Key Points
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A primary focus of CVD prevention is LDL-C and blood pressure lowering and improvement of other cardiometabolic risk factors.
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Current dietary guidelines for chronic disease prevention emphasize an overall healthy dietary pattern based on foods rather than on targeting specific nutrients.
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Strategies used in clinical practice for CVD prevention, specifically LDL-C and blood pressure lowering, include the Therapeutic Lifestyle Changes (TLC) and Dietary Approaches to Stop Hypertension (DASH) diets.
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Dietary patterns for weight loss are most dependent on calorie control, but modification of the macronutrient profile may target cardiovascular risk factors, including blood pressure, lipids, and lipoproteins.
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Key components of heart-healthy dietary approaches include reduced intake of saturated fatty acids, trans –fatty acids, and cholesterol and increased intake of fruits and vegetables, whole grains, reduced-fat dairy, and heart-healthy protein (from plant and low–saturated fatty acid animal sources).
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Additional dietary components (soluble fiber, sterols and stanols, soy protein, and unsaturated fats) and supplements (fish oil and niacin) improve CVD risk status.
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Food-based recommendations and their associated tools, such as MyPyramid (developed by the U.S. Department of Agriculture), assist consumers in implementing dietary guidelines and may assist clinicians in counseling patients.
Nutritional Goals for Prevention of Cardiovascular Disease
The goal of cardiovascular disease (CVD) prevention is to decrease CVD morbidity and mortality through pharmacologic and lifestyle (including dietary, behavioral, and physical) intervention. Reduction in major risk factors, which include total cholesterol and low-density lipoprotein cholesterol (LDL-C), systolic blood pressure, smoking prevalence, and physical inactivity, accounted for almost half of the decrease in coronary heart disease (CHD) mortality in the United States between 1980 and 2000. Healthy lifestyle practices that improve such modifiable risk factors are therefore imperative for CVD prevention, and unlike pharmacologic treatments, lifestyle interventions are accessible to everyone and have similar efficacy in “slowing” chronic disease progression. Modest dietary changes across an extended period can produce tangible results, both physically and psychologically, and may have a significant financial benefit. For example, if every adult in the United States reduced total daily calorie intake by 100 kcal, approximately 71.2 million cases of overweight and obesity could be resolved, saving an estimated $58 billion annually.
The most prominent risk factors for CVD are elevated serum total cholesterol and LDL-C, hypertension, diabetes, and cigarette smoking. Randomized controlled trials have shown that lowering of LDL-C and blood pressure, in particular, reduces risk for CVD. Statin drug trials demonstrate that for every 25 mg/dL lowering of serum LDL-C, there is a decrease in major vascular (−14%) and coronary (−16%) events. A linear relationship also exists between hypertension and CVD risk, which doubles with every increment of 20/10 mm Hg in systolic blood pressure (SBP)/diastolic blood pressure (DBP). Currently, the primary aim of nonpharmacologic dietary interventions is a reduction in LDL-C, with a secondary aim of lowering non–high-density lipoprotein cholesterol and blood pressure. Other CVD risk factors, such as increased serum triglycerides (TG) and glucose, decreased high-density lipoprotein cholesterol (HDL-C), hypertension, and increased waist circumference, which cluster as part of the metabolic syndrome, also are targets for intensive lifestyle therapy in an effort to optimize CVD prevention. Evidence for nontraditional risk factors, such as markers of thrombosis and inflammation, LDL-C particle size, and apolipoproteins, is emerging, and additional research will establish their contribution to overall CVD risk.
Current dietary guidelines advocate a food-based approach for optimal health and chronic disease risk reduction. Indeed, the American Heart Association (AHA) recommends a diet consistent with current guidelines to meet their 2020 Impact Goal to “improve the cardiovascular health of all Americans by 20% while reducing deaths from cardiovascular diseases and stroke by 20%.” The Dietary Guidelines for Americans, 2005 emphasize a balanced diet that incorporates a variety of foods that are consumed in moderation. Therefore, although specific foods and nutrients have been identified as being more or less “healthful,” it is the total dietary package that is most important. This chapter discusses the efficacy of a range of heart-healthy dietary patterns that have been scientifically evaluated for overall health promotion and CVD risk reduction. In particular, it reviews specific dietary patterns, such as the Therapeutic Lifestyle Changes (TLC) and Dietary Approaches to Stop Hypertension (DASH) diets, that are used in clinical practice for LDL-C and blood pressure lowering, respectively. Dietary strategies for weight loss also are reviewed. In evaluating dietary patterns, it is evident that a number of common foods exist between diets. The evidence supporting the benefits of specific foods and supplements on cardiovascular risk factors, with a particular focus on reducing LDL-C and blood pressure, is discussed. The information presented in this chapter will assist clinicians in implementing dietary strategies to manage CVD risk status in at-risk patients.
Dietary Patterns to Reduce Cardiovascular Disease Risk
Therapeutic Lifestyle Changes Diet
LDL-C has long been identified by the National Cholesterol Education Program (NCEP) as the primary target for CHD risk reduction. Recommendations by NCEP for testing and management of high blood cholesterol have been published in reports by the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). The evidence base for such recommendations is primarily from randomized clinical trials that have demonstrated that LDL-C lowering substantially reduces risk for CHD. Since the publication of the Adult Treatment Panel III (ATP III) guidelines, the results from several large-scale clinical trials have reinforced ATP III recommendations for therapeutic LDL-C lowering in high-risk and very-high-risk individuals. ATP III recommends TLC for the clinical management of LDL-C in persons from all risk classifications (see Table 16-1 for summary of key components). TLC may further reduce the incidence of CHD by modifying other cardiovascular risk factors beyond LDL-C. The primary focus of TLC is a reduction in saturated fatty acids (SFA) to <7% of total calories, trans –fatty acids to as low as possible, and cholesterol to <200 mg/day. Guidelines also are provided for monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA) intake (up to 20% and 10% of total calories, respectively), carbohydrate intake (50% to 60% of total calories), protein intake (approximately 15% of total calories), and dietary fiber intake (20 to 30 g/day). Additional therapeutic options for lowering of LDL-C include viscous fiber (10 to 25 g/day) and plant stanols or sterols (2 g/day). Achieving or maintaining a healthy body weight (by calorie manipulation) and participating in regular physical activity (enough moderate exercise to expend at least 200 kcal/day) also are essential TLC features. The combination of TLC with other LDL-C–lowering options may collectively reduce LDL-C levels by 24% to 37% ( Table 16-2 ). The magnitude of these effects has been established in well-controlled dietary intervention trials and further evaluated in free-living settings. The TLC dietary guidelines have been translated to food-based recommendations that are consistent with the AHA Diet and Lifestyle Recommendations 2006 (see Box 16-1 , discussed later in this chapter). Numerous dietary patterns that meet current nutrient recommendations for CVD risk reduction have been evaluated and shown to be efficacious relative to improving major risk factors for CVD. Several of these dietary patterns are discussed on the following pages.
