Severity Of Coronary Artery Atherosclerosis Research Articles

Serum levels of neuregulin-1 in patients with coronary artery disease: clinical and pathogenetic aspects

Aim. To determine the relationship between the serum level of neu-regulin-1 (NRG-1) and the severity of coronary artery (CA) atherosclerosis and clinical and paraclinical characteristics of patients with coronary artery disease (CAD).Material and methods. The study included 264 people, of which 220 were patients diagnosed with coronary CAD. The patients underwent coronary angiography using the Synergy between Percutaneous Coronary Intervention with TAXUS and Cardiac Surgery (SYNTAX) score and echocardiography. The patients were divided into groups according to SYNTAX score: group 1 — with moderate CA atherosclerosis (≤22 (n=124); group 2 — with severe CA atherosclerosis (23-32) (n=53); group 3 — with extremely severe CA atherosclerosis (≥33) (n=43). Group 4 was represented by healthy volunteers (n=44). All subjects underwent a study of the serum NRG-1 (ng/ml) level. Statistical processing of the results was carried out using Statistica 10.0 software. Differences were considered significant at p<0,05.Results. Significantly higher NRG-1 values were obtained in the control group compared to patients with CAD (p<0,001). An inverse correlation was found between the NRG-1 concentration and the severity of CA atherosclerosis (p<0,001). A decrease in NRG-1 concentration is associated with a high functional class of = heart failure (p<0,01) and low left ventricular ejection fraction (p<0,001). The significance of NRG-1 differences between groups of patients with a history of myocardial infarction (p<0,001), angina pectoris (p<0,01), permanent atrial fibrillation (p<0,01), chronic left ventricular aneurysm (p<0,01) and repeated myocardial infarction (p<0,05) in comparison with patients without these pathologies.Conclusion. The identified correlations between the NRG-1 concentration and CAD, as well as the clinical and paraclinical characteristics of patients, makes it possible to consider NRG-1 as a reliable biomarker of CA and heart failure severity and may form the basis for the development of novel diagnostic approaches.

ВЗАИМОСВЯЗЬ УРОВНЯ ПРОВОСПАЛИТЕЛЬНЫХ АДИПОЦИТОКИНОВ И ОБЪЕМНО-ЛИНЕЙНЫХ ПАРАМЕТРОВ ЭКТОПИЧЕСКИХ ЖИРОВОГО ДЕПО У БОЛЬНЫХ С ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА

Abstract. Introduction. Multispiral computed angiography of the coronary arteries is the method of choice for the early noninvasive diagnosis of coronary atherosclerosis and, therefore, coronary heart disease. Quantitative indicators of epicardial fat depot are significantly associated with coronary atherosclerosis and coupled with possible cardiovascular events without reference to traditional risk factors. Aim of this study was to establish the relationship between the proinflammatory adipocytokine levels and the volumetric-linear parameters of paracardial fat depots in patients with coronary atherosclerosis. Materials and Methods. 135 patients (74 men (52%) and 61 women (48%)) with confirmed and suspected coronary heart disease were examined, aged 45 to 80 years. All patients were divided into 2 groups: Study group and comparison group. The study group consisted of 88 patients with coronary atherosclerosis, 56 men (63%) and 32 women (37%). This group included patients with one-, two- and multivessel coronary artery lesions, as well as with hemodynamically insignificant (CAD-RADs≤2) and significant (CAD-RADs≥3) stenosis areas. The comparison group consisted of 47 patients without coronary atherosclerosis. Quantitative indicators of cardiac and abdominal fat depots were calculated for all patients by means of computed tomography. Results and Discussion. The volume of epicardial adipose tissue was significantly higher in individuals with coronary heart disease, as compared to patients in the comparison group. The volume of abdominal adipose tissue was also higher in patients of the main group (p<0.001). The volume of visceral adipose tissue in patients with ischemic heart disease was 1.43 times larger than in the comparison group (p<0.05), the area of epicardial adipose tissue did not statistically differ in the two groups (p˃0.05), and the area of visceral adipose tissue was 1.62 times (p<0.05) larger in patients with ischemic heart disease. Differences in the groups with hemodynamically insignificant and significant coronary artery stenoses were statistically valid (p˂0.05). Conclusions. In patients with coronary artery disease, the degree of increase in epicardial and abdominal fat correlates with the severity of coronary artery atherosclerosis. Laboratory tests of the adipokine-cytokine profiles is an important prognostic factor of coronary atherosclerosis severity.

