CHAPTER 25: DIAGNOSIS AND TREATMENT OF HYPERTENSION

Hypertension, elevated systemic arterial pressure, is a recognized risk factor and cause of fatal and nonfatal cardiovascular and renal disease that has become a public health problem worldwide.^1,2 Furthermore, treatment of hypertension with widely available antihypertensive drugs is highly effective for long-term prevention of cardiovascular disease, as demonstrated in well-controlled randomized clinical trials.³ Of the most common risk factors for premature cardiovascular mortality, the reduction of hypertension-through effective treatment-has been predicted to have the greatest preventive effect globally over the next decade.⁴

The diagnosis of hypertension has, in the past, been based on measurements in the office or clinic. Clinic blood pressures have been the basis for assessing response to treatment in the large randomized clinical trials that have provided the evidence for establishing the effectiveness of antihypertensive drug treatment. However, the development of technologies for accurate measurement of arterial pressure outside the clinic and during usual activity, through 24-hour ambulatory blood pressure monitoring and home blood pressure assessment, has led to expansion of the terms used to define hypertension. Table 25–1 provides current classification of hypertensive disorders as recommended in recent guidelines.

Based on clinic measurements alone, patients may be classified by the height of the pressure: optimal or normal pressure, prehypertension overlapping with high-normal pressure, and definite hypertension. The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) further subdivided definite hypertension into stage I, 140–159/90–99 mm Hg, and stage II, more than 160/100 mm Hg.⁵ The panel report for JNC 8 suggested that, for older patients, a cutoff of 150 mm Hg systolic pressure was more consistent with evidence from clinical trials.⁶ This conclusion has been questioned and remains controversial, however.⁷ Results from two recently conducted studies, Systolic Blood Pressure Intervention Trial (SPRINT) and Secondary Prevention of Small Subcortical Strokes (SPS3), may influence selection of lower thresholds for defining hypertension in future guidelines.^8,9 Although the terms prehypertension and hypertension are widely used, it is important to recognize that that they can misrepresent the risk associated with a verbal diagnosis compared with the risk associated with a given level of pressure. The risk of a systolic pressure of 139 mm Hg is the same as that for 141 mm Hg, yet the former may be labeled as “prehypertension” and the latter as “hypertension.”

With the introduction and implementation of 24-hour ambulatory blood pressure monitoring and systematic home blood pressure monitoring have come the recognition that blood pressure measured out of the office/clinic may differ substantially from office/clinic pressure. White coat hypertension and masked hypertension are now widely recognized and confer different predictions for future cardiovascular risk.¹⁰ The risk of white coat hypertension is nearly that of normal blood pressure, but the risk of masked hypertension is nearly or equal to that of sustained hypertension (elevated pressure both in and out of the clinic).¹¹ The importance of out-of-office blood pressures for accurate prognosis is now supported by several national and international guidelines.^12,13,14,15

Prevalence

National and international surveys indicate that hypertension is highly prevalent in adult populations throughout the world and is increasing in relation to increased overweight and, all too often, reduced daily exercise. In the United States, the prevalence of hypertension has been nearly constant, at about 30%, over the past several years, as recorded in National Health and Nutrition Examination Survey (NHANES) results. However, awareness, treatment, and control have steadily increased, although they may be reaching a plateau (Fig. 25–1).¹⁶ In a recent survey, hypertension prevalence was similar in adult men and women (~ 25%), but higher in black (self identified African Americans; ~ 40%) than white (~ 25%) groups. Hypertension in children may be increasing due to higher rates of overweight,¹⁷ and underdiagnosed based on age-related criteria.¹⁸ Young adults with higher and increasing blood pressures may be at greater risk for eventual cardiovascular disease, as indicated by coronary artery calcification.¹⁹ These considerations imply that despite higher detection rates, hypertension will continue to be a major challenge for effective prevention of cardiovascular disease in the United States in the next decades.

Consequences of Hypertension: Pathology

Hypertension is the direct or contributing cause of a wide range of cardiovascular and renal pathology. Stroke, “brain attacks”, can result from cerebral hemorrhage or thromboembolism with brain infarction. The source of emboli may be the carotid arteries, aorta, or cardiac thrombi. Intracerebral arteriosclerosis may also be the cause of cerebral infarction. Coronary artery disease with myocardial infarction is all too common in hypertensive patients, who often have the presence of other coronary risk factors. Multiple infarcts may lead to congestive heart failure with low ejection fraction (systolic heart failure). The increased left ventricular afterload of sustained hypertension induces left ventricular hypertrophy with reduced compliance and the syndrome of heart failure with preserved systolic function.²⁰ This syndrome may result in repeated episodes of pulmonary congestion; bilateral renal artery stenosis should be considered as well in this setting.²¹ Left ventricular hypertrophy adds a burden to left atrial contraction. Dilation of this chamber is a risk factor for atrial fibrillation, for which hypertension is a known risk factor.^22,23

Hypertension contributes to atherosclerosis in many arteries: the carotid arteries, aorta, renal arteries, and peripheral arteries. Hypertension, usually when sustained at very high pressures, is linked to aortic dissection. Hypertension also participates in the formation of atherosclerotic aortic aneurysms.

Renal pathology due to hypertension (nephrosclerosis) may occur alone, but often accompanies the chronic renal disease diabetic nephropathy.

Cardiovascular Risk of Hypertension and Benefit of Treatment

Follow-up surveys relating eventual cardiovascular disease with initial or baseline measurement of blood pressure have invariably shown a high degree of correlation between level of pressure and future disease-related events for untreated patients.¹ The benefit of antihypertensive drug treatment has now been firmly established by randomized clinical trials that have been summarized in meta-analyses and other studies.^24,25 The relative benefit of blood pressure reduction appears to be similar, irrespective of the pretreatment level of pressure. However, the absolute benefit (eg, in the number needed to treat to prevent a single event) varies widely, being much lower in persons with higher pressure and risk than in the many individuals with minimal elevations of pressure and overall lower cardiovascular risk profiles.²⁶ Neither age nor choice of antihypertensive drug class affects the relative benefit of antihypertensive treatment.²⁷

