Cardiovascular, Pulmonary, and Neuropsychiatric Short- and Long-Term Complications of COVID-19.

Beginning with the various strategies of the SARS-CoV-2 virus to invade our bodies and manifest infection, and ending with the recent long COVID, we are witnessing the evolving course of the disease in addition to the pandemic. Given the partially controlled course of the COVID-19 pandemic, the greatest challenge currently lies in managing the short- and long-term complications of COVID-19. We have assembled current knowledge of the broad spectrum of cardiovascular, pulmonary, and neuropsychiatric sequelae following SARS-CoV-2 infection to understand how these clinical manifestations collectively lead to a severe form of the disease. The ultimate goal would be to better understand these complications and find ways to prevent clinical deterioration.

All-Cause Mortality and Trimethylamine N-Oxide Levels in Patients with Cardiovascular Disease.

INTRODUCTION: Trimethylamine N-oxide (TMAO) is an organic compound with a well-established involvement in the pathogenesis of cardiovascular disease (CVD). However, data on the links between TMAO levels and cardiovascular mortality in Polish patients are lacking. OBJECTIVES: We aimed to assess the relationship between serum TMAO levels and 5-year mortality in Polish patients with CVD. PATIENTS AND METHODS: We retrospectively assessed serum TMAO levels in 1,036 consecutive patients (median age, 62 years; men, 61%) hospitalized between 2013 and 2015. Correlations between TMAO levels and 5-year mortality as well as anthropometric and biochemical parameters were assessed for the whole population and the subgroups of patients with acute coronary syndrome, stable coronary syndrome (SCS), chronic heart failure (HF), and atrial fibrillation (AF). RESULTS: In the univariate analysis, increased TMAO levels predicted 5-year mortality without clinically significant power (hazard ratio [HR], 1.01; 95% CI: 1.006-1.018; p < 0.0001). However, even this weak effect was lost in the multivariate analysis after adjustment for age, sex, comorbidities, and laboratory parameters. In the whole study group, TMAO levels in the fourth quartile of concentration (>6.01 µM) predicted 5-year mortality only in the univariate analysis (HR: 1.55; 95% CI: 1.34-1.79; p < 0.0001). In subgroup univariate analysis, TMAO levels predicted 5-year mortality in patients with SCS, chronic HF, and AF. CONCLUSIONS: Despite the promising results of previous studies, our study shows that the level of TMAO has at most moderate value in predicting all-cause mortality. TMAO levels depend on other clinical variables, which limits the use of TMAO as an independent predictor of mortality in these patients.

Citrulline and long-term mortality in patients with cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD. OBJECTIVES: To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed. MATERIAL AND METHODS: Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed. RESULTS: The median citrulline level in the study population was 22.5 µM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027). CONCLUSIONS: Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.

Diurnal Variability of Platelet Aggregation in Patients with Myocardial Infarction Treated with Prasugrel and Ticagrelor.

BACKGROUND: Contemporary antiplatelet treatment in acute myocardial infarction (AMI) is based on one of two P2Y12 receptor inhibitors, prasugrel or ticagrelor. The aim of this study was to compare diurnal variability of platelet reactivity between patients receiving prasugrel and ticagrelor during the initial phase of maintenance treatment after AMI. METHODS: It was a prospective, two-center, pharmacodynamic, observational study. Blood for platelet testing was sampled at four time points on day four after AMI (8:00, 12:00, 16:00, 20:00). Diurnal variability of platelet reactivity was expressed as a coefficient of variation (CV) of the above-mentioned measurements. RESULTS: 73 invasively-treated patients were enrolled (ticagrelor: n = 47, prasugrel: n = 26). CV was greater in patients treated with ticagrelor compared with prasugrel according to a VASP assay (47.8 [31.6-64.6]% vs. 21.3 [12.9-25.5]%, p < 0.001), while no statistical differences were detected when the CVs of platelet aggregation according to Multiplate were compared between ticagrelor- and prasugrel-treated patients. Ticagrelor-treated patients showed more pronounced platelet inhibition than prasugrel at 16:00 and 20:00 (VASP16:00: 20.6 ± 15.0 vs. 24.9 ± 12.8 PRI, p = 0.049; VASP20:00: 18.6 ± 17.7 vs. 26.0 ± 11.7 PRI, p = 0.002). CONCLUSIONS: Ticagrelor shows greater diurnal variability in platelet aggregation than prasugrel during the initial maintenance phase of AMI treatment, and this is due to the continuous increase of platelet inhibition after the morning maintenance dose. Both drugs provide an adequate antiplatelet effect early after AMI. Evaluation of the clinical significance of these findings warrants further investigation.

