Pathophysiology
Atherosclerosis is a persistent disorder in which arterial plaques cause arterial hardening. Increased plasma cholesterol levels lead to altered arterial endothelial permeability, allowing lipids, particularly Low-density lipoprotein cholesterol (LDL-C) particles, to migrate into the artery wall (Bergheanu et al., 2017). Monocytes in circulation bind to endothelial cells expressing adhesion molecules such as selectins.
Most of the coronary thrombi are exacerbated by plaque rupture, preceded by erosions, and then calcified nodules infrequently. Rupture-prone plaques typically consist of a large, tender, lipid-rich necrotic core surrounded by a thin and distended fibrous cap (Bergheanu et al., 2017). Vulnerable plaques constitute macrophages, monocytes, and T‑cells; through their impacts on macrophages, T-cells increase plaque susceptibility.
Risk Factors and Causes of Atherosclerosis
Atherosclerosis initiates the formation of arterial plaque, and this damage may be caused by risk factors, including bad lifestyle choices and genetics. Inflammatory cells migrate to the injured portions of the arteries and produce chemical signals. Smoking and lack of regular physical exercise increase the risk of high cholesterol levels, which may contribute to plaque formation (Hida et al., 2017). In addition, high blood pressure may damage arterial walls over time, causing plaque to accumulate. Finally, when a person has illnesses like psoriasis and rheumatoid arthritis, excessive levels of inflammation might end up stimulating their blood vessels, which can contribute to plaque formation, increasing the risk of arteriosclerosis.
Possible Consequences of Atherosclerosis
Coronary artery disease (CAD), commonly known as coronary heart disease, is caused by atherosclerosis of the arterial system supplying the heart and is the major cause of cardiac arrest. Peripheral artery disease (PAD) often refers to atherosclerosis of the arteries in the lower limbs and is a leading etiology of limb amputation. According to estimates, PAD and CAD affect over 200 million people worldwide (Hess et al., 2017). The increased rigidity of the artery wall is the primary etiology of essential hypertension (Gates, 2020). Decades precede the development of essential hypertension when arterial stiffness due to atherosclerosis occurs (Gates, 2020). It implies the age-related increase in the prevalence of essential hypertension.
Prevention Strategies for Atherosclerosis
The diet must always be the first step toward a cardiovascular (CV)-healthy lifestyle. Regarding hypertension management as a significant factor in the prevention of atherosclerosis, the Dietary Approaches to Stop Hypertension (DASH) regimen has shown efficacy (Kernan et al., 2021). Numerous vital responses of the cardiovascular system, including platelet activation, have been displayed to be highly responsive to the toxins in cigarette smoke (Kernan et al., 2021). Numerous studies have suggested that excellent management of diabetes mellitus is advantageous over the long run but that too strict control may increase the risk of severe hypoglycemia in the near term (Kernan et al., 2021). Blood glucose management may reduce the onset and advancement of microvascular problems.
The significance of exercise in reducing Cardiovascular death has been the focus of research for some time, and it now seems to be proven. According to research, the modest exercise of at least half an hour nearly daily is related to substantial reductions in mortality risk (Kernan et al., 2021). In addition, physical exercise is advantageous for atherosclerosis risk markers such as high blood pressure. Nonetheless, it must be borne in mind that acute intensive physical exercise tends to raise the risk of heart attack death and the incidence of myocardial infarction (Kernan et al., 2021). This seems to be true for both confirmed and occult chronic heart disease patients.
Treatment Modalities of Atherosclerosis
Antiplatelet treatment may stabilize the susceptible patient by lowering the quantity of local thrombus development and vascular stress. Aspirin is useful for secondary treatment in atherosclerotic vascular disease clients (Zhang et al., 2017). Additionally, antiplatelet medications such as prasugrel, clopidogrel, and ticagrelor help reduce the risk of CHD. Antihypertensive treatment aids in the treatment of atherosclerosis patients. Multiple clinical studies have shown that B-blockers prevent recurrent acute myocardial infarction (AMI), sudden cardiac death, and overall mortality in AMI clients (Zhang et al., 2017). It has been shown that inhibiting angiotensin II decreases inflammatory symptoms in atherosclerotic individuals (Zhang et al., 2017). Suppression of the Renin-Angiotensin System (RAS) also enhances endothelial function.
Given the significant negative link between high-density (HDL) lipoprotein and cardiovascular disease risk, nicotinic acid as a treatment option for reducing LDL-C while increasing high-density lipoprotein has lately attracted fresh attention. Niacin significantly decreases cardiovascular disease as well as atherosclerosis development (Zhang et al., 2017). Plaque stability implications of anti-diabetic thiazolidinediones have recently been examined. Rosiglitazone substantially decreased the proportion of cluster of differentiation (CD4) positive lymphocytes without affecting the proportion of plaque macrophages (Zhang et al., 2017). Nevertheless, macrophage activation was dramatically decreased, resulting in a rise in collagen type-I concentration, indicating that rosiglitazone therapy may transform unstable plaques into more stable ones.
Recent investigations have shown that matrix metalloproteinases (MMPs) are highly expressed in atherosclerotic plaques and contribute to fibrous cap thinning by destroying the extracellular matrix. To limit plaque progression and stabilize rupture-prone plaques, the discovery of medicines that selectively target lesional MMPs, like MMP-9, may be a helpful therapeutic strategy. As it is effective and typically safe, lowering LDL-C with statins remains the foundation of medical management of atherosclerotic disease. Ezetimibe should be considered for high-risk individuals with statin sensitivity or who do not achieve the required LDL-C level after extensive statin therapy (Zhang et al., 2017). Future PCSK-9 inhibitors, either monoclonal antibodies or novel methods, appear to be strong medicines for dyslipoproteinaemia.
References
Bergheanu, S. C., Bodde, M. C., & Jukema, J. W. (2017). Pathophysiology and treatment of atherosclerosis. Netherlands Heart Journal, 25(4), 231–242.
Gates, P. (2020). Arteriosclerosis with superimposed atherosclerosis is the cause not the consequence of essential hypertension. Medical Hypotheses, 144, 110236.
Hess, C. N., Norgren, L., Ansel, G. M., Capell, W. H., Fletcher, J. P., Fowkes, F. G. R., Gottsäter, A., Hitos, K., Jaff, M. R., Nordanstig, J., & Hiatt, W. R. (2017). A structured review of antithrombotic therapy in peripheral artery disease with a focus on revascularization. Circulation, 135(25), 2534–2555.
Hida, T., Imagama, S., Ando, K., Kobayashi, K., Muramoto, A., Ito, K., Ishikawa, Y., Tsushima, M., Nishida, Y., Ishiguro, N., & Hasegawa, Y. (2017). Sarcopenia and physical function are associated with inflammation and arteriosclerosis in community-dwelling people: The Yakumo study. Modern Rheumatology, 28(2), 345–350.
Kernan, W. N., Viera, A. J., Billinger, S. A., Bravata, D. M., Stark, S. L., Kasner, S. E., Kuritzky, L., & Towfighi, A. (2021). Primary Care of Adult Patients After Stroke: A Scientific Statement From the American Heart Association/American Stroke Association. Stroke, 52(9).
Zhang, J., Zu, Y., Dhanasekara, C. S., Li, J., Wu, D., Fan, Z., & Wang, S. (2017). Detection and treatment of atherosclerosis using nanoparticles. WIREs Nanomedicine and Nanobiotechnology, 9(1).