Recent clinical trials and meta-analyses have focused on goals of treatment to be achieved by antihypertensive drug therapy for maximum benefit. Is less than 140/90 mm Hg sufficient or is a lower goal (< 120 mm Hg) achievable and beneficial? For nondiabetic hypertensive patients, the SPRINT trial provides compelling evidence that lower is better. The usual goal group had a baseline systolic pressure of 140 mm Hg that fell to 136 mm Hg after 1 year. The intensive treatment group, with a similar baseline systolic pressure had a fall to 121 mm Hg with a highly significant 25% reduction in the primary outcome, a 27% reduction in death from any cause, and a 43% reduction in cardiovascular deaths (Fig. 25–2).⁸ In the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, designed similarly to SPRINT, no significant benefit was observed in the primary outcome for the low-goal cohort of diabetic hypertensive patients, which had an on-treatment systolic pressure of 119 mm Hg, compared to the usual-goal cohort, which had 1-year pressure of 134 mm Hg. However, in subgroup analysis, stroke rate was 47% (P < .01) lower in the low-goal group.²⁸ Furthermore, the low-goal group of ACCORD had a significant 13% (P = .02) reduction in new atrial fibrillation or new atrial P-wave abnormalities compared to the usual-goal group.²⁹ The SPS3 trial compared the usual (130 to 139 mm Hg) and a low (< 130 mm Hg) systolic pressure goal in hypertensive participants included because of a recent lacunar stroke. The primary event rate (stroke) for the lower goal target was 19% (P = .08) lower than for the usual-care group.⁹ The optimal on-treatment blood pressure for prevention of a second stroke was 120–129/65–70 mm Hg, with higher rates above and below this range.³⁰ The results of these recent trials are highly likely to be influential in the development of new guidelines for treatment of hypertension.

Most hypertensive patients are initially identified during office or clinic visits when seen for checkups or nonemergent symptoms. Some are found at community screening programs and then referred for medical assessment. Hypertension is mostly a silent disorder. The goals for initial evaluation are:

• Estimating the average blood pressure

• Considering the overall cardiovascular risk status

• Determining presence or absence of target organ pathology

• Some assessment for identifiable hypertension

• Beginning the process of education that will lead to the patient’s recognition and collaboration in long-term reduction in risk (ie, adherence and prevention)

Hypertensive emergencies will be dealt with separately in a later section. This section will focus on those examinations and tests performed for outpatients (Table 25–2).

Medical History

A careful and well-focused medical history is the foundation for initial appraisal of the five goals stated above. For overall cardiovascular risk, use of tobacco and presence or absence of diabetes and/or lipid status are crucial. Target organ status includes assessment of neurologic function for history of stroke or transient ischemic attacks, cardiac and coronary artery disease (ie, angina or dyspnea), renal function, and symptoms of peripheral vascular disease (claudication). Clues to presence of identifiable disease may be detected: symptoms of sleep apnea syndrome or rare disorders suggested by unusual symptoms or family history. The initial history can be the setting of discussion about lifestyle issues of exercise and diet as well as considering value of antihypertensive drug treatment. Use of one of the many now available risk estimators may aid in portraying the patient’s potential for future cardiovascular disease.³¹

Physical Examination

The physical examination provides a risk profile of its own, with measurement of weight and height and calculation of body mass index. Waist circumference is helpful as a clue to the metabolic syndrome. Target organ pathology may be revealed if there are carotid bruits or signs of peripheral artery disease. The chest examination may be abnormal because of signs of congestion or effusion. Cardiac auscultation can be useful for signs of left ventricular hypertrophy, abnormal rhythm, or heart failure. Diminished peripheral pulses indicate peripheral arterial occlusive disease. Clues to identifiable hypertension, such as abdominal bruit or signs of endocrine disease, may be detected. Neurologic status with regard to signs of a previous stroke is important.

Blood Pressure Measurement: Clinic

Clinic blood pressures should be as accurate and unbiased as possible.³² Patients should be seated comfortably. An appropriate cuff size is necessary; large adult cuffs are mandatory for most large or obese patients. There is growing recognition that automated devices, such as the BpTRU Omron or Welch Allyn units, are more likely to be accurate when compared to the stethoscope and hand-inflated cuff.^33,34 Furthermore, automated devices can take multiple readings. Some record measurements and transmit them to the electronic record system. Often the first measurement is higher than subsequent ones, so that several pressures are needed to establish the average.³⁵ Blood pressures should be taken in both arms when seated, also in the standing position, especially in older patients and in those with dizziness, to unmask orthostatic hypotension.³⁶

Blood Pressure: Central Aortic Pressure

Brachial artery pressures are measured using the upper arm cuff and a sensor that detects sounds (auscultation) or pulse waves, oscillometry.³² Brachial artery pressures fail to duplicate central aortic pressures, which are closer to intracarotid and renal artery pressures (those arteries nearest to the brain, heart, and kidneys, which are the target organs for hypertension-related cardiovascular disease). Central aortic pressures can only be measured directly by aortic catheterization. However, indirect methods have been developed that rely on mathematical models of the brachial pressure waveform transformed to estimated central aortic pressure. Cross-sectional studies suggest that central aortic pressures correlate better with target organ damage than brachial artery pressures.³⁷ Some recommend that use of central aortic pressure estimation be expanded for use in both the initial and subsequent evaluation of hypertensive patients. Those with lower central aortic pressures than brachial pressures during treatment may require less medication for control of their hypertension.³⁸ Whether measurement of central aortic pressure will be valuable for predicting benefit in reduction of event-based outcomes in randomized trials is uncertain at this time.

Blood Pressure Measurement: Out-of-Office—Ambulatory and Home Monitoring

Ambulatory blood pressure measurement, a noninvasive fully automated technique in which multiple blood pressure measurements are recorded over an extended period (typically 24 hours), has gained acceptance in several national and international guidelines.^12,13,14,39 Prospective studies have documented that the average level of ambulatory blood pressure predicts risk of morbid events better than clinic blood pressure.⁴⁰ Normal 24-hour ambulatory blood pressure values for adults (nonpregnant) are less than 130/80 mm Hg (< 135/85 mm Hg when awake during the day and < 120/75 mm Hg, when sleeping, during the night).⁴¹ The normal fall in systolic and diastolic pressure during sleep is 10% to 20%. Those with a normal nocturnal fall have been labeled “dippers,” and those with either no fall or an increase in pressure during sleep are labeled as “nondippers” or “reverse dippers.”

Ambulatory blood pressure monitoring is valuable for determining whether the patient’s usual pressure, in “real life,” is either higher or lower than the clinic pressure. When the clinic pressure is high, but ambulatory pressure is normal, the diagnosis of white coat hypertension (or white coat effect) can be made (see Table 25–1). The risk of future cardiovascular events in people with white coat hypertension is nearly the same as in those with normal pressure but may be slightly higher when the clinic pressure is in the high normal range.^42,43 Trials have not yet established to determine whether antihypertensive treatment of white coat hypertension is beneficial. Prognosis is best related to nocturnal average pressures. Dippers have a better outlook than nondippers.

