Cardiology Intensive Board Review, 3th Edition

Chapter 11 - Hypertension

Amanda R. Vest, Leslie S. Cho

QUESTIONS

1.A 35-year-old woman at 24 weeks of pregnancy is found to have several blood pressure readings in the range of 145 to 158 mmHg systolic, 80 to 92 mmHg diastolic. This is her first pregnancy and she has no prior history of hypertension. She reports bilateral mild ankle swelling and nausea, but no right upper quadrant pain, visual changes, headaches, or dyspnea. A 24-hour urine collection shows 360 g protein. The hemoglobin is 8.0 g/dL and the platelet count is 43,000 cells/mm3. Which of the following is the correct diagnosis?

a.Chronic hypertension

b.Gestational hypertension

c.Preeclampsia

d.Eclampsia

2.A 42-year-old woman presents for post hospitalization follow-up. She was recently admitted to hospital for 3 days due to sudden-onset dyspnea. Her blood pressure on presentation was 164/98 mmHg. Her examination and chest radiograph were consistent with pulmonary edema. She responded well to intravenous diuretics and was discharged on lisinopril. She has no family history of hypertension. On examination during the clinic visit, her blood pressure is 158/90 mmHg. She is normal in weight and has a normal cardiovascular examination except for a right-sided carotid bruit. Her blood tests are notable for a rise in creatinine from 0.9 to 1.8 mg/dL since hospital discharge. What is the most appropriate follow-up investigation?

a.Coronary angiogram

b.Duplex ultrasonography of the renal arteries

c.Urinary catecholamines

d.24-Hour urinary-free cortisol

3.An 83-year-old woman presents to cardiology clinic for follow-up of her hypertension and coronary artery disease. Her only current symptom is dizziness on standing from a sitting position. The dizziness caused her to lose balance and fall on two occasions. Her current resting blood pressure is 144/90 mmHg with pulse 60 beats per minute (bpm). Her medications include hydrochlorothiazide 25 mg daily, doxazosin 2 mg daily, metoprolol XL 50 mg daily, simvastatin 40 mg daily, and aspirin 81 mg daily. What changes in medication therapy would you recommend?

a.Discontinue hydrochlorothiazide and start lisinopril 20 mg daily.

b.Discontinue atenolol and increase hydrochlorothiazide to 50 mg daily.

c.Discontinue doxazosin and initiate clonidine 0.4 mg twice daily.

d.Discontinue doxazosin and start lisinopril 5 mg daily.

e.Discontinue doxazosin and increase metoprolol to 100 mg daily.

4.A 64-year-old woman with hypertension, stage III chronic kidney disease (CKD), and diabetes is not yet at blood pressure goal on the following antihypertensives: lisinopril 40 mg, hydrochlorothiazide 25 mg, and metoprolol XL150 mg. Which of the following additional agents is contraindicated?

a.Aliskiren

b.Hydrochlorothiazide

c.Amlodipine

d.Methyldopa

5.A 57-year-old woman with multidrug-resistant hypertension presents to her primary care doctor with multiple complaints. Her antihypertensive regimen consists of valsartan, hydralazine, amlodipine, captopril, and hydrochlorothiazide. Which of the following pairings of medication and side effect are most likely to be correct?

a.Valsartan and cough

b.Hydralazine and ankle edema

c.Amlodipine and insomnia

d.Captopril and constipation

6.A 19-year-old young man presents with an aortic root diameter of 4.4 cm and a strong family history of aortic dissection. His father died of a type A dissection at age 42, and his older brother recently underwent aortic root repair for an aneurysm measuring 5.6 cm in diameter. Both brothers have the fibrillin-1 gene mutation. The patient currently receives metoprolol 50 mg daily, with a pulse of 55 bpm and blood pressure measurements in the range of 115 to 125/65 to 75 mmHg. Which additional medication should be added?

a.No additional medications

b.Amlodipine

c.Ramipril

d.Losartan

7.A 62-year-old man with type 1 diabetes mellitus receives intermittent hemodialysis for his end-stage renal disease. His blood pressure has become elevated over the past year and has not reached goal levels despite initiation of three antihypertensive medications. He takes several medications for comorbid conditions, several of which may be exacerbating his elevated blood pressure. Medications for which of the following conditions would not be expected to have a side effect of hypertension?

a.Diabetes

b.Anemia

c.Hyperparathyroidism

d.Glaucoma

e.Osteoarthritis

8.A 58-year-old man with resistant hypertension returns for outpatient follow-up. His blood pressure is 168/79 mmHg and pulse 70 bpm, despite 25 mg hydrochlorothiazide daily, 200 mg metoprolol XL daily, 320 mg valsartan daily, 10 mg amlodipine daily, and a 0.1 mg/24 hour clonidine patch. He is considering entering a sympathetic denervation trial and has some questions about the procedure. Which of the following is the most accurate brief description of the denervation procedure?

a.Access through a femoral vein, cryoablation of a unilateral renal artery

b.Access through a femoral artery, radiofrequency ablation of a unilateral renal artery

c.Access through a femoral vein, radiofrequency ablation of bilateral renal arteries

d.Access through a femoral artery, alcohol ablation of bilateral renal arteries

e.Access through a femoral artery, radiofrequency ablation of bilateral renal arteries

f.At this time renal denervation cannot be recommended for this patient population

9.Which of the following patient characteristics is a risk factor for development of angiotensin-converting enzyme inhibitor (ACEI)-induced angioedema?

a.Diabetes

b.Female gender

c.Age <45 years

d.Age >65 years

10.A 76-year-old man with hypertension has inadequate blood pressure control on chlorthalidone 25 mg daily. His primary care doctor is choosing a second antihypertensive agent. Which of the following comorbidities would be an evidence-based indication for choosing ramipril over amlodipine as the second agent?

