The etiology of primary hypertension is multi-source, and more and more data have found that children have a trajectory phenomenon of blood pressure during growth, that is, the phenomenon that individual blood pressure continues to be constant at the corresponding percentile during a certain period, inferring that primary hypertension may begin in childhood, and also suggesting that interventions should be made in childhood to prevent or delay the onset of hypertension.
I. Etiology of primary hypertension
Hypertension in children can be divided into primary and secondary hypertension. Unlike adult hypertension, hypertension in children is mostly secondary hypertension. The younger the child, the more likely the cause of hypertension is secondary; in adolescents, the cause of hypertension is closer to that of adults, with 85%-95% belonging to primary hypertension.
The causes of hypertension in children aged 1-6 years have been reported to be, in order of prevalence, substantial renal disease, renal vascular disease, endocrine disease, aortic constriction, and finally primary hypertension. Primary hypertension, medically induced hypertension, renal parenchymal disease, renal vascular disease, endocrine disease, and aortic constriction. It is evident that primary factors of hypertension gradually replace secondary factors as children grow older.
The exact cause of primary hypertension is uncertain and may be related to family history, high body mass index (BMI), etc. The relationship between BMI and hypertension is particularly strong. The incidence of hypertension increases with BMI, and 30% of overweight children (BMI >95th percentile) develop hypertension. Studies suggest that as BMI increases in children, the prevalence of hypertension increases accordingly. Maintaining normal body mass in childhood may reduce the incidence of hypertension in adulthood. Reduced body mass in adolescents can lead to a decrease in blood pressure.
In addition, excessive salt consumption, low exercise, impatience, stress, smoking, alcohol consumption, noise, and special personal history (e.g., being born as a small for gestational age child and low birth weight child) are also associated with primary hypertension. There is a negative correlation between potassium and calcium intake and hypertension. In addition, a high-fat, high-calorie diet in children is strongly associated with the development of hypertension, and sleep duration in children is negatively associated with the prevalence of hypertension.
Second, the diagnosis of primary hypertension
1.Primary hypertension
Primary hypertension can occur in children and adolescents. Hypertension and prehypertension have become prominent health problems in young people. Children with hypertension should be evaluated for other cardiovascular disease risk factors and sleep history.
Children with essential hypertension are often in stage 1, often with a positive family history of hypertension or cardiovascular disease, and are often overweight. Data on healthy adolescents from school health screening programs demonstrate a correlation between hypertension and obesity and a significant increase in the number of overweight children, suggesting that hypertension and prehypertension have also become prominent health problems in children and adolescents. Overweight children are often associated with some degree of insulin resistance (prediabetes), and overweight and increased blood pressure are also components of the insulin resistance syndrome (or metabolic syndrome). The aggregation of other cardiovascular disease risk factors (e.g., high triglycerides, low HDL, centripetal obesity, hyperinsulinemia) in insulin resistance syndrome is significantly higher in hypertensive children than in normotensive children.
Consultation, physical examination, and laboratory tests in hypertensive children should include evaluation of other cardiovascular risk factors, including lipid and glucose tolerance abnormalities in addition to elevated blood pressure and overweight. To detect other cardiovascular risk factors, fasting lipid and glucose levels should be measured in children who are overweight and in the 90th to 94th percentile of blood pressure, and in children with blood pressure above the 95th percentile. If there is a family history of type 2 diabetes, glycated hemoglobin or glucose tolerance testing may be considered. Because of the association between hypertension and sleep disturbances, children with hypertension should be asked about sleep.
2. Secondary hypertension
Secondary hypertension is more common in children than in adults, and history and laboratory tests are important to detect the cause of hypertension. A more detailed examination should be performed to evaluate younger children with stage 2 hypertension and children with clinical signs of systemic disease associated with hypertension.
A detailed history and physical examination should be performed in children with elevated blood pressure, looking for signs and symptoms suggestive of renal disease (hematuria, edema, and weakness), cardiac disease (chest pain, exertional dyspnea, and palpitations), and other systemic diseases such as endocrine and rheumatologic diseases. Past history was noted for history of trauma, urinary tract infection, snoring and other sleep disorders, and for family history and medication history of hypertension, diabetes mellitus, obesity, sleep apnea, renal disease and other cardiovascular diseases (hyperlipidemia, stroke) and endocrine diseases. Since overweight is closely associated with hypertension, BMI should be measured during the physical examination.
