Hypertension

Hypertension, commonly referred to as "high blood pressure" or HTN, is a medical condition in which the blood pressure is chronically elevated.^[1] While it was previously referred to as arterial hypertension, the word "hypertension" without a qualifier usually refers to arterial hypertension. Hypertension can be classified as either essential (primary) or secondary. Essential hypertension indicates that no specific medical cause can be found to explain a patient's condition. Secondary hypertension indicates that the high blood pressure is a result of (i.e. secondary to) another condition, such as kidney disease or certain tumors (especially of the adrenal gland). Persistent hypertension is one of the risk factors for strokes, heart attacks, heart failure and arterial aneurysm, and is a leading cause of chronic renal failure. Even moderate elevation of arterial blood pressure leads to shortened life expectancy. At severely high pressures, defined as mean arterial pressures 50% or more above average, a person can expect to live no more than a few years unless appropriately treated.^[2]

Hypertension is considered to be present when a person's systolic blood pressure is consistently 140 mmHg or greater, and/or their diastolic blood pressure is consistently 90 mmHg or greater.^[3] Recently, as of 2003, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure^[4] has defined blood pressure 120/80 mmHg to 139/89 mmHg as "prehypertension." Prehypertension is not a disease category; rather, it is a designation chosen to identify individuals at high risk of developing hypertension. The Mayo Clinic website specifies blood pressure is "normal if it's below 120/80" but that "some data indicate that 115/75 mm Hg should be the gold standard." In patients with diabetes mellitus or kidney disease studies have shown that blood pressure over 130/80 mmHg should be considered high and warrants further treatment. Even higher numbers are considered diagnostic using home blood pressure monitoring devices.

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Factors of essential hypertension

Although no specific medical cause can be determined in essential hypertension, the most common form, several factors may contribute to it, including salt sensitivity, renin homeostasis, insulin resistance, genetics and age.

Salt sensitivity

Sodium is an environmental factor that has received the greatest attention. Approximately 60% of the essential hypertension population is responsive to sodium intake^{[citation needed]}. This is due to the fact that increasing amounts of salt in a person's bloodstream causes the body to draw more water, increasing the pressure on the blood vessel walls.

The effects of excess amounts of salt in the body depend on how much excess salt (or salty foods) is eaten in a specific time versus how well the kidneys functioned. When the salt content of the blood elevates, water is attracted from around the cells (in muscles and organs) and into the blood, in order to dilute blood salinity. There is salt as sodium outside every cell in your body. When the salt content of the fluid around your cells goes up, it attracts water from your blood and swelling occurs. Your kidneys are responsible for regulating salt and water levels in your body. When salt and water levels increase around cells, the excess is drawn into your blood, which is filtered by your kidneys. Your kidneys remove excess salt and water from your blood, both of which are excreted as urine. When your kidneys do not work well, fluid builds up around cells and in your blood. Your heart is the pump that pushes your blood around. If there is more fluid in your blood, your heart has to work harder and your blood pressure can go up because there is more pressure on the walls of your blood vessels. Your heart can get weaker or worn out from the extra work.

Salt has been blamed in the past as causing high blood pressure. New research suggests that too little calcium or potassium also has an impact on blood pressure.

Role of renin

Renin is an enzyme secreted by the juxtaglomerular apparatus of the kidney and linked with aldosterone in a negative feedback loop. The range of renin activity observed in hypertensive subjects tends to be broader than in normotensive individuals. In consequence, some hypertensive patients have been defined as having low-renin and others as having essential hypertension. Low-renin hypertension is more common in African Americans than Caucasians and may explain why they tend to respond better to diuretic therapy than drugs that interfere with the renin-angiotensin system.

High Renin levels predispose to Hypertension: Increased Renin → Increased Angiotensin II → Increased Vasoconstriction, Thirst/ADH and Aldosterone → Increased Sodium Reabsorption in the Kidneys (DCT and CD) → Increased Blood Pressure.

