Integrated Approach to Coronary Artery Disease


Cardiovascular risk factor

Relative risk

Smoking

2.87

Hypertension

1.91

Elevated Apo B/ Apo A1

3.25

Diabetes

2.37

Abdominal obesity

1.12

Psychosocial factors

2.67

Daily consumption of fruits and vegetables

0.7

Regular physical activity

0.86



Nutritional imbalance, sedentary lifestyle, stress and depression, smoking, and air pollution play a key role in the pathogenesis of risk factors for CHD and the onset and progression of atherosclerotic disease [9, 10]. Also, what is commonly called “genetic predisposition” seems to be increasingly linked to genome activation patterns in response to environmental influences, as demonstrated by the acquisition of the local, most high-profile, cardiovascular risk of migrants from areas with a low incidence of coronary heart disease [11, 12]. The concept of an epigenetic modulation of coronary artery disease, with traces that can be transmitted transgenerationally, is taking hold [9]. These traces are stable but reversible, and this indicates the importance of prevention with an integrated approach to the care of CHD [9, 1113].

Currently, it is thought that one of three children born in the year 2000 will go on to develop diabetes during his or her lifetime [14]. Consequently, for the first time in history, it is possible for children to have a shorter life expectancy than their parents [12, 15].

As stated by Stephen Devries [8, 16]: “an integrative approach acknowledges the great value and potentially lifesaving benefits of modern pharmacology and procedures, while at the same time recognizing the limitations of these approaches when they are used in isolation.” Most drug and interventional therapy patterns are studied in the context of acute illness and do not fit or even fall into the context of chronic disease [9, 11, 12, 17].

Devries [16] states, “an integrative approach is ideally suited for prevention and treatment of coronary disease because it addresses many of the root causes, especially those influenced by lifestyle.” Thus, cardiologists should become familiar with a broader spectrum of therapies beyond those that typically constitute conventional cardiovascular care (Fig. 16.1).

A333495_1_En_16_Fig1_HTML.gif


Fig. 16.1
In summary: staged integrative approach to coronary heart disease. Don’t smoke, promote risk factors reduction (diabetes, hypertension, hyperlipidemia), regular exercise, provide a comprehensive nutritional plan (adding fiber and omega-3 fatty acids, vegetables, whole grain bread, and cereals), evaluate for depression, anxiety or anger proneness, and manage stress

The Coronary Artery Surgery Study (CASS) demonstrated that patients with healthy hearts, but with one, two, or three stenotic major heart vessels, did surprisingly well without surgery, regardless of the number or severity of blockages [18]. This result correlates with what has emerged from the COURAGE study, where the benefits of coronary revascularization compared with optimal medical therapy were lacking, in the case of stable coronary artery disease, although angiographically critical [1922]. Moreover, there is evidence that prolonged dual antiplatelet therapy following placement of a drug-eluting stent increases major bleeding but is not associated with a decrease in composite rates of death or myocardial infarction [23, 24]. From these observations coronary artery stenosis does not estimate correctly the possible presence of a reduction of flow in the artery. Furthermore, acute coronary events often arise from “mild” coronary lesions that are far less than 50% obstructive [25]. These seemingly harmless plaques are more “vulnerable,” having a large lipid core and thin fibrous cap, which make them likely to rupture and evolve into a complete thrombotic occlusion and a potentially lethal cardiac event [26]. This is the explanation for the anecdotal familiar to most clinicians and patients about the individual who sailed through a stress test with “normal” results, only to suffer a cardiac catastrophe a short time later.

But what determines the catastrophe precisely at some point in the patient’s history?

A possible answer to this question comes from the study of coronary microcirculation to understand the dense network of factors that, adjusting endothelial function, can maintain the balance between health and cardiovascular disease. For an extended discussion of the issue, please see our recent reviews [9, 1113]. Briefly, we focus on the functional restriction to blood flow, which may lead to ischemia even in the absence of atherosclerotic plaques or angiographically critical plaques. The mechanism that drives myocardial ischemia concerns the regulation of coronary microcirculation in which several factors converge: neurotransmitters, cytokines, and hormones. In turn, these mediators are involved in the activation and operation of the integrated chronic stress axis, on which the psychological and emotional profiles and lifestyle of the subjects play a key role [9, 11, 12].

We agree with Stephen Devries when he says [16]: “The finding that a coronary event can rapidly develop from what angiographically appears to be a ‘mild’ coronary lesion emphasizes the need to prevent coronary lesions from developing, rather than to focus on reducing the severity of severe stenoses with interventional procedures.” We would add that more resources should be invested in the field of preventive medical research and basic research into understanding the origin of these phenomena.



