2014-11-16

                     Cardiovascular Disease

Cardiovascular disease is defined as medical conditions affecting the cardiovascular system, including heart, blood vessels(arteries and veins).

Cardiovascular Disease: Coronary heart disease

Coronary heart disease is a condition of blockage of  blood flow in the arteries, as a result of hardening arterial wall, cholesterol building up, chemicals, such as cadmium clog up arteries, etc. causes of narrowing coronary arteries. The disease also disrupts the small blood vessels which supply blood and oxygen to the heart. Coronary heart disease (CHD) is the leading cause of death in the United States.

A. Symptoms
Some people may have the diseases without any noticeable symptoms
1. Chest pain
Epidemiological studies, linking chest pain for the possibility of coronary heart disease have raised concerns of many physicians in a finding of  a best tool to rule out the risk of the disease in patients of their care. Fortunately, according to the data collected from a multicenter Swiss clinical cohort study of 672 consecutive patients with chest pain, history and physical examination is considered as a complementary tool for ruling out coronary heart disease(2).

2. Emotional distress and fatigue
Long term impact of emotional distress may induce lesser quality of life and increase risk of morbidity and mortality in patients with coronary heart disease (CHD), according to Dr Denollet J. at the University Hospital of Antwerp(3).

3. Dyspnoea
Shortness of breath and impaired breathing are associated to symptoms of coronary heart disease (CHD), the Exercise Tolerance Test, according to the study in observation of the relationship between chest pain/dyspnoea-heart rate during exertion in patients(4)

4. Weakness
It may be a result of not enough blood flow to nourish the organs in the body.

5. Depression and anxiety
Approximately about 42% and 31% of patients are experience the symptoms of anxiety and depression in chest pain population. The comparison of the test also indicated that males are more like to suffer the symptom of depression but females are more likely to experience symptom of anxiety(5)

6. Other symptoms
According to Dr. Hwang SY, at the Chosun University
a. 7.8% of the younger patients and 13.4% of the older patients were found to have atypical symptoms.
b. Older patients were more likely to complain of indigestion or abdominal discomfort, nausea and/or vomiting, and dyspnea and less likely to have chest pain and pains in the arm and shoulder(6).
7. Etc.

B. Causes and Risk Factors
B.1. Causes
Causes of Coronary heart disease is due to narrowing coronary arteries that lead to the blockage of the blood flow in the arteries as a result of hardening arterial wall, cholesterol and plague building up on the arterial wall. the disease also limits the small blood vessels to supply blood and oxygen to the heart.

B.2. Risk Factors
1. Heredity
Coronary heart disease runs in the family, according to Dr. Swerdlow DI and the research team at the University College London in the evaluation of  the Sources of data, the published literature  of CHD genetics in the last 5 years(7).

2. High level of cholesterol
People with levels of cholesterol in the blood are above healthy levels are at increased risk of coronary heart disease(8). But high density lipoprotein cholesterol (HDL-cholesterol) has showed to associate to a negative risk factor for coronary heart disease(9).

3. Obesity
Waist circumference (WC), is associated with increased coronary heart disease (CHD) risk regardless of the level of BMI. Men with normal BMI and obese WC are found to associate with CHD risk than those with obese BMI and obese WC(10).

4. High blood pressure
patient with systolic blood pressure (SBP) over 140 mm Hg are at increased risk of coronary heart disease (CHD), depending to the levels of low-density lipoprotein cholesterol (LDL-C)(11)

5. Diabetes
People who have Diabetes are not only at increased risk of coronary heart disease, but also are dramatically increased risks of death from fatal CHD, according to  Dr/ Hu FB, at Harvard School of Public Health(12).

6. Processed meats and high saturated and trans fat diet
Consumption of processed meats, but not red meats, is associated with higher incidence of CHD and diabetes mellitus(13). Replacement of saturated fatty acids SFA with polyunsaturated fat modestly lowers coronary heart disease risk by 10%(14) and  consumption of TFA from partially hydrogenated oils showed not only increase cardiovascular risk factors and but also contributed significantly to increased risk of CHD(15).

7. Personality
Types of personality may be influence the risk of coronary heart disease (CHD), but anti-social’ patient is associated to with cardiovascular mortality, according to the study of14,445 participants, aged 39-54 in 1993(16).

8. Periodontal disease
Patients with Periodontal disease are associated at substantial risk of CHD, as it causes cause both local infection and bacteremia, eliciting local and systemic inflammatory(17).

9. Age
Higher than 80% of coronary heart disease-related mortality occurs in patients ≥65 years of age.

10. Gender
Women are more susceptible to Coronary heart disease (CHD)women than men but men had more CHD deaths attributable to diabetes than women(18).