Insulin resistance

Insulin is a polypeptide hormone secreted by the pancreas. Its main purpose is to regulate the levels of glucose in the body antagonistically with glucagon through negative feedback loops. Insulin also exhibits vasodilatory properties. In normotensive individuals, insulin may stimulate sympathetic activity without elevating mean arterial pressure. However, in more extreme conditions such as that of the metabolic syndrome, the increased sympathetic neural activity may over-ride the vasodilatory effects of insulin. Insulin resistance and/or hyperinsulinemia have been suggested as being responsible for the increased arterial pressure in some patients with hypertension. This feature is now widely recognized as part of syndrome X, or the metabolic syndrome.

Sleep apnea

Sleep apnea is a common, under-recognized cause of hypertension.^[5] It is often best treated with nocturnal nasal continuous positive airway pressure, but other approaches include the Mandibular advancement splint (MAS), UPPP, tonsilectomy, adenoidectomy, sinus surgery, or weight loss.

Genetics

Hypertension is one of the most common complex disorders, with genetic heritability averaging 30%.^{[citation needed]} Data supporting this view emerge from animal studies as well as in population studies in humans. Most of these studies support the concept that the inheritance is probably multifactorial or that a number of different genetic defects each have an elevated blood pressure as one of their phenotypic expressions.

More than 50 genes have been examined in association studies with hypertension, and the number is constantly growing.

Age

Over time, the number of collagen fibers in artery and arteriole walls increases, making blood vessels stiffer. With the reduced elasticity comes a smaller cross-sectional area in systole, and so a raised mean arterial blood pressure.

Other etiologies

There are some anecdotal or transient causes of high blood pressure. These are not to be confused with the disease called hypertension in which there is an intrinsic physiopathological mechanism as described below.

Etiology of secondary hypertension

Only in a small minority of patients with elevated arterial pressure, can a specific cause be identified (in 90 percent to 95 percent of high blood pressure cases, the American Heart Association says there's no identifiable cause). These individuals will probably have an endocrine or renal defect that, if corrected, could bring blood pressure back to normal values.

Renal hypertension

Hypertension produced by diseases of the kidney. This includes diseases such as polycystic kidney disease or chronic glomerulonephritis. Hypertension can also be produced by diseases of the renal arteries supplying the kidney. This is known as renovascular hypertension; it is thought that decreased perfusion of renal tissue due to stenosis of a main or branch renal artery activates the renin-angiotensin system.

Adrenal hypertension

Hypertension is a feature of a variety of adrenal cortical abnormalities. In primary aldosteronism there is a clear relationship between the aldosterone-induced sodium retention and the hypertension.

Cushing's syndrome (hypersecretion of cortisol)

Both adrenal glands can overproduce the hormone cortisol or it can arise in a benign or malignant tumor. Hypertension results from the interplay of several pathophysiological mechanisms regulating plasma volume, peripheral vascular resistance and cardiac output, all of which may be increased. More than 80% of patients with Cushing's syndrome have hypertension.

In patients with pheochromocytoma increased secretion of catecholamines such as epinephrine and norepinephrine by a tumor (most often located in the adrenal medulla) causes excessive stimulation of [adrenergic receptors], which results in peripheral vasoconstriction and cardiac stimulation. This diagnosis is confirmed by demonstrating increased urinary excretion of epinephrine and norepinephrine and/or their metabolites (vanillylmandelic acid).

Genetic causes

Hypertension can be caused by mutations in single genes, inherited on a mendelian basis.^[6]

Coarctation of the aorta

Drugs

Certain medications, especially NSAIDS (Motrin/ibuprofen) and steroids can cause hypertension. Imported licorice (Glycyrrhiza glabra) inhibits the 11-hydroxysteroid hydrogenase enzyme (catalyzes the reaction of cortisol to cortison) which allows cortisol to stimulate the Mineralocorticoid Receptor (MR) which will lead to effects similar to hyperaldosteronism, which itself is a cause of hypertension. [Reference: Harrisons Internal Medicine, online edition (2007-04-14)]

Spinal misalignment

Another claimed cause of hypertension is the misalignment of vertebrae within the spinal column, specifically the atlas vertebra. The Journal of Human Hypertension published the results of a clinically controlled trial in which patients with hypertension and a misaligned atlas vertebra were chosen to undergo chiropractic treatment. The study showed a significant lowering of blood pressure in hypertensive patients after only one chiropractic adjustment of the atlas vertebra. The study showed a decrease in blood pressure immediately following the adjustment as well as a full eight weeks following the adjustment. The decrease in blood pressure was equal to taking two blood-pressure drugs at once.

