PROGNOSTIC VALUE ENDOTHELIAL MONOCYTE ACTIVATING POLYPEPTIDE – ІІ IN PATIENTS WITH ACUTE MYOCARDIAL INFARCTION IN COMBINATION WITH 2 DIABETES MELLITUS AS A MARKER OF RECURRENT CARDIOVASCULAR EVENTS WITHIN 6 MONTHS OF OBSERVATION

The aim of the research. Analyze the prognostic value of endothelial monocyte activating polypeptide – ІІ as a marker of recurrent cardiovascular events in patients with acute myocardial infarction with type 2 diabetes mellitus within 6 months of follow-up after a coronary event. Materials and methods. The research involved 120 patients. All subjects were included in 2 groups: group 1 - patients with acute myocardial infarction (AMI) and type 2 diabetes mellitus (DM), group 2 - patients with AMI (n = 50). The control group included 20 healthy individuals. Examination of patients was performed on the basis of the cardiology department for patients with acute myocardial infarction KNP "City Clinical Hospital №27" HMR and the 1st cardiology department of Kharkiv Clinical Hospital by rail №1 branch "Health Center" of the Joint Stock Company "Ukrainian Railways" . The participants of the research on the first day of AMI were determined the level of human endothelial monocyte activating polypeptide – ІІ (EMAP-II) in the serum using enzyme-linked immunosorbent assay using a commercial test system manufactured by Bioassay Technology Laboratory (China) in accordance with the enclosed instructions on enzyme-linked immunosorbent assay "Labline-90" (Austria). General clinical and instrumental examinations were performed on patients who were part of the 1st, 2nd groups and control groups. People who participated in the research were informed about the purpose, objectives, materials and methods of the research by signing an informed consent to participate in it. During the research, measures were taken to ensure the anonymity of each of its participants. Statistical processing of survey results was performed using software package StatSoft Inc USA - "Statistica 6.0". Research results. The average level of EMAP-II in patients who were in the 1st group was 4.54 ± 0.331 ng / ml, the 2nd - 2.74 ± 0.21 ng / ml, in the control group - 1.1 ± 0.037 ng / ml (p <0.05). A recurrent cardiovascular event in the form of recurrent AMI occurred in 19 patients (27.14%) who were part of the 1st group and in 7 patients (14%) who belonged to the 2nd group. The research found that the value of EMAR-II> 5.42 μmol / l in patients with AMI in combination with type 2 diabetes and> 2.64 μmol / l in patients with AMI without concomitant type 2 DM is a predictor recurrence of AMI within 6 months of follow-up after a coronary event. Based on the results of the research, a multifactor logistic regression model for the prognosis of recurrent AMI in patients with AMI in combination with type 2 DM was developed using EMAR-II for 6 months of follow-up after a coronary event. Conclusions. Thus, the level of endothelial monocyte activating polypeptide – ІІ in patients with acute myocardial infarction correlates with the presence of comorbid pathology in the form of type 2 diabetes mellitus, having the highest level in its presence, reflecting endothelial dysfunction that pathogenetically combines these diseases. According to the above, to date, the question remains about the prognostic value of endothelial monocyte activating polypeptide – ІІ in acute myocardial infarction in patients with concomitant type 2 diabetes mellitus during the 6-month follow-up period after a cardiovascular event. It is advisable to further research the rate of endothelial dysfunction - endothelial monocyte activating polypeptide – ІІ as a predictor of recurrent cardiovascular events in patients with acute myocardial infarction in combination with concomitant type 2 diabetes mellitus within 6 months after the coronary event.

LPA Genotypes and Haplotypes Are Associated with Lipoprotein(a) Levels but Not Arterial Wall Properties in Stable Post-Coronary Event Patients with Very High Lipoprotein(a) Levels

Lipoprotein(a) [Lp(a)] levels are an independent risk factor for coronary artery disease (CAD). Two single-nucleotide polymorphisms (rs10455872, rs3798220) and number of KIV-2 repeats in the gene encoding Lp(a) (LPA) are associated with Lp(a) and CAD. Our aim was to investigate whether in patients with stable CAD and high Lp(a) levels these genetic variants are associated with increased Lp(a) and arterial wall properties. Blood samples underwent biochemical and genetic analyses. Ultrasound measurements for the functional and morphological properties of arterial wall were performed. Genotypes of rs10455872 and haplotypes AT and GT showed significant association with Lp(a) levels. Patients with GG showed significantly higher Lp(a) levels compared with those with AG genotype (2180 vs. 1391 mg/L, p = 0.045). Patients with no AT haplotype had significantly higher Lp(a) compared to carriers of one AT haplotype (2158 vs. 1478 mg/L, p = 0.023) or two AT haplotypes (2158 vs. 1487 mg/L, p = 0.044). There were no significant associations with the properties of the arterial wall. Lp(a) levels significantly correlated also with number of KIV-2 repeats (r = −0.601; p < 0.0001). In our patients, these two LPA polymorphisms and number of KIV-2 repeats are associated with Lp(a), but not arterial wall properties.

