A-LA-content; g/tablespoon
Flaxseed oil
8.5
Flaxseed
2.2
Walnut oil
1.4
Canola oil
1.3
Soja oil
0.9
Walnuts
0.7
Olive oil
0.1
Plant-based n-3 PUFAs may particularly reduce CHD risk when seafood-based n-3 PUFA intake is low, which has implications for populations with low consumption or availability of fatty fish [104]. However even in persons (without cardiovascular disease or malignancies) consuming adequate marine n-3 PUFAs, plant-based dietary n-3-PUFA alpha-linolenic acid (supplied mainly by walnuts and olive oil) was associated with an additional protective effect on all-cause mortality as could be shown in the PREDIMED study [138].
The mechanisms underlying the protective effects of omega-3 fatty acids are poorly understood. Telomere length is an emerging marker of biological age. Telomeres are tandem repeat DNA sequences (TTAGGG) that form a protective cap at the ends of eukaryotic chromosomes. Among patients with coronary artery disease, there was an inverse relationship between baseline blood levels of marine omega-3 fatty acids and the rate of telomere shortening over 5 years, suggesting that this could be one mechanism by which n-3 PUFAs might have a protective effect [41].
More recent studies however failed to demonstrate a benefit from use of omega-3 fatty acids in patients with multiple risk factors in a large general practice cohort who were treated according to the standard of care [131] or in patients early after acute myocardial infarction [130] who were treated according to current guidelines. The event rates in the control groups were lower than expected, and it is conceivable that the modern cardiovascular therapy (in patients recognized to be at increased risk) delivers already the effects formerly achieved by omega-3 fatty acids.
2.2.2 Fruits and Vegetables
The role of fruits and vegetables for the prevention of ischemic events has been examined in the Nurses’ Health Study and the Health Professionals Follow-Up Study. 84,251 women 34–59 years of age who were followed for 14 years in the Nurses’ Health Study and 42,148 men 40–75 years who were followed for 8 years in the Health Professionals Follow-Up Study were free of diagnosed cardiovascular disease, cancer, and diabetes at baseline. Participants in both studies completed mailed questionnaires about medical history, health behaviors, and occurrence of cardiovascular and other outcomes every 2 years.
After adjustment for standard cardiovascular risk factors, persons in the highest quintile of fruit and vegetable intake had a 31 % lower risk for ischemic stroke [70] and a 20 % lower relative risk for coronary heart disease [71] compared with those in the lowest quintile of intake. Green leafy vegetables and vitamin C-rich fruits and vegetables contributed most to the apparent protective effect of total fruit and vegetable intake. The optimal effect was reached with 5 servings per day, which is the current recommendation.
In the European Prospective Investigation into Cancer and Nutrition, a one portion (80 g) increment in fruit and vegetable intake was associated with a 4 % lower risk of fatal ischemic heart disease or ischemic stroke [23].
The results of the Cardiovascular Risk in Young Finns Study suggest that high consumption of fruits and vegetables during childhood and early adulthood is related to less arterial stiffness after 27 years of follow-up in young adulthood [1]. In the longitudinal CARDIA cohort study, higher intake of fruits and vegetable during young adulthood was associated with lower odds of prevalent coronary artery calcium after 20 years of follow-up [101].
A multicenter study from Europe [117] extends these findings to a diabetic population, where intake of vegetables, legumes, and fruits was associated with reduced risks of all-cause and CVD mortality. The findings support the current state of evidence from general population studies suggesting that the protective potential of vegetable and fruit intake is also seen in diabetic patients.
The results of these different studies reinforce the importance of establishing a high intake of fruits and vegetables as part of a healthy dietary pattern beginning early in life and continuing this pattern throughout late adulthood.
2.2.3 Whole grain Products
Although whole grain products are metabolically favorable, their prognostic implications have not been adequately examined. Whole grain products decrease total cholesterol and LDL cholesterol by about 18 %, decrease postprandial glucose levels, decrease the risk for type 2 diabetes mellitus, and improve insulin sensitivity in overweight and obese adults. Their influence on bodyweight however remains unresolved. There are no prospective studies evaluating the effect of whole grain products or diets on coronary death or on the occurrence of coronary artery disease. A retrospective analysis of ten US American and European studies found consumption of dietary fiber from cereals and fruits inversely associated with risk of coronary heart disease: for each 10 g cereal or fruit fiber intake, risk reductions of 10 and 16 % respectively for all coronary events were observed and 25 and 30 % risk reductions respectively for deaths; there were however no risk reductions for vegetable fiber intake. The results were similar for men and women [125].