^[7]

Pathophysiology

Most of the secondary mechanisms associated with hypertension are generally fully understood, and are outlined at secondary hypertension. However, those associated with essential (primary) hypertension are far less understood. What is known is that cardiac output is raised early in the disease course, with total peripheral resistance (TPR) normal; over time cardiac output drops to normal levels but TPR is increased. Three theories have been proposed to explain this:

• Inability of the kidneys to excrete sodium, resulting in natriuretic factors such as Atrial Natriuretic Factor being secreted to promote salt excretion with the side-effect of raising total peripheral resistance.
• An overactive renin / angiotension system leads to vasoconstriction and retention of sodium and water. The increase in blood volume leads to hypertension.
• An overactive sympathetic nervous system, leading to increased stress responses.

It is also known that hypertension is highly heritable and polygenic (caused by more than one gene) and a few candidate genes have been postulated in the etiology of this condition.^[8][9][10]

Signs and symptoms

Hypertension is usually found incidentally - "case finding" - by healthcare professionals during a routine checkup. The only test for hypertension is a blood pressure measurement. Hypertension in isolation usually produces no symptoms although some people report headaches, fatigue, dizziness, blurred vision, facial flushing or tinnitus. ^[11]

Malignant hypertension (or accelerated hypertension) is distinct as a late phase in the condition, and may present with headaches, blurred vision and end-organ damage.

Hypertension is often confused with mental tension, stress and anxiety. While chronic anxiety and/or irritability is associated with poor outcomes in people with hypertension, it alone does not cause it. Accelerated hypertension is associated with somnolence, confusion, visual disturbances, and nausea and vomiting (hypertensive encephalopathy). ^[12]

Hypertensive urgencies and emergencies

Hypertension is rarely severe enough to cause symptoms. These typically only surface with a systolic blood pressure over 240 mmHg and/or a diastolic blood pressure over 120 mmHg. These pressures without signs of end-organ damage (such as renal failure) are termed "accelerated" hypertension. When end-organ damage is possible or already ongoing, but in absence of raised intracranial pressure, it is called hypertensive emergency. Hypertension under this circumstance needs to be controlled, but prolonged hospitalization is not necessarily required. When hypertension causes increased intracranial pressure, it is called malignant hypertension. Increased intracranial pressure causes papilledema, which is visible on ophthalmoscopic examination of the retina.

Complications

While elevated blood pressure alone is not an illness, it often requires treatment due to its short- and long-term effects on many organs. The risk is increased for:

• Cerebrovascular accident (CVAs or strokes)
• Myocardial infarction (heart attack)
• Hypertensive cardiomyopathy (heart failure due to chronically high blood pressure)
• Hypertensive retinopathy - damage to the retina
• Hypertensive nephropathy - chronic renal failure due to chronically high blood pressure

Pregnancy

Main article: Hypertension of pregnancy

Although few women of childbearing age have high blood pressure, up to 10% develop hypertension of pregnancy. While generally benign, it may herald three complications of pregnancy: pre-eclampsia, HELLP syndrome and eclampsia. Follow-up and control with medication is therefore often necessary.

Children and adolescents

As with adults, blood pressure is a variable parameter in children. It varies between individuals and within individuals from day to day and at various times of the day. The epidemic of childhood obesity, the risk of developing left ventricular hypertrophy, and evidence of the early development of atherosclerosis in children would make the detection of and intervention in childhood hypertension important to reduce long-term health risks; however, supporting data are lacking.

Most childhood hypertension, particularly in preadolescents, is secondary to an underlying disorder. Renal parenchymal disease is the most common (60 to 70%) cause of hypertension. Adolescents usually have primary or essential hypertension, making up 85 to 95% of cases. ^[13]

Diagnosis

Measuring blood pressure

Diagnosis of hypertension is generally on the basis of a persistently high blood pressure. Usually this requires three separate measurements at least one week apart. Exceptionally, if the elevation is extreme, or end-organ damage is present then the diagnosis may be applied and treatment commenced immediately.

Obtaining reliable blood pressure measurements relies on following several rules and understanding the many factors that influence blood pressure reading^[14].

