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Sunday, 16 November 2014

(Preview of Chapter one) Most common diseases of 50 plus - Cardiovascular Disease: The Efficacy of Preventions, Managements and Treatments


                     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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(117) http://www.tcmtreatment.com/images/diseases/introduction.htm 
(118) http://www.tcmtreatment.com/images/diseases/heartdisease.htm



 Cardiovascular Disease: Ischemic heart disease 


Ischemic heart disease is a condition of  reduced blood supply of the heart muscle, as a result of  coronary artery disease caused by plague building up in the arteries.
A. Symptoms
Reduction of blood flow to the heart muscle may be resulting in a number of symptoms, which can vary in intensity among individuals.

1. Angina pectoris
Angina pectoris is condition of chest pain as a result of lack of blood supply to the heart muscle, due to obstruction or spasm of the coronary arteries of the heart's blood vessels.

2. Acute coronary syndrome
Acute coronary syndrome is defined as any group of symptoms caused by obstruction of the coronary arteries, mostly due to  ST elevation myocardial infarction (30%), non ST elevation myocardial infarction (25%), or unstable angina (38%)


a. ST elevation myocardial infarction
St elevation myocardial infarction is a heart attack as a result of blockage of blood flow to the heart long enough time to cause damage or die of the heart muscle.

b. Unstable angina 
Unstable angina, a type of acute coronary syndrome is a medical condition as a result of the heart not enough blood flow and oxygen cause of heart attack.

c. Myocardial infarction
 Myocardial infarction, a severe chest pain can not be relieved by rest as a result of acute heart damage. Ischemic heart disease is the leading cause of all morbidity and mortality in the United States(1).

3. Heart failure 
Heart failure is a condition in which the heart can't pump and/or fill enough blood to meet the body's needs due to weakness of the heart muscle, causing difficulty in breathing or swelling of the extremities.

4. Fatigue and depression
Patients with  type-D personality are predictable to both symptoms of fatigue  and depression , but not others(2)

5. Other symptoms include 
a. Clammy skin
b. Nausea with or without vomiting
c. Pain in the neck or jaw
d. difficulty in breathing or rapid breathing
e. swelling of the extremities
f. Pain on Shoulder or arm
g. Etc.
6. Etc.

Causes and Risk Factors
B.1. Causes

Cause of  Ischemic heart disease is a result of reduced blood supply of the heart muscle, due to coronary artery disease caused by plague building up in the arteries.

B.2. Risk Factors 
1. Diabetes 
Obese Diabetics are at robust risk of ischemic heart disease, according to the study of patients who attend a tertiary hospital outpatient clinic and sugested that weight loss in type 2 diabetes should use cardiac endpoints as their primary outcomes(3).

2. High lever of blood cholesterol
In a 7.5 years follow up study,among 2,034 men, who at the first examination were without signs of ischemic heart disease (IHD), 75 cases of IHD were found as a result of increased high levels of blood cholesterol(4)

3. Hypertension
Epidemiological evidence suggested a strong correlation of hypertension and increased risk of  ischemic heart disease(5).

4. High blood triglycerides 
High blood triglycerides is associated to increased risk of  Ischemic heart disease. According to the study by National Taiwan Universit, low HDL-C was significantly associated with acute coronary events, and triglyceride levels are related to all-cause deaths after the coronary event(6).

5. Obesity 
In the document of Concomitant ischemic heart disease (IHD), in 350 normotensives (4%) and in 119 hypertensives (13.8%)showed  a strong association between obesity and hypertension(7).

6. Lack of physical activity
 Study among employed men with pre-existing cardiovascular disease (CVD), showed that among gainfully employed men with pre-existing CVD, a high physical fitness was associated with a substantially reduced risk for IHD and all-cause mortality(8).

7. Smoking and other tobacco use
  Strong evidences suggested the association between smoking and peripheral arterial disease than ischemic heart disease(9)

8. Family history of heart disease
 Inherited factors have shown to effect the development of premature ischemic heart disease, but risk of IHD declines with age(10).