Whole grain products for breakfast were associated with a lower occurrence of heart failure, as an observational sub-study on 21,000 physicians for more than 20 years of follow-up from the British Physician’s Health Study suggested. It remains however unclear at present whether this benefit was achieved by prevention of hypertension and/or myocardial infarction [32]. In female type 2 diabetics, bran appears to be of prognostic benefit as shown in the Nurses’ Health Study [57]. As mentioned above in the Nurses’ Health Study and the Health Professionals Follow-Up Study replacement of 5 % of the total caloric content of saturated fats by a caloric equivalent of whole grain was associated with a 9 % reduction of the cardiovascular risk [89]. A recent meta-analysis of the association between whole grain intake and coronary heart disease risk indicated that whole grain intake has a protective effect against coronary heart disease in Europe as well as in the United States [156]. A more quantitative recent meta-analysis [169] based on 14 studies which included 786,076 participants, 97,867 total deaths, 23,957 CVD deaths, and 37,492 cancer deaths concluded that for each 16 g/day daily consumption increase in whole grain (≈1 serving per day), relative risks of total mortality was 0.93 (95 % CI, 0.92–0.94; P < 0.001), the cardiovascular mortality was 0.91 (95 % CI, 0.90–0.93; P < 0.001), and the cancer mortality was 0.95 (95 % CI, 0.94–0.96; P < 0.001).
2.2.4 Meat
Lower consumption of red meats is part of the overall dietary recommendation for a Mediterranean-type diet, which is supported by the European Society of Cardiology [126] and also by the American Heart Association [109, 110]. Several constituents of red meats could potentially increase cardiometabolic risk, including saturated fatty acids, cholesterol, and heme iron; in processed meats, high levels of salt and other preservatives [107] are associated with higher incidence of CHD and diabetes mellitus [100]. Although not strictly related to cardiovascular disease but also of health concern for the CV patient is the recent statement of the International Agency for Research on Cancer that consumption of processed meats is “carcinogenic to humans” (Group 1) on the basis of sufficient evidence for colorectal cancer. Additionally, a positive association with the consumption of processed meat was found for stomach cancer. The Working Group classified consumption of red meat as “probably carcinogenic to humans” (Group 2A) [9]. Thus lower consumption of red meat, particularly of processed meat, should have a twofold favorable effect on health.
2.2.5 Snacks and Sweets
The diet of the coronary patient is characterized by quite a few restrictions and some degree of fat and cholesterol reduction. Therefore the addition of snacks to the diet is often more than welcome, particularly if these snacks have a beneficial effect on the course of the disease or at least modify risk factors in a favorable way or improve endothelial function.
2.2.5.1 Nuts and Almonds
Tree nuts, peanuts, and almonds have been thoroughly analyzed with respect to their effect on prognosis and lipid profile of persons with hypercholesterolemia.
Observations from the Adventist Health Study have shown that frequent consumption of nuts is associated with a substantial, independent reduction in the risk of myocardial infarction and death from ischemic heart disease [46]. In a small study on young healthy, normal-weight, nonsmoking males, replacement of 20 % of daily calories with walnuts decreased LDL cholesterol levels by 16.3 % and HDL cholesterol by 5 %, resulting in overall favorable changes of the lipid profile [135]. In two large, independent cohorts of nurses, in the Nurses’ Health Study and of male health professionals in the Health Professionals Follow-Up Study, the frequency of nut consumption was inversely associated with total and cause-specific mortality, independently of other predictors of death [6]. This inverse association between nut consumption and CHD risk has also been found in the prospective Physicians’ Health Study primarily due to a reduction in the risk of sudden cardiac death [4].
The average nut consumption in the Adventists’ and the Nurses’ Health Study was about 20 g/day – a handful. In a randomized nutritional study, larger but still moderate quantities of walnuts (84 g/day) within a cholesterol-lowering diet favorably modified the lipoprotein profile in normal men and decreased serum levels of LDL cholesterol by 16 % if the intake of total dietary fat and calories was maintained. The ratio of LDL cholesterol to HDL cholesterol was also lowered by the walnut diet and endothelial function was improved [134].
The beneficial effect of nuts on prognosis is plausible. Nuts are rich in monounsaturated and polyunsaturated fatty acids, which makes them a palatable choice of healthy fats. Monounsaturated fats may contribute to decreased CHD risk by amelioration of lipid profile, by reducing postprandial triglyceride concentrations, and by decreasing soluble inflammatory adhesion molecules in patients with hypercholesterolemia. Moreover, the relatively high arginine content of nuts has been suggested as one of the potential biological mechanisms for their cardioprotective effect, because consumption of arginine-rich foods is associated with lower CRP levels [82].
