High blood pressure or hypertension is an extremely common and dangerous condition and is rampant among most, but not all, societies of the world. Although initially without symptoms (it's a "silent condition"), hypertension requires treatment. Over time elevated pressure causes damage to blood vessels and to the organs the vessels supply with blood, called target organs. This vascular damage can result in stroke, heart attack, kidney failure, heart failure and damage to the eyes, called retinopathy. High blood pressure is the major underlying cause of these common and disastrous medical conditions. Persons with untreated hypertension face a shorter life and a reduced quality of life.

An individual's blood pressure is easily determined. The flow of blood from your heart through your blood vessels creates pressure against the walls of these vessels. This pressure is read using a blood pressure cuff and recorded as a systolic number over a diastolic number. The systolic is the peak pressure achieved when the heart beats; the diastolic is the pressure when the heart relaxes between beats. Blood pressures less than 120/80 mm Hg (systolic/diastolic) are usually considered ideal.

Population studies throughout the world have verified the risks of high blood pressure and have defined what level is "too high". Blood pressure is considered high when the systolic pressure is greater than 140 mm Hg and the pulse pressure (systolic minus diastolic) is greater than 60 mm Hg, or when the diastolic pressure is above 90 mm Hg.

The number of persons with high blood pressure is staggering. More than 50 million Americans are estimated to have this condition. It's no wonder that so many of us combine a trip to the grocery store with a stop at the blood pressure machine before going on to the frozen food section. The blood pressure apparatus, not by chance, is usually located in the pharmacy.

Figure 1 shows the percentage of men and women of various ages in the USA who have high blood pressure.

Figure 1:

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Life Style Modification and Medications Are Used To Help Control Blood Pressure

Medical research has taught us that lifestyle modifications can be effective in lowering blood pressure. To some extent physical activity, improved dietary habits and stress modification can also reduce other cardiovascular risk factors associated with high blood pressure. Many persons with known hypertension, and other known risk factors as well, nevertheless, will not attempt lifestyle modification. The reasons may be cultural, psychological, or motivational. This is sad, because even if complete control of high blood pressure is not achieved by lifestyle modification it may still be possible to reduce the number of medications and the dosages needed to reduce blood pressure. Even some people who make an earnest attempt at modifying their lifestyle often find that this isn't enough for adequate control -- i.e. down to below 140/90mm Hg. This is why doctors need to prescribe drugs. Scientific studies have proven that pharmacological treatment decreases cardiovascular morbidity and mortality. Protection has been demonstrated for stroke, coronary events, heart failure, progression of kidney disease, progression to more severe hypertension, and all cause-mortality with drug treatment.

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What Is The Best Medication For Your Hypertension?

When there is failure to control blood pressure with lifestyle modification the next step is medication; but which drug is best for you? On any given day if you were to ask people who were picking up blood pressure medication in a pharmacy which medication they were taking for their high blood pressure you would get a variety of answers. This is because there are numerous medications to control blood pressure. They all differ in how they work, but they all rely upon mechanisms already in place within the body. To understand the options for medications let's look at what factors determine blood pressure, what factors regulate blood pressure and the role of the kidneys and other physiological mechanisms in blood pressure control.

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I. The Basic Determinants of Blood Pressure (The Pump and The Pipes)

Blood pressure is the force the flowing blood exerts against artery walls. Blood pressure is determined by the actions of your heart muscle, (the pump), and the status of your arteries, (the pipes). When your heart pumps blood into your arteries during each heart beat, the pressure within your arteries rapidly increases. The peak level it reaches is your systolic blood pressure. While your heart muscle is relaxing and your heart is filling with blood to get ready for the next heartbeat, your arterial pressure is decreasing. This is because the blood is draining out of your large arteries into your body organs. The lowest level to which your blood pressure decreases between heartbeats is your diastolic pressure. The systolic minus the diastolic is your pulse pressure (See Article # 10, "How Badly Are Your Arteries Hardening With Aging?"). Thus, you can see that blood pressure is dependent upon and determined by the volume of blood within your heart and arteries and the mechanics of your heart and arteries on this volume of blood.

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II. Factors That Regulate The Pump and The Pipes

The systolic pressure is determined by how much blood the heart (the pump) pumps into the arteries (the pipes) during each beat, the stiffness of the large arteries (the pipes), and how well the blood can be transferred from large to small arteries, a process controlled by the structure and the tone of the smaller blood vessels.

