Articles

Hypertension

Introduction

Blood pressure is the amount of force required for the heart to circulate blood through the body. Systolic blood pressure represents the maximal blood pressure during systole, and diastolic blood pressure the minimum pressure at the end of ventricular diastole. Arterial blood pressure can be defined hemodynamically as the product of cardiac output and total peripheral resistance. Cardiac output is the main determinant of systolic pressure while peripheral resistance largely determines the level of diastolic pressure.

Under normal physiologic conditions, the blood pressure stays within narrow limits. It may reach a peak during emotional or physical stress, and falls the lowest during sleep. Generally, blood pressure tends to be lower in women than men, it tends to be higher in blacks than whites, and it rises with age.

Hypertension is a cardiovascular disease characterized by elevation of blood pressure above arbitrary values considered normal for people of similar racial and environmental background. (1) Hypertension affects the vasculature of all major organs (heart, brain, kidneys), and myocardial infarction and congestive heart failure account for the majority of deaths secondary to hypertension.

The Sixth Joint National Committee on the Detection, Evaluation, and Treatment of High Blood Pressure (JNC-VI) classifies hypertension in adults as follows: (2)

Statistic

World health Organization, 2007.

  • World wide, high blood pressure is estimated to cause 7.1 million deaths, about 13% of the total and about 4.4% of the total disease burden. 
  • There are, by a conservative estimate, at least 600 million hypertension sufferers worldwide.

Malaysia Ministry of Health, 2002.

  • Prevalence of hypertension among adults aged 30 years and above was 29.9% equivalent to 2.19 million Malaysians in 1996.
  • By the year 2010, it is projected that 2.99 million Malaysians will have hypertension.

American Heart Association, 2002.

    High blood pressure (hypertension) killed 44,619 Americans in 2000 and contributed to the deaths of about 118,000. As many as 50 million Americans age 6 and older have high blood pressure. One in five Americans (and one in four adults) has high blood pressure. Of those people with high blood pressure, 31.6 percent don't know they have it. Of all people with high blood pressure, 14.8 percent aren't on therapy (special diet or drugs), 26.2 percent are on inadequate therapy, and 27.4 percent are on adequate therapy. The cause of 90–95 percent of the cases of high blood pressure isn't known; however, high blood pressure is easily detected and usually controllable. High blood pressure affects more than one out of every three African Americans.

Signs and Symptoms

[span class=alert]The following list does not insure the presence of this health condition. Please see the text and your healthcare professional for more information.[/span]

Patients with uncomplicated, primary hypertension are usually asymptomatic, at least initially. Often, it is not until target organ damage occurs that cardiovascular, cerebrovascular or symptoms of renal disease appear. Often, patients with essential hypertension may present with only elevated blood pressure, with all other portions of the physical examination appearing normal.

It should be emphasized that a single reading of high blood pressure does not constitute a diagnosis of hypertension. If a blood pressure taken on two or more subsequent days is 140/90 mm Hg or higher, then a diagnosis of hypertension can be confirmed. Some basic laboratory tests (addressed elsewhere in this monograph) should be performed before any pharmacologic intervention is begun. These tests will provide a baseline for monitoring drug-induced metabolic changes and a base with which to compare disease progression.

Some of the target organs where changes are seen include the brain, heart, kidney, and eye. Hypertension, more than any other variable, predisposes individuals to developing atherothrombotic brain infarction (the most common variety of stroke). The relationship between hypertension and accelerated development of atherosclerosis, coronary artery disease, and congestive heart failure (CHF) has been clearly established. CHF and myocardial infarction (MI) account for the majority of deaths secondary to hypertension. Renal complications of untreated moderate hypertension include accelerated atherosclerosis of renal arteries and nephrosclerosis. Atherosclerosis and reduced kidney function occurs in all adults with increasing age, but occur more rapidly in the presence of mild to moderate hypertension. Hypertension can cause disturbances in vision due to a variety of retinopathies that develop. Hemorrhages in the vitreous humor or the retina may occur. Nonspecific changes include an increased light reflex, increased tortuosity of vessels, and arteriovenous nicking. Papilledema in hypertensive patients is indicative of a malignant stage of hypertension and requires immediate treatment.

