Chronic Venous Disease

Blood circulation in the human body 
The circulatory system (cardio-vascular system) in the human body consists of the heart (a pump) and blood vessels (pipes).  The main function of the cardiovascular system is to supply body’s tissues with oxygen, nutrients, elements of the immune system, hormones and many other substances. It is built by two main circuits – systemic and pulmonary. The systemic circuit supplies oxygen rich blood to the organs in the body and returns oxygen poor blood from the organs back to the heart. The pulmonary circuit carries unoxygenated blood to the lungs and carries blood enriched with oxygen back to the heart.

Blood vessels are arteries, arterioles, capillaries, venules and veins (Tucker 2018).

Venous vessels

  • Carry away blood from the tissues to the heart
  • Have larger lumen and thinner vessel wall
  • Blood pressure is low
  • Blood moves passively (it is not forced by a pump)
  • Hydrostatic pressure plays a significant role
  • HAVE VALVES – they protect from blood flowing back


Arterial vessels

  • Carry blood from the heart to the tissues
  • Have smaller lumen and thicker wall
  • Blood pressure is high
  • Blood moves actively – it is pumped by the heart
  • Have no valves – they are not necessary


Capillaries

  • Have very thin walls – a single layer of cells
  • This is the place where the exchange of oxygen and other substances between blood and cells of the surrounding tissue is carried out
  • Fine structures susceptible to damage
  • Permeability increases as a result of impairing factors – efflux of excess fluid into the surrounding tissue


What varicose veins are?
Varicose veins (curved, twisted or elongated veins) are among the most common medical problems of the adult population (Chieh-Min Fan 2005). It is estimated that they are the seventh most common disease in the US, requiring medical care (Chieh-Min Fan 2005). It is difficult to determine the prevalence of varicose veins due to the differences in the selection criteria and the research methods used. According to various statistical data, chronic venous disease affects 50 to 80% of women, and 10 to 50% of men (Robertson 2008).
  
Varicose veins are a stage of a progressive disease called chronic venous disease (CVD). It starts with early non-specific stigmata, which slowly and steadily evolve into more bothersome and incapacitating illness, involving the lower limbs. The veins of the legs are exposed to the greatest burden, because blood in these veins must overcome significant weight, in order to move towards the heart. In medicine, the stages of the disease are classified from the mildest one, C0, to the most severe CVD – C6 5 (Eklöf 2004), (Guidelines-ESVS- Management of Chronic Venous Disease 2015):

  • C0 No apparent changes. Important non-specific signs for an early stage of CVD are: tension in the calves, swelling of the legs and ankles, itching or pain in the legs. Do not ignore them. Timely measures can significantly slow down the progression of the disease.
  • C1 Telangiectases or retiular veins. If you notice tiny vessels in the form of fibers or a spider net on your legs, you may have early stage CVD. Often they are of red or purple color. Apart from being a cosmetic problem, they also present a medical problem revealing initial development of CVD.
  • C2 Varicose veins. These are the typical enlarged veins – plenty of prominent vessels of irregular shape, twisted, sometimes painful with localized pressure. This stage of the disease should raise an awareness. A specialist consultation is indicated.
  • C3 Swelling of the ankle and calf due to CVD. This is a sign that CVD advances and it impacts the proper functioning of the capillaries.
  • C4 Skin changes. Brownish-purple discoloration of the skin, eczemas and crusts appear. Skin is dry. You should seek specialist advice. 
  • C5 Healed venous ulcer. A scar of a healed ulcer is seen on the lower part of the leg (around and above the ankle). A specialist consultation is indispensable.
  • C6 Active venous ulcer. This the most severe form of CVD.  It presents with big ulcer near the ankle which does not heal. It requires urgent vein specialist intervention! The treatment is long and difficult.


Risk factors
The development of varicose veins is a result of a complicated interaction of multiple factors, including sex, age, familial predisposition, pregnancy, obesity and lifestyle (Chieh-Min Fan 2005).
 
Age and sex. Prevalence of varicose veins in women is approximately twice as high as that in men (Laurikka 2002) and it increases with increasing age (Cesarone 2002). It has been estimated that at the age of 40, 50 and 60 years of age the prevalence is 22%, 35% and 41%, respectively (Laurikka 2002).