Normal or high normal pressures measured in the clinic may not accurately predict out-of-office pressures. Masked hypertension refers to the finding that either ambulatory or home pressures are elevated, despite normal or high-normal pressures in the clinic. Criteria for masked hypertension are given in Table 25–1. In contrast to white coat hypertension, masked hypertension is associated with increased target organ pathology, notably left ventricular hypertrophy and carotid artery thickening.⁴⁴ Antihypertensive drug therapy is expected to be effective in preventing cardiovascular events, as is the case with sustained hypertension. However, definitive clinical trials for masked hypertension are not yet available.

Home blood pressure monitoring is becoming a more widely used strategy for classification of hypertension and for monitoring response to treatment.⁴⁵ In fact, the first prospective study demonstrating that out-of-office measurement provides superior prediction of cardiovascular disease was performed with a self-recording device that required manual inflation, not suitable for measurements during sleep.⁴⁶ Subsequent studies have confirmed the value of home monitoring.^47,48 Home pressure monitoring has the limitation that nocturnal pressures are not measured. However, the predictive accuracy of home monitoring is superior to that of clinic measurement and nearly that of 24-hour ambulatory monitoring. Devices for home monitoring are now widely available and distributed in several national surveys of developed nations. Some devices are linked to telemetry strategies for transmission to provider’s offices for review and feedback. Home blood pressure monitoring can be combined with self-titration of medication that may reduce the need for unnecessary clinic visits.⁴⁹ This approach is effective in lowering blood pressure compared with usual office-based care.⁵⁰

Use of the Laboratory for Biochemical Testing and Imaging

There is general agreement that in the absence of clues to identifiable hypertension, efficient use and appropriate selection of laboratory resources can be confined to those needed to define cardiovascular risk, target organ pathology and establish a baseline for treatment. The following are suggested:

• Urinalysis

• Multichannel blood test to include serum creatinine, Na, K, HCO₃, calcium, and glucose (fasting)

• Serum lipids: total cholesterol, high-density lipid cholesterol, low-density lipid cholesterol, triglycerides

• Electrocardiogram

The value of echocardiography and nuclear or echo-based exercise stress testing is unclear for asymptomatic hypertensive patients. The results of the above tests combined with blood pressure measurement can be used to calculate a comprehensive risk value using one of the currently available formulas, some of which include C-reactive protein or other biomarkers.³¹

The Search for Identifiable Hypertension

A comprehensive discussion of this spectrum is far beyond the scope of this chapter. What is most important is that clinicians be aware of those forms of identifiable hypertension that are most likely to be found in their practices and the initial findings that suggest their presence. These are summarized in Table 25–4.

After the initial assessment, appropriate follow-up reassessment is crucial. In clinical trials, intervals of 3 to 6 months between clinic visits are often used. However, in ordinary practice, the constraints of travel time, demands of employment, and other responsibilities compete with medical needs. A survey of hypertension care in the United Kingdom found that, for those with clinic pressures of at least 150 mm Hg systolic pressure, increased cardiovascular event rates were related to (1) failure to intensify treatment, (2) delays of more than 1.4 months for intensification, and (3) delays in follow-up of more than 2.7 months after intensification.⁵¹ In general, the higher the blood pressure, the greater the need for shorter intervals between revisits.⁵ Home blood pressure monitoring is becoming widely available, and communication between provider and patient can be achieved by telephone or computer. The development of telemetry/telemedicine as a strategy for management of hypertension is being explored to increase adherence to medication, reduction of blood pressure to goal, and minimizing the need for office or clinic visits.⁴⁹

This section will summarize treatment of arterial hypertension in the clinic, where this therapy is most often prescribed. Such treatment also occurs in the emergency department, where the presentation may be a true hypertensive emergency or, now more often, a life-threatening event,⁵² or one of lesser risk in which hypertension is part of a more complex picture, a hypertensive urgency.

Goals for Treatment

The rationale for treatment of hypertension is to prevent future cardiovascular and renal disease. There are two components to treatment: improvement in lifestyle patterns and prescription of antihypertensive drugs. The minimum goal as reflected in several guidelines has been to achieve clinic pressures of less than 140/90 mm Hg (systolic/diastolic).^5,53 A recent advisory from panel members of the JNC 8 process, on the basis of a conservative examination of trial evidence, accepted a higher goal of less than 150/90 mm Hg for older patients.⁶ This view is controversial and has been criticized as too permissive and could result in failure to treat some who might benefit.^54,55 Publication of the SPRINT trial, for nondiabetic hypertensive patients, provides the basis for a lower goal for systolic pressure—in the range of 120 to 130 mm Hg.⁸ For diabetic hypertensives, best available evidence suggests a goal of about 135 mm Hg systolic pressure.^28,56,57 It is unknown, at present, whether antihypertensive drug treatment will provide effective prevention for those with office/clinic hypertension, but normal pressures outside the office (white coat hypertension) as documented by either 24-hour ambulatory blood pressure monitoring or home pressure monitoring. However, lifestyle improvement is recommended for those who are overweight, underexercised, smoke, or otherwise have risky habits.

Lifestyle Intervention

For those with pretreatment clinic blood pressures in the range of 140 to 150 mm Hg, lifestyle improvement may be effective in achieving the desired goal. Weight reduction, avoiding a high dietary salt intake, adherence to the Dietary Approaches to Stop Hypertension (DASH) diet, and increased exercise may be effective. In 6- to 12-month studies of those with stage 1 hypertension, the DASH diet lowered systolic and diastolic blood pressures, respectively, to 6 to 8 mm Hg and 3 to 4 mm Hg more than controls.⁵⁸ Reduced fat intake may also be beneficial for lowering low-density lipid cholesterol and serum triglycerides.⁵⁹ Smoking cessation, while having no effect on blood pressure, is nonetheless mandatory for cardiovascular prevention.

Antihypertensive Drug Treatment: Overview

The value of antihypertensive drug therapy for prevention of fatal and nonfatal cardiovascular disease has been firmly established by well-controlled randomized clinical trials. At present, there is an abundant array of drug classes to be prescribed to achieve control of hypertension (see Table 25–4). A fairly small fraction of people with hypertension, about 15% to 20%, can be often controlled with a single drug class, as is the case with younger patients. Most with higher average pressures will require two or more drug classes to achieve current goals.