Uncomplicated, primary hypertension

  • Usually, initially asymptomatic
  • A blood pressure taken on two or more subsequent days is 140 (systolic)/90(diastolic) mm Mercury or higher
  • Hypertension predisposes individuals to developing atherothrombotic brain infarction
  • May accelerate hardening of the arteries, coronary artery disease, congestive heart failure and/or heart-attack
  • May cause kidney problems such as atherosclerosis of renal arteries and/or nephrosclerosis
  • May cause visual disturbances such as increased light reflex, increased tortuosity of vessels and/or arteriovenous nicking
  • Often not until target organ damage occurs that cardiovascular, cerebrovascular, or symptoms of renal disease appear
  • May cause papilledema which is malignant stage of hypertension and requires immediate treatment 

Treatment Options

Conventional

A careful history checking for chest pain, palpitations, dizziness, dyspnea, slurred speech, orthopnea, and loss of balance should be taken to assess the likelihood of cardiovascular and cerebrovascular complications. Patients may be taught to self-record blood pressure measurements. These should be routinely monitored.

Antihypertensive medications can be divided into eight classes: diuretics, central alpha 2-agonists, adrenergic inhibitors, beta-blockers, ACE inhibitors, calcium channel blockers, vasodilators, and postganglionic sympathetic inhibitors. Drug selection should be based on safety, efficacy, cost and presence of concomitant diseases and other risk factors. An algorithm for the treatment of hypertension has been developed by the JNC-VI, published in NIH publication No 98-4080, November 1997, and is summarized as follows:

There are specific clinical situations that make drug choices more difficult, and must be carefully reviewed. Some of these include hypertension in childhood, hypertension in pregnancy, age, ethnicity, renal insufficiency, tachycardia, hyperlipidemia, gout/hyperuricemia, and angina.

Nutritional Supplementation


Coenzyme Q10 (CO-Q10)

Coenzyme Q10 is a nutrient that plays a supportive role in cardiovascular health and may have a significant effect on blood pressure. In one study, 109 patients with symptomatic essential hypertension started high-dose coenzyme Q10 (average dose 225mg/day) in addition to their regular blood pressure medications. On average, these patients had been diagnosed with essential hypertension for 9.2 years. Coenzyme Q10 therapy caused significant improvement in functional status, which allowed for a substantial reduction in the use of antihypertensive drugs within the first one to six months. After 6 months, 51 percent of the patients were able to stop taking from one to three antihypertensive drugs after initiating therapy with coenzyme Q10. (3)

An eight-week randomized, double-blind trial evaluated the effectiveness of coenzyme Q10 (60mg twice daily) or a placebo in patients receiving antihypertensive medications. After eight weeks of follow-up, the patients taking coenzyme Q10 had lower systolic and diastolic blood pressure, fasting and 2-hour plasma insulin, glucose, triglycerides, lipid peroxides, malondialdehyde, and diene conjugates. At the same time, patients taking coenzyme Q10 also registered increases in HDL cholesterol, vitamins A, C, E, and beta-carotene. These findings suggest that coenzyme Q10 lowers blood pressure, possibly by decreasing oxidative stress and improving insulin response in patients with known hypertension who are taking conventional antihypertensive drugs. (4)

In a recent review, one group of researchers noted that 34 controlled trials and several open-label and long-term studies on the clinical effects of CoQ10 have been published in the scientific literature. These authors also state that the attainment of higher blood levels of CoQ10 (above 3.5mcg/ml) by administering larger doses of CoQ10 appears to enhance both the magnitude and rate of clinical improvement. (5)

Some categories of prescription drugs can inhibit the body’s ability to synthesize coenzyme Q10. Drugs that may deplete coenzyme Q10 include sulfonylureas, biguanides, beta-blockers, hydralazine-containing vasodilators, thiazide diuretics, centrally acting antihypertensives (clonidine and methyldopa), the "statin" cholesterol lowering drugs, tricyclic antidepressants, and phenothiazines. (6)


Magnesium

Magnesium supplementation given orally is therapeutically useful in the treatment of patients with uncomplicated essential hypertension, especially those with high plasma renin activity. In patients with essential hypertension, magnesium apparently suppresses circulating Na+, K(+), ATPase inhibitory activity, resulting in a reduction in vascular tone with a subsequent lowering of blood pressure. (7)

Double-blind studies have been published reporting that magnesium provides a moderate lowering of systolic and diastolic blood pressure in patients with mild to moderate essential hypertension. (8) , (9) Also, when magnesium was administered to patients with mild to moderate hypertension who were being treated with beta-blockers, it resulted in a significant decrease in both supine and standing systolic blood pressure, indicating that it might be used to enhance the effectiveness of existing antihypertensive medications. (10) Doses in the range of 300-600mg/day are frequently used.