A rare case of cardiac calcified amorphous tumor in a 34-year-old woman diagnosed at autopsy

Abstract Introduction/Objective Cardiac calcified amorphous tumor (CAT) is an uncommon, non-neoplastic heart lesion with an unknown incidence due to its rarity. Some authors have reported a female predominance of 62.5%. Many cases are associated with end-stage renal disease, diabetes mellitus and coronary artery disease. Dysfunction of calcium- phosphorus metabolism and hypercoagulability are thought to contribute to its pathogenesis. This is the first case reported from our institution. Methods/Case Report We present the case of a 34-year-old woman with a remote history of ulcerative colitis, type 1 diabetes mellitus, hypertension, Hashimoto thyroiditis, cardiomegaly, and end-stage renal disease on continuous hemodialysis. She had multiple hospitalizations for mesenteric ischemia and small bowel resections. She was admitted multiple times in 2021 for complaints of pain in bilateral thighs, shortness of breath, frequent loose stools, and abdominal pain. She was poorly compliant with hemodialysis. A chest x-ray showed severe enlargement of the cardiac silhouette. A CT angiogram of the abdomen and pelvis showed arteriosclerosis of the superior mesenteric, inferior mesenteric and celiac arteries. The patient presented to the hospital in February 2022 with continuous abdominal pain, gluteal pain, and diarrhea. Her creatinine was consistently elevated at 3.52 mg/dL. On the sixth day of admission, she was found unresponsive and was pronounced dead. Autopsy showed cardiomegaly (600 grams) with left ventricular hypertrophy, recent myocardial infarction of the posterolateral left ventricle and moderate to severe coronary artery atherosclerosis. There were lesions composed of calcified amorphous material involving the mitral valve, the endocardium and subendocardial portions of the left and right ventricles, consistent with multifocal cardiac calcified amorphous tumor. The largest lesion measured 4.0 cm. The cause of death was myocardial infarction complicating type 1 diabetes mellitus and end-stage renal disease. Results (if a Case Study enter NA) NA Conclusion CATs are usually asymptomatic but possible symptoms include dyspnea and syncope. As a result, they are often incidental findings. The calcified deposits may embolize, causing pulmonary embolism and cerebral infarction. CAT is most frequently observed in the left heart, especially on the mitral annulus; however, the right side of the heart can also be affected. End-stage renal disease is a predisposing condition, as seen in this patient.

Association of lipoprotein(a) with severity of coronary artery atherosclerosis in patients with acute coronary syndromes

Abstract Background Elevated level of lipoprotein (a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. However, the association of Lp(a) with acute coronary syndromes (ACS) has not been sufficiently studied. Purpose To evaluate the relationship between high serum levels of Lp(a) and (i) factors that play a role in the long-term development of the severity of coronary artery disease (CAD), (ii) extent of CAD amongst patients with ACS. Methods In this study we enrolled 74 consecutive patients hospitalized for ACS in tertiary cardiology center form December 2022 to January 2023. Patients characteristics were compared for patients with Lp(a) <75 nmol/L (53 patients) and ≥75 nmol/L (21 patients). Logistic regression analyses were performed to evaluate the relationship of Lp(a) with severity of CAD. Results In the studied population, the mean age of patients with high Lp(a) levels was 65 years. They were more likely to have arterial hypertension and hypercholesterolemia than those with normal Lp(a) levels (p <0.05). There were no significant differences in distribution of ACS subtype between groups. On univariate analysis, triple vessel CAD [odds ratio (OR) 4.22, 95% confidence interval (CI) 1.34-13.27, p = 0.014), and multivessel CAD (OR 3.05, 95% CI 1.06-8.81, p = 0.040) were significantly associated with abnormal Lp(a) levels. Multivariable determinants of of high Lp(a) levels were also triple vessel CAD (OR 4.19, 95% CI 1.33-13.26, p = 0.013), and multivessel CAD (OR 3.04, 95% CI 1.05-8.80, p = 0.042). Conclusions Lp(a) ≥75 nmol/L was closely associated with the extent and severity of CAD in patients with ACS.

