Evaluation of Hypertension

Hypertension represents one of the most common, yet most eminently treatable of the major cardiovascular risk factors. As such, its detection, evaluation, and treatment are primary care priorities. This chapter focuses on its diagnosis and evaluation (see Chapter 14 for Screening and Chapter 26 for Management). Encountering an elevated blood pressure necessitates confirming the diagnosis, ruling out secondary causes, determining disease severity and degree of targetorgan damage, and stratifying for total cardiovascular risk (which helps guide therapy).

DEFINITION AND CLASSIFICATION OF HYPERTENSION (1,2)

Classification

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 last report, JNC VII, it continued to recommend eliminating the traditional designations of “mild,” “moderate,” and “severe” hypertension to avoid the misleading notion that mild hypertension is not a significant health risk. Instead, they designate three stages:

Prehypertension: DBP 80 to 89 mm Hg, systolic blood pressure (SBP) 120 to 139 mm Hg
Stage 1: DBP 90 to 99 mm Hg, SBP 140 to 159 mm Hg
Stage 2: DBP 100 mm Hg or greater, SBP 160 mm Hg or greater

Prehypertension is designated to highlight both the increased risk of developing sustained hypertension in this group and the increased risk of cardiovascular complications. This is especially true for those with diabetes, the obese, and African Americans (Table 19-1).

PATHOPHYSIOLOGY AND CLINICAL PRESENTATION (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21)

Pathophysiology

Control of blood pressure and the pathophysiology of “essential” hypertension (no detectible secondary cause) are still incompletely understood, but the interactions of polygenic mechanisms and environment appear to play major roles. An expression of such inherited defects in blood pressure regulation is the strong familial predisposition to essential hypertension that is observed. Mechanistic subtypes are likely as are several abnormal mechanisms 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, but several elements of blood pressure control deserve elaboration and provide a rational basis for evaluation and treatment.

Selected Mechanisms of Blood Pressure Control and Their Role in Hypertension

The primary determinants of blood pressure are cardiac output and total peripheral resistance. Each is affected in turn by a variety of factors, which have multiple control points (Fig. 19-1).

TABLE 19-1 Classification of Blood Pressure for Adults Aged 18 Years and Older

Category		Systolic (mm Hg)	Diastolic (mm Hg)
Normal^a		<130	<85
High normal		130-139	85-89
Hypertension^b
	Stage 1 (mild)	140-159	90-99
	Stage 2 (moderate)	160-179	100-109
	Stage 3 (severe)	>180	>110
Criteria represent individuals not taking antihypertensive drugs and not acutely ill. When systolic and diastolic pressures fall into different categories, the higher category should be selected to classify the individual’s blood pressure status. For instance, 160/92 mm Hg should be classified as stage 2, and 180/120 mm Hg should be classified as stage 4. Isolated systolic hypertension is defined as a SBP of ≥140 mm Hg and a DBP of <90 mm Hg and staged appropriately (e.g., 170/85 mm Hg is defined as stage 2 isolated systolic hypertension). In addition to classifying stages of hypertension on the basis of average blood pressure levels, the clinician should specify the presence or absence of target-organ disease and additional risk factors. For example, a patient with diabetes and a blood pressure of 142/94 mm Hg plus LVH should be classified as having “stage 1 hypertension with target-organ disease (LVH) and with another major risk factor (diabetes).” This specificity is important for risk classification and management.
^aOptimal blood pressure with respect to cardiovascular risk is <120 mm Hg systolic and <80 mm Hg diastolic. However, unusually low readings should be evaluated for clinical significance. ^bBased on the average of two or more readings taken at each of two or more visits after an initial screening.
From The Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure. Sixth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). Arch Intern Med 1997;157:2413, with permission. Copyright© 1997 American Medical Association. All rights reserved.

Figure 19-1 Factors involved in the control of blood pressure. (From Kaplan NM. Clinical hypertension. 5th ed. Baltimore, MD: Williams & Wilkins, 1990:57, with permission. Copyright © 1990 Wolters Kluwer Health.)

Defects in Excretion of Excess Sodium.

The kidney plays a major role through its handling of salt and water excretion; many, if not all, hypertensive individuals have some degree of salt sensitivity, with an inherited defect in the ability to excrete excess sodium. This leads to an increase in intravascular volume that is corrected by an as-yet unidentified factor—the putative “natriuretic hormone”—that inhibits the Na⁺-K⁺-ATPase pump. The net result is an increase in intracellular sodium, which raises free intracellular calcium. The rise in intracellular calcium heightens vascular tone and elevates blood pressure. Natriuresis is effected at the cost of a higher resting blood pressure. In addition, in salt-sensitive patients, a high sodium intake has been associated with higher levels of and increased responsiveness to norepinephrine. Saltsensitive hypertension might also be induced by subtle renal injury caused by excess angiotensin II or excess catecholamines.

