Meat Consumption and Cardiovascular Disease Research Paper

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Introduction

Cardiovascular disease (CVD), particularly coronary heart disease (CHD), continues to be a major cause of mortality, morbidity, and disability in the United States and other industrialized countries. In 2004 the prevalence of CVD in the U.S. population was estimated to be 33% (79 400 000 persons), and it accounted for 871 517 deaths (36.3% of all 2 398 000 deaths in 2004). In 2007, the direct and indirect costs of CVD in the United States are estimated to be $431.8 billion. In Europe, CVD accounts for over 4.35 million deaths each year (49% of all deaths). Overall CVD is estimated to cost the EU economy € 169 billion annually (Petersen et al., 2005). Globally, CVD was responsible for 16.7 million deaths in 2002, about one third of deaths worldwide. In recent years the burden of CVD has steadily increased in developing countries as well. Around 80% of all CVD deaths worldwide now occur in low and middle-income countries. It is estimated that by 2020, CVD will be responsible for 19 million deaths in developing countries (Murray and Lopez, 1996).

The best strategy for primary prevention of CVD is a healthy lifestyle, including maintenance of normal weight, regular exercise, no smoking, and consumption of a limited amount of alcohol. In addition, dietary factors play a critical role in the development of CVD. While foods from animal sources contain important nutrients that may not be readily available from plant sources, high consumption of meat has been shown to be strongly and positively associated with risk of morbidity and mortality from CVD, diabetes mellitus, and certain cancers. Animal fats from meat and dairy products are currently the major source of saturated fats in the U.S. diet.

Data from surveys conducted by the USDA show that since the early twentieth century, consumption of meat in the United States has progressively increased and now exceeds nutritional needs, contributing to high rates of CVD and other chronic diseases. According to USDA data, in 2000 total meat consumption (red meat, poultry, and fish) amounted to an average 195.5 pounds per person, which is 57 pounds higher than the level in 1950–59. Each American consumed an average of 7 pounds more red meat (mostly beef ) than in 1950, 46 pounds more poultry, and 4 pounds more fish and shellfish. However, consumption of red meat, primarily beef, peaked in 1970–79 and has since been on the decline: average annual per capita consumption of red meat increased from 106.7 pounds in 1950–59 to 129.5 pounds in 1970–79, but steadily decreased to 113.5 pounds by 2000 (USDA, 2003).

This research paper reviews current research on the association of meat (red meat/poultry) and fish consumption to CVD risk factors such as hypercholesterolemia, hypertension, and diabetes, and to morbidity and mortality related to CVD; it also summarizes current nutritional guidelines and recommendations by the USDA and American Heart Association (AHA) for primary prevention of cardiovascular disease.

Meat Consumption And CVD Risk Factors

Numerous studies have examined the association of meat consumption – red meat, poultry, and fish – to CVD risk factors such as high blood pressure, high cholesterol, and diabetes. Compared with individuals who eat meat frequently, those who do not eat any meat or eat meat only rarely (less than once a week) have on average lower cholesterol levels and lower risk of type 2 diabetes. They also have lower mean weights, consume less alcohol, report more physical activity, and in general exhibit healthier dietary patterns (Thorogood et al., 1987; Slattery et al., 1991; Tande et al., 2004).

Meat Consumption And Cholesterol

Tande et al. (2004) used data from 9111 men and women ages 20–59 years who participated in the National Health and Nutrition Examination Survey III (NHANES III) to examine the associations between the five major food groups as delineated by the food guide pyramid and serum lipid levels. In linear regression analyses adjusted for age, sex, body mass index (BMI), waist to hip ratio, education, income, smoking, ethnicity, activity, and menopausal status, higher meat intake was associated with higher LDL-cholesterol ( p = 0.02). In the Oxford Vegetarian Study on about 6000 vegetarians and 5000 nonvegetarians from the U.K., mean total cholesterol and LDL-cholesterol concentrations (adjusted for age and sex) were significantly lower in vegans than in meat eaters, with similar intermediate levels among persons who ate fish but not meat or those who were lactoovovegetarians. Mean HDL-cholesterol levels were highest among fish eaters with similar levels among the other groups (Thorogood et al., 1987). These differences in plasma lipid concentrations persisted with further adjustment for BMI (Thorogood et al., 1989). In stepwise multiple linear regression analyses, after adjusting for age, meat consumption was positively associated with mean total cholesterol levels in both men and women (Appleby et al., 1995). Among 518 men ages 70–89 from the Zutphen Study, dietary intake was assessed by the cross-check dietary history method and participants were aggregated by cluster analysis into four groups, including one group characterized by high meat consumption (which also had higher intake of eggs, cheese, and edible fats), and another group by a healthy dietary pattern. Mean total serum cholesterol was 0.26 mmol/L higher in the high meat cluster compared with the healthy diet cluster (Huijbregts et al., 1995). Cross-sectional data from the Coronary Artery Risk Development in Young Adults (CARDIA) study showed that individuals who ate red meat and poultry less than once a week (n = 47; approximately 1% of CARDIA cohort) had lower mean levels of total plasma cholesterol ( p = 0.001), LDL-cholesterol ( p = 0.001), and triglycerides ( p = 0.015) than those who ate meat more frequently (Slattery et al., 1991).