9. Excessive drinking
  Heavy drinking is associated with an increase in the prevalence of type 2 diabetes mellitus (DM), coronary heart disease (CHD), stroke, peripheral arterial disease (PAD), and overall cardiovascular disease (CVD)(11)

10. Unhealthy diet
Diet high in saturated fat and trans fat can lead to cholesterol building up in the arterial wall,  decreasing blood flow and oxygen to the heart muscle.

11. Stress, coping, and social support as psychosocial factors
The high prevalence of psychiatric problems and psychosocial stresses have found among patients with IHD, causing deterioration of the prognosis(12).

12. Sickle-cell disease
Sickle cell disease (SCD) is an inherited chronic haemolytic anaemia whose clinical manifestations arise from the tendency of the haemoglobin to polymerize and deform red blood cells into the characteristic sickle shape due to a single nucleotide change in the β-globin. Sickle cell anaemia (SCA) is associated with recurrent multi-organ ischemia and infarction(13).

13. Shift work and metabolic syndrome
Other researchers suggested that Shift work and metabolic syndrome also associated to increased risk of  Ischemic heart disease(14).

 I would like to summarize this section by quoting the study by Dr. Fowkes FG and the research team at University of Edinburgh, "Multiple regression of risk factors on measures of peripheral arterial disease showed associations with diabetes mellitus (but not impaired glucose tolerance), systolic blood pressure, and serum cholesterol; inverse association with high-density lipoprotein cholesterol; and only univariate association with triglycerides. In multiple logistic regressions of risk factors on six separate indicators of cardiovascular disease, the only consistent difference was that smoking increased the risk of peripheral arterial disease (range of odds ratios, 1.8-5.6) more than heart disease (range of odds ratios, 1.1-1.6)"(15).

14. Etc.

C. Diagnosis and tests
Diagnosis of ischemic heart disease are depending to the nature symptoms for discovering the disease in its early stages to prevent a heart attack from occurring
1. Electrocardiogram or electrocardiography (ECG)
Electrocardiogram or electrocardiography (ECG) is the test to diagnose the heart conditions by measuring the electrical activity of the heart and highly recommendation for patients showing symptoms of severe chest pain. An abnormal patterns on the EKG may be an indication of Ischemia. In some cases, exercise testing, an exercise ECG test or 'stress test' as ECG recording is taken while you are exercising  to induce the symptoms of chest pain in finding the causes.
2. X ray
X ray may be necessary to rule out other causes of the disease.
3. Blood tests
The aim of the blood test is to monitor the activity of the heart, including cardiac enzyme tests to test for the damage of heart muscle.
4. Echocardiogram (echo)
Echocardiogram (echo) provide your doctor an image of your heart using sound waves by identifying the overall function of your heart, including the structure, thickness, movement of each heart valve, etc.
Some researchers indicated that Exercise testing, whether by echocardiography or ECG, is more useful at excluding CAD than confirming it. Clinicians have concentrated on individualising the treatment of CAD, but there is great scope for individualising the diagnosis of CAD using exercise testing(16).
5. Coronary angiography
The aim of the test is to provide information of  your heart functioning and to identify the narrowing and blockage of the coronary arteries.
6. Radionuclide stress test
The aim of the test is to identify whether the blockage in a coronary artery results in diminished blood flow to a part of the cardiac muscle.
7. Etc.

D. Preventions
D.1. The Do`s and Do not`s list (Similar to
Coronary heart disease)

D.2. Diet to prevent Ischemic heart disease
1. Avocados, 
native to the Caribbean, Mexico, South America and Central America, belonging to the flowering plant family Lauraceae are a commercially valuable fruit cultivated in tropical climates throughout the world, A green-skinned, pear-shaped fruit  ripens after harvesting.
a. Cholesterol
Avocado oil a relative to saturated (coconut oil), monounsaturated (olive oil) and polyunsaturated (corn oil) fats showed an 
atherogenic effects in induced high levels of serum HDL cholesterol in the rabbits fed the two monounsaturated fats(30).

b. Dietary fiber
Diabetes are at risk of Ischemic heart disease. Increased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals(31).

c. Heart diseases
c.1.The Beta-Sitosterol, a 
chemical compound found in avocado  showed effectively in reducing the bad cholesterol and leaving the good cholesterol untouched by inhibiting the amount our body can not absorb(32).

c.2. It also reduce the risk of autoimmune diseases such as multiple sclerosis(33) and development of ischemic heart disease in relation to autoimmune thyroid disease(33a).

