bubble_chart Overview

Primary hypertension is a common cardiovascular disease in adults, which can lead to cerebral apoplexy and coronary heart disease with a high mortality rate. The cause of the disease remains unknown to this day. Since the 1970s, longitudinal epidemiological studies on children's blood pressure have been conducted both domestically and internationally. These studies have found that blood pressure in children exhibits a tracking phenomenon during growth, meaning an individual's blood pressure consistently remains within the corresponding percentile over a certain period. This suggests that primary hypertension may begin in childhood. Consequently, it has been proposed that interventions should be implemented during childhood to prevent or delay the onset of hypertension, thereby improving public health. Currently, the percentile method is widely favored for assessing hypertension in children. Hypertension is defined as systolic and/or diastolic blood pressure values exceeding the 95th percentile for the child's age and gender, while values between the 90th and 95th percentiles are considered high-normal blood pressure. Since children are often nervous during their first blood pressure measurement, which can affect the readings, repeated measurements must be taken over several weeks. A diagnosis of hypertension should only be made if the values exceed the threshold in at least three separate measurements.

bubble_chart Epidemiology

Since the 1980s, various blood pressure sampling surveys of healthy children have been conducted in China. Due to differences in measurement methods and diagnostic criteria, the prevalence of hypertension ranges from 0.5% to 9.36%. A recent survey in Beijing in 1988 of 5,916 school-age children, using the aforementioned hypertension criteria, reported a prevalence as high as 9.36%, which warrants attention.

bubble_chart Etiology

Hypertension secondary to other disease causes is classified as secondary hypertension, while those with unknown disease causes are categorized as primary hypertension (Table 26-30). In recent years, it has been found that primary hypertension is not uncommon, mostly mild hypertension, while severe hypertension in childhood is predominantly secondary. Active efforts should be made to identify the disease cause and strive to eliminate it for a potential cure.

Table 26-30 Causes and Diagnostic Methods of Pediatric Hypertension

Disease Cause	Diagnostic Methods Beyond History and Symptoms
1. Primary Hypertension	Positive family history, obesity, grade I elevated blood pressure, absence of other positive signs or laboratory findings
2. Secondary Hypertension
(1) Kidney parenchymal sexually transmitted diseases:
① Acute and chronic glomerulonephritis (including renal lesions from connective tissue diseases)	Urinalysis, urine concentration function, hematuria creatinine levels, urine Addis count, blood lupus erythematosus cells, antinuclear antibody testing, serum protein electrophoresis, blood moistening and tonifying body measurement, renal biopsy if necessary
② Pyelonephritis	Urinalysis, midstream urine culture, intravenous pyelography
③ Polycystic kidney, renal hypoplasia	Renal function tests, intravenous pyelography
④ Nephroblastoma	Abdominal mass, urinalysis, intravenous pyelography
⑤ Hemolytic uremic syndrome	Complete blood count, platelets, reticulocytes, blood bilirubin, blood electrolytes, urinalysis, renal function tests
(2) Renal vascular sexually transmitted diseases:
① Renal artery stenosis, embolism	Abdominal or lumbar vascular murmurs, intravenous pyelography, isotope renography, renal artery
② Renal vein thrombosis	Angiography, renal vein renin activity measurement
(3) Cardiovascular system diseases:
① Aortic coarctation	High blood pressure in upper limbs, low blood pressure in lower limbs, weaker and delayed pulses in lower limbs compared to upper limbs, echocardiography, aortic angiography
② Aortitis	Vascular murmurs at affected sites, weak or absent peripheral pulses, aortic angiography, other methods similar to renal artery stenosis
(4) Endocrine diseases:
① Secondary to long-term corticosteroid or ACTH therapy	History, Cushingoid facies, obesity
② Hypercortisolism	Urine 17-ketosteroid measurement, plasma and urine free cortisol measurement, dexamethasone suppression test, abdominal B-ultrasound and CT examination
③Primary hyperaldosteronism	Blood electrolyte measurement, blood and urine aldosterone measurement, plasma renin activity measurement, abdominal B-ultrasound and CT scan
④Pheochromocytoma	Intravenous pyelography, 24-hour urinary vanillylmandelic acid (VMA) measurement, phentolamine test, abdominal B-ultrasound and CT scan
⑤Neuroblastoma	Abdominal or thoracic mass, anemia, intravenous pyelography, 24-hour urinary dopamine measurement, abdominal B-ultrasound and CT scan
(5) Central nervous system disorders:
①Intracranial tumors, hemorrhage, edema	Cerebrospinal fluid examination, fundus examination, brain CT scan
②Encephalitis	Neurological examination, cerebrospinal fluid examination
(6) Poisoning:
①Lead poisoning	Basophilic stippling of red blood cells, cerebrospinal fluid examination, long bone and skull X-ray examination
②Mercury poisoning	Urinary mercury measurement

