LABORATORY
EVALUATION OF
HYPERTENSIVE PATIENTS

Laboratory Evaluation of Hypertensive Patients

1. Detect target organ damage.
2. Find other conditions that might influence the prognosis and therapy.
3. Diagnose secondary or curable forms of hypertension.

I. ROUTINE LABORATORY TESTS

(Recommended in all Hypertensive Patients)

1. Urine analysis.
2. Serum creatinine and blood urea.
3. Blood glucose.
4. Serum potassium.
5. Serum cholesterol.
6. Serum uric acid.
7. Electrocardiogram.

1. Urine Analysis
a. Proteinurea
· A sign of renal parenchymal and renovascular hypertension.
· Present in accelerated and malignant hypertension

· Macroalbuminuria is very rare in uncomplicated essential hypertension

Laboratory Evaluation of Hypertensive Patients

b. Pus cells
· Present in renal stones, urinary tract infections
· Hypertensive patients are more liable to develop renal stones and urinary tract infections than normotensive subjects.

2. Blood Urea and Serum Creatinine
· Elevated in primary renal disease, renovascular hypertension or in some cases of renal damage secondary to severe hypertension.
· Influence the choice and dosage of antihypertensive drugs.

3. Blood Glucose
· Diabetes mellitus and impaired glucose tolerance are more common in hypertensive than normotensive subjects.
· Presence of diabetes multiplies the cardiovascular risk of hypertension and requires early and aggressive control of blood pressure.
· Choice of antihypertensive drugs can be influenced by the presence of diabetes. Thiazide diuretics can sometimes impair glucose tolerance.

4. Serum Potassium
· Normal range: 3.5- 5.5 mEq/L.
· Accurate estimation through a reliable laboratory is essential.
· Can be falsely elevated due to hemolysis, stasis, muscle exercise while taking the blood sample.
· If less than 3.5 mEq/L repeat testing on other two separate occasions.
· Important causes of low serum potassium:

1. Diuretic therapy.
2. Primary aldosteronism.

Laboratory Evaluation of Hypertensive Patients

3. Secondary aldosteronism.
4. Chronic laxative use.
5. Renal tubular defects.

6. Psychogenic vomiting.
· If serum potassium is less than 3.0 mEq/L and patient is not receiving diuretics or laxatives, estimate 24 hours urinary potassium. If urinary potassium is more than 30 mEq/24 hours, primary aldosteronism should be suspected and more investigations are reqiured.
· Important causes of high serum potassium:

1. Faulty technique, hemolysis.
2. Renal failure.

3. Iatrogenic (drug induced) in presence of impaired renal function:
- Excessive potassium supplementation.
- Potassium sparing diuretics, e.g., spironolactone.
- ACE inhibitors.

5. Serum Cholesterol
· Normal level: less than 200 mg/dl.
· Hypercholestrolemia (serum cholesterol > 220 mg/dl).
- Hypercholesterolemia is more prevalent in hypertensives than in normotensives.
- Multiplies the cardiovascular risk of hypertension.
· Serum cholesterol greater than 240 mg/dl is an indication for:

1. Repeat measurement of serum cholesterol, initially and periodically.
2. Detailed lipid profile, i.e. estimate HDL and LDL cholesterol, and triglycerides.
3. Prescribe diet and if necessary drug intervention depending upon global risk profile and level of cholesterol.
4. Earlier and aggressive control of blood pressure.

Laboratory Evaluation of Hypertensive Patients

6. Serum Uric Acid
· Inversely correlates with renal blood flow.
· Hyperurecemia does not need treatment unless producing symptoms (gout) or very high (> 10-12 mg/dl).
· Hyperuricemia (serum uric acid > 6 mg% in females and > 8 mg% in males) is present in:

1. Chronic renal failure.
2. Treatment with thiazide diuretics.
3. Primary or genetic metabolic defect.
4. Common in obesity.