The most effective two-drug combinations consist of a renin-system blocking agent (angiotensin-converting enzyme inhibitor [ACEI] or angiotensin-receptor blocker [ARB]) and a thiazide-type diuretic or a renin system blocker and a calcium channel blocker (CCB). When the two-drug combination is not fully effective, adding the third component will often be successful (ie, renin system blocker, diuretic, and CCB). The benefit of adding a drug class appears to be substantially greater than up-titrating dosage with a single drug class.⁵⁹

Resistant Hypertension

When blood pressure remains above treatment goals, despite combining drugs from three classes, it is referred to as “resistant” hypertension. Despite a substantial increase in control of hypertension in many countries, resistant hypertension still has a prevalence of 20% to 30%.⁶⁰ Frequently, apparent resistant hypertension is caused by a lack of adherence to prescribed medication. This lack may result from a variety of causes, such as limited health knowledge, unavailable primary care facilities, inability to pay, or lack of insurance. A large white coat effect may obscure the much lower average pressures at home, so that pseudo–resistant hypertension is present. Use of 24-hour ambulatory blood pressure monitoring or home pressure monitoring is justified when the white coat effect is suspected. Conversely, out-of-office monitoring of blood pressure may reveal masked hypertension for which more intensive antihypertensive treatment is necessary to prevent target organ pathology.⁶¹

Identifiable hypertension may be present in resistant hypertension, such as bilateral renal artery stenosis or primary aldosteronism.⁶² Treatment of definite resistant hypertension may include maximizing drug doses as well as addition of alternate drug classes and counseling to increase adherence.^60,63 Even when primary aldosteronism is not confirmed, addition of spironolactone may be effective in drug treatment of resistant hypertension.⁶⁴ Minoxidil or high-dose nifedipine has also been shown to be effective for treatment of definite resistant hypertension, if these drugs are tolerated.^65,66

True resistant hypertension conveys increased risk of future cardiovascular disease leading to exploration of interventional modalities: baroreflex activation therapy (BAT)⁶⁷ and bilateral renal denervation (RDN).⁶⁸ BAT requires neck surgery with planting of stimulating electrodes on the right, left, or both carotid sinus nerves. Substantial reduction in blood pressure has been reported in small series. At this time, it remains a research intervention with an uncertain future because of the small size of series and practical considerations.⁶⁹ RDN has been extensively evaluated in uncontrolled series and in randomized trials compared to sham procedures. Results have been inconsistent. Meta-analyses of RDN compared to various comparison groups in trials and a large registry have reported that RDN was not significantly more effective than use of antihypertensive drug treatment in the comparison groups.^70,71 RDN is approved for treatment of resistant hypertension in some countries, but health authorities in the United States, Canada, and the United Kingdom consider the procedure to be a research intervention.

Hypertensive Emergencies

A hypertensive emergency is defined by rapid increase in blood pressure linked to an immediate threat to target organs: aortic dissection, pulmonary congestion, symptomatic coronary heart disease, progressive renal disease, stroke, or encephalopathy.^52,72 A distinct form of cerebral edema, posterior leukoencephalopathy, has been associated with hypertensive emergencies explaining the encephalopathy that may cause loss of vision, altered mental status, and seizures.⁷³ Although there is no blood pressure threshold for the diagnosis of hypertensive emergencies, most end-organ damage is noted with systolic blood pressures exceeding 220 mm Hg or diastolic blood pressures exceeding 120 mm Hg. The condition is usually related to a rapid increase in pressure from already high levels in established hypertension, perhaps related in poor adherence to antihypertensive medications. However, abrupt increases in pressure with threat to target organs may appear without prior warning as in some patients with pheochromocytoma or some forms of renal disease (eg, scleroderma renal crisis). The medical history should include queries about use of nonsteroidal anti-inflammatory drugs (NSAIDs), alcohol, and substance use. Alcohol withdrawal syndromes may mimic hypertensive encephalopathy. Cocaine or diet pill overdose may raise pressure quickly and even cause cerebral hemorrhage. In hypertensive emergencies in these patients, immediate but monitored reduction of pressure, often accomplished with parenteral medications, is essential to prevent long-term damage.

In addition to very high arterial pressure, people with hypertensive emergencies may have signs of (1) increased intracranial pressure (papilledema, retinal hemorrhages, and exudates), (2) aortic dissection, and (3) pulmonary congestion. The electrocardiogram may show left ventricular enlargement, and the chest x-ray will indicate congestion. Often, renal function will be impaired with proteinuria and microscopic hematuria.

Patients with a hypertensive emergency must be treated in an emergency department or intensive care unit with rapid-acting, controllable medications and continued monitoring to achieve reduction in arterial pressure until stable or the immediate threat is dealt with (eg, proximal aortic dissection requiring surgery). Intravenous medications are usually required to reduce pressure to the range of 150–160/less than 110 mm Hg within a few hours. The medications described below should be considered for intravenous use in achieving the therapeutic goal. Once blood pressure reduction to a safe range has been achieved, patients can be transitioned to oral medications, usually two- or three-drug combinations. Close follow-up and adjustment of medications in the clinic are necessary to achieve long-term control of hypertension in patients admitted for hypertensive emergencies, regardless of the cause.

Sodium nitroprusside is the drug of choice for most hypertensive emergencies because it has an immediate onset of action and can be titrated quickly and accurately. The duration of effect is 1 to 2 minutes. Thiocyanate levels must be followed in patients who have hepatic or renal insufficiency to prevent toxic buildup.

Parenteral labetalol is another first-line agent for hypertensive emergency. Its onset of action is 5 to 10 minutes, and the duration of action is about 3 to 6 hours. Labetalol can be used safely in most patients, but caution should be exercised in patients who have severe bradycardia, congestive heart failure, or bronchospasm.

Nicardipine is a dihydropyridine CCB administered parenterally by continuous infusion for hypertensive crises. The onset of action of this drug is 5 to 10 minutes, and the duration of action is 1 to 4 hours after discontinuing the infusion. Nicardipine is contraindicated in patients with heart failure.

Esmolol is a cardioselective β-blocker with a short duration of action. It reduces systolic blood pressure and mean arterial pressure, as well as heart rate, cardiac output, and stroke volume. There is a notable decrease in myocardial oxygen consumption. Peak effects are generally seen within 6 to 10 minutes after a bolus dose, and the effects resolve 20 minutes after discontinuing the infusion.

Fenoldopam is the first selective dopamine-1 receptor agonist approved for in-hospital short-term management of severe hypertension up to the first 48 hours of treatment. Fenoldopam is a good choice in these patients because of the improvement in renal perfusion, diuresis, and lack of production of toxic metabolites. Tolerance develops to fenoldopam after 48 hours.