In a small controlled trial, Sacks et al. (1981) examined the effect of meat intake (250 grams of beef/day) for 4 weeks among 21 strict vegetarians, showing a significant increase in plasma total cholesterol by 19% at the end of the 4-week period. No changes in plasma HDL-cholesterol were observed. A more recent randomized clinical trial comparing the effects of lean red meat and lean white meat consumption on serum lipid levels of 191 men and women with hypercholesterolemia demonstrated reductions in LDL-cholesterol (by 1%-3%) and elevations in HDL-cholesterol (by about 2%) in both groups in 36 weeks of treatment (Davidson et al., 1999).

Meat Consumption And Blood Pressure

The association of meat consumption and blood pressure (BP) has not been clearly elucidated, possibly due to the confounding effects of saturated fats and dietary cholesterol which are contained in meat and have been directly associated with BP (Stamler et al., 1996, 2002). However, numerous studies have reported that BP is lower among vegetarians than nonvegetarians (Sacks and Kass, 1988; Fraser, 2003), and addition of meat to a vegetarian diet has been shown to increase BP (Sacks et al., 1981). In a small clinical trial among 21 strict vegetarians, there was a significant increase in their systolic BP by 3% after consumption of 250 grams of meat daily for 4 weeks compared with control values. No significant changes in diastolic BP were observed (Sacks et al., 1981).

Among 41 541 U.S. female nurses aged 38–63 years who completed a semi quantitative food frequency questionnaire and were free of diagnosed hypertension, cancer, or CVD at baseline, meat intake was directly associated with systolic but not diastolic BP. Within the meat food group, processed meats, hamburger, and beef were directly associated and chicken was inversely and significantly associated with BP. Fish intake was not associated with BP (Ascherio et al., 1996). Steffen and colleagues (2005) examined the association of meat consumption with 15-year incident high BP among 4304 men and women baseline ages 18–30 years from the CARDIA study. Consumption of meat (red and processed meat, poultry, fish) and eggs were positively associated with the risk of developing high BP, even after adjustment for potential explanatory factors such as lifestyle behaviors, nutrients, and physiologic measures. In subanalyses, there was no association between poultry or fish and the development of elevated BP ( p for trend was 0.19 and 0.21, respectively); however, red and processed meat intake was positively associated with elevated BP. Among 1710 men ages 41–57 years from the Chicago Western Electric Study, higher intakes of beef/ veal/lamb and poultry were associated with greater increases in systolic and diastolic BP over 7 years of follow-up. For example, men who reported intake of 8 to 20 or more servings of 120-gram portions of meat per month had, respectively, 5.4 mmHg and 6.0 mmHg greater increase in systolic BP ( p-values less than 0.05), and 2.0 mmHg and 2.5 mmHg greater increase in diastolic BP ( p-values 0.08 and 0.03) than men who consumed less than 8 servings of meat per month. Adjustment for various nutrients did not greatly impact the meat and poultry–BP associations. Men with higher levels of fish intake had less of an increase in BP over time although these findings were not significant (Miura et al., 2004).

Meat Consumption And Diabetes

In a study involving Seventh-Day Adventists, total meat consumption was associated with a higher prevalence of type 2 diabetes and with a higher incidence of diabetes as mentioned on death certificates. Compared with vegetarians (defined as those who consumed meat less than 1 day a week), the age-adjusted prevalence ratio for self-reported diabetes at baseline was 1.9 (95% CI, 1.4–2.6) for male nonvegetarians and 1.6 (95% CI, 1.3–2.0) for female nonvegetarians (i.e., those who consumed meat on 1 or more days per week). Multivariate-adjusted risk of prevalent diabetes was about three times higher for nonvegetarian men and more than twice as much for nonvegetarian women who ate meat 6 or more days per week than for their vegetarian counterparts. Meat consumption was positively associated with any mention of diabetes on the death certificate among men but not among women. In multivariate-adjusted analyses, risk of diabetes mention on the death certificate was almost twice as high for all nonvegetarian men combined (i.e., men who ate meat at least 1 day a week) and more than three times as high for nonvegetarian men who ate meat 6 or more days a week than for vegetarian men (Snowdon and Phillips, 1985).