Secondary hypertension is most commonly caused by renal parenchymal diseases, accounting for about 80% of cases. Among these, various types of acute and chronic glomerulonephritis (including renal lesions caused by connective tissue diseases) are the most frequent, followed by chronic pyelonephritis and other congenital urinary tract disorders. Renal vascular diseases account for about 12% of secondary hypertension cases, with renal artery stenosis being the most common. In neonatal hypertension, 93% are due to renal vascular diseases, which is related to the increased use of umbilical artery catheters leading to umbilical artery thrombosis in recent years. There are also reports of infant hypertension caused by umbilical vein thrombosis due to excessive fluid loss from severe diarrhea and blood concentration. Endocrine disorders causing hypertension are mostly adrenal diseases, such as Cushing's syndrome and pheochromocytoma. Neuroblastoma, due to tumor cells secreting catecholamine-like substances, is a common cause of hypertension in infants under 2 years old. Among cardiovascular system disorders, coarctation of the aorta is a common cause of hypertension in children, although its incidence is lower domestically than abroad, it must be carefully ruled out. Takayasu arteritis is one of the common causes of severe hypertension in children in China. Additionally, hypertension can result from nervous system disorders and heavy metal poisoning (lead and mercury).

bubble_chart Pathogenesis

The mechanism of disease of primary hypertension is still unclear. Extensive experimental research and clinical observations have confirmed that primary hypertension is closely related to heredity. If one parent has primary hypertension, their children have a higher probability of developing hypertension. Moreover, children from hypertensive families, whether they have hypertension or not, exhibit a more pronounced blood pressure increase in sodium-loading tests compared to children without a family history of hypertension, suggesting that excessive salt intake contributes to the occurrence of hypertension. Recent studies have found abnormal ion transport in the somatic cell membranes of primary hypertension patients, which is also closely related to heredity. Whether this constitutes the mechanism of disease of primary hypertension remains to be confirmed. Body weight is an important factor affecting children's blood pressure. Obesity in hypertensive children often leads to a decrease in blood pressure when weight is reduced. Other factors, such as excessive sympathetic nerve excitability, mental stress, and insufficient sleep, can increase blood pressure due to the overproduction of adrenaline and noradrenaline, but direct evidence linking these factors to hypertension is still lacking.

The level of stirred pulse pressure depends on stroke volume and total peripheral vascular resistance. Any factor that increases cardiac output, such as increased blood volume due to water and sodium retention or enhanced myocardial contractility, or increases peripheral vascular resistance, such as neural or endocrine factors causing peripheral stirred pulse contraction, can elevate blood pressure. The former increases systolic pressure, while the latter significantly raises diastolic pressure. Other factors contributing to hypertension include certain unit factors that alter blood pressure through the aforementioned direct determinants, the most important of which is the renin-angiotensin-aldosterone system. Renal diseases, especially renal vascular diseases, reduce renal blood perfusion pressure, decrease effective circulating blood volume, or increase sympathetic nerve activity, all of which stimulate the juxtaglomerular cells to secrete large amounts of renin. Renin is a proteolytic enzyme that catalyzes the hydrolysis of angiotensinogen (an α₂ globulin) produced by the liver into angiotensin I, which is inactive. When it flows through various blood vessels, especially the pulmonary circulation, it is converted into active angiotensin II by the action of converting enzymes. The latter has a strong vasoconstrictive effect, leading to hypertension, while indirectly stimulating the adrenal cortex's zona glomerulosa to secrete aldosterone, causing renal tubular sodium retention, expanding blood volume, and increasing blood pressure. Hypertension in children with acute glomerulonephritis and most kidney excess parenchymal diseases is often related to water and sodium retention and increased blood volume, with renin levels in the blood mostly within the normal range. In advanced stage glomerulosclerosis, vasoconstrictive high-renin hypertension may also occur.