Phentolamine is available for intravenous use and is an alpha-receptor adrenergic antagonist that is valuable for treating a hypertensive emergency in patients with pheochromocytoma. When tachycardia occurs in this setting, a rapid beta-blocker, such as esmolol or intravenous metoprolol, can be given to control heart rate.

Intravenous nitroglycerine may be considered when the clinical picture indicates significant myocardial ischemia. This is used as a temporizing step in stabilizing a patient who will most often be prepared for a cardiac intervention.

Intravenous furosemide, a rapidly acting loop diuretic, may be useful in management of acute pulmonary congestion associated with severe hypertension. Duration of action is short, a few hours, so that repeated dosing may be needed.

Hypertensive Urgencies

A hypertensive urgency is defined as the presence of a very high blood pressure (eg, > 180/110 mm Hg) in the absence of the characteristics of a hypertensive emergency, as described above. Although the blood pressure may be markedly elevated, the major problem can be another critical medical event, such as myocardial ischemia or stroke.⁷² Some may seek emergency care because of high pressures, without any associated symptoms. The increased use of home blood pressure monitoring may account, in part, for this emerging pattern. The role of anxiety or pain in those patients without cardiac or cerebrovascular disease needs study. In the absence of other medical problems that require emergency care, immediate management of hypertensive urgencies is problematic. Often, without specific treatment, blood pressure will fall substantially and patients can be discharged from the emergency department within a few hours. The role of antihypertensive medication for hypertensive emergencies is entirely uncertain with regard to future risk. Although several drugs may rapidly lower pressure, there is a risk of hypotension as well. When the patient is asymptomatic and clinically stable, outpatient management with close follow-up is appropriate. Long-term blood pressure control is essential, but the reduction can be achieved over a period of weeks. Patient education to achieve understanding of the real risk of elevated blood pressure, value of daily medication, and periodic follow-up is crucial because those with hypertensive urgencies are at greater risk for long-term cardiovascular pathology.⁷⁴

Properties of Antihypertensive Drug Classes

This section will provide an overview and concise description of the currently used antihypertensive drug classes.

Diuretic Drugs

Thiazide-Type Diuretics

The thiazides and related drugs (eg, chlorthalidone, indapamide) have been the mainstay of antihypertensive drug treatment since the 1960s as single agents or in effective two-drug combinations together with (1) potassium-sparing diuretics and (2) beta-receptor blockers, ACEIs, and ARBs. Adverse reactions to these drugs are well characterized, the most frequent being hypokalemia and elevated uric acid. The latter may be a cause of gout. Hypercalcemia may occur with thiazide diuretics and might result from underlying hyperparathyroidism. Chlorthalidone was used in several of the early clinical trials; it has the advantage of a longer duration of action compared to hydrochlorothiazide and may be slightly more effective, but it is also more likely to elicit hypokalemia.⁷⁵

Potassium-Sparing Diuretics

The two available mineralocorticoid receptor antagonists, spironolactone and eplerenone, may be valuable for treatment of primary aldosteronism or for thiazide-related hypokalemia. When renal function is normal, these drugs infrequently cause hyperkalemia at usual doses. Spironolactone has been found to be effective for resistant hypertension, often in combination with several other drugs, including renin system blockers (ACEIs, ARBs, or direct renin antagonists). In this setting, careful monitoring for hyperkalemia is necessary.⁷⁶

Amiloride and triamterene block the sodium epithelial channel of the distal renal tubule. This channel mediates the action of aldosterone, so that these agents can also correct the hypokalemia of thiazide-type diuretics. They have very little effect on blood pressure.

Loop-Active Diuretics

Furosemide, bumetanide, torsemide, and ethacrynic acid are diuretics whose site of action is proximal to the thiazide site. They are more effective than thiazides when renal function is impaired. Their adverse reactions are similar to those of the thiazides, except for the lack of hypercalcemia. In general, the loop diuretics are preferred in the presence of congestive heart failure. The unique feature of ethacrynic acid is the lack of a sulfur group, so that it may be used for those infrequent patients with allergic reactions to both the thiazides and furosemide. The loop diuretics are often given together with renin system blockers for effective combinations in those with reduced glomerular filtration rates. Combining a loop diuretic with a thiazide-type diuretic (eg, furosemide and metolazone) may be effective for refractory edema, but very close monitoring for hypokalemia or hyponatremia is required.⁷⁷

Renin System Blockers

The differences in the effects of the renin system blockers is important when testing the renin system for identifiable hypertension. Blockade of the renin system with two or three drugs is not recommended because of the risk of hyperkalemia and lower glomerular filtration rate.^83,84

Angiotensin-Converting Enzyme Inhibitors

The ACEIs were the first renin system blockers to become widely used antihypertensive drugs, most often in combination with thiazide-type diuretics. This combination is highly effective for sustained reduction in blood pressure and usually well tolerated. The ACEIs are also kininase inhibitors that may account for characteristic adverse effects: dry cough (5%–10%) and rare occurrence of urticarial angioedema reactions (swelling of the lips or tongue) that can be fatal. When used in renal disease with proteinuria, most often diabetic nephropathy, ACEIs reduce urinary protein excretion and may retard progression of renal impairment. Similarly, ACEIs may be beneficial for retardation of renal impairment in African Americans with chronic renal disease.⁷⁸ ACEIs, like all renin system blockers, may reduce aldosterone secretion when the renin-angiotensin-aldosterone system is normal but not when primary aldosteronism is present.

Angiotensin II Receptor Antagonists

The ARBs block the angiotensin II type 1 receptor that mediates vasoconstriction by vascular smooth muscle and also stimulation of adrenal aldosterone production. The effects of ARBs are similar to those of the ACEIs except that kinin potention is absent. Cough with use of ARBs is not different from placebo administration in controlled blinded trials or when ARBs are given to patients with ACEI cough.^79,80 An ARB has been shown to significantly lower blood pressure in prehypertensives for a year, preventing new hypertension in comparison with placebo.⁸¹ At the end of the trial, most people had an increase in pressure to pretreatment levels but some remained at lower levels. A small fraction of hypertensives will have full control of hypertension when taking ARBs, but these drugs are most effective in combination with a thiazide type diuretic or a CCB.

Direct Renin Inhibitors

Aliskiren is a direct-acting renin inhibitor that is an effective antihypertensive agent that, as monotherapy, has a similar effect on blood pressure as an ARB.⁸² Like the other renin system blockers, aliskiren is more effective in combination with either a thiazide diuretic or CCB. ACEIs or ARBs increase plasma renin activity and lower aldosterone in those with normal renin systems. Unlike ACEIs or ARBs, aliskiren reduces the assay of plasma renin activity and serum aldosterone.