| Component | Recommendation |
|---|---|
| LDL-raising nutrients | |
| Saturated fatty acids | <7% of total calories |
| Cholesterol | <200 mg/day |
| Therapeutic options for LDL lowering | |
| Increased viscous (soluble) fiber | 10-25 g/day |
| Plant stanols and sterols (2 g/day) | 2 g/day |
| Energy intake | Adjust calorie intake to achieve a healthy body weight or to prevent weight gain |
| Physical activity | Participate in enough moderate exercise to expend at least 200 kcal/day |
| Macronutrients | |
| Monounsaturated fatty acids | Up to 20% of total calories |
| Polyunsaturated fatty acids | Up to 10% of total calories |
| Total fat | 25%-35% of total calories |
| Carbohydrate | 50%-60% of total calories |
| Protein | Approximately 15% of total calories |
| Dietary fiber | 20-30 g/day |
| Dietary Component | Dietary Change | Approximate LDL Reduction |
|---|---|---|
| Saturated fat | <7% of calories | 8%-10% |
| Trans- fat | <1% of calories | 1%-2% |
| Dietary cholesterol | <200 mg/day | 3%-5% |
| Weight reduction | Lose 10 pounds | 5%-8% |
| Soy protein | 3%-5% | |
| Other LDL-lowering options | ||
| Viscous fiber | 5 to 10 g/day | 3%-5% |
| Plant sterol and stanol esters | 2 g/day | 6%-15% |
| Cumulative estimate | 24%-37% | |
Portfolio Diet
The portfolio diet incorporates four key cholesterol-lowering strategies, plant sterols (1.0 g/1000 calories), viscous fiber (8.2 g/1000 calories), soy protein (22.7 g/1000 calories), and almonds (14 g/1000 calories), within a reduced total fat diet (<30% of total calories). The portfolio diet is largely vegetarian, and SFA is limited to <7% of total calories and cholesterol to <200 mg/day. Sources of viscous fiber include eggplant and okra, oat bran, barley grains, and psyllium. Soy protein is obtained from soy milk and other soy products (such as soy burgers and sausages), and beans, chick peas, and lentils provide additional vegetable protein.
In a controlled 1-month dietary intervention with hyperlipidemic individuals, the portfolio diet reduced LDL-C by 29%, compared with an 8% reduction achieved by a low SFA (<7% of total calories) and cholesterol (<200 mg/day) diet alone (also known as a Step II diet). A subsequent trial compared the effectiveness of the portfolio diet on LDL-C lowering with statin therapy. In this study, subjects completed three 1-month intervention treatments in a randomized crossover design: a very low saturated fat diet (control or Step II diet), a control diet plus 20 mg lovastatin (statin), and the portfolio diet. LDL-C was reduced by 8%, 33%, and 29% following the control, statin, and portfolio diets, respectively. These results clearly illustrate the effectiveness of the portfolio diet over a traditional cholesterol-lowering diet and suggest that in controlled settings, the portfolio diet may be as potent as first-generation statin drugs for lowering of LDL-C. However, this dietary pattern is limited in its effects on HDL-C and TG.
When the portfolio diet is implemented in a free-living setting, its effectiveness is reduced. In a 12-month study, subjects were instructed to follow a self-selected low-fat diet (Step II diet) that incorporated the portfolio of cholesterol-lowering foods (plant sterols, viscous fiber, soy protein, and almonds). Subjects were advised to follow a vegetarian diet (without eggs, dairy products, or meat) that included 5 to 10 servings of fruits and vegetables per day, with additional plant protein and fiber from dried legumes. If meat or dairy products were consumed, subjects were counseled to choose options with reduced SFA and cholesterol. After 12 months, LDL-C was reduced by 12.8%. This reduction is appreciably less than that achieved in the metabolically controlled study, which is probably due to dietary compliance. The authors reported a significant correlation between total dietary adherence and change in LDL-C, and by 12 months, the majority of subjects had returned to an omnivorous diet (59 of 66).
When the individual components of the portfolio diet were evaluated, subjects were most compliant for almonds (79%) and plant sterol–enriched margarine (67%), whereas compliance for viscous fiber and soy protein was 55% and 51%, respectively. Despite these challenges, 32% of subjects experienced LDL-C reductions of >20%. The results of this study demonstrate the difficulty of adhering to a plant-based diet in a free-living setting. However, for subjects who do achieve this, the portfolio diet is particularly effective at lowering LDL-C. For other individuals, a focus on the incorporation of individual components (such as almonds or plant sterol–enriched margarine) may be most efficacious, particularly as plant sterols were identified as the primary LDL-C–lowering dietary component of the portfolio diet.
In addition to effects on LDL-C, the portfolio diet targets other CVD risk factors, such as LDL particle size and C-reactive protein (CRP) level. The portfolio diet significantly reduces small LDL-C subfractions <25.5 nm (−0.69 mmol/L); this effect is comparable to that achieved by statins and greater than that by a Step II diet alone and translates to a 19% reduction in 13-year risk for CHD. Interestingly, this study reported that baseline CRP levels predicted LDL-C particle size change in response to the portfolio diet. Individuals with plasma CRP levels <3.0 mg/L at baseline showed significant reductions in LDL-C particle <25.5 nm concentration, with no change in individuals with CRP levels >3.0 mg/L. When individuals with high CRP levels (>3.5 mg/L) were removed from the analysis, CRP level was significantly reduced by statins (16%) and the portfolio diet (24%) but not by the Step II diet (15%). These outcomes illustrate the importance of therapeutic interventions, such as the portfolio diet, that address multiple CVD risk factors, both traditional and emerging,
DASH and DASH-Sodium Trials
The DASH trial was a randomized controlled feeding intervention that evaluated the effects of three dietary patterns on blood pressure, lipids, and lipoproteins. The DASH dietary pattern, which is rich in fruits and vegetables (8 to 10 servings/day) and low-fat dairy products (2 or 3 servings/day), includes whole grains, legumes, fish, and poultry and is limited in added sugars and fats. It is high in dietary fiber (∼30 g/day), magnesium, potassium, and calcium and low in total fat (27% of total calories), SFA (<7% of total calories), and cholesterol (150 mg/day). In this study, 459 adults with mildly elevated blood pressure (SBP <160 mm Hg and DBP 80 to 95 mm Hg) were randomized to consume a Western diet (control diet; 48% carbohydrate, 15% protein, 37% total fat, 16% SFA), a fruits and vegetables diet (which provided more fruits and vegetables and fewer snacks and sweets than in the control diet but otherwise had a similar macronutrient distribution), or the DASH diet for 8 weeks. Sodium intake (3000 mg/day) was similar across all diets, and body weight remained constant throughout the intervention.
Compared with a Western diet, the DASH diet lowered SBP and DBP by −5.5 mm Hg and −3.0 mm Hg, respectively. It also reduced total cholesterol (−9.5%), LDL-C (−9.1%), and HDL-C (−9.2%), with no change in TG. Smaller reductions in blood pressure were observed in subjects consuming the fruits and vegetables diet (SBP, −2.8 mm Hg; DBP, −1.1 mm Hg); total cholesterol, LDL-C, HDL-C, and TG did not change. Stratified by hypertension status, the DASH diet reduced SBP and DBP by −11.6 mm Hg and −5.3 mm Hg, respectively, in stage 1 hypertensives (SBP >140 mm Hg, DBP >90 mm Hg, or both), with less dramatic effects in normotensive individuals (SBP/DBP, −3.5/−2.2 mm Hg). The most substantial reductions were observed in hypertensive African Americans; the DASH diet reduced SBP by −13.2 mm Hg and DBP by −6.1 mm Hg.
