Hypertension is one of the greatest health problems facing industrialized nations and continues to be a major contributing factor in the development of, and death from CAD, stroke, heart failure, and renal failure. Because uncomplicated hyper-tension is an asymptomatic condition, many people are un-aware that they have it. Campaigns by national medical orga-nizations have raised public awareness, and the mass screening of patients has resulted in an increased recognition of the prob-lem so that now only an estimated 30 % of patients with hyper-tension are unaware of their diagnosis. This has contributed to significant decreases in the rates of death from stroke and coro-nary artery disease (CAD). Nonetheless, and only 50 % of pa-tients with hypertension are on therapy, and only 30% have their blood pressure controlled to ideal levels. Because of the asymptomatic nature of this disease (at least until complica-tions develop) and the frequent side effects associated with

treatment, initiation of medical therapy and continued compli-ance with a treatment regimen is an ongoing challenge.

As currently defined, systemic hypertension is present in an adult (age18) if the systolic blood pressure is greater than or equal to 140mm Hg or the diastolic blood pressure is greater than or equal to 90 mm Hg. According to this definition, an estimated 50 million adult Americans have hypertension. This is a somewhat arbitrary definition in that it is not derived from any pathophysiologic data but, rather, from an analysis of the range of pressures in the population and the risks of associated morbidity and mortality. Nonetheless, the current definitions make clinical sense because the longterm risk of cardiovascular morbidity and mortality clearly rises in direct relation to in-creases in systemic blood pressure.

Hypertension can be further classified into various stages reflecting mild, moderate, or severe elevations in blood pres-sure (Table 13). When there is a discrepancy between the classification of the systolic and diastolic blood pressures, the higher category should be used to classify the patient's hyper-tension. The diagnosis of hypertension is generally not based on a single elevated blood pressure measurement; rather, it re-flects a pattern of elevated blood pressure, with abnormally high values obtained on at least three separate occasions. The normal blood pressure in children and pregnant women is slightly lower, although care must be taken in making the for-mal diagnosis of hypertension in children and adolescents be-cause the blood pressure frequently normalizes in adulthood.

The incidence of hypertension increases with age and is more common in African-Americans than in whites. It is more common in younger men than in women, although this differ-ence does not exist after the age of 55 and is reversed after the age of 75. Despite advances in the treatment of hypertension, much is still unknown regarding the etiology of the disease. In 90% to 95 % of patients, no identifiable cause of the hyperten-sion is found and the patients are said to have primary or essen-tial hypertension. Familial patterns of primary hypertension are common and suggest that genetic factors are important. However, environmental factors, such as obesity, alcohol con-sumption, sedentary lifestyle, and salt intake, likely play a role. Proposed pathophysiologic mechanisms include excessive renal sodium retention, overactivity of the sympathetic nervous system reninangiotensin excess, hyperinsulinemia, and alter-ations in vascular endothelium. This last mechanism may re-sult from a decrease in endothelium-derived vasorelaxing sub-stances (e. g. nitric oxide) or an increase in endothelium-de-rived constricting factors (e. g. , endothelin). Several of these factors may be present in a given individual and may mediate the hypertensive response through alterations in eirculating blood volume, constriction of vascular smooth muscle, and/or vascular hypertrophy. In approximately 5% of hypertensive patients, the elevated blood pressure is the direct result of an-other disorder (Table 14).

Evaluation of the Hypertensive Aptient

The initial evaluation of a patient with hypertension should include a thorough history and physical examination and limited laboratory studies. The goals of this evaluation are to assess the patient for the presence and extent of hypertensive target organ damage, identify clinical factors that may influ-ence the choice of therapy (e. g. , renal failure, heart failure), determine the presence of other cardiovascular risk factors, and recognize the occasional patient with a secondary, and there-fore potentially reversible, cause of hypertension. Hyperten-sion itself is rarely symptomatic, although symptoms possibly attributable to the elevated blood pressure include headaches (usually occipital ), blurred vision, fatigue, dizziness, epis-taxis, dyspnea, and chest pain. In secondary hypertension, specific symptoms may develop that give clues to the underly-ing cause of the elevated blood pressure. Examples include weakness, polyuria, and muscle cramps caused by hypokalemia in primary hyperaldosteronism; weight gain and emotional la-bility in Cushing' s syndrome; and headaches, palpitations, and hyperhidrosis in patients with pheochromocytoma. With chronic or severe hypertension, symptoms of organ damage may be present and include symptoms of congestive heart fail-ure, CAD, cerebrovascular disease, uremia, and aortic dissec-tion. Other historical features of importance include a history of alcohol use, prescription or nonprescription drug use (e. g. , 0ral contraceptives, anabolic steroids), dietary sodium intake, and a family history of hypertension.

After confirming the presence of hypertension, the physi-cal examination should focus on recognizing evidence of end-0r-gan damage. The blood pressure and pulse should be checked in both arms and compared with the pressure in the legs to ex-clude the diagnosis of aortic coarctation. The fundoscopic ex-amination should be carefully performed because it allows di-rect visual assessment of the extent of vascular injury and clas-sification of the severity of hypertensive disease based on reti-nal changes (hypertensive retinopathy). "AV nicking" and "copper wire changes" in the arterioles characterize mild (grade I and ]I )retinopathy, whereas retinal hemorrhages and exudates (grade 1]I ) and papilledema (grade 1g ) reflect severe and potentially life-threatening disease. Evidence of left ventricular enlargement or failure should be noted. A thorough vascular examination should identify the presence of carotid or peripheral vascular disease, and abdominal bruits (reflecting possible renal artery stenosis) should be listened for carefully. A neurologic examination should be performed to search for ev-idence of prior strokes.

