Hypertension

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Hypertension (HTN) or high blood pressure, sometimes called arterial hypertension, is a chronic medical condition in which the blood pressure in the arteries is elevated. Blood pressure is summarised by two measurements, systolic and diastolic, which depend on whether the heart muscle is contracting (systole) or relaxed between beats (diastole). This equals the maximum and minimum pressure, respectively. There are different definitions of the normal range of blood pressure. Normal blood pressure at rest is within the range of 100–140 mmHg systolic (top reading) and 60–90 mmHg diastolic (bottom reading). High blood pressure is said to be present if it is often at or above 140/90 mmHg.

Hypertension is classified as either primary (essential) hypertension or secondary hypertension; about 90–95% of cases are categorized as “primary hypertension” which means high blood pressure with no obvious underlying medical cause.[1] The remaining 5–10% of cases (secondary hypertension) are caused by other conditions that affect the kidneys, arteries, heart or endocrine system.

Hypertension puts strain on the heart, possibly leading to hypertensive heart disease and coronary artery disease.[2] Hypertension is also a major risk factor for stroke, aneurysms of the arteries (e.g. aortic aneurysm), peripheral arterial disease and chronic kidney disease. Dietary and lifestyle changes can improve blood pressure control and decrease the risk of health complications, although drug treatment is still often necessary in people for whom lifestyle changes are not enough or not effective. The treatment of moderately high arterial blood pressure (defined as >160/100 mmHg) with medications is associated an improved life expectancy while treatment of milder elevation is not.

Causes
Primary hypertension
Main article: Essential hypertension
Primary (essential) hypertension is the most common form of hypertension, accounting for 90–95% of all cases of hypertension.[1] In almost all contemporary societies, blood pressure rises with aging and the risk of becoming hypertensive in later life is considerable.[16] Hypertension results from a complex interaction of genes and environmental factors. Numerous common genetic variants with small effects on blood pressure have been identified[17] as well as some rare genetic variants with large effects on blood pressure[18] but the genetic basis of hypertension is still poorly understood. Several environmental factors influence blood pressure. Lifestyle factors that lower blood pressure include reduced dietary salt intake,[19][20] increased consumption of fruits and low fat products (Dietary Approaches to Stop Hypertension (DASH diet)), exercise,[21] weight loss[22] and reduced alcohol intake.[23] Stress appears to play a minor role[6] with specific relaxation techniques not supported by the evidence.[24][25] The possible role of other factors such as caffeine consumption,[26] and vitamin D deficiency[27] are less clear cut. Insulin resistance, which is common in obesity and is a component of syndrome X (or the metabolic syndrome), is also thought to contribute to hypertension.[28] Recent studies have also implicated events in early life (for example low birth weight, maternal smoking and lack of breast feeding) as risk factors for adult essential hypertension,[29] although the mechanisms linking these exposures to adult hypertension remain obscure.[29]

Secondary hypertension
Main article: Secondary hypertension
Secondary hypertension results from an identifiable cause. Renal disease is the most common secondary cause of hypertension.[8] Hypertension can also be caused by endocrine conditions, such as Cushing’s syndrome, hyperthyroidism, hypothyroidism, acromegaly, Conn’s syndrome or hyperaldosteronism, hyperparathyroidism and pheochromocytoma.[8][30] Other causes of secondary hypertension include obesity, sleep apnea, pregnancy, coarctation of the aorta, excessive liquorice consumption and certain prescription medicines, herbal remedies and illegal drugs.

Pathophysiolog

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Main article: Pathophysiology of hypertension

A diagram explaining factors affecting arterial pressure

Illustration depicting the effects of high blood pressure
In most people with established essential (primary) hypertension, increased resistance to blood flow (total peripheral resistance) accounts for the high pressure while cardiac output remains normal.[32] There is evidence that some younger people with prehypertension or ‘borderline hypertension’ have high cardiac output, an elevated heart rate and normal peripheral resistance, termed hyperkinetic borderline hypertension.[33] These individuals develop the typical features of established essential hypertension in later life as their cardiac output falls and peripheral resistance rises with age.[33] Whether this pattern is typical of all people who ultimately develop hypertension is disputed.[34] The increased peripheral resistance in established hypertension is mainly attributable to structural narrowing of small arteries and arterioles,[35] although a reduction in the number or density of capillaries may also contribute.[36] Hypertension is also associated with decreased peripheral venous compliance[37] which may increase venous return, increase cardiac preload and, ultimately, cause diastolic dysfunction. Whether increased active vasoconstriction plays a role in established essential hypertension is unclear.[38]

