The definition of hypertension is somewhat arbitrary because actuarial data show that morbidity and mortality related to complications of hypertension increase almost linearly with increasing levels of either systolic blood pressure (SBP) or diastolic blood pressure (DBP). Hence, no critical level of blood pressure exists beyond which risk becomes highly magnified. In the United States, hypertension is defined as a systolic pressure of 140 mm Hg or greater and a diastolic pressure of 90 mm Hg or greater. Once diagnosed, risk must be further refined for each patient. The risk of hypertension derives not only from the absolute level of blood pressure, but also from the presence or absence of other cardiovascular risk factors. Factors besides hypertension identified by the Framingham Study as significant contributors to cardiovascular risk include cigarette smoking, elevated serum cholesterol, a low high-density-lipoprotein (HDL) cholesterol, glucose intolerance, and electrocardiographic evidence of LVH with strain. In addition, African American race, male gender, and age greater than 50 years need to be taken into account. A patient with borderline hypertension, a moderately elevated serum cholesterol level, and a history of smoking has a fivefold higher risk of incurring cardiovascular disease than a patient with borderline hypertension alone.

The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure (JNC), a national consensus group, has issued several reports that include recommendations of the classification of hypertension. In its most recent report, JNC VII, it continues to recommend eliminating the traditional designations of “mild,” “moderate,” and “severe” hypertension to avoid the misleading notion than mild hypertension is not a significant health risk. Instead, they designate three stages:

Prehypertension is designated to highlight the increased risk of developing sustained hypertension in this group (Table 19.1).

Control of blood pressure and the pathophysiology of hypertension are still incompletely understood. It has become increasingly clear that hypertension is a polygenic disorder with probable variable penetrance and phenotype in which environment may play a modifying role. Thus, it represents a complex interaction of multiple genetic and environmental factors playing varyingly significant roles in particular patients. Because there is a strong familial predisposition to hypertension, much of the pathophysiology is likely to be an expression of inherited defects in the regulation of blood pressure. There are probably several mechanistic subtypes of “primary” hypertension. It is also likely that several abnormal mechanisms are present in any one individual. Although several single-gene mutations have been found, the prevalence of these in the hypertensive population is rare. It is usually not possible to identify specific etiologic mechanisms in a given case. Nonetheless, several elements deserve elaboration and provide a rational basis for evaluation and therapy.

Key items facilitating determination of etiology include age of onset, level at time of onset, family history, medications taken, and response to therapy. Sudden onset at a young age, very high pressure, no family history, and refractoriness to treatment suggest a secondary cause. One also checks for contributing factors (e.g., prior renal disease, salt and alcohol excess, cocaine abuse, and recent weight gain) and reviews medications for agents that may elevate blood pressure or exacerbate hypertension (e.g., amphetamines, oral contraceptives, corticosteroids, excess thyroid hormone, over-the-counter sympathomimetics, and nonsteroidal antiinflammatory drugs [including Cox-2 inhibitors]). Taking note of additional cardiovascular risk factors (e.g., smoking, hypercholesterolemia, diabetes, obesity) and of symptoms or history of cardiovascular disease, heart failure, peripheral vascular disease, or stroke helps to determine overall risk, which is essential to guiding therapy (see Chapter 26).

Awareness of the symptoms associated with secondary etiologies is essential. Complaints such as hirsutism, easy bruising, paroxysms of palpitations and sweats, weakness, muscle cramps, and leg claudication should all suggest a secondary form of hypertension. Other clues to a secondary cause—especially renovascular disease—are onset at the extremes of age, rapid and severe course, and refractoriness to medication (see later discussion).

After a careful determination of the blood pressure (see previous discussion), the remainder of the physical examination focuses on weight and pulse measurements; the skin for stigmata of Cushing's syndrome, chronic renal failure, or neurofibromatosis; fundoscopy for arteriolar narrowing, increased vascular tortuosity, arteriovenous nicking, hemorrhages, or exudates; the thyroid for enlargement or nodularity; carotid pulses for bruits or diminution of pulse; lungs for signs of heart failure; heart for left ventricular lift and S₄ and S₃ heart sounds; peripheral vasculature for pulses, bruits, and abnormalities in bilateral arm and leg pressure measurements and simultaneous radial and femoral pulse palpation; abdomen for masses and bruits; and the neurologic exam for focal deficits.