Pregnancy. Pregnancy is a main predisposing factor for the development of varicose veins and likely the primary reason for the 2-fold higher prevalence in females than males. Development of new varicose veins is observed in 28% of all pregnancies (Stansby 2000) and prevalence increases with the number of births. It was determined that prevalence in women of none, one, two, three and four consecutive pregnancies is 32%, 38%, 43%, 48%, and 59%, respectively (Laurikka 2002). Although the exact mechanism of venous insufficiency in pregnancy is not completely clear, it is accepted that hydrostatic and hormonal factors are the likely cause (Chieh-Min Fan 2005).

Heredity. Heredity is a principal risk factor. Positive family history for enlarged veins is associated with significantly elevated risk for development of varicose veins. It is estimated to be (Boisseau 2014):

  • 20% in those with two non-affected parents,  
  • 25-62% with one affected parent, and 
  • 90% with both parents affected. 

Obesity and long-lasting standing position. The body mass index (BMI) is a risk factor for varicose vein in women, but not in men (Fowkes 2001). It is assumed that deposition of subcutaneous fat destroys the dermal venous net, decreases the drainage and stimulates the congestion of venous blood. The long-lasting stаnding position is an independent risk factor for development of venous insufficiency (Laurikka 2002).

Until recently it was accepted, that the reason for the varicose veins to occur is a chronic inflammation of the vessel wall and the venous valves. However, in the latest years, as a result of accumulated scientific evidence, this perception has changed and now contemporary medicine worldwide considers the degradation of the vessel wall to be the primary cause of varicose veins, and the inflammation – secondary to that (Boisseau 2014). The strength and elasticity of venous wall are partially genetically coded and depend highly on the wall’s structural elements – collagen type I, collagen type III and elastin. When they are of insufficient quantity or improper proportion, veins lose their normal tone, elasticity and flexibility (Sansilvestri-Morel 2001). Under these circumstances, under the blood’s hydrostatic pressure, the vein enlarges and the valves cannot exert their natural functions, which is to keep blood flowing in one direction. Reflux occurs (a backflow of blood through the valve) which additionally injures the venous valves and vessel wall, thus leading to inflammation and resulting in structural changes of the venous wall – diminished synthesis of collagen type III. It becomes, harder, less elastic, elongated and twisted (MacColl 2015).

Understanding the processes involved in the development and progression of the disease provides an opportunity for therapeutic targets, which could be effective not only for alleviating the signs and symptoms of CVD, but also for slowing progression (Perrin 2011).

Contemporary scientific approach in the treatment of varicose veins should be complex, and directed towards the primary cause of disease - the weakened vessel wall, as well as influencing the chronic inflammation. 

Treatment of chronic venous disease (CVD)
The mode of treatment is determined by the disease stage. It can be conservative or surgical (Mallick 2016).

Conservative treatment
Compression stockings: improve venous hemodynamics (Ibegbuna 2003) and decrease the edema (Motykie 1999). The use of compression stockings at each stage of CVD is an important part of the successful treatment of the disease.
Pharmacological treatment: Pharmacological treatment of the disease is an integral part of CVD treatment at each stage of the disease by influencing its etiological and pathophysiological mechanisms (Perrin 2011).

IMPACT ON THE PATHOPHYSIOLOGICAL MECHANISMS OF THE DISEASE
Inflammation plays a key role in the progression of the venous diseases and contributes to complications like blood clots and leg ulcers. Inhibiting the inflammation can offer prevention of disease-associated complications. The currently available medications, directed against various elements of the inflammatory cascade, are venotonic agents (Bergan 2006):

Micronized purified flavonoid fraction (MPFF) have the highest statistically significant reduction of inflammation and edema, improvement of the lymphatic drainage, faster healing of venous ulcers and increase of capillary resistance (Nicolaides  2008), (Perrin 2011).

Ruskus extract increases capillary resistance (Perrin 2011).

Calcium dobesilate improves capillary resistance and decreases the swelling (Perrin 2011). There are some drawbacks related to safety. Cases of transient agranulocytosis have been reported (Nicolaides 2008).

Escin increases capillary resistance (Perrin 2011).

Rutin and rutosides improve capillary resistance and decrease edema (Perrin 2011).