12. Race
Dr. Escobedo LG and scientists at the National Center for Chronic Disease Prevention and Health Promotion,  African Americans had about twice the risk for sudden, nonsudden, or other coronary death as did Caucasians(19).

13. Substance abuse
Although there are some controversy regarding the effect of opium addiction on the coronary artery disease (CAD), but according to researchers at the Kerman University of Medical Sciences, opium is an independent risk factor for CAD(20).

14. Lack of regular exercise
Few older adults in the United States achieve the minimum recommended amount of physical activity(21).

15. Smoking
CHD Smokers with serum cholesterol and systolic BP levels in the highest quintiles is associated to  approximately 20 times greater than nonsmoking men with systolic BP and cholesterol levels in the lowest quintile(22).

16. Psychological stress and chronic anxious behavior
Psychological stress and chronic anxious behavior may be responsible for new development or promotion of coronary heart disease as they have a tremendous impact on heart and biological rhythm of the body(23).

17.  Hyperuricemia (HUA)
HUA is a condition of abnormally elevated blood level of uric acid. It has been found to be a predictor of coronary heart disease and renal dysfunction in patients with type 2 diabetes mellitu(24).

18. Other factors
Patient with ankle-brachial index ABI+ are associated to increased risk of major major cardiovascular diseases(25).

Finally, we would like to summarize the risks with a study of Dr. Walden R and Dr. Tomlinson B. at the Biomolecular and Clinical Aspects, atheromatous vascular degenerative disease, high levels of low-density lipoprotein (LDL) cholesterol, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, insufficient consumption of fruits and vegetables, excess consumption of alcohol, and lack of regular physical activity are associated to risk of coronary artery disease (CAD), cerebrovascular disease, and peripheral vascular disease, and the subsequent development of heart failure and cardiac arrhythmias(25a).

C. Diagnosis and tests
1. Coronary angiography

Coronary angiography is an imaging test which uses a special dye (contrast material) and x-rays to see inside the arteries and blood flows through your heart with the a mild sedative to help you relax.

2. Computed Tomography angiography

A noninvasive way 3D technique with  a contrast material to produce pictures of major blood vessels throughout the body with the use of x-rays with catheters, or computed tomography (CT) or magnetic resonance imaging (MRI).

3. Echocardiogram

Echocardiogram  also known as cardiac ECHO is anultrasound technique used for visualizing the structures of the heart.

4. Electrocardiogram (ECG)

The electrocardiogram (ECG or EKG) is a diagnostic tool routinely used to assess the electrical and muscular functions of the heart(26).

6. Exercise stress test

An exercise stress test such as walk or run on a treadmill or pedal a stationary bike is a screening tool used to test how your heart function under exercise stress.

7. Heart CT scan

Heart CT scan  is a computed tomography (CT) scan of the heart with the use of uses x-rays to create detailed pictures of the heart and blood vessels.

8. Magnetic resonance angiography

Magnetic resonance angiography is an MRI to produce image blood vessels for examination.

9. Nuclear stress test

A nuclear stress is a nuclear imaging method to measure blood flow to your heart muscle both at rest and during stress on the heart.

10. Etc.

Some researchers suggested that pattern-recognition techniques applied to proton nuclear magnetic resonance (1H-NMR) spectra of human serum can correctly diagnose not only the presence, but also the severity, of coronary heart disease.

D.1. The Do`s and Do not`s list

1.  Healthy diet

Healthy lifestyle, is one of most effective and inexpensive to prevent  coronary artery disease (CAD with no harmful effects. Five items are associated with lower cardiac risk: non-smoking, BMI ≤25, regular exercise (30 min/day), healthy diet (fruits, vegetables, low-saturated fat, and 5-30 g alcohol/day)(31).

a. Low intake of saturated and trans fats

Saturated and trans fats increase low-density lipoprotein (LDL), or “bad,” cholesterol level, as it can cause clot up and hardening arterial wall, thus increasing the risk of cardiovascular risk and mortality(27).

b. Increase intake fish and olive oil

Strong evidence suggested that fish oil is associated with coronary heart disease risk reduction. frequent intake of fish oil can prevent arrhythmias, lower heart rate and blood pressure, decrease platelet aggregation, and lower triglyceride levels(28). Consumption of olive oil and vegetable oil was inversely associated with serum cholesterol and glucose levels and systolic blood pressure(29).

c. High amount intake of fiber

Consumption of dietary fiber from cereals and fruits is inversely associated with risk of coronary heart disease, according to the study of over 6 to 10 years of follow-up, 5249 incident total coronary cases and 2011 coronary deaths occurred among 91058 men and 245186 women(30). A fiber-rich diet not only lowers your LDL cholesterol level, but also provides nutrients in protection against CHD(30).

d. Low intake of salt and sugar
d.1. Reduce intake of fructose
Increased dietary fructose intake in rodents study showed to recapitulate many aspects of metabolic syndrome by causing hypertension, insulin resistance and hyperlipidaemia(32).

d.2. Prevent weight gain and control diabetes and prediabetes
Healthy Eating and Exercise Lifestyle Program-HEELP on weight, body mass index (BMI), waist circumference and exercise, showed a positive effect in  induced weight loss and improved exercise behaviour in obese people with CHD and T2DM(33).

d.3. Mediterranean style low-carb diet

The best approach to the dietary prevention of CVD is a Mediterranean style low-carb diet represented in the LOGI pyramid(34).

