Overview of Hypertension
Hypertension with elevated homocysteine has no obvious symptoms in the early stages, but poor blood pressure control can lead to dizziness, headache, and other manifestations of elevated plasma homocysteine levels, low folate levels, and the MTHFR C677TT genotype, including general therapy, drug therapy.
Definition
Type H hypertension is hypertension with elevated homocysteine.
Hypertension is a cardiovascular syndrome characterized by elevated arterial pressure in the body circulation, and homocysteine (Hcy) is an amino acid produced in the liver, muscle, and some other tissues.
Studies have shown that elevated Hcy can greatly stimulate the growth of arterial smooth muscle cells, disrupting the normal function of vascular smooth muscle and leading to an increased risk of cardiovascular morbidity.
The concept of H-type hypertension has been proposed because patients with hypertension accompanied by elevated homocysteine have a greatly increased risk of stroke [1].
Classification
Type H hypertension is graded like hypertension as an in-office systolic blood pressure ≥140 mm Hg and/or a diastolic blood pressure ≥90 mm Hg without the use of antihypertensive medications.Hypertension is further categorized into grades 1 to 3 based on the level of elevated blood pressure.
H-type hypertension grade 1
Systolic blood pressure is 140 to 159 mmHg and/or diastolic blood pressure is 90 to 99 mmHg.
H-type hypertension grade 2
Systolic blood pressure is 160 to 179 mmHg and/or diastolic blood pressure is 100 to 109 mmHg.
H-type hypertension grade 3
Systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg.
Simple systolic H-type hypertension
Systolic blood pressure ≥ 140 mmHg and diastolic blood pressure < 90 mmHg.
Morbidity
The prevalence of hypertension in China is 29.6%, and is higher in men than in women [1].
H-type hypertension accounts for 80.3% of all hypertensive patients in China [2].
Etiology
Pathogenesis
Abnormalities in the metabolic pathway of homocysteine in the body may lead to the accumulation of homocysteine in the body, and elevated homocysteine may increase the risk of cardiovascular and cerebrovascular diseases [3].
Homocysteine metabolism is mainly affected by the following factors.
Nutrition-related factors
Low levels of folic acid, vitamin B12 and vitamin B6 cause elevated homocysteine levels in the body and increase the risk of H-type hypertension [4].
Genetic Factors
MTHFR C677T gene polymorphism is strongly associated with H-type hypertension.
MTHFR C677T gene mutation is an important risk factor for increasing the incidence of H-type hypertension.
Behavioral lifestyle factors
Excessive intake of methionine in the daily diet and remethylation of methionine to produce homocysteine cause hyperhomocysteinemia.
Poor behavioral habits such as smoking, heavy alcohol consumption, and excessive coffee intake impede intestinal absorption of vitamins, causing homocysteine levels to rise.
Conditions such as overweight and obesity can also increase homocysteine levels.
Disease-related factors
Renal insufficiency, which prevents extra-renal metabolism of homocysteine, can cause homocysteine levels to rise.
Hypothyroidism can also cause elevated homocysteine levels, leading to hyperhomocysteinemia.
Pathogenesis
Elevated homocysteine causes insulin resistance, contributing to the development of hypertension.
Elevated homocysteine affects the function of endothelial cells. On the one hand, oxidative stress occurs, and homocysteine affects the activity of nitric oxide synthase, whose diminished activity inhibits the rate of enzyme synthesis, which leads to vascular endothelial cell damage; on the other hand, endoplasmic reticulum stress is a major factor leading to endothelial cell dysfunction.
Elevated homocysteine causes proliferation of vascular smooth muscle cells. Hyperplastic vascular smooth muscle cells thicken the wall, increase intravascular resistance, and increase blood pressure; elevated homocysteine also causes calcium ions to accumulate in the smooth muscle cells, and increases blood pressure.
Elevated homocysteine causes a significant increase in arterial vascular stiffness, leading to an increase in arterial vascular systolic pressure and an increase in blood pressure.
Symptoms
Main Symptoms
Most have a slow onset and initially lack specific clinical manifestations.
Poor control of blood pressure may result in dizziness, headache and other common symptoms of hypertension, and typical hypertensive headache can disappear after blood pressure drops.
