Hypertension
Amal Abdellatif*
Mohamed B. Elshazly*
Parag H. Joshi
John W. McEvoy
* Joint First Authors (Contributed Equally)
INTRODUCTION
Epidemiology
Hypertension (HTN) is one of the most common reasons for primary health care visits and prescription of chronic medications.1 Hypertension directly increases the risk for premature death owing to cardiovascular diseases (CVD), including coronary artery disease (CAD), heart failure (HF), ischemic stroke, intracerebral hemorrhage,2 kidney disease, and retinal vascular disease. Consequently, high blood pressure (BP) is the major global contributor to all-cause morbidity and mortality, resulting in an estimated 10.4 million deaths and 218 million disability-adjusted life years (DALYs) in 2017.3
By lowering the diagnostic threshold of HTN, the 2017 American College of Cardiology/American Heart Association (ACC/AHA) HTN clinical practice guidelines have significant global epidemiologic and clinical implications. Implementing these guideline recommendations renders 46% of U.S. adults as hypertensive, translating to 103.3 million hypertensive Americans.4 Further, 53% of U.S. adults already on antihypertensive medication are considered undertreated by the new guidelines.4 The resultant boost in the global prevalence of HTN from 26% to 31% translated to at least 1.8 billion hypertensive individuals worldwide.5
Hypertension is more prevalent in older populations, and in non-Hispanic Blacks compared to Hispanics and non-Hispanic Whites.6 Because of the progressive loss of arterial elasticity, systolic blood pressure (SBP) consistently increases with advancing age, whereas diastolic blood pressure (DBP) peaks at the fifth decade before gradually decreasing in both sexes.7
Risk Factors
Careful risk factor assessment of the patient is of chief importance because it guides the treatment approach and dictates the need for and intensity of pharmacotherapy, or the lack thereof. Modifiable risk factors for essential (primary) HTN include obesity; physical inactivity; diets rich in sodium, saturated fats, and trans fats; excessive consumption of alcohol and tobacco, diabetes mellitus, psychosocial stress, and obstructive sleep apnea. Nonmodifiable risk factors include family history (genetic susceptibility), advancing age, black race, male sex (especially below the age of 65 years), and chronic kidney disease (CKD). All hypertensive patients should have their CVD risk factor profile assessed, so that they can be managed and advised accordingly. A separate discussion on HTN in the context of other CVD risk factors follows under the sub section “Cardiovascular Risk-Based Treatment Approach.”
PATHOGENESIS
The pathogenesis of HTN is multifactorial and poorly understood. BP is a function of several dynamic factors including vascular tone and elasticity, cardiac output, blood volume, blood viscosity, vascular reactivity, and hormonal effects. The interplay of genetics, inflammation, sympathetic activation, environmental factors, and psychosocial elements also contributes to the complex pathogenesis of HTN.
Genetic Link
Genetic studies on HTN suggest distinct heritability patterns of primary (essential) and secondary HTN. Primary HTN tends to be associated with numerous common genetic variants or loci (also known as single nucleotide polymorphisms, SNPs), which have been identified through genome-wide association studies.8 The distinct loci that independently influence BP impart a cumulative risk to the development of primary HTN; the number of risk alleles present proportionally raises the risk of disease. However, the heritability of HTN is only partially explained by the presence of such SNPs. Along with these SNPs, certain environmental factors like age, body mass index, sex, and salt consumption can modify the probability of HTN development.9
In contrast to the polygenic contributions to primary HTN, linkage analysis in family-based studies has shown the association of monogenic mutations with the development of secondary HTN. Thus far, 13 genes have been identified that lead to the development of familial hypertensive syndromes including classes of familial hyperaldosteronism and congenital adrenal hyperplasia.
Immunologic Role
Psychosocial Stressors
CLINICAL PRESENTATION
Definitions and Guidelines
The relevance of HTN to CV mortality is a function of the correlation between BP levels and CVD risk as established in multiple observational studies and randomized controlled trials (RCTs).12 Based on this large body of evidence, the 2017 ACC/AHA HTN clinical practice guidelines13 provide more stringent definitions for HTN than previous versions, with the recommendation to assign the higher stage when SBP and DBP on office BP readings are discordant:
Normal BP | SBP <120 mm Hg and DBP <80 mm Hg |
Elevated BP | SBP 120-129 mm Hg and DBP <80 mm Hg |
Stage 1 HTN | SBP 130-139 mm Hg or DBP 80-89 mm Hg |
Stage 2 HTN | SBP ≥140 mm Hg or DBP ≥90 mm Hg |
The European Society of Cardiology (ESC) and National Institute for Health and Care Excellence (NICE) guidelines endorse the following definitions14,15:
Stage 1 HTN | SBP ≥140 mm Hg or DBP ≥90 mm Hg |
Stage 2 HTN |
Accurate Blood Pressure Measurement
Accurate BP measurement is critical for the diagnosis and management of HTN. The diagnosis of HTN entails a mul-tistep process, where BP measurements are obtained at two or more timepoints and settings in order to ensure the accuracy of readings and evaluate for less obvious diagnoses like white coat and masked HTN. Equivalent thresholds for HTN diagnosis within various measurement settings are outlined in Table 100.1.