16.2 Nutrition


From Hippocrates, we know that “food is medicine.” Nutrition represents the best tool available for prevention and treatment of CHD as demonstrated by the striking results of the Lyon Diet Heart study [27]. This study, conducted in individuals who survived myocardial infarction, shows that a Mediterranean-style diet leads to a 73% reduction in cardiovascular events, including myocardial infarction and cardiac death, after 27 months in comparison with controls. After 5 years of follow-up the benefit of the Mediterranean-style diet was maintained with a 72% reduction in cardiovascular events [28].

The cornerstone of the Mediterranean diet consists in eating a lot of vegetables (especially dark green leafy vegetables [29]) and fruit, nuts, and fish, in using olive oil and in a low to moderate intake of red meat and refined carbohydrates. Thus, it is possible to recommend a daily consumption of five servings of vegetables and two servings of fruit [16].

A single high-fat meal transiently impairs endothelial function and blood flow [30].

In the Mediterranean diet, chicken or fish substitute red meat, reducing the risk of CHD of 30% [31, 32] to 40% [33].

The Mediterranean diet emphasizes the consumption of whole grains to reduce CHD risk [34]. Indeed, refined grains favor atherosclerosis, releasing more glucose into the circulation and triggering higher insulin levels. This process is accompanied by reduced levels of high-density lipoprotein (HDL) and increased levels of atherogenic small dense low-density lipoprotein (LDL) [35]. Examples of whole grains include barley, buckwheat, quinoa, polenta, and brown rice.

As suggested by Hallfrisch et al. [36]: “the manner in which grains are prepared also has important health implications. Consuming pulverized grains, even whole grains, results in a higher blood glucose level than when the intact grain is eaten. Therefore, boiled whole grains are typically a healthier choice than bread made from the flour of whole grains.”

Moreover, increasing consumption of nuts, another key element of the Mediterranean diet, to two handfuls per day reduces LDL [37] and the risk of CHD [38]. The nutmeg oil contains substances with platelet anti-aggregating action [39]: eugenol, isoeugenol, safrole, elemicin, myristicin, and limonene. The mechanism of action is the inhibition of cyclooxygenase [40, 41].

Finally, curcumin, soy beans extracts protect heart function against myocardial ischemia–reperfusion injury by activation of the JAK2/STAT3 signaling pathway [4244].


16.3 Exercise


Along with nutrition, exercise is the other natural cornerstone to be added for cardiovascular health maintenance and for the treatment of CHD and its consequences. It must be emphasized that the intensity of exercise is less important than the frequency and consistency [45]. The two best forms of exercise to reduce cardiovascular risk are aerobic exercise (30 min of brisk walking every day) and resistance training (two to three sessions per week of light resistance training interspersed with stretching [45] or yoga [46, 47]).

In patients with ischemic heart disease or cardiovascular risk factors, it is good practice to run a stress test or a cardiopulmonary test for proper exercise prescription [5].

As we recently described [9, 11, 12], exercise alone is not enough: we have to take care of the mental aspects of our patients. Bergh et al. [48] have shown exercise to be an effective advantage in terms of prevention and treatment of cardiovascular diseases, must be accompanied by good psychological resistance to stress. In fact, low-stress resilience in adolescence is associated with increased risk of CVD in middle age. The association remains after adjustment for physical fitness: higher physical fitness is inversely associated with CVD risk; however, this is significantly attenuated by low-stress resilience [48].


16.4 Supplements


Change in lifestyle is the basis of a program of primary and secondary prevention of cardiovascular disease. The optimization of lifestyle is vital, to treat dyslipidemia before it is necessary to use statins. We want to recall that 33% of heart attacks occur in individuals with a total cholesterol above 200 mg/dL [49]. For the integrated care of dyslipidemia see Chap. 14.

We would like to focus attention on the availability of some lipid-lowering supplements only (Table 16.2) that can be employed in patients philosophically opposed to the use of statins or who are not able to tolerate them for the onset of side effects (myalgia). They are: fiber (psyllium 10 g per day) [50, 51]; plants containing phytosterols and stanols (1.8 g per day as a single dose, added to certain margarines or in pill form) [52]; niacin, a vitamin B (500 mg per day, titrated upward by 500-mg increments every 6–8 weeks as needed, to a maximum of 2,000 mg per day, checking liver function and flushing. To avoid niacin flush, niacin must be taken with dinner or after dinner with apple sauce or with aspirin. Flush-free niacin compounds are ineffective) [53, 54], red yeast rice (600 mg twice daily, then 1,200 mg b.i.d) [5559], and fish oil (not the total fish oil, but its eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids lower triglyceride values with a dosage of 1,000 mg per day for prevention and 1,000 mg to 4,000 mg for the treatment of hypertriglyceridemia) [60].


