order to establish whether or not red meat intake represents an additional risk factor for ischemic heart disease (IHD). 2. Methods We performed an electronic search in Medline (with PubMed interface), Scopus and ISI Web of Science using the keywords “red” AND “meat” AND “coronary artery disease” OR “coronary heart disease” OR “acute coronary syndrome” OR “ischemic heart disease” OR “myocardial infarction” in “Title/Abstract/Keywords” and with no language or date restriction, to identify epidemiological studies on the association between red meat intake and the overall risk of IHD (i.e., fatal and non-fatal cases). The documents that could be identified were systematically reviewed by two authors (G.L. and C.M.) and the references were also hand-searched to identify other pertinent items. 3. Results A total number of 53 documents could be identified after elimination of replicates among the three scientific databases and 3 additional studies could be detected from the relative references. Forty five items were excluded after accurate reading of title, abstract or full text (see Fig. 1). Therefore, 11 studies (8 prospective and 3 case–control)
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were finally selected for this systematic literature review (Table 1) (Ascherio, Willett, Rimm, Giovannucci, & Stampfer, 1994; Bernstein et al., 2010; Burke et al., 2007; Hu et al., 1999; Kabagambe, Baylin, Siles, & Campos, 2003; Kontogianni, Panagiotakos, Pitsavos, Chrysohoou, & Stefanadis, 2008; Nagao, Iso, Yamagishi, Date, & Tamakoshi, 2012; Oliveira, Lopes, & Rodriguez-Artalejo, 2010; Qi, van Dam, Rexrode, & Hu, 2007; Takata et al., 2013; Whiteman et al., 1999). Inter-rater agreement was 96% (kappa statistics, 0.90; p b 0.001). The different types of meat and the diagnostic criteria for IHD used in the single studies are provided in Table 2. The first study that investigated the relationship between IHD and red meat consumption was published by Ascherio et al. (1994). The authors conducted a large prospective study, including 44,933 men with no previous history of CVD, who were followed up for 4 years. A total number of 844 incident cases of coronary artery disease (CAD) (249 nonfatal myocardial infarctions, 137 coronary disease fatalities and 458 bypass operations or angioplasties) were recorded on follow-up (rate of incident CAD: 1.9%). A slightly higher but non-significant risk of CAD was found in men consuming red meat (prevalently beef) ≥ 4 times per week compared to those reporting intake of ≤ 1 per month (RR, 1.38; 95% CI, 0.77–2.29). Interestingly, a slight but non-significant risk of CAD was also observed in subjects in the highest quintile of beef, chicken, liver and other processed meat consumption (RR, 1.18; 95% CI, 0.78–1.80). In a following prospective study, 80,082 women were followed up for 14 years (Hu et al., 1999). A total number of 939 incident cases of major CAD events were recorded during follow-up (rate of incident CAD: 1.2%). In the fully-adjusted multivariate model, no association was found between larger consumption of red meat and higher risk of CAD (RR of increment of 1 serving per day, 1.09; 95% CI, 0.91–1.30; p = 0.35 for trend). Whiteman et al. (1999) performed a prospective study including 10,522 subjects, who were followed up for 9 years. Overall, 144,939 incident cases of IHD were recorded during follow-up (rate of incident IHD: 1.4%). An inverse association was found between intake of fresh or frozen red meat and mortality for IHD (RR, 0.55; 95% CI, 0.31–0.99). Kabagambe et al. (2003) performed a case–control study, including 485 survivors of a first acute myocardial infarction (AMI) who were matched for age, gender and area of residence with 508 healthy
Fig. 1. Description of the search methodology.