542 Ceftriaxone-induced Kounis syndrome in the time of COVID-19

A 53 years old male subject with diabetes mellitus, hypertension, dyslipidaemia, obesity, and history of perianal abscess was admitted to the local hospital for generalized maculopapular rash on his trunk and limbs, which was accompanied by intense itching, sweating, hypotension, and severe chest pain. The rash and the accompanying signs/symptoms appeared 10 min after the administration of ceftriaxone (2 g) as antibiotic therapy for the perianal abscess. The patient had no clinical history for any type of allergy. At the first medical contact, an urgent electrocardiogram was taken showing ST-segment elevation in the anterior–lateral leads. The patient was still then treated with methylprednisolone and adrenalin i.v. as an anaphylactic shock was suspected. Afterwards, the patient was admitted in the emergency department, where he showed flu-like symptoms, chills, and fever. An echo-fast showed left ventricular wall motion abnormalities with hypokinesia of the anterior and posterior wall and moderate mitral regurgitation with normal EF. Laboratory tests showed increased levels of high-sensitivity cTnT (32.8 ng/l; NV &lt; 14), white blood cells (13.74 × 103/μl; NV 5.2–12.4 × 103), IL-6 (10.54 pg/ml; NV &lt; 7), C-reactive protein (PCR) (29.3 mg/l; NV 0–3). As for the cutaneous manifestations, flu-like symptoms, and blood test results (elevation of IL-6 and PCR despite an increase of white cell count) a SARS COV-2 swab was done. As recently noted in several preliminary studies, COVID-19 patients indeed show erythematous rash, and localized or widespread urticaria as initial manifestations in acute severe cases along with the humoural acute-phase response. The latter made it complicated to distinguish viral infection vs. drug administration as the underlying cause of the event. In the meantime, the patient started the treatment for an acute coronary syndrome and acetylsalicylic acid 100 mg, clopidogrel 300 mg orally, and enoxaparin dose subcutaneously were administered. Chest pain disappeared 30 min later and the ECG returned to normal 40 min after drug administration. Subsequently, the swab test result turned to be negative for SARS-CoV-2 and the patient was transferred to our centre for an emergency coronary angiography that revealed proximal subocclusive thrombotic stenosis and middle 70–80% thrombotic stenosis of the left anterior descending (LAD) coronary artery and a 80% thrombotic stenosis of the distal portion of the circumflex. Both vessels’ respective stenoses were treated with PCIs. When considering all together the anamnestic, laboratory, and instrumental/invasive findings, a case of Kounis Syndrome (KS) was suspected. Kounis syndrome (KS) has been indeed defined as cardiovascular symptoms that occur secondary to allergic or hypersensitivity insults mainly elicited by specific medications in male patients. KS involves the following three recognized variants: Type 1: the acute coronary event is secondary to spasm; Type 2: coronary thrombosis is the main culprit, and Type 3: the coronary event occurs secondary to drug-eluting stent thrombosis. Therefore, the patient was finally discharged with the diagnosis of ST-elevated MI likely secondary to a type II KS.

Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial

Objective: The haptoglobin (Hp)2-2 phenotype (~35-40% of people) is associated with increased oxidation and dysfunctional high-density lipoprotein (HDL) in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL-cholesterol and lower triglycerides have not reliably prevented cardiovascular disease (CVD) in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the ACCORD lipid trial (NCT00000620). <p>Research Design and Methods: Cox proportional hazards regression models quantitfied the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n=1,795) separately from those without (n=3,201). </p> <p>Results: Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable-adjusted hazard ratio: 0.74, 95% CI: 0.60-0.90, compared to no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16, 0.87-1.56, p, interaction=0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was most effective in participants with severe dyslipidemia (p, interaction=0.01), and and in males (p, interaction= 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (p, interaction= 0.002). </p> <p>Conclusions: The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial. </p>

Haptoglobin Phenotype Modifies the Effect of Fenofibrate on Risk of Coronary Event: ACCORD Lipid Trial