Adrenal diseases cause hypertension through their secreted hormones, such as: ① Primary hyperaldosteronism, the mechanism of which has been described above; ② Hypercortisolism, where large amounts of glucocorticoids cause water and sodium retention and stimulate the production of angiotensin, leading to hypertension; ③ Pheochromocytoma, where tumor cells secrete excessive adrenaline and noradrenaline. Adrenaline increases cardiac output by enhancing myocardial contractility and heart rate, thereby raising systolic pressure. Noradrenaline, in addition to the above effects, strongly constricts peripheral blood vessels, increasing both systolic and diastolic pressure.

Main stirred pulse coarctation causes upper limb hypertension due to mechanical obstruction, but in a few advanced stage cases, blood vessels do not decrease after surgical relief of the coarctation, possibly due to increased renin or peripheral vascular resistance. Large stirred pulse arteritis causes renal stirred pulse stenosis or severe stenosis of the descending main stirred pulse, affecting renal blood perfusion and resulting in high-renin hypertension.

Central nervous system disorders such as polyradiculitis, poliomyelitis, intracranial hemorrhage, tumors, encephalitis, etc., may occasionally cause severe hypertension. The mechanism of disease is believed to be due to the disease affecting the stability of the autonomic nervous system, leading to sympathetic nerve excitation. Increased intracranial pressure may be a contributing factor.

bubble_chart Clinical Manifestations

The symptoms vary depending on the degree of blood pressure elevation, the presence of underlying diseases, and their severity. Children with grade I hypertension often show no obvious symptoms and are only discovered during physical examinations. When blood pressure is significantly elevated, symptoms such as dizziness, headache, nausea, and vomiting may occur. As the condition progresses, secondary changes in the fundus, brain, kidneys, and cardiovascular system may develop, manifesting as vertigo, visual disturbances, convulsions, hemiplegia, aphasia (symptoms of hypertensive encephalopathy), or heart failure. Therefore, blood pressure must be measured in children presenting with convulsions or heart failure. Symptoms of renal damage are often not obvious, but nocturia may appear in the advanced stage. Certain diseases have specific symptoms: for example, pheochromocytoma may present with profuse sweating, palpitation, tachycardia, weight loss, and excessive catecholamines in the blood; Cushing's syndrome may include weakness, obesity, body shape changes, hirsutism, and ecchymosis; primary aldosteronism may present with periodic muscle hypotonia, weakness, hand and foot convulsions, polyuria, and polydipsia; adrenal genital syndrome is clinically characterized by the coexistence of masculinization and hypertension.

Positive signs differ depending on the underlying disease. During physical examination, blood pressure in all four limbs must be measured, and the carotid pulse as well as peripheral pulses should be palpated. In children with coarctation of the aorta, the blood pressure in the upper limbs is more than 2.67 kPa (20 mmHg) higher than in the lower limbs; in severe cases, the femoral pulse may disappear, and blood pressure in the lower limbs may be undetectable. Attention must also be paid to abdominal, lumbar, and cervical vascular murmurs. In renal vascular diseases, about half of the children may have audible vascular murmurs. Abdominal palpation should also be performed. If a mass is detected, it may indicate hydronephrosis, polycystic kidney disease, pheochromocytoma, neuroblastoma, or Wilms' tumor.