7. Electrocardiogram
· Normal in the majority of young patients with mild and moderate hypertension.
· P wave abnormalities (broad and deep p wave in chest lead V1, notched and wide p in standard lead II):
- Sign of cardiac involvement.
- Common in patients with abnormal left ventricular function.
- May precede signs of left ventricular hypertrophy.
· Left ventricular Hypertrophy - Voltage Criteria:
- SV1 + RV5 or RV6 > 35 mm
- Deepest S + Tallest R in chest leads > 45 mm
- R aVL > 11 mm
- R1 + S3 > 25 mm
- RV6 > RV5
· Signs of Left Ventricular Hypertrophy:
- Carry a poor prognosis.
- A powerful independent coronary risk factor.
- Indication for early and aggressive drug treatment of hypertension.
- May suggest associated hypertrophic cardiomyopathy.

Laboratory Evaluation of Hypertensive Patients

· Left Ventricular Strain and Myocardial Infarction Pattern:
- May be present in absence of history or symptoms of myocardial ischemia (silent infarction in 25% of cases).
- An indication of evaluation and aggressive management of hypertension.
· Signs of Electrolyte Abnormalities:
- ST, T wave changes.
- Present in hyper or hypo-kalemia, magnesemia and calcemia.
· Negative or biphasic T wave in anterioletral chest leads
- Common in hypertensives.
- Causes: Myocardial ischemia, electrolyte disturbances, left ventricular hypertrophy, autonomic imbalance, hypertrophic cardiomyopathy.
· Atrioventricular (A-V) Conduction Defects: Heart block
- Grade II or III A-V block are contraindications to treatment with beta – adrenergic blockers and verapamil.

II. Additional Laboratory Tests
1. Detailed Lipid Profile

Indications

1. Hypercholesterolemia
2. Coronary artery disease

2. Hemoglobin and Hematocrite

Indications

1. Skin pallor (anemia).
2. Renal failure – renal disease.
3. Unexplained symptoms: Fatigue, shortness of breath.
4. Collagen diseases.

Laboratory Evaluation of Hypertensive Patients

3. Urine Culture

Indications

1. Pus cells in urine.
2. History of pyelonephritis.
3. Elderly with prostatic symptoms.
4. Chest X-ray

Indications

1. Unexplained prolonged cough or shortness of breath.
2. Heart failure.
3. Suspected coarctation of the aorta: Rib notching.
4. Suspected pheochromocytoma: Mediastinal tumour from sympathetic ganglia.
5. Echocardiography

· More sensitive and specific than ECG for the diagnosis of left ventricular hypertrophy.
· Can assess left ventricular function (systolic and diastolic).
· Detect evidence of coronary artery disease: Scarring and wall motion abnormalities.
· Echocardiographic evidence of left ventricular hypertrophy favours early start of drug therapy.
· Diagnose associated conditions: Hypertrophic cardiomyopathy, aortic or mitral valve disease.

Indications

1. Resistant hypertension: In absence of target organ damage suspect, white coat effect.
2. Mild hypertension when there is difficulty to decide about initiation of therapy because of marked variability in blood pressure readings.
3. Mild or borderline hypertension associated with high home blood pressure readings.

Laboratory Evaluation of Hypertensive Patients

4. Symptoms or signs of heart disease, e.g., shortness of breath, chest pain, cardiac murmurs.
5. Electrocardiographic abnormalities.

III. Extended Laboratory Evaluation

Indications

1. Moderate and severe hypertension before the age of 30 years.
2. Hypertension of recent onset after the age of 50 years.
3. Resistant hypertension.
4. Symptomatic hypertension.
5. Accelerated or malignant hypertension.
6. Unexplained sudden failure of hypertension control.
7. Features indicative of secondary forms upon initial screening, e.g., hypokalemia, abdominal bruits.

Tests in Search For Secondary Hypertension

A) Biochemical Tests
1. Twenty- four hours urine collection

Normal levels

a. Vanillylmandelic Acid*(VMA): Up to 7 mg/24 hrs.
b. Metanephrines: Up to 1.3 mg/24 hr.
c. Free Catecholamines: 100-150 mg/24 hr.
d. Potassium: Up to 30 m Eq/24 hr on unrestricted diet.

It should exceed 30 mEq/24 hr in cases of primary aldosteronism.

