Prediction Of Coronary Atherosclerosis Severity in Individuals with Coronary Heart Disease Associated with Chronic Obstructive Pulmonary Disease

Rationale and relevance of the topic

Coronary heart disease (CHD) occupies one of the leading places in the structure of healthcare in terms of the number of visits. In the last ten years, it has been the leading cause of disability and mortality among patients with cardiovascular diseases in economically developed countries of the world.

According to the WHO report, more than 17 million people die from cardiovascular diseases every year, of which more than 7 million die from CHD [1]. In Russia, the situation also remains critical: according to the Ministry of Health, the incidence of CHD increased by 4.76% from 2020 to 2023 [2].

From an epidemiological point of view, the growing incidence of CHD is associated with an increase in the proportion of the elderly population, high stress levels, the prevalence of metabolic disorders, including obesity and diabetes, as well as low commitment of the population to a healthy lifestyle. These factors create a significant burden on healthcare systems both in Russia and worldwide.

The main cause of coronary heart disease is coronary atherosclerosis, which is often diagnosed at late stages. Early detection of this disease is complicated by the fact that many biomarkers of coronary atherosclerosis are poorly available, expensive, or require invasive research methods [3]. In recent years, promising studies have emerged related to the use of molecular biomarkers such as microribonucleic acids (miRNA) and circulating endothelial cells. These biomarkers have shown high potential in identifying early stages of atherosclerosis and assessing the risk of cardiovascular complications [4]. Chronic obstructive pulmonary disease (COPD) and coronary heart disease often occur together, significantly increasing morbidity and mortality. These conditions share common pathophysiological mechanisms, including chronic inflammation, systemic oxidative stress, and endothelial dysfunction, which enhance the severity of coronary atherosclerosis. Modern studies confirm that patients with COPD have an average 30% higher risk of developing cardiovascular diseases, including coronary heart disease [5].

In order to refute or confirm the need for the study, we conducted a critical review of the literature published over the past 10 years. From all of the above, it should be noted that the main goal of the study is to search for new strategies that improve the efficiency of predicting the severity of coronary atherosclerosis in patients with coronary artery disease against the background of chronic obstructive pulmonary disease.

Comorbidities such as diabetes mellitus, hypertension and metabolic syndrome aggravate the clinical management of patients with COPD and coronary artery disease. They contribute to increased inflammatory processes and the development of endothelial dysfunction, a key mechanism in the pathogenesis of atherosclerosis. In addition, patients with combined pathologies have low exercise tolerance and higher levels of depression, which further reduces the quality of life and adherence to treatment [6]. According to large studies, patients with COPD and coronary artery disease have a higher mortality rate from cardiovascular events, especially among older populations [7]. Effective management of these diseases requires a multidisciplinary approach including cardiologists, pulmonologists and internists. New therapeutic strategies aimed at reducing inflammation and modulating oxidative stress occupy an important place. For example, interleukin-1β inhibitors (canakinumab) have been shown to reduce the risk of cardiovascular events in patients with high levels of inflammation, which confirms the promise of this direction [8,9]. Recent advances in prognostic models, including the use of coronary artery calcium score (CACS), have provided physicians with valuable tools for risk stratification and management [10]. CACS serves as a non-invasive marker for assessing the presence and severity of coronary artery disease and can predict cardiovascular outcomes. Comprehensive risk calculators integrating CACS data and other parameters such as body mass index (BMI), cholesterol level and family history improve the accuracy of prognostic models. However, even these tools have limitations, such as lack of effectiveness in patients with comorbidities, which highlights the relevance of research to improve them [10].

One promising area is the use of inflammatory biomarkers such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and tumor necrosis factor alpha (TNF-α). These markers not only help assess the degree of inflammation in coronary artery disease but also predict the risk of cardiovascular events. Studies show that patients with elevated hs-CRP levels have a two-fold higher risk of myocardial infarction or stroke, even in the absence of clinically significant atherosclerosis [11].

There is ongoing controversy regarding the optimal approach to managing coronary artery disease and COPD. These two conditions often coexist, worsening the clinical picture and increasing the risk of adverse outcomes. Effective management requires taking into account both respiratory and cardiovascular health. However, standard treatments such as statins, beta blockers and antiplatelet agents may not provide sufficient control over both diseases simultaneously. This highlights the need for new therapeutic approaches aimed at reducing inflammation and oxidative stress, key mechanisms in the pathogenesis of both diseases [11]. At the ERS Congress in 2015, scientists J. Feary and N. Barnes presented data from the Health Improvement Network computer database, which includes more than 5 million case histories. They demonstrated that patients with COPD are several times more likely to suffer from cardiovascular diseases (CVD) [12].

Determining the exact prevalence of COPD and IHD comorbidity presents significant methodological challenges. According to the literature, the frequency of COPD detection in patients with IHD varies widely (4-60%), which is due to differences in diagnostic criteria. Multicenter studies demonstrate that IHD occurs in 7-13% of patients with COPD, while the reverse comorbidity (COPD with IHD) is recorded in 26-35% of cases. As shown in the works of Soriano J.B., angiographically verified IHD is detected in more than 30% of patients with a confirmed diagnosis of COPD [13].