Also almonds used as supplements in the diet of hyperlipidemic subjects significantly reduce coronary heart disease risk factors: 73 g of almonds produced a significant 9.4 % reduction of LDL cholesterol, a 12 % reduction of the LDL-HDL ratio, a 7.8 % reduction of lipoprotein(a), and a reduction of oxidized LDL concentrations by 14.0 % – all significant and most likely beneficial for the course of the disease [82].
Also a macadamia nut-based diet high in monounsaturated fat has potentially beneficial effects on cholesterol and low-density lipoprotein cholesterol levels when compared with a typical American diet [24]. These changes are probably a result of the nonfat (protein and fiber) as well as the monounsaturated fatty acid components of the nut, but other additive effects of the numerous bioactive constituents may contribute to this effect.
A traditional Mediterranean diet enriched with nuts in a weight reduction program enhanced – as mentioned above in the PREDIMED study – the reversion of metabolic syndrome by 30 % compared with the control diet group [139].
In addition the consumption of peanuts and other nuts is significantly associated with a lower risk of gallstone disease – a welcomed side effect in persons with increased cholesterol levels. A review found the prognostic effects of nut and peanut studies somewhat greater than expected on the basis of the magnitude of the blood cholesterol lowering seen from the diet. Thus, in addition to a favorable fatty acid profile, nuts and peanuts may contain other bioactive compounds that could contribute to their multiple cardiovascular benefits. Other macronutrients include plant protein and fiber; micronutrients including potassium, calcium, magnesium, and tocopherols; and phytochemicals such as phytosterols, phenolic compounds, resveratrol, and arginine. Nuts and peanuts are food sources that are a composite of numerous cardioprotective nutrients, and if routinely incorporated in a healthy diet, the population risk of CHD would therefore be expected to decrease markedly [82].
The strongest argument for the beneficial prognostic effects however provides the already mentioned PREDIMED study, a randomized primary prevention trial involving persons at high cardiovascular risk: the study showed a significant reduction in major cardiovascular events among participants assigned to a Mediterranean diet – one component of which was supplementation with 30 g of walnuts, hazelnuts, or almonds per day – as compared with a control diet [38, 52].
2.2.5.2 Chocolate
In the sixteenth century, Aztec Emperor Montezuma was a keen admirer of cocoa, calling it a “divine drink, which builds up resistance and fights fatigue. A cup of this precious drink permits a man to walk for a whole day without food” was supposedly Hernán Cortés, the conquistador of the Aztecs convinced (cited in [20]). In the language of the Aztecs, this drink was called chocolatl. With the discovery of the New World, cocoa came to Europe in the sixteenth century. Also today the consumption of chocolate is often associated with or followed by an intense feeling of pleasure and gratification, where the desire of repetitive consumption is often difficult to resist (personal experience and unpublished observation). The total chocolate consumption in Germany is approximately 11.5 kg per person and year and even greater than the chocolate consumption of the Swiss of 11.1 kg per person and year (including the sales to tourists) ( Fig. 2.1).
Fig. 2.1
Per capita annual chocolate consumption in kg in different European countries (Swiss 2015, other countries 2014); [61]
Because of its high caloric content (500–600 kcal/100 g), chocolate consumption may be an important aspect of overall energy balance in men as well as in women. It could contribute to 7–8 kg overweight/year in Germany if chocolate was used as an add-on to a normocaloric diet. The high fat and sugar content limit its use in a diet with the aim to minimize risk factors. Yet regular cocoa consumption – an essential ingredient for chocolate production – prevented high blood pressure in Kuna Indians of Panama [20]. Recent investigations have shown that flavanol-rich dark chocolate induces coronary vasodilation, improves coronary vascular function, and decreases platelet adhesion even in a short-term experiment 2 h after consumption. These immediate beneficial effects were paralleled by a significant reduction of serum oxidative stress and were positively correlated with changes in serum epicatechin concentration [45]. The possible beneficial effects of cocoa on cardiovascular health by activation of nitric oxide (NO) and influencing antioxidant, anti-inflammatory, and antiplatelet effects, which in turn might improve endothelial function, lipid levels, blood pressure, insulin resistance, and eventually clinical outcome, have been reviewed [20]. Cocoa is contained in dark chocolate rather than in milk chocolate. The content of the bitter-tasting flavanols is responsible for the vasodilating and antioxidative effects of the chocolate, whereby epicatechin is probably the dominant if not the sole mediator. Interestingly the procyanidins, which are polymerized chains of epicatechin and catechin, and which represent the vast majority of the polyphenol content of cocoa, are also as flavanols present in red wine, apples, and tea [58] and presumably responsible for the beneficial vascular effects. Unfortunately – or rather on purpose – in the regular production process of the chocolate, the bitter-tasting flavanols are largely eliminated by a process called “dutching” [59]. Accordingly the liberal consumption of chocolate as a preventive measure is probably limited by the bitter taste. In the regular chocolate these prognostic beneficial ingredients have been partially eliminated to better please the taste of the majority of the consumers ( Fig. 2.2).
