Vitamin D and cardiovascular system

Vitamin D and cardiovascular system: a deep analysis of relationships, mechanisms, clinical manifestations and prospects

Section 1: Biochemistry and metabolism of vitamin D

1. Vitamin D forms: Vitamin D is not a single compound, but is a group of secosteroids, of which vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol) are most important for humans. Vitamin D2 is synthesized by plants and mushrooms under the influence of ultraviolet (UV) radiation from ergosterol, while vitamin D3 is synthesized in the human skin of 7-dehydrocholesterol under the influence of UV radiation. The food sources of vitamin D2 are enriched products, mushrooms and some plants, and vitamin D3 is oily fish (salmon, mackerel, sardines), egg yolk and cod liver. Both vitamins are biologically inert and require further activation in the body.

2. Synthesis and sources of vitamin D: The synthesis of vitamin D3 in the skin is the main source of vitamin D for most people. The effectiveness of the synthesis depends on many factors, including geographical breadth, time of year, time of day, skin pigmentation, use of sunscreen and age. The higher the geographical latitude, the less UV radiation reaches the surface of the Earth, especially in the winter months, which reduces the synthesis of vitamin D. Dark people have a higher level of melanin, which absorbs uf-in radiation, reducing the synthesis of vitamin D. With age, the skin ability synthesize vitamin D also decreases. The food sources of vitamin D, although important, are often insufficient to maintain the optimal level of vitamin D in the blood, especially in people with limited stay in the sun or risk factors for vitamin D.

3. Metabolism and activation of vitamin D: Vitamin D, obtained from food or synthesized in the skin, is subjected to two sequential hydroxylating for activation. The first hydroxylation occurs in the liver under the influence of the 25-hydroxylase enzyme (CYP2R1), forming a 25-hydroxyvitamin D [25(OH)D]also known as calciol. 25 (OH) D is the main circulating form of vitamin D and is used to assess the status of vitamin D in the body. The second hydroxylation occurs in the kidneys under the action of the 1-alpha-hydroxylase enzyme (CYP27B1), forming 1.25-dihydroxyvitaminit [1,25(OH)2D]also known as calcitriol. Calcitriol is a biologically active form of vitamin D and is associated with the vitamin D (VDR) receptor in various body tissues, having its biological effects.

4. Regulation of vitamin D metabolism: Vitamin D metabolism is strictly regulated by various factors, including the level of parathyroid hormone (PTH), calcium and phosphate in the blood. The low level of blood calcium stimulates the secretion of PTG, which increases the activity of 1-alpha-hydroxylase in the kidneys, increasing the level of calcitriol. Calcitriol, in turn, increases calcium absorption in the intestines, mobilization of bone calcium and reabsorption of calcium in the kidneys, increasing the level of calcium in the blood. The high level of calcium and phosphate in the blood suppresses the activity of 1-alpha-hydroxylase and stimulates the activity of 24-hydroxylase (CYP24A1), which inactivates calcitriol, turning it into 24.25 (OH) 2D. This complex regulation system ensures the maintenance of the optimal level of calcium and vitamin D in the body.

5. Vitamin D (VDR) receptor: VDR is a member of a family of nuclear receptors that regulate the expression of genes in response to liganda binding. VDR is present in almost all tissues of the body, including the heart, vessels, kidneys, bones, intestines and immune cells. After binding with calcitriol, VDR forms a heterodimer with a retinoid X-receptor (RXR) and is associated with elements of response to vitamin D (VDRE) in promotional areas of target genes, regulating their transcription. VDR plays a key role in the regulation of calcium homeostasis, bone metabolism, immune function, proliferation and differentiation of cells, as well as in the regulation of blood pressure and the function of the cardiovascular system.

Section 2: The effect of vitamin D on the cardiovascular system

1. Epidemiological data: Numerous epidemiological studies have shown the relationship between vitamin D deficiency and an increased risk of developing cardiovascular diseases (SVD), including arterial hypertension, coronary heart disease (CPS), heart failure, stroke and sudden heart death. The meta-analyzes of these studies confirmed that the low level 25 (OH) D in the blood is associated with an increased risk of development of the SVD and mortality from the SVD. However, it should be noted that epidemiological studies cannot prove a causal relationship, and the results of some studies were contradictory.

