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Ambulatory Care - Hypertension - Fast Facts | NEJM Resident 360

Hypertension is a very common condition encountered in the outpatient setting and responsible for a significant portion of the mortality and morbidity from cardiovascular disease (CVD). The harms of hypertension are so well recognized today that it’s hard to believe medicine did not emphasize the importance of treating high blood pressure (BP) until the second half of the 20th century. In this section, we will cover the following:

• Guidelines

• Diagnosis and Treatment

• Resistant Hypertension

Stroke Mortality Rate in Each Decade of Age Versus Usual Blood Pressure at the Start of That Decade

Ischaemic Heart Disease Mortality Rate in Each Decade of Age Versus Usual Blood Pressure at the Start of That Decade

(Reprinted from The Lancet, Age-Specific Relevance of Usual Blood Pressure to Vascular Mortality: A Meta-Analysis of Individual Data for One Million Adults in 61 Prospective Studies. Lancet 2002, with permission from Elsevier.)

Guidelines

In 1977, the Joint National Committee (JNC) on Detection, Evaluation, and Treatment of High Blood Pressure sponsored by the National Heart, Lung, and Blood Institute (NHLBI) published the first guideline on hypertension. As shown in the chart below, over the course of the next four decades, many landmark clinical trials continued to shape our understanding of hypertension management and the optimal BP. 

Ultimately, it is important to individualize the approach to hypertension management when deciding treatment options and goals. For each patient, consider these factors:

• underlying conditions

• age

• cardiovascular risk

• treatment preferences

• potential for adverse medication effects

Trials Influencing Blood-Pressure Thresholds at Which Antihypertensive Medications Should Be Used

(Source: Lessons in Uncertainty and Humility — Clinical Trials Involving Hypertension. N Engl J Med 2016.)

Recommendations

In 2015, the Systolic Blood Pressure Intervention Trial (SPRINT) showed a mortality and cardiovascular benefit in patients with a high risk of cardiovascular disease, but without diabetes or stroke, when treated to a target systolic BP of <120 mm Hg versus <140 mm Hg. However, some experts expressed concern regarding the generalizability of these findings because of the way in which BP was measured in the study — a mean of three measurements after the patient was seated for 5 minutes of quiet rest — potentially leading to lower readings than in typical practice. Notably, in the intensively treated group, the average achieved systolic BP remained above 120 mm Hg and was associated with more hypotensive adverse effects.

2017 ACC/AHA Guidelines**:** In 2017, the ACC, AHA, and nine other societies published the current guidelines. These guidelines are heavily influenced by the results of the SPRINT trial and redefine BP categories and hypertension as follows:

2017 Blood Pressure and Hypertension Categories

The 2017 guidelines also incorporates 10-year risk of arteriosclerotic cardiovascular disease (ASCVD), as defined by the ACC/AHA risk estimator, into the treatment decision-making process. In brief, the newly recommended treatment algorithm is as follows:

Some experts have expressed concern that these guidelines will lead to the diagnosis of many more patients with hypertension and lead to excessive, unnecessary treatment. Ultimately, it is important to take the new guidelines into consideration as well as the risks, benefits, and preferences of the individual patient when deciding treatment options and goals.

2020 International Society of Hypertension issued Global Hypertension Practice Guidelines: These international guielines define grade 1 hypertension as a systolic BP of 140−159 mm Hg and/or diastolic BP of 90−99 mm Hg and grade 2 hypertension as ≥160 systolic and/or ≥100 diastolic following repeated examination. 

Diagnosis and Treatment

Measuring Blood Pressure

The first step in treating hypertension requires properly measuring BP. Key points for accurate BP measurements include the following:

• Diagnosis of hypertension should be based on the average of two or more properly measured readings at two or more follow-up visits after the initial screening visit.

• The patient should sit quietly for 5 minutes if possible before measuring.

• Use the right size cuff for the patient’s arm.

• Check BP in both arms at the first screening and use the arm with the higher reading for subsequent measurements.

Consider ambulatory BP monitoring in patients who might have white coat hypertension (high BP only in a health care setting), which is associated with minimal increased risk of CVD. In contrast, masked hypertension (normal office BP with elevated ambulatory BP) is associated with a risk of CVD and all-cause mortality similar to sustained hypertension. At present, data are not clear on how to screen for masked hypertension or the benefits of treating it.

Lifestyle Interventions

All patients should start with lifestyle interventions, such as weight loss, the DASH diet, dietary sodium reduction, potassium supplementation, regular exercise (at least 150 minutes of moderate activity a week), and restricted alcohol use (two standard drinks per day for men and one per day for women).

Medications

The following table lists first- and second-line agents recommended in the 2017 ACC/AHA guideline, with specific notes for different classes.