Calcium Channel Blockers

Dihydropyridine Calcium Channel Blockers

There are many dihydropyridine calcium channel blockers (DHP CCBs). Several either have prolonged duration of action (eg, amlodipine) or have been formulated in long-acting delivery systems (eg, nifedipine ER), so that they are effective when given once daily. The hemodynamic effect of these agents is to reduce peripheral resistance with minimal reflex increase in heart rate—and with minimal effects on the renin-angiotensin system. DHP CCBs are widely used and are effective as monotherapy but often combined with renin system blocker for greater effectiveness (eg, benazepril and amlodipine). The first-pass intestinal absorption of CCBs is increased by concurrent intake of grapefruit or natural grape fruit juice; the most effect has been found with felodipine.^85,86,87,88 The increased levels of felodipine may be sufficient to lower blood pressure, a possible adverse effect in elderly patients. The major adverse effect for this class is pedal or ankle edema that can be bothersome and, occasionally, severe. Prolonged use of DHP CCBs may lead to gingival hyperplasia, requiring dental care.

Non–Dihydropyridine Calcium Channel Blockers

Diltiazem and verapamil are like DHP CCBs blockers of the L-channel of smooth muscle and cardiac tissue. They are effective antihypertensive agents, often given together with inhibitors of the renin system. However, their antihypertensive effect overlaps that of the thiazide-type diuretics with little additive potential. These two drugs differ from the DHP CCBs by inhibiting cardiac AV conduction, so can be used for management of supraventricular arrhythmias. They should not be combined with beta-receptor blockers because of the risk of bradycardia. These drugs are usually well tolerated, but they may cause edema. Verapamil can cause bothersome constipation.

Antiadrenergic Drugs Used for Hypertension

Beta-Receptor Blockers

At one time, beta-receptor blockers, especially when combined with thiazide-type diuretics, were a major component of antihypertensive drug treatment and had an important role in several clinical trials. The effectiveness of beta-blockers either as monotherapy or in combination with a diuretic, for prevention of cardiovascular disease in the absence of coronary artery disease (especially for stroke), has been questioned, particularly now that combinations of renin system blockers and either diuretics or CCBs have become available.^89,90 However, the value of beta-blockers for management of coronary heart disease, especially angina, remains well accepted.⁹¹ In general, the most used beta-receptor blockers have a long duration of action, are more selective beta₁-blockers with no beta₂-blocking action, and have no sympathomimetic effect. Beta-receptor blockers combined with alpha-blockers (carvedilol, labetalol) or agents with vasodilator activity (nebivolol) are now available. Whether they are more effective for treatment of hypertension with coronary artery disease remains uncertain.

Adverse effects of beta-blockers are well known and include bradycardia, fatigue, bronchospasm, or worsening of asthma (for beta-blockers that act on the beta₂ receptor such as propranolol or timolol). Cold fingers, simulating Raynaud’s phenomenon, may occur.

Alpha-Receptor Blockers

The prototype alpha-receptor blocker is prazosin, which produces vasodilation by blocking vascular alpha receptors. This drug has a relatively short duration of action; terazosin (twice a day) or doxazosin (once a day) are preferable. The alpha-blockers may be combined with a beta-blocker as combined antiadrenergic receptor antagonism for persons with highly variable blood pressure associated with tachycardia. Like the alpha-receptor blocker phenoxybenzamine, doxazosin may be used to treat hypertension associated with pheochromocytoma. The alpha-receptor blockers are effective for reducing symptoms of prostatism, so they offer a “two for one” benefit for men with hypertension and bothersome prostatic enlargement. However, doxazosin was associated with increased occurrence of heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), so careful monitoring for signs of heart failure is warranted when this drug is used.⁹²

Centrally Acting Antiadrenergic Drugs and Neuron Depletor

Methyldopa is considered safe for use in pregnancy-related hypertension, including preeclampsia, but has been superseded by recently developed drugs; see section on Pregnancy and Hypertension, below. Clonidine, an alpha-receptor agonist, acts within the brain and may also reduce peripheral neuron release by presynaptic inhibition. As an oral preparation, clonidine must be given two to three times daily; withdrawal overshoot hypertension is a risk of missed doses. The transdermal therapeutic system for transcutaneous delivery of clonidine over a 7-day period may be useful for nonadherent patients or those who cannot take oral medication.^93,94

Direct Vasodilators

Hydralazine, a direct-acting vasodilator, may release nitric oxide as part of its action. This drug has a short duration of action and must be given three times daily to be effective; no long-acting formulation is available. Adverse reactions to hydralazine include fluid retention, tachycardia, and drug-induced lupus erythematosus.

Minoxidil is a very potent vasodilator with a longer duration of action; it can be given once or twice daily. Minoxidil opens the ATP-potassium channel of vascular smooth muscle cells.⁶⁵ This drug may reduce blood pressure in highly resistant hypertension, when alternatives fail. However, edema and tachycardia need management, usually with a loop diuretic (eg, furosemide) and a beta-blocker. When used to treat hypertension, minoxidil can cause hair growth that may be disfiguring, so adherence to treatment is problematic. High-dose nifedipine has reduced the need for minoxidil for treatment of resistant hypertension.⁹⁵

Ethnic Status

The prevalence and severity of hypertension is not entirely uniform in comparing populations with different ethnic status, as reflected in national surveys. The ongoing NHANES has examined prevalence of hypertension in several categories, as self reported: non-Hispanic white (white), non-Hispanic black (black), Hispanic, other (American Indian, Native Alaskan, Asian or Pacific Islander), and other race not specified. Prevalence of hypertension was about 25% for non-Hispanic whites and Hispanic groups but about 35% for non-Hispanic black individuals.⁹⁶ In the United States, the prevalence of hypertension has been relatively constant in the past decade, but increasing fractions of all groups are being treated (64%–77%) and controlled (64%–77%).⁹⁷ An increase in use of multidrug combinations has paralleled increased control.⁹⁸ The most recent assessment found that treatment rates were 77% in non-Hispanic whites, 75% in non-Hispanic blacks, but 68% in Mexican Americans. For both non-Hispanic whites and non-Hispanic blacks, about 45% were being controlled on treatment. Evidence from the large randomized trial comparing a thiazide-type diuretic, chlorthalidone, with an ACEI, lisinopril, or theCCB, amlodipine as initial and continuing first-drug treatment indicates that black hypertensives have better control of blood pressure and equal or lower event rates when given the diuretic, compared with the other two agents.⁹⁹ This pattern is consistent with observations that black hypertensives may be more salt sensitive, on average, compared to nonblack populations. However, other dietary factors may be relevant, as black hypertensives had greater blood pressure reductions than nonblacks when given the DASH diet.¹⁰⁰ Treatment goals for nondiabetic black hypertensives, with blood pressures below 140/90 mm Hg, are supported by the results of the SPRINT trial, in that reduction of the primary event rate (25%) was similar for blacks and nonblacks.⁸