Table 16.2
Alternative therapies for reduction of low-density lipoprotein cholesterol. Modified from Rakel [16]






















Product

Percentage of reduction

Psyllium (10 g/day)

7 %

Sterol and stanol (1.8 g/day)

14 %

Niacin (up to 2 g/day)

15–20 %

Red yeast rice (2,400 mg/day)

20–30 %

Coenzyme Q10 (CoQ10) is an essential component of mitochondrial energy production and is commonly deficient in elderly people, in subjects taking statins and beta-blockers, and in patients with heart diseases in general [61]. Its supplementation could be useful for improving myalgia in patients with a history of statin-related muscle symptoms [6265]. Moreover, CoQ10 (100 mg to 200 mg per day) seems to improve systolic function in the case of heart failure [66], to halve the frequency of angina attacks in stable patients, and to increase treadmill exercise tolerance [67].

The action of vitamin D receptors regulates blood pressure and vascular arterial function [68] and a deficiency in vitamin D correlates with higher cardiovascular risk, especially in hypertensive subjects [69]. However, even if data about the efficacy of its supplementation are inconclusive, values higher than 30 ng/mL are desirable [16]. It can be helpful in reducing the risk of muscle pain associated with statins [70].

Selective folic acid supplementation has not proven to be useful for the prevention of cardiovascular events, but foods rich in folate (dark green leafy vegetables) are associated with significant benefit [7173].

Vitamin E exists in eight isomers: four tocopherols and four tocotrienols. Studies have focused only on the alpha-tocopherol fraction of vitamin E, with no cardiovascular benefit [7477]. Probably, in the future, gamma and delta tocopherols may be more beneficial [78, 79].

Heart ischemia reduces the levels of carnitine (see Chap. 17 on heart failure) increasing the risk for angina [61]. Its supplementation (900 mg q.d.) improves angina and CHD [8084], allowing the heart muscle to utilize limited oxygen more efficiently, improves exercise tolerance, exerts a cardioprotective and slightly anti-extrasystolic beats function, and represents a good alternative to drugs in patients with stable angina pectoris [18].

Pantethine is a component of coenzyme A that decreases during ischemia: its supplementation 900 mg q.d. determines a lipid-lowering effect [18]. It could be useful in treating angina [85].

Magnesium deficiency may produce coronary vasospasms and non-occlusive myocardial infarction [8689]. Magnesium supplementation in the first hour after an acute infarction reduces immediate and long-term complications and death rates, dilating coronary arteries, inhibiting platelet aggregation, reducing infarct size, and helping to manage arrhythmias and angina [9092].

Arginine supplementation (3–6 g/day) could be effective in cases of angina pectoris because of its ability to increase nitric oxide levels, thereby improving blood flow, reducing thrombosis and improving rheology [9396]. Higher doses could be unsafe [97].


16.5 Phytomedicine


In cardiovascular medicine, there are many compounds of herbal medicine that can be used for therapy [98] and many drugs used in hospitals in western standard clinical practice are derived from plants, such as digitalis, hypericum, valerian, or senna [99]. On the other hand, we are discovering in plants new principles and extracts potentially active on the cardiovascular system that can be used as herbal medicines or become the basis for new drug products [100], such as astragaloside IV [101104] and naringenin [105], compounds with anti- inflammatory activity, that inhibit the NF-kB factor.

The epidemiological evidence reported above on the use of herbs and these introductory examples serve to demonstrate how the cardiologist or internist should familiarize themselves with the use of herbs because: many herbal remedies interfere with most of the antiplatelet agents, anticoagulants, anti-arrhythmics and diuretics [106, 107]; many sub-clinical diseases find in herbal medicine an helpful and economic help, that can be integrated into standard clinical practice [99]; many substances of plant origin, anti-oxidants, or food (Mediterranean diet [108, 109] or plant-based diets [110, 111]), are useful in the prevention of endothelial damage from atherosclerosis or other risk factors (smoking, free reactive oxygen radicals, hypercholesterolemia) [112, 113].


16.5.1 Dark Chocolate


Regular consumption of dark chocolate is associated with low serum concentrations of C-reactive protein [114, 115], blood pressure-lowering [116], platelet anti-aggregation effects [117], endothelial protection [118, 119], coronary vasomotion improvement [120], and insulin sensitivity increase [121, 122].