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G. Lippi et al. / Meat Science 108 (2015) 32–36
Table 1 Description of prospective and case–control studies investigating the association between red meat intake and ischemic heart disease. Authors
Setting
Study design Study population
Ascherio et al. (1994)
USA
Prospective
44,933 men aged 40 Incident CAD to 75 followed up for (rate: 1.9%) 4 years
Hu et al. (1999)
USA
Prospective
80,082 women aged 34–59 years followed up for 14 years
Incident coronary heart disease (rate: 1.2%)
Whiteman et al. (1999)
USA
Prospective
10,522 subjects aged 35–64 years followed up for 9 years
Kabagambe et al. (2003)
Costa-Rica Case–control 485 patients with acute myocardial infarction and 508 matched healthy controls
Incident ischemic heart disease mortality (rate: 1.4%) Prevalence of acute myocardial infarction
Burke et al. (2007)
Australia
Prospective
514 subjects followed Incident coronary up for 14 years heart disease (rate: 25%)
Qi et al. (2007)
USA
Prospective
6161 women with diagnosis of type 2 diabetes at 30 years of age, followed up for 20 years
Kontogianni Greece et al. (2008)
Case–control 848 patients with acute coronary syndrome and 1078 matched healthy controls Case–control 820 patients with acute myocardial infarction and 2196 matched healthy controls
Oliveira et al. (2010)
Portugal
Bernstein et al. (2010)
USA
Prospective
84,136 women aged 30 to 55 years followed up for 26 years
Nagao et al. (2012)
Japan
Prospective
51,683 subjects followed up for 18.4 years
Takata et al. China (2013)
Prospective
136,424 subjects aged 40 to 70 years followed up for 5.5–11.2 years
Endpoint
Incident coronary heart disease (rate: 8.9%)
Prevalence of acute coronary syndrome
Adjustment
Results
Age, body mass, smoking habits, alcohol consumption, hypertension, diabetes, hypercholesterolemia, family history of CAD, profession, total energy, vitamin E, total iron, heme iron Age, body mass, cigarette smoking, menopausal status, history of CAD, vitamin E supplement use, alcohol consumption, hypertension, aspirin use vigorous exercise Age, sex, smoking habits
No significant higher risk of CAD with larger red meat consumption (RR, 1.38; 95% CI, 0.77–2.29)
Significant lower risk of mortality for ischemic heart disease with larger fresh or frozen red meat consumption (RR, 0.55; 95% CI, 0.31–0.99) Age, sex, smoking habits, alcohol intake, No significant higher risk of acute diabetes, hypertension, history of CAD, myocardial infarction with larger intake waist-to-hip ratio, physical activity, of red meat and pork (OR, 1.69; 95% CI, socioeconomic status, years living at current 0.93–3.06) residence since age 18, and intake of dietary fiber, total energy, and trans-fat Age, sex, total cholesterol, mean arterial Higher risk of coronary heart disease pressure and waist girth with larger intake of processed red meat (HR, 2.21; 95% CI, 1.05–4.63), but not with fresh red meat (data not reported) Age, body mass, smoking habits, alcohol No significant higher risk of coronary consumption, physical activity, aspirin use, heart disease with larger total red meat consumption (RR, 1.36; 95% CI, 0.97–1.91) diabetes duration, hypertension, hypercholesterolemia, postmenopausal hormone use, family history of CAD, cereal fiber, glycemic load, polyunsaturated fat-to-saturated fat ratio, trans fat, multivitamin use vitamin C Body mass, smoking, physical activity, Higher risk of acute coronary syndrome educational status, history of CAD, with larger intake of total red meat (OR, hypertension, hypercholesterolemia, 1.52; 95% CI, 1.47–1.58) diabetes and special medications
Prevalence of acute Age, sex, education, total energy intake, myocardial infarction intakes of fruit, refined cereals and white meat, smoking status, regular physical activity, history of CAD, body mass, menopause and hormone replacement therapy Incident coronary Age, time period, total energy, cereal fiber, heart disease alcohol consumption, trans fat, body mass, (rate: 3.8%) cigarette smoking, menopausal status, history of early CAD, multivitamin use, vitamin E supplement, aspirin, physical exercise Incident ischemic Age, body mass, alcohol intake, mental heart disease stress, walking time, sports participation, mortality education, hypertension, diabetes, total (rate: 1.0%) energy and energy-adjusted food intakes Incident ischemic heart disease mortality (rate: 0.4%)
No significant higher risk of CAD with larger red meat consumption (RR, 1.09; 95% CI, 0.91–1.30)
Higher risk of acute myocardial infarction with larger intake of red meat and pork (OR, 1.74; 95% CI, 1.43–2.12)
Higher risk of coronary heart disease with larger intake of total red meat (RR, 1.29; 95% CI, 1.12–1.49), but not with larger intake of beef (RR, 1.08; 95% CI, 0.92–1.27)
No significant higher risk of ischemic heart disease with larger total red meat consumption in men (HR, 0.70; 95% CI, 0.47–1.04) and women (HR, 1.23; 95% CI, 0.82–1.85) Age, total caloric intake, income, occupation, Higher risk of mortality for ischemic heart education, comorbidity index, physical disease with larger intake of total red activity, vegetable intake, fruit intake, fish meat in men (1.54; 95% CI, 1.02–2.32) but intake, smoking habits and alcohol not in women (HR, 1.28; 95% CI, consumption 0.84–1.96)
HR, hazard ratio; OR, odds ratio; RR, relative risk.