a.Heart failure with preserved ejection fraction (HFPEF)

b.Peripheral arterial disease

c.Sleep apnea

d.Aortic aneurysm

11.A 30-year-old man with no past medical history presents to his primary care physician complaining of new-onset morning headaches that have been ongoing for the past few weeks. His blood pressure is noted to be 220/100 mmHg with a gradient between his brachial and popliteal arteries. On auscultation, there is a II/VI systolic crescendo–decrescendo murmur heard across the precordium. His electrocardiogram is significant for left ventricular hypertrophy. A chest X-ray shows cardiomegaly with evidence of rib notching. The patient most likely has what valvular abnormality?

a.Bicuspid aortic valve

b.Mitral regurgitation

c.Tricuspid regurgitation

d.Pulmonary stenosis

12.A 55-year-old man with diabetes mellitus presents to his cardiologist with a blood pressure of 165/95 mmHg. According to the JNC (Joint National Committee) 8 guidelines, what is his target blood pressure measurement?

a.Prehypertension, 140/90 mmHg

b.Stage 2, 130/80 mmHg

c.Stage 1, 140/90 mmHg

d.Stage 2, 110/70 mmHg

13.What is the mechanism of action of the antihypertensive medication aliskiren?

a.ACEI

b.Nonselective β-blockade

c.Angiotensin receptor blocker (ARB)

d.Direct renin inhibitor

14.A 35-year-old woman with no past medical history, not receiving oral contraceptives, and with a family history of hypertension presents with a gradual increase in blood pressure over the past few years. Today in clinic her blood pressure is 155/95 mmHg. What is the most appropriate next step?

a.Patient has essential hypertension; start thiazide diuretic

b.She is asymptomatic; therefore, observe patient and have her follow-up in 1 year

c.Have her follow-up in a few weeks for repeat blood pressure measurements

d.Renal magnetic resonance imaging (MRI)

15.A 68-year-old man with coronary artery disease, hypertension, diabetes mellitus, and stage II hypertension presents for routine follow-up in the cardiology clinic. His blood pressure is 180/100 mmHg. He is compliant with all his medications and is currently on hydrochlorothiazide, lisinopril, metoprolol, amlodipine, and isosorbide mononitrate. He recently has had two episodes of noncardiogenic pulmonary edema in the setting of an ejection fraction of 55% with no evidence of diastolic dysfunction. What is the most appropriate next step in the management of his hypertension?

a.Addition of minoxidil

b.Renal MRI

c.Discussion of medical adherence

d.Addition of hydralazine

16.A 44-year-old woman had a blood pressure of 115/75 mmHg a few years ago. She now has a blood pressure of 155/75 mmHg, which was confirmed on a repeat visit. How much has her risk for cardiovascular disease increased?

a.No change

b.Twofold

c.Fourfold

d.Tenfold

17.Which of the following antihypertensive agents is a known cause of autoimmune hemolytic anemia?

a.Metoprolol

b.Methyldopa

c.Captopril

d.Losartan

18.A patient is initiated on an ACEI. What is the recommended cutoff for rise in creatinine before stopping the medication?

a.10% increase in creatinine

b.20% increase in creatinine

c.35% increase in creatinine

d.50% increase in creatinine

19.A 68-year-old man with hypertension and history of a stroke presents for further management of his hypertension. He is currently prescribed a thiazide diuretic; however, his blood pressure remains elevated. From the standpoint of decreasing his future risk of stroke, which of the following drug classes would be most beneficial?

a.Calcium channel blocker

b.ACEI

c.ARB

d.β-Blocker

20.A 56-year-old woman presents to your clinic for physical examination. She has no significant past medical history and is asymptomatic. Her vital signs are significant for a blood pressure of 145/95 mmHg. What are the next steps in her evaluation for hypertension?

a.She should return in 1 year for her yearly physical examination.

b.She should have a repeat blood pressure measurement at a later time point during her visit and return in a few weeks to obtain repeat testing if that measurement is elevated.

c.Start patient on thiazide diuretic at the initial clinic visit.

d.Begin evaluation for secondary causes of hypertension.

21.A 45-year-old woman with no significant past medical history is noted to have a blood pressure of 145/90 mmHg in the outpatient clinic. This is confirmed on repeat visits. Which of the following tests would not be indicated at this time?

a.Electrocardiogram

b.Urinalysis

c.Creatinine

d.Urine metanephrines

22.A 26-year-old man with no significant history presents to his primary care physician with complaints of episodic palpitations, morning headaches, and diaphoresis. He denies any illicit drug use. His physical examination is notable for a blood pressure of 230/120 mmHg. His ophthalmologic examination is significant for AV nicking. What is the most appropriate next step?

a.Toxicology screen

b.Urine metanephrines

c.MRI thorax

d.Start thiazide diuretic with follow-up in 1 month

23.A 65-year-old man with a history of hypertension and dyslipidemia is admitted to the coronary care unit with a diagnosis of a myocardial infarction. He undergoes an emergent cardiac catheterization with insertion of a drug-eluting stent to his left circumflex coronary artery. His vital signs show a blood pressure of 170/90 mmHg with a heart rate of 85 bpm and no evidence of heart failure on examination. Which of the following medications would be most appropriate to treat this patient’s hypertension?

a.Amlodipine

b.Verapamil

c.Metoprolol

d.Nitroprusside

24.Which of the following antihypertensive drug classes is most effective at reducing carotid intimal thickness?

a.Calcium channel blocker

b.β-Blocker

c.ACEI

d.Thiazide diuretic

25.What is the long-term antihypertensive mechanism of action for thiazide diuretics?

a.Decreased plasma volume

b.Natriuresis

c.Decreased cardiac output

d.Decreased peripheral resistance

26.A 46-year-old woman, status post orthotopic heart transplantation, is currently taking mycophenolate, prednisone, and tacrolimus as an immunosuppressive regimen. On routine laboratory evaluation, she is found to have leukopenia. Mycophenolate levels have not been elevated in the past few months. Which of the following antihypertensive agents is the most likely culprit?

a.Hydrochlorothiazide

b.Metoprolol

c.Captopril

d.Clonidine

27.A 34-year-old man with isolated essential hypertension presents to clinic and is found to have a blood pressure of 180/100 mmHg after intensive lifestyle modifications. What is the most appropriate next step?

a.Start hydrochlorothiazide.

b.Start hydrochlorothiazide and lisinopril.

c.Repeat blood pressure in 4 weeks.

d.Start amlodipine.

