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Wednesday, July 14, 2010

Antihypertensive therapy in pregnancy

A 35-year-old woman who is 15 weeks pregnant is referred for evaluation of chronic hypertension. She discontinued her antihypertensive regimen when she learned that she was pregnant.

On physical examination, heart rate is 90/min and blood pressure is 160/98 mm Hg. Cardiac and pulmonary examinations are normal.

Laboratory Studies
Blood urea nitrogen 6 mg/dL
Creatinine 0.6 mg/dL
Sodium 136 meq/L
Potassium 3.7 meq/L
Bicarbonate 23 meq/L

Treatment with which of the following agents is most appropriate for this patient?
A Hydrochlorothiazide
B Labetalol
C Lisinopril
D Losartan

Answer and Critique (Correct Answer = B)

Key Point
Labetalol or methyldopa is the preferred treatment for chronic hypertension in pregnant patients.

The most appropriate treatment for this patient is labetalol therapy. This agent has been used extensively in pregnancy because of its combined α-and β-blocking properties. Methyldopa also has been used extensively in pregnancy and is one of the only agents in which long-term follow-up of infants exposed in utero has proved to be safe.

Diuretic agents may interfere with the normal physiologic volume expansion associated with pregnancy. Therefore, initiation of diuretic therapy during pregnancy usually is not recommended in the absence of renal insufficiency. However, if needed, patients with hypertension treated with chronic diuretic therapy before conception may continue treatment with these agents at lower doses. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are contraindicated in pregnancy because of adverse effects on fetal renal function, particularly after second- and third- trimester exposure. There is no clear association between these drugs and teratogenic effects after first-trimester exposure. However, avoidance of these drugs is indicated during all trimesters of pregnancy because of the risk for negative fetal outcomes.

Multidrug antihypertensive therapy

A 59-year-old black man is evaluated during a routine follow-up office visit. He has occasional headaches but has otherwise been well. He had an anterior myocardial infarction 18 months ago and has hypertension, compensated congestive heart failure, type 2 diabetes mellitus, dyslipidemia, and mild chronic renal insufficiency. He is compliant with therapy, which includes metoprolol, lisinopril, amlodipine, metformin, atorvastatin, and aspirin.

On physical examination, heart rate is 62/min and blood pressure is 142/88 mm Hg. BMI is 24. Jugular venous pressure is 6 cm H2O. Cardiac examination reveals a regular rhythm; normal S1 and S2; and no S3, S4, or murmurs. The lungs are clear. There is no edema.

Laboratory studies: serum creatinine, 1.3 mg/dL; LDL cholesterol, 68 mg/dL; and spot urine albumin–creatinine ratio, 45 mg/g.

Which of the following is the most appropriate next step in this patient's management?
A Add clonidine
B Add hydrochlorothiazide
C Discontinue metoprolol; add hydralazine and isosorbide mononitrate
D Measure 24-hour urine catecholamines
E Reevaluate blood pressure in 2 to 3 months

Answer and Critique (Correct Answer = B)

Key Points

* Multidrug antihypertensive therapy is often needed to achieve optimal blood pressure control in patients with diabetes mellitus.
* An ineffective multidrug antihypertensive regimen should be considered a failure only if it includes a diuretic.

The addition of hydrochlorothiazide to this patient's medication regimen is the most appropriate next step. Patients with concomitant diabetes mellitus and hypertension typically require multidrug therapy to achieve target blood pressure goal (<130/80 mm Hg in this patient). Because this patient also has mild chronic kidney disease (calculated creatinine clearance, 69 mL/min) with microalbuminuria, ischemic heart disease, and congestive heart failure, blood pressure control is imperative. Adding a diuretic to a multidrug antihypertensive regimen may help to achieve a patient's blood pressure goal, and a regimen is not considered ineffective until a diuretic has been included.

Hydrochlorothiazide is administered once daily and is inexpensive and effective. Black patients usually respond less predictably well to angiotensin-converting enzyme (ACE) inhibitors, but the addition of a diuretic can help to equalize the effectiveness of these agents to that of white patients. Multiple trials have shown that β-blockers and ACE inhibitors are indicated in this setting. These agents prevent the progression of diabetic nephropathy, improve survival in heart failure, and provide secondary prevention of the acute coronary syndrome. Routine questioning of the patient about compliance is indicated, because compliance with therapy is a significant problem in hypertension management.