Helicobacter pylori Seropositivity and the Severity of Coronary Artery Atherosclerosis

Background: A review of many kinds of literature has suggested the theory of infections to are a risk for atherosclerosis of the coronaries, many of medical researchers reported that Helicobacter pylori pathogenesis extends beyond the gastrointestinal system to be a risk factor for inflammatory-induced atherosclerosis including that of the coronary vessels.
 Objective: To detect a relationship between the seropositivity of Helicobacter pylori bacteria in the blood with the severity of coronary artery atherosclerosis.
 Patients and Methods: A total of 125 patients were taken in this study including both sex male and female with different age groups all of them admitted to cardiac center hospital in Erbil City in Iraq. Patients were suspected to have coronary artery atherosclerosis based on symptoms and primary cardiac diagnostic tools, Angiography was performed to confirm or exclude coronary artery lesions by catheterization in the cath lab of the hospital. Blood samples were taken from patients including the patients’ group and control group and a C-reactive protein (CRP) test with Helicobacter pylori IgG antibody test was done for them by using an Enzyme-linked immunosorbent assay (ELIZA) apparatus. Coronary angiography Confirmed the presence of atherosclerosis and the severity of it according to the number of vessels and the degree of luminal stenosis.
 Results: The results show that the most of patients with atherosclerosis (83.5%) a high level of C-reactive protein. Also, a positive significant correlation was detected between the Helicobacter pylori concentration and the number of narrowed vessels based on the results of this study Helicobacter pylori.
 Conclusion: According to the results Helicobacter pylori has a significant risk predictor for the severity of coronary atherosclerosis. However, evidence on this fact is not sufficient which further studies are needed.

Helicobacter pylori Seropositivity and the Severity of Coronary Artery Atherosclerosis

Background: A review of many kinds of literature has suggested the theory of infections to are a risk for atherosclerosis of the coronaries, many of medical researchers reported that Helicobacter pylori pathogenesis extends beyond the gastrointestinal system to be a risk factor for inflammatory-induced atherosclerosis including that of the coronary vessels. Objective: To detect a relationship between the seropositivity of Helicobacter pylori bacteria in the blood with the severity of coronary artery atherosclerosis. Patients and Methods: A total of 125 patients were taken in this study including both sex male and female with different age groups all of them admitted to cardiac center hospital in Erbil City in Iraq. Patients were suspected to have coronary artery atherosclerosis based on symptoms and primary cardiac diagnostic tools, Angiography was performed to confirm or exclude coronary artery lesions by catheterization in the cath lab of the hospital. Blood samples were taken from patients including the patients’ group and control group and a C-reactive protein (CRP) test with Helicobacter pylori IgG antibody test was done for them by using an Enzyme-linked immunosorbent assay (ELIZA) apparatus. Coronary angiography Confirmed the presence of atherosclerosis and the severity of it according to the number of vessels and the degree of luminal stenosis. Results: The results show that the most of patients with atherosclerosis (83.5%) a high level of C-reactive protein. Also, a positive significant correlation was detected between the Helicobacter pylori concentration and the number of narrowed vessels based on the results of this study Helicobacter pylori. Conclusion: According to the results Helicobacter pylori has a significant risk predictor for the severity of coronary atherosclerosis. However, evidence on this fact is not sufficient which further studies are needed.

The Association Between Common Bile Duct Diameter and the Severity of Coronary Artery Atherosclerosis, Based on Calcium Score

Objective: The aim was to assess the relationship between the coronary calcium score and the common bile duct (CBD) diameter, to determine whether the increase in CBD diameter in patients without hepatobiliary disease could represent cardiovascular disease, or the extent of atherosclerosis in coronary arteries. Materials and Methods: The study cohort consisted of 103 patients referred for computed tomographic angiography (CTA) for coronary artery assessment. None of the patients had a gallbladder, biliary, or pancreatic disease or surgery history. The Agatston score determined the rates of arterial calcification. The diameter of the CBD was measured for a sonogram. Results: There was a statistically significant relatively strong correlation between calcium score and CBD diameter ( r = 0.44, P = .001), independent of baseline variables, such as demographics and cardiovascular risk profiles. In the multivariable regression model, advanced age (beta = 0.825, P = .005), history of hypertension (beta = 0.591, P = .034), and history of coronary stenting (beta = 1.339, P = .001) were shown to be the main determinants of CBD dilatation. Conclusion: A statistically significant correlation existed between the CBD diameter and calcium score, within the coronary arteries and this could represent a shared pathophysiology between CBD dilatation and the severity of coronary atherosclerosis.

