Course Of Coronary Artery Disease Research Articles

Serum N-glycomic profiling identifies candidate biomarker panels for assessing coronary artery stenosis severity

Stenosis severity may escalate over the course of coronary artery disease (CAD), increasing the risk of death for the patient. Conventionally, the assessment of stenosis degree relies on invasive coronary angiography (ICA), an invasive examination unsuitable for patients in poor physical condition or those with contrast allergies and one that imposes a psychological burden on patients. Although abnormal serum N-glycan profiles have exhibited robust associations with various cardiovascular diseases, including CAD, their potential in diagnosing CAD stenosis remains to be determined. In this study, we performed a comprehensive analysis of serum N-glycome from 132 patients who underwent ICA and 27 healthy controls using MALDI-TOF-mass spectrometry. The patients who underwent ICA examination were categorized into four groups based on stenosis severity: no/mild/moderate/severe stenosis. Twenty-seven N-glycans were directly quantified, and 47 derived glycan traits were obtained. Notably, among these 74 glycan features, 18 exhibited variations across the study groups. Using a combination of least absolute shrinkage and selection operator and logistic regression analyses, we developed five diagnostic models for recognizing stenosis degree. Our results suggested that alterations in serum N-glycosylation modifications might be valuable for identifying stenosis degree and monitoring disease progression in individuals with CAD. It is expected to offer a noninvasive alternative for those who could not undergo ICA because of various reasons. However, the diagnostic potential of serum N-glycan panels as biomarkers requires multicenter, large cohort validation in the future.

Risk Factors Association with Transcriptional Activity of Metalloproteinase 9 (MMP-9) and Tissue Inhibitor of Metalloproteinases 1 (TIMP-1) Genes in Patients with Heart Failure.

The aim of the study was to assess the occurrence of classic risk factors in the study group of patients with heart failure and to link them with the transcriptional activity of the examined genes: metalloproteinase 9 (MMP-9) and the tissue inhibitor of metalloproteinases 1 (TIMP-1). A total of 150 (100%) patients qualified for the study, including 80 (53.33%) patients with heart failure in the course of coronary artery disease, 40 (26.67%) with coronary artery disease without heart failure, and 30 (20.00%) in whom the presence of atherosclerotic changes in the coronary arteries was excluded. The material for molecular tests was peripheral blood collected from patients within the first 24 h of hospitalisation. A quantitative analysis of transcriptional activity was performed using the RT-qPCR technique. The most common classic risk factors among the patients in the study group were arterial hypertension (117; 78.00%) and overweight/obesity (102; 68%). In the group of patients with coronary artery disease and heart failure burdened with overweight/obesity, a significantly higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene was found in comparison to patients who were not burdened with this risk factor. The analysis also showed the statistically significant higher transcriptional activity of the metalloproteinase 9 (MMP-9) gene in a group of patients with coronary artery disease and heart failure who smoked. The examined patients with heart failure due to myocardial ischemia were burdened with numerous cardiovascular risk factors, the most common of which were arterial hypertension, obesity/overweight, and hypercholesterolemia. A significant increase in the transcriptional activity of the metalloproteinase 9 (MMP-9) gene in the presence of risk factors (male sex, overweight/obesity, smoking) indicates another pathomechanism of their action and participation in the development and progression of heart failure during myocardial ischemia. There is a need for systematic information and educational activities promoting a healthy lifestyle with the elimination of modifiable risk factors for cardiovascular diseases.

Clinical features of coronary artery disease and 5-year survival of patients after myocardial infarction against the background of depressive disorders

Aim. To assess the features of the clinical picture of coronary artery disease (CAD) and the prognosis of patients with myocardial infarction with depressive disorder (DD).
 Materials and methods. We examined 101 patients with stable CAD who had myocardial infarction more than six months ago: 67 CAD patients with depression (Group 1) and 34 CAD patients without depression (Group 2). The clinical picture of CAD was assessed by complaints, angina self-monitoring diaries, and exercise tests. The presence and severity of DD was determined using psychometric scales: BDI (Beck Depression Scale), HADS (Hospital Anxiety and Depression Scale) and the opinion of a psychiatrist. Five-year survival information was obtained through telephone interviews with patients and their relatives.
 Results. In patients with CAD and DD in comparison with patients without DD self-monitoring diaries revealed more frequent angina attacks: 9 [6; 12] vs 6 [4; 7] per week (p=0.0001), the greater need for sublingual nitrates: 2 [0; 9] pills vs 0 [0; 4] pills (p=0.0001). DD significantly reduced exercise tolerance: 370 [250; 450] meters vs 435 [350; 500] meters using the six-minute walk test (p=0.04), according to the results of bicycle ergometry – 50 [25; 75] W vs 75 [50; 75] W (p=0.03). After 5 years of follow-up patients with comorbidities (CAD and DD) had a greater number of deaths: 13 (19.4%) vs 2 (5.9%), respectively, survived – 54 (80.6%) vs 32 (94.1%) (Gehan–Wilcoxon test, p=0.04).
 Conclusion. The comorbidity CAD and DD leads to a worsening of the clinical course of CAD and prognosis, which actualizes the need for verification of the diagnosis of DD and timely prescription of antidepressant therapy.