2. Moderate exercise

Intensive exercise is not healthy for any age as it lowers the immune function prone for disease invasion, especially to elder. Moderate exercise enhances the blood flow and immune function, thus protecting again diseases and reducing the risk of progression of chronic diseases(35).

3. Maintaining a healthy weight

Over weight or obesity can cause increased risk of coronary heart diseases, but men with obese WC
are  associated with increased CHD risk regardless of the level of BMI, according to Dr. Park YS and Dr. Kim JS. at the Sungkyunkwan University School of Medicine(36).

4. Quitting smoking

Prevalence of smoking is increasing in women in some populations and a risk factor for coronary heart disease(37).

5. Moderate consumption of Green tea, coffee and alcohol

Regular consumption of moderate quantities of coffee and (green) tea seems to be associated with a small protection against CAD(38).

6. Managing stress

Music listening may have a beneficial effect on blood pressure, heart rate, respiratory rate, anxiety, and pain in persons with CHD(39). In the total chest pain population  prevalence of anxiety and depressive symptoms was estimated to be 42% and 31%(40), according to the stress conducted by Yasouj University of Medical Sciences.

7. Say No to drug
Drug abuse (heroine and cannabis) may be associated to increased risk of acute coronary syndrome(41).

8. Relaxation

Reduction of SBP, DBP, heart rate, body fat%, total cholesterol, triglycerides and LDL after regular yogic practices is beneficial for cardiac and hypertensive patients(42).

9. Etc.

D.2. Diet to prevent Coronary heart disease
The aim of diet is to reduce the risk of underlining causes of coronary heart diseases, such as lowering cholesterol, lower blood pressure, reduced risk of diabetes, lipid perioxidation, etc.

1. Dulse
Dulse is a red seaweed of genus Palmaria, belong to Family Palmariaceae grown attached to rocks by a “holdfast” in the North Atlantic and Northwest Pacific. It is commonly used in Ireland and Atlantic Canada both as food and medicine. Dulse can be found in many health food stores or fish markets or can be ordered directly from local distributors.
a. Health benefits
Seaweeds a, the traditionally consumed vegetable in Asia were found to consist many important functional activities, such as antioxidant, antimutagenic and anticoagulant effect, antitumor activity, and an important role in the modification of lipid metabolism in human body(43).

b. Antioxidant
The 1-butanol soluble extract from Grade 1 dulse (reduced UV-exposure)and Grade 2 dulse (greater UV exposure) found in dulse inhibited (p0.03) AAPH-induced lipid peroxidation(44).

d. Chlorophyll
Chlorophyll, a green pigment found in almost all plants, algae, and cyanobacteria, beside it is best known for its cleansing body and healing to vital organs properties. It it also reduces the binding of carcinogens to DNA in the liver and other organs.(46).

2. Green tea
Green tea contains more amount of antioxidants than any drinks or food with the same volume, and is the leaves of Camellia sinensis, undergone minimal oxidation during processing, originated from China. Green tea has been a precious drink in traditional Chinese culture used exceptional in socialization for more than 4000 thousand years. Because of their health benefits, they have been cultivated for commercial purposes all over the world.
Theaflavin-enriched green tea extract showed to be effective adjunct to a low-saturated-fat diet to reduce LDL-C in hypercholesterolemic adults(47).

3. Flax seed
Flax seed is native to the region of the eastern Mediterranean to India and also known as common flax or linseed. Flax is an erect annual plant, grown to 1.2 m tall. The leaves are 20–40 mm long and 3 mm broad.

b. Hyperlipidemia
Diet supplemented with flax and sesame seeds mixture in pregnant diabetic rats ameliorated lipid parameters, antioxidant enzyme activities, reduced level of glutathione and significantly decreased malonaldialdehyde levels.(52)

c. Cardiovascular diseasesFlaxseed can modestly reduce serum total and low-density lipoprotein cholesterol concentrations, reduce postprandial glucose absorption, decrease inflammation, and raise serum levels of the omega-3 fatty acids(53).

d. Hypercholesterolemic atherosclerosis
Type II flaxseed reduced risk of the development of atherosclerosis by 69%(54).

f. Omega 3 fatty acids
Besides well known for its benefits for the maintenance of a healthy cardio-vascular system, it also found to prevent blood clotting(55).