P2Y4 nucleotide receptor: A novel target for anti-inflammatory therapies to improve myocardial infarction outcome

Human P2Y4 is a UTP receptor, while in mice it is activated by both ATP and UTP. P2Y4 knockout (KO) in mice protects against myocardial infarction and leads to increased adiponectin secretion by adipocytes and lower cardiac inflammation under ischemia. The main objective is to investigate the anti-inflammatory mechanisms of cardioprotection in P2Y4 KO ischemic mice, and explore the relevance of these data in humans. We performed left anterior descending artery ligation on wild-type and P2Y4 KO mice to investigate the inflammatory state of their pericardial adipose tissue under ischemia. In parallel, in a population study comprising patients with coronary artery disease (CAD) and age-matched control individuals, we analyzed P2RY4 gene mutations and their potential association with CAD severity and fasting plasma parameters. We demonstrated that P2Y4 KO mice displayed adipocyte beiging with increased PD-L1 expression and a higher number of regulatory leukocytes in their pericardial adipose tissue after left anterior descending artery ligation, compared to wild-type mice. Interestingly, the reduction of T cell infiltration and cardiac fibrosis observed in P2Y4 KO heart was lost after injection of anti-PD-L1 blocking antibody in ischemic mice. We also identified a N178T loss-of-function mutation of the human P2Y4 receptor found less frequently in CAD patients than in control individuals. In coronary patients, carriers of the N178T variant had significantly reduced Duke jeopardy and Gensini cardiac severity scores, as well as lower resting heart rates and reduced plasma levels of N-terminal pro-brain natriuretic peptide and fasting glucose. Accordingly, P2Y4 KO mice had significantly improved glucose tolerance and insulin sensitivity compared with their wild-type littermate controls. The present study defines P2Y4 receptor as a negative regulator of PD-L1 and adiponectin, and as a potential target for anti-inflammatory therapies. The combined effect of P2Y4 loss on adipocyte beiging and regulatory leukocyte increase highlights this nucleotide receptor as an important player in post-ischemic cardiac response. We also identified a frequent loss-of-function P2Y4 variant associated with less severe coronary artery atherosclerosis and lower fasting plasma glucose in CAD patients. P2Y4 antagonists could thus have therapeutic applications in the treatment of myocardial infarction and type 2 diabetes.

Loss-of-function N178T variant of the human P2Y4 receptor is associated with decreased severity of coronary artery disease and improved glucose homeostasis.

Human P2Y4 is a UTP receptor, while in mice it is activated by both ATP and UTP. P2Y4 knockout (KO) in mice protects against myocardial infarction and is characterized by increased adiponectin secretion by adipocytes, and decreased cardiac inflammation and permeability under ischemic conditions. The relevance of these data has, however, not been explored to date in humans. In a population study comprising 50 patients with coronary artery disease (CAD) and 50 age-matched control individuals, we analyzed P2RY4 mutations and their potential association with CAD severity and fasting plasma parameters. Among the mutations identified, we focused our attention on a coding region polymorphism (rs3745601) that results in replacement of the asparagine at residue 178 with threonine (N178T) located in the second extracellular loop of the P2Y4 receptor. The N178T variant is a loss-of-function mutation of the human P2Y4 receptor and is encountered less frequently in coronary patients than in control individuals. In coronary patients, carriers of the N178T variant had significantly reduced jeopardy and Gensini cardiac severity scores, as well as lower resting heart rates and plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP). Regarding fasting plasma parameters, the N178T variant was associated with a lower concentration of glucose. Accordingly, P2Y4 KO mice had significantly improved glucose tolerance and insulin sensitivity compared with their WT littermate controls. The improvement of insulin sensitivity resulting from lack of the P2Y4 receptor was no longer observed in the absence of adiponectin. The present study identifies a frequent loss-of-function P2Y4 variant associated with less severe coronary artery atherosclerosis and lower fasting plasma glucose in coronary patients. The role of the P2Y4 receptor in glucose homeostasis was confirmed in mouse. P2Y4 antagonists could thus have therapeutic applications in the treatment of myocardial infarction and type 2 diabetes.

Trajectories and determinants of left ventricular ejection fraction after first myocardial infarction in current era of primary coronary interventions