28.A 62-year-old man with isolated essential hypertension, currently taking hydrochlorothiazide 25 mg PO daily, comes to you for his first clinic visit. He notes that his blood pressure at home is always less than 140/80 mmHg, but in clinic it is always at least 155/95 mmHg. What is the next step?

a.Increase dose of thiazide

b.Addition of second antihypertensive medication

c.Do nothing as he has white coat hypertension

d.Evaluate for secondary causes of hypertension

29.A 48-year-old man with diabetes mellitus, hypertension, and hyperlipidemia presents to the emergency room with hypertensive emergency. His mean arterial pressure is 150 mmHg, pulse 58 bpm. The electrocardiogram is notable for sinus bradycardia with PR prolongation (260 milliseconds) and no ST deviations or T-wave abnormalities. Which medications would be the most appropriate therapy for this patient?

a.Intravenous nitroprusside

b.Sublingual nifedipine

c.Intravenous labetalol

d.Intravenous nitroglycerin

30.A 48-year-old obese man with hypertension, dyslipidemia, and diabetes mellitus presents to the outpatient clinic for his yearly physical. He has refused medications in the past, but now is willing to consider treatment. His blood pressure is 145/95 mmHg with a heart rate of 80 bpm. His laboratory data are significant for a creatinine of 1.3 mg/dL with the presence of microalbuminuria. Which of the following mediations would be most appropriate?

a.Carvedilol

b.Lisinopril

c.Chlorthalidone

d.Terazosin

31.A 34-year-old woman with essential hypertension is considering becoming pregnant. Which of the following medications would be absolutely contraindicated to control her blood pressure during pregnancy?

a.Methyldopa

b.Labetolol

c.Captopril

d.Nifedipine

32.A 48-year-old Caucasian man with impaired fasting glucose presents to his physician for a follow-up visit after he was noted to have a blood pressure of 150/95 mmHg. On repeat evaluation his blood pressure is 155/95 mmHg. Which of the following medications would be the least favored?

a.Hydrochlorothiazide 25 mg PO daily

b.Lisinopril 10 mg PO daily

c.Atenolol 25 mg PO daily

d.Chlorthalidone 25 mg PO daily

33.A 65-year-old African American man with isolated hypertension presents to clinic for his yearly physical examination. He is noted to have a blood pressure of 170/95 mmHg. He is currently prescribed lisinopril and metoprolol. Which of the following medication changes would be most appropriate?

a.Continue current medications at increased doses

b.Conversion of patient to a calcium channel blocker and thiazide diuretic

c.Addition of clonidine

d.Stopping lisinopril because of concern for renal artery stenosis

34.A 42-year-old woman with a new diagnosis of diabetes mellitus presents for management of hypertension. She was previously an avid athlete, but over the past few years has noted increased weight gain, a radial fracture after a minor fall, and increasing hirsutism. She is currently on hydrochlorothiazide, amlodipine, and lisinopril. What is the most appropriate next step in the management of this patient’s hypertension?

a.Referral to nutrition specialist to assist her with weight loss

b.Addition of clonidine

c.24-Hour urine cortisol test

d.MRI of the brain

35.A 69-year-old woman with diabetes mellitus and hyperlipidemia and no history of hypertension is noted at her yearly clinic visit to have new-onset hypertension with a blood pressure of 180/110 mmHg. She undergoes screening for secondary causes of hypertension and is found to have a pheochromocytoma. What of the following medications is contraindicated as monotherapy?

a.Metoprolol

b.Lisinopril

c.Phentolamine

d.Hydrochlorothiazide

36.A 42-year-old man presents for a routine physical examination. He is noted to have a body mass index of 30 kg/m2, impaired fasting glucose, and a blood pressure of 135/85 mmHg. What is the best treatment plan for this individual?

a.Aggressive lifestyle modification

b.Institute thiazide diuretic regimen

c.No treatment at this time

d.Initiate ACEI

37.A 50-year-old man with CKD and hypertension has a blood pressure of 165/110 mmHg. What is this patient’s target blood pressure according to the JNC 8 guidelines?

a.140/90 mmHg

b.130/80 mmHg

c.120/80 mmHg

d.110/70 mmHg

38.A 36-year-old patient, status post heart transplantation, is found to have hypertension. He is currently taking prednisone, mycophenolate, and cyclosporine. Which of the following antihypertensive medications would increase cyclosporine levels?

a.Lisinopril

b.Hydrochlorothiazide

c.Diltiazem

d.Metoprolol

39.A 56-year-old man with resistant hypertension begins to take a new antihypertensive agent. Within the next few weeks he is diagnosed with pericarditis. Which of the following agents is most likely responsible?

a.Carvedilol

b.Minoxidil

c.Amlodipine

d.Captopril

40.A 27-year-old woman presents to the cardiology clinic for evaluation of uncontrolled hypertension. She was diagnosed 2 years ago and is currently taking hydrochlorothiazide, lisinopril, and amlodipine. She denies nonadherence and has a blood pressure of 170/100 mmHg that is equal in both arms. On routine laboratory examination, she has a potassium level of 2.9 mEq/L with a sodium level of 148 mEq/L. What is the most appropriate diagnostic test?

a.Renal MRI/magnetic resonance angiography

b.Morning renin and aldosterone concentrations

c.Adrenal vein sampling

d.24-Hour urine cortisol concentration

41.A 58-year-old obese man with hypertension, diabetes mellitus, hyperlipidemia, and recent myocardial infarction presents for his annual physical examination. He is currently prescribed atenolol, hydrochlorothiazide, amlodipine, and quinapril. His blood pressure is at target values. His HbA1c is at goal. However, he has noted increasing lower extremity edema over the past few months and had a near-fatal car accident after falling asleep while driving. His echocardiogram reveals an ejection fraction of 65% with no evidence of diastolic dysfunction. Which of the following management decisions would be most appropriate at this time?

