Overview
Vascular disease describes conditions affecting the arteries and veins of the circulatory system. Blood leaves the heart and enters the aorta, which is the largest artery in the body, before travelling through progressively smaller arteries, carrying oxygen and nutrient-rich blood to tissues. Following this, the blood travels back through the veins to the heart and lungs where the oxygenation process begins again.
The vascular system is essential in delivering the blood needed to keep organs and tissues alive and removing waste substances. When blockages or restrictions form in the arteries this can have devastating consequences, such as loss of oxygen to an area of the body, leading to cell death. When this happens in the lower limb this can result in tissue death and can require amputations. Blockages in the venous system can damage venous valves, leading to venous insufficiency and lower limb ulceration.
A good understanding of the vascular system and vascular disease is essential to prevent vascular disease from presenting, and to reduce further development.
Causes of vascular disease
Atherosclerosis
Plaque in the arteries can consist of fatty substances, cholesterol, calcium and cellular waste products, amongst other substances. Over time, plaque can build up in the arteries and harden, forming a narrowing, which can reduce the flow to tissues below. This process is known as atherosclerosis.
The process of atherosclerosis typically begins with damage or injury to the inner layer of an artery. In response to this damage, the body's immune system initiates an inflammatory response, attracting white blood cells to the site.1 These white blood cells and other substances accumulate within the artery wall, forming fatty deposits known as plaques. These restrictions in the artery can lead to stroke and heart attack, which are the most common causes of death worldwide.2
Risk factors include:
- High blood pressure- higher pressure in the arteries increases the likelihood of arterial injury
- High cholesterol- this can contribute to a higher deposition of plaque
- Smoking- increases the circulating plaque and causes inflammation of arteries
- Diabetes- causes calcification (hardening) of the arteries, contributing to narrowings
- Obesity- causes an increase in inflammatory pathways which contribute to atherosclerosis
Furthermore, some people are genetically predisposed to higher levels of atherosclerosis. One example of this is familial hypercholesterolaemia, a genetic condition where there are high levels of damaging cholesterol known as low-density lipoprotein (LDL) in the blood. This can result in developing atherosclerosis at a young age and can lead to an early heart attack.3
Additionally, certain genes have been identified as associated with lipid metabolism, such as genes responsible for cholesterol creation and transport. Mutations in inflammatory genes can also increase the likelihood of developing atherosclerosis, as this can increase arterial damage.4
Blood clots
Blood clot formation, also known as coagulation or thrombosis, is a complex physiological process that helps to prevent excessive bleeding when a blood vessel is injured. The endothelium are cells which line the wall of blood vessels, and when vascular injury takes place the endothelium is exposed, causing platelets to adhere to the lining and become activated5.
When the activated platelets release granules containing clotting factors, they bind together and form a plug at the site of injury.6 The coagulation cascade (the process of forming clots) is activated, along with fibrin formation, which all lead to the creation of a blood clot.
There is a higher likelihood of developing a blood clot after periods of prolonged immobility, such as after a long hospital stay, or during air travel. One reason behind this is that there is a muscle in the calf which is activated on walking, and acts as a pump, forcing movement of blood up the venous system and preventing stasis.
Certain medical conditions result in blood that is more likely to coagulate, such as in the cases of malignancy, pregnancy, diabetes mellitus and hyperlipidaemia, along with the use of oral contraceptives.7 For people with these conditions blood thinners may be essential to prevent blood clots.
Vasculitis
Vasculitis is a condition involving inflammation of the arteries, capillaries or veins of the vascular system. Causes of vasculitis can be infections, allergic reactions or certain medications. Vasculitis can also be autoimmune in nature, where the immune system attacks its own vessel walls, causing inflammation, weakening of the vasculature, and narrowings or blockages8.
There are multiple different types of vasculitis depending on the size of the vessel affected. Large vessel vasculitis affects the larger arteries, with examples being Takayasu’s arteritis and Temporal arteritis (giant cell arteritis). Medium vessel vasculitis affects the medium-sized arteries such as polyarteritis nodosa. Small vessel vasculitis affects smaller vessels such as arterioles, venules and capillaries, such as granulomatosis with polyangiitis (GPA).
Symptoms of vascular disease
Peripheral artery disease (PAD)
PAD is a condition involving narrowings or blockages in the arteries, which can reduce the flow of blood to the arteries beyond. PAD results in a reduced supply of oxygenated blood reaching the muscles of the leg or foot. In its milder form, this can result in intermittent claudication, where there is pain and cramping in the legs on exercise, as muscles require a higher amount of oxygenated blood that is not available.
In more severe forms, sufferers of PAD may get pain and cramping in the leg at rest, particularly at night, where hanging the legs off the side of the bed can improve blood flow and provide temporary relief to symptoms. Other symptoms of PAD can include numbness, weakness, or inadequate wound healing. Changes in skin colour can also be seen, with skin appearing pale initially due to reduced perfusion of tissues, then blue and eventually red.9
Aneurysms
Aneurysms are where there is a dilation in all three walls of an artery. The term aneurysm is used when the typical diameter of the artery increases by 50%.
Abdominal aortic aneurysms (AAA) are located in the abdominal region of the largest artery in the body, the aorta, and can be silent until found incidentally or through national screening programmes. The arterial walls are composed of three layers, the adventitia, the media and the intima. In an AAA, all three layers of the vessel wall dilate to form a balloon.