Pediatric hypertension can be classified into four grades based on fundus abnormalities: Grade I: normal fundus; Grade II: focal arteriolar constriction; Grade III: exudates with or without hemorrhage; Grade IV: optic disc edema. Grade III or IV fundus changes indicate malignant hypertension and the potential for rapid progression to hypertensive encephalopathy, necessitating aggressive antihypertensive treatment.

bubble_chart Diagnosis

Since grade I hypertension often lacks obvious subjective symptoms and is easily overlooked, blood pressure measurement should be included as one of the routine physical examination items for children. Those with high-normal blood pressure should be followed up regularly. For children with grade I hypertension, a detailed medical history, comprehensive physical examination, and routine urine tests should be conducted. A family history of hypertension, myocardial infarction, or cerebral hemorrhage, combined with obesity in the child and no other positive physical signs besides grade I hypertension, suggests primary hypertension. If blood pressure remains elevated, especially with a diastolic pressure above 13.3 kPa (100 mmHg), further laboratory tests must be performed (see Table 26-30).

First, renal diseases should be considered. In addition to routine urine tests, renal function tests and midstream urine cultures should be performed. Intravenous pyelography (IVP) has a high positive rate and is a valuable screening test for renal hypertension, as it can detect congenital malformations, renal tumors, hydronephrosis, and compare kidney sizes. If the difference in kidney size exceeds 1 cm and the smaller kidney shows delayed contrast excretion within 3 minutes, renal artery stenosis is suspected. However, a normal IVP does not rule out renal vascular disease. Renal arteriography is the most valuable method for diagnosing renal artery stenosis. Renal scintigraphy or renal scans can supplement IVP in suspicious cases, estimating the percentage of total renal function contributed by the affected kidney to help determine surgical suitability. Elevated plasma renin activity suggests renovascular hypertension, but false-negative cases may occur. Currently, renal vein renin activity measurement is more commonly used, where venous catheters are placed in both renal veins during arteriography to collect blood for renin activity testing. If the ratio of renin activity between the two sides exceeds 1.5:1, surgical removal of the high-renin-producing kidney is indicated, with a good postoperative prognosis.

If endocrine disorders are suspected, urinary vanillylmandelic acid (VMA) testing can be performed. In cases of pheochromocytoma or neuroblastoma, VMA levels may increase more than twofold. Urinary dopamine testing can help differentiate between pheochromocytoma and neuroblastoma: dopamine levels do not increase in the former but do in the latter. For suspected Cushing's syndrome, 24-hour urinary 17-hydroxycorticosteroids and 17-ketosteroids can be measured; the former increases while the latter remains normal or slightly elevated. Plasma and urinary cortisol concentrations may also be elevated. In primary aldosteronism, plasma renin activity is reduced, while plasma and urinary aldosterone concentrations are increased. For localization of adrenal disorders, B-ultrasound and CT scans are commonly used, with B-ultrasound being simpler and more accessible. However, for smaller tumors, adrenal isotope scanning has a higher positive rate.

bubble_chart Treatment Measures

For primary grade I hypertension, non-pharmacological treatment should be tried first. Attention should be paid to establishing a regular lifestyle, eliminating various mental stress factors, strengthening dietary guidance, and limiting salt intake to 2–2.5 g/d. Obese children should reduce their weight and increase physical exercise. If blood pressure still shows no downward trend after 1/2–1 year or if there is target organ involvement or underlying disease, pharmacological treatment may be tried. For children with secondary hypertension, treatment should target the disease cause. In recent years, for patients with renal artery stenosis, percutaneous balloon catheter angioplasty can be performed simultaneously with angiography, and for those with more localized lesions or fibromuscular dysplasia, medication may not be necessary. Since the 1980s, antihypertensive drugs have further developed, especially the clinical application of angiotensin-converting enzyme inhibitors and calcium channel blockers, which has expanded the means of treating hypertension. Currently, commonly used antihypertensive drugs in pediatrics can be summarized as follows:

1. Diuretics: By promoting sodium excretion and reducing blood volume, they exert an antihypertensive effect, suitable for mild grade II hypertension. In severe hypertensive patients, combined use with other antihypertensive drugs can enhance their effects. Pay attention to water and electrolyte balance during application.

(1) Hydrochlorothiazide: 1–2 mg/kg per day, divided into two doses.

(2) Furosemide: Suitable for hypertensive children with renal insufficiency. If azotemia and oliguria worsen during treatment, the drug should be discontinued. Dose: 1–2 mg/kg per dose, 1–2 times daily. Intravenous injection may be used if necessary.