IMPACT ON THE DISEASE ETIOLOGY
Collagen is vital for elasticity, flexibility and strength of blood vessels (Czech 2016). Collagen type I supports the strength, and collagen type III – elasticity of vessels. Regulation of the balance between the synthesis of collagen type I and that of type III is of paramount importance for the mechanical properties of blood vessels. This balance depends on a vigorous control of biosynthesis and degradation of collagens type I and III (Sansilvestri-Morel 2001).
There is research evidence that patients with HVD have increased synthesis of collagen type I in the venous wall and decrease synthesis of collagen type III. The result is hardened and less elastic vessels (Sansilvestri-Morel 2001). On one hand, this is due to heredity, which preserves the genetic defects in the connective tissue synthesis (collagen and elastane), which leads to weakened vein wall and earlier onset of CVD (Atta 2012); on the other, to the inflammatory process in the venous wall, which adds to the degradation of collagen type III (MacColl 2015).
Collagen is produced primarily by fibroblasts in the connective tissue. Activation of fibroblasts leads to increased production of collagen (Sibilla 2015). In the last decade it has been proven that the intake of specific hydrolyzed collagen activates fibroblasts and results in statistically significant 1.2 to 2.4 fold increase in the collagen biosynthesis (Schunck 2013). 
How is the synthesis of specific collagen increased (Sibilla 2015):

  • Free amino acids from the collagen chain supply the structural elements for the formation of collagen and elastane fibers
  • Collagen di- and tripeptides serve as ligands, binding to membrane receptors on fibroblasts and stimulating production of new collagen, elastin and hyaluronic acid.

Every collagen type has a specific sequence of its building amino acids, which determines its specific properties. An important criterion for the synthesis of a specific collage is the aminoacid sequence in the di- and tripeptides (Aoki 2012).
The specific collagen peptides, which can be administered orally, have shown that they can induce significant increase of collagen type I and III expression in human fibroblasts. The same research study concludes, that collagen peptides can be an option for the treatment and prevention of pathologic changes in the connective tissue (Schunck 2013).

Surgical treatment (Beale 2005):

  • stripping

Minimally invasive treatment:

  • endogenous laser ablation (EVLA)
  • radio frequency ablation  (RFA)
  • sclerotherapy                                           
  • mini-phlebotomy

Non-invasive methods:

  • transdermal laser therapy 


A GUIDE TO HEALTHY AND BEAUTIFUL LEGS (Özdemir 2017):

  1. AVOID LONG-LASTING STANDING OR SITTING POSITION. 
    If your job requires longer periods of standing or sitting, take short breaks to walk and perform circular movements with your feet (CDC 2017).
  2. DO SPORTS REGULARLY (Araki 1994; Heinen 2012).
    Everyday walking, swimming, jogging, cycling and dancing are the best exercise for the circulation of the blood in your veins. 
  3. DECREASE OVERWEIGHT AND TAKE MEASURE FOR ANY CONSTIPATION. 
    They increase the venous pressure. Eat fiber rich diet, drink plenty of liquids and limit the intake of fats, coffee and alcohol.            
  4. FREQUENTLY LIFT YOUR FEET HIGH. 
    At the end of the day relax your legs by lifting the higher than the level of your heart.        
  5. WEAR LOOSE CLOTHING. 
    Tight clothing compresses the veins and obstructs venous drainage.  
  6. WEAR SHOES OF APPROPRIATE HIGHT. 
    Avoid shoes with flats sole, as well as heels higher than 5 cm.              
  7. AVOID LONG EXPOSURE TO SUN. 
    Heat causes venous distention.
  8. END YOUR DAY WITH A COOL SHOWER TO YOUR FEET. 
    Move the shower handle from the feet upwards. This will improve venous function and will diminish the pain and the heavy feeling in your feet.
  9. AVOID HOT BATHS, SAUNAS AND MINERAL SPRINGS. 
    The heat provokes inflammation and swelling. 
  10. MASAGE YOUR LEGS AS FREQUENTLY AS POSSIBLE. 
    Start from the feet and continue upwards.
  11. VISIT YOUR DOCTOR REGULARLY. 
    If you experience pain and weariness in your legs, swelling of ankles or the veins on your legs become visible, visit your general practitioner.

If you experience pain and weariness in your legs, swelling of ankles or the veins on your legs become visible, visit your general practitioner.


Reference

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