4. Blueberry
a. Antioxidant Capacity
Fruit wines made from blueberries and blackberries may have potential health, especially for its  phenolic compounds(56).

b.  Metabolic Syndrome
Blueberries showed to lower systolic and diastolic blood pressure and lipid oxidation and improve insulin resistance(57).

c. Cardiovascular diseases
Since blue berry contains high amount of antioxidant, it reduces ROS production and the effects of oxidative stress and improves cardiac function(58).

5. Wolfberry
Wolfberry is the common name for the fruit of two very closely related species, the genus of Lycium, belong to family Solanaceae, native to native to southeastern Europe and Asia.

a. Cholesterol
Herbal extract Cortex Lycii significantly prolonged low-density lipoprotein oxidation in vitro(59).

b. Hypochlolesterolemic and antioxidative effects
Tyramine derivatives from Lycii Cortex Radicis (LCR), the root bark of lycium (Lycium chenese Miller) showed to reduce significant level of liver cholesterol(60).

d. Free radicals
In test mice, aqueous extract of Lycium barbarum (LBAE) and ethanol extract of Lycium barbarum (LBEE) reduce liver damage and oxidative changes(62).

6. Coriander
Coriander is an annual herb, genus Coriandrum in the family Apiaceae, native to southern Europe and North Africa to southwestern Asia. All parts of the plant are edible, but the fresh leaves and the dried seeds are the parts most commonly used in cooking.
a. Antioxidant
Like most plants with spice taste, coriander contains high levels of antioxidant which protect our body’s cells from oxidation damage, thus reducing the DNA alternation due to free radicals(66).

f. Hypolipidemic effect
Coriander seeds were found to have a significant hypolipidemic effect by lowering of levels of total cholesterol and triglycerides, and increasing levels of high-density lipoprotein(67).

7. Eat plenty of Fruits, evgatables and reduce intake of red meats
8. Etc.

D.3. Antioxidants to prevent Coronary heart disease
Vitamin C, Vitamin E, and ß-Carotene supplements have showed to reduce risk of coronary heart disease, through its nutrient affect on plasma lipid and lipoprotein levels, blood pressure, and body weight and antioxidant activities in inhibition of multiple proatherogenic and prothrombotic oxidative events(68).

1. Bioflavonoids or vitamin P
Discovered by Szent-Gyorgyi and his colleagues back in the 1930`s. In Laboratory tests, B
bioflavonoids reduce the fragility and “permeability” in capillaries and prevent the clotting up of arterial as a result of oxidation.

2. Vitamins C and E, beta-carotene
Recent research findings have suggested that antioxidants such as vitamin C, E and beta carotene play an important role in the prevention of atherosclerosis. Data from animal studies showed they are able to prevent oxidative modification of low density lipoproteins (LDL).

3. Alpha-tocopherol
Alpha-tocopherol, a antioxidant found abundant in vitamin E, decrease lipid peroxidation and platelet aggregation, adhesion and inflammatory. Epidemiological studies suggest that low levels of antioxidants are associated with increased risk for cardiovascular disease.

4. Vitamin C and E
Studies showed in take of 500mg of vitamin C and 400 IU of vitamin E induce retardation of  the progression of coronary atherosclersis.

5. Chlorophyl
Antioxidant chorophyll in the green algae inhibits the chemical cadmium of smoking, by preventing from oxidation cause of building up of plaque along the walls of arteries.

6. 2-dithiole-3-thione (D3T)
D3T induced a number of cellular antioxidants and metabolism of lipophilic, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NADH:quinone oxidoreduc- tase-1 (NQO1) in protection against H9c2 cell injury caused by various oxidants and simulated ischemia-reperfusion.

7. Selenium
Deficiency of of a co-enzyme selenium, is required in maintaining the glutathione redox cycle and in promotion of more susceptible to oxidative injure.
8. Etc.
D.4. Phytochemicals to prevent Ischaemic heart disease
1. Omega-3 Fatty Acids
a. Systolic blood pressure, triglycerides and LDL cholesterol
Diet supplemented with EPA plus DHA showed to lower systolic blood pressure and triglycerides but raise LDL cholesterol in compareison to n-3 and n-6 fatty acids from plants(49).

b. Cardiovascular effects
EPA/DHA-rich diet showed to increase levels of  LDL-cholesterol, apolipoprotein B (apoB)(the primary apolipoproteins of chylomicrons and low-density lipoproteins) concentrations(50).

c.  Health effects
Perilla frutescens seeds, a good source of polyunsaturated fatty acids (PUFAs), are most beneficial to human health and in prevention of different diseases like cardiovascular disorders, cancer, inflammatory, rheumatoid arthritis etc.(51).

d. Obesity
Intake of Omega-3 Fatty Acids of obese individuals may be effective in reduced inflammatory and endothelial activation marker.(52).

