Hypertension, Outpatient Case File
Eugene C. Toy, MD, Gabriel M. Aisenberg, MD
Case 6
A 56-year-old man comes into your clinic as a new patient. Seven years ago at a work-related health screening, he was diagnosed with hypertension and hypercholesterolemia. At that time, he saw a physician who prescribed a diuretic and encouraged him to lose weight, modify his diet, and exercise. Since that time, he has not followed up with any clinician. Last month, a routine optometry examination showed hypertensive retinopathy, and he was instructed to follow up with a physician. He brings the optometry report to this visit, which describes arteriovenous crossing defects and increased arteriolar light reflex. He denies chest pain, shortness of breath, dyspnea on exertion, or paroxysmal nocturnal dyspnea. He smokes one pack of cigarettes per day and has done so since he was 15 years old. He typically drinks two glasses of wine with dinner. On examination, the patient is obese; you calculate his body mass index (BMI) as 30 kg/m2. His blood pressure is 168/98 mm Hg in the right arm and 170/94 mm Hg in the left arm, and his heart rate is 84 beats per minute (bpm). He has no thyromegaly or carotid bruits. Cardiac examination reveals an S4 gallop. No cardiac murmurs are auscultated. Lung and abdomen examinations are normal.
▶ What is the most likely diagnosis?
▶ What are your next steps?
ANSWERS TO CASE 6:
Hypertension, Outpatient
Summary: A 56-year-old man is being evaluated as a new patient with
- Blood pressure of 168/98 mm Hg in the right arm and 170/94 mm Hg in the left arm
- Fundoscopic examination revealing hypertensive retinopathy
- Cardiac fourth heart sound, consistent with a thickened, noncompliant ventricle
- Multiple cardiovascular risk factors, including his age, obesity, and smoking
Most likely diagnosis: Stage 2 hypertension with end-organ damage (left ventricular hypertrophy and hypertensive retinopathy).
Next steps:
- Use laboratory evaluation and a baseline electrocardiogram (ECG) to assess for end-organ damage.
- Assess patient’s overall cardiovascular risk status, including lipid profile.
- Rule out secondary causes of hypertension.
ANALYSIS
Objectives
- Underline the initial evaluation of a patient with hypertension. (EPA 1, 3)
- List the most common antihypertensive medications and their indications and cautions regarding their usage. (EPA 4, 12)
- Describe the various causes of secondary hypertension and when to pursue these diagnoses. (EPA 2, 3)
Considerations
This is a 56-year-old man with severe hypertension who has physical examination evidence of hypertensive end-organ damage (hypertensive retinopathy and left ventricular hypertrophy). He has multiple risk factors for atherosclerotic disease. The most likely diagnosis is essential hypertension, but secondary causes still must be considered. Although you have measured his blood pressure only once in your clinic, he has been told before that he is hypertensive, and he already appears to have end-organ damage of hypertension. His blood pressure is above 160 mm Hg systolic or 100 mm Hg diastolic which places him in stage 2 hypertension. He should be started on two-drug therapy without further delay.
APPROACH TO:
Hypertension
DEFINITIONS
DIEATRY APPROACHES TO STOP HYPERTENSION (DASH) DIET: Diet rich in fruits, vegetables, legumes, and low-fat dietary products and low in snacks, sweets, meat, and saturated fat, with an emphasis of a sodium intake lower than 2300 mg/d.
ELEVATED BLOOD PRESSURE: Systolic blood pressures 120 to 129 mm Hg and diastolic < 80 mm Hg.
ESSENTIAL HYPERTENSION: Elevated blood pressure without a known cause, also called primary or idiopathic hypertension. It comprises approximately 80% to 95% of all cases of hypertension.
LIFESTYLE MODIFICATION: A cornerstone in the treatment of hypertension, consisting of regular aerobic activity, weight loss, decreased salt intake, and adherence to a DASH–type dietary plan. Alcohol consumption should be moderated, no more than two glasses of wine per day for men and one glass per day for women.
SECONDARY HYPERTENSION: Elevated blood pressure with a known underlying cause, such as renal artery stenosis or primary aldosteronism. Prevalence is approximately 5% to 20% of all cases of hypertension.