Potential role of mitochondrial dysfunction in arrhythmogenesis in coronary artery disease

Introduction. Coronary artery disease (CAD) continues to be the most common pathology in the structure of cardiovascular diseases over the past decades, both in Russia and around the world. In the normal condition, the mitochondria of all body cells have the same function capabilities due to the carriage of the same genome. Therefore, it is possible to assess the respiration activity of cardiomyocyte mitochondria by the respiration of mitochondria from peripheral blood leukocytes.Aim: To compare respiratory activity of mitochondria of peripheral blood leukocytes in patients diagnosed with coronary artery disease and coronary artery disease with developed cardiac rhythm disorders (CRD).Material and methods. The studied groups included 45 patients with CAD without CRD and 39 patients with CAD complicated by CRD. Mitochondria were isolated from peripheral blood leukocytes by differential centrifugation. The rate of oxygen loss in pyruvate-malate and succinate incubation buffers was measured when isolated mitochondria were introduced, as well as when palmitic acid was added to the medium. Oxygen consumption rate for the V3 (active phosphorylating) and V4 (nonphosphorylating) metabolic sates was determined, and on their basis respiratory control coefficient was calculating using the formula V3/V4. Statistical data processing was carried out using STATISTICA 13.0 software.Results. Oxygen consumption rate in mitochondria of patients with uncomplicated CAD and CAD with CRD had no significant differences in either pyruvate-malate or succinate buffers. When palmitic acid was added to the incubation medium, the mitochondria of CAD patients without CRD significantly increased oxygen consumption rate in both incubation media. Mitochondria of CAD patients with CRD did not change oxygen consumption rate in both metabolic states after the addition of palmitic acid in incubation media.Conclusion. On the basis of the data obtained, it can be concluded that the function capabilities of mitochondria in the complicated course of CAD has been exhausted, which manifests itself in the inability to increase ATP synthesis in response to the introduction of additional substrates.

Percutaneous coronary intervention in patients admitted with acute coronary syndrome within 6 months after COVID-19 (retrospective single-center study)

BACKGROUND: Assessing clinical manifestations in patients during the period of destabilization of the course of coronary artery disease after COVID-19 coronavirus infection remains a clinical problem. Identifying features of coronary artery lesions in such patients will help to prevent the development of complications and may influence the tactics of active dynamic monitoring.
 AIM: To evaluate the structure of coronary artery lesions and clinical manifestations in patients with acute coronary syndrome that developed within 6 months after COVID-19 new coronavirus infection.
 MATERIALS AND METHODS: A comparative analysis of the results of coronary artery stenting in 157 patients admitted with acute coronary syndrome has been carried out. The 1st group included 69 patients who had COVID-19 (vaccinated — 24.6%) during the 6 months preceding acute coronary syndrome; in the 2nd — 88 patients without a history of COVID-19 (vaccinated — 42%). All the patients had drug-eluting stents implanted in the infarct-related artery. Long-term results have been observed in 151 (96.2%) patients.
 RESULTS: Before the development of acute coronary syndrome, dispnoe was more often observed in patients of the 1st group (36; 52%) than in patients of the 2nd group (13; 14.8%). There were no focal neurological symptoms in the patients of both groups. Dizziness more often preceded acute coronary syndrome in the patients of the 1st group (26; 38.2%) compared to the control group (5; 5.7%). Decreased motivation and fatigue were detected in 27 (67.5%) patients in the 1st group, which was more common than in the 2nd group (13; 32.5%). Acute coronary syndrome with ST elevation was treated in 47 % and 38.6% of the patients in the 1st groups and the 2nd, respectively. The development of acute coronary syndrome with ST segment elevation with previous clinical manifestations of post-covid syndrome in the 1st group was observed in 95.8%, whereas in the absence of post-covid syndrome in 53.3%. The mean value of LVEF in patients who had COVID-19 was 55.9 ± 14%, which was significantly lower than in the patients in the control group (63.2 ± 5.5%; р 0.001). During the course of coronavirus infection in the patients in the first group, lung damage of degrees I–II according to CT scan data was observed in 76.8% of the patients and in 23.2% of degrees III–IV. The frequency of lesions of the circumflex branch in the 1st group was 15.9%, in the 2nd — 11.4% (р = 0.403); of the right coronary artery — 33.3%, and 22.7% (р = 0.41); of the diagonal branch — 5.8%, and 3.4% (р = 0.47); of the left main coronary artery — 5.8%, and 6.8% (р = 0.79), of the left anterior descending branch — 52.2%, and 35.2% (р = 0.033), respectively. The incidence of vasospastic angina in the 1st group was 53.6%, in the 2nd — 15.9% (р 0.0001). ST segment elevation in lead AVR as a manifestation of subendocardial ischemia was registered in the 1st group — 40.6%, the 2nd — 11.4% (р 0.0001). All the patients had drug-eluting stents implanted in the infarct-related artery. Overall survival (in-hospital and long-term) was 100% for the first group and 100 % for the second one.
 CONCLUSIONS: In the structure of coronary arteries lesions after COVID-19 new coronavirus infection in patients with acute coronary syndrome, damage to the anterior interventricular artery dominates (52.2%). The likelihood of having a left anterior descending lesion during the development of acute coronary syndrome with ST segment elevation in patients who have had COVID-19 is 1.5 times higher. The structure of clinical manifestations after COVID-19 in patients before the development of acute coronary syndrome is dominated by shortness of breath (52 %) and decreased motivation and fatigue (67.5 %).