controls. A slightly but not significantly higher intake of meat and pork was reported for cases than for controls (1.44 versus 1.14 servings/day; p N 0.05). When study participants were classified according to quintiles of dietary intake, those in the highest quintile of red meat and pork ingestion exhibited a higher risk of AMI compared to those in the lower quintiles (odds ratio [OR] of the highest versus the lowest quintile, 1.69; 95% CI, 0.93–3.06; p = 0.02 for trend). Burke et al. (2007) performed a small prospective study including 514 subjects, who were followed up for 14 years. A total number of 130 CAD events were recorded on follow-up (incidence rate of CAD: 25%). A larger intake of processed red meat (i.e., N 4 serves/month) was found to be significantly associated with increased risk of CAD
(HR, 2.21; 95% CI, 1.05–4.63), whereas no higher risk was observed in subjects consuming fresh red meat (data not reported). Qi et al. (2007) designed a prospective study including 6161 women reporting a diagnosis of type 2 diabetes at 30 years of age, and who were followed up for 20 years. Overall, 550 incident cases of CAD (259 nonfatal myocardial infarctions, 153 coronary heart deaths and 138 bypass operations or angioplasties) were recorded during follow-up (incidence rate of CAD: 8.9%). In the fully-adjusted multivariate analysis, larger intake of total red meat was not found to be significantly associated with incident CAD (RR, 1.36; 95% CI, 0.97–1.91). Kontogianni et al. (2008) performed a case–control study including 848 patients with acute coronary syndrome (ACS) (no demographical
G. Lippi et al. / Meat Science 108 (2015) 32–36 Table 2 Definition of endpoints and type of red meat investigated in the different studies. Authors
Definition of endpoints
Ascherio et al. (1994)
Fatal coronary disease (including Beef sudden death), nonfatal myocardial infarction, coronary artery bypass graft, percutaneous transluminal coronary angioplasty Nonfatal myocardial infarction or Total red meat (beef, pork, or fatal coronary disease lamb as a main dish; beef as a sandwich or mixed dish; hamburger; hot dog; processed meat; bacon) Mortality from acute myocardial Total red meat (fresh or frozen infarction; chronic ischemic red meat, excluding pies, burgers heart disease and sausages) Survivors of a first acute Total red meat (beef and pork myocardial infarction products)
Hu et al. (1999)
Whiteman et al. (1999) Kabagambe et al. (2003) Burke et al. (2007)
Acute myocardial infarction, other acute and subacute forms of ischemic heart disease, old myocardial infarction, angina pectoris, other forms of chronic ischemic heart disease Fatal and nonfatal myocardial Qi et al. (2007) infarction, coronary revascularization (coronary bypass surgery or coronary angioplasty) Kontogianni First event of acute myocardial et al. infarction, first event of unstable (2008) angina corresponding to class III of Braunwald classification Oliveira Newly admitted cases of acute et al. myocardial infarction (2010) Bernstein Fatal and non-fatal acute et al. myocardial infarction (2010) Nagao et al. Ischemic heart disease (2012) (ICD-10 codes 120–125) Takata et al. Ischemic heart disease (2013) (ICD-9 codes 410–414)
Type of red meat investigated
Processed red meat (i.e., bacon, canned meat, salami, other sausage); fresh red meat (beef, lamb or mutton, mince)
Total red meat (beef, pork, or lamb as a main dish; beef as a sandwich or mixed dish; hamburger; hot dog; processed meat; and bacon) Total red meat (any type)
Total red meat (beef, pork, and pork products including smoked ham, bacon and sausages) Total red meat; beef (main dish); bacon; hot dog; hamburger; Total red meat (beef, pork, poultry, liver and processed meat) Total red meat (beef, lamb, pork, pig, cow, sheep, and organ meat including heart, brain, liver, tongue, tripe and intestine)