Abstract Background Left ventricular ejection fraction (EF) is an independent predictor of adverse outcomes after myocardial infarction (MI). However, contemporary data from the PCI era of MI therapy on trajectories and determinants of EF are scarce. Purpose The present study aimed to describe the epidemiology of systolic dysfunction and EF recovery among consecutive patients hospitalized for their first MI. Methods Data from a single-centre prospectively-designed AMBITION registry of consecutive patients hospitalized for MI between years 2017 and 2021 at a large tertiary cardiology centre were utilized. Results Out of 1593 patients in the registry, 1065 were hospitalized for MI type I and had no previous history of heart failure (HF) or coronary artery disease. Revascularisation was performed in 93.5% of patients: 901 (84.6%) underwent PCI, 89 (8.4%) CABG and 6 (0.6%) both. At discharge, EF<40% was present in 238 (22.3%), EF 40–50% in 326 (30.6%) and EF >50% in 501 (47.0%), respectively. Patients with EF<40% were more often those who suffered subacute and anterior STEMI, had higher heart rate at admission and higher maximal troponin level, and more often HF signs requiring intravenous diuretic therapy (Table 1). In the multivariate Cox analysis, EF<40%, together with age, glomerular filtration rate, glycemia level, clinical signs of HF, and atrial fibrillation were associated with increased mortality risk. Among subjects with EF<40%, the control follow-up EF determined on a median 153 days (IQR 101–407) after discharge was available in 166 patients. Among these, systolic function recovered to EF>50% in 38 (22.9%) and improved to EF 40–50% in 45 (27.1%). Improvement in systolic function to EF>40% was predicted by lower severity of coronary artery atherosclerosis (GENSINI score), by higher discharge EF, by the lower leukocyte count, the absence of atrial fibrillation during MI hospitalization and glycemia level (Table 2). Recovery of systolic function was associated with lower mortality risk (log-rank p=0.012). Conclusion In the current era of primary coronary intervention, only 22% of patients after the first MI have EF below 40%. Of them, EF improves in 50%, and full recovery is observed in 23% of patients. Severity or coronary atherosclerosis, inflammatory response to MI, atrial fibrillation and glucose metabolism may all affect EF recovery. These observations provide novel therapeutic targets for EF recovery. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Ministry of Health, Czech Republic

Hypertension and clinical outcomes in patients with familial hypercholesterolemia.

Hypertension is a known risk factor for cardiovascular disease; however, its impact on clinical outcomes in patients with heterozygous familial hypercholesterolemia (HeFH) is unclear. Hence, we aimed to investigate the effects of hypertension on severity of coronary artery atherosclerosis and cardiovascular outcomes in patients with HeFH. A total of 480 patients with clinical or molecular diagnosis of definite or probable familial hypercholesterolemia according to Dutch Lipid Clinic Network criteria (DLCN score ≥6) were included in the study. They were divided into the two groups according to their blood pressure status: hypertension group and normotension group. The severity of coronary stenosis was assessed by a number of diseased vessels, Gensini, Syntax, and Jeopardy scores. All individuals were followed up for cardiovascular events (CVEs) and cox proportion hazard models were used to evaluate the association of hypertension with cardiovascular outcomes. Patients with hypertension had more severe coronary stenosis and a higher incidence of CVEs compared with the ones with normotension (log-rank P < 0.001). After multivariable adjustment, there was a 2.1-fold increased risk of CVEs among patients with hypertension compared with patients with normotension (adjusted hazard ratio 2.06, 95% confidential interval 1.17-3.65, P < 0.01). Hypertension control status was also associated with CVEs even after adjustment of multiple variables. However, no combined effect on increased cardiovascular risks was detected in this HeFH cohort. In patients with HeFH, hypertension is an independent risk factor for cardiovascular events. Moreover, blood pressure control status in patients with hypertension is associated with the worse outcomes.

Preliminary study of carotid variables under ultrasound analysis as predictors for the risk of coronary arterial atherosclerosis.

BackgroundCarotid atherosclerosis by ultrasound scanning can be considered as an ideal window to reflect systemic artery atherosclerosis, which has aroused wide concern for predicting the severity of coronary artery atherosclerosis clinically. Ultrasound radio frequency (RF) data technology has enabled us to evaluate the carotid structure and elastic function precisely, for predicting the severity of coronary artery atherosclerosis.MethodsPatients with suspected coronary artery disease (CAD) underwent coronary angiography and were assigned to four groups according to whether atherosclerotic plaque was found or not and it caused stenosis. Carotid artery intima‐media thickness (IMT) and arterial stiffness were investigated by quality intima‐media thickness (QIMT) and quality arterial stiffness (QAS) techniques during ultrasound scanning. Univariable and multivariable modeling were used to investigate correlations of carotid parameters to coronary artery atherosclerosis. Receive operating characteristic (ROC) curves were used to evaluate diagnostic performance of these ultrasound variables.ResultsCarotid IMT and stiffness variables pulse wave velocity (PWV), α, β and compliance coefficient (CC) were statistically different between every two‐group's comparisons. IMT correlated with stiffness variables significantly with r = 0.70, 0.77, 0.63, and −0.39, respectively. All variables correlated with the severity of coronary atherosclerosis with the odd ratio (OR) of 1.73, 1.67, 1.19, 1.23, and 0.56 accordingly as IMT, PWV, α, β and CC were concerned. The AUC of IMT, PWV, α, β and CC were 0.9257, 0.8910, 0.8016, 0.9383, 0.8581 with correctly classified rate of 88.16%, 83.77%, 78.07%, 86.84%, and 81.58%, respectively.ConclusionsCarotid artery IMT and stiffness variable PWV, α, β and CC presented favorable predicting and differentiating values for patients with coronary atherosclerosis of different severity.