STAGE 1 HYPERTENSION: Blood pressures 130–139/80–89 mm Hg.
STAGE 2 HYPERTENSION: Blood pressures equal to or greater than
140/90 mm Hg.
CLINICAL APPROACH
Background and Epidemiology
Hypertension is not diagnosed based on one blood pressure measurement. In general, a diagnosis of hypertension requires repeatedly elevated measurements, ideally including measurements outside of the clinic setting. This can involve the patient checking their blood pressures at home or ambulatory blood pressure monitoring (ABPM). ABPM consists of sending a patient home with an automated blood pressure cuff that measures over a 24-hour period. Either of these methods gives a more accurate measurement of a patient’s overall blood pressure than clinic readings alone.
One well-described phenomenon is “white coat hypertension,” in which patients have elevated blood pressures in the clinic, but normal blood pressures by ABPM or home measurement. The clinical significance and treatment goals for white coat hypertension are currently unclear. The inverse of white coat hypertension is “masked hypertension,” in which a patient has normal clinic blood pressures but elevated measurements on ABPM or home measurement. These patients have
an elevated risk of cardiovascular morbidity and mortality and should be treated despite normal clinic measurements.
Cardiovascular risk factors and hypertensive target organ damage should be identified. The major risk factors for cardiovascular disease (CVD) are age, cigarette smoking, dyslipidemia, diabetes mellitus, obesity, kidney disease, and a family history of premature CVD.
Pathophysiology
Underlying causes of hypertension must then be considered. Essential or idiopathic hypertension is the most common form of hypertension, comprising 80% to 95% of cases, but approximately 5% to 20% of cases of hypertension have secondary causes (Table 6–1). To identify the secondary (and potentially reversible) causes of hypertension, the clinician must be aware of the clinical and laboratory manifestations of the processes. A secondary cause of hypertension should be suspected and worked up when patients have any of the following clinical features: age of onset before 25 or after 55, presentation with evidence of end-organ damage, refractory hypertension requiring three or more antihypertensive medications, hypertension that has suddenly become uncontrolled, a rising creatinine level with the use of angiotensin-converting enzyme (ACE) inhibitors, or other clinical signs of a secondary cause.
Clinical Presentation
Target organ damage of hypertension includes left ventricular hypertrophy, nephropathy, retinopathy, and cerebrovascular disease. A complete history and physical examination, including fundoscopic examination; auscultation of the major arteries for bruits; palpation of the abdomen for enlarged kidneys, masses, or an enlarged abdominal aorta; evaluation of the lower extremities for edema and perfusion; and a neurologic examination, should be standard. Some initial
laboratory testing is also indicated for a patient with a new diagnosis of hypertension (Table 6–2).
Treatment
Therapy Based on Staging. Initial therapy should be based on the stage or degree of hypertension. For those with elevated blood pressure (blood pressure 120–129/ < 80 mm Hg), lifestyle modifications and 3- to 6-month follow-up are the only interventions indicated unless they have another comorbid condition, such as heart failure or diabetes, which necessitate the use of an antihypertensive.
Patients with stage 1 hypertension (blood pressure 130–139/80–89 mm Hg) should be risk assessed for CVD; those with a 10-year CVD risk > 10% should be started on a single antihypertensive agent along with lifestyle modifications, whereas those with lower CVD only require lifestyle modification and 3- to 6-month follow-up.
Patients with stage 2 hypertension (> 140/90 mm Hg) will need lifestyle modification and antihypertensive medication. Patients starting antihypertensive agents should receive 1-month follow-up to evaluate whether the patient’s blood pressure goals are being met or require intensification of therapy.
In 2015, the National Institutes of Health–sponsored systolic blood pressure intervention trial (SPRINT trial) showed that for patients age 50 or older with at least one other cardiovascular risk factor, a target blood pressure of 120 mm Hg (rather than 140 mm Hg) produced a 30% risk reduction in cardiovascular events, stroke, and cardiovascular death.
Lifestyle Changes. Counseling patients on lifestyle changes is important at any blood pressure level and includes weight loss, limitation of alcohol intake, increased aerobic physical activity, reduced sodium intake (< 6 g NaCl or 2.3 g sodium), cessation of smoking, and adherence to a DASH diet.