Clonidine has more side effects than similar agents and is not vasculo- or renoprotective; therefore, it is not indicated until all first-line agents have been tried. Hydralazine combined with nitrates is used as an alternative to ACE inhibitors or angiotensin-receptor blockers in patients intolerant to both, and can be added to standard heart failure therapy in black patients with heart failure. Hydralazine and nitrates have not been shown to have the same cardioprotective properties as ACE inhibitors. Patients with diabetes typically require three to four antihypertensive drugs, and this patient's medication regimen should not raise suspicion for a secondary cause of hypertension, such as pheochromocytoma. Moreover, this patient has no additional signs or symptoms suggestive of pheochromocytoma. Measurement of 24-hour urine catecholamines is therefore not indicated. Reevaluation in 2 to 3 months is not appropriate because blood pressure control in this setting is imperative to prevent morbidity and mortality.

Tuesday, July 13, 2010

Targeted BP for DM and Renal Failure Patient

A 57-year-old woman is evaluated in the office for intermittent claudication of the left calf that she has had for 5 years. The symptoms reproducibly occur after she walks 100 yards and resolve after 5 minutes of rest. The patient has an 80-pack-year smoking history but no longer smokes; she also has hypertension, type 2 diabetes mellitus, hypercholesterolemia, and chronic stable angina. Her medications are atenolol, atorvastatin, lisinopril, low-dose aspirin, and glyburide.

On physical examination, the blood pressure is 142/94 mm Hg in both upper extremities, and heart rate is 66/min. Carotid artery pulsations are brisk, with a right carotid artery bruit. The lungs are clear. Cardiac examination discloses an S4. There is a left femoral artery bruit with absent pulses in the left foot and trace pulses in the right foot.

Which of the following is the maximum acceptable blood pressure limit in this patient?
A <140/90 mm Hg
B <140/85 mm Hg
C <130/90 mm Hg
D <130/80 mm Hg

Answer and Critique (Correct Answer = D)

Key Point
The target blood pressure for patients with diabetes mellitus or renal failure is <130/80 mm Hg.

Hypertension is an independent risk factor for peripheral artery disease, and current guidelines support aggressive blood pressure management. For the general population, a blood pressure target of <140/90 mm Hg is associated with a decrease in cardiovascular complications, and a target pressure of <130/80 mm Hg is indicated for patients with diabetes mellitus (such as this patient) or renal failure.

1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-72. [PMID: 12748199] [PubMed]

Monday, July 12, 2010

Hypertension associated with Sleep Apnea (Apnoea)

A 48-year-old man is evaluated in the office for poorly controlled hypertension. His blood pressure has been elevated for 12 years and remains between 150/105 mm Hg and 170/105 mm Hg despite the use of multiple medications. He also has poor exercise tolerance and fatigue and often falls asleep in the afternoon. Medications are atenolol, amlodipine, and hydrochlorothiazide.

On physical examination, blood pressure is 168/110 mm Hg. He is obese (BMI 35) and appears plethoric. The remainder of the examination is normal.

Laboratory Studies
Creatinine 1.4 mg/dL
Sodium 140 meq/L
Potassium 3.9 meq/L
Bicarbonate 25 meq/L

Which of the following is the most likely cause of this patient's resistant hypertension?
A Pheochromocytoma
B Primary hyperaldosteronism
C Renovascular hypertension
D Sleep apnea syndrome

Answer and Critique (Correct Answer = D)

Key Point
Sleep apnea is associated with resistant hypertension and is particularly prevalent in obese patients.

Sleep apnea syndrome may contribute to resistant hypertension as well as to increased cardiovascular and cerebrovascular disease risk. Patients may have excessive fatigue and may fall asleep while driving or working. This condition has a higher prevalence in overweight men. The pathogenesis of sleep apnea syndrome is complex and linked to obesity, insulin resistance, and increased sodium retention. Several studies have shown that patients with sleep apnea syndrome have increased activity of the sympathetic nervous system, which also occurs in obesity. Coexistent insulin resistance and impaired glucose tolerance also may be present in these patients.

Renovascular hypertension may cause resistant hypertension but is less common than sleep apnea. In addition, the patient's age, obesity, plethora, and daytime sleepiness are more suggestive of sleep apnea than renovascular hypertension. Atherosclerotic renovascular hypertension usually develops in older patients, whereas fibromuscular dysplasia of the renal arteries often presents in younger patients and is more common in women.

Primary hyperaldosteronism may be present in as many as 10% of patients with resistant hypertension and should be included in the differential diagnosis. However, this condition is less likely in a patient who takes hydrochlorothiazide and has a normal potassium level.

Pheochromocytoma is a rare form of hypertension mediated by excess catecholamines. This condition causes palpitations, diaphoresis, tremor, flushing, and headaches. Diagnosis of pheochromocytoma may be difficult, and the clinical manifestations vary significantly. This patient's presentation is not fully consistent with this condition, and sleep apnea is more likely because it is more common and more likely to be associated with obesity, plethora, and daytime sleepiness.