2. Catechin
Catechin is phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in white tea, green tea, black tea, grapes, wine, apple juice, cocoa, lentils, etc.
a.  Body-weight regulation
Green tea has been proposed as a tool for obesity management as strategies for weight loss and weight maintenance, and in the regulation of lipolysis, and the sympathetic innervation(The nerve supply) of white adipose(white fat) tissue(53).

b. Cholesterol
Consumption of GTCs is associated with a statistically significant reduction in total and LDL cholesterol levels but not triglyceride levels54).

c. Antioxidant activity
Polyphenolic compounds (included catechins) in the berries of edible honeysuckle is considered  as good sources of phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, against a number of chronic illness, including cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases(55).

d. Glucose levels
Intake of green tea catechin, epigallocatechin gallate (EGCG), in a green tea extract, showed significant differences in changes in glucose and insulin as well as LDL cholesterol concentrations(56).

3. Theaflavin with reddish in color, is a phytochemical of Flavan-3-ols, in the group of Flavonoids (polyphenols), formed in tea leaves during fermentation.
a. Cholesterol
Theaflavin, showed to reduce  total cholesterol, LDL-C, HDL-C, and triglyceride levels in the 240 men and women 18 years or older on a low-fat diet with mild to moderate hypercholesterolemia study.(57).

b. Antioxidanta and cardio-protective effects
Theaflavin (TF(1), a derivative of theaflavin, exhibited its antioxidants effects for scavenging ROS and preventing the hydroxyl radical-induced DNA damage in vitro.(58). In rat study, the derivatives also exerted it cardio-protective activity(59).

4. Resveratrol is a type of natural phenol in the group of Stilbenoids, produced naturally by many plants when under attack by bacteria or fungi. It has been studied by many researchers for it health benefits in treating chronic diaereses, including cancer, diabetes, heart disease, etc.
a. Cardio-protective effects
Resveratrol reduce ventricular remodeling and increased cardiac function through its angiogenic, antihypercholesterolemic, antihypercholesterolemic, antihypercholesterolemic, and antidiabetic effects(60a)

b. Lipid metabolism
Resveratrol enhanced the lipid metabolism in C57BL/6J mice induced by high-fat diet(60b)

c. Diabetes and Obesity
Resveratrol affects insulin secretion and blood insulin concentration and hyperglycemia in animals and rat studies(60c).

5. Garlic has been used in traditional Chinese and herbal medicine over thousands of year as antibacterial, antiviral, and antifungal agent and for treatment of other conditions such as parasites, respiratory problems, poor digestion, low energy, etc.

a. Antioxidant against oxidation
According to the study of " Antioxidant Health Effects of " by Carmia Borek, posted in (Journal of Nutrition. 2001;131:1010S-1015S.)© 2001 According to the American Society for Nutritional Sciences, aged Garlic Extract(AGE) contains a wide range of antioxidants that can act in synergistic or additive fashion and protect cells against oxidative damage, thus helping to lower the risk of heart disease, stroke, cancer(60d).

b. Cholesterol, heart disease and stroke
Epidemiological evidences showed that garlic slightly lowered blood cholesterol, LDL cholesterol and triglycerides. the study at East Carolina University found that aged garlic extract given at 2.4-4.8 gm a day, for six months, lowered cholesterol by 5-7%, and reduced LDL, triglycerides and blood pressure in men with high cholesterol(60e).

c. Blood circulation
Allyl sulfides, a major chemical of garlic and its bioflavonoids consist many powerful health benefits. In cardiovascular health, clinical experiments, regular consumption of garlic improves circulation, decrease calcium deposits and the size of arterial plaque in coronary arteries(60f)

d. High blood pressure
Eleven of 25 studies included in the systematic review suggests that garlic preparations are superior to placebo in reducing blood pressure in individuals with hypertension(60g).

f. Arteriosclerosis
Animal fed with garlic showed a significant in increased HDL levels. and reduction of the risk of atherosclerosis by 72%(60h)

E. Treatments

E.1. In conventional medicine perspective
The aims of the treatment of Coronary heart disease (CHD) is to provide enough blood supply to the heart for oxygen demand, and prevent worsening of the disease. But if you have blood pressure, diabetes, or high cholesterol levels, you may be asked to take certain medicines to prevent coronary artery disease or prevent coronary artery disease from getting worse.
1. Medication and over counter medicine to treat symptoms of the disease
1.1. Aspirin
a. Many researchers believe that daily intake aspirin can reduce the risk of blood clots from forming in your arteries. Dr. Sanmuganathan PS and the research team at the Royal Hallamshire Hospital, indicated that Aspirin treatment for primary prevention is safe and worthwhile at coronary event risk(88).
b. Side effects are not limit to
b.1. Stomach pains
b.2. Feelings of nausea
b.3. Vomiting.
b.4. Allergic reaction to some people
b.5. Aspirin may interact with other medicine, such as blood thinning medicine
b.6. Etc.