Pharmacotherapy. For most patients with hypertension, lowering blood pressure itself reduces cardiac risk and is more important than the choice of agent. Several different drugs appear to be equally effective as initial monotherapy. Thiazide diuretics, calcium channel blockers, ACE inhibitors, or angiotensin II receptor blockers (ARBs) are all widely used and acceptable choices. When considering initial therapy in patients of African descent, evidence shows benefit from the use of thiazide diuretics or long-acting calcium channel blockers over other antihypertensives. ACE inhibitors or ARBs should be used for initial monotherapy in patients with diabetic nephropathy or those with nondiabetic chronic kidney disease complicated by proteinuria because of their ability to reduce intraglomerular pressure via inhibition of angiotensin II–mediated efferent arteriolar vasoconstriction. Beta-blockers are not recommended for initial monotherapy unless there is a specific indication, such as ischemic heart disease. If patients have markedly elevated blood pressures at baseline (stage 2 hypertension), a single agent will often not be able to achieve good blood pressure control, and patients will often require combination therapy with two or more agents. Whatever drug class is used, a long-acting formulation that provides 24-hour efficacy is preferred over short-acting agents for better compliance and more consistent blood pressure control. A list of oral antihypertensive drugs is extensive (Table 6–3).
For some patients, there are specific compelling indications to use specific drug classes. ACE inhibitors or ARBs are the agents of choice in hypertensive patients with diabetes or systolic heart failure. Beta-blockers would be first-line agents in patients with hypertension and coronary artery disease or a history of tachyarrhythmias. Alpha-blockers may be considered in men with hypertension and benign prostatic hypertrophy. Most patients ultimately need more than one drug to control their blood pressure. It is critical to tailor the treatment to the patient’s personal, financial, lifestyle, and medical factors and to periodically review compliance and adverse effects.
SELECTED CAUSES OF SECONDARY HYPERTENSION
Renal Causes
The most common cause of secondary hypertension is renal disease (renal parenchymal or renovascular). Renal artery stenosis is caused by atherosclerotic disease with hemodynamically significant blockage of the renal artery in older patients or by fibromuscular dysplasia in younger adults. The clinician must have a high index of suspicion, and further testing may be indicated, for instance, in an individual with diffuse atherosclerosis. Abrupt elevations in creatinine after using an ACE inhibitor or ARB, a renal bruit, recurrent pulmonary edema, or low potassium may be suggestive of renal artery stenosis. Initial imaging options include renal ultrasound, computed tomographic (CT) angiography, or magnetic resonance (MR) angiography, with MR angiography having the highest sensitivity and specificity. Captopril-enhanced radionuclide scan is less useful diagnostically (interrater variability) but may provide functional information about the stenotic kidney. Surgical or angioplastic correction of the vascular occlusion may be considered.
Polycystic kidney disease is inherited as an autosomal dominant trait. The classic clinical findings are positive family history of polycystic kidney disease, bilateral flank masses, flank pain, elevated blood pressure, and hematuria. Other causes of chronic renal disease very commonly lead to hypertension.
Endocrine causes
Primary hyperaldosteronism is an increasingly recognized cause of hypertension, contributing to as much as 5% to 10% of patients with hypertension. Although hyperaldosteronism “classically” presents with hypertension, metabolic alkalosis, and hypokalemia, more than half of patients will have normal bicarbonate and
Abbreviations: ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blockers; BPH, benign prostatic hypertrophy; CHF, congestive heart failure; MI, myocardial infarction.
Data from Kasper DL, Fauci AS, Hauser SL, et al. Harrison’s Principles of Internal Medicine. 19th ed. 2015. Copyright © McGraw Hill LLC. All rights reserved.
potassium levels. A more common presentation is severe hypokalemia provoked by diuretics. Hyperaldosteronism can be screened for with a renin/aldosterone ratio. If abnormal, further workup should be pursued to confirm the diagnosis and determine if the hyperaldosteronism is due to adrenal adenoma or adrenal hyperplasia.
Hyperthyroidism may also cause hypertension. The patient will have a widened pulse pressure with increased systolic blood pressure and decreased diastolic blood pressure, as well as a hyperdynamic precordium. The patient may have warm skin, tremor, and thyroid gland enlargement or a palpable thyroid nodule. A low level of serum thyroid-stimulating hormone (TSH) and elevated levels of thyroid hormones (eg, free T4) are diagnostic.