Once the presence of hypertension is confirmed, blood pressure should be measured in both upper and lower extremities (note aortic constriction if lower extremity blood pressure is lower than upper extremity or if the femoral artery pulses are very weak). Most children with hypertension have a normal physical examination except for elevated blood pressure.
Most children with secondary hypertension have renal or renal vascular disease as the etiology, so laboratory screening tests should be performed. Plasma renin activity is a common screening test for salt corticosteroid-associated disease, and PRA is often low or undetectable and often accompanied by hypokalemia. PRA levels are elevated in children with renal artery stenosis, but 15% of children with transarterial angiography suggestive of renal artery stenosis have normal PRA levels.
Stenosis of one or both renal arteries can lead to the development of hypertension. The possibility of renal vascular hypertension should be noted in children with previous umbilical artery cannulation or neurofibromatosis. In children, recommended investigations include standard renal artery Doppler ultrasound, and renogram. Angiography is the gold standard, but invasive arterial puncture is only indicated in older children. mRA is increasingly used in the evaluation of renal vascular disease in children. it is best for detecting lesions in the main and proximal branches of the renal artery, but requires a period of body positioning and is more difficult to use in pediatric patients. Spiral CT can also be used in children.
Evaluation of target organ damage
If blood pressure is found to be higher than normal, the cause should be further defined, secondary factors should be excluded, and target organs including the heart, blood vessels, kidneys, brain, and retina should be evaluated.
1. Heart: Left ventricular hypertrophy is most common in children and adolescents with hypertension, with a prevalence of about 14%-42%. Left ventricular hypertrophy is an independent risk factor for cardiovascular events in adults. No relevant studies have been performed in children and adolescents, but the presence of left ventricular hypertrophy is an indication for pharmacological treatment of hypertension. Echocardiography is the method of choice to assess left ventricular hypertrophy. Left ventricular hypertrophy in children is defined as the 95th percentile value.
2. Vascular: Early changes in the vessel wall are intimal thickening, which can progress to atherosclerosis. Intimal thickening of arteries in children with familial hypercholesterolemia. Intima-media thickening is also associated with overweight and obesity, regardless of hypertension. Arterial stiffness is increased in children with hypertension.
3. Kidney: Hypertensive renal damage is manifested by reduced renal function and decreased glomerular filtration rate. The glomerular filtration rate is calculated by the Schwartz Formula, which is based on age, height, and serum creatinine, with an age-dependent coefficient (0.33 for preterm infants, 0.45 for full-term infants, 0.55 for children aged 2-12 years, 0.55 for girls aged 13-18 years, and 0.70 for boys aged 13-18 years). Transient elevations in serum creatinine that occur early in the course of angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors do not indicate deterioration in renal function. In addition, proteinuria is a marker of glomerular injury, suggesting abnormal glomerular filtration barrier, and may be an indication for antihypertensive therapy.
4. Brain: Epilepsy, stroke, and visual impairment are serious complications of hypertension in children and adolescents that have received insufficient clinical attention and can be effectively avoided by early diagnosis and treatment. In addition to neurological and ophthalmological evaluation, EEG, CT, MR, etc. should be performed in acute patients to exclude intracranial hemorrhage, inactive infarction, and cerebral white matter lesions.
5. Fundus: Small arterial lesions caused by hypertension in children and adolescents can occur at an early stage. To date, retinopathy due to hypertension in children has been less studied. Studies have shown that 51% of patients have retinal abnormalities, with a diastolic blood pressure increase of 10 mm Hg and retinal artery narrowing of 1.43-2.08 mm.
6. Genetics: Hypertension is a polygenic genetic disorder, and all known genes are associated with abnormal renal sodium transport, increased volume, and decreased renin. Routine genetic screening is not useful in children and adolescents.