ПРЕДИКТОРЫ ГОСПИТАЛЬНЫХ ОСЛОЖНЕНИЙ И ДЛИТЕЛЬНОЙ ГОСПИТАЛИЗАЦИИ У ПАЦИЕНТОВ, ПЕРЕНЕСШИХ КОРОНАРНОЕ ШУНТИРОВАНИЕ: РОЛЬ СВОБОДНЫХ ЖИРНЫХ КИСЛОТ И ИНДЕКСОВ ИНСУЛИНОРЕЗИСТЕНТНОСТИ

Introduction. Often, carbohydrate metabolism disorders (type 2 diabetes mellitus, prediabetes) are detected in patients with severe coronary heart disease who are preparing for elective coronary bypass surgery. Insulin resistance can occur even in the absence of manifest disorders of carbohydrate metabolism and have its own influence on the course of coronary artery disease. With regard to the prognosis of coronary artery bypass grafting, the role of insulin resistance is not clearly defined, there are isolated reports on the relationship between the estimated indices of insulin resistance and free fatty acids and the number of postoperative complications of CABG Purpose of the study. To study the effect of carbohydrate metabolism disorders and insulin resistance indicators on the immediate results of coronary bypass grafting (CABG). Materials and methods. 383 consecutive patients who underwent CABG in 2011-2012 at the Research Institute of the KPSSZ were included, free fatty acids and fasting insulin in plasma were determined in all patients, insulin resistance indices HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), QUICKI (Quantitative Insulin Sensitivity Chek) were calculated Index) and Revised-QUICKI, McAuley. A logistic regression analysis was performed to identify predictors of the composite endpoint of hospital stay after CABG >10 days or significant complication. Perioperative characteristics were analyzed in two cohort groups: group 1 - patients with a combined endpoint (CCT>10 days), n=291, and group 2 (n=92) without CCT. Results. In the CCT group, the median age was higher, and the proportion of women was 30% versus 14.1% (p=0.003). Patients of the 1st group (with CCT) had a higher percentage of type 2 diabetes mellitus (37.5% versus 17.4%, p<0.001, more people with obesity (p<0.001) and a higher percentage of combined operations (p =0.007) In group 1 (with CCT), the median of glucose (p=0.031), glycated hemoglobin HbA1c (p=0.009), free fatty acids (p=0.007) and Revised-QUICKI (p=0.020) was higher than In a binary regression, the predictors of the combined endpoint (significant complications or hospital stay after CABG >10 days) were female gender, age, left atrial size, and free fatty acids before surgery (p<0.001). per 1 mmol l, the probability of the endpoint increased by 255.9%, and with an increase in LA by 1 cm - by 219.5%, each year of age added 6.9% to the probability of the index event.For this model, the statistical significance was χ2 (2 ) = 38.337, p<0.001 The Nagelkerke R2 value was 0.336 (explaining 33.6% of the combined variance of the results) and the model correctly classified 78.5% of the cases. At the same time, fasting glucose, insulin, lipid levels, HOMA, QUICKI, Revised-QUICKI, McAuley indices did not show their relationship with the studied outcome. Conclusions: In the group with a complicated postoperative period of CABG, there were significantly more women, patients with DM 2, and obese individuals, there was a higher median of free fatty acids and the Revised-QUICKI index. Free fatty acids and type 2 diabetes mellitus were independent predictors of hospital complications or length of stay after CABG.

The influence of hypothyroidism on the course of coronary artery disease in patients with reduced left ventricular ejection fraction