Glucocorticoid excess states, including Cushing syndrome, and iatrogenic (treatment with glucocorticoids) classically present with thinning of the extremities, truncal obesity, round moon face, supraclavicular fat pad, purple striae, acne, and possibly psychiatric symptoms. Excess corticosteroids cause secondary hypertension due to a combination of mineralocorticoid activity and upregulating vascular sensitivity to vasoconstrictors. Dexamethasone suppression testing of the serum cortisol level aids in the diagnosis of Cushing syndrome.
Pheochromocytoma is a rare catecholamine-releasing adrenal tumor that typically produces hypertension. Classic clinical manifestations include paroxysmal headaches, palpitations, diaphoresis, pallor, and chest pain. It can be diagnosed by elevated urinary and plasma metanephrine and normetanephrine.
Other Causes
Obstructive sleep apnea (OSA) is another fairly common cause of hypertension. Obstructive sleep apnea is caused by abnormal relaxation of the upper airway musculature, resulting in hypoxic and hypercarbic episodes during sleep. Over time, this can lead to systemic vasoconstriction, systolic hypertension, and pulmonary hypertension. Strongly suspect OSA in a patient with obesity, snoring, daytime sleepiness, and a crowded palate. OSA is diagnosed with “sleep studies” (ie, polysomnography) and treated with nighttime continuous positive airway pressure.
Coarctation of the aorta is a congenital narrowing of the aortic lumen and usually is diagnosed in younger patients by finding hypertension along with discordant upper and lower extremity blood pressures. Coarctation of the aorta can cause leg claudication, cold extremities, and delayed or diminished femoral pulses as a result of decreased blood pressure in the lower extremities. Rib notching may be seen on chest x-ray due to development of collateral circulation. In children, echocardiography is often diagnostic, while adults may require CT or MR angiography.
CASE CORRELATION
- See also Case 7 (Hypertensive Encephalopathy/Pheochromocytoma).
COMPREHENSION QUESTIONS
6.1 A 30-year-old woman is noted to have blood pressures in the 160/100 mm Hg range. She also has increased obesity, especially around her abdomen, which also shows some striae. She has been bruising very easily and has increased hair growth on her face and chest. Which of the following most likely to reveal the diagnosis?
A. Thyroid-stimulating hormone
B. MR angiography of the renal vessels
C. Dexamethasone suppression test and serum cortisol
D. Urinary metanephrine
6.2 A 45-year-old man is diagnosed with essential hypertension based on two blood pressures of 150/100 and 156/102 mm Hg during two separate visits. He has no other medical problems. Which of the following would most likely provide prognostic information regarding this patient?
A. Vascular biopsy
B. End-organ effects from hypertension
C. Patient’s enrollment in a clinical trial
D. Measurement of serum homocysteine levels
6.3 A 34-year-old woman contemplating pregnancy is diagnosed with stage 1 hypertension, and after an evaluation she is noted to have no complications. Which of the following antihypertensive classes may be appropriate for this individual?
A. Beta adrenergic blockers
B. Angiotensin-converting enzyme inhibitors
C. Direct renin inhibitors
D. Angiotensin receptor blockers
E. Thiazide diuretics
6.4 A 45-year-old African American man is noted to have blood pressures of 145/90 mm Hg and 150/96 mm Hg on two separate occasions. He has no other medical problems and no signs or symptoms suggestive of secondary hypertension. Which of the following is the best initial therapy for this patient?
A. Chlorthalidone
B. Lisinopril
C. Metoprolol succinate
D. Clonidine
E. Spironolactone
ANSWERS
6.1 C. This question addresses secondary causes of hypertension. This patient’s central obesity, abdominal striae, hirsutism, and easy bruisability are consistent with Cushing syndrome, which can be diagnosed with a dexamethasone suppression test and serum cortisol. TSH (answer A) would be useful for evaluating for hyperthyroidism causing hypertension, which would present with weight loss, heat intolerance, and tremor. MR angiography (answer B) is a good diagnostic test for renal artery stenosis, which may present with a renal bruit. Urinary metanephrine (answer D) can evaluate for pheochromocytoma, which presents with paroxysmal hypertension, headaches, and diaphoresis.
