Atherosclerotic cardiovascular disease
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These studies suggest that inflammation plays a key role in atherosclerotic cardiovascular disease, and targeting it therapeutically may provide novel treatments, while chronic kidney disease and lifestyle changes also influence disease progression and outcomes.
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Atherosclerotic Cardiovascular Disease: An Overview
Introduction to Atherosclerotic Cardiovascular Disease
Atherosclerotic cardiovascular disease (ACD) is the leading cause of mortality worldwide, characterized by the buildup of atheromatous plaques within the arterial walls, leading to cardiovascular complications such as myocardial infarction and ischemic stroke . This chronic inflammatory condition involves a complex interplay between lipid metabolism, immune responses, and endothelial dysfunction .
Pathophysiology of Atherosclerosis
Endothelial Dysfunction and Lipid Accumulation
Atherosclerosis begins with endothelial dysfunction, which is triggered by factors such as oxidative stress and disturbed shear stress. This dysfunction leads to the accumulation of lipids, particularly oxidized low-density lipoprotein (oxLDL), within the arterial walls . The oxLDL is taken up by macrophages, transforming them into foam cells and exacerbating the inflammatory response.
Inflammatory Processes
Inflammation plays a central role in the progression of atherosclerosis. Immune cells, including monocytes, macrophages, and T cells, infiltrate the arterial wall and contribute to plaque formation and instability . Pro-inflammatory cytokines and chemokines are released, perpetuating the inflammatory cycle and promoting further lipid accumulation and plaque growth .
Plaque Formation and Rupture
The atheromatous plaques consist of a lipid core surrounded by a fibrous cap. Over time, these plaques can become unstable and rupture, leading to thrombus formation and acute cardiovascular events such as myocardial infarction or ischemic stroke . Factors such as high levels of inflammatory mediators and oxidative stress contribute to plaque instability and rupture .
Epidemiology and Risk Factors
Global Burden
ACD is the leading cause of death globally, with significant variations in mortality rates based on economic development. High-income countries have seen a reduction in ACD mortality due to better management of risk factors, while low- and middle-income countries are experiencing an increase in ACD-related deaths due to rising prevalence of obesity, diabetes, and other risk factors.
Traditional and Emerging Risk Factors
Traditional risk factors for ACD include high body mass index (BMI), hypertension, hypercholesterolemia, and diabetes. Emerging risk factors such as chronic kidney disease (CKD) also play a significant role, as CKD patients exhibit increased inflammation and vascular calcification, exacerbating atherosclerosis .
Immune Mechanisms in Atherosclerosis
Innate and Adaptive Immunity
Both innate and adaptive immune responses are involved in the pathogenesis of atherosclerosis. Innate immune cells such as neutrophils, monocytes, and macrophages initiate and sustain the inflammatory response, while adaptive immune cells, including T and B lymphocytes, modulate the progression and stability of atherosclerotic plaques .
Role of T Cells
T cells, particularly CD4+ and CD8+ T cells, play crucial roles in atherosclerosis. CD4+ T cells respond to oxLDL antigens and facilitate plaque formation, while CD8+ T cells contribute to plaque rupture through their cytotoxic effects. Regulatory T cells (Tregs) help mitigate pathological inflammation, highlighting the potential of T cells as therapeutic targets.
Therapeutic Approaches
Anti-inflammatory Treatments
Given the central role of inflammation in atherosclerosis, targeting inflammatory pathways has emerged as a promising therapeutic strategy. Clinical studies, such as the Canakinumab Anti-inflammatory Thrombosis Outcome Study (CANTOS), have shown that anti-inflammatory treatments can reduce cardiovascular events by targeting specific pro-inflammatory cytokines like interleukin-1 beta.
Lipid-lowering Therapies
Lowering LDL cholesterol levels remains a cornerstone of ACD management. Statins are widely used to reduce LDL levels and have been shown to decrease the risk of major cardiovascular events. However, additional therapies are needed to address the residual risk associated with inflammation and other non-lipid factors .
Conclusion
Atherosclerotic cardiovascular disease is a complex and multifaceted condition driven by lipid accumulation, inflammation, and immune responses. Understanding the intricate mechanisms underlying atherosclerosis and targeting both traditional and emerging risk factors are crucial for developing effective prevention and treatment strategies. Continued research into the inflammatory and immune aspects of atherosclerosis holds promise for novel therapeutic approaches to reduce the global burden of this disease.
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