Sympathetic Hyperactivity.

Catecholamines affect blood pressure regulation both centrally via the vasomotor centers in the brain and peripherally through the action of the sympathetic nervous system, increasing peripheral resistance and cardiac output. As noted, excessive responsiveness to norepinephrine and increased levels are seen in persons with sodium retention. In borderline hypertension, there are subgroups with a defect in autonomic control that results in excessive sympathetic and reduced parasympathetic activity. An exaggerated pressor response to external stressful stimuli has been demonstrated in some hypertensive patients and in their normotensive offspring. Also described are “hyperkinetic” hypertensive patients, who are generally young and present with tachycardia and elevated cardiac output; their hypertension may reflect the interaction of an underlying predisposition and various environmental stimuli. The hypertension associated with pheochromocytoma provides a model for secondary hypertension due to excessive catecholamine production.

Psychosocial Factors.

Type A personality, depression, and anxiety are commonly thought to increase risk of hypertension (presumably through autonomic effects). However, under study conditions, time urgency, impatience, and hostility better correlate in dose-response fashion with the long-term risk than do achievement striving, competitiveness, anxiety, and depression.

Renin-Angiotensin-Aldosterone System.

Renin is normally secreted by the kidney’ s juxtaglomerular apparatus in response to decreased intravascular volume, decreased perfusion pressure, β-adrenergic stimulation, or hypokalemia. It acts on angiotensinogen (a decapeptide produced in the liver) to form angiotensin I, which is converted in the lung by angiotensin-converting enzyme (ACE) to angiotensin II, a potent vasoconstrictor. Angiotensin II also acts on the adrenal cortex to release aldosterone, which increases sodium and water reabsorption in the nephron’ s distal tubule, raising intravascular volume.

Renin.

The precise pathophysiologic role of renin in hypertension appears to be far more complex than was initially thought and much remains to be understood, but in patients with primary hypertension, about 15% have a high renin level, the remainder showing normal or low levels. Renin may be inappropriately high in some hypertensive patients, perhaps due to a defect in adrenal cortical responsiveness to angiotensin II, chronically elevating aldosterone production, sodium retention, and intravascular volume. Most patients with renovascular hypertension due to fibromuscular hyperplasia manifest elevated renin levels, but not necessarily those with renal artery stenosis due to atherosclerotic disease. There are also local renin-angiotensin systems within the brain, heart, kidney, endothelium, and placenta, which may play a significant role in the development of hypertension and in some of its consequences.

Angiotensin.

Angiotensin II may also contribute to the adverse effects of hypertension through its deleterious effects on cardiac muscle and vessel walls, where it is a potent stimulus to inflammation and fibrosis. It also interferes with nitric oxide-dependent vascular dilation and probably plays a role in the development of arteriolar dysfunction and hypertrophy, which can increase peripheral resistance.

Aldosterone.

A proportion of patients with hypertension has levels of aldosterone that, while still in the physiologic range, are higher than those predicted for the level of blood pressure. Offspring of patients with hypertension who have higher physiologic levels of aldosterone have been shown to have a higher risk of developing hypertension.

Nitric Oxide Deficiency and Oxidative Stress.

Deficiency of nitric oxide (which has a role in normal endothelial vasodilation) is being explored as a cause of hypertension. Increased oxidative stress by enhanced production of superoxides and inhibition of nitric oxide could be a mechanism by which minor elevations in plasma renin and angiotensin II result in sustained hypertension.

Hyperinsulinism.

The increased frequency of hypertension in patients with type 2 diabetes has stimulated search for a common mechanistic link. Hyperinsulinemia is associated with
increased plasma catecholamines and renal sodium reabsorption. Insulin also enhances the pressor responses to angiotensin II and serves as a potent growth factor for vascular smooth muscle, increasing peripheral resistance. Insulin levels are higher in obese, nondiabetic hypertensive individuals than in their normotensive counterparts, suggesting a mechanistic link between obesity and hypertension. Relative insulin resistance has also been identified in nonobese, hypertensive patients and in nonhypertensive, nonobese offspring of hypertensive parents, suggesting that elevated insulin levels may also occur as a consequence of a genetic defect.

Calcium.

Increased intracellular calcium appears to increase vascular tone. Alteration in calcium binding at the cellular level may lead to increased levels of free intracellular calcium with a resultant increase in vascular tone.

