Evaluation and Management of Hypertension

Measuring Blood Pressure

Proper methods should be used to accurately measure and document blood pressure for the diagnosis, classification, and management of hypertension. Fig. 64.1 lists steps recommended to obtain reliable BP readings, and Table 64.5 lists common mistakes leading to inaccurate BP measurements as well as information regarding correct BP cuff selection. Key elements for success in office settings include proper preparation of the patient, use of a validated upper-arm BP measurement device, correct technique, and averaging of readings. During the initial visit, BP should be measured in both arms (and in the leg if aortic coarctation is suspected). For proper BP assessment, it is important to take the BP in the correct way at least twice on any occasion and on at least two, and preferably three, separate days for the initial diagnosis of hypertension. The 2015 US Preventive Services Task Force (USPSTF) guidelines on hypertension recommend that all individuals 18 years or older be screened for elevated BP, and the ACC/AHA guidelines suggest the use of out-of-office blood pressure measurements to confirm the diagnosis of hypertension and to titrate medications.

Pseudohypertension is a problem occasionally encountered in examining patients with very stiff and difficult-to-compress blood vessels due to arterial wall calcification. The pressure required to compress the stiff brachial artery and to stop the audible blood flow with a standard BP cuff can be much greater than the actual intraluminal BP obtained invasively. Osler’s maneuver can be used to identify this condition by inflating the BP cuff at least 30 mm Hg above the palpable systolic pressure and then trying to “roll” the brachial or radial artery underneath the fingertips. Pseudohypertension may be present when something resembling a stiff tube is felt underneath the skin because a normal artery should not be palpable when empty. It is important to identify pseudohypertension as it tends to occur in the elderly and chronically ill, including those with chronic kidney disease (CKD), who are also more prone to orthostatic and postprandial hypotension, which can be aggravated by the unwarranted intensification of BP treatment.

Electronic oscillometric devices are increasingly used to measure BP at home and in the office setting, and have become the clinical standard for BP measurement. This is due to environmental concerns about mercury toxicity, the need for frequent calibration with aneroid sphygmomanometers, errors due to auscultation and inappropriately rapid deflation of the cuff, and the greater convenience and cost savings associated with use of oscillometric devices. The cuff is inflated until the disappearance of the brachial pulses is detected. Upon deflation, sensors detect the increasing amplitude in the brachial pulsation and measure the mean arterial pressure. The systolic and diastolic BP readings are then derived from the mean arterial BP. Typically, systolic BP is slightly lower and diastolic BP is slightly higher when measured with electronic devices when compared to invasively measured arterial pressure.

Also available are specialized electronic devices to perform automated office blood pressure monitoring (AOBP) in the office setting. With AOBP, multiple BP readings are recorded using a fully automated sphygmomanometer with the patient resting quietly and sitting alone. Proper timing, patient positioning, cuff size, and placement are still necessary to be certain that the readings are accurate. There are currently three validated devices available for performing AOBP, and each can be programmed to take multiple consecutive BP measurements in intervals of typically 1 to 2 minutes. The devices differ in the number of readings taken and the number of minutes before the first BP measurement is recorded. Ideally, oscillometric devices should be preprogrammed (when possible) to record repeated measurements at 1-minute intervals after the 5-minute rest period. AOBP has the same cut-point as home BP and awake ambulatory BP (130/80 mm Hg) for defining hypertension because systolic pressure readings typically are 5 to 10 mm Hg lower with AOBP than with auscultatory measurement. In 2011 the Canadian Hypertension Education Program recommended AOBP for the diagnosis of hypertension, in 2013 the European Society of Hypertension recommended using AOBP if feasible, and in 2017 the ACC/AHA stated that there is a growing evidence base to support the use of AOBP measurements.

AOBP has some specific advantages, including that AOBP is not associated with the white-coat effect (the response in some patients in which BP readings taken by doctors and nurses tend to be higher because of increased patient anxiety), multiple readings are obtained, and readings better correlate with awake ambulatory BP readings when compared with manual office readings, as demonstrated in the Conventional Versus Automated Measurement of BP in the Office (CAMBO) study. Results from the Systolic Blood Pressure Intervention Trial (SPRINT) also indicate that unattended and attended automated office BP measurements result in similar BPs when the core recommendations for accurate BP measurement are followed.

