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Medical nutrition therapies most effective in reducing CVD are evidence-based, promote healthful qualitative and quantitative/caloric dietary intake, and conducive to long-term patient adherence [27] (Figure 1).
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Regarding fats, increased saturated fat dietary intake may promote atherogenesis via increased low-density lipoprotein cholesterol (LDL-C) levels, increased apolipoprotein B levels, increased LDL particle number, increase inflammation, and endothelial dysfunction [28], [29], [30], [31]. With isocaloric intake, CVD risk is reduced when saturated fats are replaced by unsaturated fats [32]. Although banned by the US Food and Drug Administration in 2019, trans fats are sometimes still reportedly found in foods such as cakes, pies, cookies, biscuits, microwavable breakfasts, stick margarine, crackers, microwave popcorn, doughnuts, and frozen pizza, especially when their polyunsaturated fat components are artificially hydrogenated into partially hydrogenated oils. Both saturated fats and trans-fats increase LDL-C levels, with trans-fat consumption most associated with increased CVD risk [32], [33].
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Regarding isocaloric carbohydrate intake, CVD risk is reduced when ultra-processed carbohydrates are replaced by fiber rich complex carbohydrates found in healthful whole foods including whole grains, vegetables, and fruits [32], [34]. Ultra-processed carbohydrates promote weight gain and increase the risk of post-prandial hyperglycemia, hyperinsulinemia, hypertriglyceridemia, inflammation, endothelial dysfunction, sympathetic hyperactivity, and hypercoagulability, [35] all CVD risk factors [36], [37].
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The “diets” with the best evidence for CVD prevention are the Mediterranean Diet and “Dietary Approaches to Stop Hypertension” (DASH) [38]. Both dietary patterns prioritize vegetables, fruits, whole grains, fat-free or low-fat dairy products, fish, poultry, lean meats, nuts, seeds, legumes, and fiber.
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Other evidence-based diets include vegetarian and Ornish diets [38]. A vegetarian meal plan includes plant-based foods such as vegetables, fruits, whole grains, legumes, seeds, and nuts. Some “vegetarian diets” allow for eggs and milk; animal meats are discouraged [39]. Higher plant protein intake may be associated with small reductions in risk of overall and CVD mortality [40]. While healthful plant-based diet (whole grains, fruits, vegetables, oils, tea, and coffee) may reduce CVD risk, unhealthful plant-based food intake (juices, sweetened beverages, ultra-refined grains, potatoes/fries, and sweets) may increase CVD risk [41]. In addition to genetics and other factors, a dietary intake of unhealthful non-meat, plant-based foods may help account for a relatively high rate of CVD among many vegetarians from India [42]. The Ornish Diet is illustrative of a highly fat-restricted nutritional intervention wherein macro and micronutrients are best eaten as natural whole food. The Ornish Diet includes vegetables, fruits, whole grains, legumes, and soy with limited amounts of green tea [43], [44].
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The Ketogenic Diet is a very low carbohydrate diet (e.g., less than 50 grams per day) that discourages unhealthful ultra-processed and refined foods, discourages foods high in glycemic index/load, and discourages foods rich in trans fatty acids [27], [45]. Ketogenic diets may promote short term weight loss in patients with pre-obesity or obesity, lower postprandial glucose/insulin levels, lower blood pressure, lower triglyceride levels, and raise high density lipoprotein cholesterol (HDL-C) levels. Especially if the relatively high proportion of dietary fat with the ketogenic diet is composed of saturated fats and dietary cholesterol, then LDL-C levels may increase, which may prompt consideration of replacing saturated fats with monounsaturated and/or polyunsaturated fats and reducing dietary cholesterol intake [27], [45], [46], [47], [48], [49]. If weight loss in a patient with metabolic disease is suspected to have promoted increased cholesterol intestinal absorption, then reducing dietary cholesterol intake and adding a cholesterol absorption inhibitor (e.g., ezetimibe) and a statin might be considered [27], [50]. No long-term prospective clinical trial supports the ketogenic diet as reducing CVD. Just as the types of carbohydrates may help determine the effect of low-fat dietary consumption on CVD risk factors, CVD, and mortality, so it is likely the type of consumed fats may help determine the effect of long-term low carbohydrate diet on CVD risk and mortality [51].