(3) Spironolactone: An aldosterone antagonist with sodium-excreting and potassium-retaining effects, suitable for patients with adrenal hyperplasia, tumors, or secondary hyperaldosteronism. Dose: 1.5–3 mg/kg per day, divided into three doses.

2. Adrenergic receptor blockers

(1) Phentolamine: An α-receptor blocker, used in the preoperative preparation stage for pheochromocytoma, especially when the child has a hypertensive crisis. It can be slowly injected intravenously at 0.1–0.5 mg/kg per dose or infused at 1–4 mg/(kg·min), with close monitoring of blood pressure. Side effects include tachycardia.

(2) Prazosin: A selective α₁ receptor blocker that lowers blood pressure by reducing peripheral vascular resistance, without the side effect of tachycardia. Long-term use does not lead to drug tolerance, and it has synergistic effects when combined with diuretics and β-blockers. Dose: 0.02–0.05 mg/kg per day, divided into three doses. Common side effects include vertigo and weakness. To reduce reactive syncope, the initial dose should be minimized and taken at bedtime.

(3) Propranolol: A β-receptor blocker. Its antihypertensive mechanism is not fully understood but may be related to the inhibition of β-receptors in the vasomotor center and renal juxtaglomerular apparatus. Suitable for patients with high-output, high-renin hypertension. Combined use with diuretics and vasodilators can enhance efficacy. Side effects are minimal, but it is contraindicated in patients with heart failure and bronchial asthma. Dose: 0.5–2 mg/kg per day, starting with a small dose, divided into three doses.

(4) Labetalol: Has both α- and β-receptor blocking effects. It acts rapidly with high efficacy and has no adverse effects on the heart, brain, or kidneys. It can be used for mild, moderate, and grade III hypertension. Intravenous injection can be used for emergency treatment of hypertensive crisis, starting with 0.25 mg/kg. If ineffective, 0.5 mg/kg can be given after 10 minutes, slowly injected intravenously. If necessary, a final dose of 1.0 mg/kg can be given, with a total dose ≤ mg/kg. The effect begins within minutes after intravenous injection, with stable antihypertensive effects. After efficacy is achieved, switch to oral administration.

3. Vasodilators: The mechanism of action involves directly dilating small stirred pulse smooth muscles, reducing total peripheral resistance, thereby exerting antihypertensive effects. Due to vasodilation and blood pressure reduction, secondary sympathetic excitation may cause side effects such as increased heart rate, enhanced myocardial contractility, and water-sodium retention. Therefore, combining them with propranolol and/or diuretics can enhance therapeutic efficacy. Commonly used ones include

(1) Hydralazine: Since this drug does not cause a decrease in renal blood volume, it can be used for renal failure. It is often combined with diuretics and β-blockers to treat moderate to grade III hypertension. The daily dose is 0.75–1 mg/kg, divided into 3–4 doses.

(2) Minoxidil: Its antihypertensive effect is stronger than the above drug. Combined with β-blockers and diuretics, it is suitable for severe hypertension that is unresponsive to other medications, and can also be used in patients with renal failure. The starting dose is 0.1–0.2 mg/kg, taken once daily, and can later be increased by 50–100%. The effective dose is usually 0.25–1.0 mg/kg per day, with a maximum dose of 50 mg per day. Side effects, in addition to those mentioned above, include hirsutism.

(3) Diazoxide: A non-diuretic thiazide derivative. It acts rapidly, with effects beginning 1–2 minutes after intravenous injection, peaking at 2–3 minutes, and lasting 4–24 hours. The dose is 2–5 mg/kg per administration, injected intravenously and rapidly. If ineffective after one injection, it can be repeated after 30 minutes. It is the drug of choice for hypertensive crisis. Side effects include nausea, sodium retention, and hyperglycemia.

(4) Sodium nitroprusside: Used for hypertensive crisis, it is diluted in 5% glucose solution and administered intravenously via infusion pump at a rate of 0.5–8 μg/kg per minute. Effects begin within seconds of infusion and cease 1–2 minutes after stopping. The infusion rate can be adjusted to control the speed of blood pressure reduction, making it safer than other drugs for treating hypertensive crisis. It must be freshly prepared, and the infusion should be protected from light. The main side effect is thiocyanate toxicity, manifesting as weakness, nausea, vomiting, followed by disorientation, psychiatric symptoms, muscle rigidity, rash, and bone marrow suppression. If used for more than 2 days, blood thiocyanate levels should be monitored and kept below 10 mg/dL.