1.2. Beta-blockers
a. Beta blocker has been used to lower heart rate, blood pressure, and enhance oxygen to the heart. but withdrawal syndrome immediately following the cessation of beta-blocker use has shown to induce acute precipitant of angina and myocardial infarction in hypertensive patients who have no prior history of coronary heart disease(89).

b. Side effects are not limit to
b.1. the medicine can cause allergic reaction to certain people, such as: rash, itching, swelling, dizziness, trouble breathing.
b.2. Easy bruising or bleeding,
b.3. Swollen hands or feet,
b.4. Confusion,
b.5. Depression
b.6. Etc.

1.3. Nitroglycerin
a. Nitroglycerin is used to treat ischemic cardiac pain. and improve blood flow to the heart. Transdermal nitrate has shown to improve the quality of life in ambulant patients and suppressed of silent ischemic attacks and reduced anginal attacks in some studies(90).

b. Side effects are not limit to
b.1. Dizziness
b.2. Lightheadedness, or fainting when sitting up or standing
b.3. Flushing of face and neck
b.4. Headache
b.5. Irritation
b.6. Nausea
b.7. Vomiting
b.8. Etc.

1.4. Calcium channel blockers
a. The medicine used to relax arteries, lower blood pressure, and reduce strain on the heart.  Clopidogrel(class antiplatelet agent) without calcium-channel blockers (CCBs), does not increase the mortality or composite thromboembolic events in elderly CAD patients, but clopidogrel combined with nondihydropyridine CCB is associated with significantly increased composite thromboembolic events in comparison with dihydropyridine CCB(91).

b. Side effects are not limit to
b.1. Stomach pain
b.2. Constipation
b.3. Drowsiness
b.4. Fatigue Feelings of a rapidly or forcefully beating heart (palpitations)
b.5. Flushing or hot flashes
b.6. Headaches
b.7. Nausea
b.8. Etc.

1.5. Statins
a. The medicine used to lower cholesterol. Dr. Biasucci LM, said that statins enhance pleiotropic effect behind their lipid lowering function, educe inflammation, which plays an important role in the atherosclerotic process”(92).

b. Side effects are limit to
b.1. Headache
b.2. Nausea
b.3. Vomiting
b.4. Constipation
b.5. Diarrhea
b.6. Weakness
b.7. Muscle pain
b.8. Etc.
1.6. Etc.

2. Minimally invasive surgical methods
2.1. Coronary angioplasty (PTCA)
Coronary angioplasty (PTCA) is a procedure used to open narrow or blocked coronary (heart) arteries to restore blood flow to the heart muscle.
2.2. Stent
A stent is a small mesh tube that’s used to treat narrow or weak arteries by improving blood flow and prevent the arteries from bursting.
2.3. Atherectomy
Atherectomy is a minimally invasive surgical method of  involving the removal of he plaque burden within the vessel.
2.4. Brachytherapy
Brachytherapy is a minimally invasive surgical method use of a type of energy, called ionizing radiation, to clear the blockage of the arteries.
2.5. Etc.

3. Surgery
Surgery may be necessary for certain patient depending to the severity of the disease or ineffective to the treatment of medication or failure of minimally invasive surgical methods.
3.1. Coronary artery bypass grafting (CABG)
Coronary artery bypass grafting (CABG) is a surgical procedure performed to reduce the risk of death from coronary artery disease by bypass atherosclerotic narrowings as arteries or veins from elsewhere in the patient’s body to improve the blood supply to the heart muscle(93).

3.2. Off-pump bypass surgery
CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine, but patients in the off-pump group had shown tio worse composite outcomes and poorer graft patency than did patients in the on-pump group in a 1 year of follow-up study(94).

3.3. Minimally invasive direct coronary artery bypass (CAB)
Minimally invasive direct coronary artery bypass (CAB) is a surgical procedure performed if only the front or right coronary arteries need bypass by replacing the blocked artery with an artery from the chest   without opening your chest to detour the blockage. The surgery showed significant advantages of decreased morbidity, shorter hospital stays, and recovery time(95).

3.4. Transmyocardial laser revascularization (TMR)
Indirect revascularization is a therapeutic approach in case of severe angina not suitable for percutaneous or surgical revascularization, through a create transmyocardial channels by a laser energy bundle delivered on left ventricular epicardial surface. Benefits of the procedure are related mainly to the angiogenesis caused by inflammation and secondly to the destruction of the nervous fibers of the heart(96).