Some commonly used drugs may deplete magnesium levels and increase the risk of various forms of cardiovascular disease. They include aminoglycosides, corticosteroids, digoxin, loop and thiazide diuretics, and estrogen-containing medications. (11)


Potassium

A large and growing body of scientific research from animal experimentation, observational epidemiology, and randomized clinical trials strongly suggests that lowering dietary salt and increasing potassium intake may help improve blood pressure and cardiovascular health. (12) Studies report that people consuming diets containing foods that are high in potassium have a lower incidence of hypertension. (13) Epidemiological evidence reveals that increasing potassium intake can lower blood pressure in individuals who have essential hypertension, and increasing dietary potassium can also result in a reduction of antihypertensive medications. (14) In general, potassium’s antihypertensive effect is considered moderate, with its effects being more pronounced in individuals who initially have higher blood pressure and lower potassium intake. (15)


Vitamin C

In a review of studies between 1980-1996 it was found that 10 out of 14 studies reported an inverse association between plasma vitamin C and blood pressure, and three out of four reported an inverse relationship between blood pressure and vitamin C intake. (16) The results of a randomized, double-blind, placebo-controlled study reported that administration of vitamin C to patients with hypertension resulted in a lowering of blood pressure. (17) However, in a double-blinded, randomized, controlled trial of 439 Japanese subjects with atrophic gastritis, long-term use of vitamin C at 500mg per day had no effect on lowering blood pressure in these high risk patients. (18)


Calcium

The research on the relationship between calcium and blood pressure is conflicting. Some studies report a calcium-induced hypotensive effect, while others report no effect. In any event, the magnitude of calcium’s blood pressure reduction effect is regarded as modest. (19) A representative example is an eight-week trial of 51 patients with mild essential hypertension. They were randomly divided, with one group (31 patients) receiving 1 gram of oral calcium daily and the second group receiving a placebo. At the end of the eighth week, those treated with calcium reported a significant decrease in blood pressure, with the greatest reduction being 6 mm Hg in the systolic pressure and 3 mm Hg reduction in diastolic pressure. (20)


Omega-3 Fatty Acids

Omega-3 fatty acids exert mild antihypertensive effects. It is suggested that the mechanism of action is probably due to a combination of benefits resulting from being incorporated into vascular phospholipids where they help to lower the formation of endothelial contractile substances. (21) Several studies have reported that relatively large doses of omega-3 polyunsaturated fatty acids effectively lower blood pressure in humans. The results from the following study indicates that supplementation with a moderate dose of highly purified eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is able to reduce blood pressure in mild hypertensive patients. Subjects were randomly assigned to receive either EPA and DHA ethyl esters (2.04 gm EPA and 1.4 gm DHA) or olive oil (4 gm/day) as a placebo for a period of four months. The blood pressure lowering effect of the omega-3 fatty acids was maximum after two months. The treatment resulted in a lowering of both systolic (-6 mm Hg) and diastolic (-5 mm Hg) blood pressure, indicating that 4 gm/day of highly purified EPA and DHA effectively lower blood pressure in patients with mild hypertension. (22)

Herbal Supplementation


Coleus

Coleus is a relatively new medicinal herb in the United States, although it has been extensively researched in India over the last twenty years. There have been studies conducted to support its hypotensive (blood pressure lowering) and spasmolytic effects. (23) , (24) Most studies have been done with the isolated extract, forskolin, but research supports that the whole plant is actually more effective.