Diabetes and Hypertension

Diabetes, largely type 2, is present in 10% to 20% of the adult US population, with higher fractions in older age groups. A prospective survey conducted in several communities in the United States reported that beta-receptor blockers may significantly increase the incidence of type 2 diabetes, but diuretics and ACEIs had no discernable effect.¹⁰¹ For those with diabetes, the benefit-to-risk ratio for beta-blockers should be considered when hypertension occurs with or without coronary heart disease. It is well established that the concurrence of diabetes and hypertension confers a two- to three-fold greater risk of future cardiovascular disease compared to hypertension alone.^102,103 There had been general acceptance of the need to control hypertension in persons with diabetes; the predicted goals for such treatment had been less than 130/80 mm Hg for office pressures.⁵ However, the results of the ACCORD trial combined with several large prospective surveys support a goal of about 135/85 mm Hg for office pressures.^28,56 The value of renin system–blocking drugs, particularly the ACEIs and ARBs, may be additive to blood pressure reduction for diabetics for prevention of renal disease and reduction of microalbuminuria or proteinuria. It has been suggested that diabetic hypertensives are relatively resistant to antihypertensive drug treatment,¹⁰⁴ but the experience from ACCORD indicates that currently available drugs in combination at appropriate doses can achieve treatment goals well below 140 mm Hg systolic pressure.

Elderly, Older Patients

Antihypertensive drug treatment is effective for prevention of cardiovascular disease in healthy elderly populations, age 80 years and above, as evidenced by the Hypertension in the Very Elderly Trial (HYVET).¹⁰⁵ In the SPRINT trial, intensive treatment aimed at a goal of less than 120 mm Hg systolic pressure was more effective in those older than 75 years of age, approximately 25% of the trial population, compared to those 50 to 75 years of age.⁸ However, many older patients are more likely to be less healthy that those enrolled in HYVET or SPRINT. Often, coronary heart disease with or without heart failure, previous stroke, cognitive dysfunction, and other chronic conditions are present, affecting optimal decisions for best outcomes.¹⁰⁶ Orthostatic hypertension may be asymptomatic until increased medication is given to achieve lower goals.³⁶ Risk of falls and serious fractures may occur with intensive treatment of more frail elderly.¹⁰⁷

Choice of antihypertensive drugs for elderly patients should take into account that the beneficial clinical trials were based on either a diuretic^108,109 or CCB¹¹⁰ as initial treatment. Beta-receptor blockers, useful for angina, nonetheless may not be as effective for prevention of stroke as ARBs (Losartan Intervention for Endpoint [LIFE] trial).¹¹¹ Also, they have potential for bradycardia and exacerbation of obstructive pulmonary disease. No matter which drugs are chosen, careful monitoring for adverse reactions is necessary to maintain full function and quality of life.

Coronary Heart Disease

Coronary heart disease and hypertension are often clustered together in aging populations with highly prevalent risk factors, smoking, diabetes, and lipid disorders. The management of acute coronary syndromes will be covered elsewhere. The focus of this section is treatment of hypertension with established coronary artery disease, either as angina or following an acute syndrome, but without heart failure. A recent comprehensive guideline is addressed to management of hypertension in coronary heart disease.⁹¹ The value of diuretics, beta-receptor blockers, and ACEIs for hypertension with angina is strongly supported. The role of the DHP CCBs is less clear, although these drugs can be effective for angina when added to beta-receptor blockers.¹¹² Verapamil or diltiazem, the non–DHP CCBs, may be effective when beta-blockers cannot be given. ARBs may be helpful for those who cannot tolerate ACEIs, usually because the ACEIs have caused bothersome cough or angioneurotic edema.⁸⁰

Stroke, Cerebrovascular Disease

Once a stroke has occurred, or there is evidence of cerebrovascular disease, antihypertensive drug therapy still has an important role for preventing additional pathology. One trial has reported that the combination of an ACEI and diuretic is effective for preventing the second stroke.¹¹³ Apart from elevated blood pressure, per se, as a risk factor for recurrent stroke or stroke in persons with transient ischemic attacks, intervisit blood pressure variability has recently be identified a contributing independently to risk.¹¹⁴ A review suggests that CCBs may reduce interindividual blood pressure variability, compared to beta-blockers and ACEIs, and thereby have an additive benefit for treating hypertension in poststroke patients.

Carotid artery stenosis, another manifestation of generalized atherosclerosis, is often found in hypertensive patients, detected by the finding of a carotid bruit or by screening with carotid artery ultrasound. The benefit of screening of asymptomatic patients is uncertain at this time.¹¹⁵ Those with asymptomatic carotid stenosis and hypertension should receive treatment until the usual goals are met. When symptoms occur, implying imminent risk of stroke, it is less clear whether aggressive reduction of arterial pressure is desirable¹¹⁶ until a successful carotid intervention occurs.

Chronic Renal Disease

Hypertension is well associated with chronic renal disease of various types with and without proteinuria. Diabetic nephropathy is the most likely form to be encountered, but the glomerular diseases, adult polycystic kidney disease, and others may be seen. The goals for treatment of hypertension in chronic kidney disease are both to slow deterioration of renal function and to minimize risk of cardiovascular disease, as recommended in several evidence-based guidelines. However, the optimal goal for on-treatment blood pressure remains uncertain. Increased risk of progression to end-stage renal disease is related to the height of systolic pressure, but it is inversely related to diastolic pressure in older patients.¹¹⁷ Ambulatory blood pressure monitoring is helpful in defining risk in chronic renal disease.¹¹⁸ This may be the result of the greater importance of nocturnal hypertension in chronic renal disease.¹¹⁹ Aggressive treatment of hypertension in nondiabetic renal disease is supported by clinical trial evidence.¹²⁰ ACEIs and ARBs can reduce proteinuria in diabetic and nondiabetic renal diseases and, in some studies, retard progression of renal deterioration. Treatment of persons with minimal proteinuria or microalbuminuria with ACEIs may prevent the appearance of increased protein excretion.¹²¹