Fig. 2.2
A 70 % chocolate which improves endothelial function (www.chocosuisse.ch accessed 22 February 2009)
Thus chocolate with high flavanol content has beneficial effects on endothelial function and can probably be enjoyed without untoward effects as a snack by persons who are fond of bitter chocolate. The bitter flavor will probably prevent any excessive caloric intake.
2.2.6 Non-pharmacological Decrease of the Postprandial Rise in Glucose
The postprandial rise in glucose appears to be of some importance for the development of diabetes and cardiovascular events; it also correlates with indicators of oxidative stress. A moderate (20 g of alcohol) “aperitif” results in a decrease of the postprandial rise in glucose; two tablespoons of vinegar, e.g., with salad before a meal with a high glycemic index, have a similar effect as well as almonds, walnuts, or peanuts ( Figs. 2.3 and 2.4).
Fig. 2.3
Vinegar reduces postprandial glucose. The addition of two tablespoons of vinegar to two slices of white bread significantly reduced the postprandial glucose increase (Modified from O’Keefe et al. [118])
Fig. 2.4
Almonds reduce postprandial glucose. The postprandial increase in the area under the curve for glucose was reduced by 58 % when 90 g of almonds were added to a high glycemic index meal ( p < 0.01) (Modified from O’Keefe et al. [118])
These components – which are part of the Mediterranean diet – can result in a noticeable decrease of postprandial lipid and glucose levels [118].
2.2.6.1 Glycemic Index
The glycemic index (GI) is an empiric measure describing the influence of carbohydrates on glucose-insulin homeostasis based on the extent to which they raise blood glucose levels 2 h after their consumption. Less refined carbohydrates with a high fiber content have a lower GI.
Food consumption with a low GI decreases postprandial glucose, insulin levels, and triglycerides, improves the total cholesterol/HDL cholesterol ratio, may support the decrease of body weight, and possibly has – via this pathway – a favorable effect on the development of diabetes and CHD. This concept may be particularly useful in type III hyperlipoproteinemia [118, 125]. However, whether these improvements translate into improved clinical outcomes is not known.
In randomized trials, reduced-glycemic-index diets have not resulted in increased weight loss beyond that explained by caloric restriction. In some aspects low-glycemic-index diets have features resembling the Mediterranean diet [97]. In a 5-week controlled feeding study, diets with low glycemic index of dietary carbohydrate, compared with high glycemic index of dietary carbohydrate, did not result in improvements of metabolic parameters or blood pressure if the baseline diet was structured as a DASH (Dietary Approaches to Stop Hypertension)-type diet. The DASH-type diet is rich in fruits, vegetables, and low-fat dairy and reduced in fats and cholesterol. Thus the negative prognostic importance of the glycemic index of single food items is diminished in persons consuming a “healthy” diet [137].
2.3 Dietary Patterns
Although scientific investigation of macro- and micronutrients remains essential to elucidate biological mechanisms, the concept of cardiovascular prevention by nutrition has moved from focusing on individual components of a diet to emphasizing a food pattern.
2.3.1 Mediterranean Diet
In general the type of diet is part of the lifestyle, and there may be some residual bias when correlating a diet with the occurrence of cardiovascular events. The Mediterranean lifestyle used to be more relaxed compared to the Central European or US American lifestyle.
The Mediterranean diet has been favored since the Seven Countries Study as promoting longevity and good cardiovascular health [73, 74].
In 1999 the Lyon Diet Heart Study had shown in a randomized interventional study that a strict Mediterranean diet in patients after myocardial infarction is associated with a 45 % reduction of the CV event rate [26]. The Mediterranean diet is a class 1 recommendation (Evidence Level B) in the European Society of Cardiology guidelines for CV prevention [127] and is also recommended by the AHA and ACC [36].
2.3.1.1 Mediterranean Diet Scores and Prognostic Implications (Observational Studies)
In the meantime however the components of the Mediterranean diet have been analyzed in many countries and have been correlated with events in more than half a million persons. The Mediterranean diet is characterized by a high proportion of vegetables, legumes, fruits, and cereals (primarily unprocessed), frequent fish consumption, less dairy products, rarely meat, a moderate consumption of alcoholic beverages mostly as wine and preferably with meals, and a small amount of saturated fatty acids, but a high proportion of unsaturated fatty acids, particularly olive oil.