2. Arterial hypertension: Vitamin D deficiency is associated with an increased risk of developing arterial hypertension. Vitamin D plays a role in the regulation of blood pressure (blood pressure) through several mechanisms, including the suppression of the renin-angiotensin-aldosterone system (RAAS), regulation of endothelial function, reducing inflammation and oxidative stress, as well as regulation of the level of calcium in the cells of the smooth muscles of blood vessels. Studies have shown that the addition of vitamin D can reduce systolic and diastolic blood pressure in patients with arterial hypertension and vitamin D. deficiency.

3. Corny heart (coronary heart disease): Vitamin D deficiency is associated with an increased risk of IBS, including angina pectoris, myocardial infarction and sudden heart death. Vitamin D can have a protective effect on the heart and blood vessels through several mechanisms, including improving the function of endothelium, reducing inflammation and oxidative stress, inhibiting the aggregation of platelets and proliferation of smooth muscle blood vessel cells, as well as regulation of calcium levels in myocardial cells. Studies have shown that the addition of vitamin D can reduce the risk of IBS and mortality from coronary heart disease in patients with vitamin D.

4. Heart failure: Vitamin D deficiency is associated with an increased risk of development of heart failure and a deterioration in its forecast. Vitamin D can have a positive effect on the myocardial function through several mechanisms, including improving myocardial contractility, a decrease in inflammation and oxidative stress, regulation of calcium levels in myocardial cells and improving the energy metabolism of cardiomyocytes. Studies have shown that the addition of vitamin D can improve the function of the left ventricle and reduce mortality in patients with heart failure and deficiency of vitamin D.

5. Stroke: Some studies have shown the relationship between vitamin D deficiency and an increased risk of stroke, especially ischemic stroke. Vitamin D can have a protective effect on the brain through several mechanisms, including improving the function of endothelium, reducing inflammation and oxidative stress, inhibiting platelet aggregation and regulation of calcium levels in neuron cells. However, the results of studies on the influence of vitamin D on the risk of stroke were contradictory, and additional studies are needed to confirm this connection.

6. Atherosclerosis: Vitamin D deficiency can contribute to the development of atherosclerosis – the main pathological process underlying the majority of the SVD. Vitamin D can have an anti -anaterosclerotic effect through several mechanisms, including a decrease in inflammation and oxidative stress, inhibiting the adhesion of monocytes to endothelium, a decrease in the proliferation of smooth muscle cells of blood vessels and the regulation of lipid metabolism. Studies have shown that vitamin D deficiency can contribute to the progression of atherosclerosis, and the addition of vitamin D can slow down this process.

7. Vitamin D exposure mechanisms on the cardiovascular system: Vitamin D affects the cardiovascular system through several mechanisms, including:

   • Regulation of renin-angiotensin-aldosterone system (RAAS): Vitamin D inhibits the expression of the renin gene in the kidneys, reducing the activity of RAS, which leads to a decrease in blood pressure and a decrease in the risk of heart failure.
   • Endotothelial function regulation: Vitamin D improves the function of the endothelium, increasing nitrogen oxide products (NO), which is a powerful vasodilator and antiplatelet.
   • Reducing inflammation and oxidative stress: Vitamin D has anti -inflammatory and antioxidant properties, reducing the level of inflammatory cytokines and oxidative stress markers, which play an important role in the development of SVD.
   • Regulation of calcium levels in the cells of smooth muscles of blood vessels and cardiomyocytes: Vitamin D regulates the level of calcium in the cells of the smooth muscles of blood vessels, reducing their contractility and vasoconstriction. In cardiomyocytes, vitamin D regulates the level of calcium, improving myocardial contractility.
   • Inhibition of proliferation of smooth muscle cells of blood vessels: Vitamin D inhibits the proliferation of smooth muscle cells of blood vessels, preventing the formation of atherosclerotic plaques.
   • Inhibition of platelet aggregation: Vitamin D inhibits platelet aggregation, reducing the risk of thrombosis and development of coronary heart disease and stroke.

Section 3: Clinical manifestations of vitamin D deficiency and its connection with cardiovascular diseases

1. Symptoms of vitamin D: Vitamin D deficiency is often asymptomatic, especially in the early stages. However, a prolonged and pronounced deficiency of vitamin D can lead to various symptoms, including:

   • Fatigue and weakness: Vitamin D deficiency can cause fatigue, weakness and energy reduction.
   • Bone pain and muscles: Vitamin D deficiency can lead to pain in bones and muscles, especially in the legs, back and ribs.
   • Muscle weakness: Vitamin D deficiency can cause muscle weakness and increased risk of falls.
   • Frequent infections: Vitamin D deficiency can weaken the immune system and increase susceptibility to infections.
   • Depression: Vitamin D deficiency is associated with an increased risk of depression and other mental disorders.
   • Increased blood pressure: Vitamin D deficiency can help increase blood pressure.
   • Joint pain: Vitamin D deficiency can aggravate joint pain in arthritis.