Additional hypotensive benefits can be achieved by following a DASH diet with further reductions in sodium. The DASH-Sodium trial compared the hypotensive effects of three levels of sodium restriction (high, 3200 mg/day; intermediate, 2300 mg/day; and low, 1500 mg/day) within a Western or DASH diet. In both the Western and DASH diets, sodium restriction progressively lowered blood pressure; however, the effect of sodium on blood pressure was more pronounced in subjects following the Western than the DASH dietary pattern ( Fig. 16-1 ). From highest to lowest sodium level, the reduction in SBP/DBP was 6.7/3.5 mm Hg on the Western diet and 3.0/1.6 mm Hg on the DASH diet.
For each level of sodium restriction, the DASH diet elicited lower blood pressure responses than the Western diet did, with the lowest blood pressure observed in subjects consuming the DASH diet with the lowest sodium level. The hypotensive effects of sodium restriction alone or with the DASH diet were consistent across several subgroups, including African Americans, hypertensive individuals (SBP ≥140 mm Hg or DBP ≥90 mm Hg), older adults (>45 years), and women, with mean reductions of 9.6 to 11.6 mm Hg for SBP and 4.7 to 5.7 mm Hg for DBP.
Mediterranean-Style Diets
The Mediterranean diet is a whole food–based dietary pattern that has been associated with a reduced incidence of CVD and its associated risk factors. This dietary pattern is representative of the traditions of Crete, Greece, and southern Italy in the 1960s, when the incidence of chronic disease was substantially lower than that of other countries. Key components of this dietary pattern include olive oil as the principal dietary fat source, abundant plant foods (fruits, vegetables, grains, cereals, nuts, and seeds), fish and shellfish, dairy in low to moderate amounts, poultry, eggs, and limited amounts of red meat and sweets. Moderate wine consumption (one or two 5-ounce glasses/day for men and one 5-ounce glass/day for women) also was allowed.
The cardioprotective benefits of the Mediterranean diet may in part be attributed to its nutrient profile, low SFA and high MUFA (from olive oil), and high fiber and phytosterol intake (>400 mg/day) from plants. Several clinical intervention trials have been undertaken to evaluate the benefits of the Mediterranean diet on CVD risk; however, comparisons among studies are challenging as each trial has differed with respect to nutrient profile and the specific foods used to implement the diet.
Lyon Diet Heart Study
The Lyon Diet Heart Study demonstrated that a Mediterranean-type diet, rich in α-linolenic acid, was more effective than a modified-fat diet in secondary prevention of coronary events. This study randomized 605 post–myocardial infarction patients to consume either a Mediterranean-type diet (30% of total calories from fat, 8% from SFA, 13% from MUFA, and 5% from PUFA and 203 mg/day of cholesterol) or a modified-fat diet consistent with a Step I diet with a mean follow-up of 46 months. Patients in the Mediterranean-type diet intervention group received instructions from the study dietitian and cardiologist to increase their intake of bread, fish, and root and green vegetables; to consume fruit daily; to eat less meat (beef, lamb, and pork to be replaced with poultry); and to replace butter and cream with margarine supplied by the study. The fatty acid composition of the margarine was similar to that of olive oil, except that it was higher in linoleic acid (16.4% versus 8.6% kcal) and α-linolenic acid (4.8% versus 0.6% kcal). Control group subjects followed a diet that provided 34% of calories from fat, 12% from SFA, 11% from MUFA, and 6% from PUFA and 312 mg/day of cholesterol. After 48 months, subjects consuming the Mediterranean-type diet (n = 219) had a 50% to 70% lower risk of mortality from heart disease than did subjects consuming a low-fat diet (n = 204). These outcomes occurred despite similar plasma lipids and lipoproteins, blood pressure, body mass index, and smoking status in the two groups, indicating that other risk factors, such as thrombogenesis, are involved in coronary protection.
Medi-RIVAGE Study
The Mediterranean Diet, Cardiovascular Risks and Gene Polymorphisms (Medi-RIVAGE) study is a 12-month, parallel dietary intervention trial designed to compare the effects of a Mediterranean-type diet and a low-fat diet on CVD risk factors. The low-fat diet was based on AHA guidelines and aimed for a total fat intake of <30% of total calories with equal contributions (10% each) from SFA, MUFA, and PUFA. A higher dietary fat intake (35% to 38% of total calories) was recommended for subjects in the Mediterranean-type diet arm, with an emphasis on MUFA (18% to 20% of total calories) from olive oil. SFA and PUFA each contributed 10% of total calories. The low-fat and Mediterranean-type diets were similar in their relative contributions from protein (∼15%), carbohydrate (∼55% to 60%), and cholesterol (<300 mg/day). However, the Mediterranean-type diet was higher in fiber (25 g/day compared with 20 g/day in the low-fat group) and allowed two glasses of wine per day for men and one glass for women. Alcohol was to be avoided in the low-fat group.
After 3 months of intervention, both groups (total n = 212) had similarly reduced their total fat, SFA, and cholesterol intake. The only macronutrient that differed between the groups was MUFA, which was higher in the Mediterranean-type diet group (15.6%) than in the low-fat diet group (13.4%). Significant reductions in total cholesterol were observed in both groups (Mediterranean-type diet, −7.5%; low-fat diet, −4.5%), with a trend toward reductions in LDL-C (Mediterranean-type diet, −11.4%; low-fat diet, −5.0%). Compared with baseline, both groups showed a decrease in triglycerides, glucose, and insulin, although these did not differ between groups. This lack of distinction between the two diets is not surprising given their similar macronutrient composition at 3 months of intervention.
PREDIMED Study
The Prevención con Dieta Mediterránea (PREDIMED) study is an ongoing multicenter clinical trial designed to evaluate the effects of a Mediterranean diet on the primary prevention of CVD in 7000 asymptomatic subjects ( www.predimed.org ). Men (55 to 80 years) and women (60 to 80 years) with diabetes or three or more major cardiovascular risk factors will be randomized to consume either a low-fat diet (total fat <30%, based on AHA dietary guidelines) or a Mediterranean-type diet supplemented with either 30 g/day of mixed nuts (15 g walnuts, 7.5 g hazelnuts, and 7.5 g almonds) or 1 L/week of olive oil. Participants will be observed for a median duration of >5 years and evaluated for primary clinical outcomes (cardiovascular death, myocardial infarction, and stroke).