data reported) and 1078 matched healthy controls. Overall, larger consumption of total red meat was found to be associated with an increased risk of ACS (OR, 1.52; 95% CI, 1.47–1.58). Oliveira et al. (2010) performed another case–control study including 820 patients with AMI and 2196 matched healthy controls from the same geographical area. In the fully adjusted multivariate analysis, higher consumption of red meat and pork (i.e., ≥ median) was found to be significantly associated with an increased risk of AMI (OR, 1.74; 95% CI, 1.43–2.12). Bernstein et al. (2010) conducted another large prospective study, including 84,136 women who participated to the Nurses' Health Study and were followed up for 26 years. A total number of 3162 CAD events (2210 incident nonfatal infarctions and 952 deaths from CAD) were recorded during follow-up (rate of incident CAD: 3.8%). In the fully adjusted risk model, women in the highest quintile of total red meat intake exhibited a higher risk of CAD than those in the lowest quintile of intake (RR, 1.29; 95% CI, 1.12–1.49). Each increment of 1 serving of total red meat per day was also associated with a 16% (95% CI, 9–23%) higher risk of CAD. In sub-analysis of red meat types, the association with CAD was found to be significant for larger consumption of processed meat (RR, 1.20; 95% CI, 1.03–1.40), bacon (RR, 1.41; 95% CI, 1.12–1.76) and hamburger (RR, 1.42; 95% CI, 1.10–1.84), but not for larger intake of beef as the main dish (RR, 1.08; 95% CI, 0.92–1.27).
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More recently, Nagao et al. (2012) performed a prospective cohort study including 51,683 subjects, who were followed up for a median period of 18.4 years. A total number of 537 deaths for CAD were recorded during follow-up (incidence rate of CAD mortality: 1.0%). A larger consumption of total red meat was not found to be significantly associated with mortality for CAD in women (HR, 1.23; 95% CI, 0.82–1.85), whereas a trend towards a negative association was found in men (HR, 0.70; 95% CI, 0.47–1.04; p = 0.038 for trend). Finally, Takata et al. (2013) performed another large populationbased prospective cohort study including 136,424 subjects, who were followed up for median period of 11.2 years (women) and 5.5 years (men). Although no association between larger intake of total red meat and death for IHD was found in the female cohort (HR, 1.28; 95% CI, 0.84–1.96), men consuming larger intake of total red meat exhibited a significantly increased risk of mortality for IHD (HR, 1.54; 95% CI, 1.02–2.32). 4. Discussion The relationship between red meat intake and cardiovascular mortality remains controversial (McAfee et al., 2010), thus making the public health care concerns that larger intake of red meat would substantially increase the burden of cardiovascular disorders mostly unfounded. Overall, the evidence of the current scientific literature seemingly attests that no definitive conclusions can be drawn about the putative relationship between red meat intake and both fatal and non-fatal IHD. Although a larger intake of red meat was found to be a significant risk factor for myocardial ischemia in four studies (2 prospective and 2 case–control), no significant association was found in five other trials (4 prospective and 1 case–control) (Table 1). Moreover, in the study of Burke et al. (2007) a significant association with risk of IHD was found with larger intake of processed red meat (i.e., bacon, canned meat, salami other sausage), but not with fresh red meat (beef, lamb or mutton, mince). Similar evidence was reported by Bernstein et al. (2010), showing that the risk of coronary heart disease was higher in subjects consuming larger amounts of total red meat but not in those with higher intake of beef. It is also noteworthy that a negative association between total red meat intake and IHD was reported in one prospective study (Whiteman et al., 1999), whereas a similar trend was observed in the male cohort men in the prospective study of Nagao et al. (2012). Additional evidence that limiting red meat is unnecessarily restrictive and may also carry adverse health consequences has been recently brought. Interestingly, a recent study including 1152 subjects (635 women and 517 men) failed to find a significant association between red or processed meat intake and serum cholesterol level or blood pressure (Wagemakers, Prynne, Stephen, & Wadsworth, 2009). A very modest association could only be observed between red or processed meat intake and waist circumference in men (p = 0.04) but not in women (p N 0.05). The lean red meat contains a very modest amount of saturated fat and its consumption within an appropriate