Pulse pressure (the difference between systolic and diastolic blood pressure) is frequently increased in older people with hypertension. This can mean that systolic pressure is abnormally high, but diastolic pressure may be normal or low — a condition termed isolated systolic hypertension.[39] The high pulse pressure in elderly people with hypertension or isolated systolic hypertension is explained by increased arterial stiffness, which typically accompanies aging and may be exacerbated by high blood pressure.[40]

Many mechanisms have been proposed to account for the rise in peripheral resistance in hypertension. Most evidence implicates either disturbances in renal salt and water handling (particularly abnormalities in the intrarenal renin-angiotensin system)[41] and/or abnormalities of the sympathetic nervous system.[42] These mechanisms are not mutually exclusive and it is likely that both contribute to some extent in most cases of essential hypertension. It has also been suggested that endothelial dysfunction and vascular inflammation may also contribute to increased peripheral resistance and vascular damage in hypertension.[43][44] Interleukin 17 has garnered interest for its role in increasing the production of several other immune system chemical signals thought to be involved in hypertension such as tumor necrosis factor alpha, interleukin 1, interleukin 6, and interleukin 8.

Signs and Symptoms

Hypertension is rarely accompanied by any symptoms, and its identification is usually through screening, or when seeking healthcare for an unrelated problem. A proportion of people with high blood pressure report headaches (particularly at the back of the head and in the morning), as well as lightheadedness, vertigo, tinnitus (buzzing or hissing in the ears), altered vision or fainting episodes.[5] These symptoms, however, might be related to associated anxiety rather than the high blood pressure itself.[6]

On physical examination, hypertension may be suspected on the basis of the presence of hypertensive retinopathy detected by examination of the optic fundus found in the back of the eye using ophthalmoscopy.[7] Classically, the severity of the hypertensive retinopathy changes is graded from grade I–IV, although the milder types may be difficult to distinguish from each other.[7] Ophthalmoscopy findings may also give some indication as to how long a person has been hypertensive.[5]

Secondary hypertension
Main article: Secondary hypertension
Some additional signs and symptoms may suggest secondary hypertension, i.e. hypertension due to an identifiable cause such as kidney diseases or endocrine diseases. For example, truncal obesity, glucose intolerance, moon face, a hump of fat behind the neck/shoulder, and purple stretch marks suggest Cushing’s syndrome.[8] Thyroid disease and acromegaly can also cause hypertension and have characteristic symptoms and signs.[8] An abdominal bruit may be an indicator of renal artery stenosis (a narrowing of the arteries supplying the kidneys), while decreased blood pressure in the lower extremities and/or delayed or absent femoral arterial pulses may indicate aortic coarctation (a narrowing of the aorta shortly after it leaves the heart). Labile or paroxysmal hypertension accompanied by headache, palpitations, pallor, and perspiration should prompt suspicions of pheochromocytoma.[8]

Hypertensive crisis
Main article: Hypertensive emergency
Severely elevated blood pressure (equal to or greater than a systolic 180 or diastolic of 110—sometimes termed malignant or accelerated hypertension) is referred to as a “hypertensive crisis”, as blood pressure at this level confers a high risk of complications. People with blood pressures in this range may have no symptoms, but are more likely to report headaches (22% of cases)[9] and dizziness than the general population.[5] Other symptoms accompanying a hypertensive crisis may include visual deterioration or breathlessness due to heart failure or a general feeling of malaise due to renal failure.[8] Most people with a hypertensive crisis are known to have elevated blood pressure, but additional triggers may have led to a sudden rise.[10]

A “hypertensive emergency”, previously “malignant hypertension”, is diagnosed when there is evidence of direct damage to one or more organs as a result of severely elevated blood pressure greater than 180 systolic or 120 diastolic.[11] This may include hypertensive encephalopathy, caused by brain swelling and dysfunction, and characterized by headaches and an altered level of consciousness (confusion or drowsiness). Retinal papilloedema and/or fundal hemorrhages and exudates are another sign of target organ damage. Chest pain may indicate heart muscle damage (which may progress to myocardial infarction) or sometimes aortic dissection, the tearing of the inner wall of the aorta. Breathlessness, cough, and the expectoration of blood-stained sputum are characteristic signs of pulmonary edema, the swelling of lung tissue due to left ventricular failure an inability of the left ventricle of the heart to adequately pump blood from the lungs into the arterial system.[10] Rapid deterioration of kidney function (acute kidney injury) and microangiopathic hemolytic anemia (destruction of blood cells) may also occur.[10] In these situations, rapid reduction of the blood pressure is mandated to stop ongoing organ damage.[10] In contrast there is no evidence that blood pressure needs to be lowered rapidly in hypertensive urgencies where there is no evidence of target organ damage and over aggressive reduction of blood pressure is not without risks.[8] Use of oral medications to lower the BP gradually over 24 to 48h is advocated in hypertensive urgencies.[10]