The volume of blood your heart (the pump) is able to pump into your arteries (the pipes) with each heart beat is determined, in part, by how much blood fills your heart (the pump) prior to its beat and, in part, by how strong the heart (the pump) contracts to push the blood out during each beat.

The "tightness" or stiffness of these vessels (the pipes) is determined by two general properties: the extent to which vascular smooth muscle cells in the wall of your large arteries (the pipes) are contracting, and the properties of the scaffold in which the pipes are imbedded, or the matrix, which is composed of proteins like collagen and elastin. With aging systolic pressure and pulse pressure increase because the large arteries (the pipes) have become stiff. (See Article # 10, "How Badly Are Your Arteries Hardening With Aging?" ).

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III. The Role of the Kidneys in the Regulation of Blood Pressure

Blood volume, a major determinant of blood pressure, is regulated to a large degree by the kidneys. The arteries (pipes) within kidneys, when operating normally, sense when blood volume is too high or to low, and adjust it towards normal. The pipes accomplish this by regulating the amount of sodium and water passing through their walls and into the urine. When kidneys sense a low pressure within their pipes they secrete renin, an enzyme, which triggers production of angiotensin, a hormone. Angiotensin triggers the release of aldosterone, another hormone which helps regulate sodium and water balance by retaining sodium and water and excreting potassium. This increases blood volume. When sodium or blood volume is too high, other substances are produced that act on the kidney to evoke an increased loss of sodium into the urine, thus decreasing blood volume.

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IV. The Role of Neurotransmitters and Endothelial Cells Substrates In The Regulation of Blood Pressure

Heart muscle contraction is rapid and transient. Each contraction or beat produces a "pulse". In contrast, the blood vessels muscles' contraction is long lasting. This is called "tone". The robustness of your heart muscle's contraction and the tightness of your vascular smooth muscle cells tone are regulated by nerve endings within them that ultimately connect to the brain. Neurotransmitter substances liberated from these nerve endings circulate in the blood and bind to heart and vascular muscle cells to regulate the vigor of their contraction. (See Article #7 "Brain-Heart Communication Withers With Aging"). Likewise, endothelial cells, those cells lining the inner part of your blood vessels, sense a change in blood pressure or flow and liberate substances like nitric oxide, or prostaglandins, that have multiple actions on your arteries to keep blood pressure under control. For example, an acute response to nitric oxide production by your endothelial cells is a reduction in blood pressure. Endothelin, another substance produced by endothelial cells, constricts blood vessels and raises blood pressure. The major mechanisms that regulate blood pressure are summarized in the following table.

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Blood Pressure Medications Work On Specific Physiological Mechanisms

You can see why there are so many medications available for the control of hypertension. Years of biomedical research has lead to the discoveries of ways to control blood pressure by using medications aimed at specific mechanisms within the body that regulate blood pressure. These mechanisms control blood volume, arterial stiffness, and some also determine the robustness of your heart's contraction.

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Categories of Blood Pressure Medications

A. Diuretics
Diuretics (often called "water pills") act upon the urine ducts within your kidneys to let more sodium chloride and water pass into your urine rather than being taken back into your kidney's blood stream and into your main blood stream. This action decreases the blood volume and fluid volume throughout the body, thus lowering blood pressure. Diuretics also cause blood vessels to dilate, further reducing blood pressure.

B. Beta Adrenergic Receptor Blockers (Beta Blockers)
Beta Blockers block the effects of the sympathetic support system, the system that responds to stress by raising blood pressure. They block the effects of catecholamines, thus easing the heart's pumping action and widening blood vessels. (See Article #8 "Messages Transmitted From The Brain Fine Tune The Heart" ).

C. Calcium Channel Blockers
Calcium Channel Blockers bind to calcium channels on the surface of heart and vascular cells, to interfere with calcium flow into the cell (See Article #6 "The Essence Of The Heartbeat Changes With Aging"). This decreases the strength of contractions of the heart and widens the blood vessels. Some calcium channel blockers act selectively on blood vessels and not on the heart.

D. ACE (Angiotensin Converting Enzyme) Inhibitors and Angiotensin II Receptor Blockers (ARBs).
ACE inhibitors reduce the production of angiotensin, a chemical that causes arteries to constrict, and thus block angiotensin's effectiveness. This causes the arteries and veins to dilate and reduces blood pressure. Angiotensin II receptor blockers inhibit the binding of angiotensin to these receptors and thus block its action on your heart, kidney and blood vessel cells.