The laboratory evaluation of high blood pressure has three purposes: (a) to ascertain the degree of end-organ damage resulting from hypertension, (b) to identify patients at high risk for the development of cardiovascular complications, and (c) to screen for secondary possibly reversible forms of the disease.

Despite the wide array of sophisticated diagnostic techniques now readily available, there is increasing evidence that the diagnosis of secondary hypertension can be made accurately and economically by the alert physician on the basis of a careful history, a physical examination, and only a few simple diagnostic tests. Extensive laboratory evaluation of patients with high blood pressure is unwarranted.

Initial studies need include little more than a complete blood count, urinalysis, blood urea nitrogen (BUN), creatinine, potassium, calcium (with albumin), fasting blood sugar, total and high-density lipoprotein cholesterol, and electrocardiogram (ECG). The urinalysis, BUN, and creatinine can provide evidence of primary renal disease (e.g., azotemia, proteinuria, active sediment) and of extent of renal compromise (rise in creatinine). Fasting blood sugar, serum cholesterol, and ECG provide data regarding cardiovascular risk and presence of left atrial enlargement and ventricular hypertrophy. Serum potassium is a valuable screening test for primary aldosteronism and should be known before pharmacologic therapy is instituted. Total cost of these determinations is reasonable. In most patients, evaluation can and should stop here.

More-extensive routine laboratory evaluation of patients with high blood pressure has come under a great deal of criticism. The yield in the absence of clinical evidence for a secondary cause is low, and such testing is not cost-effective. It was hoped that renin profiling would help identify the underlying pathophysiology in patients with primary disease, guide workup for secondary causes, and rationalize selection of therapy. However, the renin assay continues to suffer from difficulties with accuracy and reliability, except in certain research laboratories. Moreover, most hypertensives have normal renin levels, undermining the value of widespread testing. Finally, when renin profiling has been used to guide choice of therapy, benefit has been hard to demonstrate.

Echocardiography for detection of LVH has been useful in research studies, with presence of LVH associated with an increased risk of cardiovascular complications. However, its
routine use adds little to the assessment, except in the setting of refractory hypertension, where definitive evidence of end-organ hypertrophy helps one distinguish between true and apparent refractoriness to therapy (see Chapter 26). When the need to search for LVH is less pressing (e.g., in the patient with newly encountered blood pressure elevation), the ECG can provide a reasonable though less sensitive estimate. Of interest, however, is the finding from the Framingham data that the presence of LVH on ECG confers higher risk than that found only on echocardiogram.

Patients at somewhat higher risk for secondary hypertension include those with abrupt onset (especially if female and younger than 35 years of age, without a family history of hypertension, or older than age 50 years and with evidence of diffuse atherosclerosis), with severe hypertension (DBP >110 mm Hg), or with failure to respond to maximum medical therapy despite full compliance. Fortunately, in most patients at high risk for secondary hypertension, a specific diagnosis will be suggested by history and physical examination, supplemented by a few well-chosen laboratory studies (Table 19.2).

Incorporating the findings of the workup for cardiovascular risk factors, clinically overt cardiovascular disease, and target-organ damage into a risk profile helps to guide therapy (see Chapter 26). The most important factors predicting cardiovascular risk include the presence of diabetes mellitus, clinical cardiovascular disease, and target-organ damage. Damage to target organs (manifested by hypertensive retinopathic changes, signs of LVH with remodeling, and proteinuria or renal insufficiency) indicates significant risk of subsequent cardiovascular morbidity and mortality. Similarly, manifestations of overt cardiovascular disease (e.g., angina, claudication, congestive heart failure, stroke, carotid bruit) portend poor outcome if hypertension remains untreated. The JNC VI identifies three risk categories of increasing severity (A, B, and C) based on these determinants, which can be used to guide clinical decision making:

Combining these risk categories with the stage of hypertension provides a rational guide to the urgency of therapy and the intensity of the treatment program (see Chapter 26).