Sudden Cardiac Death in Schizophrenia During Hospitalization: An Autopsy-Based Study.

Schizophrenia is a severe mental disorder that is often comorbid with heart dysfunction and even sudden cardiac death (SCD). Clinical studies of SCD in schizophrenia have been largely reported, while there are limited autopsy studies that directly showed whole-scale information of such events. In this study, we present nine autopsy-based SCD cases in schizophrenia patients who died suddenly during hospitalization. Their medical records before and during hospitalization, and postmortem autopsy findings were summarized. These decedents had an average duration of schizophrenia for 6.83 ± 3.75 years with a male/female ratio of 4:5. They were all on intermittent antipsychotics medication before hospitalization and died within 15 days after hospitalization. Seven of the nine cases (77.8%) died of organic heart diseases such as severe coronary artery atherosclerosis (n = 4), myocarditis (n = 1), cardiomyopathy (n = 1), and pulmonary thromboembolism (n = 1). Two cases remained unexplained after systemic autopsy and toxicological examinations. Postmortem autopsy identified hepatic steatosis (n = 6) and respiratory inflammation (n = 3) as the most common associate extra-cardiac lesions. Our data provided autopsy-based data of SCD cases in schizophrenia and highlighted an intensive care of such patients during hospitalization.

Preexisting Cardiovascular Risk Factors and Coronary Artery Atherosclerosis in Patients with and without Cancer.

Cancer survivors suffer a higher risk of coronary artery atherosclerosis (CAA). Whether cancer patients had increased baseline CAA burden prior to cardiotoxic therapy remains unclear. We conducted a case-control study, and 286 consecutive patients were finally included. Among these patients, 181 had newly diagnosed cancer and 105 had nonmalignant diseases. Cancer was confirmed by biopsy. The severity of CAA was determined by coronary angiography and evaluated using the percentage of stenosis or Gensini scoring (GS). Patients with cancer versus cancer-free controls were older (OR = 1.052, 95% CI: 1.021–1.084, p < 0.001), more commonly male (OR = 0.048, 95% CI: 1.004–2.676, p=0.048), and more severely exposed to smoking (OR = 1.020, 95% CI: 1.007–1.033, p=0.003). Cancer patients were significantly more commonly complicated by ≥90% coronary stenosis than the gender- and age-matched cancer-free controls (9/93 versus 1/93, OR = 4.875, 95% CI: 1.024–23.213, p=0.047). After adjustment for age, gender, hypertension, diabetes, smoking history, blood glucose, and total cholesterol, cancer was significantly associated with high GS (adjusted OR = 2.208, 95% CI: 1.077–4.524, p=0.031). Our study demonstrated that cancer patients had increased CAA burden prior to cardiotoxic therapy. Further study is necessary to investigate the link between CAA and cancer.

Association of Helicobacter pylori Infection and Severity of Coronary Artery Atherosclerosis in Patients with Suspected Coronary Artery Disease

Association of Helicobacter pylori Infection and Severity of Coronary Artery Atherosclerosis in Patients with Suspected Coronary Artery Disease

Biological markers of endothelial dysfunction and fibrosis, macro- and microcirculation alterations in patients with obstructive and nonobstructive coronary artery disease and diabetes mellitus