16.5.2 Green Tea, Black Tea, and Coffee


As revealed by Kuriyama et al. [123125], green tea consumption reduces mortality from cardiovascular disease of all causes, acting on the control of inflammation and vascular atherosclerosis. Moreover, epidemiological studies have shown a reduction in the risk of stroke derived from the intake of coffee or tea, independently of known cardiovascular risk factors [126, 127]. The anti-oxidant properties of coffee, cocoa, and tea [128] are well known for their benefits for the cardiovascular system, the coronary area in particular, owing to the action of the polyphenols contained in these foods [129]. Coffee contains over a thousand chemicals, many formed during the roasting process. From a physiological point of view, the potential bioactives are caffeine, the diterpenes cafestol and kahweol, found in the oil, and the polyphenols, most notably chlorogenic acid [130, 131]. Black tea consumption, with its anti-oxidant flavonoids, reverses endothelial dysfunction in patients with coronary artery disease [132134].

Experimental data show that the polyphenols in green and black tea protect the endothelium in an equivalent manner [135, 136] and that the consumption of tea causes rapid improvements in the hemorheological parameters and in the function of endothelial progenitor cells, and may represent an important factor for cardiovascular protection, especially in smokers [137, 138]. The age of an individual correlates with the state of his arteries: during life, risk factors (smoking, hypertension, diabetes, hyperlipidemia, stress) cause damage to the endothelium of the vascular system in several places, constituting the first event of a series of processes that lead to the formation of atheroma and thrombus. The elements located under the endothelium, mainly collagen fibers, mediate the response and activation of platelets in a process in which platelet activating factor (PAF) plays and important role, being involved in the pathogenesis of thrombosis, vascular permeability, and endothelial damage.


16.5.3 Vitis vinifera and Polygonum cuspidatum


Another plant that recently entered the handbook of cardiovascular herbal medicine is Vitis vinifera: from its seeds resveratrol and of procyanidins are extracted [139, 140]. Procyanidins are indicated in the prevention of post-ischemic myocardial injury [141, 142], disorders of peripheral venous insufficiency, and in protecting endothelial cells, performing an anti-oxidant action that may also be useful in the treatment and prevention of many degenerative and chronic inflammatory conditions [143, 144]. Resveratrol is a phytoalexin, also present in other plants (such as in Polygonum cuspidatum), which has an anti-inflammatory activity (COX-2 inhibitor) [145] and a weak phyto-estrogenic action [146], prevents certain stages of carcinogenesis and also increases the activity of some anti-HIV drugs, such as zidovudine and didanosine [99]. Moreover, the anti-oxidant properties of red wine were demonstrated, also capable of inhibiting the formation of NF-kB, implicated in the pathogenesis of atherosclerosis [147]. Resveratrol has an antiplatelet activity and inhibits the oxidation of lipoproteins [146]. In summary, the grape contains a number of substances very useful in the prevention of cardiovascular disease [148, 149]. The resveratrol is present in the husk of the grains of grapes in a dose of 50–100 mg/g, while in wine it is present in an amount equal to 0.1–0.15 mg/L [99].


16.5.4 Salvia miltiorrhiza


There are some interesting therapeutic perspectives regarding the use of Salvia miltiorrhiza (Bunge), a typical plant of traditional Chinese medicine (Danshen) from which extracts of roots are used [150]. The plant contains a number of fat-soluble substances (tanshinones I, IIA, and IIB) and soluble (salvianolic acids A and B), which have the following properties: antiplatelet activity [151]; they release nitric oxide by endothelial cells [152]; they protect the myocardium from ischemic damage and reduce the area of myocardial necrosis by activation of the JAK2/STAT3 signaling pathway [4244, 153]; and they stimulate coronary vasodilation and protect the central nervous system from ischemic damage [100]. According to current scientific evidence, despite the interesting results, there is not sufficient security to be able to definitively recommend the use of Salvia miltiorrhiza because of the poor methodological quality of the studies available. However, it is a very promising medicinal plant for preventing cardiovascular and cerebrovascular ischemic diseases. There may be interactions with antiplatelet drugs and oral anticoagulants.


16.5.5 Ginkgo biloba


In recent decades, the Ginkgo biloba leaves have been studied and used as a source of active metabolites able to treat atherosclerosis: in fact, they contain a mixture of flavonoid glycosides and terpene derivatives, which have vascular properties [154]. In particular, the terpene derivatives called ginkgolides and bilobalides, named according to their chemical structure with the letters of the alphabet (A, B, C, M, J) are potent antagonists of PAF [155]; they also antagonize coronary PAF-induced vasoconstriction, PAF-induced thrombus formation, and appear to significantly reduce the consequences of stroke [99]. Flavonoids of ginkgo biloba, in addition to reducing arteriolar spasm and inducing anti-inflammatory activity, increase the release of insulin from Langerhans cells [156].