E. Vasodilators
Other vasodilators, for example hydralazine or nitrates, also expand blood vessels.

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How Does Your Doctor Choose the Correct Medication for You?

With all the medications available for the treatment of high blood pressure how does your doctor decide which is best for you? The report of the 6th Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure has recommended that drug therapy be initiated with a diuretic, a beta blocker, a calcium channel clocker, or an ACE inhibitor. Your physician selects the appropriate starter drug, a decision that may be influenced by your age and race and the presence of coexisting diseases or conditions, such as kidney disease, that may contraindicate a certain drug, or conversely indicate one drug over another. These are rough guidelines, and there are many additional factors that your doctor considers. If the first choice drug is ineffective, or causes intolerable side effects, another drug can be tried. If the first drug is only partially effective, but well tolerated, its dose can be increased, or a second drug can be added. The object is to lower blood pressure effectively while causing few side effects. In severe cases a patient may be prescribed three or four medications combined. All of these medications will be working one way or another on the mechanisms discussed above.

Determining the best medication or combination of medications for each patient is a challenge for both the patient and the physician, and can be frustrating. It's necessary to work closely with a physician who listens carefully to the patient's reporting of possible side effects and who monitors the patient's blood pressure closely while titrating the dosages of the types and combinations of drugs which work.

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What Does The Future Hold For Treating of Blood Pressure and Retarding Vascular Aging?

It's becoming apparent to high blood pressure experts that changes within the arterial wall often precede elevations of blood pressure. Thus, these changes within the walls of the arteries may not only be made worse when blood pressure is sustained at higher levels, but may in fact be a cause of the high blood pressure.

Many substances that are produced in hypertensive individuals not only cause blood pressure to change but also directly affect the blood vessel, heart and kidney structure. Angiotensin II is a prototype, but there are several such other substances. In fact, the effects of substances that your body produces, like angiotension II, may also be a cause of blood vessel stiffening that occurs with aging. Defects of endothelial cell function associated with hypertension and aging can lead to a structural rearrangement of blood vessels. One result is thickening of the walls of arteries, due in part to fibrosis, or the accumulation of excess connective tissue.

A serious result of untreated hypertension is thickening of the heart wall, called left ventricular hypertrophy or LVH. LVH is an adaptation of the heart to an increased afterload caused by elevated arterial pressure. Afterload is defined as the mechanical load encountered by the heart following the onset of contraction. It is basically the combination of forces that resist the flow of blood from the heart. Increased pressure within blood vessels causes an increase in afterload. With aging afterload increases additionally, due to the increased stiffness of the arteries that accompanies the aging process.

Medications that retard blood vessel and organ (heart, kidney) structural damage associated with high blood pressure or that occur with aging may become the mainstay of pharmacological hypertensive and vascular aging treatment in the near future. Presently available interventions upon the vascular wall remodeling associated with increased blood pressure to reduce blood vessel stiffening include ACE inhibitors or angiotensin II receptor blockers and calcium channel blockers.

A new approach under investigation now to reduce vascular stiffening is to attempt to break cross-links between collagen molecules within the vascular matrix. Crosslinks, formed by glycosylation end products (known as AGE's) appear to toughen tissues and may cause some of the deterioration associated with aging. They have been linked to stiffening of connective tissue (increased collagen), hardening of the arteries, clouding of the eyes, loss of nerve function, and less efficient kidneys. New drugs are being developed which may block AGE formation. Should this strategy of breaking these crosslinks work, it would likely be additive to the aforementioned drugs. Ideally, these crosslink-breaker drugs could be used as a preventive agent - essentially, an anti-aging formula. The long-term results of such a discovery and subsequent intervention on the general population could have important implications in reducing national health care costs by contributing to a dramatic reduction in morbidity and mortality attributable to hypertension and hypertension-related complications of stroke, heart failure, and end-stage renal disease. It will take years of additional testing to determine the full potential of such drugs.

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The Paradox

It would appear that many of us are unwisely waiting for that "anti-aging formula" to be developed rather than acting now to reduce the risks associated with untreated hypertension. Having knowledge of the proven risks of elevated arterial pressure and given the availability of numerous effective pharmaceutical therapies, it's a paradox why (1) many doctors are not as aggressive as they should be in properly treating high blood pressure, especially in older persons, and (2) why all individuals are not aggressive in having their blood pressure routinely measured, and treated if necessary.

Dr. Ed is a physician/scientist, who is internationally recognized for studies that range from humans to molecules on how the heart and blood vessels work in health and disease as the body ages.

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