2. Risk factors for vitamin D: There are various factors that can increase the risk of vitamin D deficiency, including:

   • Geographical latitude: People living in high latitudes have an increased risk of vitamin D deficiency due to lack of sunlight in the winter months.
   • Pigmentation leather: Burning people have an increased risk of vitamin D deficiency due to a higher level of melanin, which absorbs UV-in radiation.
   • Age: With age, the ability of the skin to synthesize vitamin D decreases.
   • Obesity: Obesity is associated with a lower level of vitamin D in the blood, since vitamin D accumulates in adipose tissue and becomes less accessible to circulation.
   • Liver and kidney diseases: Diseases of the liver and kidneys can disrupt metabolism and activation of vitamin D.
   • Some drugs: Some drugs, such as glucocorticoids, antifungal drugs and anticonvulsants, can reduce the level of vitamin D in the blood.
   • Limited Sun stay: People who spend little time in the sun or use sunscreen, have an increased risk of vitamin D. deficiency.
   • Insufficient consumption of vitamin D with food: People who do not use enough products rich in vitamin D have an increased risk of vitamin D. deficiency.
   • Malibsorption: Diseases associated with impaired absorption of nutrients in the intestine, such as Crohn’s disease and celiac disease, can lead to vitamin D.

3. The relationship of vitamin D deficiency to arterial hypertension: Vitamin D deficiency is an independent risk factor for the development of arterial hypertension. Studies have shown that people with a low level of vitamin D in the blood have higher blood pressure and increased risk of arterial hypertension. The addition of vitamin D can reduce blood pressure in patients with arterial hypertension and vitamin D deficiency. The mechanisms through which vitamin D deficiency contributes to the development of arterial hypertension, include violation of the regulation of RAAS, impaired endothelium, increased inflammation and oxidative stress, as well as impaired regulation of calcium levels in smooth muscles cells vessels.

4. The relationship of vitamin D deficiency with coronary heart disease (coronary artery disease): Vitamin D deficiency is an independent risk factor for the development of coronary heart disease. Studies have shown that people with a low level of vitamin D in the blood have an increased risk of the development of angina pectoris, myocardial infarction and sudden heart death. The addition of vitamin D can reduce the risk of IBS and mortality from coronary heart disease in patients with vitamin D deficiency. The mechanisms through which vitamin D deficiency contributes to the development of coronary heart disease, includes impaired endothelium function, increased inflammation and oxidative stress, inhibiting the aggregation of platelets and spraying smooth muscle cells of vascular Calcium in myocardial cells.

5. The relationship of vitamin D deficiency to heart failure: Vitamin D deficiency is an independent risk factor for the development of heart failure and its worsening forecast. Studies have shown that people with a low level of vitamin D in the blood have an increased risk of heart failure and the worst prognosis of the disease. Adding vitamin D can improve the function of the left ventricle and reduce mortality in patients with heart failure and deficiency of vitamin D. The mechanisms through which vitamin D deficiency contributes to the development of heart failure, include impaired myocardial contractility, increased inflammation and oxidative stress, impaired regulation of calcium in myocardial cells and violation of energy metabolism cardiomyocytes.

6. The relationship of vitamin D deficiency to stroke: Some studies have shown the relationship between vitamin D deficiency and an increased risk of stroke, especially ischemic stroke. The mechanisms through which vitamin D deficiency can contribute to the development of stroke, include impaired endothelium function, increased inflammation and oxidative stress, inhibiting platelet aggregation and regulation of calcium levels in neurons cells. However, the results of studies on the influence of vitamin D on the risk of stroke were contradictory, and additional studies are needed to confirm this connection.

Section 4: Diagnostics and treatment of vitamin D deficiency in patients with cardiovascular diseases

1. Diagnosis of vitamin D: Diagnosis of vitamin D deficiency is based on measuring level 25 (OH) D in the blood. Level 25 (OH) d <20 ng/ml (50 nmol/l) is considered a deficiency of vitamin D, level 20-29 ng/ml (50-74 nmol/l) is considered the insufficiency of vitamin D, and the level of ≥ 30 ng/ml (75 nmol/l) is considered a sufficient level of vitamin D. It is recommended to determine the level of 25 (OH) D to identify and correct the deficiency of the deficiency Vitamin D.