Assessing Cardiovascular Risk and End-Organ Damage

The evaluation of each hypertensive patient should include a detailed personal and family history, thorough physical examination, and selected tests focused on addressing the above three key questions. Key components of the history and physical examination are listed in Table 64.6 .

A detailed personal history of hypertension includes its onset, duration, severity and related symptoms, presence of other CV risk factors, and target-organ complications. The medication history should include the prior and current use of any prescription and over-the-counter agents. Special attention should be paid to antihypertensive medications with their related clinical responses and adverse effects, as well as common offending agents, such as nonsteroidal antiinflammatory drugs (NSAIDs), oral contraceptives, and cold/cough remedies. NSAIDs can increase BP directly and can decrease the efficacy of antihypertensive medications by inhibiting the vasodilatory and natriuretic effects of prostaglandins and potentiating vasoconstrictive effects of angiotensin-II. Dietary salt intake, alcohol consumption, tobacco use, physical activity, and weight changes should be recorded. With the increasing prevalence of obesity, essential hypertension manifests at a younger age, often in the 30s. In addition, more elderly patients are expected to develop essential hypertension as systolic BP increases throughout life. Family history of hypertension, diabetes, and related CV complications should also be noted, as a positive family history further increases the individual’s CV risk. Excluding monogenic causes of hypertension, available data suggest that the heritability of essential hypertension ranges from 20% to 40%.

Physical examination should start with measurement of height, weight, and waist circumference, and calculation of body mass index (BMI). BP is usually measured in sitting and standing positions on the initial evaluation, and at least once in both arms (and at least one leg if aortic coarctation is suspected). Subsequent BP measurements are obtained in the seated position from the arm with the higher initial BP reading.

The optic fundi are the only places where blood vessels can be directly examined. The fundoscopic examination looks for arteriolar narrowing (grade 1), arteriovenous compression (grade 2), hemorrhages and/or exudates (grade 3), and papilledema (grade 4), which not only provide information on the degree of target-organ damage related to BP but also provide important prognostic information on overall CV outcomes.

Bruits in the neck, abdomen, and groin should be noted. Bruits may simply result from vascular tortuosity, particularly with high-flow vessels. However, they may be a sign of vascular stenosis and irregularity and be a clue to vascular damage leading to future loss of target-organ function. The radial artery is similarly distant from the heart as the femoral artery, and the pulse should arrive at approximately the same moment when palpating both sites simultaneously. In aortic coarctation, a palpable delay in the arrival of the femoral pulse compared with the radial pulse supports this diagnosis, as does an interscapular murmur heard during auscultation over the back of the patient. A systolic BP in the leg behind the knee (popliteal) lower than the brachial value suggests the presence of aortic or iliac obstruction, but it may also reflect more peripheral arterial disease in certain patients, such as smokers and those with target-organ damage. Patients should be advised that measuring leg BP may be uncomfortable given the large cuff and the amount of pressure required to occlude the femoral artery.

Cardiac examination by palpation may reveal a displaced apical impulse, indicative of left ventricular enlargement. A sustained apical impulse may suggest left ventricular hypertrophy (LVH). Auscultation should focus on listening for an S4 that is heard with left ventricular stiffness. An S3 indicates impairment in left ventricular function and usually underlying heart disease when crackles are present on lung examination, although the presence of S3 and crackles is uncommon on initial office evaluation of new hypertensive patients. The lower extremities should also be examined for peripheral arterial pulses and edema. The loss of pedal pulses is a sign of peripheral vascular disease (target-organ damage) and is associated with higher CV risk.

Finally, a brief neurologic examination for evidence of remote stroke should assess gait, bilateral grip strength, speech, memory, and mental acuity. Given the link between hypertension and future loss of cognitive function, it is useful to establish the baseline cognitive function before starting antihypertensive medications, as some patients may complain of memory loss after starting pharmacotherapy.