A large TORCH (Towards a Revolution in COPD Health) study revealed that cardiovascular pathologies become the main cause of death in half of patients with COPD [14]. Data from the ARCS (Atherosclerosis Risk Communities Study) and CHS (Cardiovascular Health Study) projects confirm that severe COPD significantly increases the likelihood of cardiovascular events such as myocardial infarction, transient ischemic attacks, and strokes [15]. The work of Donaldson G.C. and colleagues found that the peak risk of these complications occurs during periods of exacerbation of severe COPD [15]. Another promising direction is the study of the role of the microbiome in the pathogenesis of COPD and coronary heart disease. Recent studies have shown that an imbalance in the intestinal microbiome can contribute to chronic inflammation and endothelial dysfunction, which in turn aggravates the course of both diseases [16,17]. Experimental data indicate that correction of the microbiota with probiotics and prebiotics can reduce the inflammatory response and reduce the risk of cardiovascular events [18,19].

Research by Boev S.S. and co-authors (2016), dedicated to the relationship between coronary heart disease (CHD) and chronic obstructive pulmonary disease (COPD), identified a number of biomarkers of cardiovascular pathologies that may be associated with COPD exacerbations. The work "Association of coronary heart disease and chronic obstructive pulmonary disease: therapeutic problems and their clinical implications" emphasizes that the identification of these markers is important for understanding comorbidity and optimizing therapy. For example, during an exacerbation of COPD, the level of troponin in the patient's blood usually increases, even in the absence of a diagnosis of myocardial infarction. This phenomenon is likely associated with systemic inflammation, which increases during an exacerbation [Error: cross-reference source not found].

J.D. Maclay and colleagues described in their study an increase in the level of circulating platelet-monocyte aggregates in patients with COPD, which may increase the risk of cardiovascular events, including coronary heart disease [20]. Exacerbation of COPD creates a significant burden on the cardiovascular system. This is manifested by an increase in pressure in the pulmonary artery, an increase in the need of the respiratory muscles for oxygen, as well as hyperactivation of the sympathoadrenal and renin-angiotensin-aldosterone systems. At the same time, there is a release of proinflammatory cytokines, which contributes to the progression of coronary heart disease. Thus, the acute phases of COPD are a key risk factor for the development of cardiovascular pathologies. The common comorbidity of COPD and CVD is associated with common risk factors: smoking, older age, male gender, low physical activity, obesity, obstructive sleep apnea, secondary hyperaldosteronism, and adverse effects of drugs (e.g., glucocorticosteroids and β2-agonists) used in the treatment of COPD [22]. COPD is defined as a respiratory disease characterized by chronic respiratory symptoms and persistent airflow limitation that progresses against the background of an abnormal inflammatory response [23]. This chronic systemic inflammatory response affects not only the lungs but also the endothelial cells of the cardiovascular system, creating conditions for the co-development of COPD and CAD.

COPD and CAD share numerous common pathophysiological mechanisms that contribute to their co-occurrence and progression. Both conditions are characterized by chronic systemic inflammation and oxidative stress, which play a critical role in atherogenesis and associated cardiovascular complications. The inflammatory response in COPD involves neutrophil recruitment and production of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. These molecules promote lung parenchymal destruction, vascular remodeling, and endothelial injury [23].

Oxidative stress, accompanied by increased reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, increases inflammation and tissue injury, creating a vicious cycle. These processes aggravate both respiratory and cardiovascular pathologies, increasing the severity of the disease [24]. Endothelial dysfunction is a key common feature in both chronic obstructive pulmonary disease and coronary atherosclerosis, potentially acting as a linking factor in the development of coronary heart disease. Endothelial dysfunction caused by chronic inflammation and oxidative stress plays an important role in the pathogenesis of both conditions. Particular attention is paid to the role of the receptor for advanced glycation end products (RAGE), which is involved in these processes. RAGE activation is associated with increased oxidative stress and inflammatory response, which leads to vascular remodeling and the development of diseases such as emphysema and atherosclerosis [25]. Scientific studies have established that increased RAGE expression is associated with worsening endothelial dysfunction and the formation of atherosclerotic plaques, which increases the severity of cardiovascular complications in patients with COPD [26]. The combination of pathophysiological effects of COPD and ischemic heart disease requires an integrated therapeutic approach aimed at treating both conditions simultaneously. The main therapeutic goals are to reduce inflammation, eliminate oxidative stress and restore endothelial function.

The aim of this study is to analyze documented cases of coronary artery disease that occur in individuals with ischemic heart disease with a correlating disease of COPD. An important aspect of the work is to discuss the significance of the obtained results, especially in the context of the growing significance of this pathology.

Research objectives:

• To review articles published in official sources on cases of coronary atherosclerosis in individuals with ischemic heart disease against the background of COPD;
• To systematize literary data;
• To draw conclusions about the prognosis of coronary atherosclerosis.