Etiology
Primary hypertension
This is the most common situation, when no underlying cause can be found to account for elevated blood pressure. It is also referred to as essential hypertension. A genetic basis has been suggested.[22] Lifestyle influences such as obesity, sedentary lifestyle, excess alcohol intake, and high sodium intake are all thought to promote the development of essential hypertension.[20][23][24][25][26]
Secondary hypertension
In a minority of cases, an underlying, often reversible cause can be found. This may be suspected in a younger patient (<40 years of age), when blood pressure is resistant to first-line medication, or if previously well-controlled hypertension suddenly becomes difficult to manage without any change in medication adherence.
Vascular
One of the most common secondary causes of hypertension is renal artery stenosis. This may be entirely asymptomatic but, if hypertension is difficult to control and the patient is young, renal artery stenosis should be excluded. Stenosis is usually due to fibromuscular dysplasia or atherosclerosis, but other causes include extrinsic compression of the artery by an adjacent tumor or a proximal aneurysm of the renal artery.
Coarctation of the aorta is a congenital narrowing of the aorta. When presenting in adults with hypertension, this narrowing is usually distal to the ligamentum arteriosum, although coarctation can occur before or at the site of the ligamentous insertion. There is usually hypertension in the upper limbs but weak or absent pulses in the lower limbs. This combination of signs will raise suspicion of a coarctation on clinical exam.
Preeclampsia is a syndrome of hypertension with proteinuria in pregnant women. Its exact cause is unknown, but the placenta is thought to release factors, perhaps in response to hypoxia, that affect the vascular endothelium in susceptible women. It can also occur up to 2 months after birth. Women with preexisting hypertension, diabetes, or autoimmune disease are thought to be at greater risk of developing preeclampsia.
Renal
Chronic kidney disease: a decrease in the glomerular filtration rate will stimulate the kidneys to up-regulate production of renin to raise the blood pressure and renal perfusion. Fluid overload will also contribute as the kidneys fail to excrete volumes required for homeostasis. Both of these mechanisms can lead to hypertension.
Nephrotic syndrome: a syndrome of proteinuria, hypoalbuminemia, and edema caused by damage to the filtering capability of the renal glomeruli. Hypertension in this setting is not common, but can occur due to salt and water retention and fluid overload. ACE inhibitors are the first-choice agent for blood pressure control in nephrotic syndrome, as they may also reduce proteinuria.
Glomerulonephritis: a condition characterized by inflammation of the glomeruli. Hypertension is a main feature of this syndrome, via mechanisms similar to those in chronic renal failure.
Obstructive uropathy: this can produce hydronephrosis, and the back-pressure on the kidneys can result in renal failure and elevated blood pressure through similar mechanisms.
Polycystic kidneys: hypertension is a common presenting symptom, and it is often apparent before renal function abnormalities. Hypertension with polycystic kidney disease can present at a young age (20 to 34 years) and is associated with a high incidence of left ventricular hypertrophy.
Endocrine
Pheochromocytoma: this is a neuroendocrine tumor of the adrenal glands. Hypertension results from excessive secretion of epinephrine and norepinephrine. It can also occur as part of a multiple endocrine neoplasia syndrome. Patients may present with malignant hypertension or hypertension that is resistant to usual pharmacologic therapy.[27]
Hyperaldosteronism: excess production of aldosterone by the adrenal glands results in sodium and water retention and potassium excretion. The excess production of aldosterone is usually due to a solitary adrenal adenoma (Conn syndrome), but hyperaldosteronism and consequent hypertension can also be the result of adrenal hyperplasia. Despite the fact that primary hyperaldosteronism is the most common cause for secondary hypertension, it is a diagnosis that is frequently missed.[28]
Cushing syndrome: excess production of cortisol by a pituitary or adrenal tumor, or the use of exogenous corticosteroids, can result in Cushing syndrome. It can be adrenocorticotropic hormone-dependent or -independent. Hypertension results as cortisol enhances the vasoconstrictor effect of catecholamines.
Hyperthyroidism: may be a secondary cause of hypertension in approximately 1% to 3% of hypertensive patients; data are sparse.[29][30] Excess thyroxine exacerbates the effect of the sympathetic nervous system. It thereby increases vascular resistance and cardiac output. This can lead to an isolated systolic hypertension. Hypertension should respond to treatment of the underlying cause.