Several laboratory studies are recommended in the routine evaluation of the hypertensive patient. Testing should include hemoglobin or hematocrit, urinalysis with microscopic examination, serum potassium, bicarbonate, creatinine, fasting glucose, lipid profile, and 12-lead electrocardiogram (ECG). Assessing albuminuria is important as albuminuria has been associated with increased CV risk and may warrant more aggressive BP reduction. Assessing kidney function is also an important part of the evaluation as CKD is not only a sign of target-organ damage but also a common cause of hypertension. Depending on the degree of glomerular filtration rate (GFR) loss, up to 90% of patients with advanced CKD or end-stage kidney disease (ESKD) have hypertension. Uric acid may be checked in those with a history of gout as diuretics can increase uric acid level and lead to gouty flares. In some cases, checking calcium, thyroid-stimulating hormone (TSH), or other thyroid studies may be reasonable when clinically indicated.

Plasma renin activity and serum aldosterone levels are useful in screening for aldosterone excess and salt sensitivity. However, these measurements are usually reserved for patients with hypokalemia or metabolic alkalosis or those who fail to achieve BP control on a three-drug regimen (that includes a diuretic). A suppressed renin activity level with a normal aldosterone level and an increased aldosterone-to-renin ratio supports a contribution of dietary sodium excess to hypertension; this scenario should respond well to dietary salt restriction and diuretics. It is worth noting that primary aldosteronism is more common than previously thought. In patients referred to one hypertension center in Italy, 11% had primary hyperaldosteronism, with 5% having a potentially curable aldosterone-secreting adenoma and 6% having idiopathic hyperaldosteronism. In the same study, only 50% of patients with a confirmed aldosterone-producing adenoma had hypokalemia, underscoring the importance of considering this diagnosis in patients with normal levels of potassium. A recent study that included participants with normotension ( n = 289), stage 1 hypertension ( n = 115), stage 2 hypertension ( n = 203), and resistant hypertension ( n = 408) showed that for every BP category there was a continuum of renin-independent aldosterone production, where greater severity of production was associated with higher BP. Adjusted prevalence estimates of biochemically overt primary aldosteronism were present in 11.3% of normotensives, 15.7% of stage 1 hypertensives, 21.6% of stage 2 hypertensives, and 22.0% of resistant hypertensives. This indicates that prevalence of primary aldosteronism is high and largely unrecognized.

Additional testing may be indicated in some patients depending on the clinical situation. Limited echocardiography is more sensitive than an ECG for detection of LVH. The presence of LVH, a sign of target-organ damage, can help establish or reinforce the need of antihypertensive therapy, especially in those who have borderline BP and/or are reluctant to start antihypertensive medications.

Ambulatory and Home BP Monitoring

Since BP can be influenced by an environment such as an office or hospital, ambulatory BP monitoring (ABPM) or home BP monitoring (HBPM) is useful in establishing or excluding the diagnosis of hypertension in those with white-coat hypertension or masked hypertension ( Fig. 64.2 ). ABPM and HBPM are also useful in assessing the adequacy of BP control in outpatients and helping identify those with morning surges in BP (i.e., >55 mm Hg increase in systolic BP during the early waking hours compared with sleeping). The morning surge has been associated with increased risk of cerebrovascular diseases, including brain white matter lesions and stroke. In addition, ABPM is helpful in screening for nocturnal hypertension or nondipper status (i.e., <10% reduction in nighttime BP compared with daytime). Data from large ABPM cohorts suggest that nighttime BP provides the greatest information regarding CV risk. CV risks associated with elevated nighttime BP levels outweigh the risks associated with elevated routine office BP measurements and those of the cumulative daytime hours. In addition, the BP variability data from ABPM suggest that a greater degree of BP variability during the 24 hours of monitoring is associated with a greater risk of CV target-organ damage. ABPM is typically programmed to take BP measurements every 15 to 30 minutes during awake hours and every 30 to 60 minutes during sleep hours. It is important for patients to complete the diary correctly so that the hours of sleep (including naps) can be incorporated into the ABPM report.

Current estimates suggest that more than half of hypertensive patients measure their BP at home. Home BP monitors are relatively inexpensive and reasonably accurate. An updated list of validated devices can be found at www.validatebp.org . Specific recommendations have been published on how to incorporate HBPM into overall BP assessment. For the diagnosis of hypertension, it is recommended to take two BP readings in the morning between 7 a.m. and 10 a.m. and two measurements in the evening between 7 p.m. and 10 p.m. for 7 consecutive days.