With the development of the disease, or the occurrence of cardiac, cerebral, renal and other complications, may appear related target organ damage symptoms, such as heart fatigue, palpitations, eyelid swelling, foamy urine and other clinical manifestations.
Complications
H-type hypertension and cerebrovascular disease
Homocysteine is a new risk factor for cardiovascular and cerebrovascular diseases, and the incidence of H-type hypertension stroke will increase exponentially.
For every 5 μmol /L increase in homocysteine, the risk of stroke increases by 59%; for every 3 μmol /L decrease, the risk of stroke decreases by 24% [5].
A 10 μmol /L increase in homocysteine levels increases the risk of recurrent stroke by 30% [5].
H-type hypertension and cardiovascular disease
The incidence of cardiovascular disease is significantly higher in patients with type H hypertension than in patients with essential hypertension [6].
Increased levels of homocysteine damage endothelial cells, increasing endothelin levels in the body, increasing blood pressure, and becoming a risk factor for atherosclerosis and coronary heart disease.
H-Hypertension and Kidney Damage
Increased homocysteine levels can lead to disorders of lipid metabolism in the body and accelerate plaque calcification, leading to renal atherosclerosis and impaired renal function [7].
Consultation
Department of Medicine
Cardiovascular Medicine
When a physical examination reveals elevated homocysteine levels, abnormal blood pressure, or daily symptoms such as persistent elevation and abnormal fluctuation of blood pressure, unexplained headache, dizziness, etc., it is recommended to consult a doctor promptly.
Emergency Department
When the patient’s blood pressure rises sharply and symptoms such as headache, blurred vision, impaired consciousness, aphasia, hemiparesis, etc. are present, it is considered that there are complications related to hypertension, such as cerebral hemorrhage or cerebral infarction, etc., and timely consultation in the Emergency Department is required.
Preparation
Consultation: registration, preparation of information, common problems
Tips
Avoid stimulants (e.g., strong tea, coffee, cola) before the visit.
Avoid strenuous exercise before consultation.
If symptoms such as nausea, vomiting, severe headache, etc. occur, it is recommended to call the 120 emergency number for transportation to the hospital.
Preparation Checklist
Symptom list
Its need to pay attention to the time of occurrence of symptoms, special manifestations, etc.
What is the daily morning blood pressure and bedtime blood pressure for the last 14 days?
Have there been any drastic fluctuations in blood pressure recently compared to the past?
Have you had any headaches or dizziness recently? When do they occur? How is it relieved?
Any recent panic, chest tightness, shortness of breath? Is it related to physical activity?
Is there any foamy urine and how long has it lasted?
Any facial edema, lower extremity edema, and how long has it lasted?
Medical history list
How many years of history of hypertension? Do you take antihypertensive medication regularly? Do you monitor your blood pressure? How is the blood pressure control recently?
What was the previous blood pressure situation?
Any history of stroke, cardiovascular disease, diabetes, peripheral vascular disease, hyperlipidemia?
Any family history of hypertension?
Checklist
Test results from the last six months, which can be brought to the doctor’s office
Laboratory tests, e.g. homocysteine level measurement, blood biochemistry, blood routine, urinalysis, 24-hour urine protein quantification, etc.
Functional tests, such as cardiac ultrasound, 24-hour ambulatory blood pressure, electrocardiogram, etc.
Imaging tests, such as cranial CT, cranial MRI, etc.
Medication list
Medication in the past 3 months, such as medication or package, can be carried to the doctor
Antihypertensive drugs: e.g. nifedipine, amlodipine tablets, etc., enalapril tablets, valsartan, furosemide, etc.
Diagnosis
Diagnosis is based on
Medical history
May have a family history of H-type hypertension
Clinical manifestations
Symptoms
Clinical symptoms of H-type hypertension are consistent with hypertension.
Early symptoms are not obvious, and dizziness and headache may occur when blood pressure is poorly controlled.
With the development of the disease, or the occurrence of cardiac, cerebral, renal and other complications, there may be related target organ damage symptoms, such as cardiac fatigue, palpitations, eyelid swelling, foamy urine and other clinical manifestations.
