Atherosclerosis

Atherosclerosis . Important pathological process in which lipids are deposited in the intimate layers of the arteries.

Summary

[ disguise ]

• 1 Generalities
• 2 Epidemiology and frequency
• 3 Etiopathogenesis
  • 1 Theory of reaction against aggression
  • 2 Monoclonal theory
  • 3 Theory of focal clonal senescence
  • 4 Lysosomal theory
• 4 Etiological factors
  • 1 Hyperlipidemia
  • 2 Arterial hypertension
  • 3 Smoking
  • 4 Genetic factors
  • 5 Physical inactivity
  • 6 Obesity
  • 7 Diabetes mellitus
  • 8 Trace elements
  • 9 Enzymes
• 5 Pathological anatomy
  • 1 Early injuries
  • 2 Intermediate injuries
  • 3 Complicated injuries
  • 4 Location
• 6 Clinical picture
  • 1 Cardiac manifestations
  • 2 Neurological manifestations
  • 3 Renal manifestations
  • 4 Abdominal manifestations
  • 5 Peripheral manifestations
• 7 Diagnosis
  • 1 Chest X-ray
  • 2 Electrocardiogram
• 8 Treatment
  • 1 Prophylactic treatment
  • 2 Treatment of the disease
  • 3 Invasive procedures
• 9 Localized calcification or Mönckeberg sclerosis
• 10 Fonts

Generalities

Atherosclerosis results from the action of various factors, such as lipid metabolism , blood coagulation elements , cytokines, hemodynamics and risk factors. The lesion is characterized by an infiltration of immunocompetent cells , such as macrophages and T lymphocytes , intimal proliferation of the arterial wall, and lipid accumulation.

Epidemiology and frequency

The highest frequency is found in individuals over 50 years of age, however, other research has shown that the formation of the atherosclerotic lesion that is a precursor to atheroma (the fatty streak) can begin from infancy , which denies the concept. that this disease is a process of senile evolution. It occurs in both sexes, although more frequently in men; It is noted that women of reproductive age are protected by the action of estrogens , since the frequency increases in this sex during menopause .

No direct relationship between atherosclerosis and race has been established ; however, some studies indicate that Europeans and Anglo-Saxons are affected more frequently than Japanese, Indians and Africans, which seems to be more related to dietary and social habits. than with the racial factor.

Etiopathogenesis

There are several theories that try to explain the pathogenesis of atherosclerosis, among which are the following:

Theory of reaction against aggression

It is the most accepted and indicates that intimal endothelial cells are subjected to repeated injuries that cause a loss of the normal function of these cells, which act as a barrier to permeability.

By reducing functioning cells, the subendothelial tissue is exposed to high concentrations of plasma constituents, which triggers the adhesion of monocytes and platelets; Then the monocytes migrate into the intima to become macrophages, which together with platelet aggregation cause the formation of microthrombi and release of secretory products from platelets and macrophages, which stimulate the proliferation of smooth muscle cells and cause a matrix deposit. conjunctiva and lipid accumulation .

Monoclonal theory

This indicates that proliferative lesions of the intima are a consequence of the multiplication of individual smooth muscle cells .

Focal clonal senescence theory

This hypothesis states that the process of arteriosclerosis contributes to the intrinsic development of aging .

Lysosomal theory

It suggests that alterations in lysosome function aid atherogenesis by increasing lipid deposition in smooth muscle cells , which may be related to a relative deficit in cholesterol ester hydrolase activity in lysosomes .

Etiological factors

There are certain circumstances and habits that occur more frequently in individuals who develop atherosclerosis, compared to the general population; These are known as risk factors. Most people with atherosclerosis have one or more risk factors in addition to aging.

These factors are classified as reversible and irreversible. Among the first are hypercholesterolemia, high blood pressure and smoking , and the irreversible ones are age, sex and genetic factors.

Hyperlipidemia

Hypercholesterolemia and hypertriglyceridemia are important factors, since as age increases, cholesterol and triglyceride levels also rise .

For example, at birth, the cholesterol level is 1.5 mmol/L (60 mg/dl), at one month, the average is 3 mmol/L (120 mg/dl) and after one year it is 4.3 mmol/L (175 mg/dl). In the third decade there is another increase, and this continues until age 50 in men and until somewhat later in women.

The increase in cholesterol is associated with the elevation of low-density lipoproteins (LDL), and that of triglycerides, with very low-density lipoproteins (VLDL) and the remnants of their catabolism (intermediate-density lipoproteins).

HDL (high-density lipoprotein) carries 20% of total cholesterol and those with high HDL-cholesterol have a lower risk of suffering from ischemic heart disease. HDL levels are higher in women than in men.

There are factors that increase the level of HDL, such as: estrogen , regular active exercise and moderate alcohol consumption; Their levels, androgens and tobacco decrease .

Arterial hypertension

It affects men and women equally, and diastolic hypertension is the most important. The pressure changes caused by hemodynamic forces (forces generated by blood flow) determine a multiplication of the intimal [cells].