Third, the treatment of primary hypertension
1.Primary hypertension
(1) Non-pharmacological treatment
Lifestyle is closely related to blood pressure, and control of body mass index is the most basic treatment for obesity-related hypertension. Regular physical activity and limiting sedentary time can improve the effect of controlling body mass. Dietary modifications should be made in children with pre-hypertension and hypertension. Appropriate dietary modifications include reducing the intake of sugary drinks and high-energy snacks; increasing the intake of fresh fruits, vegetables, fiber and non-saturated fatty acids and reducing salt intake; and recommending a regular diet that includes a healthy breakfast. Analysis of randomized studies found that salt intake in infancy can affect blood pressure in adolescence. In summary, a healthy lifestyle for all children and adolescents includes regular physical activity, a diet rich in fresh fruits and vegetables, fiber, a low-fat diet, limited salt intake, and adequate sleep time and quality sleep. Evidence suggests that life factors during infancy determine future cardiovascular disease risk, and early prevention is more important, such as discouraging maternal smoking, at least during breastfeeding; reducing salt intake while breastfeeding helps with blood pressure control.
(2) Medication
Children with hypertension should be identified as an indication before starting pharmacotherapy; monotherapy should be started when indicated; the goal of treatment is to reduce blood pressure to below the 95th percentile in the absence of other comorbidities and to below the 90th percentile in the presence of other comorbidities; severe symptomatic hypertension should be treated with intravenous antihypertensive drugs.
The long-term prognosis of untreated hypertension in children is unclear, and no studies have been reported on the effects of long-term antihypertensive medications on growth and development, so it is important to clarify the indications before starting drug therapy. The indications for antihypertensive drug therapy in children include symptomatic hypertension, secondary hypertension, hypertension with target organ damage, type 1 and type 2 diabetes mellitus with hypertension, and unsatisfactory antihypertensive effect of non-pharmacological treatment. Other indications depend on the clinical situation, for example, because the presence of multiple cardiovascular risk factors can increase the risk of cardiovascular disease in an exponential rather than a simple additive manner, antihypertensive drug therapy should be considered in children with hypertension who are also hyperlipidemic.
To date, no antihypertensive drug has been actually approved for the treatment of hypertension in children and adolescents, and there are many legal issues involved. Diuretics and β-blockers, recommended as the treatment of choice in previous reports, have many years of experience in the safety and efficacy of pediatric hypertension treatment and are suitable for pediatric use. In addition some newer drugs such as ACEI, ARB and CCB have also been found to have high safety and efficacy in clinical trials. In some special cases, specific types of antihypertensive drugs should be used, such as ACEI class or angiotensin receptor antagonists in children with diabetes and proteinuria, and angiotensin receptors and calcium channel blockers in children with migraine. All antihypertensive medications should be started at the lowest recommended dose and gradually increased until blood pressure is satisfactorily controlled. After the highest recommended dose is reached, another type of medication should be added. Care should be taken to consider the complementary effects of drugs when combining drugs, such as ACEI with diuretics, vasodilators with diuretics or β-blockers.
In children with essential hypertension without comorbidities and without target organ damage, the goal of blood pressure control is to reduce blood pressure to below the 95th percentile of blood pressure in children of the same sex, age, and height. However, in children with renal disease, diabetes mellitus, or hypertensive target organ damage, the blood pressure control goal is to reduce blood pressure to below the 90th percentile for children of the same sex, age, and height. Severe symptomatic hypertension at blood pressure levels above the 99th percentile can occur in children, often with renal disease, and requires urgent treatment. Hypertensive crisis in children is often accompanied by symptoms of hypertensive encephalopathy, which can lead to convulsions. Hypertensive crisis should be treated with emergency intravenous antihypertensive medication, with the goal of lowering blood pressure by about 25% within 8 hours of presentation and to normalize it over the next 24 to 48 hours.
2.Secondary hypertension
(1) Etiological treatment
After the etiology is clearly defined, treatment of the etiology should be considered. Depending on the type of disease, special medication, interventional therapy (e.g. renal artery stenosis, aortic constriction) or surgical treatment (e.g. adrenal tumor, malformed kidney) should be used to treat the primary cause. Medications are sometimes needed to control hypertension before etiologic treatment.
(2) Drug treatment
The prevention and treatment of hypertension in children and adolescents is an important issue that requires the participation of the whole society, relevant specialists, hypertensive physicians, pediatricians, other health care workers, schools, parents, etc. There is still a lack of evidence in the diagnosis and treatment of hypertension in children and adolescents, which needs to be explored in future work.