2. Almond, 
most widely cultivated seed in the world for it economic and health benefit, consists of an outer hull and a hard shell with the seed (nut) inside is native to the Middle East.
a. . Cholesterol
Almond consumption between 
25 to 168 g/day showed a significantly lowered total cholesterol levels and LDL cholesterol with non significant effect on HDL cholesterol, triglycerides, or LDL/HDL ratio(34).

b. Antioxidants
Bioactive compounds and DPPH (2,2-diphenyl-1-picrylhydrazyl) found in 
almond green husks showed a significant radical scavenging activity,  inhibition of β-carotene bleaching and lipid peroxidation in pig brain tissue(35).

c.  Cardiovascular diseases
Omega 3 fatty acid found in almond prevents the risk of cardiovascular diseases by reducing arrhythmias and altering production of prostaglandins in reduced inflammation and improved platelet and endothelial function(36).


3. Salmon is the common name for Salmonidae, a anadromous, born in fresh water, migrate to the ocean, then travel thousands of miles in the deep sea cold water throughout their life cycle and within to five years returning to the exacted location where they were born to reproduce and die.
a. Triacylglycerols
 Intake of fish and omega-3 (n-3) fatty acids is associated with a reduced concentration of plasma triacylglycerols (TAG). According to study, intake of cod or salmon may lower TAG(37).


b. Weight loss
 n3 long-chain polyunsaturated fatty acids (n3-LCPUFA), found abundantly in salmon showed to induce weight loss at the end of the 1-month period of 43 children participants(38).


c. Cholesterol
Replacement of fish oil by vegetavle oil also found to reduce levels of total cholesterol
through 
SREBP2, (a gene controls cholesterol homeostasi) mediation in reductions in dietary cholesterol(39).

d. Coronary heart disease
Omega-3-fatty acids play a protective role in the prevention of CHD,  Intake of almon oil  decrease triglycerides in patients with hypertriglyceridemia and increase of cholesterol in patient with  hypercholesterolemia(40).


e. Antioxidants
Intake of vitamin E after ingestion salmon oil, not only exhibits a pro-oxidative activity, but also increases the anti-oxidative capacity of the liver(41).


4. Soy sauce is a seasoning produced by fermenting soybeans and filamentous fungus, along with water and salt after a period of sometime, to yield a moromi or thick mash of cereal to obtain soy sauce by pressing it to liquid form. Tamari is made by collecting the liquid pressed and the liquid drained from miso after a certain time of fermentation. 
a. Cardiovascular health
Soy protein has shown a cardioprotective effects as compared to other proteins,  but these observations have not been confirmed by randomized placebo-controlled trials(42).


b.  Hypolipidemic effect
In a 4-week randomized, double-blind, placebo-controlled parallel group study, SPS of soy sauce showed to reduce lipid absorption, and suggested that soy sauce may bea potentially promising seasoning for the treatment of hyperlipidemia(43).


5. Pear, 
cultivated in the cool temperated weather regions all over the world for commercial purposes, is Genus Pyrus containg over 30 difference species, belongs to the family Rosaceae and native to western Europe and north Africa east right across Asia.
a.  Antioxidants
 A review of 18 cultivars of cactus pears studied, the red and purple cactus pears showed a great stability when exposed to OH•
(44).

b. Stroke
Higher intake of white fruits and vegetables was inversely associated with incidence of stroke.  For each 25-g/d increased in white fruit and vegetable consumption risk of stroke is reduced by 
9%(45).

c. Dietary fiber

Daily intake of right amount of fibers can prevent and treat diabetes, a major risk factor for cardiovascular diseases. Increased consumption of vegetables, whole grains, and soluble and insoluble fiber is associated with improved glucose metabolism in both diabetic and nondiabetic individuals(46).

