How should a patient with a complex internal medicine case, such as hypertension, be diagnosed and treated?

Diagnosis and Treatment of Hypertension

Initial Diagnostic Approach

Hypertension is diagnosed when blood pressure is ≥130/80 mm Hg based on proper measurement technique with at least two readings per visit over at least two visits. 1

Blood Pressure Measurement Technique

• Have the patient sit quietly with back supported for 5 minutes before measurement 1
• Use correct cuff size with air bladder encircling at least 80% of the arm (adult large cuff for most patients) 1
• Support the arm at heart level during measurement 1
• Take minimum of 2 readings at 1-minute intervals and average them 1
• Measure both arms and use the arm with higher pressures for future measurements 1
• Measure supine and upright pressures during follow-up to detect orthostatic changes 1

Essential Diagnostic Workup

All hypertensive patients require a comprehensive evaluation to identify secondary causes, assess cardiovascular risk, and detect organ damage. 1

Medical History Must Document:

• Duration, severity, and progression of hypertension 1
• Family history of hypertension and cardiovascular disease 1
• Current medications including over-the-counter drugs, NSAIDs, steroids, sympathomimetics 1
• Symptoms suggesting secondary causes: daytime sleepiness, loud snoring, witnessed apnea (sleep apnea); palpitations, diaphoresis, episodic hypertension (pheochromocytoma) 1
• Adherence to prior medications and adverse effects 1

Physical Examination Must Include:

• Fundoscopy to document retinopathy presence and severity 1
• Auscultation for carotid, abdominal, or femoral bruits (suggests renal artery stenosis) 1
• Palpation of femoral pulses and comparison of arm-to-thigh blood pressures (aortic coarctation) 1
• Assessment for Cushing's features: moon facies, central obesity, pigmented abdominal striae, interscapular fat deposition 1
• Heart rate measurement at rest (increased rate indicates increased cardiovascular risk) 1
• Pulse palpation to detect arrhythmias, especially atrial fibrillation 1

Routine Laboratory Tests Required:

• Hemoglobin/hematocrit 1
• Fasting plasma glucose 1
• Serum lipid panel (total cholesterol, LDL, HDL, triglycerides) 1
• Serum potassium, sodium, creatinine with estimated GFR 1
• Serum uric acid 1
• Urinalysis with microscopic examination and dipstick for protein 1
• Test for microalbuminuria 1
• 12-lead ECG 1

When to Suspect Secondary Hypertension:

Secondary causes are found in 20-40% of patients with malignant hypertension, requiring appropriate diagnostic workup. 1

Investigate further when:

• Young patients, especially women (fibromuscular dysplasia) 1
• Older patients with atherosclerotic disease risk (renal artery stenosis) 1
• Elevated aldosterone/renin ratio (primary aldosteronism) 1
• Chronic kidney disease with creatinine clearance <30 mL/min 1
• Worsening renal function 1

Do not perform diagnostic renal arteriograms without suspicious noninvasive imaging first. 1

Do not perform abdominal CT to screen for adrenal adenomas without biochemical confirmation of hormonally active tumors. 1

Out-of-Office Blood Pressure Monitoring

• Consider 24-hour ambulatory blood pressure monitoring (ABPM) or home blood pressure monitoring (HBPM) to confirm diagnosis, identify white-coat hypertension, detect hypotensive episodes, and maximize cardiovascular risk prediction 1
• ABPM is the most objective method to document white-coat effect 1

Treatment Strategy

Lifestyle Modifications (First-Line for All Patients)

All patients with blood pressure ≥120/80 mm Hg should implement lifestyle modifications. 2, 3

Weight Loss

• 10 kg weight loss reduces systolic BP by 6.0 mm Hg and diastolic BP by 4.6 mm Hg 1
• Greatest benefit occurs in patients already receiving antihypertensive therapy 1
• Recommend for all overweight or obese patients with resistant hypertension 1

Dietary Modifications

• Reduce sodium intake to <100 mEq/24 hours (approximately 2.3 g sodium or 6 g salt daily) 1
• Dietary salt reduction lowers systolic BP by 5-10 mm Hg and diastolic BP by 2-6 mm Hg 1
• Increase potassium intake 2
• Adopt high-fiber, low-fat dietary pattern 1

Physical Activity

• Regular exercise is effective in lowering BP and preventing hypertension 2, 4

Alcohol Moderation

• Limit daily alcohol to ≤2 drinks (1 ounce ethanol) per day for men: 24 ounces beer, 10 ounces wine, or 3 ounces 80-proof spirits 1
• Cessation of heavy alcohol ingestion significantly improves hypertension control 1

Pharmacologic Treatment

When drug therapy is required, first-line therapies are thiazide or thiazide-like diuretics, ACE inhibitors or angiotensin receptor blockers, and calcium channel blockers. 2, 4

Initiation Criteria

• Begin pharmacologic therapy based on BP level and presence of high atherosclerotic cardiovascular disease risk 2
• Start with low-dose chlorthalidone unless specific indication for different drug exists 3