Similarly, among 42 504 men aged 40–75 years and free of diagnosed diabetes and CVD at baseline, consumption of processed meats five or more times a week was associated with a 46% higher risk of type 2 diabetes compared with infrequent intake ( p for trend under 0.0001). However, intake of unprocessed red meat (beef, lamb, or pork) and of poultry (chicken or turkey with or without skin) was not associated with risk for type 2 diabetes (Dam et al., 2002). In the Nurses’ Health Study (NHS), consumption of processed meat, but not other meats, was positively associated with a 6-year risk of type 2 diabetes after adjustment for BMI, prior weight change, and alcohol and energy intake (Colditz et al., 1992). A subsequent report from the NHS among 69 554 women showed that with longer follow-up (14 years) not only processed meats but also red meat were positively associated with type 2 diabetes. The highest quintiles of red meat and total processed meat intake were associated with 36% and 60% higher risk of type 2 diabetes, respectively, compared with the lowest quintiles of intake. In analyses with meat intake as a continuous variable, each 1-serving increase in red meat and in total processed meat intake was associated with 26% and 38% higher risk of diabetes, respectively (Fung et al., 2004). These findings suggest that processed meat may confer a higher risk for diabetes than red meat. Processed meats contain a high level of nitrites (commonly used for the preservation of meat) and interaction of nitrites with amines from the meat can lead to the formation of nitrosamines (some of which are b-cell toxins) in the food or in the stomach. Both nitrites and nitrosamines have been positively associated with the risk of type 1 diabetes, although their association with type 2 diabetes is unclear (Virtanen et al., 1994; Parslow et al., 1997).

Meat Consumption And CVD Morbidity And Mortality

In general, diets high in red meat have been associated with increased CVD risk whereas higher intakes of fish and poultry have been associated with lower CVD risk (Hu et al., 2000; Fung et al., 2001; He et al., 2004a, 2004b). A report on 44 875 men aged 40–75 from the Health Professionals Follow-up Study found that a ‘prudent’ dietary pattern which included higher intakes of fruit, vegetables, whole grain, fish and poultry, was associated with a lower risk of CHD, whereas a ‘Western’ dietary pattern characterized by red meat, processed meat, high fat dairy products, refined grains, and sweets was associated with higher CHD risk (Hu et al., 2000). Similar associations of these dietary patterns with risk of CHD and stroke were reported by the NHS (Fung et al., 2004a, 2004b).

Much of the data on meat consumption and cardiovascular diseases come from longitudinal studies of California Seventh-Day Adventists (Snowdon et al., 1984; Snowdon, 1988; Fraser, 1999), a conservative religious group whose members are discouraged from consuming meat, fish, coffee, and eggs, and prohibited from using alcohol and tobacco. About half of all Adventists are lacto-ovovegetarians (i.e., exclude meat but not dairy and eggs from their diets), and there is considerable variation in past and current levels of meat consumption among vegetarians and nonvegetarian Adventists, respectively (Snowdon et al., 1984). Snowdon and colleagues reported the relationship of meat consumption and 21-year risk of ischemic heart disease (IHD) mortality among 25 153 men and women (baseline ages 45–84) from the Adventists Mortality Study, whose dietary habits were assessed by a questionnaire at baseline in 1960 (Snowdon et al., 1984; Snowdon, 1988). Usual meat consumption (specifically meat and poultry) was assessed by a single question, that is, ‘How many days per week do you eat meat?’ Fish consumption was assessed separately. Vegetarians were defined as individuals with meat/poultry intake less than 1 day a week. Because red meat and poultry intake was assessed together by a single question, differences in their association with risk could not be assessed. Meat consumption was positively associated with fatal IHD in both men and women. Furthermore, the observed higher age-adjusted risks of fatal IHD for nonvegetarian men and women were similar among those with versus without a history of heart disease at baseline, that is, 43% and 35% versus 49% and 37%, respectively. In subsequent analyses combining individuals with and without baseline heart disease and stratified by level of meat consumption (6 or more, 3–5, 1–2, and less than 1 day/week, i.e., vegetarians/reference group), meat intake was significantly and positively associated with IHD in all age groups except in the oldest group for men and in the two older age groups (ages 65–74 and 75–84) for women. Positive associations between meat consumption and IHD were stronger in men than in women, and, overall, strongest in younger (ages 45–54) than older men. In age-adjusted analyses, men who ate meat 6 or more days a week had almost a threefold higher risk of fatal IHD compared with those who ate meat less than 1 day a week; for women, risk (computed for the 45–64 year age group since number of deaths were small in the 45–54 age group) was nonsignificantly higher by 26%. In multivariate analyses adjusted for age, marital status, cigarette smoking history, obesity, and frequency of egg, cheese, milk, and coffee consumption, findings were similar. Daily consumption of meat was associated with 70% higher risk of IHD for men and 37% higher risk for women compared with no meat intake (p values were less than 0.001 and 0.02, respectively) (Snowdon et al., 1984; Snowdon, 1988). Meat consumption had no clear association with stroke among either men or women from the Adventists Mortality Study (Snowdon, 1988).