Laboratory Evaluation of Hypertensive Patients

e. Aldosterone: Urinary aldosteeone ia a reliable method for assessing its production, has 96% sensitivity and 93% specificity in detecting primary aldosteronism. It is at or above

8 mcg/24 hr, with urinary sodium level of 250 mEq/24 hr or more in patients with primary aldosteronism.

f. Free Cortisol: If greater than 50 mcg/24 hrs is diagnostic of Cushing’s syndrome.

2. Plasma Hormonal Measurements

a. Plasma Catecholamine Levels
· Before drawing plasma samples the patient must be resting for at least 30 minutes.
· In patients with pheochromocytoma plasma catecholamines are usually elevated to more than 2,000 pg/ml.
· In patients where plasma catecholamine levels are 500-2,000 pg/ml, the failure of 0.3 mg of clonidine given orally to supress catecholamines after 3 hours is a strong indication of the presence of pheochromocytoma.

b. Plasma Aldosterone Level
· Normal: Baseline normal values overlap with values of patients with primary aldosteronism. Correlation with 24 hr sodium excretion in urine is recommended.
· Saline infusion (2 L normal saline over 4 hours) causes suppression of plasma aldosterone to less than 5 mcg/dl in normal subjects. High levels are present in patients with primary aldosteronism.

c. Plasma Cortisol

· 8 A.M. plasma cortisol after 1 mg dexamethasone at midnight greater than 5 mcg/dl, suspect Cushing’s syndrome.

d. Plasma Renin-Sodium Profile
· Patients should be off drugs for at least three weeks (diuretics), 6 weeks (spironolactone), 2 weeks other drugs.

· Markedly suppressed plasma renin activity (PRA): below 0.5 ng/ml/hr in primary aldosteronism.

Laboratory Evaluation of Hypertensive Patients
· Elevated PRA: If more than 2.5 ng.ml/hr evaluate for renal artery stenosis.
· For other causes of increased PRA, see chapter 2.

e. Plasma Renin/Aldosterone Ratio. See chapter 11 on primary aldosteronism.

B) Imaging

1. Abdominal sonography (ultrasound) for diagnosis of renal abnormalities and other abdominal masses.

2. Abdominal Computerized Axial Tomography (CAT) for suspected pheochromocytoma and suprarenal cortical tumours.

3. Digital subtraction angiography (DSA):
- Injecting contrast material into peripheral vein.
- It has limited resolution and is non diagnostic in patients with impaired renal and cardiac function.
- 7.4% of all renal DSAs can not be interpreted.
- Its value as an initial screening test for renovascular hypertension is limited and recently not recommended.

4. Selective renal arteriography for definitive diagnosis of renal artery stenosis.
5. Echocardiography for the diagnosis of thoracic coarctation of the aorta. Positioning of the transducer in the suprasternal notch and directing the ultrasound beam towards the aortic arch and begining of descending thoracic aorta.

Laboratory Evaluation of Hypertensive Patients

6. Rapid-Sequence “Hypertensive Intravenous Pyelography” - (IVP):
- For diagnosis of renovascular hypertension.
- It is no longer used in many centers and being replaced by other tests because of its low level of accuracy, together with the high doses of dye and radiation. See chapter 10 on renal artery stenosis.

7. Renal Scan:
- Radioisotopic study using technetium – 99 diethylene triamine penta acetic acid (99 Tc–D TPA) to examine glomerular filtration and iodohippurate – 131 to measure renal blood flow.
· Images and time appearance of the isotopes are evaluated simultaneously.
· Expensive and of questionable accuracy for screening renal artery stenosis.

Other Tests

A) Ambulatory 24-hours Blood Pressure Recording (ABP)

- Noninvasive measurement of blood pressure by automatic or semiautomatic technique every 15-60 minutes day and night.
- Record is analyzed for:

1. Average 24 hr systolic and diastolic pressures.
2. Average day time and sleep pressures.
3. Pressures at work and at home.
4. Pressures recorded during unexplained symptoms.
5. Peak pressures and number of measurements above normal.

· Indications

1. Borderline hypertension with target organ damage.
2. Suspected white coat hypertension (present in 20–30% of hypertensives).
3. Resistant hypertension.