For instance, measurements in control of hypertension should be at least 1 hour after caffeine, 30 minutes after smoking and without any stress. Cuff size is also important. The bladder should encircle and cover two-thirds of the length of the arm. The patient should be sitting for a minimum of five minutes. The patient should not be on any adrenergic stimulants, such as those found in many cold medications.

When taking manual measurements, the person taking the measurement should be careful to inflate the cuff suitably above anticipated systolic pressure. The person should inflate the cuff to 200 mmHg and then slowly release the air while palpating the radial pulse. After one minute, the cuff should be reinflated to 30 mmHg higher than the pressure at which the radial pulse was no longer palpable. A stethoscope should be placed lightly over the brachial artery. The cuff should be at the level of the heart and the cuff should be deflated at a rate of 2 to 3 mmHg/s. Systolic pressure is the pressure reading at the onset of the sounds described by Korotkoff (Phase one). Diastolic pressure is then recorded as the pressure at which the sounds disappear (K5) or sometimes the K4 point, where the sound is abruptly muffled. Two measurements should be made at least 5 minutes apart, and, if there is a discrepancy of more than 5 mmHg, a third reading should be done. The readings should then be averaged. An initial measurement should include both arms. In elderly patients who particularly when treated may show orthostatic hypotension, measuring lying sitting and standing BP may be useful. The BP should at some time have been measured in each arm, and the higher pressure arm preferred for subsequent measurements.

BP varies with time of day, as may the effectiveness of treatment, and archetypes used to record the data should include the time taken. Analysis of this is rare at present.

Automated machines are commonly used and reduce the variability in manually collected readings ^[15]. Routine measurements done in medical offices of patients with known hypertension may incorrectly diagnose 20% of patients with uncontrolled hypertension ^[16]

Home blood pressure monitoring can provide a measurement of a person's blood pressure at different times throughout the day and in different environments, such as at home and at work. Home monitoring may assist in the diagnosis of high or low blood pressure. It may also be used to monitor the effects of medication or lifestyle changes taken to lower or regulate blood pressure levels.

Home monitoring of blood pressure can also assist in the diagnosis of white coat hypertension. The American Heart Association^[17] states, "You may have what's called 'white coat hypertension'; that means your blood pressure goes up when you're at the doctor's office. Monitoring at home will help you measure your true blood pressure and can provide your doctor with a log of blood pressure measurements over time. This is helpful in diagnosing and preventing potential health problems."

Distinguishing primary vs. secondary hypertension

Once the diagnosis of hypertension has been made it is important to attempt to exclude or identify reversible (secondary) causes.

• Over 91% of adult hypertension has no clear cause and is therefore called essential/primary hypertension. Often, it is part of the metabolic "syndrome X" in patients with insulin resistance: it occurs in combination with diabetes mellitus (type 2), combined hyperlipidemia and central obesity.
• Secondary hypertension is more common in preadolescent children, with most cases caused by renal disease. Primary or essential hypertension is more common in adolescents and has multiple risk factors, including obesity and a family history of hypertension. ^[18]

Investigations commonly performed in newly diagnosed hypertension

Tests are undertaken to identify possible causes of secondary hypertension, and seek evidence for end-organ damage to the heart itself or the eyes (retina) and kidneys. Diabetes and raised cholesterol levels being additional risk factors for the development of cardiovascular disease are also tested for as they will also require management.

Blood tests commonly performed include:

• Creatinine (renal function) - to identify both underlying renal disease as a cause of hypertension and conversely hypertension causing onset of kidney damage. Also a baseline for later monitoring the possible side-effects of certain antihypertensive drugs.
• Electrolytes (sodium, potassium)
• Glucose - to identify diabetes mellitus
• Cholesterol

Additional tests often include:

• Testing of urine samples for proteinuria - again to pick up underlying kidney disease or evidence of hypertensive renal damage.
• Electrocardiogram (EKG/ECG) - for evidence of the heart being under strain from working against a high blood pressure. Also may show resulting thickening of the heart muscle (left ventricular hypertrophy) or of the occurrence of previous silent cardiac disease (either subtle electrical conduction disruption or even a myocardial infarction).
• Chest X-ray - again for signs of cardiac enlargement or evidence of cardiac failure.