Relationships between Circulating Matrix Metalloproteinases, Tissue Inhibitor TIMP-2, and Renal Function in Patients with Myocarditis.

INTRODUCTION: Under physiological conditions, the myocardial extracellular matrix (ECM) is maintained by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). However, changes in the balance between MMPs and TIMPs can lead to pathological remodeling of the ECM, which contributes to cardiovascular and kidney diseases. The aim of our study was to assess levels of MMPs and TIMP-2 in patients with myocarditis and their relationship to renal function. MATERIALS AND METHODS: Forty five patients with myocarditis who underwent CMR were included, comprising 11 with concurrent chronic kidney disease (CKD). Blood samples were obtained to assess serum levels of MMP-2, MMP-3, MMP-9, and TIMP-2. RESULTS: Serum MMP-2, MMP-3, and TIMP-2 levels negatively correlated with the ejection fraction in patients with myocarditis, while MMP-3 levels correlated with longitudinal deformation (p < 0.05). Serum MMP-2, MMP-3, and TIMP-2 levels also negatively correlated with renal function, as assessed by the estimated glomerular filtration rate (eGFR) (p < 0.05). Patients with myocarditis and concurrent CKD had higher levels of MMP-2 and TIMP-2 than those without kidney damage. CONCLUSIONS: (1) We demonstrated that MMP-2, MMP-3, and TIMP-2 concentrations were related to left-ventricular ejection fraction, and MMP-3 levels correlated with longitudinal deformation, indicating MMPs play an important role in the post-inflammatory remodeling of the myocardium. (2) A negative correlation between the eGFR and MMP-2, MMP-3, and TIMP-2 and a positive correlation between creatinine and MMP-3 levels indicate the role of MMPs and TIMP-2 in renal dysfunction.

Role of skeletal muscle perfusion and insulin resistance in the effect of dietary sodium on heart function in overweight.

AIMS: Weight excess and insulin resistance predispose to heart failure. High sodium consumption may contribute to the development of cardiac impairment in insulin-resistant individuals by promoting inadequate skeletal muscle microvascular perfusion response to insulin. We sought to investigate the association of dietary sodium reduction with muscle perfusion, insulin sensitivity, and cardiac function in overweight/obese insulin-resistant (O-IR) normotensive subjects. METHODS AND RESULTS: Fifty O-IR individuals with higher than recommended sodium intake were randomized to usual or reduced sodium diet for 8 weeks; 25 lean, healthy subjects served as controls for pre-intervention measurements. Echocardiography and muscle perfusion were performed during fasting and under stable euglycaemic-hyperinsulinaemic clamp conditions. O-IR patients demonstrated subclinical cardiac dysfunction as evidenced by lower left ventricular global longitudinal strain (GLS), e' tissue velocity, and left atrial strain and reduced muscle perfusion. The intervention arm showed improvements in insulin resistance [glucose infusion rate (GIR)], GLS, e', atrial strain, and muscle perfusion in fasting conditions, as well as improved responses of GLS and muscle perfusion to insulin during clamp. Significant interactions were found between the allocation to low-salt diet and improvement in muscle perfusion on change in GIR at follow-up (P = 0.030), and between improvement in muscle perfusion and change in GIR on change in GLS response to insulin at follow-up (P = 0.026). Mediation analysis revealed that the relationship between the reduction of sodium intake and improvement in GLS was mediated by improvements in muscle perfusion and GIR (decrease in beta coefficient from -0.29 to -0.16 after the inclusion of mediator variables to the model). CONCLUSIONS: The reduction of dietary sodium in the normotensive O-IR population improves cardiac function, and this effect may be associated with the concomitant improvements in skeletal muscle perfusion and insulin resistance. These findings might contribute to refining heart failure preventive strategies.

