Minggu, 15 Februari 2009

Hipertensi

Hypertension, also referred to as high blood pressure, HTN or HPN, is a medical condition in which the blood pressure is chronically elevated. In current usage, the word "hypertension"[1] without a qualifier normally refers to systemic, arterial hypertension.[2]

Hypertension can be classified 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 tumours (pheochromocytoma and paraganglioma).

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.[3]

In individuals older than 50 years, hypertension is considered to be present when a person's systolic blood pressure is consistently 140 mm Hg or greater or when the diastolic blood pressure is consistently 90 mm Hg or greater. Beginning at a systolic pressure of 115 and diastolic pressure of 75 (commonly written as 115/75 mm Hg), cardiovascular disease (CVD) risk doubles for each increment of 20/10 mmHg.[4] Prehypertension is defined as blood pressure from 121/81 mm Hg to 139/89 mm Hg. Prehypertension is not a disease category; rather, it is a designation chosen to identify individuals at high risk of developing hypertension.[4] The Mayo Clinic specifies that blood pressure is normal if it is 120/80 or below.[5] Patients with blood pressures over 130/80 mm Hg along with Type 1 or Type 2 diabetes, or kidney disease require further treatment.[4]

Resistant hypertension is defined as the failure to reduce BP to the appropriate level after taking a three-drug regimen.[4] The American Heart Association released guidelines for treating resistant hypertension.[6]

Causes

[edit] Essential (primary) hypertension

By definition, essential hypertension has no identifiable cause. However, several risk factors have been identified, including obesity,[7] salt sensitivity, renin homeostasis, insulin resistance, genetics, and age.

[edit] Obesity

The risk of hypertension is 5 times higher in the obese as compared to those of normal weight and up to two-thirds of cases can be attributed to excess weight. More than 85% of cases occur in those with a Body mass index greater than 25.[7]A definitive link between obesity and hypertension has been found using animal and clinical studies, from these it has been realised that many mechanisms are potential causes of obesity induced hypertension.These mechanisms include the activation of the sympathetic nervous system as well as the activation of the renin–angiotensin-aldosterone system.[8]

[edit] Sodium sensitivity

Sodium is an environmental factor that has received the greatest attention. Approximately one third of the essential hypertensive population is responsive to sodium intake.[9] This is because increasing the amount of salt in a person's bloodstream causes cells to release water (due to osmotic pressure) to equilibrate the concentration gradient between the cells and the bloodstream, thereby increasing the pressure within the blood vessel walls[citation needed]. The increased Na+ stimulates ADH and thirst mechanisms, leading to a concentrated urine and the kidneys holding onto water along with the person increasing the intake of water. Also, the water movement between cells and the interstitium plays a minor role compared to this.

[edit] 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 white Americans, and may explain why African Americans tend to respond better to diuretic therapy than drugs that interfere with the Renin / angiotension system.

High Renin levels predispose to Hypertension: Increased Renin → Increased Angiotensin II → Increased Vasoconstriction, Thirst/ADH and Aldosterone → Increased Sodium Resorption in the Kidneys (DCT and CD) → Increased Blood Pressure. Some authorities claim that potassium might both prevent and treat hypertension.[10]

[edit] Insulin resistance

Insulin is a polypeptide hormone secreted by cells in the islets of langerhans, which are contained throughout 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[citation needed]. This feature is now widely recognized as part of syndrome X, or the metabolic syndrome.

[edit] Genetics

Hypertension is one of the most common complex disorders.The etiology of hypertension differs widely amongst individuals within a large population.[11] More than 50 genes have been examined in association studies with hypertension, and the number is constantly growing.One of these gene is angiotensinogen (AGT) gene, studied extensively by Kim et al. They showed that increasing the number of AGT increases the blood pressure and hence this may cause hypertension.[12] Twins have been included in studies measuring ambulatory blood pressure, from these studies it has been suggested that essential hypertension contains a large genetic influence. [13] Supporting data has emerged from animal studies as well as clinical studies in human populations.The majority 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.However, the genetic influence upon hypertension is not fully understood at the moment. It is believed that linking hypertension-realted phenotypes with specific variations of the genome may yeild definitive evidence of heritability. [14]

Another view is that hypertension can be caused by mutations in single genes, inherited on a mendelian basis.[15]

[edit] Age

Hypertension can also be age related, if this is the case it is likely to be multifactorial. One possible mechanism involves a reduction in vascular complicance due to the stiffening of the arteries. This can build up due to isolated systolic hypertension with a widened pulse pressure. A decrease in glomerular filtration rate is related to aging and this results in decreasing efficiency of sodium excretion. The developing of certain diseases such as renal microvascular disease and capillary rarefaction may relate to this decrease in efficiency of sodium excretion. There is experimental evidence that suggests that renal microvascular disease is an important mechanism for inducing slat-sensitive hypertension.[16]

[edit] Vitamin D

It has been suggested, as a result of several studies, that vitamin D deficiency is associated with cardiovascular risk factors. It has been observered that individuals with a vitamin D deficiency have higher systolic and diastolic blood pressures than average. Vitamin D inhibits renin secretion and its activity, it therefore acts as a “negative endocrine regulator of the renin-angiotensin system”. Hence a deficancy in vitamin D leads to an increase in renin secretion. This is one possible mechanism of explaining the observed link between hypertension and vitamin D levels in the blood plasma. [17]

[edit] Secondary hypertension

Secondary hypertension results from an identifiable cause. With treatment of the underlying cause, secondary hypertension can resolve without the need for anti-hypertensive medications.