Coleus is reported to have two significant mechanisms of action. First, it is claimed to activate the enzyme, adenylate cyclase. (25) This action would have the effect of increasing cyclic adenosine monophosphate (c-AMP) within the cells. Coleus reportedly creates c-AMP activation independent of receptor site specificity. (26) The stimulation of c-AMP has an impact on body chemistry in several ways. It stimulates thyroid function, increases insulin secretion, inhibits mast cell release of histamine, and increases the burning of fats as fuels. (27) Coleus is claimed to inhibit platelet activating factor (PAF) by possibly directly binding to PAF receptor sites. (28) , (29) PAF is a key factor in allergic and inflammatory pathways. By inhibiting it, neutrophil activation may be inhibited, vascular permeability reduced, smooth muscle contraction decreased, and coronary blood flow increased. (30)


Hawthorn

Hawthorn is used as a vasodilator and circulatory stimulant. (31) , (32) Doctors in Europe in its standardized form in various cardiovascular and peripheral circulatory conditions have used it extensively. Its combination of effects on the heart leads to its use as a tonic, especially for the elderly, where mitral stenosis and minor heart failure may be present. Studies have reported a reduction in blood pressure due to arteriosclerosis and chronic nephritis with the use of hawthorn. (33) , (34) It is also used for peripheral vascular diseases, such as Raynaud’s disease. European physicians use hawthorn to help maintain digoxin levels while decreasing the need for the pharmaceutical medication. Hawthorn is reported to have the ability to regulate both low and high blood pressure. Its bioflavonoids reportedly dilate both peripheral and coronary blood vessels. (35) This leads to its use in decreasing angina attacks. The proanthocyanidin (PCO) content is claimed to support the spasmolytic effects. (36) The PCO content is also thought to be responsible for the coronary circulatory effects, increasing the amplitude of the heartbeat. (37) Hawthorn’s glycoside component reportedly increases the vagal tone of the heartbeat. (38) It is also thought that hawthorn inhibits angiotensin-converting enzyme. (39) It has a slight diuretic effect, which may help lower high blood pressure. Laboratory studies have reported that proanthocyanidins may actually aid in reversing atherosclerotic plaque. (40)


Garlic

Garlic has been reported to lower total cholesterol, LDL cholesterol and triglycerides, and increase HDL cholesterol. (41) , (42) , (43) Garlic may be of benefit in the prevention of heart disease and atherosclerosis. (44) , (45) Garlic may inhibit platelet aggregation and influence blood viscosity through its fibrinolytic activity. (46) , (47) , (48) This leads to the use of garlic in the prevention of strokes, heart attacks, and various thrombus events. (49) , (50) , (51) Also, the antioxidant effect in aged garlic has been reported to be beneficial in preventing stroke and arteriosclerosis. (52)

A recent study reported no effect of garlic oil on serum lipids. (53) However, the product used was garlic oil, which is processed and heated garlic. The impact of processing is an important fact to keep in mind when recommending garlic supplements. Changes can occur in the active constituents when exposed to cooking or other processing which can render the garlic product virtually ineffective. Cooking is known to denature proteins, and therefore, may inactivate the enzyme (allinase) that is necessary in converting alliin into allicin, the major bioactive constituent in garlic.

Also, research has reported that allinase may be irreversibly inhibited by stomach acid and may fail to form adequate amounts of allicin or other thiosulfinates below a pH of 3.6. (54) , (55) The quality of garlic supplements varies greatly in the marketplace. Of further note, as reported in a few laboratory studies, is the potential for large amounts of allicin to damage liver tissue if absorbed due to its oxidation potential. (56) , (57) However, there are positive studies using high quality garlic preparations standardized to allicin potential without adverse effects.

Homeopathic

Cactus grandiflorus

Typical Dosage: 6X or 6C, 30X or 30CConstricting sensation; Pain radiates to the left arm

Glonoinum

Typical Dosage: 6X or 6C, 30X or 30CSudden palpitations; Feels as if blood rushes to the head; Throbbing headache

Natrum muriaticum

Typical Dosage: 6X or 6C, 30X or 30CPains in chest; Shortness of breath

Acupuncture & Acupressure

Acupuncture
Wang, et al. treated 54 cases of Stage I and Stage II hypertension with micropuncture and blood letting therapy. The main acupuncture points treated were: Baihui (DU20), Taiyang (Extra 2), Dazhui (D14), Quchi (LI11), and Weizhong (B40). Additional points were included for treatment as the symptoms of individual patients dictated. The acupoints, 3-4 points per session, were punctured 0.2-0.3cm deep with three-edged needles by the pricking method (some of the acupoints were also treated with cupping). The control group was given compound Verticil Tablets. The total effective rates of the two groups were 88.9% and 73.6%, respectively (p

Aromatherapy

Aromatherapy for Hypertension

While many essential oils have properties that affect the circulatory system, in hypertension the approach is to promote relaxation and stress reduction. For this reason, it is recommended that supplementary activities that promote relaxation and stress reduction be a part of any aromatherapy program for hypertension. These would include baths, massage, breathing exercises and meditation.