The influence of acute coronary syndrome on levels of clopidogrel active metabolite and platelet inhibition in patients with and without CYP2C19*2(681 G>A), *3(636 G>A) and ABCB1(C3435C> T) gene polymorphisms.

INTRODUCTION: Although ticagrelor and prasugrel remain the standard antiplatelet treatments in acute coronary syndrome (ACS), numerous patients still present with indications for clopidogrel use. AIM: We aimed to assess the levels of clopidogrel active metabolite and to evaluate the effect of the drug on platelet inhibition in patients with ACS as compared with those with stable coronary disease. Patients were assessed for the presence of the most common genetic polymorphisms that reduce the absorption (ABCB1) and activation (CYP2C19*2 and CYP2C19*3) of clopidogrel to exclude the effect of genetic variability on drug concentrations and activity. MATERIAL AND METHODS: This single-center, open-label, prospective study included 199 patients hospitalized due to ST-segment elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI) in Killip class I-III, who underwent percutaneous coronary intervention. The control group included 22 patients with stable coronary artery disease. RESULTS: The mean (SD) levels of active clopidogrel were 17.1 (12.3) ng/ml in controls and 16.4 (12.0) ng/ml in the whole study group (p < 0.68). No differences were noted in clopidogrel levels between patients with STEMI and NSTEMI (mean (SD), 17.6 (2.3) ng/ml and 15.1 (11.5) ng/ml; p < 0.45) or between STEMI and NSTEMI groups and controls (p < 0.38 and p < 0.61, respectively). No effect of ABCB1 or CYP2C19 polymorphism was observed in the study subgroups. CONCLUSIONS: We concluded that ACS does not affect the levels of clopidogrel active metabolite or platelet inhibition in patients in Killip class I-III with or without CYP2C19 or ABCB1 gene polymorphisms.

Platelet Reactivity and Response to Aspirin and Clopidogrel in Patients with Platelet Count Disorders.

BACKGROUND: Platelet reactivity and response to antiplatelet drugs, acetylsalicylic acid (ASA) and clopidogrel, in patients with thrombocytopenia and thrombocythemia can have a potentially important effect on the outcome. The effectiveness and safety of antiplatelet drugs in such patients has not been well examined. Measuring the effect of ASA and clopidogrel on platelets could help guide the therapy. Nevertheless, platelet response to antiplatelet drugs is not routinely measured in platelet count disorders and relevant evidence is scarce. AIMS: The study aimed to measure platelet reactivity and response to ASA and clopidogrel in patients with platelet count disorders. MATERIALS AND METHODS: This was a cross-sectional study of consecutive patients hospitalized in cardiology and hematology departments in the years 2018-2019. The study included patients with thrombocytopenia (PLT < 150 G/L) and thrombocythemia (PLT > 450 G/L) on ASA or dual antiplatelet therapy (DAPT; ASA plus clopidogrel). Controls included patients on antiplatelet drugs with normal platelet count. Platelet reactivity was measured in whole blood (Multiplate aggregometer, Roche, Switzerland) using arachidonic acid (AA), adenosine-5'-diphosphate (ADP), and thrombin receptor agonist peptide-6 (TRAP) as agonists. Platelet aggregation was expressed in arbitrary units (AU). AA-induced aggregation was used as a measure of response to ASA with a cut-off above 30 AU showing high on-treatment platelet reactivity to ASA (HTPR-A). ADP-induced aggregation measured response to clopidogrel with a cut-off above 48 AU for high on-treatment platelet reactivity to clopidogrel (HTPR-C). TRAP-induced aggregation measured baseline platelet reactivity not affected by oral antiplatelet drugs. RESULTS: The study included 174 patients. There were 64 patients with thrombocytopenia, 30 patients with chronic thrombocythemia, and 80 controls. All patients were on 75 mg of ASA and 32% of them additionally on 75 mg of clopidogrel due to a history of recent coronary artery angioplasty. AA- and ADP-induced aggregation was comparable between thrombocytopenic patients and controls (median (IQR) 19 (7-28) vs. 23 (15-38) for AA AU and 32 (16-44) vs. 50 (32-71) for ADP AU, respectively), while it was significantly higher in thrombocythemic patients (median (IQR) 80 (79-118) for AA AU and 124 (89-139) for ADP AU). TRAP-induced aggregation showed significantly lowest aggregation in thrombocytopenic (median (IQR) 41 (34-60) for TRAP AU) and highest in thrombocythemic patients (median (IQR) 137 (120-180) for TRAP AU). HTPR-A was frequent in thrombocythemic patients in comparison with thrombocytopenic patients and controls (60% vs. 4% vs. 15%, respectively; p < 0.0002). HTPR-C was highly common in thrombocythemic patients and least common in thrombocytopenic ones in comparison with controls (80% vs. 8% vs. 40%, respectively; p < 0.001). CONCLUSION: Chronic thrombocytopenia does not significantly affect platelet reactivity and response to ASA and clopidogrel in comparison with controls. Thrombocytosis significantly increases platelet reactivity and attenuates response to both ASA and clopidogrel.