Background. Thyroid hormones play a fundamental role in the homeostasis of the cardiovascular system. Cardiovascular diseases are among the most common diseases worldwide, causing a significant percentage of mortality, hospitalizations, and disability. The purpose of the study is to evaluate the impact of hypothyroidism on the course of atherosclerotic lesions of coronary arteries and major cardiovascular events in patients with heart failure with reduced left ventricular ejection fraction after myocardial revascularization using percutaneous coronary intervention (PCI). Materials and methods. This prospective observational one-center study included 103 patients with ischemic cardiomyopathy, heart failure with reduced left ventricular ejection fraction, with and without hypothyroidism who underwent PCI. The result of revascularization was evaluated within 2 years. Inclusion criteria: age over 18 years, coronary artery disease, left ventricular ejection fraction less than 40%. Results. Patients with hypothyroidism had a worse lipid profile and, as expected, a higher baseline thyroid-stimulating hormone (TSH). According to echocardiography, patients with hypothyroidism had thickening of the left ventricular myocardium walls, which is indicated by a probable increase in the dimensions of the left ventricular posterior wall (11.40±0.98 mm; p<0.001). In the first group, patients had higher myocardial mass indicators as one of the criteria for left ventricular hypertrophy (172.73±12.72g/m2; p<0.001). After multivariate analysis using Cox proportional hazards regression, an elevated TSH level was still associated with significantly higher rates of cardiovascular mortality (risk ratio (RR) 0.85; 95% confidence interval (CI) 0.75–0.95; p<0.001), repeat PCI (RR 0.75; 95% CI 0.65–0.85; p<0.05) and decompensation due to heart failure (RR 0.88; 95% CI 0.78–0.96; p<0.05). Conclusions. Hypothyroidism is associated with a higher incidence of the primary composite endpoint of repeat PCI, hospitalizations for decompensated heart failure, and the secondary endpoint of cardiovascular mortality compared to euthyroid patients over two years of follow-up. Maintaining adequate control of TSH in patients with coronary artery disease and heart failure with reduced ejection fraction is prognostically important for preventing cardiovascular events.

Causes and risk factors for stent restenosis in patients after percutaneous coronary interventions

Percutaneous coronary intervention (PCI) is one of the main components in the treatment of the coronary artery disease (CAD) and especially its acute forms. Nevertheless, restenosis of stented coronary arteries, which significantly worsens the course of CAD, remains a significant clinical problem of this technology. Prevention of this complication requires a modern understanding of the complex pathogenetic mechanisms of restenosis. Based on the literature data, the frequency of restenosis development in stents with medical coatings is in the range from 3 to 20 %. The mechanism of restenosis is multifactorial and includes biological, mechanical, and genetic factors. The main mechanical causes are insufficient expansion of the stent or its destruction, and biological factors include local inflammation, leading to aggressive neointimal proliferation and late neoatherosclerosis. The search for genetic factors and possibilities of influence on the development of this complication is still ongoing. Intracoronary imaging is crucial for identifying mechanisms of restenosis and selecting individual therapy.

Coronary artery disease in a patient with Addison’s disease: a case report and literature review

BackgroundAddison’s disease which is due to dysfunction of the adrenal gland, with abnormal secretion of glucocorticoids and mineralocorticoids, is rare. By inducing inflammation and disorders of water and electrolyte metabolism, Addison’s disease may accelerate progression of co-existed cardiovascular diseases. Addison’s disease combined with cardiovascular disease is infrequent, only 10 cases in the literature.Case presentationWe reported a 51-year-old male patient with unstable angina pectoris and hypotension. Changes on coronary angiography within 2 years suggested rapid progression of coronary artery disease in a patient with low cardiovascular risk. An additional clue of skin hyperpigmentation, fatigue and further examination confirmed the diagnosis of Addison’s disease caused by adrenal tuberculosis. After hormone replacement treatment, the frequency and severity of the angina pectoris were alleviated significantly, as were hypotension, hyperpigmentation and fatigue.ConclusionsThe combination of Addison’s disease and coronary artery disease in one patient is rare. Addison’s disease can induce inflammation and disorders of water and electrolyte metabolism, which may further accelerate the course of coronary artery disease. Meanwhile, the hypotension in Addison’s disease may affect the coronary blood flow, which may result in an increased susceptibility to unstable angina in the presence of coronary stenosis. So, we should analyze comprehensively if the coronary artery disease progress rapidly.

How to Unmask Hidden Cardiovascular Diseases through Preparticipation Screening in Master Athletes?

Cardiovascular disease (CVD) is the most common cause of death globally in general population. Sport activity is an effective and recommended non-pharmacological method of CVD prevention. Presently, the group of people practicing sport regularly is constantly growing due to increasing awareness of its health benefits. However, vigorous-intensity exercises can reveal previously undetected disease. Master athletes over 35 years old are particularly exposed to sudden cardiac death (SCD) mainly in the course of coronary artery disease (CAD). Another common disease in veteran athletes is hypertension. It is known that regular endurance training can lower blood pressure at rest, so arterial hypertension in athletes is usually masked by adaptation to effort. Despite of normal or high-normal blood pressure in the office, the values during exercises and in ambulatory blood pressure monitoring (ABPM) can exceed the norm. Hidden hypertension have the same negative impact on cardiovascular system. It increases the risk of (1) atherosclerosis and therefore myocardial infarction or stroke, (2) left ventricular hypertrophy with diastolic and/or systolic heart failure, myocardial fibrosis and ventricular arrhythmias, (3) left atrial enlargement increasing the risk of atrial fibrillation and stroke and (4) aortic dilation/dissection. Through these complications hypertension can lead to SCD during sport activities, therefore it is important to recognize this disease early and start a proper treatment. To enable safe participation in sports competition detailed guidelines for screening were created, but they mainly concern CAD. We propose an additional scheme of screening in master athletes including the detection of hidden hypertension to prevent its consequences.