The areas most affected by atherosclerosis are those of arterial bifurcation, since variations in blood flow pressure occur there; In these areas, what is known as decreased lateral pressure occurs, which acts as an initial stimulus.

Atherosclerosis is rare in the pulmonary circulation, where very low blood pressures predominate; They only occur when there is a disease that causes increased lung pressure.

Smoking

When this risk factor is eliminated or reduced, the possibility of developing the disease also decreases and reaches the same risk as in non-smokers after having quit the habit for a year. It is noted that carbon monoxide , a component of cigarettes , produces hyperlipidemia.

Genetic factors

Premature atherosclerosis often appears to run in families; In some cases it is attributed to the inheritance of risk factors, but in others these are not identified, which is why the presence of genetic determinants of protective factors, such as HDL, and other non-lipid factors, such as apoprotein B and lipoprotein (a).

Physical inactivity

It has been observed that individuals with a more active life are less likely to suffer sudden death , and although the mechanism by which physical activity reduces the risk of atherosclerosis is not known, it is suggested that it increases HDL values.

Obesity

Its effect is more evident before the age of 50 and a close relationship has been identified between the type of obesity (abdominal) and ischemic heart disease; In addition, this type of obesity is associated with other risk factors, such as hypertriglyceridemia, hypercholesterolemia, hyperglycemia and HBP; A fundamental role of obesity in the age-related elevation of cholesterol and triglyceride levels is also noted.

Mellitus diabetes

Atherosclerosis is accelerated in diabetic patients by various factors: hyperglycemia, hyperlipidemia, lipoprotein abnormalities associated with diabetes , increased hypertension and hyperinsulinemia.

The lumen of the artery is lined by endothelial cells, which serve as a barrier between the substances circulating in the plasma and the cells of the arterial walls. The main function of these cells is to maintain a balance between coagulation and anticoagulation, which occurs continuously in the vascular walls; but in diabetes, endothelial cells are damaged by hyperglycemia, hyperlipidemia, and hypertension. It has recently been pointed out that immune complexes produce an alteration of the balance in favor of intravascular coagulation, platelets adhere and aggregate and form the clot, and cholesterol is deposited on the arterial walls.

Trace elements

A possible relationship is assessed between the deficiency of some trace elements ( manganese , chromium , zinc , cadmium ) and some qualities of water : hardness, reactivity due to the presence of cobalt , fluorine , with the development of atherosclerosis. These can influence lipid metabolism and blood pressure control.

Enzymes

Enzymes have been found that intervene in metabolic processes, such as the synthesis of cholesterol and its esters (cholesterol esterase, fatty acid transferase, etc.); enzymes related to the metabolism of triglycerides and phospholipids (lipoprotein lipase, phospholipase); enzymes that intervene in the metabolism of connective tissue (hyalurodinase, chondroitin-sulfatase), and basic enzymes that catalyze the metabolic processes inherent to any type of tissue (glucose-6-phosphate dehydrogenase).

Pathological anatomy

Atherosclerosis is a localized nodular form of arteriosclerosis, and lesions can be classified as early, intermediate, and complicated.

Early injuries

There are two types of lesions: initial and fatty stretch marks. The initial lesions are focal, small and non-obstructive, detectable chemically or with the microscope and it is observed that the endothelial cells contain pinocytotic vesicles loaded with lipids ; They are seen in children and are located in areas susceptible to atherosclerosis.

Fatty streaks can be seen with the naked eye on the endothelial surface of the aorta and coronary arteries , they are small and non-obstructive, and they increase during puberty in the aorta. These lesions may or may not progress depending on the hemodynamic forces and the levels of atherogenic lipoproteins; Initially, stretch marks contain two types of cells: foam cells, which consist of macrophages filled with lipids, mainly in the form of cholesterol, and T lymphocytes, especially CD8+ with some CD4+.

Intermediate injuries

They are made up of fibrous plaques and represent the most characteristic lesion of atherosclerosis; They appear first in the abdominal aorta , carotid and coronary arteries , and progressively increase with age.

complicated injuries

They consist of a calcified fibrous plaque in which there are variable degrees of necrosis, thrombosis and ulceration; As necrosis and accumulation of debris increase, the arterial wall progressively weakens and ruptures with the formation of aneurysms and hemorrhages , and if the plaque is mobilized, arterial emboli occur.

Location

The greatest involvement develops in the abdominal portion of the aorta and more in the lower extremities than in the upper extremities. It is also common in the coronary arteries and their main branches, a short distance from the coronary orifices, and in the cervical and cerebral arteries, whose distribution is patchy.

Clinical picture

There is no defined clinical picture, since the symptoms are the result of ischemia of the organ whose arteries have been affected.

Cardiac manifestations

Atherosclerosis of the coronary arteries causes myocardial infarction and angina pectoris . After a silent period, atherosclerosis can produce ectasia and develop an aneurysm with increased lumen caliber. This frequently occurs in the aorta and predisposes to rupture and dissection rather than stenosis.