These findings were supported by results from the more recent Adventists Health Study (1976–1998) cohort of 34 192 California Seventh-Day Adventists aged 25 years and older, in whom baseline dietary assessment was conducted by a food-frequency questionnaire (including questions regarding 51 different foods or food groups). In multivariate analyses adjusted for age, smoking, BMI, exercise, hypertension, and intake of several foods, beef consumption was significantly associated with fatal IHD in men; risk of fatal IHD was about twofold higher in men who ate beef less than three times a week and exceeded twofold (p < 0.0001) in men who ate beef three or more times a week than in vegetarians. However, no associations of beef consumption and fatal IHD were observed among women. Furthermore, beef consumption was not significantly associated with the incidence of nonfatal myocardial infarction (MI) (Fraser, 1999). In the Oxford Vegetarian Study, 6115 non-meat eaters (mean age 38.7 þ 16.6) and 5015 meat eaters (mean age 39.3 þ 15.4) were recruited between 1980 and 1984 through the Vegetarian Society of the U.K. and the news media. Nonvegetarians were nominated by vegetarians from among their family and friends. Diet was assessed by a simple food frequency questionnaire. During 12 years of follow-up, non-meat eaters had significantly lower standardized mortality ratios for IHD than meat eaters; compared with the general population, mortality was 49% lower for meat eaters and 72% lower (p < 0.01) for non-meat eaters. The unadjusted risk of IHD death for non-meat eaters was 45% lower than that for meat eaters. However, with adjustment for smoking, BMI, and social class, the association weakened and became nonsignificant (Thorogood et al., 1994; Applyby et al., 1999). In a cohort of 4336 men and 6435 women (43% vegetarians) followed on average for 16.8 years, a vegetarian diet was associated with 15% lower mortality from IHD, but these findings were not significant (Key et al., 1996). A report, which combined data for 76 172 men and women from five prospective cohort studies, compared mortality rates between vegetarians (persons who did not eat any meat or fish) and nonvegetarians with other similar lifestyles. IHD mortality rate was 24% lower in vegetarians than in nonvegetarians after a mean follow-up of 10.6 years. Compared with persons who ate meat at least once a week, IHD mortality was 20% lower in persons who ate meat occasionally but less than once a week, 34% lower in persons who ate fish but not meat, 34% lower in lactoovovegetarians, and 26% lower in vegans (Key et al., 1999).

Menotti and colleagues reported associations between food groups and a 25-year risk of CHD mortality among 12 763 middle-aged men from the Seven Countries Study. Animal food groups were directly correlated and fish and vegetables were inversely correlated with CHD mortality (Menotti et al., 1999). Among women who participated in the NHS, consumption of red meat was associated with significantly higher risk of CHD by 43% per each 1serving/day, whereas consumption of poultry and fish was associated with 49% lower risk of CHD after adjustment for age. These associations were attenuated and became nonsignificant after multivariate adjustment. The ratio of red meat to poultry and fish was more strongly associated with CHD risk and remained significant after multivariate adjustment; CHD mortality risk was 32% higher for the highest compared with the lowest quintile of intake ( p–trend, 0.001) (Hu et al., 1999). In a report from the Iowa Women’s Health Study on 29 017 postmenopausal women, Kelemen and colleagues (2005) estimated a 15-year risk of CHD mortality from a simulated isoenergetic substitution of dietary protein for carbohydrates and of vegetable for animal protein (with adjustment for carbohydrates). Among women in the highest quintile of intake, CHD mortality risk was significantly lower by 30% from the substitution of vegetable for animal protein compared with women with the lowest quintile of intake ( p–trend, 0.02). No association with risk of CHD mortality was seen when animal protein was substituted for carbohydrates. However, CHD mortality was significantly associated with red meats; risk of CHD mortality was 44% higher for the highest versus lowest quintile of intake when red meat was substituted in place of number of servings of carbohydrate-rich foods ( p trend, 0.02). No association with poultry or fish was observed.