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A common weight reduction strategy in patients with pre-obesity and/or obesity involves portion control and caloric restriction to obtain a daily energy deficit (i.e., 500 – 750 kcal per day) [52]. This can be achieved by either continuous energy restriction or time-mediated caloric restriction (e.g., intermittent fasting, fasting-mimicking diets, and time restricted eating). Intermittent fasting may involve alternate day fasting or fasting 2 days per week (5:2). A fasting-mimicking diet may involve 5 days per week of low-calorie, low carbohydrate, proportionately higher fat nutritional intake [53]. Overall, intermittent fasting may reduce total caloric intake, facilitate weight reduction in patients with pre-obesity or obesity, improve cognitive function and improve CVD-related metabolic parameters (e.g. improve insulin sensitivity, blood pressure, lipids, and inflammatory markers) [53], [54], [55]. Weightreduction with intermittent fasting may be achieved while preserving resting metabolic rate and lean body mass, [27], [56] especially if accompanied by routine physical activity. Time-restricted eating (TRE) can be defined as caloric consumption limited to a 6 – 10-hour period during the active day. In some patients, TRE can improve CVD risk factors such as body weight, glucose tolerance, blood pressure, atherogenic lipids, and hepatic steatosis [56], [57], [58], [59]. Prioritizing early in the day eating (i.e., breakfast) may promote greater diet-induced thermogenesis and relatively favorable effects on blood glucose and insulin concentrations compared to eating large evening meals. [60], [61]. Some clinicians may have concerns that that fewer meals per day is less healthful than multiple small meals per day. However, in an isocaloric setting, greater meal frequency (“grazing” with multiple small meals and frequent snacks) may not afford clinically meaningful weight loss, anthropometric, energy balance, or other health advantages over 3 standard meals per day [62], [63], [64], [65]. Conversely, neither intermittent fasting or TRE may promote greater weight loss than continuous energy restriction [66], [67].
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In patients without vitamin deficiency, [54] dietary supplements do not reduce CVD [68], [69], [70]. In fact, calcium supplementation may be associated with increased CVD risk [71]. Conversely, vitamin D and calcium intake in the form of healthful whole food consumption (e.g., fruits and vegetables) are associated with reduced risk of CVD [72]. A notable example is the consumption of dairy products containing micro- and macronutrients (e.g., proteins, calcium, magnesium, potassium, vitamins) that may reduce inflammation and reduce CVD risk [73], [74]. The balanced nutrients within “whole food” or “full fat” dairy consumption may help explain why dairy intake is often reported to have a neutral or favorable effect on CVD risk, even when some of the fatty acids in dairy foods are saturated fats [75], [76], [77], [78].
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Intake of foods rich in omega-3 fatty acids is associated with reduced CVD risk [79] and meta-analyses suggest supplements containing a combination of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) may also reduce CVD events [80], [81]. A prospective clinical trial (i.e., Reduction of Cardiovascular Events with Icosapent-Ethyl Intervention Trial or REDUCE-IT) demonstrated reduced major adverse cardiac event with icosapent ethyl (purified EPA) among patients at high CVD risk and baseline hypertriglyceridemia [78]. In contrast to meta-analyses of non-prospective EPA and DHA supplement studies, the prospective, randomized Outcomes Study to Assess STatin Residual Risk Reduction With EpaNova in HiGh CV Risk PatienTs With Hypertriglyceridemia (STRENGTH) trial of a free fatty acid, omega-3 carboxylic acid preparation was stopped early for futility, suggesting that administration of concentrated capsules of EPA and DHA (beyond nutritional intake) does not reduce CVD events in patients with hypertriglyceridemia [82], [83]. Thus, the potential CVD benefit of omega-3 fatty acid consumption may depend on baseline CVD risk, statin use, CVD outcomes studied, and the composition of the omega-3 fatty acid [84].
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While genetics play a role in CVD risk, unhealthful dietary intake, physical inactivity, and cigarette smoking can also independently affect CVD risk. Favorable lifestyle adoption is associated with a nearly 50% lower relative risk of coronary artery disease than unfavorable lifestyle [85]. Barriers exist to healthful eating patterns, such as cost, convenience/preparation time, and family taste preferences. Clinicians should also be aware of challenges in food availability, education regarding healthful food preparation, and limitations of federal food assistance programs, which disproportionately affect low-income individuals [86], [87]. Methods to implement healthful nutrition include educating patients regarding evidenced-based meal plans and dietary practice guidelines, [38] and referring patients to a dietitian nutritionist to implement medical nutrition therapy to help manage CVD risk factors and reduce CVD risk [88], [89]. Other cost-effective patient advice includes suggesting no-salt fruits and vegetables, legumes (i.e., a low calorie, nutrient dense option associated with decreased all-cause mortality), milk, yogurt, carrot, cabbage, non-sweetened whole grain cereals and low sodium foods – which sometimes even if canned, may be cost effective nutrient dense options [90].
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