[edit] Sleep apnea

Sleep apnea is a common, under-recognized cause of hypertension.[18] It is often best treated with nocturnal nasal continuous positive airway pressure, but other approaches include the Mandibular advancement splint (MAS), UPPP, tonsilectomy, adenoidectomy, septoplasty, or weight loss.

[edit] Liquorice

Consumption of liquorice (which can be of potent strength in liquorice candy) can lead to a surge in blood pressure.[19] People with hypertension or history of cardio-vascular disease should avoid liquorice raising their blood pressure to risky levels. Frequently, if liquorice is the cause of the high blood pressure, a low blood level of potassium will also be present.

Liquorice extracts are present in many medicines (for example cough syrups, throat lozenges and peptic ulcer treatments).

[edit] 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 / angiotension system.

[edit] 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.

[edit] Cushing's syndrome

Cushing's syndrome is a condition where both adrenal glands can overproduce the hormone cortisol. 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).

[edit] Coarctation of the aorta

The congenital abnormality aortic coarctation can result in hypertension.

[edit] Drugs

Certain medications, especially NSAIDs (Motrin/Ibuprofen) and steroids can cause hypertension. 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.[20]

[edit] Rebound hypertension

High blood pressure that is associated with the sudden withdrawal of various antihypertensive medications. The increases in blood pressure may result in blood pressures greater than when the medication was initiated. Depending on the severity of the increase in blood pressure, rebound hypertension may result in a hypertensive emergency. Rebound hypertension is avoided by gradually reducing the dose (also known as "dose tapering"), thereby giving the body enough time to adjust to reduction in dose.

Medications commonly associated with rebound hypertension include centrally-acting antihypertensive agents, such as clonidine and beta-blockers.

[edit] Apparent mineralocorticoid excess syndrome

autosomal recessive disorder results from mutations in gene encoding 11β-hydroxysteroid dehydrogenase which normal patient inactivates circulating cortisol to the less-active metabolite cortisone. Cortisol at high concentrations can cross-react and activate the mineralocorticoid receptor, leading to aldosterone-like effects in the kidney, causing hypertension.

[edit] Glucocorticoid remediable aldosteronism

is an autosomal dominant disorder in which the increase in aldosterone secretion produced by ACTH is no longer transient, causing of primary hyperaldosteronism, the Gene mutated will result in an aldosterone synthase that is ACTH-sensitive, which is normally not.

[edit] Polycystic kidney disease

is a cystic genetic disorder of the kidneys, PKD is characterized by the presence of multiple cysts (hence, "polycystic") in both kidneys, can also damage the liver, pancreas, and rarely, the heart and brain. It can be autosomal dominant or autosomal recessive, with the autosomal dominant form being more common and characterized by progressive cyst development and bilaterally enlarged kidneys with multiple cysts, with concurrent development of hypertension, renal insufficiency and renal pain.

[edit] 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.

[edit] Pathophysiology

Most of the mechanisms associated with secondary hypertension are generally fully understood. 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:

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.[21][22][23]

[edit] Diagnosis

[edit] Measuring blood pressure

Main article: 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.[24]

For instance, measurements in control of hypertension should be at least 1 hour after caffeine, 30 minutes after smoking or strenuous exercise and without any stress. Cuff size is also important. The bladder should encircle and cover two-thirds of the length of the (upper) arm. The patient should be sitting upright in a chair with both feet flat on the floor for a minimum of five minutes prior to taking a reading. 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.[25] Routine measurements done in medical offices of patients with known hypertension may incorrectly diagnose 20% of patients with uncontrolled hypertension[26]

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[27] 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."

Some home blood pressure monitoring devices also make use of blood pressure charting software. These charting methods provide printouts for the patient's physician and reminders to take a blood pressure reading. However, a simple and cheap way is simply to manually record values with pen and paper, which can then be inspected by a doctor.

Systolic hypertension is defined as an elevated systolic blood pressure. If systolic blood pressure is elevated with a normal diastolic blood pressure, it is called isolated systolic hypertension. Systolic hypertension may be due to reduced compliance of the aorta with increasing age.[28]

[edit] 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.

[edit] 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:

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.