Sauvaget and colleagues (2003) examined the associations of animal product intake with risk of stroke mortality in a cohort of 37 130 men and women from Japan, who responded to a mailed survey, including a 22-item food frequency questionnaire, and who were followed for 16 years. Consumption of beef and pork or of pork products was not associated with higher risk of stroke mortality. A positive but nonsignificant association of chicken intake with stroke mortality risk was observed (i.e., 43% higher risk for almost daily consumption versus none). Among participants with the highest tertile of intake of animal products combined (beef and pork, chicken, pork products, milk, eggs, dairy products, fish, broiled fish), risk of all stroke mortality and risk of intracerebral hemorrhage mortality was significantly lower by 12% and 24%, respectively ( p–trend, 0.03), compared with persons with the lowest tertiles of intake. In a case-control study of lifestyle risk factors, stroke cases were obtained from a population-based register of acute cerebrovascular events in Perth, Western Australia. Consumption of meat more than four times a week was associated with higher risks of all strokes combined and first-ever strokes, in persons without prior history of any stroke or transient ischemic attack ( Jamrozik et al., 1994). However, when controls were followed prospectively for 4 years, consumption of meat more than four times a week was associated with lower risk of fatal vascular events (deaths from CHD, stroke, ruptured aortic aneurysm, peripheral vascular disease, or mesenteric thrombosis) by 38%, major vascular events (fatal vascular events, nonfatal MI, or nonfatal stroke) by 40%, and first-ever major vascular events by 44%, compared with less intake ( Jamrozik et al., 2000).

Fish Consumption And Cardiovascular Disease

Fish And CHD

While numerous studies have investigated the association of fish consumption with CHD mortality, there are little data from randomized clinical trials. Prospective epidemiologic studies have yielded inconsistent findings. Some studies showed an inverse association between fish intake and risk of CHD mortality (e.g., Kromhout et al., 1985; Norell et al., 1986; Kromhout et al., 1995; Oomen et al., 2000; Mozaffarian et al., 2003; Jarvinen et al., 2006), whereas others found no association (e.g., Curb and Reed, 1985; Vollset et al., 1985; Fraser et al., 1992; Salonen et al., 1995; Osler et al., 2003). Among 1822 men aged 40–55 and free of CVD at baseline from the Chicago Western Electric study, there was an inverse graded association between fish consumption and 30-year mortality from CVD and CHD, particularly nonsudden death from MI. In multivariate-adjusted analyses, risk of CHD mortality was lower by 38%, 16%, and 12% for men who consumed 35 g or more, 18–34 grams, and 1–17 grams of fish per day, respectively, compared with those who consumed none ( p trend, 0.04). Risk of death from MI (sudden and nonsudden) was lower by 44%, 24%, and 12%, respectively (p trend, 0.02). The observed inverse association of fish consumption and CHD mortality risk was accounted for by the relation of fish consumption to nonsudden death from MI; men who consumed 35 or more grams a day had a 67% lower risk (p trend, 0.007) compared with those who did not consume fish (Daviglus et al., 1997).

Among 20 551 male U.S. physicians ages 40–84, free of MI, CVD, and cancer at baseline, consumption of fish at least once a week was associated with a 52% lower 11-year risk of sudden cardiac death compared with less than once a month fish consumption (analyses were adjusted for potential confounders; p, 0.04). Lower risk of sudden death was seen at all levels of fish consumption, but the magnitude of risk reduction did not differ substantially at intake levels greater than one serving week, suggesting a possible threshold effect. Fish consumption and omega-3 fatty acids were not associated with lower risk of total MI, nonsudden cardiac death, or total CVD mortality (Albert et al., 1998).

Among 18 244 Chinese men aged 45–64 years followed for an average of 12 years, those who consumed at least one serving of fish and shellfish ( 50g) a week had a 44% lower risk of fatal MI compared with those with less intake. In analyses adjusted for age, total energy intake, and known CVD risk factors, men who consumed 200 or more grams (four or more servings) of fish/shellfish a week had a 59% lower risk of fatal MI compared with those who consumed less than 50 grams a week. Seafood intake was not associated with risk of death from stroke or IHD other than acute MI. In analyses examining fish and shellfish intake separately, the inverse associations with acute MI persisted and were significant for both fresh/ salted fish intake (70% of total seafood consumed) and shellfish intake (30% of total seafood consumed) (Yuan et al., 2001).

Among 41 578 middle-aged Japanese men and women, higher fish intake was significantly associated with lower 11-year CHD risk, primarily nonfatal cardiac events, compared with moderate fish intake of once a week (about 20 grams/day) after adjustment for CVD risk factors and selected dietary variables. Risks of total CHD and definite MI were lower by 37% and 56%, respectively, among persons in the highest quintile of fish intake (8 times/week, median intake 180 grams/day) compared with those in the lowest quintile (once/week, median intake 23 g/day). The inverse association was primarily seen for nonfatal CHD events (risk was significantly lower by 57%) but not for fatal CHD events. These findings suggest that higher levels of fish intake can even further reduce the risk of initial CHD events compared with moderate intake (Iso et al., 2006). Higher fish consumption was also significantly associated with lower 16-year risk of CHD morbidity and mortality among 84 688 U.S. women aged 34–59 years who were free of cancer and CVD at baseline. Compared with women who rarely ate fish (less than once a month), multivariate-adjusted risk of CHD (CHD deaths and nonfatal MI) was lower by 21%, 29%, 31%, and 34% for those who ate fish one to two times a month, once a week, two to four times a week, and five or more times a week, respectively ( p trend, 0.001). The inverse association was stronger for risk of CHD mortality (p trend, 0.01) than for nonfatal MI ( p trend, 0.10); women who ate fish five or more times a week had a significantly lower risk of CHD mortality by 45%, whereas their risk of nonfatal MI was nonsignificantly lower by 23% (Hu et al., 2002).

