—Edited from <Yale-G First Aid: Crush USMLE Step 2CK and Step 3> By Yale Gong, M.D., Sr. Medical Advisor at www.medicine.net (Copyrighted)

Hypertension (disease) is a leading risk factor for cardiovascular disease (CVD), which carries the highest death rate among all diseases.

Systemic Hypertension

Systemic hypertension (HTN Disease) as an adult disorder is newly defined as a state of repeatedly elevated blood pressure (BP) ≥ 130/80 mmHg (stage 1) measured on three separated occasions. Both systolic and diastolic pressures are important in determination of the circulation and functions of organs. However, systolic hypertension is a more powerful predictor of cardiovascular conditions and clinical prognosis after 50 y/a due to the stiffening of arteries, while diastolic pressure may tend to decrease slightly. By etiology it is classified into primary and secondary hypertension.

Key facts:

An estimated 1.28 billion adults aged 30–79 years worldwide have hypertension, mostly with primary hypertension and living in low- and middle-income countries.

An estimated 46% of adults with hypertension are unaware that they have the condition.

Less than half of adults with hypertension are diagnosed and treated.

Approximately 20% with hypertension have it under control.

Updated conceptions:

Hypertension by office-based blood pressure:

Normal blood pressure: systolic < 120 mmHg and diastolic < 80 mmHg;

Prehypertension (Elevated BP): systolic 120 to 129 mmHg and diastolic < 80 mmHg;

Stage 1 hypertension: systolic 130-139 mmHg or diastolic 80-89 mmHg;

Stage 2 hypertension: systolic ≥ 140 mmHg or diastolic ≥ 90 mmHg;

Isolated systolic hypertension: BP ≥ 130/< 80 mmHg;

Isolated diastolic hypertension: BP < 130/≥ 80 mmHg.

I. Primary (Essential) Hypertension

It’s the hypertension without a definable cause and it accounts for > 95% of all hypertensive cases. It’s mostly resulted from either high peripheral resistance or elevated cardiac output. Hypertension is a multi-factorial disease; more factors imply more risk. Screening for hypertension may be started at age 18 or in the middle age. The interval depends on individual’s conditions.

Etiology

1. Sympathetic nervous system hyperactivity: Mostly in young patients.

2. Renin-angiotensin system hyperactivity: Causing increased intracellular Na-Ca-water retention; mostly in young White and Asian populations.

3. Abnormal cardiovascular or renal development: Abnormal aortic elasticity or reduced micro-vascular network and nephrons numbers (associated with low birth weight).

4. Defect in natriuresis: Causing insensitive natriuresis and thus salt-sensitive hypertension.

5. Risk factors: About 50% of risk is due to lifestyle factors—high-Na diet, smoking, obesity, hyperlipidemia, limited exercise, and sleep apnea; and the other half is due to genetics (family history of hypertension or heart disease), advanced age, male gender, the Black population, etc.

Essentials of diagnosis

1. Common symptoms include headaches (typically back of the head and in the morning), lightheadedness, vertigo, tinnitus, altered vision, and fainting episodes. Other possible findings include systolic click, heart sound S4 and/or loud S2, increased cardiac size, and hypertensive retinopathies (copper wires, artery-vein nicking, papilledema, cotton wool spots, hard exudates, and flame hemorrhage).

2. Diagnosis: Mainly based on physical examination (P/E) results: BP ≥ 140/90 mmHg (either one) on > 3 tests separated by > 30 min.

Classification and management are summarized in the table below.

Treatment

Antihypertensive therapy (BP control) has shown to produce a nearly 50% relative risk (RR) reduction in the incidence of heart failure, a 30-40% RR reduction in stroke, and a 20-25% RR reduction in myocardial infarction. Major mechanisms include decreases in blood volume, cardiac output, and arterial tension. Goals of treatment are BP < 140/90 mmHg for most patients and < 130/80 mmHg for patients with chronic diseases (diabetes, kidney disease, etc.).

1. Nonpharmacologic therapy (lifestyle modification):

This includes exercise, weight reduction, alcohol restriction, and Dietary Approaches to Stop Hypertension (DASH) diet—low in salt, fat, sugar, and red meats, and high in vegetables, fruits, whole grains, poultry, fish, and nuts.

2. Pharmacologic therapy:

Initial monotherapy in uncomplicated hypertension—One of the following four main classes:

(1) Thiazide diuretics (chlorthalidone or indapamide); (2) Long-acting calcium channel blockers (such as amlodipine); (3) ACE inhibitors; (4) Angiotensin II receptor blockers (ARBs).

The main exceptions to modest and gradual BP lowering over the first 24 hours:

(1) The acute phase of an ischemic stroke—The blood pressure is usually not lowered unless it is ≥185/110 mmHg (candidates for reperfusion therapy) or ≥ 220/120 mmHg (non-candidates for reperfusion therapy. The blood pressure should be stabilized and maintained at or below 180/105 mmHg for at least 24 hours after thrombolytic treatment.

(2) Acute aortic dissection—The systolic BP should be rapidly lowered to a target of 100-120 mmHg (to be attained in 20 min).

The best selection of antihypertensive is based on specific conditions of the patient, as summarized in the table below.