Neurological manifestations

They are caused by the involvement of the arteries that supply the CNS and cause cerebral vascular accidents.

Kidney manifestations

It can cause stenosis of the renal artery and thus contribute to the pathogenesis of arterial hypertension and the manifestations of renal failure .

Abdominal manifestations

Occasional mesenteric ischemia produces intestinal infarction, causing abdominal pain crises.

Peripheral manifestations

Atherosclerosis of the branches of the aorta that supply the lower limbs (iliac, femoral, popliteal, etc.) causes intermittent pain in the calf, thigh and hip muscles, which is exacerbated during walking and forces the patient to stop suddenly. frequency (intermittent claudication); In the physical examination, weakness of the pulses and coldness of the affected limb with trophic changes of the skin, subcutaneous cellular tissue and muscles, and ulcerative lesions in the lower limbs are detected.

Diagnosis

The histological study is the only one that allows a certain diagnosis to be made, however there are some tests that can help discover the etiological factors, such as: glycemia, which reveals diabetes mellitus ; serology, to differentiate an atherosclerotic aneurysm from a syphilitic one; urea and creatinine, to determine if there is kidney damage, and the lipidogram, which is the most useful laboratory test, whose figures are the following:

• Cholesterol ..3.87 to 6.50 mmol/L
• Total lipids .4.5 to 10.0 g/L
• LDL cholesterol .1.30 to 4.90 mmol/L
• HDL cholesterol:

Male: less than 0.91 mmol/L Female: less than 1.16 mmol/L

• Triglycerides ..0.34 to 1.70 mmol/L
• ß-lipoproteins .3.6 to 6.4 g/L

The turbidity test will be altered.

Torax X ray

It reveals the presence of an aortic aneurysm and atheromatous plaques in the aortic arch. Through angiography, deformations of the vascular lumen are observed; myocardial perfusion defects demonstrable with imaging techniques using radioactive isotopes. Digital plethysmography with exercise, which shows atherosclerosis of the lower limbs.

Electrocardiogram

It shows the characteristic alterations of the T wave and the ST segment in the course of ischemic heart disease.

Despite the aforementioned, the detection of atherosclerosis is usually done when a clinical complication appears due to decreased blood flow in a vessel.

The most reliable indicator currently is ischemic heart disease, which is synonymous with coronary heart disease and atherosclerotic heart disease; stroke is a less reliable criterion.

Treatment

Prophylactic treatment

It is aimed at eliminating risk or etiological factors, and includes the following measures:

• Avoid obesity .
• Avoid a sedentary life.
• Eliminate the factors that determine constant tension.
• Reduce foods rich in cholesterol .
• Eliminate the habit of smoking.
• Control diabetes mellitus and high blood pressure .

Treatment of the disease

There is no specific medication, but treatment for hyperlipidemia is recommended:

• Fibric acid derivatives (decreases VLDL): clofibrate, 2g/d, and genfibrocil, 1.2g/d. and nicotinic acid (decreases VLDL and LDL): 2 to 4 g/d.
• Bile acid binding resins (promote steroid excretion and increase LDL elimination): cholestyramine, 12 to 16 g/d, and colestipol, 15 to 20 g/d.
• HMG-CoA reductase inhibitors (block cholesterol synthesis and increase receptor-mediated clearance of LDL): lovastatin, 10 to 80 mg/d; simvastatin, 10 to 40 mg/d, and provastatin, 10 to 40 mg/d.
• Probucol: its mechanism is unknown and it acts on LDL; dose: 1g/d.
• Estrogens : Premarin, 0.625 mg/d, and estradiol, 2 mg/d. Its mechanism is unknown.

Invasive procedures

• Portal-iliac bypass, with the purpose of interrupting the enterohepatic circulation of bile acids.
• LDL apheresis, plasmapheresis and portocaval shunt.

Currently, it is noted that there are several nutrients ( lipids , carbohydrates , ethanol ) that play a fundamental role in the diet of patients with atherosclerosis, in particular lecithin of plant origin and more recently the phospholipid polyene (phospholipids with linoleic acid). , known as essential phospholipid (EPL), as it modifies the metabolism of lipids and lipoproteins, which is why IV infusion of these products is suggested; The recommended dose is 4.5 to 30 g/d for EPL, and 18 g/d for lecithin.

Localized calcification or Mönckeberg sclerosis

This type of arteriosclerosis is common in the lower extremities and in the arteries of the genital tract in both sexes, which it affects equally. It is rare in people under 50 years of age. The process involves degeneration of smooth muscle cells followed by calcium deposition . On palpation the radial artery can be found as a rigid tube.

The diagnosis is made through X-rays , which demonstrate the presence of regular concentric calcifications in the transverse sections and the appearance of train rails in the longitudinal sections. Changes in the mean are isolated and do not produce stenosis of the lumen, so they have little effect on circulation. However, in the lower extremities medial calcification is frequently associated with atherosclerosis and causes arterial occlusion. These variations, which can also cause aortic valve disease, are common in the elderly.