A review published in 1999, which quantified the fish intake–mortality relationship based primarily on only four cohort studies, reported that the inverse association between fish consumption and CHD mortality was evident among ‘high-risk’ but not ‘low-risk’ populations. The authors concluded that consumption of up to 40 to 60 grams of fish daily had a dose-dependent association with markedly lower CHD mortality for individuals who were high risk (i.e., had adverse risk factors or unhealthy lifestyle behaviors), but that there were no added benefits of fish consumption for persons at low risk for CHD and with a healthy lifestyle (Marckmann and Gronbaek, 1999). However, a recent meta-analysis of 13 cohorts from 11 independent cohort studies comprising 222 364 participants (3032 CHD deaths) with an average 11.8 years of follow-up found a consistent inverse association between fish consumption and CHD mortality rates. Compared with those who never consumed fish or ate fish less than once a month, individuals with a higher fish intake had lower CHD mortality: in pooled multivariate analyses, risks for CHD mortality were 11%, 15%, 23%, and 38% lower with fish intake of one to three times a month, once a week, two to four times a week, and five or more times a week, respectively, compared with no fish intake. Inverse associations were more evident among studies with a follow-up period of 12 years or longer. A dose–response relationship between fish consumption and CHD mortality was observed: that is, each 20 grams/ day higher intake of fish was associated with a 7% lower risk of CHD mortality ( p trend, 0.03) (He, 2004). Another meta-analysis of 19 observational studies (including 14 cohort and 5 case-control studies) found that risks of fatal CHD and total CHD were lower by 17% and 14%, respectively, for those who consumed any fish compared with little or none ( p < 0.005 for both) (Whelton et al., 2004).

The benefits of fish consumption on CHD mortality rates have also been demonstrated in diabetic populations. Among 5103 diabetic women from the NHS who were free of any history of heart disease or stroke at baseline, higher consumption of fish was associated with lower CHD and total mortality, even after adjustment for established cardiovascular risk factors. Compared with women who rarely ate fish (<1 serving/month), risk of CHD (adjusted for age, smoking, and other CHD risk factors) was 30%, 40%, 36%, and 64% lower with fish consumption one to three times a month, once a week, two to four times a week, and five or more times a week, respectively (p trend < 0.002). The inverse association persisted with adjustment for dietary factors related to CHD, including fiber, trans-fatty acids, polyunsaturated to saturated fats ratio, or fruits, vegetables, and red meat intake. Consumption of fish five or more times a week was associated with a significantly lower risk of fatal CHD by 59% and of nonfatal MI by 72% compared with intake of less than one serving a month. Additional adjustment for fruits, vegetables, and red meat did not affect the estimated risks (Hu et al., 2003). Moreover, fish consumption has been associated with significantly reduced progression of coronary atherosclerosis in diabetic women with CHD. Among 229 postmenopausal women with coronary atherosclerosis, changes in the mean minimum coronary artery diameter, the mean percentage of stenosis, and the development of new coronary lesions were evaluated by quantitative coronary angiography at baseline and after 3.2±0.6 years. Compared with lower fish intakes, consumption of two or more servings of fish or one or more servings of tuna or dark fish a week was associated with smaller increases in the percentage of stenosis (4.54±1.37% vs. -0.06±1.59% and 5.12± 1.48% vs. 0.35 ± 1.47%, respectively; p < 0.05 for both) in diabetic women after adjusting for age, CVD risk factors, and dietary intakes of fatty acids, cholesterol, fiber, and alcohol. No significant associations were found in nondiabetic women. Higher fish consumption was also associated with smaller declines in minimum coronary artery diameter and fewer new lesions (Erkkila et al., 2004).