Values from the first day are discarded, and the subsequent 6 days’ values are averaged. For the diagnosis of hypertension in untreated patients, hypertension is not present if the average is less than 120/80 mm Hg, but hypertension is likely present if the value is greater than 130/80 mm Hg. Suggested corresponding values for clinic, HBPM, daytime, nighttime, and 24-hour ambulatory blood pressure measurements are listed in Table 64.7 . When patients are using HBPM for monitoring and titrating medications it is recommended that they measure BP in the morning before taking antihypertensive medications and in the evening before dinner, with two readings at each time of day 1 minute apart. Patients do not need to measure home BPs daily but should obtain readings for 3 to 7 days a few weeks after initiating or changing medication and before clinic visits. Clinicians should adjust hypertension therapy based on the average of all readings over the 3- to 7-day monitoring period (minimum of 12 readings).

ABPM and HBPM have important similarities, but they also have meaningful differences. They are viewed as complementary rather than alternative techniques because they provide different information regarding BP. Table 64.8 compares similarities and differences among the various techniques available for BP measurement.

The National Center for Health and Clinical Excellence (NICE) in the United Kingdom recommended using ABPM or HBPM to confirm all new diagnoses of hypertension. Similarly, the 2015 USPSTF guidelines recommended that the diagnosis of hypertension be confirmed with ABPM. However, the USPSTF and, more recently, the ACC/AHA guidelines recognize that ABPM is not widely available because of equipment cost and lack of widespread insurance coverage; these guidelines, therefore, state that out-of-office blood pressure measurements are required to confirm the diagnosis of hypertension and that either HBPM or ABPM is acceptable to make the diagnosis. Currently, Medicare and most insurance companies do not provide financial coverage for ABPM in patients with established hypertension but provide coverage for its use to diagnose white-coat hypertension and, more recently, coverage for masked hypertension has been added. The Centers for Medicare & Medicaid Services (CMS) recently proposed expansion of Medicare coverage for ABPM and may soon announce a decision regarding coverage for such monitoring for patients with established hypertension. Since January 2020, there is now a CPT code to bill for HBPM or self-monitored BP (SBPM). The 2020 CMS fee schedule includes reimbursement for HBPM, including billing for one-time patient education and training using a validated device provided by the patient. Monthly reimbursement requires documentation of a minimum of 12 readings reported to the physician and communication of a treatment plan by the physician to the patient.

Lifestyle Modifications

Several nonpharmacologic approaches are used in lowering BP. In obese patients, the most effective measure to reduce BP is weight loss. For all patients, reducing dietary sodium intake to less than 100 mmol/day (2300 mg of sodium) and increasing physical activity to at least 30 minutes daily on most days of the week are high-yield lifestyle modifications. Finally, limiting alcohol intake to two drinks a day for men (one drink a day for women) helps reduce BP. Other approaches, including modification of intake of fish oil, garlic, and green tea and supplementation of potassium, magnesium, and calcium, have had variable success in managing BP. Although they do not appear harmful, these approaches lack robust data to support their widespread use in the management of patients with elevated BP or sustained hypertension. Table 64.9 summarizes the effects of various lifestyle modifications on BP.

There is evidence for the benefit of lifestyle measures in hypertension management. The Dietary Approaches to Stop Hypertension (DASH) Study showed that a diet low in sodium and high in fruits, vegetables, and calcium is effective in lowering BP. In addition, the Trials of Hypertension Prevention (TOHP2) and Trials of Non-Pharmacological Interventions in the Elderly (TONE) reported that in middle-aged (TOHP2) and elderly (TONE) subjects with mild to moderate hypertension, diet, exercise-induced weight loss, and sodium restriction can be sustained and are associated with significant BP reductions. A meta-analysis of 24 randomized, controlled trials showed that dietary modifications are associated with significant incremental reductions in BP. The authors found that the net reduction in systolic and diastolic BP was 3.1 mm Hg and 1.8 mm Hg, respectively. From this same analysis, it appears that some dietary patterns are more effective than others, as the DASH diet was associated with the greatest overall reduction in BP with a net reduction in systolic and diastolic BP of 7.6 mm Hg and 4.2 mm Hg, respectively.