Original and generic clopidogrel: A comparison of antiplatelet effects and active metabolite concentrations in patients without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and *3.

BACKGROUND: Ticagrelor and prasugrel are widely used as antiplatelet therapy after coronary angioplasty. However, there is a group of patients with indications for clopidogrel treatment. This population includes patients with chronic or acute coronary syndrome who are treated invasively and have contraindications to the use of novel antiplatelet drugs due to antithrombotic treatment (particularly with non-vitamin K antagonist oral anticoagulants). A wide range of generic forms of clopidogrel are available on the market. However, it is unclear whether they are as effective as the originator drug. OBJECTIVES: In the current study, we aimed to assess the concentrations of the active metabolite of clopidogrel and its effect on platelet aggregation inhibition in patients receiving the originator drug in comparison with those receiving generic clopidogrel. MATERIAL AND METHODS: We enrolled 22 healthy individuals without polymorphisms in the ABCB1 gene and the allele variants CYPC19*2 and CYPC19*3. All participants received a loading dose of clopidogrel (600 mg), followed by a maintenance dose of 75 mg for the next 3 days. On day 3, blood samples were obtained 1 h after drug administration to assess active metabolite concentrations using liquid chromatography with tandem mass spectrometry. In each participant, platelet aggregation was assessed with light transmission aggregometry after 5-µmol/L and 10-µmol/L adenosine diphosphate (ADP) stimulation. Assays were performed for the originator clopidogrel and 2 different generic groups. RESULTS: The mean ± standard deviation (SD) concentrations of active clopidogrel did not differ between the originator drug and 2 generic products with clopidogrel (12.7±5 pg/µL compared to 13.0 ±4 pg/µL compared to 14.4 ±4 pg/µL). Platelet aggregation inhibition after stimulation with 5 µmol/L and 10 µmol/L ADP was similar for all preparations. CONCLUSIONS: In comparison with original clopidogrel, the use of its generic form does not affect the blood concentrations of the active metabolite or its antiplatelet effect.

Simultaneous placement of leadless pacemaker and dialysis catheter in patient with exhausted vasculature.

The problem with limited venous access may occur in patients receiving long-term hemodialysis treatment with no possibility of arteriovenous access or in patients with cardiac implantable electronic device-related infection leading to the removal of cardiac implantable electronic device. We present a case report where both situations occur simultaneously. Using recent development in cardiac pacing-leadless cardiac pacemaker-we manage to overcome the vascular access problem. The described case emphasizes the necessity of multispecialty collaboration and gains of new pacing technology in patients who need placement of vascular access for hemodialysis and cardiac implantable electronic device where vascular access is scarce.

