Hypertension

Etiology of Essential Hypertension

Environment

A number of environmental factors have been implicated in the development of hypertension, including salt intake, obesity, occupation, alcohol intake, family size, stimulant intake, excessive noise exposure, and crowding.

Salt Sensitivity

Sodium is the environmental factor that has received the greatest attention. It is to be noted that approximately 60% of the essential hypertension population is responsive to sodium intake.

Insulin Resistance

Insulin is a polypeptide hormone secreted by the pancreas. Its main purpose is to regulate the levels of glucose in the body, it also has some other effects. 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. It is best treated with weight loss and nocturnal nasal positive airway pressure.

Genetics

Hypertension is one of the most common complex genetic disorders, with genetic heritability averaging 30%. 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 multi-factorial 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.

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 above.

Etiology of Secondary Hypertension

Only in a small minority of patients with elevated arterial pressure can a specific cause be identified. These individuals will probably have an endocrine or renal defect that if corrected would bring blood pressure back to normal values.

Renal Hypertension

Hypertension produced by diseases of the kidney. A simple explanation for renal vascular hypertension is 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.
In patients with pheochromocytoma increased secretion of catecholamine 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).

Hypercalcemia

Coarctation of the Aorta.

Diet

Certain medications, especially NSAIDS (Motrin/ibupofen) and steroids can cause hypertension. Ingestion of imported licorice (Glycyrrhiza glabra) can cause secondary hypoaldosteronism, which itself is a cause of hypertension.

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.

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.
  Is 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.

Signs and Symptoms

Hypertension is usually found incidentally - "case finding" - by healthcare professionals. It normally produces no symptoms.

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.

It is recognized that stressful situations can increase the blood pressure;

Hypertension is often confused with mental tension, stress and anxiety. While chronic anxiety is associated with poor outcomes in people with hypertension, it alone does not cause it.

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

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.

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.

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. 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. Routine measurements done in medical offices of patients with known hypertension may incorrectly diagnose 20% of patients with uncontrolled hypertension.

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 90% 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.
• In hypertensive children most cases are secondary hypertension, and the cause should be pursued diligently.

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

Doctors recommend weight loss and regular exercise as the first steps in treating mild to moderate hypertension. These steps are highly effective in reducing blood pressure, although most patients with moderate or severe hypertension end up requiring indefinite drug therapy to bring their blood pressure down to a safe level. Discontinuing smoking does not directly reduce blood pressure, but is very important for people with hypertension because it reduces the risk of many dangerous outcomes of hypertension, such as stroke and heart attack. An increase in daily calcium intake has also been shown to be highly effective in reducing blood pressure.

Mild hypertension is usually treated by diet, exercise and improved physical fitness. A diet rich in fruits and vegetables and low fat or fat-free dairy foods and moderate or low in sodium lowers blood pressure in people with hypertension. This diet is known as the DASH diet (Dietary Approaches to Stop Hypertension), and is based on National Institutes of Health sponsored research. Dietary sodium (salt) may worsen hypertension in some people and reducing salt intake decreases blood pressure in a third of people. Regular mild exercise improves blood flow, and helps to lower blood pressure. In addition, fruits, vegetables, and nuts have the added benefit of increasing dietary Potassium, which offsets the effect of sodium and acts on the kidney to decrease blood pressure.

Reduction of environmental stressors such as high sound levels and over-illumination can be an additional method of ameliorating hypertension. Biofeedback is also used particularly device guided paced breathing.

Medications

There are many classes of medications for treating hypertension, together called antihypertensive, 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). 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, 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®)
• Calcium channel blockers such as amlodipine (Norvasc®), diltiazem, verapamil
• Diuretics: eg, bendroflumethiazide, chlortalidone, hydrochlorothiazide (also called HCTZ)
• Finally combination products (which usually contain HCTZ and one other drug)

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

The ALLHAT study showed a slightly better outcome and cost-effectiveness for the thiazide diuretic chlortalidone compared to anti-hypertensive. 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 male patients.

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. Although 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. 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.