Symptoms of an AAA can be a pulsating feeling in the abdomen. Serious symptoms of AAA are experiencing abdominal pain or discomfort and back pain, as this can indicate a split in the walls of the aneurysm or possible rupture. In these cases, emergency medical attention should be sought immediately.10
Thoracic aortic aneurysms (TAA) are located in the thoracic region of the aorta which can include the aortic root, ascending aorta, aortic arch, and descending aorta. Symptoms are rare, with around 95% of patients experiencing none.11 In rare occasions patients can experience chest or upper back pain. Other symptoms include difficulty swallowing or breathing, and hoarseness.
Deep vein thrombosis (DVT)
DVT is where there is a blood clot in any of the deep veins in the body, and can stop the blood from travelling back to the heart. A DVT can become life-threatening if the clot breaks off and travels to the heart, and then onto the lungs, which is called a pulmonary embolism. DVT results in swelling, pain and tenderness, and redness or discolouration in the region affected.12
As described by the Centre for Disease Control and Prevention (CDC), the most common sites for thrombosis are the lower leg, thigh and pelvis, and also occasionally in the arm. Symptoms of DVT include throbbing pain and swelling, usually in just one leg, and warm skin which can be painful to touch.
Summary
Vascular diseases can affect the arteries, veins and capillaries anywhere in the body. Conditions such as atherosclerosis can have multiple causes, such as high cholesterol, diabetes and high blood pressure, and can lead to peripheral arterial disease, causing ongoing symptoms with claudication. Issues with blood clot formation can cause serious conditions such as DVT. Additionally, vasculitis can lead to narrowings and blockages in the arteries which can have devastating effects. Aneurysms can be found in the arteries, commonly in the abdominal or thoracic aorta, and can often be asymptomatic. The early detection of vascular disease is essential in preventing longer-term complications and aiding the treatment pathway. If any of the above symptoms affect you, be sure to seek medical advice.
References
- Kong, Peng, et al. ‘Inflammation and Atherosclerosis: Signaling Pathways and Therapeutic Intervention’. Signal Transduction and Targeted Therapy, vol. 7, Apr. 2022, p. 131. PubMed Central, https://doi.org/10.1038/s41392-022-00955-7
- Wolf, Dennis, and Klaus Ley. ‘Immunity and Inflammation in Atherosclerosis’. Circulation Research, vol. 124, no. 2, Jan. 2019, pp. 315–27. PubMed Central, https://doi.org/10.1161/CIRCRESAHA.118.313591
- Santos, Raul D., et al. ‘Defining Severe Familial Hypercholesterolaemia and the Implications for Clinical Management: A Consensus Statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel’. The Lancet. Diabetes & Endocrinology, vol. 4, no. 10, Oct. 2016, pp. 850–61. PubMed, https://doi.org/10.1016/S2213-8587(16)30041-9.
- Wei, Yuanyuan, et al. ‘GSDME-Mediated Pyroptosis Promotes the Progression and Associated Inflammation of Atherosclerosis’. Nature Communications, vol. 14, no. 1, Feb. 2023, p. 929. PubMed, https://doi.org/10.1038/s41467-023-36614-w
- Mackman, Nigel. ‘Triggers, Targets and Treatments for Thrombosis’. Nature, vol. 451, no. 7181, Feb. 2008, pp. 914–18. PubMed Central, https://doi.org/10.1038/nature06797
- Alkarithi, Ghadir, et al. ‘Thrombus Structural Composition in Cardiovascular Disease’. Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 41, no. 9, Sept. 2021, pp. 2370–83. PubMed, https://doi.org/10.1161/ATVBAHA.120.315754
- Gialeraki, Argyri, et al. ‘Oral Contraceptives and HRT Risk of Thrombosis’. Clinical and Applied Thrombosis/Hemostasis: Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis, vol. 24, no. 2, Mar. 2018, pp. 217–25. PubMed, https://doi.org/10.1177/1076029616683802
- Moretti, Michele, et al. ‘Systemic Vasculitis: One Year in Review 2023’. Clinical and Experimental Rheumatology, vol. 41, no. 4, Apr. 2023, pp. 765–73. PubMed, https://doi.org/10.55563/clinexprheumatol/zf4daj
- Firnhaber, Jonathon M., and C. S. Powell. ‘Lower Extremity Peripheral Artery Disease: Diagnosis and Treatment’. American Family Physician, vol. 99, no. 6, Mar. 2019, pp. 362–69. PubMEd, https://pubmed.ncbi.nlm.nih.gov/30874413/
- Márquez-Sánchez, Ana Cristina, and Ekaterina K. Koltsova. ‘Immune and Inflammatory Mechanisms of Abdominal Aortic Aneurysm’. Frontiers in Immunology, vol. 13, 2022, p. 989933. PubMed, https://doi.org/10.3389/fimmu.2022.989933
- Faiza, Zainab, and Tariq Sharman. “Thoracic Aorta Aneurysm.” StatPearls, StatPearls Publishing, 2024. PubMed, http://www.ncbi.nlm.nih.gov/books/NBK554567/
- Kim, Kyung Ah, et al. ‘Endovascular Treatment for Lower Extremity Deep Vein Thrombosis: An Overview’. Korean Journal of Radiology, vol. 22, no. 6, June 2021, pp. 931–43. PubMed, https://doi.org/10.3348/kjr.2020.0675