The Links between Cardiovascular Diseases and Alzheimer's Disease.

The root cause of non-inherited Alzheimer's disease (AD) remains unknown despite hundreds of research studies performed to attempt to solve this problem. Since proper prophylaxis remains the best strategy, many scientists have studied the risk factors that may affect AD development. There is robust evidence supporting the hypothesis that cardiovascular diseases (CVD) may contribute to AD progression, as the diseases often coexist. Therefore, a lack of well-defined diagnostic criteria makes studying the relationship between AD and CVD complicated. Additionally, inflammation accompanies the pathogenesis of AD and CVD, and is not only a consequence but also implicated as a significant contributor to the course of the diseases. Of note, АроЕε4 is found to be one of the major risk factors affecting both the cardiovascular and nervous systems. According to genome wide association and epidemiological studies, numerous common risk factors have been associated with the development of AD-related pathology. Furthermore, the risk of developing AD and CVDs appears to be increased by a wide range of conditions and lifestyle factors: hypertension, dyslipidemia, hypercholesterolemia, hyperhomocysteinemia, gut/oral microbiota, physical activity, and diet. This review summarizes the literature and provides possible mechanistic links between CVDs and AD.

Platelet polyphosphate level is elevated in patients with chronic primary thrombocytopenia: A preliminary study.

BACKGROUND: Platelets are key players in hemostasis. These blood cells contain different types of granules. Recently, there has been a growing interest in the role of inorganic polyphosphate (polyP) structures stored in dense granules of platelets and secreted during platelet activation. OBJECTIVES: To measure platelet polyP levels in patients with thrombocytopenia and thrombocythemia, and to examine the relationship of this indicator with platelet aggregation. MATERIAL AND METHODS: The study included 36 patients with hematological disorders (26 with primary chronic thrombocytopenia and 10 with essential thrombocythemia (ET)) and 40 healthy subjects. Platelet reactivity was measured using whole blood impedance aggregometry. The polyP levels were isolated from lysed platelets, which were obtained from citrated platelet-rich plasma. The procedure included inactivating endogenous phosphatases, removing phosphate units derived from DNA and proteins, and finally hydrolyzing them into monophosphate units. A colorimetric assay using malachite green and ammonium molybdate was performed in order to quantify polyP levels. RESULTS: The polyP concentrations were significantly higher in the patients with thrombocytopenia than in the patients with thrombocythemia or the controls. The polyP level was not correlated with the level of aggregation. CONCLUSIONS: The higher polyP levels observed in the patients with low platelet counts may indicate the existence of a compensatory mechanism that prevents excessive bleeding in such patients. Our study provides evidence of an essential role of polyP in platelet function and the coagulation process.

Blood Platelet Count at Hospital Admission Impacts Long-Term Mortality in Patients with Acute Coronary Syndrome.

INTRODUCTION: Platelets play a fundamental role in the pathogenesis of acute coronary syndrome (ACS). The platelet count (PC) at hospital admission is easy to obtain, but whether thrombocytopenia or/and thrombocytosis impact long-term mortality (LTM) after ACS is unclear. OBJECTIVE: To evaluate the effect of PC at hospital admission on LTM in patients with ACS. METHODS: This retrospective cohort study included patients with the ICD-10 codes for unstable angina (I.20) and acute myocardial infarction (I.21, I.22). Thrombocytopenia was defined as a blood PC <150 G/L and thrombocytosis as a PC >450 G/L. Additional platelet indices which were tested included plateletcrit (PCT), the mean platelet volume (MPV), the platelet distribution width (PDW), and the platelet larger cell ratio (P-LCR). Data on all-cause death were obtained from the National Health Fund database. RESULTS: The study included 3,162 patients with a median follow-up of 27.2 months (interquartile range 12.5-46.8 months; max 68.7 months). Patients with thrombocytopenia and thrombocytosis yielded a higher maximal analyzed 5-year mortality rate in comparison with normal PC patients (45.8 and 47.7 vs. 24.2%, respectively; p < 0.00001) which was mainly driven by higher deaths at 1-2 years after ACS. The 5-year LTM was also significantly higher in patients with abnormal PCT and MPV levels in comparison with patients with PCT and MPV within the normal range. Other platelet indices (PDW, P-LCR) were not associated with a worse outcome. The Cox proportional hazards model revealed that thrombocytopenia at admission was independently associated with higher LTM after ACS (RR 1.83; 95% CI 1.1-3.0; p = 0.01). CONCLUSIONS: Both thrombocytopenia and thrombocytosis at hospital admission in post-ACS patients are associated with a significant almost two times higher 5-year mortality rate.

