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 VOLUME Vol.05 Issue02 2025 

PAGE NO. 17-19 

DOI 10.37547/ajbspi/Volume05Issue02-05 

 
 
 
 

Risk factors for atherosclerosis development in patients 

with systemic scleroderma 
 

Ganieva N.A. 

Tashkent Medical Academy, Tashkent, Uzbekistan 

 

Ziyaeva F.K. 

Tashkent Medical Academy, Tashkent, Uzbekistan 

 

Dwivedi K. 

Tashkent Medical Academy, Tashkent, Uzbekistan 

 

Koli V. 

Tashkent Medical Academy, Tashkent, Uzbekistan 

 

 

 

Received: 17 December 2024; Accepted: 19 January 2025; Published: 21 February 2025 

 

Abstract: Systemic scleroderma (SSc), also known as systemic sclerosis, is a rare autoimmune disorder 
characterized by fibrosis of the skin and internal organs, as well as vascular abnormalities. Atherosclerosis, the 
accumulation of lipids and fibrous tissue in arterial walls, is a significant cause of cardiovascular morbidity and 
mortality. Patients with systemic scleroderma are at an elevated risk for developing atherosclerosis, with vascular 
damage playing a central role in its pathogenesis. This article reviews the multifactorial risk factors contributing 
to the development of atherosclerosis in patients with systemic scleroderma, focusing on endothelial dysfunction, 
chronic inflammation, dyslipidemia, and other clinical factors. The goal of this article is to enhance the 
understanding of cardiovascular risk in this population and emphasize the importance of early diagnosis and 
targeted interventions. 

 

Keywords: Systemic scleroderma, atherosclerosis, cardiovascular diseases, endothelial dysfunction, lipid 
abnormalities, autoimmune diseases. 

 

Introduction: Systemic scleroderma (SSc) is a systemic 
autoimmune disease that primarily affects the skin but 
can also involve internal organs, including the heart, 
lungs, kidneys, and gastrointestinal tract. Vascular 
involvement is one of the hallmark features of systemic 
scleroderma and is characterized by microvascular 
abnormalities, including vasospasm, capillary loss, and 
fibrosis of the blood vessels [1]. While the primary 
clinical focus of systemic scleroderma has often been 
its fibrotic aspects, there is increasing recognition of 
the heightened risk of cardiovascular diseases (CVD) in 
these patients. Specifically, atherosclerosis, a chronic 

inflammatory process that results in the accumulation 
of cholesterol and other materials in arterial walls, has 
become a major concern in the management of 
systemic scleroderma. Atherosclerosis in SSc is a 
multifactorial process influenced by both the disease-
specific mechanisms and traditional cardiovascular risk 
factors [2,8]. The pathophysiology of atherosclerosis in 
systemic scleroderma is complex and involves 
endothelial dysfunction, inflammatory mediators, lipid 
abnormalities, and changes in the vascular smooth 
muscle. This review will examine the primary risk 
factors that predispose systemic scleroderma patients 
to atherosclerosis and discuss their clinical 

 

https://doi.org/10.37547/ajbspi/Volume05Issue02-05
https://doi.org/10.37547/ajbspi/Volume05Issue02-05


American Journal of Applied Science and Technology 18 https://theusajournals.com/index.php/ajast 

American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

implications. 

Pathophysiology of Atherosclerosis in Systemic 
Scleroderma. The pathogenesis of atherosclerosis in 
systemic scleroderma involves a combination of 
endothelial dysfunction, inflammation, and impaired 
vascular repair. In SSc, vascular injury occurs due to 
fibrosis, immune cell activation, and chronic 
inflammation. Endothelial cells in patients with 
systemic sclerosis exhibit increased permeability, 
decreased nitric oxide production, and upregulation of 
adhesion molecules, leading to the recruitment of 
inflammatory cells [3]. This results in the formation of 
an atherosclerotic plaque, which may progress more 
rapidly due to the vascular abnormalities intrinsic to 
systemic scleroderma. 

Endothelial Dysfunction and Microvascular Injury. 
Endothelial dysfunction is a critical early event in the 
pathogenesis of atherosclerosis, and it is exacerbated 
in systemic scleroderma due to microvascular damage. 
In SSc, endothelial cells are injured by both mechanical 
forces, such as shear stress from blood flow, and by 
inflammatory mediators. The presence of Raynaud's 
phenomenon, a characteristic feature of systemic 
scleroderma, can further damage the endothelium by 
causing periodic ischemia and reperfusion injury. Over 
time, endothelial cells lose their ability to maintain 
vascular tone and promote vasodilation, contributing 
to the progression of atherosclerosis [4]. 

Chronic Inflammation and Immune Activation. 
Chronic inflammation plays a pivotal role in the 
development of atherosclerosis in patients with 
systemic scleroderma. Elevated levels of 
proinflammatory cytokines, including tumor necrosis 
factor-alpha (TNF-α), interleukin-6 (IL-6), and 
interleukin-1β (IL-1β), are frequently observed in 
patients with SSc. These inflammatory cytokines 
promote the activation of endothelial cells, the 
infiltration of monocytes into the arterial wall, and the 
formation of foam cells, all of which contribute to 
plaque formation. Additionally, autoantibodies 
commonly present in SSc, such as anti-centromere and 
anti-topoisomerase I antibodies, may directly 
contribute to vascular damage and accelerate 
atherosclerotic progression through immune complex 
deposition and subsequent tissue injury. 