Inhalation Therapy
Use the following oils in a diffuser three to four times each day along with a breathing exercise program:

    Lavender (58) (Lavendula augustifolia) 4 drops Ylang Ylang (Cananga odorata) 2 drops Clary Sage (Salvia sclerea) 1 drop

Bath Therapy
The following oils may be used in a bath and the individual should soak for 15 to 20 minutes:

    Marjoram (Origanum Marjorana) 3 drops Lavender (Lavendula augustifolia) 3 drops Geranium (pelargonium graveolen) 2 drops

Massage Therapy
These oils may be mixed with a minimum of one ounce of carrier oil such as almond or sesame and may be used for massage:

    Lavender (Lavendula augustifolia) 10 drops Ylang Ylang (Cananga odorata) 6 drops Sandalwood (Santalum Album) 5 drops Marjoram (Origanum Marjorana) 1 drop Clary Sage (Salvia sclerea) 1 drop

Caution: Essential Oil therapies should not be used during pregnancy or lactation and should always be used under the direction of an experienced aromatherapist.

Traditional Chinese Medicine

Hypertension

Extensive information regarding the treatment of this health condition using Traditional Chinese Medicine is available through the link above.

Diet & Lifestyle

Since studies have conclusively shown many risk factors for development of hypertension and related diseases, any treatment plan should begin with elimination or reduction of those risk factors. Obesity, cigarette smoking, alcohol consumption, and excessive salt intake have been clearly identified as risk factors, along with hyperlipidemia and glucose intolerance. Treatment plans should therefore begin with lifestyle changes that include a sensible diet that reduces saturated fats and salt intake, as well as calorie restriction if weight loss is indicated. Participation in smoking cessation programs should be aggressively promoted, and restriction of alcohol consumption should be encouraged. Since hypertension begins as an asymptomatic disease, patient education is a vital component of therapy. Increased understanding of associated risk factors and eventual consequences will hopefully lead to greater compliance with treatment programs.

Another useful lifestyle modification is a program of moderate exercise. Studies indicate that aerobic exercise such as walking, jogging, swimming, and bicycling can reduce blood pressure, even in the absence of weight loss. Patients should consult a physician before starting any exercise program.

Weight reduction: Several large epidemiological studies have shown an association between body mass index and blood pressure in normal weight and overweight patients. Weight gain in adult life especially seems to be an important risk factor for the development of hypertension. Weight loss has been recommended for the obese hypertensive patient and has been shown to be the most effective nonpharmacological treatment approach. A modest weight loss can normalize blood pressure levels even without reaching ideal weight. In patients taking antihypertensive medication, a modest weight loss has been shown to lower or even discontinue the need for antihypertensive medication. In patients with high normal blood pressure, a modest weight loss can prevent the onset of frank hypertension. The blood pressure lowering effect of weight loss is most likely a result of an improvement in insulin sensitivity and a decrease in sympathetic nervous system activity and occurs independent of salt restriction. In conclusion, a modest weight loss that can be maintained over a longer period of time is a valuable treatment goal in hypertensive patients. (59)

Cadmium toxicity is reported to cause elevated blood pressure. The association of cadmium exposure with area of residence, blood pressure, and arterial hypertensive disease was examined in 230 reindeer herders in northernmost arctic Finland. Blood cadmium concentration averaged 10.0 nmol/l, and was three times higher in smokers than in nonsmokers (16.7 vs. 5.5 nmol/l). (60) Other heavy metals to suspect include mercury and lead.

Salt sensitivity: Salt-sensitive subjects increase their blood pressure with increasing salt intake. Because steroid hormones modulate renal sodium retention, it is hypothesized that the activity of the 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme is impaired in salt-sensitive subjects as compared with normal subjects. (61)

Rule out food allergies.