Laboratory Evaluation of Hypertensive Patients

4. Symptomatic hypertension.
5. Episodic (paroxysmal) hypertension.
6. Drug trials and evaluation of antihypertensive treatment.

· Limitations
1. Expensive.
2. Constant calibration is needed.
3. Definitions of normal and abnormals are not established.
4. There is insufficient evidence at present to recommend ABP monitoring for routine clinical use or in decision making.

· ABP Readings

1. Daytime range: 101/62 – 143/90 mmHg in normotensives.
2. Daytime average of 135/84 mmHg corresponds to clinic pressure of 140/90 mmHg.

B) Carotid Arteries Duplex Scanning

Ultrasound imaging using Doppler and two dimensional imaging of carotid arteries is indicated in patients with cerebral transient ischemic attacks, carotid artery bruits or after brain infarction.

C) Doppler Flow Measurement of Renal Arterial Flow
- Used in diagnosing renal artery stenosis.
- For accuracy and reliability (experience is necessary). See chapter 10 on renal artery stenosis.

SPECIAL LABORATORY TESTS

1. Clonidine Suppression Test

- Reliable in differentiating essential hypertension with increased plasma catecholamines level (500–2,000 pg/ml) from patients with pheochromocytoma.

Laboratory Evaluation of Hypertensive Patients
- Blood Pressure and plasma norepinephrine are measured before and three hours after a single oral dose of clonidine 0.3 mg.
- Clonidine reduces plasma norepinephrine by 50% or to normal limits in essential hypertension. Patients with pheochromocytoma are less affected.
- Beta blockers should be discontinued 48 hours before the test.

2. Captopril Test

- Sensitive screening test (74% sensitivity and 89% specificity) for the diagnosis of renovascular hypertension (RVH).
- Blood pressure and plasma renin activity (PRA) are measured before and 60 minutes after oral captopril (50 mg).
- Patients with RVH show:

1. Increase in PRA by at least 10 ng/ml/hr.

2. Increase in PRA to 12 ng/ml/hr or by 150%.
- Less reliable in patients with renal failure.
- Patients should discontinue all antihypertensive drugs 3 weeks before the test.
- Patient should be seated 30 minutes before the test and on normal salt diet.

3. Captopril Renography
- Reliable in screening patients for renal artery stenosis (92% sensitivity and 95% specificity).
- Compare isotope renograms (see renal scan) before and after a single dose of captopril (50 mg oral).
- Preparation of the patient is similar to captopril test.
- Captopril decreases glomerular filtration rate on the affected side with little change in renal blood flow (both are measured by radioactive isotopes).
- Combined Captopril renography with measurement of PRA are useful noninvasive screening tests for RVH.

Laboratory Evaluation of Hypertensive Patients

4. Dexamethasone Suppression Test
- For diagnosis of Cushing’s syndrome.
- Failure to supress plasma to less than 5 mcg/dl or urinary free cortisol levels to less than 20 mcg/24 hrs following 0.5 mg dexamethasone orally every 6 hours for 2 days is pathognomonic of Cushing’s syndrome.

5. Magnetic Resonance Imaging (MRI)

Highly sensitive and specific for pheochromocytoma and adrenal cortical tumours. It is expensive and indicated when CT scan is not conclusive in spite of great clinical and laboratory suspicion.

6. 131I meta-iodo-benzylguanidine (MIBG) Imaging
- Radio isotopic scanning with MIBG may be helpful for detection and localization of pheochromocytoma, specially scanning recurrent or metastatic tumours.
- Indicated when tumors are not visualized by CT scanning or MRI.
- Sensitivity is 88% and specificity 99%.

Spot urine analysis macroalbuminuria (> 300 mg albumin/24 hrs urine). Microalbuminuria (30-300 mg albumin/24 hrs urine) is a sign of target organ damage and correlates with other cardiovascular complications.

There is insufficient evidence at present to recommend echocardiography for routine clinical use in evaluating or making decisions in mild hypertension.

Products of catecholamine metabolism, elevated in patients with pheochromocytoma.