Dyslipidemia and Lipid Metabolism. Alterations in lipid 
metabolism are common in systemic scleroderma and 
represent a significant risk factor for atherosclerosis. 
Dyslipidemia in SSc is characterized by low levels of 
high-density lipoprotein (HDL) cholesterol, which has a 
protective effect on endothelial function, and elevated 
levels of low-density lipoprotein (LDL) cholesterol and 
triglycerides, both of which promote the formation of 

atherosclerotic plaques. The mechanisms underlying 
dyslipidemia in SSc are complex and involve altered 
lipid synthesis, oxidative stress, and inflammation 
[5,11]. This dyslipidemic profile increases the likelihood 
of lipid deposition in the arterial walls, thereby 
fostering the development of atherosclerosis. 

Hypertension. Hypertension is a common comorbidity 
in patients with systemic scleroderma and significantly 
increases the risk of atherosclerosis. Renal involvement 
in SSc, including scleroderma renal crisis, can lead to 
secondary hypertension, which accelerates the 
progression of vascular damage. Furthermore, the use 
of corticosteroids in SSc treatment may also contribute 
to elevated blood pressure. Hypertension induces 
mechanical stress on the endothelial cells, enhances 
inflammation, and promotes plaque instability, all of 
which facilitate the development of atherosclerosis. 

Immune System Dysfunction and Autoimmunity. The 
autoimmune nature of systemic scleroderma 
predisposes patients to abnormal immune responses 
that can exacerbate vascular injury. The presence of 
specific autoantibodies in SSc, such as anti-Scl-70 
(topoisomerase I), can lead to endothelial cell 
dysfunction and the promotion of vascular remodeling. 
Additionally, circulating immune complexes can 
deposit in the blood vessel walls, activating 
complement and contributing to the inflammatory 
process that drives atherosclerosis. The immune-
mediated vascular injury may be exacerbated by 
concomitant diseases, such as lupus or rheumatoid 
arthritis, which are commonly associated with systemic 
scleroderma.  

Age and Gender. Age is a well-established risk factor 
for atherosclerosis, and it remains relevant in patients 
with systemic scleroderma. The risk of cardiovascular 
disease increases with age, as the natural process of 
vascular aging contributes to endothelial dysfunction 
and plaque formation. Gender differences also play a 
role, with postmenopausal women at increased risk of 
atherosclerosis due to the loss of the protective 
cardiovascular effects of estrogen. 

Medications and Treatment-Related Factors. The 
treatment of systemic scleroderma itself may 
contribute to cardiovascular risk. Corticosteroids, 
commonly prescribed for SSc, can lead to increased 
blood pressure, dyslipidemia, and insulin resistance, all 
of which are risk factors for atherosclerosis [6,7]. 
Additionally, some immunosuppressive therapies used 
in SSc, such as cyclophosphamide, may indirectly 
increase cardiovascular risk by promoting endothelial 
dysfunction and contributing to vascular remodeling.  

Obesity and Sedentary Lifestyle. Patients with 
systemic scleroderma often experience reduced 



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American Journal of Applied Science and Technology (ISSN: 2771-2745) 
 

 

physical activity due to musculoskeletal involvement, 
joint stiffness, and skin tightness, which can contribute 
to obesity and metabolic syndrome. Obesity, in turn, is 
a well-known risk factor for the development of 
atherosclerosis. Sedentary behavior, combined with 
obesity, exacerbates the risk of developing 
cardiovascular diseases in these patients. 

Management and Prevention. Given the elevated 
cardiovascular risk in patients with systemic 
scleroderma, early screening for atherosclerosis is 
essential. Regular monitoring of blood pressure, lipid 
profiles, and markers of inflammation is recommended 
to identify those at greatest risk for atherosclerotic 
cardiovascular events. Non-invasive imaging 
techniques, such as carotid ultrasonography, can help 
assess the presence and severity of atherosclerosis in 
SSc patients [9]. Management strategies should include 
aggressive control of traditional risk factors, such as 
hypertension and dyslipidemia, as well as the 
treatment of the underlying autoimmune and 
inflammatory components of systemic scleroderma. 
Statins, angiotensin-converting enzyme inhibitors (ACE 
inhibitors), and other cardiovascular agents should be 
considered based on individual risk profiles [10]. 

CONCLUSION 

Patients with systemic scleroderma are at an increased 
risk of atherosclerosis due to a combination of 
endothelial dysfunction, chronic inflammation, 
dyslipidemia, and other disease-specific factors. The 
early identification of these risk factors and the 
implementation of targeted interventions are crucial to 
reduce the cardiovascular morbidity and mortality in 
this patient population. Clinicians must be vigilant in 
monitoring for atherosclerosis in systemic scleroderma 
and take an integrated approach to the management of 
cardiovascular risk. 

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