Clinical Lab Assessment

Some of the following laboratory testing can provide information necessary for diagnosis and treatment. In addition, the tests listed may also give insight to functional metabolism and functional nutrient status in the body.

Mineral Analysis

The evaluation of essential and/or toxic elements can be of use in the evaluation of hypertension.

Electrolytes, Plasma, Serum, or Urine

These values are monitored especially when medications are being used. Many diuretics deplete potassium. Low serum potassium (with or without alkalosis) is indication for further renal function study.

Glucose

Blood glucose levels vary in response to food intake, stress, physical exertion, and various disorders. Antihypertensive medications can produce elevations of uric acid and glucose. Elevations of serum glucose should lead to confirmatory testing such as fasting insulin, serum phosphorus, magnesium, hemoglobin A1c, and/or fructosamine.

Magnesium Level

Due to the low levels of magnesium in the average diet and its importance in smooth muscle contractility, magnesium is particularly important to assess in hypertension. (62)

References

  1. May DB, Young LY, Wiser TH. Essential Hypertension In: Koda-Kimble et al eds Applied Therapeutics: The Clinical use of Drugs, 4th ed. Vancouver, WA: Applied therapeutics; 1992:7-32.
  2. View Abstract: The Sixth Report of the National Committee on detection, evaluation, and treatment of high blood pressure (JNC-VI). Arch Intern Med. 1997;157:2413-2446.
  3. View Abstract: Langsjoen P, et al. Treatment of essential hypertension with coenzyme Q10. Mil Aspects Med. 1994;15 Suppl:S265-72.
  4. View Abstract: Singh RB, et al. Effect of hydrosoluble coenzyme Q10 on blood pressures and insulin resistance in hypertensive patients with coronary artery disease. J Hum Hypertens. Mar1999;13(3):203-8.
  5. View Abstract: Langsjoen PH, Langsjoen AM. Overview of the use of CoQ10 in cardiovascular disease. Biofactors. 1999;9(2-4):273-84.
  6. Pelton R. The Drug-Induced Nutrient Depletion Handbook. Hudson, OH: Lexi-Comp; 1999.
  7. View Abstract: Haga H. Effects of dietary magnesium supplementation on diurnal variations of blood pressure and plasma Na+, K(+)-ATPase activity in essential hypertension. Jpn Heart J. Nov1992;33(6):785-800.
  8. View Abstract: Widman L, et al. The dose-dependent reduction in blood pressure through administration of magnesium. A double blind placebo controlled cross-over study. Am J Hypertens. Jan1993;6(1):41-5.
  9. View Abstract: Geleijnse JM, et al. Reduction of blood pressure with oral magnesium supplementation in women with mild to moderate hypertension. Am J Clin Nutr. Jul1994;60(1):129-35.
  10. View Abstract: Wirell MP, et al. Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study. J Intern Med. Aug1994;236(2):189-95.
  11. Pelton R. The Nutritional Cost of Prescription Drugs. Englewood, CO: Morton Publishing; 2000:152.
  12. View Abstract: Cutler JA. The effects of reducing sodium and increasing potassium intake for control of hypertension and improving health. Clin Exp Hypertens. Jul1999;21(5-6):769-83.
  13. View Abstract: Langford HG. Dietary potassium and hypertension: Epidemiologic data. Am Intern Med. 1983;98(2):770-772.
  14. Krishna G. Potassium and blood pressure regulation. Drug Therapy. 1993:88-92.
  15. View Abstract: Kawano Y, et al. Effects of potassium supplementation on office, home, and 24-h blood pressure in patients with essential hypertension. Am J Hypertens. Oct1998;11(10):1141-6.
  16. View Abstract: Ness AR, et al. Vitamin C and blood pressure--an overview. J Hum Hypertens. Jun1997;11(6):343-50.