1. Poirier P, Giles TD, Bray GA, Hong Y, Stern JS, Pi-Sunyer FX, Eckel RH; American Heart Association; Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2006;113:898-918. Epub 2005 Dec 27. [PMID: 16380542] [PubMed]

Hypertension progress in DM

A 52-year-old woman with type 2 diabetes mellitus, hyperlipidemia, and hypertension is evaluated during a routine office visit. She has a 30-pack-year smoking history. Her mother had diabetes and required hemodialysis. Medications are insulin, metoprolol, fosinopril, hydrochlorothiazide, atorvastatin, and low-dose aspirin.

On physical examination, blood pressure is 165/95 mm Hg. Retinal microaneurysms are noted on funduscopic examination. There is no jugular venous distention. The lungs are clear. Cardiac examination reveals a regular rhythm with an S4. There is bilateral pedal edema. The distal pulses are absent in both feet.

Laboratory Studies
Hemoglobin A1c 7.2%
Glucose 180 mg/dL
Creatinine 1.2 mg/dL
24-Hour urine protein excretion 1.8 g/24 h

Which of the following factors is most likely to cause this patient's chronic kidney disease to rapidly progress to end-stage renal disease?
A Cigarette smoking
B Poorly controlled diabetes mellitus
C Poorly controlled hypertension
D Proteinuria

Answer and Critique (Correct Answer = C)

Key Point
Reduction in blood pressure slows the progression of renal disease and the development of cardiovascular disease in patients with diabetes mellitus.

Poorly controlled diabetes mellitus or hypertension, proteinuria, and cigarette smoking are all risk factors for chronic kidney disease progression. However, treatment of hypertension is the cornerstone in preserving renal function in patients with diabetic nephropathy. Reduction in blood pressure has been shown to influence progression of renal disease and the development of cardiovascular disease in patients with diabetes. The goal of treatment of blood pressure in patients with both type 1 and type 2 diabetes mellitus is to maintain a blood pressure ≤130/80 mm Hg in the absence of significant proteinuria and ≤125/75 mm Hg if accompanied by a urine protein concentration >1 g/24 h. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers constitute first-line treatment of hypertension, even in patients with advanced diabetic nephropathy.

The beneficial effect of strict metabolic control of diabetes on the progression of advanced renal disease is less established than is strict control of blood pressure. Nevertheless, metabolic control should be improved in this setting in order to minimize the risk for metabolic, microvascular, and macrovascular complications of diabetes. Proteinuria is a well-recognized risk factor for the progression of renal disease, including diabetic nephropathy. Cigarette smoking has been shown to have significant detrimental effects on the kidney and may cause increased proteinuria and an accelerated decline in renal function. Nevertheless, uncontrolled hypertension is the major factor contributing to progressive renal failure.

1. Barnett A. Prevention of loss of renal function over time in patients with diabetic nephropathy. Am J Med. 2006;119:S40-7. [PMID: 16563947] [PubMed]

Sunday, July 11, 2010

Resistance to antihypertensive therapy due to NSAIDs

An 80-year-old man is evaluated in the office during a routine examination. He has a history of hypertension, and chronic osteoarthritis was diagnosed 20 years ago. His hypertension has been well controlled on submaximal dosages of both atenolol and hydrochlorothiazide. Three months ago, he began taking ibuprofen.

On physical examination, heart rate is 60/min and blood pressure is 180/90 mm Hg without orthostatic changes. There is trace peripheral edema.

Laboratory Studies
Blood urea nitrogen 40 mg/dL
Creatinine 1.5 mg/dL
Sodium 134 meq/L
Potassium 4.9 meq/L

Which of the following treatment strategies is indicated for this patient?
A Add lisinopril
B Discontinue ibuprofen
C Increase the atenolol dose
D Increase the hydrochlorothiazide dose

Key Point
Nonsteroidal anti-inflammatory drug use is a common cause of resistance to antihypertensive therapy.

Answer and Critique (Correct Answer = B)
Discontinuation of ibuprofen is indicated for this patient. Nonsteroidal anti-inflammatory drugs (NSAIDs) frequently affect sodium excretion. However, these agents are routinely used by elderly patients, who are particularly vulnerable to the blood pressure–raising effects of these drugs because of the change in sodium excretion. Most elderly patients have musculoskeletal conditions that warrant some form of therapy, but long-term daily treatment with NSAIDs may not be necessary. Alternative treatment strategies, such as physical therapy or therapy with acetaminophen, are indicated in this setting.