Epidemiology

The level of blood pressure regarded as deleterious has been revised down during years of epidemiological studies. A widely quoted and important series of such studies is the Framingham Heart Study carried out in an American town: Framingham, Massachusetts. The results from Framingham and of similar work in Busselton, Western Australia have been widely applied. To the extent that people are similar this seems reasonable, but there are known to be genetic variations in the most effective drugs for particular sub-populations. Recently (2004), the Framingham figures have been found to overestimate risks for the UK population considerably. The reasons are unclear. Nevertheless the Framingham work has been an important element of UK health policy.

Treatment

Lifestyle modification (nonpharmacologic treatment)

• Weight reduction and regular aerobic exercise (e.g. jogging) are recommended as the first steps in treating mild to moderate hypertension. Regular mild exercise improves blood flow and helps to reduce resting heart rate and blood pressure. These steps are highly effective in reducing blood pressure, although drug therapy is still necessary for many patients with moderate or severe hypertension to bring their blood pressure down to a safe level.

• Reducing sodium (salt) diet is proven very effective: it decreases blood pressure in about 60% of people (see above). Many people choose to use a salt substitute to reduce their salt intake.

• Additional dietary changes beneficial to reducing blood pressure includes the DASH diet (Dietary Approaches to Stop Hypertension), which is rich in fruits and vegetables and low fat or fat-free dairy foods. This diet is shown effective based on National Institutes of Health sponsored research. In addition, an increase in daily calcium intake has the benefit of increasing dietary potassium, which theoretically can offset the effect of sodium and act on the kidney to decrease blood pressure. This has also been shown to be highly effective in reducing blood pressure.

• Discontinuing tobacco smoking and alcohol drinking has been shown to lower blood pressure. The exact mechanisms are not fully understood, but blood pressure (especially systolic) always transiently increases following alcohol and/or nicotine consumption. Besides, abstention from cigarette smoking is important for people with hypertension because it reduces the risk of many dangerous outcomes of hypertension, such as stroke and heart attack. Note that coffee drinking (caffeine ingestion) also increases blood pressure transiently, but does not produce chronic hypertension.

• Relaxation therapy, such as meditation, that reduces environmental stress, high sound levels and over-illumination can be an additional method of ameliorating hypertension. Jacobson's Progressive Muscle Relaxation and biofeedback are also used [1] particularly device guided paced breathing [2] [3]. Obviously, the effectiveness of relaxation therapy relies on the patient's attitude and compliance.

Impact of race

See also: Race and health

In a summary of recent research Jules P. Harrell, Sadiki Hall, and James Taliaferro describe how a growing body of research has explored the impact of encounters with racism or discrimination on physiological activity. "Several of the studies suggest that higher blood pressure levels are associated with the tendency not to recall or report occurrences identified as racist and discriminatory."^[19] In other words, failing to recognize instances of racism has a direct impact on the blood pressure of the person experiencing the racist event. Investigators have reported that physiological arousal is associated with laboratory analogues of ethnic discrimination and mistreatment.

The interaction between high blood pressure and racism has also been documented in studies by Claude Steele, Joshua Aronson, and Steven Spencer on what they term "stereotype threat".^[20]

Chiropractic

Chiropractic, which treats disorders by diagnosing and treating mechanical disorders of the spine, has shown positive results in the treatment of hypertension. The Journal of Human Hypertension published the results of a clinically controlled trial in which patients with hypertension and a misaligned atlas vertebra were chosen to undergo chiropractic treatment. The study showed a significant lowering of blood pressure in hypertensive patients after only one chiropractic adjustment of the atlas vertebra. The study showed a decrease in blood pressure immediately following the adjustment as well as a full eight weeks following the adjustment. Blood pressure in the group receiving chiropractic was lowered by an average of 17mmHg BP systolic and 10mmHg diastolic BP. The decrease in blood pressure was equal to taking two antihypertensive drugs at once. ^[7]

Medications

Main article: Antihypertensive

There are many classes of medications for treating hypertension, together called antihypertensives, which — by varying means — act by lowering blood pressure. Evidence suggests that reduction of the blood pressure by 5-6 mmHg can decrease the risk of stroke by 40%, of coronary heart disease by 15-20%, and reduces the likelihood of dementia, heart failure, and mortality from vascular disease.