Initial laboratory screening should include serum elec-trolytes to identify potential metabolic disorders associated with secondary causes of hypertension. Measures of renal function (blood urea nitrogen and creatinine levels )and the urinalysis should be evaluated, because abnormalities in renal function may reflect either primary renal disease as a cause of the hyper-tension or secondary renal disease as a result of primary hyper-tension. Assessment of the serum glucose and fasting lipid lev-els are helpful in identifying other cardiovascular risk factors. An electrocardiogram should be obtained and evaluated for evi-dence of left ventricular hypertrophy or prior myocardial in-farction. Echocardiography may be useful in selected patients to assess further the effects of hypertension on the heart.

Extreme elevations of blood pressure[ > 26.6kPa(200mm Hg) systolic and/or > 16.0kPa(120mm Hg) diastolic] may occa-sionally be noted in asymptomatic patients. These patients are considered to have accelerated hypertension or hypertensive ur-gency and require the institution of antihypertensive therapy aimed at lowering the blood pressure over the course of several hours to several days. These elevated pressures, however, are often associated with symptoms of acute end-organ damage. Confusion, visual changes, seizures, headaches, and papillede-ma may occur as manifestations of hypertensive en-cephalopathy. Death may occur as a result of intracranial bleeding. Unstable angina, acute myocardial infarction, or left ventricular failure may be precipitated by profound hyperten-sion. Hypertensive glomerulonephritis may result in protein-uria, hematuria, and acute renal failure. When these acute complications are present, patients are considered to have ma-lignant hypertension or a hypertensive emergency. These pa-tients require hospital admission and therapy aimed at immedi-ate blood pressure reduction. Acute organ damage may resolve after aggressive treatment of the hypertension.

Secondary Causes of Hypertension

In approximately 5 % of patients, a secondary cause of the hypertension can be found. Clinical features help to identify these patients, for whom a more extensive search for the etiol-ogy is warranted. Certain historical and physical examination findings (as described earlier) may point to a specific diagno-sis. Patients with new-onset hypertension who are younger than the age of 30 or older than the age of 55 have a greater likelihood of having a reversible underlying cause. Patients with poorly controlled blood pressure, despite multiple antihy-pertensive medications, and those with previously well-con-trolled hypertension who develop a sudden increase in their blood pressure also require further evaluation. Several factors may contribute to failure of adequate blood pressure control de-spite a multidrug treatment regimen. Probably the most com-mon reason for failure is medical noncompliance. Increased di-etary sodium intake may aggravate hypertension, and a variety of drugs may interfere with the effectiveness of antihyperten-sive medications. These include oral contraceptive agents, cor-ticosteroids, nonsteroidal anti-inflammatory drugs, and over-the-counter cold remedies containing ephedrine or sympath-omimetics. These factors must be excluded before embarking on an extensive work-up for secondary causes of hypertension.

Renovascular Hypertension

Renovascular hypertension accounts for 1% to 2 % of cas-es of hypertension and is the most common secondary form of the disease. The pathophysiology of renovascular hypertension relates to a hemodynamically significant stenosis of the renal artery. The consequent decrease in renal blood flow stimulates an increase in renin release from the underperfused kidney and subsequently results in the increased production of angiotensin II. Angiotensin ]l is a potent vasoconstrictor and also stimu-lates the release of aldosterone from the adrenal gland, result-ing in sodium and water retention and expansion of the in-travascular volume. Both of these effects result in elevated blood pressure. The renal artery stenosis usually results from one of two processes: atherosclerotic renal artery disease or fi-bromuscular dysplasia. Atherosclerotic renal artery stenosis usually affects the proximal aspect of the renal artery and is most common in older men. Fibromuscular dysplasia results in fibrosis and aneurysm formation of the mid and distal renal ar-teries and is most common in younger women. Both these pro-cesses are bilateral in more than 50 % of cases. Several clinical clues should raise the suspicion of renovascular hypertension. These include the sudden development of severe hypertension in a patient without a family history of hypertension, drug-re-sistant hypertension, the presence of diffuse atherosclerotic vascular disease or an abdominal bruit, and renal insufficiency in the setting of severe hypertension. Worsening of renal func-tion after institution of an angiotensin-converting enzyme (ACE) inhibitor is also a common clue to the presence of bilat-eral renal artery stenosis.

The diagnosis can be made using functional or anatomic studies. Plasma renin activity can be measured, and, if low, essentially excludes the diagnosis. If renin activity is normal or high, documentation of an increase in activity after administra-tion of an ACE inhibitor is diagnostic. Nuclear renal scan per. formed before and after administration of ACE inhibitors also yields characteristic results. Ultrasonography may demonstrate a decreased size of the affected kidney. Definitive anatomic di-agnosis is made by angiography, although advances in magnet. ie resonance angiography have made this a valuable noninvasive diagnostic technique. Treatment of renovascular hypertension involves eliminating the stenosis by surgical or percutaneous (ballon angioplasty) techniques.