6.2 B. The prognosis in hypertension depends on the patient’s other cardiovascular risks and observed end-organ damage from hypertension, such as left ventricular hypertrophy, hypertensive retinopathy, or chronic kidney disease. Vascular biopsy (answer A) is indicated in some patients with vasculitis, which may present with a wide variety of end-organ damage and inflammatory markers. Enrollment in clinical trials (answer C) is not required for effective control of hypertension. Serum homocysteine levels (answer D) are elevated in some genetic disorders as well as B12 or folate deficiency.
6.3 A. Labetalol, which is a beta blocking agent, is widely used in pregnant women and is considered safe for the fetus. ACE inhibitors, ARBs, and direct renin inhibitors (answers B, C, and D) are contraindicated in all stages of pregnancy. Thiazide diuretics (E) can cause thrombocytopenia in the fetus and is not recommended in pregnancy. Methyldopa is an older agent less effective than labetalol.
6.4 A. Chlorthalidone is a thiazide-like diuretic that is preferred over hydrochlorothiazide by many hypertension experts for its longer acting effects. Recall that thiazide diuretics or calcium channel blockers are preferred initial therapy for black patients. Lisinopril (answer B) is an ACE inhibitor, which would be a reasonable choice in a non-black patient or a necessity in a patient with diabetes. Metoprolol (answer C) is not a first-line therapy for hypertension in the absence of other indications. Clonidine (answer D) is a third- or fourth-line agent for hypertension; it is not preferred due to potent rebound hypertension when a patient discontinues the medicine. Spironolactone (answer E) is an aldosterone antagonist that can be used to treat primary hyperaldosteronism; it is occasionally used in combination with other medicines to treat refractory hypertension. It is not a first-line antihypertensive and is not indicated in this patient.
CLINICAL PEARLS
▶ In general, the diagnosis of hypertension requires two or more blood pressure measurements on at least two visits or the use of ambulatory or home blood pressure monitoring.
▶ Cardiovascular disease risk evaluation consists of identifying target organ dysfunction and cardiovascular risk factors, such as diabetes and hyperlipidemia.
▶ Most patients with hypertension have essential hypertension, but secondary causes of hypertension should be evaluated when clinically indicated.
▶ A urinalysis, ECG, comprehensive metabolic panel (CMP), and lipids are indicated in patients with newly diagnosed hypertension.
▶ First-line agents for hypertension are thiazide diuretics, ACE inhibitors, ARBs, and dihydropyridine calcium channel blockers. Many patients will require combination therapy.
▶ Renal diseases, including renovascular hypertension, are the most common causes of secondary hypertension.
▶ Lifestyle modifications consisting of dietary changes, exercise, and moderation of alcohol intake are indicated to address hypertension control and lower overall cardiovascular risk.
▶ For most patients, the degree of blood pressure reduction is the major determinant of cardiovascular risk reduction, rather than the class of antihypertensive drug used.
REFERENCES
Carey RM, Whelton PK for the 2017 ACC/AHA Hypertension Guideline Writing Committee. Prevention, detection, evaluation, and management of high blood pressure in adults: synopsis of the 2017 American College of Cardiology/American Heart Association hypertension guideline. Ann Intern Med. 2018;168:351-358.
James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014;311(5):507-520.
Kotchen TA. Hypertensive vascular disease. In: Jameson JL, Fauci AS, Kasper D, et al, eds. Harrison’s Principles of Internal Medicine. 20th ed. New York, NY: McGraw Hill; 2018:1611-1627.
Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281-1357.
The SPRINT Research Group. A randomized trial of intensive versus standard blood pressure control. N Engl J Med. 2015;373:2103-2116.
Textor S. Establishing the diagnosis of renovascular hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com/contents/establishing-the-diagnosis-of-renovascular-hypertension Accessed July 14, 2019.
Textor S. Evaluation of secondary hypertension. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. https://www.uptodate.com. Accessed July 14, 2019.
Whelton PK, Carey RM, Aronow WS, et al. 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: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71(6):e13-e115.
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