Abstract Aim of the study To analyze the association of biological markers levels of endothelial dysfunction and fibrosis with macro- and microcirculation alterations in patients with obstructive and nonobstructive coronary artery disease (CAD) and type 2 diabetes mellitus (DM). Methods 52 patients with CAD were enrolled and divided into 4 groups: 19 patients with nonobstructive CAD (1–49% stenosis) without DM (1 group: 4 men, age 64.89±7.61, body mass index (BMI) 28.14±3.69 kg/m2); 13 patients with obstructive CAD (≥50% stenosis) without DM (2 group: 9 men, age 66.92±7.02, BMI 30.4±5.91 kg/m2); 10 patients with obstructive CAD (3 group: 4 men, age 63.4±10.37, BMI 31.7±4.81kg/m2) and 10 patients with nonobstructive CAD with DM (4 group: 3 men, age 64.6±5.32, BMI 33.74±3.25 kg/m2). Patients were matched for age, sex and BMI. All patients underwent coronary angiography or coronary computed tomography angiography. Biological markers levels (E-selectin, ng/ml; tissue inhibitor of metalloproteinase 1 (TIMP-1), ng/ml) were measured using ELISA. To determine arterial damage in both macro- and microcirculation, digital reactive hyperemia photoplethysmography were performed. Endothelial function of small (Occlusion Index, OI) and large vessels (Phase Shear, PS, ms) were analyzed. Vascular remodeling of aorta (Stiffness Index, aSI, m/s) and arterioles (Reflection Index, RI, %) were studied. Results The elevation of E-selectin (1 – 21.6 [18.7; 30.4]; 2 – 31.5 [20.1; 36.9]; 3 – 42.25 [29.9; 55.3]; 4 – 42.1 [33.1; 46.5]) and TIMP-1 (1 – 416 [376; 481]; 2 – 478 [381; 539]; 3 – 534 [490; 579]; 4 – 590 [520; 782]) levels were found in all groups. Statistical analysis revealed significant differences between TIMP-1 (p1–3=0.004; p1–4=0.003) and E-Selectin (p1–3=0.013; p1–4=0.01) levels. Remodeling of large vessels was detected only in patients with obstructive CAD without DM and nonobstructive CAD with DM (2 – aSI, 9.05 [7.08; 10.58]; 3 – aSI, 8.2 [7.6; 11]). Patients in all groups had endothelial dysfunction of large vessels (PS, 1 – 5.1 [1.75; 7.75]; 2 – 6.45 [5.53; 9.03]; 3 – 7.65 [13.4; 9.5]; 4 – 4.6 [0.7; 8.1] and arterioles (IO; 1 – 1.5 [1.38; 1.78]; 2 – 1.4 [1.26; 1.53]; 3 – 1.4 [1.2; 1.7]; 4 – 1.3 [1.2; 2.0]). Structural disorders of arterioles were found in all groups, except for patients with obstructive CAD without DM (RI, 1 – 36.95 [23.4; 52.65]; 2 – 28.25 [23.35; 53.75]; 3 – 41.15 [26.5; 55]; 4 – 44.7 [20; 54.5]. The data did not show significant differences between the study groups. Conclusions The data showed that biological markers levels of endothelial dysfunction and fibrosis were increased in all groups. Significant differences revealed between the levels of E-selectin and TIMP-1 in patients with nonobstructive CAD without DM and patients with CAD and DM, regardless of the degree of stenosis. All patients had functional changes of large vessels and arterioles regardless of the severity of coronary artery atherosclerosis and presence of DM. Funding Acknowledgement Type of funding sources: None.

Is there association between epicardial obesity and the severity of coronary artery atherosclerosis?

Abstract Background To assess the diagnostic capabilities of the ultrasound method for estimation of the epicardial fat (EF) and evaluate the association of the thickness of EF and the severity of coronary atherosclerosis in coronary heart disease (CHD) patients. Methods 461 people (age Me 58 years, Q1=52; Q3=64) were examined: 182 patients with CHD (age Me 61 years, Q1=56; Q3=66; 72% men), 279 control patients without CHD, undergoing heart valve surgery (age Me 55 years, Q1=51; Q3=59; 51% men). The severity of coronary artery lesions was assessed according to the current 2013 ESC Guidelines (&amp;gt;50% for the left main coronary artery and &amp;gt;70% for other coronary arteries). Coronary angiography, heart computer tomography (CT), echocardiography (ECHO) were estimated. Statistical data analysis (SPSS, version 17.0, USA). Results In CHD patients the volume of EF (heart CT) was significantly higher than in patients without CHD (167.0 cm3 (128,9; 167,1) and 89.1 cm3 (62,7; 102,7), z=−7.060, p&amp;lt;0.001). The thickness of EF in the area of atrioventricular sulcus (according to the ECHO) most closely corresponds to the volume of EF (according to heart CT), ρ=0.731, p&amp;lt;0.001. According to multiple linear regression analysis, it was found that in patients with CHD, an increase in age by 1 year is associated with an increase in the volume of EF by 1.4 cm3 (95% CI from 1.0 to 1.9). The volume of EF in CHD patients is meen 56.7±3.1 cm3 (95% CI from 46.6 to 66.8) more than in patients without CHD. The correlation between the number of coronary arteries affected by atherosclerosis and the values of the parameters characterizing the EF was not revealed. Conclusion The volume of epicardial fat measured by cardiac CT in patients with CHD is greater than epicardial fat volume measured in subjects without ischemic heart disease. The volume of epicardial adipose tissue measured by heart CT in patients with CHD increases with age. The number of coronary arteries affected by atherosclerosis in CHD patients does not depend on the thickness and volume of epicardial adipose tissue. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): The study has been supported by the grant from the Ministry of Science and Higher Education of the Russian Federation