The effectiveness of cytoprotection in the treatment of stable angina in patients with arterial hypertension and hyperuricemia, taking into account the peculiarities of the course of coronary artery disease in wartime

The aim of the study is to establish the effectiveness of treatment of severe angina pectoris in patients with hyperuricemia, taking into consideration the peculiarities of the course of coronary artery disease (CAD) in wartime, using ranolazine – a selective inhibitor of the late sodium flow in combined pharmacotherapy.
 Materials and methods. We studied the anti-anginal effect of ranolazine in 14 patients with CAD, stable angina pectoris III-IV functional class (FC), hyperuricemia and arterial hypertension (AH) during 6 months of the 2022 year. The effectiveness of the study drug on the clinical course of angina pectoris was assessed by questionnaire and clinical examination after three months of treatment.
 The results. At the end of the second week of ranolazine use, angina attacks at rest, which were registered before the start of the observation, stopped in all patients with angina pectoris III FC and 50 % with angina pectoris IV FC. In 78.6 %, the number of angina attacks and the use of nitrates decreased by more than 2 times; 21.4 % no longer had angina attacks.
 At the end of the first month, anginal attacks were not observed in all patients with angina pectoris III FC and 50 % with angina pectoris FC IV. In 2 patients with angina pectoris IV FC (50 %), anginal attacks continued to be registered during physical exertion and emotional stress, but no more than once a week. At the same time, there were no angina attacks at rest. The same results were obtained during the survey of patients at the end of three months of observation.
 Conclusions. Ranolazine is an effective component of anti-anginal therapy, significantly affecting the patient's quality of life. Therefore, we can recommend ranolazine for patients with hyperuricemia in angina attacks that persist with insufficient effectiveness of zasic therapy with first-line drugs, especially during military conflicts

The effect of depressive disorder on the clinical presentation of coronary artery disease and five-year survival of patients after myocardial infarction

Aim. To assess the effect of depressive disorder (DD) on the clinical presentation of coronary artery disease (CAD) and five-year survival rate of patients with chronic CAD.Materials and methods. The study included 79 patients with functional class II–III exertional angina who experienced myocardial infarction more than 6 months before. The patients were divided into two groups: group 1 (n = 45) consisted of patients with CAD and depression and group 2 (n = 34) encompassed patients with CAD without depression. The clinical presentation of CAD was assessed by the results of filling out the angina pectoris self-control diary and exertion tests. The presence and severity of DD were determined using psychometric scales, such as Hospital Anxiety and Depression Scale (HADS) and Beck Depression Inventory (BDI), and verified by the psychiatrist. Information about five-year survival was obtained via telephone interviews with the patients and their relatives.Results. Patients with CAD and DD were characterized by more frequent episodes of angina pectoris during a week (10 [8; 14] vs 6 [4; 7], p = 0.000004), an increased demand for nitroglycerin (4 [0; 10] tablets vs 0 [0; 4] tablets, p = 0.001), and lower exercise tolerance (50 [25; 75] W vs 75 [50; 75] W (p = 0.06), 350 [250; 400] meters vs 435 [350; 500] meters (p = 0.01) than CAD patients without DD. The five-year survival rate was significantly lower in group 1 than in group 2 (69 [62; 72] vs 71 [68; 72] months (p = 0.04)), 35 (77.8%) vs 32 (94.1%) patients survived. In group 1, a greater number of deaths from cardiovascular accidents (10 (22.2%) vs 2 (5.9%)) was noted (log-rank test, p = 0.03).Conclusion. In patients with CAD, associated depression results in aggravation of the clinical course of CAD and poor disease prognosis, which requires timely diagnosis and treatment of DD.

Elevated level of von Willebrand factor as an additional risk factor for cardiovascular events in patients with early coronary atherosclerosis

Background. One of the urgent problem of modern cardiology is the search for markers to assess the risk of CV (cardiovascular) events in patients with CAD.Objective. To evaluate the level of von Willebrand factor (vWF) in the blood plasma of patients with early onset of CAD and the study of the relationship between vWF hyperproduction and the risk of recurrent CV events.Design and methods. We examined 80 patients who underwent acute myocardial infarction and/or surgical treatment of CAD in the amount of percutaneous coronary intervention or coronary artery bypass surgery at the age of up to 55 years (men) and up to 60 years (women).Results. The following predictors of an unfavorable course of coronary artery disease in the examined patients were identified: an increased level of vWF, a higher BMI, and hypoalphacholesterolemia at the inclusion in the study. Among patients with normal vWF, no adverse CV events were recorded after 2 years of observation. A number of factors included in the prognostic model for the development of a recurrent CV event were identified: vWF level, age, BMI, hyperglycemia, and carotid atherosclerosis. Model demonstrated 92.5 % agreement between the forecast and the observation.Conclusions. Elevated plasma vWF levels may serve as an additional risk factor for the development of recurrent CV events in patients with early manifestations of CAD.