In middle-aged persons, there was a significant inverse relation between the degree of compliance with the Mediterranean diet (as evaluated by a score) and mortality [147]. Because this score has been used extensively and repeatedly with only minor modifications in different studies [102, 159] and different countries, it will be outlined in some detail here; this score can also be used as a checklist in advising patients to change their diet into the direction of a Mediterranean diet. The traditional Mediterranean diet score includes nine components and results in values from 0 to 9 points reflecting minimal to maximal conformity with the score ( Table 2.2).
Table 2.2
Components of the Mediterranean diet score: one point for above (high intake) or below (low intake) the age and gender adjusted consumption of the corresponding nutritional item
1. High ratio of monounsaturated: saturated fatty acids |
2. High intake of legumes |
3. High intake of grains |
4. High intake of fruit and nuts |
5. High intake of vegetables |
6. High intake of fish |
7. Low intake of meat and meat products |
8. Low intake of milk and dairy products |
9. Moderate consumption of alcohol (10–50 g/day for men, 5–25 g/day for women) |
One point each is given for intake at or above the gender-specific median intake for the six components considered to be healthy (fatty acid ratio, legumes, grains, fruits, vegetables [excluding potatoes], or fish), and one point if the consumption of the items considered to be less healthy (meat and dairy products) was below the gender-specific median. One point is given for alcohol consumption within a specified range (5–25 g/day for women; 10–50 g/day for men) ( Fig. 2.5).
If participants met all the characteristics of the Mediterranean diet, their score was the highest (nine points), reflecting maximal conformance with a Mediterranean diet, and if they met none of the characteristics, the score was zero reflecting minimal or no conformity with a Mediterranean diet.
In two cohorts of elderly persons, the life-prolonging effects of the Mediterranean diet could be observed:
In the HALE Project among 2339 apparently healthy men and women, aged 70–90 years, adherence to a Mediterranean diet was associated with a 23 % lower rate of all-cause mortality [78].
In the EPIC study of more than 74,000 above 60-year-old European persons without coronary heart disease, stroke, or cancer at enrolment, a two-unit increment in the modified Mediterranean diet score was associated with a statistically significant reduction of overall mortality of 8 % [160].
Also in a prospective observational study of more than 380,000 US Americans (age range 50–71 years), a 20 % reduced total mortality and CV mortality could be seen as well as a 12–17 % reduced cancer mortality in men and women who showed with 6–9 points a good conformity with a Mediterranean diet compared to persons with a score of 0–3. This relationship was seen in smokers and never-smokers alike [102]. A similar Mediterranean diet score was used for nutritional evaluation in the HALE Project [78] and the EPIC study [160]. Thus the database for the primary preventive effects of the Mediterranean diet has been greatly strengthened.
The beneficial effects of the Mediterranean diet were confirmed in the Nurses’ Health Study in more than 74,500 women 38–63 years of age, without a history of cardiovascular disease and diabetes who were followed from 1984 to 2004.
The authors used the alternate Mediterranean diet score (Fig. 2.5) from self-reported dietary data collected through validated food frequency questionnaires administered six times between 1984 and 2002. During 20 years of follow-up, 2391 incident cases of CHD, 1763 incident cases of stroke, and 1077 cardiovascular disease deaths (fatal CHD and strokes combined) were ascertained. Women in the top alternate Mediterranean diet score quintile were at 29 % lower risk for CHD and 13 % lower risk for stroke compared with those in the bottom quintile. Cardiovascular disease mortality was 39 % lower among women in the top quintile of the alternate Mediterranean diet score ( p < 0.0001) [49]. In a Danish cohort, the Mediterranean diet score was inversely associated with total mortality and with cardiovascular and MI incidence and mortality but not with stroke incidence or mortality [157].The concept of the Mediterranean diet was confirmed for high-risk patients with stable coronary heart disease where greater consumption of healthy foods appeared to be more important for secondary prevention of coronary artery disease than avoidance of less healthy foods typical of Western diets [154].
This inverse relationship between consumption of “healthy” foods in the sense of the Mediterranean-type diet and risk of myocardial infarction was also confirmed in the INTERHEART study where dietary patterns were analyzed in patients after MI and controls in 52 countries [64]. Three dietary patterns were identified and labeled as Oriental, Western, and prudent. The “Oriental” pattern had a high loading on tofu and soy and other sauces. The second dietary pattern was labeled “Western” because of its high loading on fried food, salty snacks, and meat intake. The third dietary pattern was labeled “prudent” because of its emphasis on fruit and vegetable intake.