diet was shown to be effective to lower low density lipoprotein (LDL) cholesterol (Binnie, Barlow, Johnson, & Harrison, 2014; Li, Siriamornpun, Wahlqvist, Mann, & Sinclair, 2005). These finding was confirmed by a recent meta-analysis of eight randomized, controlled clinical trials (Maki et al., 2012), which showed that fasting lipid level profile was not significantly modified with beef consumption compared to poultry or fish intake. It was also demonstrated that lean red meat intake is not effective to induce a prothrombotic state, due to the lack of any interaction with both primary and secondary hemostasis (Li et al., 2005). Overall, total red meat consumption appears to be globally modest in developed countries and in line with current recommendations (Binnie et al., 2014). It is now clearly established that intake of total red meat is associated with the generation of a vast array of carcinogens such as heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and saturated fatty acids, which would ultimately
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promote the development of certain types of cancer, especially colorectal malignancies (Abid, Cross, & Sinha, 2014). Nevertheless, the epidemiological data that we have reviewed in this article does not support the existence of clear relationship between total red meat consumption and IHD. Some conclusions can be made. First, due to the large heterogeneity of the criteria used for diagnosing IHD and for defining red meat (Table 2), large prospective trials with standardized criteria are needed to clearly establish the relationship between IHD and different types of red or processed meat. Importantly, this latter aspect is an insurmountable drawback for meta-analyzing data in this systematic literature review, since it may be essentially misleading to arbitrarily pool the effects of different types of red or processed meat across the various studies, as clearly shown in Table 2. Then, future diet recommendations for prevention of CVD should take into account that the current literature data does not support the existence of an unquestionable relationship between large intake of red meat and the risk of myocardial ischemia. Conflicts of interests The authors declare that no conflict of interest exists. References Abid, Z., Cross, A. J., & Sinha, R. (2014). Meat, dairy, and cancer. The American Journal of Clinical Nutrition, 100(Suppl. 1), 386S–393S. http://dx.doi.org/10.3945/ajcn.113. 071597 (ajcn.113.071597). Ascherio, A., Willett, W. C., Rimm, E. B., Giovannucci, E. L., & Stampfer, M. J. (1994). Dietary iron intake and risk of coronary disease among men. Circulation, 89(3), 969–974. Bernstein, A. M., Sun, Q., Hu, F. B., Stampfer, M. J., Manson, J. E., & Willett, W. C. (2010). Major dietary protein sources and risk of coronary heart disease in women. Circulation, 122(9), 876–883. http://dx.doi.org/10.1161/CIRCULATIONAHA.109. 915165 (CIRCULATIONAHA.109.915165). Binnie, M. A., Barlow, K., Johnson, V., & Harrison, C. (2014). Red meats: Time for a paradigm shift in dietary advice. Meat Science, 98(3), 445–451. http://dx.doi.org/10. 1016/j.meatsci.2014.06.024 S0309-1740(14)00192-2. Burke, V., Zhao, Y., Lee, A. H., Hunter, E., Spargo, R. M., & Gracey, M. (2007). Health-related behaviours as predictors of mortality and morbidity in Australian Aborigines. Preventive Medicine, 44(2), 135–142. http://dx.doi.org/10.1016/j.ypmed.2006.09.008 (S0091-7435(06)00378-1). Chen, Y., McClintock, T. R., Segers, S., Parvez, F., Islam, T., & Ahmed, A. (2013). Prospective investigation of major dietary patterns and risk of cardiovascular mortality in Bangladesh. International Journal of Cardiology, 167(4), 1495–1501. http://dx.doi. org/10.1016/j.ijcard.2012.04.041 (S0167-5273(12)00462-7). Food Agriculture and Organization of the United Nations (2014). FAO world food outlook Retrieved Accessed: March, 10, 2015, from http://www.fao.org/ag/againfo/themes/ en/meat/home.html. Hu, F. B., Stampfer, M. J., Manson, J. E., Ascherio, A., Colditz, G. A., & Speizer, F. E. (1999). Dietary saturated fats and their food sources in relation to the risk of coronary heart disease in women. The American Journal of Clinical Nutrition, 70(6), 1001–1008.
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