A number of BP measurement methods are currently available and adopted with varying degrees based on cost, availability, reliability, and appropriateness as deemed by clinical judgment. The following is a brief discussion on the individual merits and limitations of these methods.
Ambulatory Blood Pressure Monitoring
The use of ambulatory BP monitoring (ABPM) is increasing in clinical practice based on a growing body of evidence supporting its superiority over both office-based and, perhaps also, home measurements.15,16 ABPM helps confirm the diagnosis of HTN, establishes otherwise hard-to-elicit diagnoses such as white coat or masked HTN, results in more reliable treatment decisions, and provides additional prognostic information.
ABPM is performed using automated portable devices that automatically measure BP every 15 to 30 minutes during the day and every 30 to 60 minutes during sleep over 24 to 48-hour intervals.15 The minimum number of recordings needed over a 24-hour period to get an accurate average BP is 10 recordings during waking hours and 5 recordings during sleep; however, European guidelines recommend 20 recordings during the awake period and 7 during sleep for a more accurate assessment.15,17 Daytime, nighttime, and 24-hour averages are then calculated using these measurements and are used to make a diagnosis of HTN based on certain equivalent thresholds (Table 100.1).
Although the use of ABPM is not widely recommended for routine screening purposes, its primary utility is in cases of diagnostic uncertainty between office-based and home BP measurements. Patients who persistently have elevated office readings that average greater than 130/80 mm Hg and reliable home BP readings that average less than 130/80 mm Hg are said to have white coat HTN,13 thought to be because of anxiety in part and an exaggerated sympathetic response. White coat HTN should be confirmed with multiple readings on different visits and out-of-office measurements, ideally with ABPM. If confirmed, patients with white coat HTN should be monitored annually with ABPM or home BP monitoring (HBPM) to detect progression to sustained HTN.13 The recommendation for continued monitoring stems from observational studies suggesting that untreated white coat HTN places patients at a greater all-cause and CVD risk relative to normotension.18 In addition, patients with white coat HTN are at an increased risk of developing sustained HTN over a 10-year period relative to their normotensive counterparts.18 The utility of ABPM in the context of white coat HTN is also evident in patients with apparently resistant HTN whose otherwise appropriate response to pharmacotherapy at home could be unrecognized because of their white coat effect in the clinical setting.15
On the other hand, patients with persistently normal office BP readings who have hypertensive ambulatory measurements have a phenotype called masked HTN.13 Detected on clinical studies that compared office BP measurement to ABPM or HBPM, masked HTN has a prevalence of 15% to 30% in subjects deemed normotensive by office measurements.19 Like white coat HTN, masked HTN has been associated with an increased risk of CVD mortality and conversion to sustained HTN.19 Accordingly, patients meeting target BPs yet suspected of having masked HTN should have ABPM or HBPM to assess its presence. These include those with mildly elevated office readings (ie, 120-129 mm Hg) who have already undergone lifestyle interventions, patients at increased CVD risk, and patients with target organ damage/remodeling like coronary heart disease, left ventricular hypertrophy, or CKD.13,15
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Another indication for the use of ABPM is to make more informed treatment decisions. In a trial comparing the treatment benefit derived from BP-lowering therapy when informed based on traditional office monitoring versus ABPM, fewer patients needed multidrug therapy and more patients were able to stop treatment altogether after the white coat effect was evident with ABPM.15 Moreover, ABPM has the advantage of exposing alterations in BP that harbor unfavorable long-term cardiovascular effects like the early morning BP surgea and nocturnal HTN, also referred to as “nondipping.” Because nocturnal BP is expected to decrease by at least 10% relative to daytime BP,15 nondipping (defined as an overnight BP decrease <10% the daytime value) is a harbinger of CVD complications.15 ABPM can theoretically be utilized to better time the administration of antihypertensives in nocturnal HTN20 and in modifying medication dose and half-life in patients with early morning surge to better manage their BP.
ABPM, although considered the gold standard in diagnosing HTN, is yet to be more widely implemented in clinical practice in many countries. The US Centers for Medicare & Medicaid Services (CMS) recently proposed to pay for expanded use of ABPM for detection of suspected white coat HTN and masked HTN.21 A systematic review conducted by the U.S. Preventive Services Task Force led to a recent endorsement of ABPM for clinical use.22 Although ABPM is widely used in many European countries, these two developments may increase its use in the United States. Cost, availability, and lack of awareness regarding its potential benefits are factors that contribute to the suboptimal use of ABPM, making HBPM the next best available alternative.