3.5. Etc.

E.2. Treatments In Herbal medicine perspective
The aim of herbal medicines is to treat the underlining causes of Coronary heart disease. If the disease is caused by structure problem then convention medical surgery could be necessary
1. Ginger
a. Anti Diabetes and hypoglycaemic effect

Raw ginger (Zingiber officinale)extract at a dose of 500 mg/kg are significantly effective in lowering serum glucose, cholesterol and triacylglycerol levels in the ginger-treated diabetic rats(97)

b.  Lower cholesterol levels
Ginger stimulates and revitalize the heart muscle and strengthen the peripheral’s circulation and  lowers elevated blood pressure and prevents blood clots in the arterial walls when taken with vitamin E(98).

2. Garlic(see the diet section for health benefits) CAUTION: Medication and Garlic could lead to uncontrolled bleeding and spell HEMORRHAGIC STROKES if it occurs in your brain. To avoid this, take caution against taking standardized garlic extract. Experts suggest eating no more than one clove of garlic a day(99).

3. Ashwagandha

Hypercholesterolemic rats fed with composite of Ashwagandha,  showed effectively in reduced plasma and hepatic lipid profiles and increased fecal excretion of cholesterol, neutral sterol, and bile acid along with increasing the hepatic HMG-CoA reductase activity and bile acid content(100).

4. Artichoke

a.  Hypercholesterolaemia
Epidemiological study insisted that people who have high levels of blood cholesterol are at   increased risk for coronary heart disease and other sequelae of atherosclerosisstroke. Artichoke leaf extract (ALE) has showed to lower the blood cholesterol in some researches(101).

b. Antioxidant capacity
High levels of antioxidant Flavonoids Artichoke enhance the immune system fighting against the forming of free radicals and guarding our body against foreign invasion such as bacteria and virus, thus reducing the risk of free radicals and bacteria and virus causes of infection and inflammation(102).
c. Blood vessel integrity protection
Artichoke has shown a property of protection of the the layer of epithelial cells that lines the interior surface of blood vessels(103).
.

5. Parsley

a. Platelet aggregation and prolongs bleeding
Parsley (Petroselinum crispum, Apiaceae), one of frequent used herb Morocco for treatment of cardiovascular diseases, showed to  inhibite significantly platelet aggregation ex vivo and prolonged bleeding time without changes in the platelet amount in oral administration animal study(104)

b. Spasmolytic effect
Parsley extract decreased the CaCl2-induced contraction and on the contraction of ileum by blocking of voltage-gated calcium channels(105).

6. Alfalfa

a.  Antioxidant
Alfalfa (Medicago sativa L.) has shown to exhibited its antioxidant effects on carbon tetrachloride intoxicated rats, through hepatoprotective and antioxidative stress properties(106)

b. Cholesterol
Alfalfa has been used in traditional medicine for treatment of high blood cholesterol. Ingestion of AS in rats decreased the concentration of plasma cholesterol, reduced intestinal absorption of exogenous and endogenous cholesterol, and increased fecal biliary excretion.(107).

c. Hyperlipoproteinemia
Diet consisting alfalfa seed normalize serum cholesterol concentrations and reduce up to 26% in total cholesterol and 30% in LDL cholesterol in patients with type II hyperlipoproteinemia(HLP)(108).

7. Hawthorn
a. Hypotensive effects
Hawthorn (Crataegus laevigata) leaves, flowers and berries have been used by herbal practitioners in the UK for treatment of hypertension. The conmparison of prescribed drugs and hawthorn extract in a randomised controlled trial demonstrated a hypotensive effect of the herb in patients with diabetes(109).

b. Cardiac effects
Two alcohol extracts of hawhorn may process a potential cardiac effects via the Na(+),K(+)-ATPase and intracellular calcium concentrations(110).

c. Cardiovascular disease
The presence of antioxidant flavonoid and other chemical components of hawthorn showed to procress the prevention and protection of cardiovascular disease(111).

d. Chronic heart failure
Ten trials including 855 patients with chronic heart failure, according to New York Heart Association classes I to II, indicated that hawthorn extract may be used as an oral treatment option for chronic heart failure, shortness of breath, decreased pressure-heart rate and fatigue, etc.(112).

e. Hyperlipemia
Yishoujiangzhi (de-blood-lipid) tablets (composed of Radix Polygori Multiflori, Rhizoma Polygonati, Fructus Lycii, Crataegus Pinnatifida and Cassia Tora) showed a 87.0% in lowering serum cholesterol and 80.8% in lowering triglyceride(113).