A pilot group of 772 participants (339 men, 433 women) was evaluated for changes in lipids and lipoproteins, blood pressure, and glucose after 3 months of intervention. Compared with the low-fat group, the Mediterranean diet with nuts reduced total cholesterol by 6.2 mg/dL and TG by 13 mg/dL. HDL-C was increased by 2.9 mg/dL and 1.6 mg/dL on the Mediterranean diet with olive oil and nuts, respectively. Both diets also produced favorable changes in SBP/DBP (nuts, −7.1/−2.6 mm Hg; olive oil, −5.9/−1.6 mm Hg) and glucose concentration (nuts, −5.4 mg/dL; olive oil, −7.0 mg/dL) compared with the low-fat diet. Although it appears that a Mediterranean diet is advantageous, the results of the PREDIMED study should be interpreted with caution as both Mediterranean intervention groups received intensive behavioral counseling and nutrition education intervention, whereas the low-fat group received simple dietary advice only.
Dietary Patterns That Emphasize Specific Macronutrients
OmniHeart Trial
The OmniHeart trial was a three-period, 6-week crossover, controlled feeding study involving 164 prehypertensive or stage 1 hypertensive subjects that evaluated the cardiovascular benefits of substituting SFA with carbohydrate, protein, or unsaturated fat. Each diet period emphasized the intake of one specific macronutrient—high carbohydrate (58% of total calories), moderate to high protein (25% of total calories, 50% of which were from plant proteins), or high unsaturated fat (31% of total calories, predominantly MUFA)—thereby enabling direct comparison of these macronutrients. Increasing unsaturated fat intake caused a 9.2% reduction in TG and a 10.3% reduction in LDL-C but no change in HDL-C (−0.6%). Protein elicited a similar response, although this was more effective than unsaturated fat in lowering TG (−16.2%) and LDL-C (−11.0%) but also caused a modest reduction in HDL-C (−5.2%).
In comparison, the high-carbohydrate diet was effective only in reducing LDL-C (−9.0%) and was accompanied by a reduction in HDL-C (−2.8%). Compared with baseline, all diets decreased SBP (−8.2, −9.5, −9.3 mm Hg, carbohydrate, protein, and unsaturated fat, respectively) and DBP (−4.1, −5.2, −4.8 mm Hg, carbohydrate, protein, and unsaturated fat, respectively); however, on stratification by hypertension status, subgroup analysis showed that in both prehypertensive and stage 1 hypertensive subjects, the moderate- to high-protein and unsaturated-fat diets reduced blood pressure more than the carbohydrate diet did. On the basis of these results, partial replacement of SFA with protein or unsaturated fat appears to be more effective than replacement with carbohydrate in improving lipids and reducing blood pressure.
Dietary Strategies for Weight Loss
Dietary guidelines issued by the U.S. government and other prominent health organizations, such as the U.S. Department of Agriculture (USDA) and the AHA, emphasize the importance of achieving and maintaining a healthy body weight for prevention of chronic disease. However, there continues to be some debate as to the most effective way to achieve weight loss and subsequently to maintain weight loss. In the design of dietary interventions for weight loss, one important aspect that has emerged in recent years is the relative contribution of fat, protein, and carbohydrate. The macronutrient profile of a diet may facilitate dietary adherence, thereby promoting weight loss, and it could promote specific changes in blood pressure, lipids, and lipoproteins as the results from the OmniHeart trial suggest. Thus far, clinical intervention trials have yielded mixed results, and studies are often thwarted by small subject numbers and inadequate follow-up; few studies have evaluated outcomes beyond 1 year, when weight regain is most pronounced. The following section discusses CVD risk factor outcomes from select weight loss trials. In reviewing these dietary effects, it is important to acknowledge the role that additional strategies, such as physical activity and behavioral therapy, may have played in improving weight loss outcomes and preventing weight regain.
Low-Fat Diets
Diabetes Prevention Program and Look AHEAD
The Diabetes Prevention Program (DPP) compared the efficacy of three treatments in preventing type 2 diabetes and metabolic syndrome in individuals at high risk on the basis of elevated fasting blood glucose concentration and impaired glucose tolerance. Participants (n = 3234) were randomized to receive either standard lifestyle recommendations (written material advising lifestyle changes) plus placebo or metformin (850 mg twice daily) or intensive lifestyle intervention (education curriculum covering diet, exercise, and behavior modification), which aimed to achieve 7% weight loss through a healthy low-calorie, low-fat diet (<25% of total calories) and 150 min/wk of physical activity.
At 1 year, participants in the lifestyle intervention group had lost substantially more weight (∼6.5 kg) than either the placebo (∼0 kg) or metformin (∼2.2 kg) groups. Weight loss was a strong predictor of reduced diabetes incidence; each kilogram of weight lost contributed to a 16% reduction in risk, and diabetes incidence was 58% and 31% lower in the lifestyle and metformin groups compared with placebo. Intensive lifestyle therapy also was most effective in preventing the development of metabolic syndrome; at 3 years, incidence rates for metabolic syndrome were 38% for the lifestyle group, 47% for metformin, and 53% for placebo. The low-fat diet (as part of the lifestyle intervention) reduced the prevalence of the individual criteria of metabolic syndrome (i.e., HDL-C was increased; TG, blood pressure, and glucose levels were reduced).
The Look AHEAD (Action for Health in Diabetes) trial, an ongoing multicenter clinical trial modeled on the DPP, is investigating the long-term effects (11.5-year follow-up) of an intensive lifestyle intervention program in 5145 individuals with type 2 diabetes. This lifestyle intervention program is similar to the DPP in that it combines dietary modification, behavior therapy (based on programs employed in DPP), and increased physical activity (175 min/wk moderate exercise) to achieve a 10% (minimum 7%) reduction in body weight. However, whereas the DPP focused on fat restriction to decrease calories, the primary method to achieve weight loss in Look AHEAD is through calorie restriction (although fat intake is considered; total fat <30% of calories, SFA <10% of calories). In addition to the “toolbox” of adherence strategies used in the DPP, Look AHEAD encourages weight loss medication (orlistat) for patients who do not meet their weight loss goals in the first 6 months. Patients randomized to the intensive lifestyle program are compared with those receiving usual care of diabetes support and education.
After 1 year of intervention, participants in the lifestyle group lost 8.6% of body weight, compared with 0.7% in the diabetes support and education group. Substantially greater improvements in glucose control (−21.5 mg/dL), SBP and DBP (−6.8/−3.0 mm Hg), TG (−30.3 mg/dL), and HDL-C (+3.4 mg/dL) were observed in the lifestyle intervention group. The primary determinants for weight loss success were greater self-reported physical activity, attendance at sessions, and consumption of meal replacements.