[edit] Prevention

The degree to which hypertension can be prevented depends on a number of features including: current blood pressure level, changes in end/target organs (retina, kidney, heart - among others), risk factors for cardiovascular diseases and the age at presentation. Unless the presenting patient has very severe hypertension, there should be a relatively prolonged assessment period within which should be repeated measurements of blood pressure. Following this, lifestyle advice and non-pharmacological options should be offered to the patient, before any initiation of drug therapy.

The process of managing hypertension according the the guidelines of the British Hypertension Society suggest that non-pharmacological options should be explored in all patients who are hypertensive or pre-hypertensive. These measures include;

  • Weight reduction and regular aerobic exercise (e.g., walking) are recommended as the first steps in treating mild to moderate hypertension. Regular exercise improves blood flow and helps to reduce resting heart rate and blood pressure.[30] Several studies indicate that low intensity exercise may be more effective in lowering blood pressure than higher intensity exercise.[31] 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 dietary sugar intake
  • Reducing sodium (salt) in the diet may be effective: It decreases blood pressure in about 33% of people (see above). Many people 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 has been shown to be effective based on research sponsored by the National Heart, Lung, and Blood Institute.[32] 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 use and alcohol consumption has been shown to lower blood pressure. The exact mechanisms are not fully understood, but blood pressure (especially systolic) always transiently increases following alcohol 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.
  • Reducing stress, for example with relaxation therapy, such as meditation and other mindbody relaxation techniques,[33] by reducing environmental stress such as high sound levels and over-illumination can be an additional method of ameliorating hypertension. Jacobson's Progressive Muscle Relaxation and biofeedback are also used,[34] particularly, device-guided paced breathing,[35][36] although meta-analysis suggests it is not effective unless combined with other relaxation techniques.[37]

[edit] Treatment

Main article: Antihypertensive

Unless hypertension is severe, lifestyle changes such as those discussed in the preceding section are strongly recommended before initiation of drug therapy. Adoption of the DASH diet is one example of lifestyle change repeatedly shown to effectively lower mildly-elevated blood pressure. If hypertension is high enough to justify immediate use of medications, lifestyle changes are initiated concomitantly.

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 id="cite_ref-37" class="reference">[38] 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:

[edit] Choice of initial medication

Unless the blood pressure is severely elevated, consensus guidelines call for medically-supervised lifestyle changes and observation before recommending initiation of drug therapy. All drug treatments have side effects, and while the evidence of benefit at higher blood pressures is overwhelming, drug trials to lower moderately-elevated blood pressure have failed to reduce overall death rates.

If lifestyle changes are ineffective or the presenting blood pressure is critical, then drug therapy is initiated, often requiring more than one agent to effective lower hypertension. Which type of many medications should be used initially for hypertension has been the subject of several large studies and various national guidelines.

The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study showed better cost-effectiveness and slightly better outcomes for the thiazide diuretic chlortalidone compared with a calcium channel blocker and an ACE inhibitor in a 33,357-member ethnically mixed study group.[41] The 1993 consensus recommendation for use of thiazide diuretics as initial treatment stems in part from the ALLHAT study results, which concluded in 2002 that "Thiazide-type diuretics are superior in preventing 1 or more major forms of CVD and are less expensive. They should be preferred for first-step antihypertensive therapy."[41]

A subsequent smaller study (ANBP2) did not show the slight advantages in thiazide diuretic outcomes observed in the ALLHAT study, and actually showed slightly better outcomes for ACE-inhibitors in older white male patients.[42]

Thiazide diuretics are effective, recommended as the best first-line drug for hypertension by many experts, and much more affordable than other therapies, yet they are not prescribed as often as some newer drugs. Arguably, this is partly because they are off-patent, less profitable, and thus rarely promoted by the drug industry.[43]

The consensus recommendations of thiazide diuretics as first-line therapy for hypertension stand against the backdrop that all blood pressure treatments have side-effects. Potentially serious side effects of the thiazide diuretics include hypercholesterolemia, and impaired glucose tolerance with consequent increased risk of developing Diabetes mellitus type 2. The thiazide diuretics also deplete circulating potassium unless combined with a potassium-sparing diuretic or supplemental potassium. On this basis, the consensus recommendations to prefer use of thiazides as first line treatment for essential hypertension have been repeatedly and strongly questioned.[44][45][46] However as the Merck Manual of Geriatrics notes, "thiazide-type diuretics are especially safe and effective in the elderly."[47]

[edit] Prognosis

It is based upon several factors including genetics, dietary habits, and overall lifestyle choices. If an individual conscious of their condition takes the necessary preventative measures to lower their blood pressure, they are more likely to have a much better outcome than someone who does not.

[edit] Complications

Diagram illustrating the main complications of persistent high blood pressure.

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:

[edit] 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.

[edit] 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.[48]

[edit] History

Sushruta (6th century BCE) explained hypertension in a manner which matches the modern symptoms of the disease.[49]

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