a.Discontinue calcium channel blocker

b.Polysomnography

c.Addition of loop diuretic

d.Maintain current regimen with advisement that his symptoms are typical with aging

42.A 56-year-old man on hydralazine, hydrochlorothiazide, lisinopril, and metoprolol begins to develop a malar rash and arthralgias. Which of the above antihypertensive agents is known to cause drug-induced lupus?

a.Hydralazine

b.Hydrochlorothiazide

c.Lisinopril

d.Metoprolol

43.A 47-year-old man with coronary artery disease, diabetes mellitus, and hypertension is currently taking clonidine. He is found to have a blood pressure of 170/90 mmHg after forgetting to take his medication for 48 hours. What is the best strategy to control his blood pressure?

a.Restart clonidine.

b.Start nitroprusside.

c.Start esmolol.

d.Add thiazide diuretic.

ANSWERS

1.c. Preeclampsia. Chronic hypertension is characterized by blood pressure ≤140/90 mmHg present before pregnancy, before the 20th week of gestation, or persisting beyond the 42nd postpartum day. Conversely, gestational hypertension develops beyond 20 weeks of gestation and usually resolves within 42 days postpartum. Preeclampsia is characterized by hypertension presenting beyond 20 weeks of gestation with >300 mg protein in a 24-hour urine collection or >30 mg/mmol in a spot urine sample, although in rare cases hypertension or proteinuria can be absent. Thrombocytopenia in this patient is very concerning for HELLP syndrome (hemolysis, elevated liver enzymes, and low platelets), a life-threatening condition showing significant overlap with preeclampsia. Eclampsia is the occurrence of seizures in a pregnant woman with preeclampsia. Edema is no longer considered to be part of the diagnostic criteria for preeclampsia because it occurs in more than half of normal pregnancies.

2.b. Duplex ultrasonography of the renal arteries. This young woman likely has hypertension secondary to fibromuscular dysplasia (FMD). FMD is a noninflammatory, nonatherosclerotic vascular condition typically affecting young women. It most frequently presents with hypertension, transient ischemic attack, stroke, or an asymptomatic cervical bruit. Sudden onset of pulmonary edema and a significant rise in creatinine after ACEI/ARB initiation are also common manifestations and reflect the presence of renal artery stenosis. About 60% to 75% of cases of FMD involve the renal arteries. Duplex ultrasonography is a noninvasive investigation that is highly specific and sensitive for renal artery stenosis, whether the stenosis is caused by atherosclerosis or FMD, and therefore is often the first test for diagnosis of this condition. Duplex ultrasonography of the carotids would also have been a good choice in this patient given the presence of a carotid bruit. The classic “string-of-beads” appearance of the arteries may be seen on angiography. The clinical history is not suggestive of pheochromocytoma (Answer c) or Cushing syndrome (Answer d).

3.d. Discontinue doxazosin and start lisinopril 5 mg daily. The likely culprit of this patient’s postural dizziness and falls is doxazosin. Elderly patients are more susceptible to drug side effects and management of hypertension should take into account such symptoms. Doxazosin demonstrated less effective blood pressure lowering than a thiazide in the antihypertensive and lipid lowering treatment to prevent heart attack trial (ALLHAT) study and was associated with excess cardiovascular events and incident heart failure. It would therefore be appropriate to discontinue doxazosin. There is minimal additional efficacy increasing from 25 to 50 mg of hydrochlorothiazide. The β-blocker should be continued due to the coronary artery disease history, but increasing to 100 mg metoprolol risks bradycardia. Clonidine 0.4 mg twice daily would also lower the heart rate and would be an excessive dose for initiation in an elderly patient who is already near blood pressure goal. The JNC recommendation of a “start low, go slow” approach in the elderly is intended to limit drug side effects, including hypotension. The discontinuation of doxazosin and initiation of 5 mg lisinopril is therefore the most appropriate option.

4.a. Aliskiren. The U.S. Food and Drug Administration issued a black box warning in 2012 that aliskiren should not be used with ACEIs or ARBs in patients with diabetes, because of the risk of renal impairment. There is also a warning to avoid the use of aliskiren with ACEIs or ARBs in patients with a glomerular filtration rate <60 mL/min. Conversely, methyldopa usually does not reduce glomerular filtration rate, renal blood flow, or filtration fraction. Normal or elevated plasma renin activity may decrease during methyldopa therapy. Hydrochlorothiazide may be a useful addition in stage III CKD but is unlikely to be effective in patients with a glomerular filtration rate <30 mL/min. Amlodipine is also a reasonable add-on medication to consider in this scenario.

5.b. Hydralazine and ankle edema. Vasodilatory lower extremity edema is most commonly seen with direct arteriolar dilators such as hydralazine and minoxidil. Dihydropyridine calcium antagonists, such as amlodipine, and α-adrenergic antagonists, such as doxazosin, are also associated with extremity edema. ACEIs are associated with an approximate 20% incidence of cough, which is purported to be bradykinin mediated. Angiotensin receptor antagonists, such as valsartan, do not directly inhibit angiotensin-converting enzyme activity or inhibit the breakdown of bradykinin. However, there are reports of angiotensin receptor antagonist-associated cough, but the incidence, severity, and frequency of dry cough in patients receiving valsartan or losartan are equivalent to those receiving placebo. Sleep disturbance is a side effect of β-blockers, especially those that cross the blood-brain barrier (e.g., propranolol and metoprolol). Constipation is a frequent side effect of verapamil.

6.d. Losartan. Both brothers carry the gene mutation for Marfan syndrome; presumably their father’s fatal aortic dissection was also a result of this connective tissue disease. Recent data suggest that the ARB losartan may slow the progression of aortic root dilatation in Marfan syndrome. Initially promising animal model studies demonstrating the benefits of transforming growth factor-beta pathway blockade by losartan have now translated into human clinical trials demonstrating benefit for patients with Marfan syndrome. In a randomized controlled trial of 233 Marfan patients, aortic root dilatation rate per MRI was significantly lower in the losartan group, when compared with controls, at a mean of 3-year follow-up.