PREMIER Trial
Recommendations for hypertension management include weight loss, sodium reduction (<100 mg/day), increased physical activity (180 min/wk), moderate alcohol consumption for those who drink alcohol (two drinks/day for men and one drink/day for women), and the DASH diet (see Table 16-3 for approximate reductions in SBP). The PREMIER (Prevention of Myocardial Infarction Early Remodeling) trial evaluated the effectiveness of these management strategies in combination, with or without the DASH diet, on blood pressure and weight loss. Individuals with untreated, elevated blood pressure (SBP 120 to 159 mm Hg and DBP 80 to 95 mm Hg) were randomized to one of three intervention groups: advice only (control), established lifestyle recommendations (as described before), or DASH plus established lifestyle recommendations. At 6 months, weight loss was significantly greater in the established (−4.9 kg) and DASH plus established (−5.8 kg) groups compared with control (−1.1 kg), although both groups experienced weight regain by 18 months (+1.1-1.5 kg).
| Modification | Recommendation | SBP Reduction (Range) |
|---|---|---|
| Weight reduction | Maintain normal body weight (body mass index 18.5 to 24.9 kg/m 2 ) | 5-20 mm Hg/10 kg |
| Adopt DASH eating plan | Consume a diet rich in fruits, vegetables, and low-fat dairy products with a reduced saturated fatty acid and total fat content | 8-4 mm Hg |
| Dietary sodium restriction | Reduce sodium intake to no more than 100 mmol/day (2.4 g sodium or 6 g sodium chloride) | 2-8 mm Hg |
| Physical activity | Engage in regular aerobic physical activity such as brisk walking (at least 30 min/day, most days) | 4-9 mm Hg |
| Moderation of alcohol consumption | Limit consumption to no more than 2 drinks/day (e.g., 24 oz beer, 10 oz wine, 3 oz 80-proof whiskey) in most men, no more than 1 drink/day in women and lighter weight men | 2-14 mm Hg |
Similar group treatment effects were observed at 6 months for blood pressure, which was reduced by 10.5/5.5 mm Hg in the established group and 11.1/6.4 mm Hg in the DASH plus established group. However, by 18 months, these changes were not significantly different compared with those observed in the advice-only group, although this is likely due to the unexpected improvement in several lifestyle factors in this group rather than to the limited effectiveness of the interventions.
Fasting insulin, glucose, lipid, and lipoprotein changes have been reported in a secondary analysis that stratified individuals according to presence of metabolic syndrome. This analysis revealed highly variable effects that differed by treatment group and metabolic syndrome status. The established and DASH plus established interventions compared with the control group lowered total cholesterol in subjects with (−7.98 and −5.91 mg/dL, respectively) and without (−7.41 and −7.06 mg/dL, respectively) metabolic syndrome. The established intervention reduced TG in both subpopulations (log transformed: with metabolic syndrome, −0.16 mg/dL; without, −0.10 mg/dL) but lowered LDL-C only in individuals without metabolic syndrome (−6.89 mg/dL). The DASH plus established group also lowered LDL-C only in individuals without metabolic syndrome (−5.13 mg/dL). Neither intervention influenced HDL-C. Insulin resistance (as determined by homeostasis model assessment) was improved by both the established and DASH plus established interventions, in subjects with and without metabolic syndrome. Despite such variable effects on independent cardiovascular risk factors, these combined behavioral interventions have a profound influence on CHD risk. Compared with advice alone, the established and DASH plus established interventions reduced estimated 10-year CHD risk by 12% and 14%, respectively.
Very-Low-Fat Diets
Multicenter Lifestyle Demonstration Project
The Multicenter Lifestyle Demonstration Project (MLDP) was a comprehensive intervention that examined the combined effects of diet, exercise, stress management, and group support on medical and psychosocial characteristics in 440 patients with coronary artery disease (CAD). The dietary component of MLDP consisted of a low-fat (<10% of total calories), high-carbohydrate (70% to 75% of total calories), moderate-protein (15% to 20% of calories), predominantly vegetarian diet that emphasized fruits, vegetables, grains, legumes, and soy products. Animal products were limited to nonfat dairy products and egg whites. Other intervention components included participation in 1 hr/day of stress management, 3 hr/wk of moderate exercise (according to American College of Sports Medicine guidelines for CAD patients), and twice-weekly group support sessions.
At 3 months, subjects had reduced their total fat intake to ∼7% of total calories and increased time spent in physical activity (∼3 to 4.0 hr/wk) and stress management (∼5.5 hr/wk). Body weight was reduced by 4 kg in men and 4.6 kg in women. Significant improvements in other cardiovascular risk factors were achieved; blood pressure (men, −5/−5 mm Hg; women, −6/−3 mm Hg), total cholesterol (men, −18 mg/dL; women, −14 mg/dL), and LDL-C (men, −19 mg/dL; women, −17 mg/dL) were reduced. These behavioral changes and cardiovascular risk factor improvements remained at 12 months. Subjects experienced a substantial reduction in angina (from 42% at baseline to 20% at 1 year for men and 53% to 27% in women), and 20% of individuals with diabetes mellitus reduced their use of glucose-lowering medication.
Popular Diets
The majority of popular diets promote extreme carbohydrate or fat restriction to achieve weight loss. Three recent trials have evaluated the efficacy of popular diets (with significantly different macronutrient compositions) for weight loss and improvements in CVD risk factors. In a 12-month randomized controlled trial involving 160 overweight or obese individuals, Dansinger and colleagues compared the effects of four popular diets: Atkins (very low carbohydrate), Zone (macronutrient balance), Ornish (very low fat), and Weight Watchers (calorie control). The low-carbohydrate diets (Atkins and Zone) achieved the greatest short-term (2 month) reductions in TG, glucose concentration, and DBP, whereas reductions in LDL-C and total cholesterol were observed in the higher carbohydrate groups (Ornish and Weight Watchers). These between-group differences were not present at 12 months. Short- and long-term weight loss (2-month range, 3.5 to 3.8 kg; 12-month range, 2.1 to 3.3 kg) were similar for all diet groups; the magnitude of weight loss was strongly associated with dietary adherence rather than with diet type.
The A to Z weight loss study compared the effects of three popular diets (Ornish, Zone, and Atkins) and a conventional low-fat (<10% of energy from SFA), high-carbohydrate diet (Lifestyle, Exercise, Attitudes, Relationships, and Nutrition [LEARN]) on weight loss in 311 premenopausal women. Women following the Atkins diet achieved greater short-term weight loss (2 months, 4.4 kg; 6 months, 5.6 kg) than did women following the Ornish, Zone, and LEARN diets, although only differences between the Atkins (4.7 kg) and Zone (1.6 kg) diets were significant at 12 months. Again, for each diet, weight loss was associated with greater dietary adherence. By 12 months, the Atkins diet produced substantially greater changes in TG (−29.3 mg/dL, significantly different from Zone), HDL-C (+4.9 mg/dL, significantly different from Ornish), SBP (−7.7 mm Hg, significantly different from all other diets), and DBP (−4.4 mm Hg, significantly different from Ornish).
Sacks and colleagues recently published outcomes from the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) study, a 2-year trial comparing the effects of three primary macronutrients on weight loss. The study design allowed direct comparison of two levels of fat (20% and 40%) and protein (15% and 25%) intake and a dose-response evaluation of carbohydrate (35% to 65% of total calories). All diets were reduced by 750 kcal from baseline and were standardized to include 8% of calories from SFA, at least 20 g/day of dietary fiber, and ≤150 mg of cholesterol per 1000 kcal.