2. Indications for determining the level of vitamin D in patients with SVD: Determination of vitamin D levels is recommended in patients with SVDs with risk factors for vitamin D deficiency, such as:

   • Arterial hypertension
   • Coronary heart disease (IBS)
   • Heart failure
   • Diabetes
   • Obesity
   • Chronic kidney disease
   • Liver diseases
   • Osteoporosis
   • Elderly age
   • Limited Sun stay
   • Dark skin

3. Treatment of vitamin D deficiency: Treatment of vitamin D deficiency includes intake of vitamin D drugs, such as vitamin D2 (ergocalciferol) or vitamin D3 (cholecalciferol). Vitamin D3 is usually preferable, since it more effectively increases the level of 25 (OH) D in the blood. The dose of vitamin D depends on the degree of deficiency of vitamin D, age, weight and concomitant diseases of the patient.

4. Recommendations for the dosage of vitamin D: General recommendations for the dosage of vitamin D for the treatment of vitamin D deficiency:

   • Vitamin D (OH) D <20 ng/ml): 5000-7000 IU Vitamin D3 per day or 50,000 IU vitamin D3 per week for 8-12 weeks, followed by a transition to a maintenance dose of 1000-2000 IU per day.
   • Vitamin D (25 (OH) D 20-29 ng/ml): 1000-2000 IU Vitamin D3 per day.
   • The supporting dose of vitamin D: 1000-2000 IU Vitamin D3 per day.

5. Vitamin D level monitoring: During the treatment of vitamin D deficiency, it is recommended to monitor level 25 (OH) D in the blood every 3-6 months to assess the effectiveness of treatment and correction of the dose of vitamin D.

6. Precautions when taking vitamin D: When taking vitamin D, it is necessary to observe precautions, such as:

   • Consultation with a doctor: Before taking vitamin D, you need to consult a doctor, especially if you have any diseases or you take other medicines.
   • Avoid overdose of vitamin D: An overdose of vitamin D can lead to hypercalcemia (an increased level of calcium in the blood), which can cause nausea, vomiting, weakness, pain in the bones and muscles, as well as damage to the kidneys.
   • Interaction with other drugs: Vitamin D can interact with some drugs such as digoxin, thiazide diuretics and antacids containing aluminum.

7. The role of vitamin K2 in combination with vitamin D: Vitamin K2 plays an important role in calcium metabolism and can improve the effectiveness of vitamin D. Vitamin K2 helps to direct calcium from the blood to the bone, preventing its deposition in soft tissues, such as arteries. Some studies have shown that the combination of vitamin D and vitamin K2 can improve bone health and cardiovascular system.

8. Alternative methods for increasing vitamin D level: In addition to taking vitamin D preparations, there are other ways to increase vitamin D levels, such as:

   • Sun stay: Regular stay in the sun (15-20 minutes a day in the middle of the day) can contribute to the synthesis of vitamin D in the skin.
   • The use of products rich in vitamin D: The use of products rich in vitamin D, such as fatty fish (salmon, mackerel, sardines), egg yolk and cod liver, can help increase the level of vitamin D in the blood.
   • The use of vitamin D products: The use of products enriched with vitamin D, such as milk, juice and breakfast flakes, can help increase the level of vitamin D in the blood.

Section 5: Clinical studies and prospects for the use of vitamin D in cardiology

1. Clinical studies of the effect of vitamin D on arterial hypertension: Clinical studies have shown that the addition of vitamin D can reduce systolic and diastolic blood pressure in patients with arterial hypertension and vitamin D. The metaminas of these studies confirmed that the addition of vitamin D can provide a moderate but statistically significant decrease in blood pressure. However, additional studies are needed to determine the optimal dose of vitamin D and detect patients who may be most beneficial from adding vitamin D.

2. Clinical studies of vitamin D effect on coronary heart disease (coronary artery disease): Clinical studies have shown that the addition of vitamin D can reduce the risk of IBS and mortality from coronary heart disease in patients with vitamin D deficiency. However, the results of these studies were contradictory, and some studies did not show the significant impact of vitamin D on the risk of coronary heart disease. Additional large -scale randomized controlled studies are needed to confirm this connection and determine the optimal strategy for using vitamin D for the prevention and treatment of coronary heart disease.

