Carotid intima media thickness is in a relation to risk factors for coronary artery disease. / Tolshchina intima-media sonnykh arterii v otnoshenii k faktoram riska dlia ishemicheskoi bolezni serdtsa.

INTRODUCTION: Carotid intima-media thickness (CIMT) is a double line pattern measured from the lumen-intima to media-adventitia interface. Measuring CIMT with B-mode ultrasound can detect early arterial wall changes. We aimed to measure CIMT in manifested atherosclerotic disease and find a relation to present risk factors. MATERIAL AND METHODS: This cross sectional study included a population of 657 patients, with documented coronary artery disease (CAD), 66,1% were men (469 pts), 33,9% were women (241 pts). The mean age of patients was 64,72 years (55,6-73,8). The measurement of CIMT (maximal and mean) was performed with B-mode ultrasound, on longitudinal view, on multiple plaque-free segments at the level of common carotid artery, on the far wall, on both sides. Multivariate regression analysis was done to estimate independent factors for CIMT, when risk factors, age, and sex included in analysis. RESULTS: The mean value of maximal CIMT was 0,96 mm (0,52-1,4), mean value of mean CIMT was 0,88 mm (range 0,61-1,15) and mean systolic blood pressure of 133,21 mm Hg (108,03-158,39) was found. Increased CIMT was found in 75,7% of patients (502 pts). Smoking was found as an independent risk factor for increased CIMT with odds ratio (OR) 4,7 (95% CI; 0,67-5,32) and diabetes mellitus with OR 1,6 (95% CI; 0,47-2,16). CONCLUSION: Diabetes and smoking are independently related to increased CIMT. These are preliminary results of National survey on 657 pts with coronary artery disease.

Thirty-day outcomes in patients with acute pulmonary embolism who discontinued anticoagulant therapy before 90 days.

BACKGROUND: The contemporary natural history of patients with acute pulmonary embolism (PE) not receiving (or early discontinuing) anticoagulant therapy has not been consistently evaluated. OBJECTIVE: To assess the rate of the composite outcome of PE-related death, sudden death, or recurrent thromboembolism (VTE) within 30 days in all PE patients in whom anticoagulation was not administered or discontinued prematurely (<90 days of anticoagulation). METHODS: We used the RIETE database to assess the incidence rates (per 100 person-days) of the composite outcome within the subsequent 30 days. The risk of these events was compared to PE patients who were anticoagulated for ≥90 days. RESULTS: Of 34,447 PE recruited from 2001 to 2017, 47 (0.14%) did not receive anticoagulants and 1348 (3.91%) discontinued it before 90 days. Fatal PE developed in 25 (53%) of those without any anticoagulation and in 45 (3.33%) with premature discontinuations. Sudden death or non-fatal recurrent VTE occurred in 6 (0.45%) and 24 (1.48%) patients, respectively. The incidence of the primary outcome declined logarithmically from 6.36 per 100 patient-days in untreated patients to 0.32-0.13 in those treated for 8-90 days. During the first week of follow-up, the incidence rate was 13.9 and 0.60-0.31 per 100 patient-days, respectively. The adjusted odds of the primary outcome was 27 fold higher in untreated than in treated patients, and progressively decreased to 2.5-7 fold higher in patients treated for at least 7 days. CONCLUSION: The incidence of the composite outcome was highest during the first week, and inversely and logarithmically correlated with the duration of anticoagulant therapy.

Venous thromboembolism in women with hormone-dependent breast cancer. To continue or discontinue hormonal treatment? Insights from the RIETE registry.

INTRODUCTION: Hormone therapy (HT) for breast cancer is associated with an increased risk of venous thromboembolism (VTE). This study examines the effects of continuing versus discontinuing HT on VTE recurrence, major bleeding, and mortality, after an acute VTE event. METHODS: Using data in the RIETE-registry from March 2001 through September 2021, we calculated incidence rates and rate-ratios (RR) for VTE events in patients on- and off HT. Cox regression models assessed the impact of HT continuation. RESULTS: Among 479 women with breast cancer on HT who developed VTE (pulmonary embolism 279, isolated deep vein thrombosis 200), 350 (73 %) continued HT. These women were slightly older (70 ± 13 vs. 67 ± 16 years) than those discontinuing HT, with no significant differences in other baseline characteristics. Over a median follow-up of 294 days, 25 (5.2 %) developed VTE recurrences, 18 (3.7 %) had major bleeding, and 73 (15.2 %) died. Rates of VTE recurrence did not differ significantly between groups (RR: 1.28, 95 % CI 0.44-3.75), except in the first three months post-VTE, where a higher rate was observed in those continuing HT (6.02/100 patients-year vs. no events). On multivariable analysis, HT continuation showed no association with VTE recurrences after adjusting for other thromboembolic risk factors (adjusted hazard ratio [aHR] 1.49, 95 % CI 0.5-4.45). CONCLUSION: Continuing HT after a VTE event in women with breast cancer does not generally affect the long-term risk of VTE recurrences but is associated with a higher risk in the first three months. These findings highlight the need for careful monitoring during this period.