Response to antiplatelet therapy in patients undergoing invasive treatment due to acute coronary syndrome complicated by cardiogenic shock.

INTRODUCTION: There are limited data on platelet reactivity and response to antiplatelet drugs in patients with cardiogenic shock. AIM: To assess platelet reactivity on dual antiplatelet therapy with acetylsalicylic acid (ASA) and ticagrelor, a novel potent P2Y12 receptor inhibitor, in patients with cardiogenic shock in the course of acute coronary syndrome (ACS) who received invasive treatment. MATERIAL AND METHODS: We enrolled 12 consecutive patients with ACS complicated by cardiogenic shock. To assess response to antiplatelet therapy during cardiogenic shock, only patients with symptoms persisting for at least 3 days and who completed a 5-day follow-up were included in the study. Patients received a loading dose of ASA (300 mg) and ticagrelor (180 mg), followed by a maintenance dose (ASA, 1 × 75 mg; ticagrelor, 2 × 90 mg). Blood samples for platelet function tests were collected. Platelet aggregation was assessed with a Multiplate whole-blood impedance aggregometer. Arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP) were used as aggregation agonists. RESULTS: Response to antiplatelet therapy assessed by aggregometry showed numerically higher on-ASA platelet reactivity on day one and statistically significant higher on-ticagrelor platelet reactivity on day one in comparison with following days. There were 2 patients with high on ASA platelet reactivity and 3 with high on ticagrelor platelet reactivity, but only on the day one. CONCLUSIONS: Some patients with cardiogenic shock in the course of ACS treated invasively show a lower response to ASA and ticagrelor only on the first day after invasive treatment, with a good response on subsequent days.

Münchausen Syndrome as an Unusual Cause of Pseudo-resistant Hypertension: A Case Report.

Münchausen syndrome can be characterized by simulated illness, pathological lying and wandering from place to place (the patient typically presents to numerous hospitals). Individuals with elevated blood pressure due to non-adherence to medication have the so-called pseudo-resistant hypertension. A 45-year-old woman was admitted to hospital on an emergency basis because of a hypertensive crisis. Despite combination antihypertensive treatment, normalization of blood pressure was not achieved and a device to produce a therapeutic arteriovenous fi stula was implanted. Aft er the procedure, a signifi cant increase in pulmonary artery pressure was observed and closure of the fistula was performed by implantation of the stent graft . The suspicion was raised that the patient had not been taking her prescribed medications. Therefore, blood samples were taken and the serum was analyzed for presence of the prescribed drugs (atorvastatin, bisoprolol, chlorthalidone, clonidine, doxazosin, furosemide, nitrendipine, oxazepam and valsartan). The results confirmed suspected failure of the patient to take the prescribed medications. Münchausen syndrome is usually first suspected when inexplicable laboratory test results are noted. To our knowledge, this is the first reported case of Münchausen syndrome with pseudo-resistant hypertension leading to the implantation of a device to produce a therapeutic arteriovenous fi stula.

Does Arterial Hypertension Affect Plasma Levels of Matrix Metalloproteinases and Their Tissue Inhibitors in Patients with Stable Coronary Artery Disease? A Preliminary Study.