3. Clinical studies of the effect of vitamin D on heart failure: Clinical studies have shown that the addition of vitamin D can improve the function of the left ventricle and reduce mortality in patients with heart failure and deficiency of vitamin D. However, the results of these studies were contradictory, and some studies did not show significant effects of vitamin D on the function of the heart and mortality. Additional large -scale randomized controlled studies are needed to confirm this connection and determine the optimal strategy for using vitamin D for the treatment of heart failure.

4. Clinical studies of vitamin D on a stroke: The results of studies on the influence of vitamin D on the risk of stroke were contradictory. Some studies have shown the relationship between vitamin D deficiency and an increased risk of stroke, especially ischemic stroke, while other studies did not show this connection. Additional large -scale randomized controlled studies are needed to determine the effect of vitamin D in the risk of stroke and detect patients who may be most beneficial from adding vitamin D for stroke prevention.

5. Prospects for the use of vitamin D in cardiology: Vitamin D is a promising therapeutic agent for the prevention and treatment of SVD. However, additional large -scale randomized controlled studies are needed to confirm its effectiveness and determine the optimal application strategy. In the future, perhaps vitamin D will be used as an addition to the standard CVD therapy to improve the prognosis and quality of life of patients.

6. Studies of the effect of vitamin D on the endothelial function: Many studies have shown that vitamin D plays an important role in maintaining and improving the endothelial function, which is a key factor in the health of the cardiovascular system. Vitamin D helps the production of nitrogen oxide (No), a powerful vasodilator that helps expand blood vessels and improves blood flow. In addition, vitamin D has anti -inflammatory properties that help reduce inflammation in endothelial cells and protect them from damage. Improving the endothelial function with vitamin D can reduce the risk of arterial hypertension, atherosclerosis and other cardiovascular diseases.

7. The role of vitamin D in the regulation of inflammation and the immune system at the SVD: Chronic inflammation plays an important role in the development and progression of many cardiovascular diseases, such as atherosclerosis and heart failure. Vitamin D has immunomodulating and anti-inflammatory properties that can help reduce inflammation in the cardiovascular system. Vitamin D regulates the production of inflammatory cytokines and activates immune cells, which helps to reduce the inflammatory process and protect the cardiovascular system from damage. Studies have shown that vitamin D deficiency can be associated with an increased level of inflammatory markers and a worsening prognosis in patients with SVD.

8. The influence of vitamin D on lipid metabolism and the development of atherosclerosis: Vitamin D can affect lipid metabolism and the development of atherosclerosis. Some studies have shown that vitamin D deficiency can be associated with an increased level of LDL cholesterol (poor cholesterol) and triglycerides, which is a risk factor for atherosclerosis. Vitamin D can also affect the function of macrophages and other immune cells that are involved in the formation of atherosclerotic plaques. Adding vitamin D can help reduce LDL cholesterol, improve the function of immune cells and slow down the progression of atherosclerosis.

9. Genetic factors and interaction of vitamin D with the cardiovascular system: Genetic factors can play an important role in determining the sensitivity to vitamin D and its influence on the cardiovascular system. Polymorphisms of genes encoding vitamin D (VDR) receptor and enzymes involved in vitamin D metabolism can affect the level of vitamin D in the blood and its effects on the heart and blood vessels. Studies have shown that some genetic variants of VDR can be associated with an increased risk of developing arterial hypertension, coronary heart disease and other cardiovascular diseases. Understanding the genetic factors affecting the interaction of vitamin D with the cardiovascular system can help in the development of personalized strategies for the prevention and treatment of SVD using vitamin D.

10. A personalized approach to the use of vitamin D in patients with SVD: The personalized approach to the use of vitamin D in patients with SVD involves taking into account the individual characteristics of the patient, such as age, gender, race, genetic factors, concomitant diseases and risk factors for vitamin D. Determination of vitamin D in the blood is an important step in the personalized approach. Based on the level of vitamin D and the individual characteristics of the patient, the doctor can determine the optimal dose of vitamin D and the reception mode. Monitoring of vitamin D levels and clinical indicators allows you to evaluate the effectiveness of treatment and timely adjust the dose of vitamin D. A personalized approach to the use of vitamin D can improve the effectiveness of the treatment of SVD and reduce the risk of side effects.