Hypertension

Blood pressure measurements higher than 120/80 mm Hg place patients at increased risk for cardiovascular disease.

In adults, classification of hypertension is based on an average of two or more blood pressure readings obtained more than 1 minute apart at two or more visits.

If single-agent antihypertensive therapy is ineffective after 1 to 3 months of treatment, switching to or adding a drug with a complementary mechanism of action is indicated.

less than 120/80

Initial treatment with two antihypertensive agents may particularly be warranted for patients whose blood pressure is more than 20 mm Hg above the blood pressure goal, and those with stage 2 or higher hypertension often require treatment with more than one agent

An elevated plasma aldosterone-plasma renin ratio accompanied by unsuppressed aldosterone excretion after correction of hypokalemia and adherence to a high-sodium diet for 3 days is diagnostic of primary aldosteronism.

In patients with primary aldosteronism who cannot be treated surgically, aldosterone inhibition with spironolactone or eplerenone may be used.

Catheter-based angiography is the most accurate method of diagnosing renovascular hypertension caused by fibromuscular disease.

Diagnosis of pheochromocytoma requires confirmation of excess catecholamine production supported by positive findings on MRI or CT scanning.

Surgical resection is the treatment of choice for pheochromocytoma and can resolve associated hypertension.

White coat hypertension is characterized by at least three separate office blood pressure measurements above 140/90 mm Hg with at least two sets of measurements below 140/90 mm Hg obtained in non-office settings, accompanied by the absence of target organ damage.

Ambulatory blood pressure measurements

Resistant hypertension is defined as blood pressure that remains above goal despite treatment with the optimal dosages of three antihypertensive agents of different classes, including a diuretic.

An elevated systolic blood pressure is the most useful outcome predictor of cardiovascular morbidity and mortality in patients older than 50 years of age.

Failure of the blood pressure to decrease by at least 10% during sleep, known as nondipping, as well as an excessive morning surge in blood pressure have been associated with increased cardiovascular risk, particularly for stroke.

Ambulatory blood pressure monitoring provides multiple blood pressure readings over a prolonged period of time. This method evaluates mean 24-hour blood pressure; mean daytime blood pressure; mean nighttime blood pressure; the average difference between waking and sleeping blood pressure to evaluate for nocturnal dipping (which may be defined as a decrease in mean arterial blood pressure of >10% during sleep); and blood pressure variability.

<120 / <80

120-139 systolic or 80-89 diastolic

140-159 / 90-99

≥160 / ≥100

JNC 7 guidelines recommend lifestyle modifications and drug treatment for all patients with stage 1 or greater hypertension, regardless of absolute risk.

• Reduce weight
• Follow DASH diet
• Participate in aerobic physical activity for 30 to 34 minutes most days
• Reduce sodium intake to <100 mmol/24 h
• Limit daily alcohol consumption to two drinks for men and one drink for women
• Smoking cessation

Autosomal dominant; gain of function of epithelial sodium channel

Elevated blood pressure, hypokalemic metabolic alkalosis, low renin and aldosterone levels, excess sodium retention

Amiloride, thiazide diuretics, spironolactone

• Liddle syndrome
• Glucocorticoid-remediable aldosteronism
• Apparent mineralocorticoid excess
• Type 2 pseudohypoaldosteronism (Gordon syndrome)
• Mineralocorticoid receptor activation
• Mutations in peroxisome-activated receptor-γ
• Hypertension and brachydactyly

Autosomal dominant; regulation of aldosterone secretion by ACTH

Elevated blood pressure, hypokalemic metabolic alkalosis, low renin levels, moderately high aldosterone levels

Aldosterone blockade, corticosteroids

Autosomal recessive; activation of mineralocorticoid receptor by cortisol

Elevated blood pressure, younger age at presentation, hypokalemic metabolic alkalosis, low renin and aldosterone levels

Thiazide diuretics, aldosterone blockade

Autosomal dominant; mutations in WNK kinases 1 and 4

Elevated blood pressure, hyperkalemia, hyperchloremic metabolic acidosis, low renin and aldosterone levels

Thiazide diuretics

Mutation in mineralocorticoid receptor

Elevated blood pressure, younger age, low renin and aldosterone levels, mineralocorticoid receptor activation by steroids such as progesterone, exacerbation in pregnancy

Thiazide diuretics

Heart failure, advanced age, volume-dependent hypertension, low-renin hypertension, systolic hypertension