BACKGROUND: Arterial hypertension (HT) is a serious and prevalent epidemiological factor in the development of coronary artery disease (CAD). Metalloproteinases (MMPs), especially MMP-2 and MMP-9, and their natural endogenous tissue inhibitors (TIMPs) are involved in the pathogenesis of HT and its complications. MMPs are also involved in the development of diabetes (DM), a risk factor for CAD. The aim of the study was to explore the influence of CAD, HT, and DM on changes in plasma levels of MMP-2 and MMP-9 and their inhibitor TIMP-4. METHODS AND RESULTS: The study involved 70 patients with stable CAD admitted for coronary angiography and 15 healthy subjects. Whole blood samples were collected prior to angiography. MMP-2, MMP-9, and TIMP-4 levels in plasma were estimated using ELISA tests. CAD patients showed a significantly increased level of TIMP-4 and decreased level of MMP-2 in comparison to healthy controls (p=0.011 and p=0.037, respectively). Concentration of MMP-2, MMP-9, and TIMP-4 did not differ in the group with and without hypertension. Patients with DM presented higher MMP-2 level than patients without DM (p < 0.001). Multiple regression analysis of the influence of independent variables such as CAD stage, DM, and HT on MMP-2, MMP-9, and TIMP-4 showed that only DM was independently associated with a higher level of MMP-2 (ß = 0.42, R 2 = 0.17, p < 0.001). CONCLUSION: Data showed that patients with CAD presented higher TIMP-4 and lower MMP-2 concentration regardless of HT and DM. HT had no effect on MMP-2, MMP-9, and TIMP-4 levels in serum. DM was independently associated with higher MMP-2 concentration; however, co-occurrence of CAD and DM was associated with the balance in the MMP-2 level. Concentration of MMP-9 did not change significantly in any of the analysed groups.

Distribution of polymorphisms in the CYP2C19 and ABCB1 genes among patients with acute coronary syndrome in Lower Silesian population.

BACKGROUND: Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel administered to treat patients with acute coronary syndrome (ACS) is still being used. However, despite the proven efficacy of this treatment regimen, thromboembolic complications have been observed in some individuals. The reason for this phenomenon is linked to the so-called increased responsiveness of platelets despite high platelet resistance (HPR). A significant role in HPR is attributed to genetically determined differences in the absorption and activation of clopidogrel. OBJECTIVES: The aim of the study was to assess the incidence of polymorphisms of the ABCB1 and CYPC19 genes that encode proteins involved in the absorption and metabolism of clopidogrel. MATERIAL AND METHODS: The analysis was performed in 199 consecutive patients from Lower Silesian voivodeship (Poland) who underwent coronary angioplasty with stenting for ACS. The single nucleotide polymorphism of the CYP2C19 and ABCB1 genes was performed using a mini sequencing or restriction fragment length polymorphism method. RESULTS: The results of this study revealed the high incidence of patients who may be unresponsive to antiplatelet treatment due to genetic causes. The CYPC19*2 allele in the form of homozygote or mutation heterozygote appeared in 26.1% of the study population. ABCB1 (C3435C> T) polymorphism was associated with 84% of patients. The total incidence of allelic disorders of low drug absorption and metabolism reached 14.6%. CONCLUSIONS: The data obtained should prompt clinicians to use more recent antiplatelet agents (ticagrelor or prasugrel) first, instead of clopidogrel.

Parameters of Oxidative and Inflammatory Status in a Three-Month Observation of Patients with Acute Myocardial Infarction Undergoing Coronary Angioplasty-A Preliminary Study.