Influence of fibrinogen and C-RP on progression of peripheral arterial disease in type 2 diabetes: a preliminary report.

BACKGROUND: Limited studies have suggested that inflammatory biomarkers play a role in the initiation and progression of atherosclerosis in diabetic patients. This study assesses the effect of inflammatory biomarkers: fibrinogen and C-reactive protein (C-RP) on the progression of peripheral arterial disease (PAD) in type 2 diabetic (T2D) patients. METHODS: Sixty two patients with T2D and PAD (mean age 60.28 ± 27 years and diabetes duration of 8.58 ± 6.17 years) were enrolled in a cohort prospective study of 36 months. Ankle-brachial index (ABI) was measured in all patients at baseline and after 36 months. Multiple linear regression analysis was used to determine the predictivity of variables for fibrinogen, C-RP, plasma lipid fractions, fasting plasma glucose, Body Mass Index (BMI), duration of diabetes status and the age on changes in ABI value. RESULTS: Linear regression analysis defined F as a predictor for endpoint value of ABI (ß = 0.469, p = 0.007). Value of C-RP determinates change of minimal value of ABI (ß = 0.449, p = 0.037) and change of mean ABI per year (ß = 0.442, p = 0.025). CONCLUSION: Our data indicate that plasma determination of fibrinogen and C-RP might have a clinical implication in defining the process of progression of PAD in T2D population.

The benefits of physical activity in middle-aged individuals for cardiovascular disease outcomes.

Regular physical activity (PA) has a positive role in preventing cardiovascular disease (CVD). Due to a trend toward a more sedentary lifestyle, the middle-aged population (35-65 years) is at greater risk of developing CVD. It is well established that PA improves cardiorespiratory fitness and reduces the risk of cardiovascular mortality and cardiovascular events, including stroke, coronary heart disease, heart failure, hypercholesterolemia, atherosclerosis, diabetes, and blood pressure. PA can potentially decrease oxidative stress and systemic inflammation, which are the two main underlying mechanisms leading to CVD. By reducing CRP, TNF-α, INF-γ, NF-κB and increasing IL-10, IL-4, and IL-8, PA can prevent the initiation and progression of CVD in middle-aged adults, highlighting the importance of being physically active for this age group. The general recommendation for PA to prevent CVD is at least 150 min/week at a moderate level of intensity; the type of PA should be adapted to the fitness level and medical condition of the individual. However, standardized guidelines for middle-aged individuals with cardiovascular events still need to be established.

Cancer-Associated Thrombosis: Trends in Clinical Features, Treatment, and Outcomes From 2001 to 2020.

Background: Despite advances in cancer and venous thromboembolism (VTE) management, the epidemiology of cancer-associated thrombosis management over time remains unclear. Objectives: We analyzed data from the RIETE (Registro Informatizado de la Enfermedad Trombo Embólica) registry spanning 2001 to 2020 to investigate temporal trends in clinical characteristics and treatments for cancer-associated thrombosis. Methods: Using multivariable survival regression, we examined temporal trends in risk-adjusted rates of symptomatic VTE recurrences, major bleeding, and death within 30 days after incident VTE. Results: Among the 17,271 patients with cancer-associated thrombosis, there was a progressive increase in patients presenting with pulmonary embolism (from 44% in 2001-2005 to 55% in 2016-2020; P < 0.001 for trend), lung (from 12.7% to 18.1%; P < 0.001) or pancreatic cancer (from 3.8% to 5.6%; P = 0.003), and utilization of immunotherapy (from 0% to 7.4%; P < 0.001). Conversely, there was a decline in patients with prostate cancer (from 11.7% to 6.6%; P < 0.001) or carcinoma of unknown origin (from 3.5% to 0.7%; P < 0.001). At the 30-day follow-up, a reduction was observed in the proportion of patients experiencing symptomatic VTE recurrences (from 3.1% to 1.1%; P < 0.001), major bleeding (from 3.1% to 2.2%; P = 0.004), and death (from 11.9% to 8.4%; P < 0.001). Multivariable analyses revealed a decreased risk over time for VTE recurrence (adjusted subdistribution HR [asHR]: 0.94 per year; 95% CI: 0.92-0.98), major bleeding (asHR: 0.98; 95% CI: 0.96-0.99), and death (aHR: 0.97; 95% CI: 0.96-0.98). Conclusions: In this multicenter study of cancer patients with VTE, there was a decline in thrombotic, hemorrhagic, and fatal events from 2001 to 2020. (Registro Informatizado de la Enfermedad Trombo Embólica [RIETE]; NCT02832245).