Weight loss was similar for participants in each group at 6 months (∼6 kg, 7% of initial weight) and 2 years (2.9 to 3.6 kg, intention-to-treat analysis). Dietary analysis showed that participants were equally compliant across the four diets; however, in general, participants failed to attain the required calorie reduction and specific macronutrient targets. At 2 years, LDL-C decreased more with the low-fat diets and the highest carbohydrate diet than with the high-fat diets or the lowest carbohydrate diet. The lowest carbohydrate diet increased HDL-C compared with the highest carbohydrate diet. TG, insulin, and blood pressure levels were reduced by all diets (except the highest carbohydrate diet did not lower insulin). These changes are not entirely consistent with the macronutrient effects reported in the OmniHeart study, which may be due to the substantial macronutrient overlap between the diet groups. The results of these three studies collectively suggest that calorie restriction is more important than macronutrient distribution for weight loss; however, modification of macronutrient intake may be instrumental for targeting of cardiovascular risk factors such as elevated blood pressure, lipids, and lipoproteins.
Key Foods and Nutrients
The dietary patterns showcased in the previous section have a number of similarities: a focus on weight control; reduced intake of SFA, trans -fat, and cholesterol; and increased intake of fruits, vegetables, whole grains, protein, and reduced-fat dairy. In combination with a heart-healthy dietary pattern, these components have profound effects on blood pressure, lipids, and lipoproteins; yet there is evidence for their independent benefits. The inclusion of other dietary factors, such as increased intake of unsaturated fats, sterols and stanols, soy protein, and fiber, allows greater flexibility for personal preference and additional targeting of specific risk factors. For patients who require a gradual introduction to dietary change, incorporation of one or a few of these strategies may elicit beneficial effects on CVD risk factors.
Key Dietary Components
Cholesterol, Saturated Fatty Acids, and Trans–Fatty Acids
Diets high in SFA and trans -fat contribute to elevated levels of total cholesterol in the blood. Sources of SFA are high-fat and processed meats, poultry or game (with skin), high-fat dairy products, butter, gravy, and palm and coconut oils. Trans -fats are commonly found in processed and fast foods, shortening, margarines, fried tortilla chips, commercial or store-bought baked goods, salad dressings, candy, and energy bars. Substituted for carbohydrate, SFA increase both LDL-C and HDL-C, whereas trans -fats increase LDL-C and decrease HDL-C.
Dietary cholesterol is naturally present in any animal food source. Dietary cholesterol raises LDL-C; however, its effects are less than those of SFA and trans –fatty acids. Whereas total fat per se does not affect LDL-C (i.e., the guidelines are built on specific fatty acid recommendations to meet LDL-C goals), it is prudent to control total fat intake within current recommended ranges (because fat is the most concentrated energy source in the diet) to achieve weight loss. Weight loss can lower LDL-C by 5% to 8%. Therefore, reduction of the intake of foods that increase LDL-C or decrease HDL-C is an important part of a heart-healthy diet. Furthermore, replacement of SFA and trans -fats in the diet with healthful foods that include unsaturated fats, proteins, or complex carbohydrates will accentuate the health benefits gained by the reduction in SFA and trans- fat intake.
Fruits and Vegetables
Fruits and vegetables are nutrient-dense and low-calorie foods that are an essential part of a healthy diet. The most abundant nutrients in fruits and vegetables are vitamin C, vitamin E, vitamin A, folate, fiber, and potassium. Many of these are antioxidants and reduce oxidative stress in the body by neutralizing damaging free radicals. Studies using antioxidants in supplement form have not been able to demonstrate their value for reduction of CVD risk ; interactions between the antioxidants and other nutrients in the whole food may be necessary to have the desired effect. For protection against chronic disease and to maintain good health, the Dietary Guidelines for Americans, 2005 recommends consumption of at least 4.5 cups (nine servings) of fruits and vegetables per day for the reference 2000-calorie level (higher or lower amounts can be consumed for other calorie levels).
Fruit and vegetable intake consistently has been associated with decreased risk for CVD in epidemiologic studies. In an analysis of more than 125,000 participants from the Nurses’ Health Study and the Health Professionals Follow-up Study, persons who ate eight or more servings of fruits and vegetables per day had a 20% reduction in risk of CHD (RR = 0.80; 95% CI, 0.69-0.93) compared with those who ate three or fewer servings per day. With each increase in serving of fruit or vegetable per day, the risk of CHD decreased by 4%; leafy greens and fruits and vegetables high in vitamin C contributed most to this effect. Consistent with these data, the Physicians’ Health Study found that men who consumed two or more servings per day of vegetables had a 22% lower risk of CHD than did men who ate less than one serving per day (RR = 0.77; 95% CI, 0.60-0.98). Furthermore, for each additional serving of vegetables per day, CHD risk was reduced by 17% (RR = 0.83; 95% CI, 0.71-0.98). In the Women’s Health Study, fruit and vegetable consumption was inversely associated with CVD risk (RR = 0.45 for highest versus lowest quintile of intake; 95% CI, 0.22-0.91). Whereas the epidemiologic studies are convincing, there is limited clinical evidence because of the paucity of controlled, nutritional prevention trials varying only in fruit and vegetable intake. Nevertheless, the DASH dietary intervention studies (described earlier) clearly demonstrate the benefit of increasing fruit and vegetable intake for the management of hypertension. In addition, because of their low energy density, fruits and vegetables may play a key role in weight loss and maintenance.
Whole Grains
Whole grains are defined as intact, ground, cracked, or flaked fruit of the grains whose principal components—the starchy endosperm, germ, and bran—are present in the same relative proportions as they exist in the intact grain. If they are processed correctly, wheat, oats, barley, brown and wild rice, corn, rye, and sorghum are whole grains. To be considered a good source of whole grains, foods must be at least 51% whole grain by weight per reference amount commonly consumed and have a whole-grain source as the first ingredient on the food label. Whereas all whole grains have many bioactive components (such as fiber, folate, phenolic compounds, lignan, and sterols), each type of grain has different levels of these components, and therefore they cannot be equated. For example, oats, barley, bulgur, rye, and whole wheat are high in fiber (>10 g fiber/100 g food), whereas brown rice, wild rice, corn, and sorghum are lower in fiber (<8 g fiber/100 g food). Soluble and insoluble fibers have different effects on and mechanisms of action in improving CVD risk factors. Specifically, soluble (viscous) fiber has been shown to reduce LDL-C levels, whereas insoluble fiber may increase short-chain fatty acid synthesis, which reduces endogenous cholesterol production. See the section on soluble (viscous) fiber for additional information.
Similar to fruit and vegetable intake, epidemiologic studies have shown whole-grain intake to be protective against CHD. These associations may be due to the various vitamins (B and E), minerals (calcium, magnesium, potassium, phosphorus, selenium, manganese, zinc, and iron), phytochemicals (such as fiber), phenolic compounds, and phytoestrogens (lignans) found in whole grains. An analysis of the Health Professionals Follow-up Study, which included more than 40,000 men, found an inverse association between higher habitual whole-grain intake and incidence of CHD (HR = 0.82; 95% CI, 0.70-0.96); indeed, there was a 6% decrease in CHD risk with every increase of 20 g in daily whole-grain intake (95% CI, 0%-13%). Higher intakes of whole grains (lowest versus highest quartiles) have been associated with a lower incidence of metabolic syndrome, fasting plasma glucose concentration, and body mass index in older adults. Although it appears that whole-grain intake is associated with a reduced risk for CVD, these results may be confounded by lifestyle characteristics. Jensen and colleagues reported that individuals who had higher intakes of whole grains generally had a lower body mass index, were more physically active, had less hypertension, and ate more fruits and vegetables and protein.