7.a. Diabetes. There are no established links between hypertension and oral or subcutaneous therapies for diabetes. However, all four other conditions can be treated with medications that may be iatrogenic causes or contributors to hypertension. Approximately 20% to 30% of patients who receive erythropoietin intravenously for anemia of CKD develop an elevation in diastolic pressure of 10 mmHg or more. Secondary hyperparathyroidism is common in CKD patients, and cinacalcet can lower parathyroid hormone levels by increasing the sensitivity of the calcium-sensing receptor to extracellular calcium. However, hypertension is an adverse effect in approximately 7% of patients. Systemic absorption of ophthalmic drops is limited, but α-adrenergic agonists such as brimonidine may raise the pulse and blood pressure. Nonsteroidal anti-inflammatory medications such as ibuprofen are a common cause of fluid retention and hypertension exacerbation, especially for patients with renal dysfunction.

8.e. Access through a femoral artery, radiofrequency ablation of bilateral renal arteries. Current renal denervation catheters are introduced via standard femoral artery access. These catheters have a radiofrequency energy electrode tip that delivers a series of 2-minute ablations along the lumen of each renal artery to disrupt the sympathetic nerve fibers. Symplicity HTN-2 was a randomized, controlled trial comparing 54 patients receiving standard medical therapy for resistant hypertension with 52 patients who underwent percutaneous renal sympathetic denervation. The denervation group demonstrated a mean 32/12 mmHg blood pressure reduction at 6 months, compared with a 1/0 mmHg reduction in controls. However, the larger Symplicity 2 study did not show any difference. Thus, at this time, renal denervation cannot be recommended as therapy.

9.b. Female gender. ACEIs are the leading cause of drug-induced angioedema in the United States because they are so widely prescribed, accounting for 20% to 40% of all emergency room visits for angioedema. ACEIs induce angioedema in approximately 0.2% of recipients and the risk appears equivalent between the different ACEI medications. Severe reactions can be observed many months or even years after initiation of ACEI therapy. One large Veteran’s Affairs study by Miller et al. documented an almost fourfold higher rate of ACEI angioedema in blacks compared with whites, a 50% higher rate in women and a 12% lower rate in patients with diabetes. Patient age quartiles were unassociated with angioedema risk.

10.b. Peripheral arterial disease. There is now evidence to support the specific use of ramipril in patients with peripheral arterial disease and intermittent claudication. Ramipril has been associated with a significant increase in pain-free and maximum treadmill walking times at 6 months, as compared with placebo. Relative to placebo, ramipril also significantly improved the physical functioning component of a quality of life score. Although blood pressure control is an important management component for hypertensive patients with HFPEF, there is no compelling evidence for superiority of one medication over another in this setting. There is also no strong evidence to guide a specific antihypertensive choice for a patient with sleep apnea, although the presence of increased sympathetic nerve activity and a nocturnal diuresis in sleep apnea patients may explain reports that β-blockers tend to lower blood pressure more than thiazide diuretics in this setting. β-Blockers and ACEIs or ARBs are commonly used for blood pressure control in patients with aortic aneurysms.

11.a. Bicuspid aortic valve. This young man has a classic presentation of coarctation of the aorta. This secondary cause of hypertension is the result of stenosis of the aorta, usually at the embryonic site of the ligamentum arteriosum and is typically distal to the origin of the left subclavian artery. The presentation in adulthood is varied and is twice as common in men. Symptoms of hypertension or congestive heart failure are common. The electrocardiogram is characterized by left ventricular hypertrophy. Right ventricular hypertrophy is common if a concomitant ventricular septal defect is present. The most common associated valvular abnormality is a bicuspid aortic valve seen in 22% to 42% of cases. Intracranial aneurysms are seen in up to 10% of cases. Patients will often have a characteristic systolic precordial murmur secondary to the development of collateral arteries. Long-term management involves surgical or transcatheter correction. Patients will often continue to have systemic hypertension after repair and should be treated accordingly.

12.b. Stage 2, 130/80 mmHg. The most recent JNC 8 guidelines recommend that patients with diabetes have blood pressure goal of less than 140/90 mmHg based on the large ACCORD-BP (Action to Control Cardiovascular Risk in Diabetes — Blood–Pressure-lowering arm) study. The new guideline makes no distinction between patients with CKD or diabetes mellitus with no or with otherwise uncomplicated hypertension in patients less than 60 years of age. The most controversial aspect of the new guideline involves patients >60 years whose treatment goal is now <150/90 mmHg if they have no CKD or diabetes mellitus.

13.d. Direct renin inhibitor. Aliskiren is a direct renin inhibitor. The renin enzyme controls the rate-limiting step in the generation of angiotensin II. Aliskiren reaches peak concentration in 2 to 4 hours with a half-life of 24 to 36 hours. It is 50% protein bound. Diarrhea is the most common side effect occurring in up to 9.5% of patients. A dose of 150 mg daily will decrease systolic blood pressure on average 12.5 mmHg with a further 2.7 mmHg decrease when the dose is increased to 300 mg PO daily as compared with placebo. Aliskiren has been shown to have similar blood pressure-lowering effects when compared with thiazide diuretics as well as ACEIs. However, to date there are limited data on the effect of aliskiren on hypertension-induced end-organ damage and clinical outcomes.

14.a. Patient has essential hypertension; start thiazide diuretic. The patient likely has essential hypertension. The age of onset is typically between the early 20s to the late 50s. The presence of a family history of hypertension, the mild elevation in blood pressure, and the gradual onset make the diagnosis of essential hypertension more likely. First-line therapy in this individual, assuming she is not trying to become pregnant, is the use of a thiazide diuretic. Reevaluation in 1 year would not be appropriate, given the long-term complications associated with uncontrolled hypertension. A repeat evaluation in a few weeks is not necessary, given the documented hypertension over the past few years. The presence of unilateral renal artery stenosis from vascular hyperplasia is a possibility; however, the clinical history is most consistent with essential hypertension.