The aim of treatment should be blood pressure control to <140/90 mmHg for most patients, and lower in certain contexts such as diabetes or kidney disease (some medical professionals recommend keeping levels below 120/80 mmHg).[4] Each added drug may reduce the systolic blood pressure by 5-10 mmHg, so often multiple drugs are necessary to achieve blood pressure control.

Commonly used drugs include:

• ACE inhibitors such as captopril, enalapril, fosinopril (Monopril), lisinopril (Zestril), quinapril, ramipril (Altace)
• Angiotensin II receptor antagonists: eg, telmisartan (Micardis, Pritor), irbesartan (Avapro), losartan (Cozaar), valsartan (Diovan), candesartan (Atacand)
• Alpha blockers such as doxazosin, prazosin, or terazosin
• Beta blockers such as atenolol, labetalol, metoprolol (Lopressor, Toprol-XL), propranolol.
• Calcium channel blockers such as nifedipine (Adalat®)^[21] amlodipine (Norvasc), diltiazem, verapamil
• Direct renin inhibitors such as aliskiren (Tekturna)
• Diuretics: eg, bendroflumethiazide, chlortalidone, hydrochlorothiazide (also called HCTZ)
• Combination products (which usually contain HCTZ and one other drug)

Influence of age and race on medication efficacy

A randomized controlled trial by the Veterans Affairs Cooperative Study Group on Antihypertensive Agents reported the influence of patient age and race on the proportion of patients whose blood pressure was controlled by different agents.^[22][23] For example:

• Less than 7% of young white patients responded to a diuretic (hydrochlorothiazide)
• Only 6% of older black patients responded to an ACE inhibitor (captopril)

The effect of age and race are in part due to differences in plasma renin activity.^[24][25]

Choice of initial medication

Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidelines.

Regarding cardiovascular outcomes, the ALLHAT study showed a slightly better outcome and cost-effectiveness for the thiazide diuretic chlortalidone compared to other anti-hypertensives in an ethnically mixed population.^[26] Whilst a subsequent smaller study (ANBP2) did not show this small difference in outcome and actually showed a slightly better outcome for ACE-inhibitors in older white male patients.^[27]

Whilst thiazides are cheap, effective, and recommended as the best first-line drug for hypertension by many experts, they are not prescribed as often as some newer drugs. Arguably, this is because they are off-patent and thus rarely promoted by the drug industry.^[28]

Due to their metabolic impact (hypercholesterinemia, impairment of glucose tolerance, increased risk of developing Diabetes mellitus type 2), the use of thiazides as first line treatment for essential hypertension has been repeatedly questioned and strongly discouraged.^{[29] [30] [31]}

Physicians may start with non-thiazide antihypertensive medications if there is a compelling reason to do so. An example is the use of ACE-inhibitors in diabetic patients who have evidence of kidney disease, as they have been shown to both reduce blood pressure and slow the progression of diabetic nephropathy.^[32] In patients with coronary artery disease or a history of a heart attack, beta blockers and ACE-inhibitors both lower blood pressure and protect heart muscle over a lifetime, leading to reduced mortality.

Advice in the United Kingdom

The risk of beta-blockers provoking type 2 diabetes led to their downgrading to fourth-line therapy in the United Kingdom in June 2006^[33], in the revised national guidelines.^[34]

Advice in the United States

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) in the United States recommends starting with a thiazide diuretic if single therapy is being initiated and another medication is not indicated.^[4]

Systolic hypertension

For more details on this topic, see Systolic hypertension.

See also

• Edible salt
• Hypertensive emergency
• Malignant hypertension
• Exercise hypertension
• White coat hypertension
• Home blood pressure monitoring
• Spontaneously hypertensive rat

References

• Television Viewing Linked To Childhood Obesity And Hypertension In Children
• Natural Remedies for High Blood Pressure from Earth Clinic's Folk Medicine Archive

Major studies

• The Framingham Heart Study
• Information on ALLHAT
• Information on ACTION - A Coronary Disease Trial Investigating Outcome with Nifedipine GITS
• Information on INSIGHT
• Information on ENCORE