Physical signs
Hypertension can be diagnosed if the systolic blood pressure is ≥140mmHg and/or the diastolic blood pressure is ≥90mmHg on three measurements taken on different days. Hypertension was also diagnosed in patients with a previous history of hypertension, who were on antihypertensive medication and whose blood pressure was normal though [8].
Cardiac auscultation is performed initially to know the heart size, presence of heart murmur, hypercardia, arrhythmia and other abnormalities, if there are positive signs can suggest that there are cardiovascular disease complications in this disease.
Abdominal auscultation can understand whether there are abdominal wall vascular murmurs, abdominal wall and renal artery abnormal pulsation, which can initially understand the renal morphology and renal vascular condition.
Observe the eyelids and bilateral lower limbs for edema.
Laboratory tests
Homocysteine level measurement
Hypertensive patients with blood homocysteine ≥ 10 μmol/L can be diagnosed with H-type hypertension.
Measurement of serum folate level
Patients with H-type hypertension are often low in folic acid and need to have their folic acid level measured.
Other biochemical indicators
Such as BNP or NT-ProBNP to understand the cardiac function; cystatin C, blood creatinine, urea nitrogen, etc. to understand the renal function.
Urine related tests
Urine analysis to know whether there is hematuria, proteinuria, tubular urine, positive suggests kidney disease; 24-hour urine protein quantification, can understand the proteinuria, 24-hour urine protein more than 3.5g suggests kidney damage.
Imaging
Cardiac ultrasound
When hypertension affects the heart, it leads to changes in heart structure and function, and the first to appear is left ventricular hypertrophy. Ultrasound can detect left ventricular hypertrophy at an early stage, as well as detecting valve damage at a later stage.
Ultrasound of carotid vessels
Can detect carotid atheromatous plaque formation.
Cranial CT
It can observe whether there is cerebral hemorrhage, cerebral infarction and other manifestations of stroke.
Other examinations
Fundus examination can determine whether hypertension is complicated by retinal damage.
Genetic analysis can clarify the genetic defect of hereditary hyperhomocysteinemia.
Diagnostic criteria and grading
Diagnostic Criteria
Diagnostic criteria for hypertension
The diagnostic criteria for in-office hypertension are generally three non-same-day measurements of systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg are required for the diagnosis of hypertension.
Hypertension is diagnosed when the patient has a history of hypertension, is using antihypertensive drugs, and has a normal blood pressure.
Diagnostic criteria for H-type hypertension
In addition to meeting the diagnostic criteria for hypertension, blood homocysteine ≥ 10 μmol/L is diagnostic of type H hypertension.
Classification of hypertension
Grade 1 hypertension, diastolic blood pressure between 90~99mmhg and/or systolic blood pressure between 140~159mmhg.
Grade 2 hypertension, diastolic blood pressure between 100~109mmhg and/or systolic blood pressure between 160~179mmhg.
Grade 3 hypertension with diastolic blood pressure ≥110 mmhg and/or systolic blood pressure ≥180 mmhg.
Differential Diagnosis
H-type hypertension is usually clearly diagnosed on the basis of blood pressure levels and homocysteine levels, without the need for a differential diagnosis.
In some cases, a differential diagnosis is required from transient elevation of blood pressure in the presence of specific conditions or secondary hypertension, as exemplified below.
Pheochromocytoma
All of them are characterized by elevated blood pressure. Pheochromocytoma usually presents with severe headache, palpitations, and excessive sweating, not accompanied by elevated homocysteine level and low folate phenomenon, which can be differentiated by imaging or pathological tissue examination.
White coat hypertension
As the name suggests, the patient’s blood pressure is elevated due to nervousness at the sight of a white coat, while his/her blood pressure is normal when measured at home, which can be identified by carrying a 24-hour ambulatory blood pressure monitor.
Treatment
Treatment principle: Reduce the incidence of other cardiovascular and cerebrovascular diseases through active treatment. Reduce or delay the damage to other target organs and reduce the disability and mortality of related events [9-10].
Treatment objective: to prevent the occurrence of hypertensive emergencies and crises.
General treatment
Changing dietary structure
Strictly control daily oil and salt intake, reduce daily cooking oil intake, eat less or no fatty meat and animal offal, and no more than 5g of salt per person per day.