Goals for antihypertensive treatment for chronic renal disease have, in recent guidelines, been set well below 140/90 mm Hg for clinic pressure.¹²² However, recent large trials do not support the lower goal, so the lower goal remains controversial.^8,123,124 Greater use of ambulatory blood pressure monitoring to assess nocturnal pressures might resolve this issue for the future.¹²⁵

Post-Transplant Hypertension

Hypertension often occurs following solid organ transplantation. Multiple mechanisms participate in blood pressure elevation, including the effects of immunosuppressive drugs: steroids and the calcineurin inhibitors cyclosporine or tacrolimus.^126,127,128 Hypertension may be slightly less prevalent with tacrolimus compared to cyclosporine.¹²⁹ Treatment of hypertension following organ transplantation is recommended, with prominence given to the value of CCBs and lack of support for ACEIs and ARBs.¹³⁰

Hypertension in Patients with Cancer

Occurrence of cancer in hypertensive patients is all too frequent and as the benefits of antihypertensive therapy reduce fatal cardiovascular disease, more survive to older age, when cancer incidence increases. Management of hypertension in many of those with cancer who remain fully active need not be any different than from treatment of those without cancer. However, incidence of new hypertension or worsening of previous hypertension in cancer patients may result from chemotherapy with the vascular endothelial growth factor (VEGF) inhibitors typified by bevacizumab. The incidence of new hypertension with these agents varies from 20% to 70%,¹³¹ with some evidence of a dose-related effect.¹³² Abrupt and life-threatening increases in arterial pressure caused by the VEGF inhibitors have been reported, including cardiac toxicity and posterior leukoencephalopathy, as seen in malignant hypertension.¹³³ A consensus panel has recommended that patients with cancer who receive VEGF inhibitors have assessment of overall cardiovascular risk and close monitoring of their blood pressure to detect and treat incident hypertension or, if already on antihypertensive medication, a significant increase in pressure. Retrospective reviews of series of patients with VEGF inhibitor–related hypertension indicate that the usual antihypertensive agents, especially ACEIs and CCBs, are effective, but diuretics may be less so.^134,135 Because these patients are often taking a variety of medications for control of cancer and hypertension, thorough familiarity with potential adverse effects and drug interactions is crucial for optimal management by the oncologist and cardiologist.

Rheumatologic Disease

Hypertension is often found in patients with various forms of arthritis or the disorders of connective tissue. As in those without rheumatologic disease, presence of hypertension nearly doubles risk of future cardiovascular disease.¹³⁶ In part, the associations may only be the concurrence of essential hypertension with the other disease, as in rheumatoid arthritis and dermatomyositis. Use of steroids or NSAID therapy for the rheumatologic diseases should be recognized as possible aggravating elements. Use of the tumor necrosis factor antagonists has been associated with a nearly two-fold higher incidence of hypertension in a prospective study.¹³⁷ However, several specific diseases have a more specific link. Scleroderma renal crisis describes rapid development of severe hypertension with renal impairment and pulmonary congestion in patients with scleroderma. The skin manifestations may be of brief duration and unrelated to the severity of the hypertensive emergency. Renin system blockers have been highly effective in reversing the high renin clinical picture by lowering blood pressure and, perhaps, by ameliorating the cutaneous disorder as well.¹³⁸ Nephritis due to systemic lupus erythematosus may be associated with hypertension. ACEIs initiated before onset of renal disease may delay onset of the nephropathy.¹³⁹ The use of high-dose glucocorticoids for treatment of systemic lupus erythematosus may contribute to the severity of hypertension in this disease. Polyarteritis nodosa may involve renal artery branches with or without infarction and produce hypertension with activation of the renin-angiotensin system that is, de facto, renovascular hypertension. The intense renal arterial inflammation may respond to steroid therapy with lessening of the hypertension; an exception to the rule that steroids frequently cause blood pressure elevations.

Cognitive Impairment

Hypertension in older patients has been associated with increased risk of cognitive impairment and dementia.¹⁴⁰ Imaging studies have indicated correlation between cognitive impairment and signs of cerebral microvascular pathology. Prospective surveys of cognitive function have been conducted within the framework of several randomized trials of therapy for prevention of cardiovascular events. A meta-analysis supports the view that antihypertensive drug treatment does not significantly increase likelihood of dementia or cognitive impairment.¹⁴¹ It has been suggested that ACEIs that cross the blood-brain barrier may be more effective in preventing cognitive impairment than those that enter the brain to a lesser extent.¹⁴² In the ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) comparing an ACEI with an ARB, there was no difference between the two with regard to rates of cognitive impairment during the study.¹⁴³

Pregnancy and Hypertension

Hypertension occurring anew during pregnancy may be a spontaneous occurrence without previous hypertension and without features of preeclampsia (gestational hypertension); may be accompanied by new proteinuria with or without edema (preeclampsia); or may be characterized by seizures (eclampsia).¹⁴⁴ Preeclampsia may be associated, not only with proteinuria (> 300 mg/24 h), but thrombocytopenia, abnormal liver function tests, and impaired renal function (the HELLP syndrome). Those with hypertension prior to pregnancy are considered to have chronic hypertension, but pressure may fall to normal levels in the first and second trimesters of gestation. Occasionally, hypertension first appears immediately after delivery (postpartum hypertension). With exception of chronic hypertension, hypertension in pregnancy or shortly after delivery is usually gone about 6 weeks after delivery. Close monitoring of blood pressure during pregnancy is necessary and use of home blood pressure monitoring may be helpful.¹⁴⁵ Ambulatory blood pressure monitoring has been explored and may be helpful when additional studies are available.¹⁴⁶

Goals and strategy for treating hypertension in pregnancy differ from the usual pattern for nonpregnant women.¹⁴⁴ Optimal care requires effective collaboration between specialties, including the internist, cardiologist, nephrologist, and high-risk obstetrician. Current guidelines suggest that new hypertension not be treated with antihypertensive drugs if clinic pressures are less than 160/105 mm Hg without any complications. For women with treated hypertension before pregnancy, pressure should be kept in the range of 120–160/80–105 mm Hg. However, the range of drug classes suitable for treating hypertension in pregnancy is a restricted one, excluding the renin system blockers, because of risk of fetal damage,^147,148 as well as the mineralocorticoid receptor blockers, spironolactone, and eplerenone. Recommended drugs are methyldopa, labetalol, and nifedipine because these have acceptable evidence of safety in pregnancy.