6. Tomato is a red, edible fruit, genus Solanum, belongs to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose
and often in green house.
a. Cardiovascular diseases
Lycopene, a phytochemical pigment, in vitro data showed showed promising preventive mechanisms of
CVD lycopene, probably through its antioxidant and anti-inflammatory effects.(47).

b. Antioxidative and Cancer Cell-Inhibiting Activities
Tomato extracts promoted growth in normal liver (Chang) cells and mildly inhibited growth of lung cancer (A549) cells, and  in lymphoma (U937) cells(48).


7. Etc.


D.3. Antioxidants to prevent Ischemic heart disease
1. Nitric oxide (NO)

Nitric oxide (NO), one of the antioxidant and peroxynitrite can inhibit pathways of oxygen radical generation, and, in turn, oxidants inhibit NO synthesis from NOS.
2. Glutathione and vitamin E
Reduced form of glutathione may act as a first line of defense against oxidative stress during ischemia–reperfusion while vitamin E may act later on during severe oxidative stress by rendering resistance to the heart against the ischemic–reperfusion injury.


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

4. Selenium
Deficiency of of a co-enzyme selenium, which is required in maintaining the glutathione redox cycle, also promote more susceptible to oxidative injure.
5. Etc.


E. Treatments
E.1. In conventional medicine perspective
 

1. Medical treatments
1. 1. Nitroglycerin
a. Nitroglycerin is used to treat ischemic cardiac pain. and improve blood flow to the heart. Transdermal nitrate delivery systems showed to improve the quality of life and reduction of anginal attacks side effects(60).
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.


1.2. Beta-blockers
a. Beta blockers are prescribed to lower heart rate, blood pressure, and enhance oxygen to the heart.

 A withdrawal syndrome immediately following the cessation of beta-blocker use may cause an acute precipitant of angina and myocardial infarction in hypertensive patients who have no prior history of coronary heart disease(61).
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. Calcium channel blockers
a. The medicine are prescribed to relax arteries, lower blood pressure, and reduce strain on the heart.  Clopidogrel combined with nondihydropyridine CCB is found to associate with significantly increased composite thromboembolic events in comparison with dihydropyridine CCB(62).
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.


1.4. Statins
a. The medicine are used to lower cholesterol. Dr. Biasucci LM,  and the scientists at the Sacro Cuore University, said" Statins have also pleiotropic effect behind their lipid lowering function: they reduce inflammation, which plays an important role in the atherosclerotic process"(63).
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.


1.5. Aspirin
a. Many researchers believe that daily intake aspirin can reduce the risk of blood clots from forming in your arteries. According to Royal Hallamshire Hospital, Aspirin treatment for primary prevention is safe and worthwhile at coronary event risk(64).
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.


2. Percutaneous Coronary Intervention (PCI )
Percutaneous Coronary Intervention (PCI ) is one therapeutic treatment used to treat the narrowed coronary arteries of the heart found in coronary heart disease and Ischemic heart disease.
 PCI treatment showed an acceptable success rate in our center in Isfahan with mortality and complications are within the range(65).


3. Coronary revascularisation
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 are grafted to the coronary arteries for improvement the blood supply to the heart muscle(66).

E.2. Treatments in herbal medicine 

1. Organic Soybean, grown worldwide with suitable climate for commercial profit and a a healthy foods is the genus Glycine, belonging to the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. The herb has been used in traditional medicine for the proper functioning of the bowels, heart, kidney, liver, stomach. etc.
a.  Insulin sensitive
Soybean normalize plasma glucose and insulin homeostasis(67).


b. Cardiovascular diseases
Soy protein reduces the levels of serum lipoprotein, low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), ration of LDL-C/high-density lipoprotein cholesterol (HDL-C), triacylglycerol/HDL-C (68).


c. Adipogenesis(
the process of cell differentiation ) and Adipolysis(Assay Kit)
Germinated soy bean protein also had an effect on inhibition of lipid storage in adypocites and increasing lipolysis(69).


d. Antioxidant effects
Extract from Virginia-grown soybean seeds had exerted its antioxidant effects in total phenolic contents (TPC), oxygen radical absorbance capacity (ORAC), and 2,2-diphenyl-1-picrylhydrazyl radical (DPPH(*)) scavenging activities.(70).


e. Diabetes and hypertension
Soybean phenolic-rich extracts has exerted anti
aiabetes and anti hypertension through inhibitory activities on α-amylase, α-glucosidase and angiotensin I converting enzyme (ACE) activities in vitro(71).