  17. View Abstract: Duffy SJ, et al. Treatment of hypertension with ascorbic acid. Lancet. Dec1999;354(9195):2048-9.
  18. View Abstract: Kim MK, et al. Lack of long-term effect of vitamin C supplementation on blood pressure. Hypertension. Dec2002;40(6):797-803.
  19. View Abstract: Moore TJ. The role of dietary electrolytes in hypertension. J Am Coll Nutr. 1989;8(Suppl S):68S-80S.
  20. View Abstract: Olivan Martinez J, et al. Effect of an oral calcium supplement in the treatment of slight-to- moderate essential arterial hypertension. An Med Interna. Apr1989;6(4):192-6.
  21. View Abstract: Beilin LJ. Dietary fats, fish, and blood pressure. Ann N Y Acad Sci. Jun1993;683:35-45.
  22. View Abstract: Prisco D, et al. Effect of medium-term supplementation with a moderate dose of n-3 polyunsaturated fatty acids on blood pressure in mild hypertensive patients. Thromb Res. Aug1998;91(3):105-12.
  23. View Abstract: Bhat SV, et al. The Antihypertensive and Positive Inotropic Diterpene Forskolin: Effects of Structural Modifications on Its Activity. J Med Chem. 1983;26:486-92.
  24. View Abstract: Baumann G, et al. Cardiovascular Effects of Forskolin (HL 362) in Patients with Idiopathic Congestive Cardiomyopathy- A Comparative Study with Dobutamine and Sodium Nitroprusside. Cardiovasc Pharmacol. 1990;16(1):93-100.
  25. Seamon KB, et al. Forskolin: Its Biological and Chemical Properties. Advances in Cyclic Nucleotide and Protein Phosphorylation Research, vol 20. New York: Raven Press; 1986:1-150.
  26. View Abstract: Doi K, et al. The Effect of Adenylate Cyclase Stimulation on Endocochlear Potential in the Guinea Pig. Eur Arch Otorhinolaryngol. 1990;247(1):16-19.
  27. View Abstract: Kreutner RW. Bronchodilator and Antiallergy Activity of Forskolin. European Journal of Pharmacology. 1985;111:1-8.
  28. View Abstract: Christenson JT, et al. The Effect of Forskolin on Blood Flow, Platelet Metabolism, Aggregation and ATP Release. Vasa. 1995;24(1):56-61.
  29. View Abstract: Agarwal KC, et al. Significance of Plasma Adenosine in the Antiplatelet Activity of Forskolin: Potentiation by Dipyridamole and Dilazep. Thromb Haemost. 1989;61(1):106-10.
  30. View Abstract: Marone G, et al. Inhibition of IgE-mediated Release of Histamine and Peptide Leukotriene from Human Basophils and Mast Cells by Forskolin. Biochem Pharmacol. 1987;36(1):13-20.
  31. View Abstract: Schüssler M. Myocardial effects of flavonoids from Crataegus species. Arzneimittelforschung. Aug1995;45(8):842-5.
  32. View Abstract: Weikl A. Crataegus Special Extract WS 1442. Assessment of objective effectiveness in patients with heart failure (NYHA II). Fortschr Med. Aug1996;114(24):291-6.
  33. Racz-Kotilla E, et al. Salidiuretic and Hypotensive Action of Ribes-Leaves. Planta Medica. 1980;29:110-14.
  34. View Abstract: Garjani A. Effects of extracts from flowering tops of Crataegus meyeri A. Pojark. on ischaemic arrhythmias in anaesthetized rats. Phytother Res. Sep2000;14(6):428-31.
  35. Wagner H, et al. Cardioactive Drugs IV. Cardiotonic Amines from Crataegus oxyacantha. Planta Medica. 1982;45:99-101.
  36. Rewerski W, et al. Some Pharmacological Properties of Flavan Polymers Isolated from Hawthorn. Arzneim-Forsch/Drug Res. 1967;17:490-91.
  37. View Abstract: Taskov M. On the Coronary and Cardiotonic Action of Crataemon. Acta Physiol Pharmacol Bulg. 1977;3(4):53-57.
  38. Petkov E, et al. Inhibitory Effect of Some Flavonoids and Flavonoid Mixtures on Cyclic AMP Phosphodiesterase Activity of Rat Heart. Planta Medica. 1981;43:183-86.