Uncommon Cases of Venous Thromboembolism.

There is a growing incidence of new cases of venous thromboembolismworldwide.Some of these patients do have a predisposition to the development of thrombosis, some of them do however have various risk factors associated with this event, but few of them have unrecognized etiology. This paper aimsto describe different scenarios of venous thromboembolism.

Deep vein thrombosis symptoms and 30-day mortality in acute pulmonary embolism.

BACKGROUND: In patients with acute symptomatic pulmonary embolism (PE), the presence of concomitant lower-limb deep vein thrombosis (DVT) has been associated with a higher mortality rate. The prognostic significance of DVT symptoms among these patients remains uncertain. METHODS: We used the RIETE (Registro Informatizado de Enfermedad TromboEmbólica) registry to compare the 30-day mortality rate in patients with PE and concomitant lower-limb DVT, according to the presence or absence of DVT symptoms. Primary outcomes were all-cause death and PE-related death within the first 30 days. RESULTS: Since March 2001 to June 2021, there were 17,742 patients with acute symptomatic PE and objectively proven concomitant lower-limb DVT. Of these, 11,984 (68%) had DVT symptoms. Most patients with or without DVT symptoms (82% vs. 81%) received low-molecular-weight heparin initially. Then, most (61% vs. 58%) switched to vitamin K antagonists. During the first 30 days of therapy, 497 patients with DVT symptoms (4.1%) and 164 (2.8%) with no DVT symptoms died (rate ratio [RR]: 1.48; 95%CI: 1.23-1.77). The rates of PE-related death were: 1.0% vs. 0.7%, respectively (RR: 1.50; 95%CI: 1.04-2.16). On multivariable analysis, patients with DVT symptoms were at increased risk for all-cause death (adjusted hazard ratio [aHR]: 1.49; 95%CI: 1.24-1.78), and PE-related death (aHR: 1.52; 95%CI: 1.05-2.20). CONCLUSION: Among patients with acute symptomatic PE and concomitant lower-limb DVT, those with DVT symptoms had an increased all-cause and PE-related mortality within 30 days. Assessment of DVT symptoms would assist with risk stratification of these patients.

Duration of Anticoagulation Therapy in Patients with Genetic Inherited Thrombophilia.

Background: Genetic factors play an important role in deep vein thrombosis (DVT). The duration of anticoagulation therapy in patients with verified genetic inheritance and previous events of DVT is still questionable. Case reports: We present three cases of siblings (two brothers and one sister) with verified Venous thromboembolism (VTE) and genetic inheritance. The first case is a 33 y.o. male who was admitted with bilateral massive pulmonary thromboembolism and DVT of the right femoral vein. He had an episode of DVT 4 years ago. Fibrinolytic therapy was introduced immediately. Afterwards, unfractionated heparin was introduced, and then switched to enoxaparin and acenocoumarol. Because of inappropriate INR, it was switched then to rivaroxaban. The imaging methods showed significant improvement, and the patient was discharged from the hospital with rivaroxaban at 2x15 mg/day for another 2 weeks and was instructed to continue 20 mg/day until his next control. In the meantime, the second case, a 36 y.o. male, brother to the first patient, came with vein thrombosis of vena saphena magna of the left leg. Treatment with Acenocoumarol was started and continued for 2 years until complete resolution of the thrombi, and then it was changed to Aspirin. The third case is the sister of the first 2 cases, a 38 y.o female with symptoms and findings almost similar to those in the second case. She was treated with Acenocoumarol for 6 months. Doppler ultrasound showed complete resolution of the thrombosis and anticoagulation therapy was stopped. Genetic investigations for mutation showed presence of homozygous gene mutation for Prothrombin (PTB G20210A) in the first patient, his brother (the second case) was compound heterozygote for PTB and for MTHFR C677T, and his sister (third case) was heterozygous only for the PTB mutation. According to the clinical (recurrent unprovoked DVT with thromboembolic complications) and genetic testing (homozygous gene mutation for PTB) in the first patient, we decided to continue the secondary thromboprophylaxis with rivaroxaban 10 mg/day indefinitely. Conclusion: Testing for genetically inherited thrombophilia should be included in the risk assessment for recurrence, and performed in all patients under 50 y.o. who have a first, non-provoked episode of thrombosis, in order to determine the duration of anticoagulation therapy.