2. Garlic (Allium sativum),
used popularly in traditional and Chinese medicine in treating common cold and flu to the Plague, blood pressure cholesterol levels, natural antibiotic, etc., is a species in the onion genus, belonging to family Amaryllidaceae, native to central Asia.
a. Cholesterol
Eating 4 cloves of garlic a day can cut total CHOLESTEROL by 70%(Fresh or Supplement), because of its sulfur compound in reduction of platelets from clumping together. 

b. Blood pressure and Atherosclerosis
 Aged garlic extract generally, a well tolerated and acceptability showed to lower systolic blood pressure in patient with uncontrolled hypertension(72). The extracts also  showed a significantly favorable improvement in oxidative biomarkers, vascular function, and reduced progression of atherosclerosis(73).

3. 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(74).

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.(75).

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)(75a).
 
4. Ginkgo 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(76).

b. Cardiovascular tissues
Ginkgo biloba extract (EGb) has shown the protection of the cardiovascular tissues against HgCl(2)-induced oxidative damage(77).


c. Hyperlipidemia
Ginkgo biloba leaves (EGB) showed a limitation of the absorption of cholesterol, and favorable regulation of profiles of essential polyunsaturated fatty acid (EFA)(78).


5. Grape seed extract
Grape Seed Extract,
used in traditional medicine as antioxidant, anti-inflammatory agents and to treat skin wounds with less scarring, allergies, macular degeneration, arthritis, enhance circulation of blood vessels, lower cholesterol, etc., is the commercial extracts from whole grape seeds containing many concentrations, including vitamin E, flavonoids, linoleic acid, oligomeric proanthocyanidins(OPCs), etc..
a. Antioxidant Activity
Phenolic content of white and red wines increased antioxidant activity dose-dependently(79).


 b. Atherosclerosis
  Polyphenolic compounds found in consumption of red wine has shown to inhibit hypercholesterolemic response to semisynthetic diet.(80).

6. Hawthorn
a. Hypotensive effects
 Hawthorn (Crataegus laevigata) leaves, flowers and berries used by herbal practitioners in the UK to treat hypertension in conjunction with prescribed drugs demonstrate a hypotensive effect in patients with diabetes(81).

b. Cardiac effects
 2 alcohol extracts of hawthorn showed to activate cardiac effects via the sodium-potassium adenosine triphosphatase(pumps sodium out of cells, while pumping potassium into cells), and intracellular calcium(involved in the initiation of electric and mechanical phenomena: depolarization, contraction of smooth and striated muscles, hormonal secretion, activation of enzymes) concentrations(82).

c. Cardiovascular disease
The presence of antioxidant flavonoid found in hawthorn may be responsible for its prevention and protection of cardiovascular disease, according to an international, multicenter, prospective clinical study(83).

d. Chronic heart failure
An index of cardiac oxygen consumption was decreased, shortness of breath and fatigue improved significantly, according to the review of literature ten trials including 855 patients of the effects of oral administration of hawthorn for treatment of chronic heart failure(84).

e. Hyperlipemia
  Yishoujiangzhi (de-blood-lipid) tablets (composed of Radix Polygori Multiflori, Rhizoma Polygonati, Fructus Lycii, Crataegus Pinnatifida and Cassia Tora) inhibited hyperlipemia through reduction of 87.0% of serum cholesterol and 80.8% of triglyceride(85).
7. Etc.

E.3. In Tranditional Chinese medicine perspective(similar to treatment of Coronary heart disease)
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(86)(87).                                      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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