Anatomic and Hemodynamic Plaque Characteristics for Subsequent Coronary Events.

ObjectivesWhile coronary computed tomography angiography (CCTA) enables the evaluation of anatomic and hemodynamic plaque characteristics of coronary artery disease (CAD), the clinical roles of these characteristics are not clear. We sought to evaluate the prognostic implications of CCTA-derived anatomic and hemodynamic plaque characteristics in the prediction of subsequent coronary events.MethodsThe study cohort consisted of 158 patients who underwent CCTA with suspected CAD within 6–36 months before percutaneous coronary intervention (PCI) for acute myocardial infarction (MI) or unstable angina and age-/sex-matched 62 patients without PCI as the control group. Preexisting high-risk plaque characteristics (HRPCs: low attenuation plaque, positive remodeling, napkin-ring sign, spotty calcification, minimal luminal area <4 mm2, or plaque burden ≥70%) and hemodynamic parameters (per-vessel fractional flow reserve [FFRCT], per-lesion ΔFFRCT, and percent ischemic myocardial mass) were analyzed from prior CCTA. The primary outcome was a subsequent coronary event, which was defined as a composite of vessel-specific MI or revascularization for unstable angina. The prognostic impact of clinical risk factors, HRPCs, and hemodynamic parameters were compared between vessels with (160 vessels) and without subsequent coronary events (329 vessels).ResultsVessels with a subsequent coronary event had higher number of HRPCs (2.6 ± 1.4 vs. 2.3 ± 1.4, P = 0.012), lower FFRCT (0.76 ± 0.13 vs. 0.82 ± 0.11, P < 0.001), higher ΔFFRCT (0.14 ± 0.12 vs. 0.09 ± 0.08, P < 0.001), and higher percent ischemic myocardial mass (29.0 ± 18.5 vs. 26.0 ± 18.4, P = 0.022) than those without a subsequent coronary event. Compared with clinical risk factors, HRPCs and hemodynamic parameters showed higher discriminant abilities for subsequent coronary events with ΔFFRCT being the most powerful predictor. HRPCs showed additive discriminant ability to clinical risk factors (c-index 0.620 vs. 0.558, P = 0.027), and hemodynamic parameters further increased discriminant ability (c-index 0.698 vs. 0.620, P = 0.001) and reclassification abilities (NRI 0.460, IDI 0.061, P < 0.001 for all) for subsequent coronary events. Among vessels with negative FFRCT (>0.80), adding HRPCs into clinical risk factors significantly increased discriminant and reclassification abilities for subsequent coronary events (c-index 0.687 vs. 0.576, P = 0.005; NRI 0.412, P = 0.002; IDI 0.064, P = 0.001) but not for vessels with positive FFRCT (≤0.80).ConclusionIn predicting subsequent coronary events, both HRPCs and hemodynamic parameters by CCTA allow better prediction of subsequent coronary events than clinical risk factors. HRPCs provide more incremental predictability than clinical risk factors alone among vessels with negative FFRCT but not among vessels with positive FFRCT.Clinical Trial RegistrationPreDiction and Validation of Clinical CoursE of Coronary Artery DiSease With CT-Derived Non-INvasive HemodYnamic Phenotyping and Plaque Characterization (DESTINY Study), NCT04794868.

Paraoxonase 2 C311S single nucleotide polymorphism is associated with type C lesions in coronary atherosclerosis

BackgroundParaoxonases (PON) 1–3 are lactonases with antioxidant and atheroprotective properties. The best known single nucleotide polymorphisms (SNPs) within the PON family, include: Q192R (rs662), L55M (rs854560) in the PON1 gene and C311S (rs7493) in the PON2 gene. Their influence on the occurrence and course of coronary artery disease (CAD) is unclear. The aim of this study was to assess the association between the most common PON1 and PON2 genetic variants with the presence of CAD, as well as their relation to coronary lesion complexity in accordance with the ACC/AHA standard. MethodsWe included 1027 individuals: 367 CAD patients qualified for coronary angiography and 660 healthy volunteers as controls. We extracted DNA from circulating blood leukocytes, amplified the PON1 and PON2 genetic sequence and used restriction enzymes to identify the SNPs. Patients with CAD underwent coronary angiography and were assigned to two groups based on lesion severity: patients with at least one type C lesion and without a type C lesion. The former where categorized into those with a significant narrowing (≥50% diameter stenosis) and those without one. ResultsWe found no association between the analyzed SNPs and symptomatic CAD. However, in patients with diagnosed CAD, the PON311S allele was independently associated with the risk of the most complex type C coronary lesion occurrence. ConclusionsOur study is the first report of an association between PON2 311S SNP and the type of coronary atherosclerotic lesions in humans.