2017 ACC/AHA Recommended Oral Antihypertensive Drugs

Drug Class	Examples	Notes
First-line Agents
Thiazide-type diuretics	Chlorthalidone,
hydrochlorothiazide, metolazone

• Preferred drug class for African Americans

• Chlorthalidone preferred agent in class based on RCT evidence

• Can worsen gout

| | Calcium-channel blockers | Dihydropyridines: amlodipine,
felodipine, nifedipine |

• Preferred drug class for African Americans

• Avoid class in the setting of heart failure with reduced ejection fraction, but amlodipine can be used if needed

• Can cause lower-extremity edema

| | ACE inhibitors or ARBs | Lisinopril, enalapril

Losartan, valsartan |

• Preferred drug class for chronic kidney disease with albumin level ≥300 mg/d

• Don’t combine both drug classes together

• ARBs can be given to patients who have history of angioedema on ACE inhibitors 6 months after stopping ACE inhibitors

| | Second-line Agents | | Loop diuretics | Torsemide, furosemide | Preferred drug class over thiazides in the setting of heart failure and/or moderate-to-severe chronic kidney disease (e.g., estimated glomerular filtration rate <30 mL/min/1.73m²) | | Mineralocorticoid receptor antagonists | Spironolactone, eplerenone |

• Preferred drug class for primary hyperaldosteronism

• Spironolactone more likely to be associated with gynecomastia than eplerenone

• PATHWAY-2 trial showed efficacy in resistant hypertension (NEJM Journal Watch summary)

| | Potassium-sparing diuretics | Amiloride, triamterene | Avoid in patients with significant chronic kidney disease (e.g., estimated glomerular filtration rate <45 mL/min/1.73m²) | | Beta-blockers | Beta-1 selective: metoprolol
tartrate, metoprolol succinate,
atenolol, bisoprolol

Beta and alpha: carvedilol, labetalol |

• Preferred drug class in the setting of ischemic heart disease or heart failure

• Metoprolol succinate, bisoprolol, and carvedilol preferred in the setting of heart failure with reduced ejection fraction

• Avoid abrupt cessation

| | Direct renin inhibitor | Aliskiren | Don’t combine with ACE inhibitors or ARBs | | Alpha-1 blockers | Doxazosin, terazosin | Can cause orthostatic hypotension in the elderly |

(Adapted from Table 18 of 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension 2018.)

Resistant Hypertension

Patients who have uncontrolled BP despite taking three antihypertensive medications including a diuretic or who need at least four medications to reach their goal are considered to have resistant hypertension. Make sure that these patients are adhering to their medication regimens, have accurate BP measurements, make lifestyle changes, and stop taking any interfering drugs or substances (e.g., alcohol, caffeine, NSAIDs, sympathomimetics). True resistant hypertension along with the following clinical features should prompt a workup for secondary causes:

• severe hypertension

• abrupt-onset hypertension

• worsening of previously controlled hypertension

• disproportionate target organ damage to degree of hypertension

• onset of diastolic hypertension in those aged ≥65

• unprovoked or excessive hypokalemia

• age <30 (can still have primary hypertension)

Causes of Secondary Hypertension and Associated Diagnostic Tests

Causes	Characteristics	Diagnostic Test(s)
Renal parenchymal disease (e.g., polycystic kidney disease)	Nocturia, frequency, hematuria, family history, elevated creatinine, abnormal urinalysis	Renal ultrasound
Renovascular disease (e.g., fibromuscular dysplasia, atherosclerotic renal artery stenosis)	Sudden worsening or onset of hypertension in older patients, abdominal bruits, increased creatinine with ACE inhibitor/ARB treatment	Renal duplex Doppler ultrasound, magnetic resonance angiography (MRA), CT, renal artery angiography
Primary aldosteronism	Fatigue, muscle weakness, hypokalemia	Plasma aldosterone/renin ratio, abnormal aldosterone level after sodium loading, adrenal CT scan, adrenal vein sampling
Obstructive sleep apnea	Snoring, poor sleep, daytime sleepiness	Screening questionnaires, polysomnography
Pheochromocytoma	Paroxysmal hypertension, palpitations, diaphoresis, headache, family history	24-hour urinary metanephrine or plasma metanephrine, CT or MRI of abdomen and pelvis
Cushing syndrome	Weight gain, central adiposity, striae, muscle weakness, hyperglycemia, depression	Dexamethasone suppression test, 24-hour urinary cortisol, midnight salivary cortisol
Hypothyroidism	Dry skin, cold intolerance, weight gain, constipation	Thyroid-stimulating hormone, free thyroxine
Hyperthyroidism	Warm moist skin, heat intolerance, anxiety, diarrhea, insomnia	Thyroid-stimulating hormone, free thyroxine
Coarctation of the aorta	Young patient, higher brachial BP than femoral, back or chest bruit	Echocardiography, MRA, CTA

(Adapted from Table 13 of 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. Hypertension 2018.)

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