Pregnancy
Main article: Gestational hypertension
Hypertension occurs in approximately 8–10% of pregnancies.[8] Two blood pressure measurements six hours apart of greater than 140/90 mm Hg is considered diagnostic of hypertension in pregnancy.[12] Most women with hypertension in pregnancy have pre-existing primary hypertension, but high blood pressure in pregnancy may be the first sign of pre-eclampsia, a serious condition of the second half of pregnancy and puerperium.[8] Pre-eclampsia is characterised by increased blood pressure and the presence of protein in the urine.[8] It occurs in about 5% of pregnancies and is responsible for approximately 16% of all maternal deaths globally.[8] Pre-eclampsia also doubles the risk of perinatal mortality.[8] Usually there are no symptoms in pre-eclampsia and it is detected by routine screening. When symptoms of pre-eclampsia occur the most common are headache, visual disturbance (often “flashing lights”), vomiting, epigastric pain, and edema. Pre-eclampsia can occasionally progress to a life-threatening condition called eclampsia, which is a hypertensive emergency and has several serious complications including vision loss, cerebral edema, seizures or convulsions, renal failure, pulmonary edema, and disseminated intravascular coagulation (a blood clotting disorder).[8][13]

Children
Failure to thrive, seizures, irritability, lack of energy, and difficulty breathing[14] can be associated with hypertension in neonates and young infants. In older infants and children, hypertension can cause headache, unexplained irritability, fatigue, failure to thrive, blurred vision, nosebleeds, and facial paralysis

Lifestyle modifications
The first line of treatment for hypertension is identical to the recommended preventive lifestyle changes[69] and includes dietary changes,[70] physical exercise, and weight loss. These have all been shown to significantly reduce blood pressure in people with hypertension.[71] Their potential effectiveness is similar to and at times exceeds a single medication.[59] If hypertension is high enough to justify immediate use of medications, lifestyle changes are still recommended in conjunction with medication.

Dietary change such as a low sodium diet is beneficial. A long term (more than 4 weeks) low sodium diet is effective in reducing blood pressure, both in people with hypertension and in people with normal blood pressure.[72] Also, the DASH diet, a diet rich in nuts, whole grains, fish, poultry, fruits and vegetables lowers blood pressure. A major feature of the plan is limiting intake of sodium, although the diet is also rich in potassium, magnesium, calcium, as well as protein.[73] Some programs aimed to reduce psychological stress such as biofeedback or transcendental meditation may be reasonable add-ons to other treatment to reduce hypertension. However several techniques such as yoga, relaxation and other forms of meditation do not appear to reduce blood pressure,[74] and, of the techniques with supportive evidence, there is limited information on whether the modest reduction in blood pressure results in prevention of cardiovascular disease.[74]

Several exercise regimes—including isometric resistance exercise, aerobic exercise, resistance exercise and device-guided breathing—may be useful in reducing blood pressure.[74]

Medications
See also: Comparison of international blood pressure guidelines
Several classes of medications, collectively referred to as antihypertensive drugs, are available for treating hypertension. Use should take into account the person’s cardiovascular risk (including risk of myocardial infarction and stroke) as well as blood pressure readings, in order to gain a more accurate picture of the person’s risks.[75] Benefit of medications is related to a person’s cardiac disease risk.[76] Evidence in those with mild hypertension (SBP less than 160 mmHg and /or DBP less than 100 mmHg) and no other health problems does not support a reduction in the risk of death or rate of health complications from medication treatment.[77] Medications are not recommended for people with prehypertension or high normal blood pressure.[59]