Gastrointestinal Incretins-Glucose-Dependent Insulinotropic Polypeptide (GIP) and Glucagon-like Peptide-1 (GLP-1) beyond Pleiotropic Physiological Effects Are Involved in Pathophysiology of Atherosclerosis and Coronary Artery Disease-State of the Art.

Simple SummaryThe presented manuscript contains the most current and extensive summary of the role of the most predominant gastrointestinal hormones—GIP and GLP-1 in the pathophysiology of atherosclerosis and coronary artery disease both in animals and humans. We have described GIP and GLP-1 as (1) expressed in many human tissues, (2) emphasized relationship between GIP and GLP-1 and inflammation, (3) highlighted importance of GIP and GLP-1-dependent pathways in atherosclerosis and coronary artery disease and (4) proved that GIP and GLP-1 could be used as markers of incidence, clinical course and recurrence of coronary artery disease, and related to extent and severity of atherosclerosis and myocardial ischemia. Our initial review may state a cornerstone for the future, however, there are still many unknowns and understatements on this topic. Due to the widespread growing interest for the potential use of incretins in cardiovascular diseases, we think that further research in this direction is desirable. For the future, we would like to recognize GIP and GLP-1 as widely implemented into clinical practice as new biomarkers of atherosclerosis and coronary artery disease. Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications.

Prediction of clinical course in patients with diffuse coronary artery disease after coronary bypass surgery

Aim. To determine the incidence, predictors and develop a model for long-term risk stratification of ischemic events in patients with coronary artery disease after coronary bypass surgery.Material and methods. This retrospective study of the clinical course in patients with diffuse coronary artery disease (CAD) after coronary endarterectomy and bypass grafting surgery. A total of 232 patients were included, while long-term outcomes were assessed in 202 patients. Among them, complete data on clinical status were obtained from survivors (n=191). The median follow-up was 60 (interquartile range, 42; 74) months, while the minimum follow-up — 12 months, the maximum was 96 months. The primary composite endpoint reflecting the unfavorable course of CAD included coronary ischemic events (recurrent angina, myocardial infarction, repeat revascularization), while secondary endpoint — allcause mortality. The factors influencing the development of primary and secondary endpoints were studied.Results. An unfavorable CAD course was diagnosed in 39 patients (20,4%), while 11 deaths were recorded (5,4%). Univariate analysis demonstrated a significant role of prior myocardial infarction in the increase in mortality rate (p=0,029). Among the factors influencing the CAD course, no significant differences were obtained for any of them. A multivariate analysis was performed to identify a high-risk group for an unfavorable course of diffuse CAD. Independent predictors were identified, the most significant contribution of which was made by multifocal atherosclerosis (odds ratio (OR)=1,99, 95% confidence interval (CI), 0,93-4,21, p=0,072), low adherence to secondary prevention measures (OR=2,21, 95% CI, 0,86-6,89, p=0,128) and diabetes (OR=1,73, 95% CI, 0,79-3,72, p=0,162). Using the results obtained, a prognostic model with high specificity (64%) and moderate sensitivity (53%) was created.Conclusion. The highest probability of an unfavorable long-term course of diffuse CAD was noted in patients with diabetes, multifocal atherosclerosis, and low adherence to secondary prevention measures. The obtained results make it possible to identify a high-risk group in this cohort of patients, determine the reserve of secondary prevention measures and a direction of actions to improve outcomes.

Serial Changes in Exercise Capacity, NT-proBNP, and Adiponectin in Patients with Acute Coronary Syndrome before and after Phase II Rehabilitation as well as at the 12-Month Follow-Up.

Background Acute coronary syndrome (ACS) causes pathophysiological changes in exercise capacity, N-terminal part of pro-brain natriuretic peptide (NT-proBNP), and adiponectin that impact the course of coronary artery disease and clinical outcomes after cardiac rehabilitation (CR). However, the serial changes and the relationship between the changes in these parameters for a prolonged term remain uninvestigated. Methods Eighty-one patients with ACS underwent a three- or four-week CR program after acute care and were followed up for 12 months. Exercise capacity on a cycle ergometer and blood levels of NT-proBNP and adiponectin were determined before and after CR as well as at the 12-month follow-up. Results Exercise capacity increased from 100 watts (in median) before CR to 138 watts after CR and 150 watts at 12 months. The NT-proBNP level (526 pg/ml before CR) remained almost unchanged after CR (557 pg/ml) and then decreased at 12 months (173 pg/ml). The adiponectin level (14.5 µg/ml before CR) increased after CR (16.0 µg/ml) and at 12 months (17.2 µg/ml). There was no significant correlation among the changes in these parameters at each observation time point. Conclusion During the observation period from before CR to the 12-month follow-up, exercise capacity, NT-proBNP, and adiponectin underwent significant changes; however, these changes were independent from each other and not correlated linearly, and they provide complementary information in clinical practice. Thus, all these parameters should be included and determined at different time points for a prolonged period of time.