Blood Pressure Targets

• Target <130/80 mm Hg for adults <65 years 2
• Target systolic <130 mm Hg for adults ≥65 years 2
• Target <130/80 mm Hg for diabetics and those with chronic kidney disease 3

Medication Selection and Titration

First-line combination therapy should include:

• Thiazide or thiazide-like diuretic (hydrochlorothiazide or chlorthalidone) 2, 3
• ACE inhibitor (e.g., lisinopril, enalapril) or ARB (e.g., candesartan) 2, 4
• Calcium channel blocker (e.g., amlodipine) 2, 4

Lisinopril dosing for hypertension:

• Initial dose: 10 mg once daily 5
• Usual maintenance: 20-40 mg once daily 5
• Maximum: 80 mg once daily 5
• Antihypertensive effect seen with 5 mg but greater reduction with 10-80 mg 5

Additional Agents for Resistant Hypertension

If BP remains uncontrolled on three-drug regimen, add medications sequentially: 3

1. Maximize diuretic therapy, consider adding mineralocorticoid receptor antagonist 1
2. Beta-blocker 3
3. Alpha-blocker 3
4. Direct vasodilator 3
5. Centrally acting alpha-2 agonist 3

Use loop diuretics instead of thiazides in patients with chronic kidney disease or those receiving potent vasodilators like minoxidil. 1

Maximizing Adherence

Simplify regimens to improve adherence: 1

• Use long-acting combination products to reduce pill burden 1
• Allow once-daily dosing whenever possible 1
• Have patients maintain home BP diary to improve follow-up and medication adherence 1
• Schedule more frequent clinic visits 1
• Involve family members in lifestyle changes 1
• Consider multidisciplinary approach with nurse case managers, pharmacists, and nutritionists 1

Ask patients directly in nonjudgmental fashion about adherence, including discussion of adverse effects, out-of-pocket costs, and dosing inconvenience. 1

When to Refer to Specialist

Refer to hypertension specialist if blood pressure remains uncontrolled after 6 months of treatment. 1

Refer to appropriate specialist for known or suspected secondary causes of hypertension. 1

Hypertensive Emergencies

Hypertensive emergency is defined as substantially elevated BP with acute hypertension-mediated organ damage (HMOD) requiring immediate BP reduction to prevent progressive organ failure. 1, 6

Recognition and Differentiation

Patients with substantially elevated BP who lack acute HMOD are NOT considered hypertensive emergency and can be treated with oral antihypertensive therapy. 1, 6

There is no specific BP threshold to define hypertensive emergency; diagnosis is based on presence of acute organ damage, not BP level alone. 1, 6

Clinical Presentations Requiring Immediate BP Lowering:

Condition	Timeline	Target BP
Malignant hypertension with/without TMA	Several hours	MAP -20% to -25% [1]
Hypertensive encephalopathy	Immediate	MAP -20% to -25% [1]
Acute ischemic stroke (SBP >220 or DBP >120)	1 hour	MAP -15% [1]
Acute ischemic stroke with thrombolytic indication (SBP >185 or DBP >110)	1 hour	MAP -15% [1]
Acute hemorrhagic stroke (SBP >180)	Immediate	130<SBP<180 mm Hg [1]
Acute coronary event	Immediate	SBP <140 mm Hg [1]
Acute cardiogenic pulmonary edema	Immediate	SBP <140 mm Hg [1]
Acute aortic disease	Immediate	SBP <120 mm Hg and HR <60 bpm [1]
Eclampsia/severe preeclampsia/HELLP	Immediate	SBP <160 and DBP <105 mm Hg [1]

Acute Management

Hypertensive emergencies require admission to intensive care unit with titratable, short-acting intravenous antihypertensive agents. 7, 8

Preferred IV agents:

• Labetalol 1, 7, 8
• Esmolol 7, 8
• Fenoldopam 7, 8
• Nicardipine 1, 7, 8
• Clevidipine 7, 8

Avoid these agents:

• Immediate-release nifedipine 7, 8
• Hydralazine 7, 8
• Nitroglycerin 7, 8
• Sodium nitroprusside should be avoided due to extreme toxicity 8

Special Situations

Sympathetic hyperreactivity (amphetamines, cocaine, sympathomimetics):

• Use benzodiazepines prior to specific antihypertensive treatment 1
• If additional BP lowering needed: phentolamine (alpha-blocker) or clonidine (central sympatholytic) 1
• Nicardipine and nitroprusside are suitable alternatives 1

Pheochromocytoma:

• Responds well to phentolamine 1
• Use beta-blockers only after alpha-blockers have been initiated 1

Common Pitfalls to Avoid

• Do not diagnose hypertension based on single visit measurements 1
• Do not use improper BP measurement technique leading to false diagnosis 1
• Do not miss white-coat hypertension; confirm with out-of-office monitoring when suspected 1
• Do not overlook secondary causes, especially in young patients or those with resistant hypertension 1
• Do not prescribe complex multi-pill regimens when combination products are available 1
• Do not rapidly lower BP in hypertensive urgencies without acute organ damage 1, 6
• Do not use sodium nitroprusside as first-line therapy in hypertensive emergencies 8