15.b. Renal MRI. The distinction between essential hypertension and secondary causes is critical in the management of a patient with long-standing hypertension that is difficult to control. In this scenario, the inability to control the patient’s blood pressure with multiple medications increases the pretest probability of a secondary etiology. In this individual, the presence of multiple cardiac risk factors, along with repeat episodes of noncardiogenic pulmonary edema, suggests the diagnosis of bilateral renal artery stenosis. Addition of further antihypertensive medications would be indicated, but not prior to initiating a workup for renal artery stenosis. A renal MRI would be the most appropriate of the mentioned answers.

16.b. Twofold. Increasing blood pressure beginning at 115/75 mmHg is noted to be a risk factor for stroke, heart failure, and myocardial infarction. For every 20 mmHg increase in systolic blood pressure and for every 10 mmHg in diastolic blood pressure, there is a twofold increase in the risk of cardiovascular disease. For the above patient, her risk of cardiovascular disease has increased by twofold.

17.b. Methyldopa. The central α-agonist methyldopa is known to cause an autoimmune hemolytic anemia in up to 20% of patients taking the medication. Other common side effects include sedation, insulin resistance, and galactorrhea. Methyldopa is not a first-line agent for treatment of hypertension and is usually reserved for pregnant patients and those with resistant hypertension.

18.c. 35% increase in creatinine. According to the JNC 7 guidelines, patients initiated on an ACEI should be continued on that medication unless the creatinine increases by more than 35% or another indication for discontinuation presents itself.

19.a. Calcium channel blocker. The Blood Pressure Lowering Treatment Trialist Collaboration Study found that calcium channel blockers provided a greater benefit in the reduction of stroke when compared with other antihypertensive agents. However, there was no difference in cardiovascular mortality or overall cardiovascular events.

20.b. She should have a repeat blood pressure measurement at a later time point during her visit and return in a few weeks to obtain repeat testing if that measurement is elevated. The JNC 7 guidelines suggest that the diagnosis of hypertension requires at least two separate blood pressure measurements during a clinic visit. The patient should be resting in a chair for at least 5 minutes and should have her arm supported at heart level when the blood pressure is measured. Blood pressure measurements should be evaluated in the contralateral arm and while standing as well. Elevations in blood pressure should be confirmed in a timely manner on a repeat visit, the timing of which is dependent on the level of hypertension and the presence of comorbid conditions. The patient in this vignette has mild isolated hypertension and should return in a few weeks (6 to 8 weeks). Those with more elevated blood pressure should return sooner. Antihypertensive medications should not be initiated on this initial visit as diurnal variations in blood pressure are common and she may not have hypertension. Ambulatory monitoring of blood pressure should be attempted. An evaluation for secondary cause is premature as the diagnosis of hypertension is not confirmed. Waiting to reevaluate the patient in 1-year time is unacceptable, as hypertension, if left untreated, increases the risk of stroke, myocardial infarction, heart failure, and renal insufficiency.

21.d. Urine metanephrines. The initial assessment of any patient with a new diagnosis of hypertension requires evaluation for evidence of hypertension-induced end-organ damage. All patients with a new diagnosis of hypertension should have the following testing: serum hematocrit, blood urea nitrogen, serum creatinine, serum potassium, serum calcium, blood glucose, an electrocardiogram, an ophthalmologic examination, a fasting lipid panel, and a urinalysis. Evaluation for secondary causes of hypertension should be limited to those with uncontrolled hypertension after treatment.

22.b. Urine metanephrines. This patient’s medical history is consistent with a diagnosis of pheochromocytoma. Pheochromocytomas arise from chromaffin cells. These tumors are most commonly found in the adrenal glands, but may be present anywhere there are sympathetic nerves. Classic symptoms are episodic palpitations, headaches, and diaphoresis. Rarely, patients may present with orthostatic hypotension. Initial diagnostic testing would involve the evaluation of a urine specimen for urine metanephrines. A toxicology screen is not indicated given his clinical history. An MRI of the abdomen would be helpful to evaluate for intra-abdominal masses, but an MRI of the thorax would be of limited benefit. Starting a thiazide diuretic would be beneficial, but ultimately the patient requires surgical therapy for correction of his hypertension.

23.c. Metoprolol. The initial choice of antihypertensive medication in this patient should be a β-blocker. Multiple studies have shown the benefit of β-blockers in the post-myocardial infarction period. The morphine in acute myocardial infarction (MIAMI-1) and International Study of Infarct Survival (ISIS-1) trials in the fibrinolytic era both showed trends toward a decrease in mortality with the use of intravenous β-blockers. The clopidogrel and metoprolol in myocardial infarction (COMMIT) trial found decreases in the rate of reinfarction and ventricular fibrillation with intravenous metoprolol followed by oral metoprolol; however, there was a 30% increase in the risk of cardiogenic shock. A meta-analysis of the post-myocardial infarction use of β-blockers has shown up to a 40% decrease in cardiovascular mortality. The American Heart Association 2013 ST-segment elevation myocardial infarction (STEMI) guidelines recommend initiation of oral β-blockers in the first 24 hours, providing that heart failure signs, evidence of a low-output state, risk factors for cardiogenic shock, or other contraindications to β-blockers are absent. However, intravenous β-blockers carry a class IIa indication in STEMI, given the concern for possible complications.

24.a. Calcium channel blocker. Calcium channel blockers are the most effective of the antihypertensive regimens at reducing carotid atherosclerosis. Studies comparing various calcium channel blockers with thiazide diuretics, ACEIs, and β-blockers have shown that calcium channel blockers have greater ability to decrease carotid intimal thickness.