Home Blood Pressure Monitoring
HBPM has become a popular modality of BP monitoring, providing valuable information that aids in the diagnosis of HTN and titration of antihypertensive treatment. Being a reliable, affordable, and convenient alternative to ABPM, its use is relatively more widespread. A meta-analysis demonstrated greater mean BP reductions when using HBPM over office-based BP, with the former achieving average BP reduction of 8/4 mm Hg more than the latter.23 Like ABPM, HBPM is useful to identify subtle entities like white coat HTN and masked HTN. Indeed, HBPM may offer better prognostic information than ABPM.16
Current guidelines recommend using automated, oscillometric devices rather than traditional auscultatory devices that present challenges for patients to use properly.13 Two readings—at least one minute apart—are recommended in the morning prior to medications as well as in the evening before dinner. At least 12 recordings over the course of a week are suggested for evaluation by the physician. A diagnosis of HTN, per American guidelines, is then made if the average of these readings is greater than or equal to 130/80 mm Hg.13
Patients should be educated and trained on proper performance with automated machines. See 
e-Figure 100.1 for patient instructions for HBPM. This includes instructions to rest for at least 5 minutes prior to recording their BP, during which time they should sit with their back straight and supported, while laying their arm on a flat surface and keeping their legs uncrossed and feet flat on the floor. Patients should also be advised to avoid any caffeinated drinks, smoking, or exercise at least 30 minutes prior to taking their BP. In addition, the devices should be brought intermittently to the clinician’s office so that their accuracy can be ascertained by the clinician through checking their readings against those of a mercury sphygmomanometer.
e-Figure 100.1 for patient instructions for HBPM. This includes instructions to rest for at least 5 minutes prior to recording their BP, during which time they should sit with their back straight and supported, while laying their arm on a flat surface and keeping their legs uncrossed and feet flat on the floor. Patients should also be advised to avoid any caffeinated drinks, smoking, or exercise at least 30 minutes prior to taking their BP. In addition, the devices should be brought intermittently to the clinician’s office so that their accuracy can be ascertained by the clinician through checking their readings against those of a mercury sphygmomanometer.Office-Based Blood Pressure Measurement
Office-based BP measurement should only be used for screening purposes as initial readings are not typically reflective of true BP levels due to the white coat effect or other factors (ie, drugs, caffeine, anxiety, and physical exertion, etc) affecting the patient’s instantaneous BP. Elevated readings on initial screening (ie, ≥130/80 mm Hg) should prompt confirmation through out-of-office measurement via HBPM or ABPM, unless the patient presents with BP greater than or equal to 160/100 mm Hg with evidence of target organ damage (ie, CKD or hypertensive retinopathy), which warrants immediate treatment.
Office BP measurement should be performed in accordance with the guidelines outlined in 
e-Table 100.1 regarding the patient’s posture and 
e-Table 100.2 regarding the appropriateness of the cuff size, while also noting the timing of the measurement with respect to BP medications and the details of auscultatory technique. An average of two or more office readings taken on two or more occasions should be used to estimate the patient’s BP.
e-Table 100.1 regarding the patient’s posture and e-Table 100.2 regarding the appropriateness of the cuff size, while also noting the timing of the measurement with respect to BP medications and the details of auscultatory technique. An average of two or more office readings taken on two or more occasions should be used to estimate the patient’s BP.Automated oscillometric BP measurement devices have become commonplace in clinical practice for their superior reliability relative to auscultatory devices and because they yield readings that are closer to daytime ambulatory readings, especially when BP is recorded with the patient unattended by a physician in a quiet room.24 Because the automated oscillometric devices can also take multiple readings in one setting, the mean BP measurement can help to diminish the white coat effect.24
CLINICAL PRESENTATION
Signs and Symptoms
The initial evaluation of a patient with suspected or confirmed HTN should aim to do the following:
Elicit other modifiable CVD risk factors: cigarette smoking, secondhand smoking, unhealthy diet, physical inactivity, obesity, dyslipidemia, diabetes mellitus13
Ascertain the extent of target organ damage (if any)
Identify red flags for secondary HTN
Estimate a prognosis based on CVD risk factors
Table 100.2 includes elements in the history, physical examination, and laboratory tests that are important to consider in the evaluation of the hypertensive patient.
DIAGNOSIS
Primary Hypertension
Primary (or essential) HTN exists when no underlying secondary cause for elevated BP is present. Making the diagnosis of primary HTN entails obtaining accurate BP measurements on two or more occasions. Whether the BP values are obtained at the clinic or at home via HBPM,
the clinician must ensure the correct measurement technique is followed, and
an average of two or more separate readings are to be recorded on two or more different occasions in order to be used for clinical decision-making.
Diagnostic thresholds for HTN are listed in Table 100.1. Algorithm 100.1 indicates steps that should be undertaken if the patient has an elevated BP on the initial office screening test. Algorithm 100.2: Recommendations for treatment and follow-up after initial hypertension diagnosis summarizes the recommended timeline of patient follow-up and treatment after initial diagnosis.
Secondary Hypertension
More extensive diagnostic testing for the hypertensive patient depends on the presence of features suggesting secondary HTN or resistant HTN (ie, failure to respond to therapies). See Algorithm 100.3 Evaluation/screening for secondary hypertension. Unlike primary HTN, secondary HTN arises owing to an underlying specific etiology whose selective treatment leads to partial or complete restoration of normal BP. Common and uncommon causes of secondary HTN are presented in Table 100.3 along with their respective clinical indications and screening tests. Clinical examination findings that should provoke screening for secondary HTN are shown in Algorithm 100.3.
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