Hypothyroidism: may be a secondary cause of hypertension in approximately 1% to 3% of hypertensive patients; data are sparse.[29][30][31] Low levels of circulating thyroid hormone may result in mild hypertension as the heart rate is slowed and there is an increase in peripheral vascular resistance to compensate.[32][33][34] Hypothyroidism can also cause elevation of cholesterol and lipid levels in the blood, thus increasing overall cardiovascular risk if left untreated.
Hyperparathyroidism: hypertension is often noted in patients with hyperparathyroidism, but a causative relationship has not been proven and the mechanism is unclear.
Sleep disorders
Patients with obstructive sleep apnea/hypopnea syndrome, or obesity hypoventilation syndrome, are often obese, with an increased risk for hypertension.[35][36][37][38] They also have an increased risk of myocardial infarction and stroke. The mechanism is unclear but may involve oxidative stress secondary to hypoxia and sympathetic autonomic activation. Such patients often have a number of cardiovascular risk factors that need to be addressed alongside treatment of their hypertension and sleep apnea/hypopnea and obesity-related conditions.
Toxic causes
Chronic alcohol excess: the relationship between alcohol, hypertension, and overall cardiovascular risk is complex and a J-shaped relationship has been suggested, with those who drink a small amount of alcohol having a lower risk than those who abstain completely. However, in various studies, people who misuse alcohol demonstrate a marked decrease in blood pressure readings when subject to alcohol abstinence (after an initial increase during the withdrawal phase). The mechanisms are unclear.[39]
Illicit drug use such as cocaine and methamphetamine misuse can lead to hypertension due to sympathetic activation. The potential for reduced compliance with antihypertensive therapy in this patient population may result in persistent high blood pressure.
Medications
In a nationally representative survey study in the US, 18% of adults with hypertension reported taking medications that may cause elevated blood pressure, most commonly antidepressants, prescription nonsteroidal anti-inflammatory drugs (NSAIDs), steroids and estrogens.[40]
Use of oral contraceptives and long-term use of NSAIDs have both been implicated in the development of hypertension: the former due to the effects of progesterone on small blood vessels; NSAIDs through effects on the kidney and fluid retention in susceptible individuals. Hypertension will usually respond to discontinuation of the drugs.
Hypertension is a common adverse effect of glucocorticoids, cyclosporine, and atypical antipsychotics.
Up to 80% of patients treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors for metastatic solid organ malignancy develop hypertension.[41]
Pseudohypertension
"White-coat hypertension" is an apparent elevation of blood pressure when readings are taken in a clinical environment. The patient may have their own blood pressure monitor at home and report normal readings. This apparent elevation is usually ascribed to anxiety or stress at having their blood pressure measured. It may subside with repeat measurements over time, or persist in the clinical environment. One way to distinguish true hypertension from falsely elevated readings is to record blood pressure over a 24-hour period or arrange measurements at home. This will avoid unnecessary treatment, although overall cardiovascular risk must still be evaluated. These patients need close follow-up, as it has been shown that untreated white-coat hypertension is associated with an increased cardiovascular risk.[42]
Resistant hypertension
Resistant hypertension (RH) is defined as above-goal elevated blood pressure despite the concurrent use of three antihypertensive drug classes, commonly including a long-acting calcium channel blocker, a blocker of the renin-angiotensin system (angiotensin-converting enzyme inhibitor or angiotensin receptor blocker), and a diuretic.[9]
Consider causes of secondary hypertension in patients with RH.
Consider nonadherence and white-coat hypertension as causes of apparent treatment-resistant hypertension. Estimates of nonadherence to hypertension medication range from 7% to 60%.[9] The American Heart Association recommends using the following question to assess adherence: “When taking multiple medications, it is common to miss doses throughout the week. How many times do you miss taking your blood pressure medication in a week?”[9] White-coat hypertension can be excluded by 24-hour ambulatory blood pressure monitoring or home blood pressure measurements.
Poor blood pressure measurement technique can give falsely elevated blood pressure readings.
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