The authors found significant, inverse, and graded associations between the intake of raw vegetables, green leafy vegetables, cooked vegetables, and fruits on the one hand and acute myocardial infarction on the other hand. Conversely, they observed a positive association between myocardial infarction and the intake of fried foods and salty snacks ( p < 0.001) and a weaker association between quartiles of meat intake and AMI ( p = 0.08) [64]. The typical US southern dietary pattern however characterized by added fats, fried food, eggs, organ and processed meats, and sugar-sweetened beverages was associated with greater hazard of CHD in a sample of 17,400 white and black adults in diverse regions of the United States with 5.8 years of follow-up [143]. In the 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk, dietary recommendations are given that are largely in agreement with the Mediterranean diet [36].
2.3.1.2 Effects of the Mediterranean Diet on Risk Indicators and Risk Factors
The exact mechanisms leading to decreased myocardial infarction, cardiovascular deaths, and all-cause deaths are not clear, but several indicators of risk such as indicators of inflammation and established CV risk factors are decreased by the Mediterranean diet.
Estruch et al. examined in the randomized controlled PREDIMED trial the effects of a Mediterranean diet supplemented with 1 l olive oil per week (for a family of four) or with 30 g of nuts/day in comparison to a low-fat diet in 772 asymptomatic persons 55–80 years of age at high cardiovascular risk.
Compared with a low-fat diet after 3 months, both Mediterranean diets lowered plasma glucose levels, systolic blood pressure, and the cholesterol-high-density lipoprotein cholesterol ratio. The Mediterranean diet supplemented by olive oil also reduced C-reactive protein levels compared with the low-fat diet [37].
In the same study the effects of the Mediterranean diet on in vivo lipoprotein oxidation were assessed. After the 3-month interventions, mean oxidized low-density lipoprotein (LDL) levels decreased in the traditional Mediterranean diet group supplemented by virgin olive oil significantly and to a lesser degree also in the group supplemented by nuts – without significant changes in the low-fat diet group. Change in oxidized LDL levels in the traditional Mediterranean diet virgin olive oil group reached significance vs. that of the low-fat group ( p = 0.02) [37].
A Mediterranean diet supplemented with nuts (30 g/day) or olive oil (one liter per week for the family) resulted within 3 months in lower blood pressure, fasting blood sugar, and inflammatory markers as compared to a low-fat diet [43].
2.3.1.3 Mediterranean Diet and Inflammation
The inflammatory reaction of the body in relation to adherence to the Mediterranean diet was assessed in more than 300 middle-aged male twins using the mentioned diet score. A 1-unit absolute difference in the diet score was associated with a 9 % (95 % CI, 4.5–13.6) lower interleukin-6 level – an established marker of inflammation related to progression of atherosclerotic disease.
Thus reduced systemic inflammation appears to be an important mechanism linking Mediterranean diet to reduced cardiovascular risk [25, 47]. The hypothesis that inflammation impairs reverse cholesterol transport at numerous steps in the pathway from initial macrophage efflux to HDL acceptor function and the final step of cholesterol flux through the liver to bile and feces was confirmed for the first time in an in vivo study. The anti-inflammatory effect of the Mediterranean diet could to some degree contribute to its beneficial effects on cardiovascular but possibly also cancer incidence [98].
However it is not only the arterial system that benefits from a high intake of plant foods and fish and less red and processed meat: also the risk for venous thromboembolic events is reduced! In a prospective study as part of the Atherosclerosis Risk in Communities (ARIC) Study, almost 15,000 middle-aged adults were followed up over 12 years for incident venous thromboembolism. At baseline the average age of study participants was 54 years. A food frequency questionnaire assessed dietary intake at baseline and after 6 years. The risk of venous thromboembolism was assessed in quintiles of fruit and vegetable intake.
There was a significant risk reduction of venous thromboembolism incidence of 40–50 % in quintiles three to five compared with quintile one.
Eating fish one or more times per week was associated with 30–45 % lower incidence of venous thromboembolism for quintiles 2–5 compared with quintile 1, suggestive of a threshold effect. High intake of red and processed meat intake (quintile 5) doubled the risk ( p trend = 0.02). Hazard ratios were attenuated only slightly after adjustment for factors VIIc and VIIIc and von Willebrand factor [151].
2.3.1.4 Mediterranean Diet and Diabetes
Considering the components of the Mediterranean diet, it may come as no surprise that the Mediterranean diet has a preventive effect for the development of diabetes. In a prospective cohort study from Spain, a relation between adherence to a Mediterranean diet and the incidence of diabetes among initially healthy participants (university graduates) could be shown [97] – after adjustment for covariables such as sex, age, years of university education, total energy intake, body mass index, physical activity, sedentary habits, smoking, family history of diabetes, and personal history of hypertension. Participants who adhered closely to a Mediterranean diet had a lower risk of diabetes. The incidence rate ratios in the fully adjusted analyses showed that a two-point increase in the score was associated with a 35 % relative reduction in the risk of diabetes with a significant inverse linear trend ( p = 0.04) in the multivariate analysis. A high adherence (7–9 points) was associated with an 80 % reduced incidence rate of diabetes compared with a low score of 0–2 [97].Thus the traditional Mediterranean diet may have considerable protective effects against diabetes.