ЧАСТОТА ИШЕМИЧЕСКОЙ БОЛЕЗНИ СЕРДЦА НА ФОНЕ РЕЗИСТЕНТНОЙ АРТЕРИАЛЬНОЙ ГИПЕРТОНИИ У ПАЦИЕНТОВ МОЛОДОГО И СРЕДНЕГО ВОЗРАСТОВ

Objective: To establish the frequency of different forms of coronary artery disease (CAD) in patients with resistant arterial hypertension (AH). Methods: Based on the data from clinical and anamnestic studies and the results of electrocardiography (ECG), Holter ECG monitoring (HM-ECG), and bicycle ergometry (VEM), 370 young and middle-aged patients (WHO, 1965), the mean age 54.1±4, with primary AH were diagnosed with CAD according to the Canadian classification (World Health Organization (WHO), 1979; with additions by All-Union Cardiology Research Centre, 1995). With daily monitoring of blood pressure (BP) against the background of antihypertensive therapy (AHT), groups of patients with controlled (CAH; n=84) and resistant (RAH; n=286) arterial hypertension were identified. Results: It was found that in young and middle-aged patients with both CAH and RAH, the frequency of stable angina pectoris (SA) was the highest, mainly due to functional classes (FC) I-II; severe functional classes of SA, and unstable angina (UA) were markedly less frequent; less than a quarter of patients had a myocardial infarction (MI), mainly due to non-Q-wave MI (non-Q-MI). In patients with CAH and RAH FC I-II of SA were predominant (in 70.2% of patients with CAH and 34.3% with RAH; p=0.0001), while FC III-IV of SA were mainly observed against the background of RAH (21% vs. 5% in patients with CAH, p=0.0015). In patients of young and middle age, against the background of RAH, the frequency of UA (18.9%; p=0.0220) and the total number of MI (25.9%; p=0.0482) was higher, than in CAH, mainly due to Q-MI (11.2%; p=0.0360), indicating the severity of coronary insufficiency. The increase in non-Q-MI against the background of RAH was statistically insignificant (p=0.5191). Conclusion: The ratio of the frequency of different forms of CAD against the background of CAH and RAH was unidirectional. However, the overall frequency of severe forms of CAD (UA and MI, especially Q-MI) in patients with RAH significantly exceeded those in patients with CAH, which allowed us to consider RAH as a factor in the progressive course of CAD. Keywords: Coronary artery disease, stable angina, unstable angina, myocardial infarction, resistant arterial hypertension, young and middle age.

The impact of concomitant anemic syndrome on the clinical course of coronary artery disease

The presence of comorbid pathology negatively affects the prognosis of patients with coronary artery disease (CAD). Today it is important to clarify the features of CAD on the background of concomitant anemia and identify the main risk factors for complications to improve the tactics of this category of patients. The aim. To investigate the influence of concomitant anemic syndrome on the clinical course of coronary artery disease, frequency and features of the main cardiovascular events. Materials and methods. The study involved 91 patients with coronary artery disease (42 men and 49 women, age – 70 (49; 93)). All patients were divided into 2 groups: the main group (n = 46) consisted of patients with coronary artery disease with iron-deficiency anemia, the comparison group (n = 45) – patients with coronary artery disease without iron-deficiency anemia. The study of the main cardiovascular events took into account re-hospitalization due to arrhythmic disorders, progression of heart failure (HF), CAD destabilization within the observed period (1 year), as well as death from cardiovascular causes. The data analysis was performed using Statistica 13.0. Results. During the year, 42 non-fatal cardiovascular events were noted in patients of both groups, however in the main group their total number was 30 (67 %) versus 12 (27 %) in the comparison group (χ2 = 13.603; P &lt; 0.05). The presence of concomitant anemia in CAD patients significantly increased the relative risk of re-hospitalizations (RR = 1.9; 95 % CI 1.230–3.112; P &lt; 0.05). Among the reasons for hospitalization in the main group, HF decompensation prevailed – 17 (57 %) patients, unstable angina – 7 (23 %), arrhythmic disorders – 6 (20 %); in the comparison group, among the reasons for re-hospitalization, 7 (57 %) had HF decompensation, 3 (25 %) had unstable angina, and 2 (17 %) cases had arrhythmic disorders. In total, 9 (19.5 %) deaths were recorded in the main group, while in the comparison group 1 (2.2 %) death was recorded during the year (χ2 = 6.995; P &lt; 0.05). The presence of concomitant anemia in patients with CAD increases the risk of fatal outcome by 8.8 times (RR = 8.8; 95 % CI 1.162–66.685; P &lt; 0.05). The presence of moderate anemia in patients with CAD significantly increases the incidence of combined critical events by 39 % during the year of follow-up compared with mild anemia (χ2 = 12.843; P &lt; 0.05). Conclusions. The presence of concomitant anemia is associated with a worsened prognosis for patients having coronary artery disease due to an increased risk of non-fatal cardiovascular events that require re-hospitalization during the year of observation, and an increased incidence of death. Increasing severity of anemia is associated with an increase in the frequency of the combined critical event during 1 year of follow-up.