Eat fresh vegetables and fruits daily. It is recommended to consume more foods with high folic acid content, such as green leafy vegetables and legumes.
In addition the preparation and cooking of food will cause the loss of folic acid, especially when boiling the loss is greater, on the basis of safe and hygienic cooking, to minimize the loss of folic acid in food.
Lifestyle Adjustment
Stop smoking and drinking.
Increase exercise appropriately, which is conducive to reducing body weight and improving insulin resistance.
Maintain a balanced mind and learn to release stress.
Medication
Antihypertensive treatment
Diuretics
Such as furosemide, spironolactone, etc.
Reduce blood volume through diuresis to lower blood pressure.
Attention to adverse reactions is low blood potassium, blood fat, blood sugar and other disorders, gout patients prohibited; renal insufficiency patients with caution spironolactone.
Calcium antagonist
Such as nifedipine, felodipine and so on.
By reducing peripheral vascular resistance and lowering blood pressure, can be used in patients with combined diabetes, coronary heart disease or peripheral vascular disease.
The main disadvantage is the occurrence of reflexive heart rate increase, facial flushing, edema and so on.
β-blockers
Such as metoprolol, propranolol and so on. Act by inhibiting myocardial contractility and slowing down the heart rate.
It is suitable for patients with different degrees of hypertension, especially those with fast heart rate.
Adverse effects are mainly bradycardia and chills in the limbs.
Angiotensin-converting enzyme preparations
Such as enalapril and fosinopril.
It has the effect of improving insulin resistance and reducing urinary protein, so it is especially suitable for hypertensive patients with diabetic nephropathy.
The main adverse effects are dry cough and angioneurotic edema.
Angiotensin receptor antagonist
Such as valsartan, irbesartan and so on.
The antihypertensive effect is slow, but long-lasting and smooth.
The object of action and adverse effects are the same as those of angiotensin-converting enzyme preparations.
Homocysteine-lowering therapy
Folic acid supplementation
You can take ordinary folic acid tablets to supplement folic acid, also recommended to use the combination of folic acid to lower blood pressure.
Vitamin B12, B6 supplementation
Methylcobalamin or hydroxocobalamin.
Prognosis
Cure
There is no self-healing without treatment.
Aggressive treatment helps to minimize strokes.
Aggressive treatment helps to slow the progression of damage to other target organs such as the heart and kidneys.
Patients with H-type hypertension can slow progression, delay the onset of complications, improve quality of life, and prolong life expectancy with long-term drug therapy.
Harmfulness
If not actively treated, it can cause complications such as cerebral hemorrhage, cerebral infarction, heart failure, angina pectoris, myocardial infarction, chronic renal insufficiency, retinopathy, aortic coarctation and so on, resulting in blurring of vision, hemiparesis, coma, which can be life-threatening.
Daily
Daily Management
Dietary management
Balanced nutrition, more vegetables and fruits.
Sodium intake must be strictly limited, with a recommended salt intake of less than 5g per person per day, and if available families can use a dosing spoon for cooking.
Low-fat diet, reduce animal fat (e.g. pork), can choose vegetable oil appropriately.
Increase the amount of protein foods, such as fish.
Increase folic acid-containing foods, such as fresh dairy products, soy products and green leafy vegetables, as appropriate.
Life management
Stop smoking and drinking.
Stick to exercise.
Maintain a good work routine, go to bed early and get up early, avoid staying up late and overworking.
Psychological management
Maintain a happy mood and avoid emotional anxiety and tension.
Follow-up
Monitor blood pressure regularly at home for a long period of time, observe and record the blood pressure control.
Regularly review homocysteine and adjust drug dosage.
Regularly review urine routine, folic acid, liver and kidney function, electrocardiogram, cardiac ultrasound, head CT, etc., to screen for the occurrence of hypertension complications.
Prevention
Pay attention to rest in life, appropriate physical exercise to enhance physical fitness.
Improve the diet structure, consume more vegetables and fruits, and have a low-salt and low-fat diet.
Adjust your mindset, avoid long-term stress and nervousness, and keep your mood happy.
Monitor blood pressure and homocysteine levels, and have regular medical checkups.