Summary: Blood Pressure Staging and Management

(Edited from American College of Cardiology and American Heart Association)

Clinical Pearl—Selection of Anti-hypertensive Medications

Adverse effects of antihypertensive agents:

(1) Diuretics (thiazides, furosemide, K⁺ sparing spironolactone): Hypokalemia (except K⁺ sparing agents), hyperglycemia, hyperlipidemia, hyperuricemia, azotemia.

(2) Beta blockers (propranolol, metoprolol, timolol, labetalol): Bronchospasm (in severe asthma), bradycardia, CHF, exacerbation, fatigue, impotence, depression.

(3) Alpha1 blockers (prazosin, doxazosin): Orthostatic hypotension.

(4) Ca blockers (CCBs): Diltiazem: decreased contractility; nifedipine: headache, flushing, peripheral edema.

(5) ACE-Is (captopril, enalapril): Cough, angioedema, rashes, leukopenia, hyperkalemia.

(6) Angiotensin-R blockers (ARBs, losartan, valsartan): Rashes, leukopenia, hyperkalemia; no cough.

(7) Vasodilators: Hydralazine: headache, lupus-like syndrome; minoxidil: orthostasis, hirsutism.

(8) Centrally acting adrenergic agonists (methyldopa, clonidine): Somnolence, orthostatic hypotension, impotence, rebound hypertension.

II. Secondary Hypertension

It’s defined as hypertension due to an identifiable organic cause; some can be surgically correctable.

Etiology, diagnosis, and treatment

1. Substance effects: Alcohol is the #1 cause in young male patients; long term oral contraceptive pills (OCPs, estrogen) use is the #1 cause in > 35 year-old, obese women. Other substances include cocaine, NSAIDs, cyclosporine, tacrolimus, decongestants, etc. Correction of the original cause is the effective therapy.

2. Renal disease: Usually a primary renal parenchymal disease (such as glomerulonephritis) can cause hypertension and is the most common cause of secondary hypertension. ACE-I can alleviate the hypertension and slow the progression of renal diseases.

3. Renal artery stenosis (RAS): (1) More than 90% of cases are caused by artherosclerotic renal ischemia in patients > age 45. (2) Fibromuscular dysplasia (FMD) is a rare cause of RAS and mostly in women < age 30.

RAS Diagnosis: (1) Clues: 1) Resistant hypertension with onset < 30 or > 50 y/a without obesity, family history, and other risk factors; 2) Refractory hypertension or newly onset hypertension that is resistant to > 3 medications; 3) There are abdominal/renal artery bruits; 4) There is a history of atherosclerosis; 5) There is abrupt deterioration of the renal function (elevation in the serum creatinine) after the use of ACE-I; 6) Malignant or accelerated hypertension with signs of end-organ damage. (2) The best screening method is a renal radionuclide flow scan with captopril (showing high rennin and aldosterone). (3) Confirmation is done by CT angiography or by renal vein renin ratio (RVRR).

RAS Treatment: (1) For atherosclerotic RAS: 1) Medical therapy first for most unilateral and bilateral RAS; 2) If hypertension still cannot be controlled, percutaneous angioplasty with stenting is recommended. Renal artery revascularization is reserved for those with complex anatomic lesions or failed stenting procedures. (2) For fibromuscular dysplasia: percutaneous angioplasty with stent is usually curative. (3) ACE-I can be a drug adjunct in elder patients for one-side stenosis, but contraindicated in bilateral renal stenosis because it can accelerate high-renin and renal failure by preferential vessel-dilation of the efferent artery.

4. Primary (hyper)aldosteronism: Most cases (70%) result from a unilateral adrenal tumor (Conn syndrome); 30% from bilateral adrenocortical hyperplasia. It is clinically characterized by hyper-aldosterone and hyper-Na, hypo-K, and hypo-renin (due to hypervolemia). Treatment: (1) Conn syndrome: Laparoscopic or open adrenalectomy is the therapy of choice. (2) Bilateral hyperplasia: Aldosterone-R antagonist—spironolactone (#1) or eplerenone (#2).

5. Cushing syndrome: It’s a group of clinical abnormalities caused by chronic or prolonged hypercortisolism. The No.1 cause is excessive use of corticosteroids (iatrogenesis). The No.2 cause is ACTH hypersecretion by the pituitary microadenoma (Cushing disease, accounting for 70% of organic hypercortisolism), characterized by hypo-K, hypertension, decreased glucose intolerance, muscle weakness, central obesity, hirsutism, striae, and “buffalo hump”. Treatment: Ketoconazole, metyrapone, cabergoline, and surgery (best for ACTH-secreting tumors).

6. Pheochromocytoma: Triad—episodic hypertension, headache, and diaphoresis. Other features include young age, paroxysmal symptoms, and endocrine tumor history (MEN IIA & IIB syndrome). Diagnosis: Based on elevated 24-hour urinary metanephrine or vanillylmandelic acid (VMA), which is a metabolite of catecholamines. CT or MRI is also helpful in diagnosis. Treatment: Alpha blockers followed by beta blockers, and then surgical resection.

7. PKD (Polycystic kidney disease): Hypertension along with a family history of PKD, flank mass, and enlarged kidneys. Treatment: Symptomatic and conservative therapies.

8. Coarctation of the aorta: Hypertension with upper limbs only; right arm BP > left arm BP, with lower limb muscle hypotrophy. Treatment options depend on conditions of the patient (age, severity, etc.). Surgical correction is the potential cure.