Vaccine-Inducted Thrombotic Thrombocytopenia and Covid-19 Vaccines: Case Series.

Vaccine-induced thrombotic thrombocytopenia (VITT) is a condition similar to heparin-induced thrombocytopenia (HIT), but it is associated with prior administration of COVID-19 vaccines without prior exposure to heparin. The incidence of VITT is not certain, but it appears to be extremely rare. Reports of unusual and severe thrombotic events, including cerebral and splanchnic venous thrombosis and other autoimmune adverse reactions, such as immune thrombocytopenia or thrombotic microangiopathies in connection with some of the SARS-CoV-2 vaccines, have caused a great deal of concern within the population and the medical community. We would like to present 4 clinical cases of VITT, hospitalized and treated in intensive care unit (ICU) of University clinic of cardiology in Skopje.

Machine Learning to Predict Outcomes in Patients with Acute Pulmonary Embolism Who Prematurely Discontinued Anticoagulant Therapy.

BACKGROUND: Patients with pulmonary embolism (PE) who prematurely discontinue anticoagulant therapy (<90 days) are at an increased risk for death or recurrences. METHODS: We used the data from the RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica) registry to compare the prognostic ability of five machine-learning (ML) models and logistic regression to identify patients at increased risk for the composite of fatal PE or recurrent venous thromboembolism (VTE) 30 days after discontinuation. ML models included decision tree, k-nearest neighbors algorithm, support vector machine, Ensemble, and neural network [NN]. A "full" model with 70 variables and a "reduced" model with 23 were analyzed. Model performance was assessed by confusion matrix metrics on the testing data for each model and a calibration plot. RESULTS: Among 34,447 patients with PE, 1,348 (3.9%) discontinued therapy prematurely. Fifty-one (3.8%) developed fatal PE or sudden death and 24 (1.8%) had nonfatal VTE recurrences within 30 days after discontinuation. ML-NN was the best method for identification of patients experiencing the composite endpoint, predicting the composite outcome with an area under receiver operating characteristic (ROC) curve of 0.96 (95% confidence interval [CI]: 0.95-0.98), using either 70 or 23 variables captured before discontinuation. Similar numbers were obtained for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The discrimination of logistic regression was inferior (area under ROC curve, 0.76 [95% CI: 0.70-0.81]). Calibration plots showed similar deviations from the perfect line for ML-NN and logistic regression. CONCLUSION: The ML-NN method very well predicted the composite outcome after premature discontinuation of anticoagulation and outperformed traditional logistic regression.

Rare Blood Groups in ABO, Rh, Kell Systems - Biological and Clinical Significance.

Background: The frequency of ABO, Rh and Kell blood group antigens differs among populations of different ethnic ancestry. There are low-frequency antigens (<1%) and high-frequency antigens (>90%). A rare blood group is defined as the absence of a high-frequency antigen in the general population, as well as absence of multiple frequent antigens within a single or multiple blood group systems. Aim: To perform red blood cell typing and to calculate the antigen and phenotype frequencies, in order to identify rare blood group donors within the clinically most important АВО, Rh and Kell systems. Material and Methods: АВО, Rh (D, C, E, c, e) and Kell (K) antigen typing was performed using specific monoclonal sera and microplate technique, while Cellano (k) typing was performed with a monoclonal anti-k, antihuman globulin and column agglutination technique. Weak ABO subgroups were determined using the absorption elution method or molecular genotyping (PCR-SSP). Results: ABO antigen frequency is: A (40.89%), O (34.22%), B (16.97%), AB (7.92%) and weak ABO subgroups (0, 009 %). The established genotypes were AxO1 (0, 0026%) and AxB (0, 001%). Rh antigen frequency is: D (85.79%), C (71.7%), c (76.0%), E (26.0%) and е (97.95%). The most common Rh pheno-type is the DCcee (32.7%) while the rarest phenotype is the DCCEE phenotype (0. 003%). The prevalence of K and k antigen is 7.5% and 99.94%, respectively. The frequency of the rare phenotype K+k- is 0.06%. Conclusion: Large scale phenotyping of blood group antigens enables the identification of blood donors with rare blood groups for patients with rare phenotypes or with antibodies to high-frequency antigens and to frequent antigens within one or more blood group systems.

Clinical characteristics, time course, and outcomes of major bleeding according to bleeding site in patients with venous thromboembolism.