25.d. Decreased peripheral resistance. The initial mechanism of action for lowering blood pressure is a decrease in plasma volume secondary to natriuresis. This triggers an increase in the activity of the rennin-angiotensin system, resulting in a return of plasma volume to normal. However, there is a long-term decrease in peripheral resistance that produces the chronic antihypertensive effects of thiazide diuretics.

26.c. Captopril. Aside from mycophenolate, the ACEI captopril is the most likely cause of this patient’s leukopenia. When immunosuppressive therapy is combined with ACEIs, there are reports of the development of anemia, neutropenia, leukopenia, and agranulocytosis. The best treatment strategy in this patient would be to use an alternative antihypertensive agent and monitor blood counts closely.

27.b. Start hydrochlorothiazide and lisinopril. The most appropriate initial step in the management of the patient in this clinical vignette is the initiation of two antihypertensive medications as recommended in the JNC 7 guidelines. In general, if patients have a blood pressure of greater than 20/10 mmHg above goal, they should be initiated on two antihypertensive agents because monotherapy will typically be ineffective in achieving target blood pressure. Most patients should be started on a thiazide diuretic when commencing treatment of hypertension, as confirmed by the results of the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack trial. Care should be taken in patients at risk for hypotension, specifically elderly patients, those with diabetes, and those with autonomic dysfunction.

28.c. Do nothing as he has white coat hypertension. The patient in the above clinical vignette has a diagnosis of white coat hypertension. It is defined as a clinic blood pressure of >140/80 mmHg in at least three clinic settings, with blood pressure measurements of <140/80 mmHg in at least two nonclinic settings, and with absence of end-organ damage. Multiple studies have been undertaken to evaluate if isolated elevations in blood pressure in the medical setting are associated with increased cardiovascular events. A 10-year follow-up study comparing cardiovascular events between patients with white coat hypertension and those with sustained hypertension found worse outcomes in those with sustained hypertension. The risk of myocardial infarction was two times greater and the risk of a cerebral vascular event was four times greater in the sustained hypertension group. Comparison of normotensive patients with those with white coat hypertension has noted a greater prevalence of left ventricular hypertrophy in the white coat hypertension group. However, there are no clear data that white coat hypertension increases long-term cardiovascular events. Treatment of white coat hypertension is associated with decreases in clinic blood pressure with no significant decrease in ambulatory blood pressure. Patients with white coat hypertension should be monitored closely for development of sustained hypertension, but do not need to be initiated on antihypertensive therapy.

29.a. Intravenous nitroprusside. Treatment of hypertensive emergency requires the use of intravenous medications to decrease the mean arterial blood pressure by 25% in the first few hours. Lower target blood pressure goals increase the risk of inducing a cerebral vascular event from decreased cerebral perfusion. Sublingual nifedipine is no longer used for hypertensive emergencies due to its dramatic and unpredictable blood pressure–lowering effects and the associated adverse clinical outcomes. Nitroprusside, labetalol, and nitroglycerin are all reasonable options. However, given the rapid onset and offset of nitroprusside, and the evidence of conduction delay that may limit labetalol use, nitroprusside would be the most appropriate medication for rapid and safe titration of blood pressure.

30.b. Lisinopril. The patient in the vignette has a target blood pressure of 130/80 mmHg according to the JNC 7 guidelines. The correct choice of initial blood pressure medication in this patient would be an ACEI. The ALLHAT study suggested that patients with diabetes mellitus have better long-term outcomes when using a thiazide diuretic compared with an ACEI. However, the patient in this vignette has evidence of protein in his urine. JNC 7 recommends that a thiazide diuretic should be first-line therapy, unless there is a specific indication. In this patient, the presence of proteinuria and diabetes mellitus makes the choice of an ACEI a better option than the thiazide. α-Blockers are not considered first-line therapy in hypertensive patients. In the ALLHAT study, there was an increased incidence of heart failure when comparing the α-blocker group (doxazosin) with the thiazide group.

31.c. Captopril. ACEIs and ARBs are contraindicated during pregnancy, because of the increased risk of congenital malformations. Methyldopa is the medication most commonly used to control blood pressure in pregnancy. There is significant evidence that it does not produce any harmful outcomes to the fetus. β-Blockers have been used in pregnancy with what appear to be safe results. However, the data are contradictory. There is some evidence that β-blockers, especially when used early in pregnancy, may increase the risk of fetal bradycardia, hypoglycemia, small placental weight, and a small-for-gestational-age fetus. Calcium channel blockers have been used in pregnancy without deleterious results, but the number of published cases is small. In general, methyldopa is the safest antihypertensive during pregnancy. β-Blockers and calcium channel blockers may be used with caution. ACEIs and ARBs are absolutely contraindicated due to teratogenic effects including renal dysplasia and intrauterine growth restriction.

32.c. Atenolol 25 mg PO daily. The least effective option is atenolol. The ALLHAT study showed that the use of thiazide diuretics as first-line therapy for treatment of uncomplicated hypertension was as effective as, if not superior to, amlodipine and lisinopril in preventing fatal coronary artery disease and nonfatal myocardial infarction. The choice of an ACEI would be reasonable, given the presence of glucose intolerance. β-Blockers would not be indicated as first-line therapy in this patient. Multiple meta-analysis comparing β-blockers with placebo or other antihypertensive agents have shown no statistically significant decreases in mortality, myocardial infarction, and stroke. The Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) trial comparing atenolol with amlodipine found a 23% greater risk of stroke in the atenolol group versus the amlodipine-based regimen.

33.b. Conversion of patient to a calcium channel blocker and thiazide diuretic. Analysis of the clinical trials in hypertension has noted that there are differences in the effectiveness of antihypertensive medications between different ethnic groups. African Americans are more responsive to calcium channel blockers and thiazide diuretics than other antihypertensive agents. This patient is on an ACEI and a β-blocker. Altering his regimen to include more effective antihypertensive agents would be indicated rather than increasing his medications, adding additional medications, or evaluating him for secondary causes of hypertension. The new JNC 8 guidelines make recommendation of medication based on the race of the patient.