4. Angiotensin-converting enzyme inhibitors The most commonly used one currently is captopril, which is suitable for high-renin hypertension but also effective for normal- and low-renin hypertension. Because it increases renal blood flow, it is also suitable for children with renal failure. Its antihypertensive effect is rapid, making it useful for hypertensive emergencies, and its efficacy is enhanced when combined with diuretics. It is now widely used and has become a first-line antihypertensive drug. The starting dose is 0.3 mg/kg per dose, gradually increased to achieve satisfactory effects, with a maximum dose of 2 mg/kg per dose, given every 8–12 hours. When discontinuing, the dose should be tapered gradually to avoid abrupt withdrawal. Excessive doses may cause toxic side effects such as proteinuria, decreased white blood cell count, and rash.

5. Calcium channel blockers These work by blocking calcium ions from entering cells, leading to vasodilation and blood pressure reduction. Nifedipine (commonly known as "heart pain" medication) has been used in pediatric practice. It has a good antihypertensive effect, with a dose of 0.2–0.5 mg/kg per dose, three times daily. The maximum single dose is 10–20 mg. Sublingual administration is more effective than oral, and rectal administration has also been used for severe hypertension. If ineffective, it can be repeated after 30–60 minutes. Side effects include facial flushing and tachycardia.

Selection of antihypertensive drugs: The principle is to start with one drug at a low dose, gradually increasing the dose to achieve the desired blood pressure-lowering effect. If the effect of one drug is unsatisfactory, a second drug may be added. A commonly used treatment regimen begins with thiazide diuretics; if ineffective, propranolol is added, and vasodilators may be introduced if necessary. In recent years, calcium channel blockers and captopril, which have excellent antihypertensive effects, are also frequently used as first-line drugs. When selecting drugs, the mechanism of hypertension should be considered to guide targeted therapy. For patients with long-term uncontrolled hypertension, the mechanism is often more complex, requiring combination therapy with drugs of different mechanisms. For example, high-renin hypertension may be treated with β-blockers or captopril, and diuretics may be added to enhance efficacy. Volume-dependent hypertension often responds well to diuretics. In endocrine disorders such as pheochromocytoma, where excessive catecholamines are secreted, phentolamine may be administered intravenously or prazosin orally. If tachycardia occurs, propranolol can be added. Minoxidil combined with propranolol and diuretics also shows good efficacy in refractory and renal hypertension.

Treatment of Hypertensive Crisis: In children, hypertensive crisis often manifests as hypertensive encephalopathy and requires urgent intravenous antihypertensive medication. The drugs of choice are sodium nitroprusside or diazoxide. To ensure adequate blood supply to vital organs such as the heart, brain, and kidneys, blood pressure reduction should not be too rapid. It is best to reduce the planned antihypertensive target by one-third to one-half within the first 6 hours of treatment. Over the next 36 to 72 hours, blood pressure should be gradually lowered to near-normal levels. Once the hypertensive crisis is alleviated, switch to oral captopril or nifedipine. While lowering blood pressure, it is essential to actively and promptly control convulsions, reduce intracranial pressure, and monitor cardiac and renal function. Special attention must be paid to maintaining fluid and electrolyte balance, especially in cases accompanied by renal insufficiency.

bubble_chart Prevention

Children with high-normal blood pressure, those with a positive family history, and obese children should be prioritized for prevention, with regular blood pressure monitoring. Promote healthy lifestyle habits widely. Ensure diets meet the normal growth and development needs of children, avoiding overweight, starting from infancy by preventing excessive milk feeding or excessive total calorie intake. Daily diets should avoid excessive high-fat and high-cholesterol foods, reduce refined rice and flour, increase vegetable intake, and encourage low-salt diets. Maintain regular physical exercise, avoid excessive mental stress such as heavy academic burdens or exposure to frightening content in TV and movies, reduce environmental noise, ensure adequate sleep, and avoid smoking and alcohol consumption.