Randomized controlled trials designed to evaluate whether whole grains are protective against CVD generally have shown a beneficial effect, albeit with mixed results. In a recent review of both observational and intervention studies, 11 of 15 intervention studies reported that whole grains were protective against CVD events. Of note is that oats and barley were more effective than whole wheat in improving CVD risk factors such as total cholesterol, LDL-C, and blood pressure. The difference in effect between the whole grains is attributed to the compositions of the grain, as oats and barley are higher in fiber, especially insoluble fiber, and have unique phytochemicals. NCEP ATP III recommends 5 to 10 g/day of soluble (viscous) fiber to lower LDL-C by 3% to 5%. Currently, the Dietary Guidelines for Americans, 2005 advise that at least half of the recommended grain servings come from whole grains and state that “consuming at least 3-ounce equivalents of whole grains per day can reduce the risk of CHD, may help with weight maintenance, and may lower risk for other chronic diseases.” Switching from refined to whole-grain products is becoming increasingly easier as more products are being made with whole grains; thus, three servings of whole grains per day is an attainable health goal.
Heart-Healthy Protein Sources
Reduction of meat intake, especially red meat, is often recommended to decrease intake of SFA and cholesterol. Animal products are the predominant source of SFA and cholesterol in the diet, but processed foods like fast food and snack foods contribute significantly. Animal products also are excellent sources of protein, and increased protein intake, from plant or animal sources, has been linked to lower blood pressure and TG, higher HDL-C, and a healthier body weight. Protein is low in energy density (4 kcal/g), and therefore replacement of fatty acids with protein may help with satiety and weight loss.
The Nurses’ Health Study found that women with a higher protein intake (∼24% of total energy) were at reduced risk for ischemic heart disease (RR = 0.75; 95% CI, 0.61-0.92) compared with women with lower intakes (∼14% of total energy). However, in an analysis of the nutritional profiles of 18- to 30-year old men and women from the Coronary Artery Risk Development in Young Adults (CARDIA) study, adults who ate meat or poultry less than once per week had lower serum TG, total cholesterol, and LDL-C levels than did those who ate meat more frequently, although the low-meat intake group also had a lower body mass index, increased reported physical activity, and a diet higher in fiber and certain vitamins.
Until recently, there have been no specific recommendations for intake of protein from animal products with regard to CVD health, other than to consume reduced-fat products. Protein intake of 10% to 20% of total daily calories from either plant or animal sources is widely accepted ; The Dietary Guidelines For Americans, 2010, however, emphasizes the importance of plant-based dietary patterns for CVD risk reduction. For all individuals, the challenge is finding good sources of low-fat protein in the diet. Meats that are high in SFA are high-fat red meat cuts and processed meats, such as hamburger, hotdogs, and bacon, and these should be limited in the diet. Full-fat dairy products also are a rich source of SFA. Low-SFA animal protein sources are lean meats (beef, ham), poultry (trimmed and without skin), fish, cottage cheese, and reduced-fat milk and dairy products. Plant protein may provide a healthier protein alternative in the diet as it is lower in SFA. Common sources of plant protein are soy, seeds, nuts, and legumes.
Reduced-Fat Dairy
Overall, epidemiologic studies of dairy intake have shown no association with increased risk for CVD, even when full-fat dairy products high in SFA are consumed. However, an analysis of the contribution of different fatty acids to CVD risk showed that an increase in the ratio of high-fat to low-fat dairy products increased risk for CVD in the Nurses’ Health Study. This suggests either a protective or minimal effect of low-fat dairy products on CVD risk. In a meta-analysis and systematic review of dairy consumption, high dairy consumers had a 29% reduced risk for metabolic syndrome and 14% reduced risk for type 2 diabetes compared with low dairy consumers.
The main mechanism by which low-fat dairy products reduce CVD risk is by lowering of blood pressure, although increased insulin sensitivity, decreased inflammation, and weight loss are emerging benefits. Dairy products are an excellent dietary vehicle for protein, vitamin A, vitamin D, vitamin B 12 , riboflavin, niacin, potassium, phosphorus, magnesium, and calcium. Increased intake of calcium, potassium, magnesium, and dairy protein has been shown to decrease blood pressure. According to a meta-analysis of 12 intervention studies, short peptide chains found in milk improve CVD outcomes by decreasing SBP (−4.8 mm Hg) and DBP (−2.2 mm Hg). These nutrients appear to be more effective when they are provided as foods, such as low-fat dairy products, than when they are taken in supplement form. This is a key principle of dietary patterns such as the DASH diet, which incorporate low-fat or nonfat dairy products within a heart-healthy diet.
By virtue of reducing the amount of fat in dairy products, it is possible to enjoy the nutritional benefits and to limit SFA intake. Replacement of high-SFA dairy foods, such as butter and ice cream, with low-fat options, like yogurt and skim milk, provides complete proteins and essential vitamins and minerals for the maintenance of health. Incorporation of low-fat dairy products into any diet increases nutritional quality without markedly increasing calories; however, consumption of fat-free dairy foods may limit the amount of fat-soluble vitamins that are absorbed. The DASH diet and TLC advise two or three servings of low-fat dairy products per day to achieve a healthy diet and to decrease risk of CVD.
Other Beneficial Dietary Components
Soluble (Viscous) Fiber
Foods rich in water-soluble (viscous) fiber include oats, barley, legumes, some fruits (such as apples and pears), and psyllium seeds. Soluble fibers have been recognized since the 1960s as having lipid-lowering effects, and there is growing evidence to support an association between intake of whole grains and decreased incidence of fatal and nonfatal CHD. The cholesterol-reducing effects of whole-grain foods such as oats and barley are associated with the soluble fiber component, beta-glucan.
Although not all individual studies have found positive outcomes, several meta-analyses concluded that regular consumption of oats can lower cholesterol. Brown and colleagues reported that 3 g/day of soluble fiber decreases total cholesterol and LDL-C by ∼0.13 mmol/L. Health claims for cholesterol reduction have been approved for both oat fiber and barley fiber. The exact mechanism by which water-soluble fibers lower serum LDL-C levels is not known. Water-soluble fibers may interfere with lipid or bile acid metabolism by downregulating genes involved in fatty acid synthesis and transport. Oat bran with beta-glucan also has been shown to increase exclusion of bile acids. Another suggested mechanism is the inhibition of hepatic cholesterol synthesis by fermentation products. Short-chain fatty acids also may regulate hepatic AMP-activated protein kinase in the liver, thereby stimulating fatty acid oxidation and inhibiting lipogenesis and glucose production. As well as having beneficial effects on lowering cholesterol, soluble fiber may reduce CVD risk by acting on glucose regulation and insulin sensitivity, body weight, inflammation, endothelial function, and blood pressure.