Discontinuing this patient's NSAID therapy is an appropriate next step to try to decrease his blood pressure. This strategy should be attempted before increasing his current medications or adding new medications, particularly because NSAIDs may contribute to renal and electrolyte disorders when used concomitantly with angiotensin-converting enzyme inhibitors or when taken by volume-depleted patients.

1. Gaziano JM. Nonnarcotic analgesics and hypertension. Am J Cardiol. 2006;97:10-6. Epub 2006 Mar 30. [PMID: 16675317] [PubMed]

White Coat Hypertension

An 85-year-old woman is evaluated in the office for resistant hypertension. She has a long-standing history of hypertension that had been well controlled with β-blocker therapy. Her physician recently died, and results of blood pressure measurement performed in a new office have been high. Records from her previous physician show that office blood pressure measurements were always normal. She also has fatigue, weakness, and dizziness, particularly after standing up. She has been unable to tolerate angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, and dihydropyridine calcium antagonist therapy. Current medications are metoprolol, 50 mg/d, and hydrochlorothiazide, 25 mg/d.

On physical examination, heart rate is 60/min and blood pressure in the supine and standing positions is 170/70 mm Hg. The remainder of the examination is normal.

Serum creatinine is 0.8 mg/dL, blood urea nitrogen is 18 mg/dL, and serum potassium is 3.6 meq/L.

Which of the following is the most appropriate next step in this patient's management?
A Ambulatory blood pressure monitoring
B Discontinuation of metoprolol
C Increase in the hydrochlorothiazide dose to 50 mg/d
D Magnetic resonance angiography of the renal arteries

Answer and Critique (Correct Answer = A)

Key Point
In selected patients, ambulatory blood pressure monitoring can exclude white coat hypertension.
The most appropriate next step in this patient's management is ambulatory blood pressure monitoring. White coat hypertension due to this patient's anxiety regarding a new physician and medication change is highly possible, and ambulatory blood pressure monitoring would confirm this diagnosis. In addition, overtreatment of hypertension in elderly patients is associated with increased adverse effects of medication, particularly symptoms associated with hypotension. Moreover, this patient's fatigue, weakness, and dizziness suggest that she is already overmedicated. Although current blood pressure targets for the elderly have not been clearly defined, a systolic blood pressure ≤160 mm Hg in this population has been associated with better outcomes. Ambulatory blood pressure monitoring is useful in this setting to document the level of blood pressure control.

Performing magnetic resonance angiography would be premature in this patient. Renovascular hypertension is a possible cause of resistant hypertension in the elderly, but her symptoms are consistent with overmedication. In addition, her long-standing history of stable hypertension is consistent with primary or essential hypertension. Increasing her hydrochlorothiazide dose before excluding a white coat effect could lead to increased symptoms. Lower doses of medication are indicated for many elderly patients, and 50 mg/d of hydrochlorothiazide most likely will be poorly tolerated in this patient.

Discontinuation of metoprolol may be reasonable. However, because of her elevated office blood pressure measurements, this agent should be discontinued only after documenting that her blood pressure is adequately controlled.

1. Fisher M, Blackwell J, Saseen J. Clinical inquiries. What is the best way to identify patients with white-coat hypertension? J Fam Pract. 2005;54:549-50, 552. [PMID: 15939009] [PubMed]

Saturday, July 10, 2010

Diuretics potentiate the blood pressure–lowering effects of ACE inhibitors and β-blockers

A 60-year-old man with type 2 diabetes mellitus, hypertension, and coronary artery disease is evaluated during a routine office visit. Medications are metformin, a β-blocker, an angiotensin-converting enzyme inhibitor, aspirin, and a statin.

On physical examination, blood pressure is repeatedly 160/90 mm Hg. There is evidence of early diabetic retinopathy.

Laboratory Studies
Blood urea nitrogen 15 mg/dL
Creatinine 1.1 mg/dL
Potassium 5.4 meq/L
Spot urine albumin–creatinine ratio 175 mg/g

Addition of which of the following agents is indicated to treat this patient's hypertension?
A An angiotensin receptor blocker
B An α-blocker
C A potassium-sparing diuretic
D A thiazide diuretic

Answer and Critique (Correct Answer = D)

Key Point
Diuretics potentiate the blood pressure–lowering effects of angiotensin-converting enzyme inhibitors and β-blockers.

Therapy with a thiazide diuretic is indicated for this patient. This patient has type 2 diabetes mellitus, coronary artery disease, possible early diabetic nephropathy, and inadequate blood pressure control. His current regimen of a β-blocker and angiotensin-converting enzyme inhibitor is appropriate for cardiovascular disease and target organ protection. The addition of a thiazide diuretic is likely to improve blood pressure control, which is indicated to prevent further progression of target organ damage.