The effect of aerobic exercise was evaluated in a meta-analysis of 54 randomized, controlled trials and demonstrated that aerobic exercise reduces systolic and diastolic BP by 3.8 mm Hg and 2.6 mm Hg, respectively. This BP reduction was noted in both overweight and normal-weight participants, as well as in normotensive individuals. Dynamic resistance exercises (such as weight lifting and circuit training) and isometric exercises (such as handgrips or weighted resistance machines) have also been shown to effectively reduce BP, and it is recommended they are performed 3 to 5 times per week.

Viewed in sum, these studies demonstrate the importance of individually evaluating the various lifestyle factors associated with hypertension in all patients as part of the initial management.

Medication Nonadherence

An important and underappreciated cause of poor BP control and apparent resistant hypertension is medication nonadherence. Medication nonadherence in hypertensive patients has been shown to be present in up to 50% of patients when using prescription claims data over the course of 2 years in Germany. Failure to recognize medication nonadherence early in the disease course may result in unnecessary testing, complications of polypharmacy, inappropriate treatment, and worse patient outcomes. Multiple studies have demonstrated that a significant fraction of patients referred for resistant hypertension are either partially or completely nonadherent. Similarly, when urinary drug metabolites were measured in patients with apparent resistant hypertension, 25% were at least partially nonadherent. Clinicians must be aware of potential barriers to adherence and routinely minimize these barriers for patients. Remediable barriers include socioeconomic factors, treatment complexity, adverse medication effects, and patient motivation. Motivation is commonly affected by depression, lack of belief in the benefit of treatment, and lack of insight into illness. Medications should preferentially include low-cost and generic antihypertensives. Adherence is inversely proportional to the frequency of dosing; so, once-daily medications and combination antihypertensive formulations should be used when available. Adverse medication effects should be addressed since patients may be reluctant to continue intolerable therapies for an otherwise asymptomatic disease. Patients require education and should be empowered in management decisions, which may improve adherence.

Principles of Pharmacologic Care

Many patients with hypertension find it difficult to make or sustain the necessary lifestyle modifications to effectively lower BP. Treatment with antihypertensive medications is recommended when BP remains above the goal despite lifestyle modifications.

Major classes of antihypertensive medications with their mechanism of actions, common side effects, and compelling indications are listed in Table 64.10 . Heart failure and stroke are the types of end-organ damage most reduced with long-term antihypertensive therapy. A large meta-analysis suggests that all five major classes of antihypertensive agents (angiotensin-converting enzyme [ACE] inhibitor, angiotensin II receptor blocker [ARB], beta-blocker, calcium channel blocker [CCB], and diuretic) can reduce target-organ damage when used to control BP effectively. Choosing an agent involves a decision-making process that takes into account demographics (age and ethnicity), drug cost, and the anticipated side-effect profile. Use of long-acting agents that can be dosed once or, at most, twice a day and use of combination therapies are preferred as this simplifies the regimen and increases adherence. The usual response to a single antihypertensive agent is a reduction in systolic BP of 12 to 15 mm Hg and diastolic BP of 8 to 10 mm Hg. Follow-up visits for BP assessment and dose titration are often scheduled in 2 to 4 weeks for single-agent therapy as most agents will exert their antihypertensive effects at that dose by then.

In patients with systolic BP greater than 20 mm Hg and/or diastolic BP greater than 10 mm Hg above the goal, beginning treatment with combination drug therapy can shorten the time to achieve BP goal, require less dose titration of antihypertensive agent, and increase the likelihood of achieving BP goal. Combination therapy is often more desirable than a stepwise approach of maximizing one agent before adding another agent because of the better efficacy in BP control and side-effect profile.

A useful approach in building an effective combination therapy is based on a convenient model, shown in Fig. 64.3 . This approach is similar to the popular “Birmingham Square” used in the United Kingdom to develop combination regimens. The art in building or adjusting a combination antihypertensive regimen is to use medications with complementary, and not overlapping, mechanisms of action and to try to minimize side effects by leveraging known pharmacology. Examples include adding an ACE inhibitor to a diuretic to reduce occurrence of hypokalemia or adding an ACE inhibitor (or an ARB) to a CCB to reduce CCB-associated edema.

Major Classes of Antihypertensive Agents and Associated Cardiovascular Benefits