Background and Objectives: Patients with acute myocardial infarction (MI) are usually treated with percutaneous transluminal coronary angioplasty (PTCA), which is burdened with a risk of postoperative complications, often accompanied by biochemical disturbances. The aim of our study was to evaluate a set of selected parameters of oxidative and inflammatory status, which could be useful in the management of post-procedural care in MI patients after PTCA. Materials and Methods: In this preliminary study, ischemia modified albumin (IMA), advanced oxidation protein products (AOPP), thiol groups (SH), total antioxidant status (TAS), insulin growth factor-1 (IGF-1), presepsin (PSP), and trimethylamine N-oxide (TMAO) were chosen as candidate biomarkers, and were determined in patients with MI who underwent PTCA at two time points: During cardiac episodes (at admission to the hospital, T0) and 3 months later (T3). Results: Most of the examined parameters were significantly different between patients and control subjects (except for IMA and TAS), but only hsCRP changed significantly during the time of observation (T0 vs. T3). Discriminant analysis created a model composed of AOPP, hsCRP, PSP, and TMAO, which differentiated male subjects into a group with MI and a control (without cardiovascular diseases). Conclusion: This set of parameters seems useful in evaluating inflammatory and oxidative status in MI patients after PTCA.

Usefulness of myocardial work measurement in the assessment of left ventricular systolic reserve response to spironolactone in heart failure with preserved ejection fraction.

AIMS: Improvement in left ventricular (LV) systolic reserve, including exertional increase in global longitudinal strain (GLS), may contribute to the clinical benefit from therapeutic interventions in heart failure with preserved ejection fraction (HFpEF). However, GLS is an afterload-dependent parameter, and its measurements may not adequately reflect myocardial contractility recruitment with exercise. The estimation of myocardial work (MW) allows correction of GLS for changing afterload. We sought to investigate the associations of GLS and MW parameters with the response of exercise capacity to spironolactone in HFpEF. METHODS AND RESULTS: We analysed 114 patients (67 ± 8 years) participating in the STRUCTURE study (57 randomized to spironolactone and 57 to placebo). Resting and immediately post-exercise echocardiograms were performed at baseline and at 6-month follow-up. The following indices of MW were assessed: global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. The amelioration of exercise intolerance at follow-up in the spironolactone group was accompanied by a significant improvement in exertional increase in GCW (P = 0.002) but not in GLS and other MW parameters. Increase in exercise capacity at 6 months was independently correlated with change in exertional increase in GCW from baseline to follow-up (ß = 0.24; P = 0.009) but not with GLS (P = 0.14); however, no significant interaction with the use of spironolactone on peak VO2 was found (P = 0.97). CONCLUSION: GCW as a measure of LV contractile response to exertion is a better determinant of exercise capacity in HFpEF than GLS. Improvement in functional capacity during follow-up is associated with improvement in exertional increment of GCW.

Plasma YKL-40 levels correlate with the severity of coronary atherosclerosis assessed with the SYNTAX score.

Introduction YKL­40 is a protein released locally by inflammatory cells. Thus, it may constitute a biomarker of inflammatory conditions, such as atherosclerosis. Objectives The aim of the study was to determine YKL­40 levels in patients with ischemic heart disease and to analyze the correlation of this biomarker with the severity of coronary atherosclerosis. Patients and methods The study included 158 patients: 52 with stable ischemic heart disease and 67 with acute coronary syndrome: ST­segment elevation myocardial infarction (STEMI; n = 47) or non-ST­segment elevation myocardial infarction (NSTEMI; n = 20). The control group included 39 individuals without abnormalities in coronary vessels. We evaluated plasma YKL­40 levels and their correlation with the severity of coronary atherosclerosis assessed with the SYNTAX score. Results Patients with myocardial infarction had higher plasma YKL­40 levels than those with stable ischemic disease (median [range], 235.3 [161.6-366.1] ng/ml vs 61.2 [53.1-83.1] ng/ml; P <0.001) or controls (median [range], 235.3 [161.6-366.1] ng/ml vs 55.7 [51.2-75.2] ng/ml; P <0.001). No differences were found in YKL­40 concentrations between STEMI and NSTEMI patients (median [range], 263 [150.3-363.7] ng/ml and 214.9 [163.4-367.6] ng/ml, respectively; P = 0.7). The SYNTAX score in patients with ischemic heart disease correlated positively with YKL­40 concentrations (R = 0.34; P <0.001). Conclusions YKL­40 can be considered a potential biomarker of coronary atherosclerosis severity.