Ginkgo (Ginkgo biloba) is an ornamental plant of eastern origin that has been growing since the Mesozoic. Traditional Chinese medicine also uses its fruits, whereas Western herbalism only uses the leaves, which contain the aforementioned terpenic derivatives with anti-PAF function and flavonoids with specific action on the microcirculation [157]. The latter, in fact, protect cell membranes by the action of oxygen free radicals and reduce endothelial progenitor cell senescence through augmentation of telomerase activity [158]; reduce arteriolar spasm; play an anti-inflammatory action [156]; reduce capillary permeability; increase the resistance of the capillaries; optimize the use of oxygen and glucose by the tissues; and regulate nitric oxide synthesis [159, 160]. Although there are conflicting data in the literature [161163], and it is therefore necessary to gather additional evidence to establish the correct indications and timing of use in various cardiovascular diseases, the extracts of the plant could be employed for the treatment of atherosclerosis and its clinical manifestations (ischemic heart disease [164], peripheral vasculopathy [165, 166], cerebrovascular disease [167]), diabetes mellitus [168], vasculitis [169], angiosclerosis of the elderly brain [170], in Raynaud’s disease and dizzy syndromes [171]. Ginkgo is also indicated in the prevention of vascular damage from high blood pressure and smoking, and in the prevention of deep vein thrombosis. Caution should be exercised when treating patients with liver disease [172], those with coagulation disorders or who are pregnant. There may be interactions with antiplatelet drugs and anticoagulants [173]. Clinical use involves the administration of the dry extract standardized to 24 % flavonoids and 6 % ginkgolides (substances that are more concentrated in the fruit can cause allergic or toxic reactions). The average dosage of standardized dry extract is 80 mg, 2–3 times a day [99].


16.5.6 Vaccinium myrtillus


Other plants studied with regard to modern cardiovascular herbalism are the blueberry (Vaccinium myrtillus) and the cranberry [174, 175]. The extracts of the berries were once considered only for their actions in reinforcing the capillaries. Today, the whole plant is used as a medicine that contains anthocyanins (cyanidin, delphinidin, pelargonidin, malvidin, peonidin, petunidin, and hirsutidin) and glycosides, including anthocyanidins, which give the purple color to the berries (and to numerous flowers of other plants) [99, 176]. Furthermore, the plant contains flavonoids and tannins [177]. The plant protects the endothelial cells because of its inhibitory action on the elastases and collagenases, making the connective tissue more stable and elastic [178]. Anthocyanosides inhibit platelet aggregation mediated by adenosine diphosphate, collagen, arachidonic acid, and PAF through the inhibition of thromboxane A2 and the degradation of AMP-c (a mechanism that appears similar to that of garlic) [99]. An antagonistic action on angiotensin II and the stimulation of the prostacyclin synthesis by the vascular wall [176, 179] have also been demonstrated. The anti-oxidant properties [180] of blueberry flavonoids are indicated in the prevention of ischemic heart disease and stroke [181183]. Procyanidins inhibit xanthine oxidase in a non competitive way [184]. Blueberry extract also protects the arteriovenous microcirculation from damage related to the process of ischemia-–reperfusion [185]. The clinical efficacy of blueberry extract was primarily detected in the retinal area [186], where the plant’s ability to sharpen night vision and to regenerate rhodopsin by increasing the activity of retinal LDH has been shown. Its active ingredients, finally, contrast capillary fragility, reducing vascular permeability, even at the peripheral level [178]. The blueberry can be employed in the treatment of patients with hypertensive retinopathy and/or diabetic and smoking patients with initial signs of micro- and macrovascular arteriosclerotic damage.


16.5.7 Allium sativum


Garlic (Allium sativum) has been used in medicine for thousands of years and has interesting cardiovascular properties [187]. These include the ability to inhibit platelet aggregation and the fibrinolytic, hypofibrinogenic, lipid-lowering, hypoglycemic, and hypotensive activities [188190]. The German Ministry of Health has officially recognized the specific role of garlic in the treatment and prevention of atherosclerosis [99, 191, 192]. In addition, the plant is the most frequently used in the presence of heart disease [193] and for cardiovascular risk reduction [194, 195]. The main constituent of fresh garlic is alliin, which is transformed in turn into allicin as soon as the bulb is bruised by the action of an enzyme called allinase [196]. Allicin, being very unstable, is partly transformed quickly into another compound called ajoene [196]. Other important constituents are vinylditin, thiosulfinates, essential oil, deoxy-fructopyranosyl-allyl-cysteine sulfoxide) and allixin [196]. Platelet aggregation is inhibited by membrane receptor blocking and has been documented in vitro and in vivo with a dose-dependent mechanism [99].