The addition of an angiotensin receptor blocker or potassium-sparing diuretic may provide renal protection and additional blood pressure control but would likely further exacerbate his hyperkalemia. Therapy with α-blockers has not been shown to have particular advantages compared with use of the other agents listed and may not lower blood pressure sufficiently.



A 39-year-old man is evaluated in the office for a 6-year history of difficult-to-control hypertension. Initially, he was treated with hydrochlorothiazide, but within 1 week, he developed profound muscle weakness; follow-up potassium concentration was 2.1 meq/L. Hydrochlorothiazide was discontinued, and he has not been on a diuretic for 6 years. He has struggled with obesity throughout his life and has a 7-year history of type 2 diabetes mellitus. His current medications are lisinopril, diltiazem, pravastatin, metformin, glipizide, and aspirin.

On physical examination, his blood pressure is 189/92 mm Hg, heart rate is 87/min, and BMI is 32.8. There is no jugular venous distention, and his lungs are clear. Cardiac examination reveals an S4. He has no edema.

Laboratory Studies
Sodium 141 meq/L
Potassium 3.1 meq/L
Chloride 104 meq/L
Bicarbonate 33 meq/L
BUN 11 mg/dL
Creatinine 0.9 mg/dL

24 hour urine:
Sodium 90 meq
Potassium 57 meq
Free cortisol 36 µg/24 h (normal <55 µg/24 h)

Which of the following is the most likely cause of this patient's hypertension?
A Cushing's syndrome
B Essential hypertension
C Hyperaldosteronism
D Pheochromocytoma
E Renovascular hypertension

Key Points

* The diagnosis of primary hyperaldosteronism is made by showing increased autonomous aldosterone synthesis with suppression of the renin-angiotensin system.
* Primary hyperaldosteronism is diagnosed in as many as 50% of patients with unprovoked hypokalemia.

Answer and Critique (Correct Answer = C)
This hypertensive patient has unprovoked hypokalemia, and his high urine potassium level indicates excessive renal potassium losses (in the presence of ongoing hypokalemia, a urine potassium concentration >30 meq/24 h identifies excessive renal potassium loss). These findings make hyperaldosteronism the most likely diagnosis listed. Hyperaldosteronism is included in the differential diagnosis of hypertension and hypokalemia. Unprovoked hypokalemia is highly suggestive of hyperaldosteronism—primary hyperaldosteronism has been identified in as many as 50% of patients with unprovoked hypokalemia. Severe hypokalemia following administration of a non–potassium sparing diuretic also is suggestive of hyperaldosteronism. Some patients with primary hyperaldosteronism are persistently normokalemic; thus, screening is also indicated in patients with early-onset, severe hypertension or resistant hypertension.

The diagnosis of primary hyperaldosteronism is made by showing increased autonomous aldosterone synthesis with suppression of the renin-angiotensin system. Although this test can be performed under random conditions, accuracy is increased if the sample is obtained after hypokalemia has been corrected and, preferably, in the absence of drugs that alter the renin-aldosterone axis, such as spironolactone (the effects of spironolactone can last 2 to 3 weeks), other diuretics, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin receptor blockers (ARBs). For a diagnosis of primary hyperaldosteronism, the plasma aldosterone concentration should be >15 ng/dL and plasma renin activity should be <1.0 ng/mL/h.

Cushing's syndrome is a reasonable consideration for a patient with difficult-to-control hypertension, obesity, and diabetes. However, this patient's 24-hour urine free cortisol is normal, ruling out Cushing's syndrome. Essential hypertension is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis. These findings more strongly suggest hyperaldosteronism. Pheochromocytoma is a very rare neoplasm that is associated with paroxysmal or sustained hypertension; however, pheochromocytoma is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis, making pheochromocytoma unlikely in this patient. Renovascular hypertension is often associated with older age and signs of other peripheral vascular disease, such as carotid bruits, claudication, diminished pulses, and coronary artery disease. Although the physical examination may be normal in patients with renovascular hypertension, the presence of abdominal, femoral, or carotid bruits increases its pretest probability. Atherosclerotic renovascular disease may be associated with renal impairment (which may worsen with ACE inhibitor or ARB therapy), which is absent in this patient. Finally, renovascular hypertension is not associated with hypokalemia, renal potassium wasting, or metabolic alkalosis.

1. Bornstein SR, Stratakis CA, Chrousos GP. Adrenocortical tumors: recent advances in basic concepts and clinical management. Ann Intern Med. 1999;130:759-71. [PMID: 10357696] [PubMed]