Sterols and Stanols
Several observational studies have evaluated the relationship between plasma phytosterol levels and CVD risk, with two large cohorts reporting a reduced risk of coronary events in individuals with higher plasma sitosterol levels. However, the Prospective Cardiovascular Münster (PROCAM) study reported a 1.8-fold increased risk of coronary events in subjects with sitosterol levels in the upper quartile compared with the lower three quartiles. CVD effects may be due to the ability of stands to inhibit cholesterol absorption, thereby reducing plasma total cholesterol and LDL-C. The greatest benefit is observed in individuals with unfavorable lipid profiles. In a meta-analysis of supplementation studies, subjects with familial hypercholesterolemia who consumed fat spreads enriched with 2.3 g of phytosterols per day significantly reduced their total cholesterol and LDL-C by 7% to 11% and 10% to 15%, respectively, compared with control.
At least 1 g/day of phytosterols is necessary to obtain a significant 5% to 8% LDL-C reduction. A meta-analysis of 41 trials showed that 2 g/day of stanols or sterols reduced LDL-C by 10%, although higher intakes added little to this effect. This outcome supports the level of plant sterols or stanols (2 g/day) recommended in the NCEP ATP III guideline for lowering of LDL-C. As the typical daily dietary intake of phytosterols in Western cultures ranges from 150 to 400 mg/day, it is necessary to consider dietary supplementation to reach the recommended intake. Phytosterols are well tolerated, can easily be incorporated into a range of foods, and are not associated with any adverse effects.
Efficacy is similar for sterols and stanols, but food form may substantially affect LDL-C reduction. Sterols incorporated into fat spreads, mayonnaise and salad dressing, milk, and yogurt appear to be more advantageous at lowering LDL-cholesterol than in food products such as croissants and muffins, orange juice, nonfat beverages, cereal bars, and chocolate. The effects of sterols or stanols on LDL-C lowering are additive with diet or drug interventions; previous studies reported greater reductions in LDL-C when statin use is combined with foods enriched with plant sterols or stanols compared with doubling of the dose of statins. Despite such positive effects on cholesterol reduction, sterols have not been shown to be effective at reducing oxidative stress and endothelial dysfunction, and there are mixed reports in the literature on their ability to reduce low-grade inflammation.
Soy Protein
There has been extensive investigation about the effects of soy protein on lipids and lipoproteins during the past decade. On the basis of the outcomes of a meta-analysis of 38 trials, the U.S. Food and Drug Administration approved the following health claim: “25 g of soy protein a day, as part of a diet low in saturated fat and cholesterol, may reduce the risk of heart disease.” The average consumption of soy protein in the studies reviewed in the Anderson meta-analysis was 47 g/day, which is almost double that recommended in the U.S. health claim. This amount was associated with significant reductions in total cholesterol (9.3%), LDL-C (12.9%), and TG (10.5%). The magnitude of reduction in total cholesterol and LDL-C was associated with baseline levels, such that individuals with higher serum cholesterol levels at baseline had the greatest reduction.
More recent meta-analyses have concluded that the extent of cholesterol reduction is much less than was initially reported. In 2006, the AHA assessed 22 randomized controlled trials since 1999 and found that consumption of isolated soy protein with isoflavones resulted in a small reduction in LDL-C (3%) but had no effect on HDL-C, TG, lipoprotein(a), or blood pressure. Taku and associates found no effect of soy isoflavones (without concurrent consumption of soy protein) on total cholesterol and LDL-C in menopausal women. Randomized controlled trials conducted since these reviews have reported similar, modest reductions in LDL-C or total cholesterol. The variable effect of soy isoflavones on cholesterol reduction may be due to the different doses of isoflavones used or may be related to the ability of individuals to convert the isoflavone daidzein into equol through bacterial fermentation in the large intestine. However, evidence to support the latter is not consistent.
Unsaturated Fats
Both the quantity and quality of dietary fat influence the risk of CVD. Intake of unsaturated fats, namely, MUFA and PUFA, is associated with a more favorable CVD risk profile as they reduce total cholesterol and LDL-C and may improve blood pressure regulation. Clinical studies have since found that when it is substituted for SFA in the diet, MUFA reduces total cholesterol and LDL-C and relative to carbohydrate increases HDL-C and reduces TG. MUFAs principally are found in vegetable oils such as olive, rapeseed (canola), and peanut oils as well as in poultry, meat, nuts, and avocado. PUFAs are composed of two classes: omega-6 (n-6) fatty acids, found in vegetable oils and nuts, and omega-3 (n-3) fatty acids, found in fatty fish, such as salmon and anchovies, and in walnuts and flax. Three of the main dietary sources of unsaturated fat and their effects on CVD risk are discussed in greater detail.
Fish (and Fish Oil)
Numerous epidemiologic and clinical studies have demonstrated associations between increased intake of marine-derived n-3 fatty acids from fish or fish oil and reduced incidence of CVD. In the U.S. Health Professionals Study, regular fish consumption was associated with a significantly lower risk of total CVD in men. It also is associated with reduced progression of coronary artery atherosclerosis in men and women with CAD, reduced risk of CAD and total mortality in diabetic women, reduced risk of thrombotic infarction, and reduced risk of cardiac arrhythmias resulting in sudden cardiac death. The n-3 fatty acids in fish are the key nutrients thought to be responsible for the benefits described, although it is plausible that the interactions between these fats and other nutrients, including trace elements, vitamins, and amino acids, also may be important to reduce CVD risk. Marine-derived n-3 fatty acids elicit cardioprotective benefits through mechanisms such as antiarrhythmic effects, TG and blood pressure lowering, reduced platelet function and aggregation, improved vascular function, and decreased inflammation. Consequently, regular consumption of marine-derived n-3 fatty acids is recommended for healthy persons and those with CHD.
Recommendations to eat fish and other seafood are included in most national dietary guidelines because of their beneficial health effects. Seafood is an important dietary source of marine-derived n-3 fatty acids, protein, vitamins D and E, and iodine. Seafood is low in SFA. Because of this unique nutrient profile, regular fish consumption is recommended as part of a healthy diet. The American Dietetic Association and Dietitians of Canada recommend two servings of fish per week, preferably fatty fish. The AHA also recommends two servings of oily fish per week (equivalent to 400 to 500 mg of marine-derived n-3 fatty acids per day) for optimal health. However, fish intake in Western cultures is typically very low (about one fish meal per week) and frequently is from sources that are low in marine-derived n-3 fatty acids (e.g., shrimp, cod, and other white fish).
Oily fish rich in marine-derived n-3 fatty acids include tuna, salmon, mackerel, sardines, herring, and trout. The amount of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is shown for a variety of fish species (both fresh and farmed) in Table 16-4 . Farmed fish provides as much EPA and DHA as wild fish do, if not more. As the fatty acid profiles of diets for farmed fish can be closely monitored, their lipid is less affected by seasonal variations and location of catch. Moreover, the EPA and DHA content of farmed salmon and trout has been reported to be ∼15% higher than that of wild catch. The nutritional content of farmed fish has been found to be at least as beneficial as that of wild fish in terms of prevention of CVD, with additional benefits arising from greater control over pollutants (including heavy metals and polychlorinated biphenyls).
