Risk factors for atherosclerosis development in patients with systemic scleroderma

American Journal Of Biomedical Science & Pharmaceutical Innovation

17

https://theusajournals.com/index.php/ajbspi

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

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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

American Journal of Applied Science and Technology

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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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