Similar results were obtained in patients after myocardial infarction [106]. In prospectively obtained data of 8291 Italian patients with a recent (<3 months) myocardial infarction, who were free of diabetes at baseline, the incidence of new-onset diabetes (new diabetes medication or fasting glucose ≥7 mmol/L) and impaired fasting glucose (fasting glucose ≥6.1 mmol/L and <7 mmol/L) were assessed up to 3.5 years. A Mediterranean diet score was assigned according to consumption of cooked and raw vegetables, fruit, fish, and olive oil. Associations of demographic, clinical, and lifestyle risk factors with incidence of diabetes and impaired fasting glucose were assessed with multivariable Cox proportional hazards regression analysis.
These patients had a 15-fold higher annual incidence rate of impaired fasting glucose and a more than twofold higher incidence rate of diabetes during a mean follow-up of 3.2 years (26,795 person-years) compared with population-based cohorts. Consumption of typical Mediterranean foods, smoking cessation, and prevention of weight gain were associated with a lower risk [106].
2.3.1.5 Meta-analysis of Mediterranean Diet Studies
The benefits of the Mediterranean diet pattern were evaluated in a meta-analysis of 514,816 subjects on the basis of 33,576 deaths occurring during the respective observation time. The overall mortality in relation to adherence to a Mediterranean diet showed that a two-point increase in the adherence score was significantly associated with a 9 % reduced risk of all-cause mortality and likewise a 9 % reduction on cardiovascular mortality as well as a 6 % lower incidence of or mortality from cancer. The message from these studies is that it is the completeness of adherence to the Mediterranean diet rather than the consumption of individual components, which is effective in improving the prognosis. Unexpectedly also the incidence of Parkinson’s disease and Alzheimer’s disease was significantly reduced by 13 % [147].
Thus a greater adherence to a Mediterranean diet is not only associated with a significant reduction in mortality from arterial cardiovascular diseases but also from a reduced incidence of venous thromboembolism. In addition other diseases that are a threat for the well-being and quality of life in the later years are decreased: cancer, Parkinson’s disease, and Alzheimer’s disease – diseases for which no specific strategies of prevention have been established. This makes it easy for the physician to recommend this type of diet to the cardiovascular patient after myocardial infarction: the side effects of this diet are most welcome [36, 127].
2.3.1.6 Mediterranean Diet in Primary Prevention: PREDIMED Study
The abovementioned randomized primary prevention PREDIMED study [37] in an older population at high cardiovascular risk (mean age 67 years, age range 55–80 years) which demonstrated in the early phase an improvement of several risk indicators showed after 4.8 years of follow-up that an energy-unrestricted Mediterranean diet supplemented with extra-virgin olive oil or nuts resulted in a substantial reduction in the risk of major cardiovascular events. The hazard ratios were 0.70 (95 % confidence interval [CI], 0.54–0.92) for the group assigned to a Mediterranean diet with extra-virgin olive oil and 0.72 (95 % CI, 0.54–0.96) for the group assigned to a Mediterranean diet with nuts, in comparison to the control group. The randomized study supported the results gained from observational studies and supports the benefits of the Mediterranean diet for the primary prevention of cardiovascular disease [38]. In a sub-study, the Mediterranean diet supplemented with olive oil or nuts was associated with improved cognitive function [162] and with a reduced incidence of invasive breast cancer in the participating women in the Mediterranean diet with extra-virgin olive oil group [158].
2.3.2 Other Dietary Patterns: Dietary Risk Score and Acute Myocardial Infarction (INTERHEART Study)
The authors from the INTERHEART study [64] computed from their data a dietary risk score (DRS) and observed a graded and positive association between this DRS and risk of AMI. Food items that were considered to be predictive (meat, salty snacks, and fried foods) or protective (fruits and green leafy vegetables, other cooked vegetables, and other raw vegetables) of CVD were used to generate a DRS. The authors used a point system. Compared with the lowest quartile, odds ratios (adjusted for age, sex, and region) varied from 1.29 in the second quartile of dietary risk score to 1.92 in the fourth quartile. The association of the score with AMI varied by region ( p < 0.0001) but was directionally similar in all regions. The population attributable ratio for this score was 30 % (95 % CI, 0.26–0.35) in participants in the INTERHEART study ( Fig. 2.6).