Fish And Stroke

Several prospective epidemiologic studies have examined the association between fish consumption and the risk of stroke. However, the findings have been conflicting, with some cohort studies reporting an inverse association between fish intake and risk of stroke after adjustment for potential confounders (e.g., Keli et al., 1994; Iso et al., 2001; Mozaffarian et al., 2005), while others have reported no significant associations (e.g., Folsom and Demissie, 2004; Nakamura et al., 2005; Myint et al., 2006). In the Health Professional Follow-up Study (43 671 men aged 40–75 years and free of CVD at baseline), consumption of fish one to three times a month was associated with 43% lower risk of ischemic stroke compared with less frequent consumption. However, a higher frequency of fish intake was not associated with further risk reduction. No significant associations were found between fish intake and risk of hemorrhagic stroke or of total stroke (He et al., 2002). In the Zutphen Study, men who ate more than 20 grams of fish a day had about a 50% lower risk of total stroke compared with those who consumed less (Keli et al., 1994). A case-control study of lifestyle risk factors for stroke, involving cases from Perth, Western Australia, reported an inverse relation of fish consumption to first stroke; with risk significantly lower by 40% with consumption of fish more than twice a month compared with less consumption. In identical multivariate risk factor models for ischemic stroke and for intracerebral hemorrhage, a significant inverse relation with fish consumption was found for intracerebral hemorrhage (risk was significantly lower by 57%) but not for ischemic stroke (risk was nonsignificantly lower by 10%) ( Jamrozik et al., 1994). However, in a cohort of Japanese men and women, risks of mortality from total stroke and intracerebral hemorrhage were significantly lower by 15% and 30%, respectively, for the highest tertile of intake compared with the lowest (Sauvaget et al., 2003).

Among 79 839 women from the NHS who were followed for 14 years, significant inverse associations were observed between fish intake and age and smoking adjusted risk of total stroke, ischemic stroke, and thrombotic infarction. With further adjustment for other CVD risk factors and dietary variables, the inverse association of fish intake with risk of thrombotic stroke remained significant. Risk of thrombotic infarction was significantly lower by 51% among women with fish intake of two or more times a week (p = 0.03) compared with those who ate fish less than once a month. Fish intake was not associated with risk of hemorrhagic stroke (Iso et al., 2001). In the NHANES I Epidemiologic Follow-up Study, white men who ate fish more than once a week experienced only a nonsignificant reduction in risk of incident fatal and nonfatal stroke by 15% compared with those who never ate fish. However, risk of incident stroke for white women who consumed fish more than once a week was about half that of women who never consumed fish after adjustment for multiple risk factors for stroke. For black women and men, any fish consumption compared with none was significantly associated with 49% lower risk of incident stroke (Gillum et al., 1996).

Differences in fish consumption at baseline were not significantly associated with higher or lower risk for total stroke mortality in the Chicago Western Electric Study cohort of 1847 men aged 40 to 55 years and free of CVD at baseline (Orencia et al., 1996). Similarly, in the Physicians’ Health Study, no significant association between fish consumption and risk of total stroke was observed; however, about half of the men in this cohort were taking aspirin which may have attenuated the effect of fish intake (Morris et al., 1995).

A meta-analysis of nine cohorts from eight independent studies comprising 200 575 participants (3491 stroke events) with an average follow-up of 12.8 years found an inverse association between fish consumption and the risk of stroke, particularly ischemic stroke. Compared with individuals who never ate fish or ate fish only once a month, in pooled multivariate-adjusted analyses, risk of total stroke was lower by 9%, 13%, 18%, and 31% for those with fish intake of one to three times a month, once a week, two to four times a week, and five or more times a week, respectively ( p trend, 0.06). In stratified analyses of three large cohort studies with data on stroke subtypes, pooled risk of ischemic stroke was significantly lower by 31%, 32%, 34%, and 35% with fish consumption one to three times a month, once a week, two to four times a week, and five times a week, respectively, compared with no fish consumption. However, there was no strong dose–response relationship ( p trend, 0.24). No significant association of fish consumption with risk of hemorrhagic stroke was found (He et al., 2004). The authors concluded that fish intake is inversely associated with the risk of stroke, particularly ischemic stroke, with a significantly lower risk of ischemic stroke by fish intake as little as one to three times a month. However, there is still insufficient data to clarify the association, if any, of fish consumption with the risk of hemorrhagic stroke (He et al., 2004).

The beneficial effects of fish consumption on mortality from CHD and stroke are postulated to stem from their relatively high content of omega-3 polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) (Kris–Etherton et al., 2003; Wang et al., 2006). Several biological effects of omega-3 fatty acids account for their protective effect on CVD (Kris–Etherton et al., 2003). A hypotriglyceridemic effect and a dose–response relationship between omega-3 fatty acid intake and triglyceride-lowering has been demonstrated (Harris et al., 1988; Grimsgaard et al., 1997; Harris, 1997). Omega-3 fatty acids have been shown to have antiarrhythmic properties which may protect against sudden CHD death (Siscovick et al., 1995, 2000; Albert et al., 1998). They decrease platelet aggregation (Agren et al., 1997; Mori et al., 1997) and additional anti-atherogenic effects have been proposed, including reduced expression of adhesion molecules and anti-inflammatory effects (De Caterina and Libby, 1996; Endres and von Schackey, 1996; Abe et al., 1998; De Caterina et al., 2000). In addition, omega-3 fatty acids have a mild BP lowering effect (Appel et al., 1993; Morris et al., 1993; Howe, 1997) and may improve endothelial function, possibly by enhancing production of nitric oxide (Chin and Dart, 1995; Harris et al., 1997). However, while numerous experimental studies have demonstrated some benefits of fish oil intake, they generally used a dose of omega-3 fatty acids that was substantially higher than quantities typically consumed in the diet. The amount of omega-3 fatty acids that need to be consumed to confer a cardioprotective effect remains unclear, although existing scientific evidence suggests that intakes between 0.5 and 1.8 grams of EPA/ DHA per day significantly reduces CVD mortality (Kris–Etherton et al., 2003).