34.c. 24-Hour urine cortisol test. This patient’s medical history is consistent with a secondary cause of hypertension, in particular, Cushing syndrome. This syndrome is characterized by an excess of cortisol. It may be secondary to a pituitary tumor/hyperplasia (Cushing disease), an adrenal tumor, or ectopic adrenocorticotropic production. Clinical manifestations include diabetes mellitus, hypertension, obesity, hypokalemia, osteoporosis, and fungal infections. The initial step in diagnosis is a 24-hour urine free cortisol test. Treatment is surgical.

35.a. Metoprolol. Pheochromocytoma is a rare cause of hypertension. Treatment ultimately requires surgical removal. The use of β-blocker monotherapy is contraindicated as part of the medical management of pheochromocytomas. The catecholamines secreted by these tumors activate both peripheral α- and β-receptors. Blockage of these peripheral β-receptors results in unopposed α-activation. This can result in severe hypertension. Typical medical management of pheochromocytomas involves the use of antihypertensives with α-blocking capability. For example, prazosin or phenoxybenzamine may be used. Only once α-blockade is established should the use of a β-blocker be entertained.

36.a. Aggressive lifestyle modification. Patients with prehypertension are at increased risk for cardiovascular events compared with normotensive individuals; therefore, care of these patients should be focused on aggressive control of all cardiovascular risk factors. Analysis of the Women’s Health Initiative compared cardiovascular outcomes in prehypertension patients with normotensive patients and found that the prehypertension patients had hazard ratios indicating a 1.58 (95% confidence interval [CI], 1.12 to 2.21) greater risk for cardiovascular death; 1.76 (95% CI, 1.40 to 2.22) greater risk for myocardial infarction; 1.93 (95% CI, 1.49 to 2.50) greater risk for stroke; 1.36 (95% CI, 1.05 to 1.77) greater risk for hospitalized heart failure; and a 1.66 (95% CI, 1.44 to 1.92) greater risk for any cardiovascular event. Not only are these patients at increased risk for cardiovascular events, but they also have a high incidence of hypertension development. In the Trial of Preventing Hypertension (TROPHY) trial, patients with prehypertension were randomized to candesartan or placebo. Over a period of 4 years, 67% of the untreated group developed hypertension as defined by the JNC 7 guidelines. These data suggest that patients with prehypertension are a high-risk population and should be treated aggressively. According to the JNC 7 guidelines, these individuals should increase their activity level, modify their diet, avoid excessive alcohol, and attempt weight loss. Initiation of antihypertensive medications should be reserved for those who progress to evident hypertension.

37.a. 140/90 mmHg. JNC 8 guidelines recommend that in patients with CKD or diabetes mellitus, the target blood pressure should be <140/90 mmHg.

38.c. Diltiazem. Patients who have undergone heart transplantation often have preexisting hypertension or develop hypertension subsequent to the heart transplant. This is a unique patient population as many of the immunosuppressive medications used after transplantation have multiple drug interactions. With respect to antihypertensive agents, most if not all calcium channel blockers have been shown to increase cyclosporine levels. Diltiazem and verapamil, in particular, are potent inhibitors of protein P-glycoprotein and CYP3A4. These enzymes are critical for the metabolism of diltiazem, and their inhibition can increase cyclosporine levels up to sixfold. It is recommended that patients who require diltiazem and are on cyclosporine have their cyclosporine dose decreased by 25% to 50%. Diltiazem can also increase tacrolimus levels.

39.b. Minoxidil. Pericarditis is a known complication of the direct vasodilator minoxidil often accompanied by a pericardial effusion. Its other major side effect is hirsutism. Prompt withdrawal of the medication once the diagnosis of a pericardial effusion or pericarditis is made is recommended. Minoxidil is a potent peripheral vasodilator and is typically reserved for patients with severe or difficult-to-control hypertension.

40.b. Morning renin and aldosterone concentrations. The patient in this vignette has secondary hypertension from Conn syndrome. This is primary hyperaldosteronism from uncontrolled secretion of aldosterone. Classic laboratory findings include hypokalemia and mild hypernatremia. The initial diagnostic test of choice is an aldosterone-renin ratio. A ratio of >20 is considered diagnostic. In this patient, the presence of lisinopril complicates the testing. ACEIs are known to decrease renin levels, and ideally the test should be done in the early morning after withdrawal of ACEI therapy. Adrenal vein sampling would be helpful in the diagnosis of primary hyperaldosteronism; however, it is not the initial test of choice. A 24-hour urine test would be more appropriate if Cushing syndrome were suspected. The patient’s clinical description is not consistent with this diagnosis. The presence of FMD should be suspected in any young woman with suspected secondary hypertension. However, the laboratory abnormalities are more suggestive of Conn syndrome than renal artery stenosis.

41.b. Polysomnography. The patient’s clinical history is consistent with the presence of obstructive sleep apnea; therefore, polysomnography (an overnight sleep study) would be the best option. Multiple studies have found evidence for increased risk of hypertension in patients with obstructive sleep apnea. There is no definitive evidence that treating patients with sleep apnea can lower blood pressure; however, there is an increasing hypertension risk as the number of overnight apneic episodes increases. Patients with >30 apnea or hypopnea episodes per hour have an odds ratio of 1.37 of developing hypertension versus those patients with <1.5 apnea or hypopnea episodes per hour.

42.a. Hydralazine. Hydralazine is known to cause a lupus-like syndrome in 5% to 20% of patients taking the medication. This syndrome is characterized by arthralgias, myalgias, pericarditis, fever, and rash. Lisinopril, metoprolol, and hydrochlorothiazide are not known to induce lupus. Other side effects of hydralazine include nausea, vomiting, tachycardia, anorexia, flushing, and diarrhea. Treatment of hydralazine-induced lupus involves withdrawal of the medication.

43.a. Restart clonidine. Rebound hypertension is a known complication of clonidine. Immediate treatment of clonidine withdrawal involves reinstitution of therapy with a slow taper. The mechanism of action is thought to be an increase in sympathetic nervous system activity.

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