The reduced platelet aggregation, the increased fibrinolysis, and the lipid-lowering action reduce the thrombotic risk [197200]. Furthermore, the molecules of ajoene determine in vitro the inhibition of the cyclo- and lipo-oxygenase equal to indomethacin [99]. Garlic enhances the inhibitory action of prostacyclin 2 and of forskolin on platelet aggregation [201]. Furthermore, adenosine deaminase is inhibited, with a consequent increase in the adenosine available on the vascular endothelium, with vasodilatory and antiplatelet activity [202, 203]. The antiplatelet activity is very effective in vitro [204], but may not be the same in vivo, because the active substances are rapidly metabolized by tissues and are themselves quite unstable [205]. Some extracts also have reduced activity in vivo: the oils distilled in a current of steam have an activity of 35 % and macerated oil 12 % [99]. The fluid extracts would be inactive after only 6 months. In animals, the extracts of garlic have been shown to prevent damage from ischemia–reperfusion injury, owing to a calcium channel blocker activity and thanks to the anti-radical properties of allylcysteine, allylmercaptocysteine, and alliin [206, 207]. The intake of the dry extract, carefully titrated, seem to have positive effects on the elasticity of the aorta of elderly patients [99, 208, 209]. The calcium channel blocker action may explain the hypotensive effect of garlic [210]. Garlic has many other pharmacological properties: cholesterol-lowering [211, 212], hypoglycemic, prevention of carcinogenesis (stomach, colon, and bladder), prevention of inflammatory and infectious diseases of the respiratory and digestive systems; immunostimulant; antimicrobial action (bacteria and viruses); reduction in the animal secretion of thyroid hormones and increased thyroid-stimulating hormone [99, 188, 195, 213]. Garlic is therefore indicated in the prevention and treatment of atherosclerosis [214], dyslipidemia [215], and hypertension [216]. Numerous preparations are available on the market; only the fresh-crushed bulbs of garlic, and some preparations of garlic powder contain sufficient allicin to be active and effective [217]. Macerated oils or essential oils are inactive [99]. For therapeutic purposes, the use of 4 g per day of fresh bulbs of garlic is recommended, which contains about 40 mg of alliin, which shed 20 mg of allicin. Dried garlic extract obtained from fresh bulbs exists, titrated and standardized in alliin and allicin to 10 %. They are preferred because they allow enough of a supply to exert adequate pharmacological action. High doses of garlic may lead to gastritis, nausea, vomiting, and diarrhea, and its use is contraindicated in cases of peptic ulcer, gastritis, cross-allergies (onion), and hypothyroidism [218]. Allergic reactions are possible in the form of contact dermatitis or asthma from garlic powder inhalation [218]. It is not recommended for use during pregnancy and lactation, and when patients are undergoing surgery because it can increase the risk of postoperative bleeding [99]. In the treatment of atherosclerosis use of the onion can be indicated (Allium cepa), which shares some of the properties of garlic [198].


16.5.8 Hawthorn and Ammi visnaga (Khella)


Extracts from hawthorn berries and flowering tops reduce angina attacks, lower blood pressure and serum cholesterol levels [219223]; enhance cardiac contractility; and improve heart energetic–metabolic processes and blood and oxygen supply, causing coronary vasodilation [99]. Dosages (t.i.d.): berries or flowers (dried): 3–5 g or as a tea; tincture (1:5): 4–6 mL (1–1.5 tsp); fluid extract (1:1): 1:2 mL (0.25–0.5 tsp), solid extract (10 % procyanidins or 1.8 % vitexin-4’-rhamoside): 100–250 mg [18].

Ammi visnaga (khella) is an ancient Mediterranean medicinal plant used historically to treat angina [224]. The mechanism of action of its constituent “khellin,” is similar to calcium channel blocking drugs and is extremely effective in relieving angina symptoms and improving exercise tolerance [225, 226]. It works synergistically with hawthorn. Dosages (t.i.d): dried powdered extract (12 % khellin content): 100 mg [18].