Primary aldosteronism, resistant hypertension, sleep apnea

Heart failure, left ventricular dysfunction, proteinuria, diabetic nephropathy, chronic kidney disease, post–myocardial infarction

Same as ACE inhibitors; useful when ACE inhibitors are not tolerated

Systolic hypertension, cyclosporine-induced hypertension, angina, coronary heart disease

Angina, heart failure, post–myocardial infarction, migraine, tachyarrhythmias

Prostatic hyperplasia

rash, loss of taste, leukopenia (captopril)

Headache, flushing, gingival hyperplasia, edema, constipation

Hyperkalemia, increased creatinine level, painful gynecomastia, menstrual irregularities, gastrointestinal distress

Target blood pressure measurements of less than 130/80 mm Hg are recommended for those with minimal proteinuria (defined as a 24-hour urine protein level below 1 g/24 h) and less than 125/75 mm Hg for those with significant proteinuria (defined as a 24-hour urine protein level above 1 g/24 h).

• The plasma aldosterone-plasma renin ratio (ARR) is a screening test for primary aldosteronism that is useful even in patients who are taking antihypertensive agents except for aldosterone blockers
• ARR is helpful only if the serum aldosterone level is above 15 ng/dL (414 pmol/L)
• ARR above 25 is generally considered abnormal.
• An elevated ARR alone is not diagnostic of primary aldosteronism unless nonsuppressible or autonomous aldosterone excess is demonstrated by the presence of a urine aldosterone excretion of 12 µg/24 h (33.2 nmol/d) or higher obtained after correction of hypokalemia and adherence to a high-sodium diet for 3 days.
• In some patients, administering an intravenous saline infusion also may demonstrate nonsuppressible serum aldosterone levels.
• Once nonsuppressible or autonomous aldosterone production is demonstrated, adrenal imaging is indicated to reveal the adrenal anatomy and identify patients with unilateral disease such as an aldosterone-producing adenoma (Conn syndrome) or primary unilateral adrenal hyperplasia. High-resolution CT with thin cuts of the upper abdomen is the preferred imaging technique.
• After biochemical confirmation of hyperaldosteronism, localization procedures differentiate aldosterone-producing adenomas or unilateral hyperplasia from bilateral hyperplasia. Adrenal vein sampling is considered the gold standard for demonstrating lateralization of aldosterone secretion and is recommended for patients who are candidates for adrenalectomy.

• Unilateral aldosterone-producing adenoma; unilateral adrenal hyperplasia; and, rarely, aldosterone-producing carcinoma can be resolved with surgery. Laparoscopic adrenalectomy without previous adrenal vein sampling may be warranted in patients less than 40 years of age if nonsuppressible hyperaldosteronism is documented and if CT scanning demonstrates unilateral adrenal abnormalities and a normal contralateral gland.
• Bilateral adrenal adenomas or hyperplasia cannot be resolved with surgery. Glucocorticoid-remediable aldosteronism, a rare form of nonprimary aldosteronism that can cause hypertension, also is not able to be cured surgically.
• If surgery is not indicated, aldosterone inhibition with spironolactone or eplerenone may be used to treat primary aldosteronism.

The best known predictors of progression to end-stage kidney disease are the glomerular filtration rate at presentation and the degree of fibrosis detected on kidney biopsy.

• MRI or CT scanning can localize the tumor in patients with a pheochromocytoma.
• Metaiodobenzylguanidine adrenal scanning is highly specific for pheochromocytomas, is helpful in diagnosing extra-adrenal tumors, and can be used to confirm positive findings on CT and MRI scanning. Metaiodobenzylguanidine scanning also may be used when a patient’s clinical presentation raises strong suspicion for pheochromocytoma and biochemical testing demonstrates excess catecholamine production but results on CT or MRI are negative.

• Surgical resection is the treatment of choice for pheochromocytoma and can resolve associated hypertension.
• Beginning 10 to 14 days before surgery, α- and β-blockers are indicated to control blood pressure and pulse rate during the preoperative period and to prevent massive outpouring of catecholamines during surgical manipulation.
• The long-acting α-blocker phenoxybenzamine should be started first. The dosage of this agent should be titrated upward to achieve blood pressure control and until adverse effects such as nasal congestion, postural hypotension, fatigue, and diarrhea develop.
• Metyrosine inhibits catecholamine synthesis and reduces tumor stores of catecholamines. This agent should be used when both α- and β-blockers are insufficient to control symptoms or are not tolerated, or when significant intraoperative manipulation of the tumor is anticipated.