Comprehensive Analysis of mRNA Expression Profiling and Identification of Potential Diagnostic Biomarkers in Coronary Artery Disease

The aim of this study is to investigate mRNA expression profiling by RNA sequencing (RNA-seq) in patients with coronary artery disease (CAD) and validate differentially expressed genes (DEGs) as novel biomarkers for CAD. Transcriptome-wide mRNA expression analysis of peripheral blood mononuclear cells was performed in five CAD patients and five controls. Functional enrichment analyses, protein–protein interaction network construction, and hub gene selection were further conducted. Relative expression levels of hub genes were validated by quantitative reverse transcription PCR in larger cohorts. Spearman correlation test and multiple linear regression analysis were applied to examine the relationship between confounding factors with severity of coronary artery atherosclerosis. Receiver operating characteristic (ROC) curve analysis was adopted to identify potentially diagnostic biomarkers for CAD. A total of 527 upregulated and 653 downregulated mRNAs were identified as DEGs in CAD patients. The relative expression levels of beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), F-box and leucine-rich repeat protein 4 (FBXL4), ubiquitin conjugating enzyme E2 D2 (UBE2D2), and ankyrin repeat and SOCS box containing 1 (ASB1) were significantly different between two groups (all p ≤ 0.05). The severity of coronary artery atherosclerosis was negatively associated with the BTRC gene relative expression level (r = −0.323, p < 0.001) and positively with UBE2D2 (r = 0.285, p < 0.001). ROC analysis of BTRC and UBE2D2 genes showed that the areas under the curve were 0.782 (95% CI: 0.720–0.845, p < 0.001) and 0.753 (95% CI: 0.681–0.824, p < 0.001), respectively. We described the characteristics of mRNA expression in the peripheral blood of CAD patients and controls by RNA-seq. Combined with Spearman correlation analysis and ROC analyses, BTRC and UBE2D2 genes had significantly diagnostic values, which may have potential to act as novel diagnostic biomarkers and therapeutic targets for CAD.

Author Response: First-Ever Ischemic Stroke and Increased Risk of Incident Heart Disease in Older Adults.

We thank Dr. Sioka et al. for their positive comments about our article1 showing a high risk of major adverse cardiovascular events after acute ischemic stroke. They also summarized the results of their study on myocardial perfusion tests among patients with a recent (<30 days) ischemic stroke.2 Dr. Sioka et al. found changes suggestive of myocardial ischemia in 62% of the cases.2 Notably, this was a wittingly selected population of patients with atherosclerotic strokes and a high prevalence of smokers (63%) and hyperlipidemia (58%). Thus, the high prevalence of asymptomatic coronary artery disease (CAD) in this study is somehow expected. Indeed, consistent with their interpretation, asymptomatic CAD is the most likely explanation for the impaired myocardial perfusion tests. However, in less selected populations, cardiovascular complications may not be due to asymptomatic CAD, since the reported prevalence of severe coronary artery atherosclerosis in patients with acute ischemic stroke and no history of CAD undergoing systematic coronary angiography is only 16%.3 Interestingly, the meaning of impaired myocardial perfusion scanning in stroke patients is not well understood. Takotsubo myocardiopathy can occur after stroke and is associated with transiently impaired myocardial perfusion tests in the absence of atherosclerotic CAD.4

The Relationship Between Earlobe Creases and the Presence, Extent, and Severity of Coronary Artery Atherosclerosis: A Regional Population-Based Autopsy Study.

The association between earlobe crease(s) and coronary artery atherosclerosis has stimulated debate and controversy over the years. Most available published studies have been conducted on living patients. Although these studies offer valuable insight into such associations in patients who exhibit symptoms, no information is available from these studies on the prevalence of earlobe creases among an asymptomatic population. Postmortem studies offer the advantage of including individuals free of symptomatic cardiovascular disease, thus providing an inbuilt control group. The atherosclerotic pathological findings of 1298 individuals who underwent coronial postmortem examination at Wellington Regional Hospital, New Zealand, between 2006 and 2013 were retrospectively studied. Earlobe creases and atherosclerosis involving the coronary arteries were semiquantitatively appraised. The presence of an earlobe crease was found to be significantly associated with coronary artery atherosclerosis.