If drug treatment is initiated the Joint National Committee on High Blood Pressure (JNC-7)[58] recommends that the physician not only monitor for response to treatment but should also assess for any side effects resulting from the medication. Reduction of the blood pressure by 5 mmHg can decrease the risk of stroke by 34%, of ischaemic heart disease by 21%, and reduce the likelihood of dementia, heart failure, and mortality from cardiovascular disease.[78] For most people, recommendations are to reduce blood pressure to less than or equal to somewhere between 140/90 mmHg to 160/100 mmHg.[75][79] Attempting to achieve lower levels have not been shown to improve outcomes[79] while there is evidence that it increases side effects.[80] In those with diabetes or kidney disease some recommend levels below 120/80 mmHg;[75][81] however, evidence does not support these lower levels.[79][82] If the blood pressure goal is not met, a change in treatment should be made as therapeutic inertia is a clear impediment to blood pressure control.[83]

The best first line agent is disputed.[84] The Cochrane collaboration, World Health Organization and the United States guidelines supports low dose thiazide-based diuretic as first line treatment.[71][84][85][86] The UK guidelines emphasise calcium channel blockers (CCB) in preference for people over the age of 55 years or if of African or Caribbean family origin, with angiotensin converting enzyme inhibitors (ACE-I) used first line for younger people.[87] In Japan starting with any one of six classes of medications including: CCB, ACEI/ARB, thiazide diuretics, beta-blockers, and alpha-blockers is deemed reasonable, while in Canada and Europe all of these but alpha-blockers are recommended as options.[59][84] When compared to placebo and other anti-hypertensive drugs as first-line therapy for hypertension, beta-blockers have greater benefit in stroke reduction, but no difference on coronary heart disease or all-cause mortality.[88] However, three-quarters of active beta-blocker treatment in the randomised controlled trials included in the review were with atenolol and none with the newer vasodilating beta-blockers.[89]

Drug combinations
The majority of people require more than one drug to control their hypertension. In those with a systolic blood pressure greater than 160 mmHg or a diastolic blood pressure greater than 100 mmHg the American Heart Association recommends starting both a thiazide and an ACEI, ARB or CCB.[71] An ACEI and CCB combination can be used as well.[71]

Unacceptable combinations are non-dihydropyridine calcium blockers (such as verapamil or diltiazem) and beta-blockers, dual renin–angiotensin system blockade (e.g. angiotensin converting enzyme inhibitor + angiotensin receptor blocker), renin–angiotensin system blockers and beta-blockers, beta-blockers and centrally acting agents.[90] Combinations of an ACE-inhibitor or angiotensin II–receptor antagonist, a diuretic and an NSAID (including selective COX-2 inhibitors and non-prescribed drugs such as ibuprofen) should be avoided whenever possible due to a high documented risk of acute renal failure. The combination is known colloquially as a “triple whammy” in the Australian health industry.[69] Tablets containing fixed combinations of two classes of drugs are available and while convenient for the people, may be best reserved for those who have been established on the individual components.[91]

Elderly
Treating moderate to severe hypertension decreases death rates and cardiovascular morbidity and mortality in people aged 60 and older.[92] There are limited studies of people over 80 years old but a recent review concluded that antihypertensive treatment reduced cardiovascular deaths and disease, but did not significantly reduce total death rates.[92] The recommended BP goal is advised as

Resistant hypertension
Resistant hypertension is defined as hypertension that remains above goal blood pressure in spite of using, at once, three antihypertensive agents belonging to different drug classes. Guidelines for treating resistant hypertension have been published in the UK[94] and US.[95] It has been proposed that a proportion of resistant hypertension may be the result of chronic high activity of the autonomic nervous system; this concept is known as “neurogenic hypertension”.[96] Low adherence to treatment is an important causes of resistant hypertension.[97]

Prevention

Much of the disease burden of high blood pressure is experienced by people who are not labelled as hypertensive.[61] Consequently, population strategies are required to reduce the consequences of high blood pressure and reduce the need for antihypertensive drug therapy. Lifestyle changes are recommended to lower blood pressure, before starting drug therapy. The 2004 British Hypertension Society guidelines[61] proposed the following lifestyle changes consistent with those outlined by the US National High BP Education Program in 2002[68] for the primary prevention of hypertension:

maintain normal body weight for adults (e.g. body mass index 20–25 kg/m2)
reduce dietary sodium intake to engage in regular aerobic physical activity such as brisk walking (≥30 min per day, most days of the week)
limit alcohol consumption to no more than 3 units/day in men and no more than 2 units/day in women
consume a diet rich in fruit and vegetables (e.g. at least five portions per day);
Effective lifestyle modification may lower blood pressure as much as an individual antihypertensive drug. Combinations of two or more lifestyle modifications can achieve even better results.

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