Alteration of Cell Membrane Function.

A variety of abnormalities in cellular sodium transport has been demonstrated to occur in some hypertensive patients. These include the Na⁺-Li⁺ countertransport system, the Na⁺-H⁺ exchange, the Na⁺-K⁺ ATPase pump, and the Na⁺-K⁺-Cl^– cotransport systems, among many others. The result of these abnormal transport systems is to increase intracellular sodium.

Clinical Presentations

Primary or “Essential” Hypertension

Primary or “essential” hypertension accounts for at least 95% of cases. Onset is usually between ages 30 and 50 years, except for isolated systolic hypertension, which is typically a disease of the persons over the age of 60 years. As noted, a family history of hypertension can often be elicited. For almost all patients, onset is gradual and at the stage 1 level at the time of diagnosis. Patients with uncomplicated disease are asymptomatic. Some patients report fatigue, headache, light-headedness, flushing, or epistaxis, but the correlation between symptoms and blood pressure is poor, except in patients with dangerous elevations in pressure. Most patients remain asymptomatic unless end-organ damage develops, leading to symptoms of congestive failure, renal failure, cerebrovascular insufficiency, peripheral vascular disease, or ischemic heart disease.

Malignant hypertension, in which DBP rises rapidly above 130 mm Hg, is a rare form of primary hypertension, accompanied by manifestations of increased intracranial pressure (restlessness, confusion, somnolence, blurred vision, nausea, vomiting, blurred disc margins, retinal hemorrhages—hypertensive encephalopathy) and heart failure (dyspnea, rales, third heart sound).

Labile Hypertension and “White-Coat” Hypertension

Labile hypertension denotes blood pressure that intermittently rises above normal levels. It often progresses to sustained hypertension and confers increased cardiovascular risk. The “white-coat” variety is characterized by blood pressure determinations that persistently exceed 140/90 mm Hg in the doctor’s office but not on home measurement or ambulatory monitoring. Persons who manifest this condition typically have SBP and DBP at least 10 mm Hg greater in the office than at home or at work. Systolic pressure is especially elevated. Although cardiovascular risk is less than that for persons with sustained hypertension, it appears that white-coat hypertension might not be as benign as originally believed; the risk of stroke increases after 6 years, as does the risk of left ventricular remodeling and transition to sustained hypertension.

Pseudohypertension

Pseudohypertension occurs in elderly persons with very stiff brachial arteries secondary to fibrosis and atherosclerotic change. The vessel walls resist compression by the blood pressure cuff, resulting in very high sphygmomanometer readings for systolic pressure, which markedly exceed the true intra-arterial pressure and simulate severe hypertension. Suggestive of the condition is the absence of target-organ changes (no retinopathy, ventricular hypertrophy, nephropathy). Osler’s maneuver (inflating the cuff above the measured SBP and seeing whether a nonpulsatile radial artery can be palpated) is purported to be helpful in confirming the condition, but its efficacy is unproven.

Pseudorefractory Hypertension

Pseudorefractory hypertension, a form of apparently refractory disease, has been described in patients who manifest a marked vasoconstrictor response to blood pressure determinations performed with an arm cuff. Their predominant elevation is in DBP, compared with the white-coat hypertensive patient, who responds with a rise in SBP. Such patients are apt to be mistaken for truly refractory hypertensive individuals because pressures may remain elevated both in the office and at home. The tipoff to this condition is the absence of end-organ damage (e.g., normal fundi, normal cardiac ultrasound) despite the apparent persistence of hypertension.

Secondary Hypertension

These forms of hypertension have definable etiologies (Table 19-2), occur within a wide age range, and are often abrupt in onset and severe in magnitude; family history is commonly negative.

Renal Artery Stenosis.

Most renal artery stenosis occurs in the context of systemic atherosclerotic disease, manifested not only by the onset or worsening of hypertension, but also by signs and symptoms of atherosclerotic disease elsewhere (e.g., femoral or carotid bruit, angina, intermittent claudication). It may be heralded by a renal bruit, abrupt onset or worsening of hypertension, or refractoriness to treatment (despite a three-drug medical regimen). It may occur in association with renal insufficiency, with rising creatinine in the setting of good blood pressure control, or secondary to the use of ACE inhibitors (when disease is bilateral). “Flash pulmonary edema” in the patient with reasonably preserved left ventricular function may be another presentation. About 10% of cases are due to fibromuscular hyperplasia, an entity most commonly affecting the media of the renal artery and occurring typically in young women with no family history of hypertensive disease who present abruptly with difficult-tocontrol hypertension.

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