16.5.9 Paeonia lactiflora and Pueraria lobata


Total glucosides of paeony (TPGs), compounds extracted from the roots of Paeonia lactiflora Pall, have been used as an anti-inflammatory drug for the treatment of rheumatoid arthritis (RA) in China and is finding application in the treatment of atherosclerotic vascular disease [227]. In an animal model, it has been found that TPGs significantly ameliorate myocardial ischemia and their action may occur by reducing oxidative stress in ischemic myocardium [228, 229].

Puerarin is one of the most important effective components of Pueraria lobata, which exhibited classic estrogen-like biological activities and had remarkable cardiovascular protective effects in in vivo and in vitro experiments [230]. The beneficial effects of puerarin for CHD treatment purposes may be due to its wide spectrum of pharmacological properties, such as vasodilation and vascular protection [231], cardioprotection [232], anti-atherosclerotic (anti-inflammation, attenuating insulin resistance, and anti-oxidant) [233] neuroprotection, alleviating pain, and inhibiting alcohol intake [234].


16.5.10 Arnica comp.-Heel® Tablets


Recently [235], the effectiveness of treatment with a tablet a day of a low-dose composite drug (Arnica comp.-Heel® tablets) has been demonstrated to reduce the risk of cardiovascular events in patients with clinically stable coronary disease. This drug contains many compounds with anti-inflammatory properties (Achillea millefolium, Aconitum napellus, Arnica montana, Atropa belladonna, Bellis perennis, Calendula officinalis, Chamomilla, Echinacea angustifolia, Echinacea purpurea, Hamamelis virginiana, Hepar sulfuris, Hypericum perforatum, Mercurius solubilis Hahnemanni, and Symphytum) able to prevent plaque instability, improving the outcome of patients with stable coronary artery disease in addition to standard therapy [235].


16.5.11 Tricks of the Trade


Hawthorn, Chinese sage, and ginkgo work well, as described in the scientific literature. Good results can be achieved in the “senile” heart with a combination of hawthorn and ginseng, when there are symptoms such as palpitations and shortness of breath with minimal exertion, sweating at the slightest effort, dizziness, very marked weakness, and weak pulse.

Pueraria is an excellent plant for preventing or treating cardiovascular problems, especially when they are linked to smoking and alcohol consumption. In our experience, it is very effective in helping the body to detoxify from alcohol and nicotine and reducing its dependence on these substances (​www.​ordfarmacistips.​it/​prof.​asp?​id=​94).

There is a need for more scientific research to clarify the effectiveness of the bud extracts traditionally used in the treatment of cardiovascular disorders. In any case, Pol Henry points out the possible use of Cornus sanguinea + Syringa vulgaris + Crataegus oxyacantha to prevent myocardial infarction; Cornus sanguinea + Zea mais the first week after infarction; Alnus glutinosa + Zea mais maize after the first week (​www.​ibs.​it/​code/​9788871723167/​piteragrave/​compendio-gemmoterapia-clinica.​html).


16.5.12 Future Perspective for Research


The Ayurvedic system of medicine uses several other plants of Indian origin for the prevention and treatment of CHD. For example: Acorus calamus (vaca), Aegle marmelos (bilva), Emblica officinalis (amalaki), Glycyrrhiza glabra (yastimadhu), Centella asiatica (mandukaparni), Nardostachys jatamansi (jatamansi), Ocimum sanctum (tulasi), Saussurea lappa (kustha or puskaramula), Terminalia arjuna (arjuna), Withania somnifera (asvagandha), and rudraksa. Their description and methods of use are beyond the scope of this chapter, but it is possible to gain a clear overview in the book by Dr Vaidya Bhagwan Dash [236].

Finally, Chen et al. [237] recently described more than 50 natural products for antithrombosis according to their anticoagulation, antiplatelet aggregation, and fibrinolysis activity.


16.6 Mind–Body Therapies and Psychological Risk


The important contributions of psycho-neuro-endocrine immunology and integrative medicine approaches to the field of cardiology is the description of the intimate mind–body connection in heart health. It is a common experience in the daily clinical practice of every cardiologist to find people who are aware of how a particular mood or difficult experiences of life “have made them sick.” But most conventional medical encounters do not include assessment of the patient’s emotional state, let alone offer therapies directed at mind–body interventions.

As we recently described [9, 11, 12]: “our inner dialogue modulates cardiovascular function. At the same event, people experience different emotional reactions and a same person during his/her life and maturation could react differently in similar, specific situations. Between event and emotion there is no automatic link.”