The continued increase in overweight and obesity globally has led to the proliferation of numerous diet strategies to promote weight loss. While some of these popular diets are based on long-standing medical advice and recommend restricting portion sizes and calories, various alternatives have been developed some of which promote a high intake of meat and other animal foods and restrict intake of carbohydrates. Long-term randomized trials comparing low-carbohydrate diets with low-fat reduced calorie diets in obese patients have demonstrated better weight loss on the low-carbohydrate diets after 6 months, but no difference after 12 months (Foster et al., 2003; Stern et al., 2004).

Much of the data on the association of meat intake and CVD outcomes are derived from studies involving vegetarian populations (e.g., Thorogood et al., 1994; Key et al., 1996, 1999; Mann et al., 1997). In general, it has been shown that vegetarians experience lower risk of CVD and greater life expectancy compared with meat eaters and that their risk increases with higher meat intake. These observations raise concerns about the level of meat consumption compatible with CVD prevention. However, CVD risk differs with the type of meat consumed and the method of food preparation, and few studies have examined associations separately for red and white meat. In the Nurses’ Health Study, red meat consumption (including processed meat) was associated with higher age-adjusted risk of CHD, while poultry and fish consumption was associated with lower risk (Hu et al., 1999). Lean red meat, trimmed of visible fat, and skinless poultry are lower in saturated fats and an important source of protein, vitamin B12, niacin, zinc, and iron. Among persons with hypercholesterolemia, dietary interventions to lower cholesterol incorporating either lean red meats (beef, veal, and pork) or lean white meats (poultry and fish), which are part of the National Cholesterol Education Program (NCEP) Step I diet, showed similar reductions in LDL-cholesterol and elevations in HDL-cholesterol. This demonstrates that lean red meat, if consumed in the recommended amounts, can be part of a healthy diet (Davidson et al., 1999). Finally, there is compelling evidence that frequent fish consumption is associated with lower risk of CVD, particularly CHD. For example, risk of CHD mortality was 38% lower with consumption of 35 or more grams of fish daily in the Western Electric Study (Daviglus et al., 1997), and 45% lower with fish consumption five or more times a week in the Nurses Health Study, compared to little or no intake (Hu et al., 2002).

Current nutritional guidelines proposed by the USDA recommend limiting daily consumption from the meat and beans group – including lean meats, poultry, fish, eggs, beans, and nuts/seeds – to about 5to 6-ounce equivalents in all among adults (1-ounce equivalent is 1 oz. of cooked lean meats, poultry, fish; 1 egg; 0.25 cup cooked dry beans or tofu; 1 tablespoon peanut butter; 0.5 oz. nuts or seeds) (U.S. Department of Health and Human Services, 2005). Recent dietary recommendations made by the AHA include limiting saturated fats to less than 7% of daily energy, and cholesterol to less than 300 mg/day, by consuming lean cuts of meat, skinless poultry, and vegetable alternatives and fat-free or low-fat dairy products, and eating fish, preferably oily fish, at least twice a week (Lichtenstein et al., 2006). The Dietary Approaches to Stop Hypertension (DASH) eating plan, which is in accordance with AHA dietary recommendations, limits intake of lean meat, poultry, and fish to less than six servings per day for a 2000 calorie diet (one serving consists of 1 oz. of cooked lean meat with visible fat trimmed away, skinless poultry, or fish; or 1 egg). Moreover, numerous studies have demonstrated the benefits of Mediterranean diets and diets high in fruits, vegetables, whole grains, and fish, and low in red meat, high-fat dairy products, and saturated fats (e.g., Appel et al., 1997; Stampfer et al., 2000; Trichopoulou et al., 2003; Knoops et al., 2004; Trichopoulou, 2004). With CVD continuing to be the leading cause of morbidity and mortality in the United States and other industrialized countries despite advances in medical technology and treatment, strong primary preventive measures are urgently required from an early age to promote healthy lifestyles, including healthy diets and increased physical activity, in order to lessen future individual and societal burden of disease.

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