Fig. 2.6
Population attributable risk and odds ratios for acute myocardial infarction associated with dietary risk score (Modified from Iqbal et al. [64])
Thus many observational and case–control studies have already suggested the prognostic importance of a healthy (prudent) or Mediterranean-type diet for a lower risk for myocardial infarction (and cancer), which was later verified by a randomized study [38].
However more randomized interventional studies are necessary to develop specific dietary recommendation for patients with CV disease and with different metabolic problems.
2.4 Drinks
The fluid requirements of the body vary depending on the environment and the physical activity. The type of fluid preferred to fulfill the requirements depend on tradition and environment.
2.4.1 Coffee or Tea Consumption and Cardiovascular Events
Coffee and tea and to a lesser degree chocolate have been the most widely used drinks during the course of the day for decades if not centuries but their relationship to the risk of coronary disease has been examined only in recent years.
2.4.1.1 Coffee
Coffee consumption has been associated with an increased risk in patients with coronary artery disease. The influence of coffee on cholesterol levels was already examined in 1989. After 9 weeks of coffee consumption, boiled coffee increased LDL cholesterol by 10 %, whereas filtered coffee showed no difference compared to a “no-coffee” group [5].
In the Health Professionals’ Follow-Up Study, almost 42,000 male employees in the hospital (age range 40–75 years) were asked about their coffee consumption, lifestyle, and risk factors every 2 years for a total of 12 years. Similarly in the Nurses’ Health Study, more than 84,000 nurses in the age range of 30–55 years were asked about their coffee consumption every 2 years for a total of 18 years. In both studies the prevalence of diabetes mellitus was examined: coffee consumption of 4–5 cups/day reduced the prevalence of diabetes mellitus by 29–30 % in males and females similarly after multivariate analysis. In males even a consumption of more than six cups of coffee per day reduced the risk of diabetes by 46 %, whereas in females there was no further decrease of the diabetes prevalence beyond the consumption of five cups of coffee [126].
In a systematic review habitual coffee consumption was associated with a substantial lower risk of type II diabetes which was also observed for decaffeinated coffee in postmenopausal women [126] as well as middle-aged and younger US women [163].Thus there may be ingredients in the coffee – other than caffeine – that protect from diabetes.
Coffee consumption in two observational studies showed no increased risk for the development of coronary artery disease. The consumption of up to five cups of coffee per day is without harm for the coronary patient and possibly beneficial by preventing or delaying the occurrence of diabetes – but beware of the sugar and cream!
Coffee consumption decreased the relative risks of stroke across categories of coffee consumption in the more than 83,000 women of the Nurses’ Health Study [163]. After adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the relative risk reduction was 43 % among never and past smokers (RR for >4 cups a day versus <1 cup a month; p < 0.001), but not significant among current smokers. Similarly there was a protective effect among non-hypercholesteremics (HR 0.77, p < 0.003), nondiabetics (HR 0.79, p = 0.009), and non-hypertensives (HR 0.72; p = 0.001). However, no protective effect was seen in women with diabetes, hypertension, or hypercholesterolemia, suggesting that the moderate beneficial effects of coffee consumption cannot override the detrimental effects of these important risk factors. The authors also observed a slightly lower risk of stroke in women who drank moderate amounts of decaffeinated coffee (2–3 cups/day vs. <1 cup/month; HR 0.84; p = 0.002) suggesting that components in coffee other than caffeine may be responsible for the potential beneficial effect of coffee on stroke risk [91]. A similar effect was seen in a large Japanese population study (more than one million person-years with a follow-up time of 13 years) where 1–2 cups of coffee per day reduced the hazard ratio for stroke by 20 % compared to persons who seldom drank coffee, but there was no effect on coronary events [80]. In a large observational study of more than 208,000 American persons (74,890 women in the Nurses’ Health Study, 93,054 women in the Nurses’ Health Study II, and 40,557 men in the Health Professionals Follow-Up Study) and more than 4.6 million person-years of follow-up significant inverse associations were observed between coffee consumption and deaths attributed to cardiovascular disease, neurologic diseases, and suicide. No significant association between coffee consumption and total cancer mortality was found. Restricting the analysis to never-smokers, the lowest hazard ratio of 0.85 (0.79–0.92) was seen for 3.1–5.0 cups of coffee per day. But even more than 5.0 cups of coffee per day were of advantage compared with non-coffee drinkers with a hazard ratio of 0.88 (0.78–0.99), confirming that even higher consumption of total coffee, caffeinated coffee, and decaffeinated coffee was of no harm and associated with lower risk of total mortality [30].
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