According to Rozanski et al. [238], specific personalities and their characteristic psychological traits (depression, anxiety, character traits, social isolation, and chronic life stress) contribute significantly to the pathogenesis and expression of coronary artery disease (CAD) because of adverse health behaviors (such as poor diet and smoking) and direct biological mechanisms, such as immune, neuroendocrine, and platelet activation. Thus, the concept of “personality” (namely “the individual differences in characteristic patterns of thinking, feeling and behaving” [239]) represents a key factor in regulating the health of the cardiovascular system.


Emotions do not automatically take away from what happens in people’s lives, but are derived from the type of internal dialogue that is done facing what happens. Different personalities are more or less vulnerable to stress, with relationships existing between different personalities and the function of the hypothalamic–pituitary–adrenal (HPA) axis [240244] and immune [245, 246] and nervous systems [247]. Different patterns of thinking, feeling, and behaving essentially modulate the cross-talk between the nervous, endocrine, and immune systems. It is just as true that the nervous, endocrine, immune, and metabolic systems and their functions could influence mental attitude [248]. In particular, “type D” personality or the “type A coronary-prone behavior,” according to Rozanski and Mittleman, are related to a higher incidence of CVD [238, 249].


Although with many nuances, it can be said that every human being can only try two great emotions in their lifetime: love (serenity, tranquility) or fear, but never both at the same time [250]. This oscillates constantly between the two poles. An inner dialogue oriented to the past or the future that is full of anxiety, distrust, jealousy, envy, ambition, regret, etc., produces fear, in its various emotional colors. An inner dialogue turned to the present, concrete, confident, proactive, compassionate, conscious, etc., produces feelings of “love,” serenity, and tranquility [250].

Thus, the emotional states most commonly linked to heart disease are stress, anxiety, and depression [251, 252]. Psychological stress alone is comparable with strenuous exercise in reducing coronary blood flow [252] or is able to mimic a heart attack (Takotsubo cardiomyopathy) [253]. The drug therapies do not appear to protect against ischemia-induced mental stress; ergometric tests are not able to detect this form of ischemia either [9, 11, 12].

Moreover, stress is a contributor to chronic dyslipidemia and increases total cholesterol by 7 mg/dL and LDL-C by 5 mg/dL within an hour of acute psychological stress [254].

The other side of the coin reveals how the methods of stress prevention and management play a vital role in the care of patients with CHD. Meditation practiced by individuals with coronary disease over 5 years was demonstrated to reduce the combined risk of a cardiovascular event and death by 43% [255, 256]. The practice of meditation reduces the cardiac workload and the levels of circulating molecular mediators of stress, blunting the expected increase in heart rate associated with infusion of isoproterenol [252].

There are many arrows in the quiver of a cardiologist. Many mind–body techniques can be recommended to patients with CHD to manage their stress and anxiety more effectively: conventional psychoactive medication or cognitive behavioral therapy, many forms of meditation, yoga, biofeedback, healing touch, Reiki, massage, and acupuncture.

As suggested by Stephen Devries [16]: “no one resource is generically superior to another. Instead, referral should be made based on an individualized assessment including the patient’s prior knowledge or history with a particular approach, the patient’s philosophical inclination, local expertise, and cost. This ‘matching’ process is truly one of the arts of integrative medicine.”


16.7 Can Lifestyle Changes Reverse CHD? The Lifestyle Heart Trial


As stated by Winston Churchill: “however beautiful the strategy, you should occasionally look at the results.”

Focus on lifestyle and especially on diet and stress management leads to very interesting results. Ornish et al. showed regression of atherosclerosis after only a year of change in lifestyle, without the use of lipid-lowering drugs [257, 258]. After 5 years, the myocardial perfusion is improved more than in the controls who were underwent conventional treatment [259].


16.8 Conventional Therapies


In addition to the change of lifestyle based on nutrition, exercise, and stress management, patients with symptomatic CHD should receive treatments according to European Society of Cardiology (ESC) or American Heart Association/American College of Cardiology (AHA/ACC) guidelines.

Milestones for the drug treatment of CHD are: aspirin, nitrates, beta blockers, and calcium channel blockers, angiotensin-converting enzyme inhibitors, and statins.

Interventional and invasive procedures, such as angioplasty and stenting or coronary bypass heart surgery, could be life-saving.

A detailed discussion of these therapies is beyond the scope of this chapter, but can be found in the ESC/AHA/ACC guideline statements [5].


References



1.

Lloyd-Jones D et al (2010) Executive summary: heart disease and stroke statistics-2010 update: a report from the American Heart Association. Circulation 121:948–954PubMed

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Apr 20, 2017 | Posted by in CARDIOLOGY | Comments Off on Integrated Approach to Coronary Artery Disease
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