8. Gingko biloba
a. Hypertension
Ginkgo may be used as protential herb for treatment of hypertension through its effect in enhanced impaired endothelium-dependent vasodilation function  and elevation of the

Calcium signalling endothelial intracellular level in Spontaneously hypertensive rats (SHR) through the nitric oxide pathway(114).

b. Cardiovascular tissues
Ginkgo biloba extract (EGb) has shown the protection of the cardiovascular tissues against  Mercury(II) chloride induced oxidative damage(115).

c. Hyperlipidemia
Ginkgo biloba leaves (EGB) enhance the regulation of polyunsaturated fatty acid (EFA)in limitation of the absorption of cholesterol, inactivation of 3-hydroxy-3-methylglutaryl-coenzyme A (an important cellular metabolic pathway  pathways)(116).
9. Etc.

E.3. In Tranditional Chinese medicine perspective
According to the A  Practical English-Chinese Library of Traditional Chinese Medicine by Dr. Enqin Zhang(Engin CAN)(117), obstructs the yang qi, and /or by blood stasis, caused by either qi deficiency or due to qi stagnation of that lead to phlegm accumulation in the chest may be the leading cause of coronary heart disease due to obstruction in the heart vessels induced precordial pain.
Dr. Enqin Zhang differentiated coronary heart disease as follow(118)
1.. Obstruction of yang qi in the chest due to accumulation of phlegm
a. Primary manifestations
A feeling of oppression over the chest or chest pain radiating to the back, accompanied by shortness of breath, white, thick, greasy coating of the tongue and smooth pulse. (This condition is of the cold phlegm type; when the tongue coating turns yellow and greasy, it becomes a phlegm-heat type).
b. Principle of treatment: Relieve the obstruction of the yang qi in the chest.

c. Formula treatment
Formula for choice: Trichosanthes, Chinese Chive, and White Liquor Decoction; in this prescription, trichosanthes fruit eliminates phlegm and reverse the adverse ascending of the qi; Chinese chive warms and activates the yang qi in the chest and relieves pain; and white liquor acts as a guide drug.

2. Blood stasis caused by qi deficiency
a. Primary manifestations: Fatigue, shortness of breath, palpitations accompanied by localized pain, dark purplish tongue with thin coating and uneven pulse. (In cases with cold extremities, intolerance of cold, pale and tender tongue and slow pulse, the blood stasis is due to yang deficiency; in cases with profuse sweating, deadly cold limbs, listlessness and fading pulse or even coma, the yang is exhausted and shock ensues. Some patients experience yin and qi deficiencies together, manifested by a hot sensation in the palms and soles, dry mouth, desire for cold drinks, reddened tongue with little or no coating and thin, rapid pulse.)
b. Principle of treatment: Invigorate the qi and promote blood circulation.
c. Formula treatment
Principle of treatment: Invigorate the qi and promote blood circulation.
Formula of choice: Yang-Invigorating and Recuperation Decoction; in this recipe, astragalus root (huang qi) invigorates the qi to promote blood circulation and strengthens the effect of the other ingredients in removing blood stasis. Other ingredients are tangkuei (dang gui), red peony root (chi shao), earth worm (di long), ligusticum root (chuan xiong), peach kernel (tao ren), carthamus flower (hong hua).
In cases with yang deficiency, add cuscuta seed (tu si zi), prepared lateral root of aconite (fu zi), and psoralea seed (bu gu zhi) to warm and replenish the yang qi.
If there is collapse, use Ginseng and Aconite Decoction combining with Aconite Decoction (including prepared lateral root of aconite, poria,  ginseng, ovate atractylodes rhizome, white peony root); in these prescriptions, prepared lateral root of aconite and ginseng recuperate the depleted yang and replenish the qi. In cases of qi and yin deficiencies, add scrophularia root (xuan shen), ophiopogon root (mai dong), schisandra berry (wu wei zi), and fresh rehmannia root (sheng di ) to the above prescriptions.

3. Blood stasis caused by qi stagnation
a. Primary manifestations: A fullness sensation or pain in the chest, dark purplish tongue with thin coating, but no symptoms of qi deficiency, such as shortness of breath and fatigue.
b. Principle of treatment: Activate qi and remove blood stasis.

c. Formula of choice: Blood House Stasis-Expelling Decoction; in this recipe, bitter orange (zhi ke) and bupleurum root (chai hu) activate the stagnated qi; platycodon root (jie geng) acts as a guide drug; and the other ingredients promote blood circulation and remove blood stasis, including tangkuei (dang gui), fresh rehmannia root (sheng di huang), peach kernel (tao ren), carthamus flower (hong hua), red peony root (chi shao), licorice root (gan cao), ligusticum root (chuan xiong), achyranthes root (niu xi).

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