BACKGROUND: Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. METHODS: We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001-07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. RESULTS: Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6-74.6% versus 50.5%, 95% CI: 48.2-52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8-47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2-23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. CONCLUSIONS: Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry).

Diabetic angiopathy.

Peripheral arterial disease is high prevalent in patients with diabetes mellitus. The purpose of this review article is to resume ethiogenesis, diagnostic methodology and treatment modalities of this condition, also known as diabetic angiopathy.

The Role of Carotid Stenosis in a Prediction of Prognosis of Coronary Artery Disease.

Aims: The aim of this paper is to indicate if carotid stenosis is predictive for the prognosis of coronary artery disease.Method and materials: Our study is a prospective cohort study. 1031 patients with proven coronary artery disease (CAD) were recruited consecutively. Carotid ultrasound was used to assess IMT, plaque, or stenosis. They were followed for 24 months for adverse cardiovascular events. Selected demographic date such as smoking history, dyslipidemia, hypertension, laboratory values, and clinical data (associated diseases and risk) were collected from each patient. Total cardiovascular events and mortality rate were followed up for the study population. The results were collected prospectively and retrospectively. The study was organized as a clinical, cross-sectional study and comparative study.From the data collected with the clinical research, a file was formed in the statistical program with the help of which the data were statistically analyzed.From the methods of descriptive statistics, absolute frequencies, percentages, arithmetic mean, median, measures of variability, minimum, maximum, standard deviation and logistic regression models were used.Result: Of the total number of patients 1026 had arterial hypertension (HTA). Data on hyperlipidemia (HLP) had been reported in 895 patients. 1.023 patients had peripheral artery disease (PAB). 1031 patients were presented with multivessel coronary artery disease (CAD). There were 1,029 patients with diabetes mellitus (DM), while 1,013 patients had coronary artery by-pass (CABG), and 1,012 had stroke (CVI). Elevated systolic blood pressure was reported in 966 patients. 184 patients had elevated triglycerides and 187 had elevated cholesterol. 1,008 patients have had a history of myocardial infarction. Carotid artery stenosis (CAS) has been found in 1,009 patients, increased body mass index (BMI) in 270 patients.1.031 patients were followed for 24 months. Cardiovascular events were reported in 54 patients (or 5.2%). Revascularization was performed in 28 (4.1%) patients, while 12 (1.8%) of patients died. Diabetes mellitus (OR 1.878 95% CI 0.491 7.184) and Carotid stenosis (OR 2.185 95% CI 0.731 6.53) were found to be predictive factors for future cardiovascular events.Conclusion: Due to our results carotid ultrasound may be a useful tool for risk stratification of coronary artery disease pts.

Immunomodulatory Effects of Dietary Polyphenols.

Functional and nutraceutical foods provide an alternative way to improve immune function to aid in the management of various diseases. Traditionally, many medicinal products have been derived from natural compounds with healing properties. With the development of research into nutraceuticals, it is becoming apparent that many of the beneficial properties of these compounds are at least partly due to the presence of polyphenols. There is evidence that dietary polyphenols can influence dendritic cells, have an immunomodulatory effect on macrophages, increase proliferation of B cells, T cells and suppress Type 1 T helper (Th1), Th2, Th17 and Th9 cells. Polyphenols reduce inflammation by suppressing the pro-inflammatory cytokines in inflammatory bowel disease by inducing Treg cells in the intestine, inhibition of tumor necrosis factor-alpha (TNF-α) and induction of apoptosis, decreasing DNA damage. Polyphenols have a potential role in prevention/treatment of auto-immune diseases like type 1 diabetes, rheumatoid arthritis and multiple sclerosis by regulating signaling pathways, suppressing inflammation and limiting demyelination. In addition, polyphenols cause immunomodulatory effects against allergic reaction and autoimmune disease by inhibition of autoimmune T cell proliferation and downregulation of pro-inflammatory cytokines (interleukin-6 (IL-6), IL-1, interferon-γ (IFN-γ)). Herein, we summarize the immunomodulatory effects of polyphenols and the underlying mechanisms involved in the stimulation of immune responses.

Cancer - Associated Thrombosis - A Study of Cases.

Research shows that the presence of cancer increases the likelihood of developing venous thromboembolism (pulmonary thromboembolism and deep vein thrombosis) from as much as fourfold up to sevenfold. It is imperative that after early diagnosis we treat cancer-associated thrombosis with grave seriousness in order to reduce its morbidity and mortality. We present 14 case reports of patients with cancer-associated thrombosis including thrombosis related to malignant hemopathies.