  39. View Abstract: Uchida S, et al. Inhibitory Effects of Condensed Tannins on Angiotensin Converting Enzyme. Jap J Pharmacol. 1987;43(2):242-46.
  40. View Abstract: Wegrowski J, et al. The Effect of Procyanidolic Oligomers on the Composition of Normal and Hypercholesterolemic Rabbit Aortas. Biochem Pharm. 1984;33:3491-97.
  41. Ernst E. Cardioprotection and Garlic. Lancet. 1997;349(9045):131.
  42. View Abstract: Steiner M, et al. A Double-blind Crossover Study in Moderately Hypercholesterolemic Men that Compared the Effect of Aged Garlic Extract and Placebo Administration on Blood Lipids. Am J Clin Nutr. 1996;64(6):866-70.
  43. View Abstract: Agarwal KC. Therapeutic Actions of Garlic Constituents. Med Res Rev. 1996;16(1):111-24.
  44. Fogarty M. Garlic's Potential Role in Reducing Heart Disease. Br J Clin Pract. 1993;47(2):64-65.
  45. View Abstract: Orekhov AN, et al. Direct Anti-atherosclerosis-related Effects of Garlic. Ann Med. 1995;27(1):63-65.
  46. View Abstract: Kiesewetter H, et al. Effect of Garlic on Platelet Aggregation in Patients with Increased Risk of Juvenile Ischaemic Attack. Eur J Clin Pharmacol. 1993;45(4):333-36.
  47. View Abstract: Bordia A. Effect of Garlic on Blood Lipids in Patients with Coronary Heart Disease. Am J Clin Nutr. 1981;34(10):2100-03.
  48. Bordia A, et al. Protective Effect of Garlic Oil on the Changes Produced by 3 Weeks of Fatty Diet on Serum Cholesterol, Serum Triglycerides, Fibrinolytic Activity and Platelet Adhesiveness in Man. Indian Heart J. 1982;34(2):86-88.
  49. View Abstract: Kendler BS. Garlic (Allium sativum) and Onion (Allium cepa): A Review of Their Relationship to Cardiovascular Disease. Prev Med. 1987;16(5):670-85.
  50. View Abstract: Arora RC, et al. The Long-term Use of Garlic in Ischemic Heart Disease - An Appraisal. Atherosclerosis. 1981;40(2):175-79.
  51. View Abstract: Koscielny J, et al. The Antiatherosclerotic Effect of Allium sativum. Atherosclerosis. May1999;144(1):237-49.
  52. View Abstract: Ide N, et al. Aged Garlic Extract Attenuates Intracellular Oxidative Stress. Phytomedicine. May1999;6(2):125-31.
  53. Garlic Oil: No Impact on Lipids. Harv Heart Lett. Sep1998;9(1):6.
  54. View Abstract: Weber ND, et al. In Vitro Virucidal Effects of Allium sativum (garlic) Extract and Compounds. Planta Med. Oct1992;58(5):417-23.
  55. Freeman F, et al. Garlic Chemistry: Stability of s-2-propenyl)-2-propene-1-sulfinothioate (allicin) in Blood, Solvents, and Simulated Physiological Fluids. J Agric Food Chem. 1995;43:2332-2338.
  56. View Abstract: Egen-Schwind C, et al. Metabolism of Garlic Constituents in the Isolated Perfused Rat Liver. Planta Med. Aug1992;58(4):301-5.
  57. View Abstract: Egen-Schwind C, et al. Pharmacokinetics of Vinyldithiins, Transformation Products of Allicin. Planta Med. Feb1992;58(1):8-13.
  58. View Abstract: Lis-Balchin M, Hart S. Studies on the mode of action of the essential oil of lavender (Lavendula angustifolia P. Miller). Phytother Res. Sep1999;13(6):540-2.
  59. View Abstract: Mertens IL, Van Gaal LF. Overweight, obesity, and blood pressure: the effects of modest weight reduction. Obes Res. May2000;8(3):270-8.
  60. View Abstract: Luoma PV, et al. Association of blood cadmium to the area of residence and hypertensive disease in Arctic Finland. Sci Total Environ. Jan1995;160-161:571-5.
  61. View Abstract: Lovati E, et al. Molecular basis of human salt sensitivity: the role of the 11beta-hydroxysteroid dehydrogenase type 2. J Clin Endocrinol Metab. Oct1999;84(10):3745-9.
  62. View Abstract: Singh RB, Rastogi SS, Mehta PJ, Cameron EA. Magnesium metabolism in essential hypertension. Acta Cardiol. 1989;44(4):313-22.