Objective: The haptoglobin (Hp)2-2 phenotype (~35-40% of people) is associated with increased oxidation and dysfunctional high-density lipoprotein (HDL) in hyperglycemia and may explain why drugs designed to pharmacologically raise HDL-cholesterol and lower triglycerides have not reliably prevented cardiovascular disease (CVD) in diabetes. We aimed to determine whether the effect of adding fenofibrate versus placebo to simvastatin on the risk of coronary artery disease (CAD) events depends on Hp phenotype in the ACCORD lipid trial (NCT00000620). <p>Research Design and Methods: Cox proportional hazards regression models quantitfied the relationship between fenofibrate therapy and CAD events in the ACCORD lipid trial in participants with the Hp2-2 phenotype (n=1,795) separately from those without (n=3,201). </p> <p>Results: Fenofibrate therapy successfully lowered the risk of CAD events in participants without the Hp2-2 phenotype (multivariable-adjusted hazard ratio: 0.74, 95% CI: 0.60-0.90, compared to no fenofibrate therapy) but not in participants with the Hp2-2 phenotype (1.16, 0.87-1.56, p, interaction=0.009). Subgroup analyses revealed that this protective effect of fenofibrate against CAD events among the non-Hp2-2 phenotype group was most effective in participants with severe dyslipidemia (p, interaction=0.01), and and in males (p, interaction= 0.02) with an increased CAD risk from fenofibrate treatment observed in females with the Hp2-2 phenotype (p, interaction= 0.002). </p> <p>Conclusions: The effect of fenofibrate added to simvastatin on risk of CAD events depends on Hp phenotype in the ACCORD lipid trial. </p>

The Importance of Echocardiography Assessment in Coronary Patients Subject to Cardiovascular Recovery Programs

Cardiovascular diseases cause approximately one-third of deaths worldwide and an increasing number of individuals with non-fatal ischemic heart disease live with chronic disabilities and impaired quality of life. Cardiac rehabilitation is designed to limit the physiological and psychological effects of cardiac illness, reduce the risk for sudden death or re-infarction, control cardiac symptoms and enhance the psychosocial and vocational status of selected patients. The study group included a group of 78 patients who had a coronary event no more than 3 months ago and who are included in cardio-vascular recovery programs. The patients were echocardiographic evaluated at the first admission and later at 6 months. The evolution of the patients was a favorable one, being objectified an increase of both the ejection fraction of the left ventricle, as well as an improvement of MAPSE and TAPSE.

The ceramide- and phosphatidylcholine- based Coronary Event Risk Test2 (CERT2) and cardiovascular mortality in men and women with type 2 diabetes

The recently introduced Coronary Event Risk Test version 2 (CERT2) is a validated cardiovascular risk predictor score that uses circulating ceramide and phosphatidylcholine concentrations. The purpose of this study was to investigate the power of CERT2 to predict cardiovascular mortality in 280 male and 121 female patients with type 2 diabetes (T2DM). Prospectively, we recorded 55 cardiovascular deaths in men and 19 in women during a mean follow-up time of 7.6±3.6 and 8.1±3.4 years respectively. Overall, cardiovascular survival decreased with increasing CERT2 risk categories (figure 1). In Cox regression models, CERT2 significantly predicted the incidence of cardiovascular mortality in male patients with T2DM (unadj. HR 1.82 [1.39–2.37] per standard deviation; p&lt;0.001), the unadj. HR in women was 1.36 [0.83–2.22]; p=0.228). After adjustment for age, BMI, current smoking, LDL cholesterol, HDL cholesterol, hypertension, and statin use the HR in men was 1.73 [1.31–2.29]; p&lt;0.001) and 1.40 [083–2.36]; p=0.210 in women. Interaction terms CERT2 x gender were non-significant both in univariate analysis (p=0.354) and after multivariate adjustment (p=0.359). We conclude that sex does not significantly impact the association of CERT2 with cardiovascular mortality in patients with T2DM. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

Employment status three years after percutaneous coronary intervention – a nationwide prospective cohort study

Background Return to work plays an important part in social readjustment after an acute coronary event, and has important implications for both the individual and the society. Updated knowledge is lacking regarding losng-term employment after percutaneous coronary intervention (PCI). Aims The aims of this study were to determine employment status three years after PCI and to assess predictors for return to work stratified by gender. Methods We included first-time PCI patients from the NorStent Trial, who were of working age (&lt;60 years; n=2488) at a three-year follow-up. Employment status were assessed using self-report. Results Fifty-seven percent of females and 73% of males who were &lt;60 years of age at the index event were employed at follow-up (p&lt;0.001). Living with a partner, higher levels of education, and living in the western part of Norway were associated with a higher chance of being employed in males, while higher levels of education were associated with a higher chance of being employed in females. Prior cardiovascular morbidity and former smoking were associated with lower chance of being employed in males, while being older was associated with lower chance of being employed in females. Conclusion A significant number of working-age coronary heart disease patients are unemployed three years after coronary revascularization. Our findings indicate a need for revised and gender specific initiatives to promote vocational support. FUNDunding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): The Northern Norway Regional Health Authority

Persistence of Lipoproteins and Cholesterol Alterations after Sepsis: Implication for Atherosclerosis Progression

(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.