Risk Factor For Cardiovascular Complications Research Articles

Prevalence and Risk Factors for Cardiovascular Complications in Patients With Diabetic Foot Ulcers: A Seven-Year Retrospective Study

Prevalence and Risk Factors for Cardiovascular Complications in Patients With Diabetic Foot Ulcers: A Seven-Year Retrospective Study

Anemia of chronic diseases in the early stages of chronic kidney disease as a risk factor for cardiovascular complications in patients with glomerulonephritis

To determine biomarkers of anemia of chronic disease (ACD) in patients with glomerulonephritis (GN) in the early stages of CKD, to assess their role as risk factors for cardiovascular complications (CVС). Seventy nine patients with GN were studied, among them: 40 with primary сhronic GN (CGN), 39 with secondary forms:19 - GN with ANCA-associated systemic vasculitis, 20 - GN with systemic lupus erythematosus (SLE) at early (all I-II) CKD stages. In all patients, the level of serum C-reactive protein (CRP), hepcidin, interferon γ, and the circulating form of protein Klotho (s-Klotho) were determined. When a relative iron deficiency was detected [transferrin iron saturation coefficient (TSAT) <20%], patients were administered parenterally iron [III] sucrose hydroxide complex (Venofer). The frequency of anemia among patients with systemic diseases is 3.2 times higher than among patients with primary CGN. Patients with anemia (group I; n=43) had higher rates of daily proteinuria (p<0.001), systolic blood pressure (p<0.05), serum levels of interferon γ (p<0.001) and hepcidin (p<0.001) and lower values of eGFR (p<0.05) than patients without anemia (group II; n=36). A strong inverse correlation was noted between the level of hepcidin and the content of iron in serum (r=-0.856; p<0.001), between the level of hemoglobin and the level of interferon γ (r=-0.447; p<0.05), hepcidin (r=-0.459; p<0.05) and CRP (r=-0.453; p<0.05). A significant inverse correlation was found between the level of hemoglobin and CVC risk factors - the value of systolic blood pressure (r=-0.512; p<0.05) and the mass index of the left ventricular myocardium (r=-0.619; p<0.01). At the same time, the contribution of 2 from 6 analyzed factors, hepcidin and eGFR, to the development of ACD was 92.5%, of which 86.6% accounted for hepcidin. A strong direct correlation was also found between a decrease in hemoglobin level and a decrease in the level of s-Klotho protein (r=0.645; p<0.001), a decrease in the level of s-Klotho and an increase in the level of serum hepcidin (r=-0.541; p<0.05). The leading value of anemia (beta -0,29; p=0,04) and depression of the s-Klotho level (beta -0,44; p=0,02) as independent cardiovascular risk factors in this group of patients was confirmed by multivariate analysis. In patients with identified deficiency of iron (n=40), after 3-4 weeks of intravenous administration of venofer, the target level of hemoglobin (Нb>120 g/l) and transferrin saturation with iron (TSAT>20%) were achieved. Among the biomarkers of ACD in patients with immunoinflammatory diseases of the kidneys (primary and secondary СGN), the increase in the serum level of hepcidin is greatest importance. The concomitant to anemia decrease in s-Klotho is a leading risk factor for CVС in CKD. Early correction of ACD with iron supplements makes it possible to achieve target levels of Hb and TSAT and have subsequently a positive effect on the production of s-Klotho and the severity of left ventricular hypertrophia.

Pre-Existing Atrial Fibrillation in Hospitalized Patients with COVID-19: Insights from the CARDIO COVID 19-20 Registry.

Pre-existing (chronic) atrial fibrillation (AF) has been identified as a risk factor for cardiovascular complications and mortality in patients with COVID-19; however, evidence in Latin America (LATAM) is scarce. This prospective and multicenter study from the CARDIO COVID 19-20 database includes hospitalized adults with COVID-19 from 14 countries in LATAM. A parsimonious logistic regression model was used to identify the main factors associated with mortality in a simulated case-control setting comparing patients with a history of AF to those without. In total, 3260 patients were included, of which 115 had AF. The AF group was older, had a higher prevalence of comorbidities, and had greater use of cardiovascular medications. In the model, AF, chronic kidney disease, and a respiratory rate > 25 at admission were associated with higher in-hospital mortality. The use of corticosteroids did not reach statistical significance; however, an effect was seen through the confidence interval. Thus, pre-existing AF increases mortality risk irrespective of other concomitant factors. Chronic kidney disease and a high respiratory rate at admission are also key factors for in-hospital mortality. These findings highlight the importance of comorbidities and regional characteristics in COVID-19 outcomes, in this instance, enhancing the evidence for patients from LATAM.

Renal artery stenosis increases the risk of incident atrial fibrillation and cardiovascular events incorporating death

Abstract Background Renal artery stenosis (RAS) remains an under-recognized clinical risk factor for cardiovascular complications. Its long-term impact on AF arrhythmogenesis is unclear. Objective To investigate the role of RAS on incident AF and related adverse cardiovascular events Methods We performed a retrospective cohort study that comprised 100 patients with ultrasonographically-confirmed atherosclerotic RAS, and 50 age- and sex-matched controls who were healthy renal transplant donors (age 52.6 ±5.6 vs 50.1 ±10.7years, women 59% vs 70%). Incident AF was ascertained from clinical records. Primary endpoint was defined as the composite of incident AF, myocardial infarction, unstable angina, heart failure, ischemic stroke, peripheral arterial disease, end-stage renal failure, and cardiovascular death. Results Over a follow-up duration of 4818 ± 2751 days, RAS was significantly associated with incident AF (9.4% versus 0%, P=0.025). Kaplan-Meier analyses showed that RAS was associated with reduced incident AF event-free survival (Log-rank Mantel-Cox=4.6 P=0.032, Figure). Multivariable logistic regression showed that after adjustment for potential confounders (including age, sex, smoking, alcohol use, history of hypertension, diabetes mellitus, myocardial infarction, heart failure, ischemic stroke, renal function and serum low-density lipoprotein level), RAS was independently associated with substantially increased risk of the primary endpoint (OR=27.8, 95%CI [2.3 – 333.9], P=0.009), Conclusions RAS is an important and under-recognized independent risk factor for AF and cardiovascular events incorporating death. Its pathophysiological implications with a view to potential interventions need to be further explored.

#1185 Cardiovascular, renal and mortality risk by the KDIGO risk classification: the first observational study in Japan

Abstract Background and Aims The prevalence of chronic kidney disease (CKD) has been increasing, affecting 850 million people worldwide and 13 million individuals in Japan. CKD is a risk factor for cardiovascular complications including heart failure, and dialysis. KDIGO risk classification is widely used for the management of people with CKD in Japan; however, risk of clinical outcomes by the KDIGO classification in Japanese population is unclear. The aim of this study is to describe the risk of major adverse cardiovascular event (MACE) and renal outcomes according to the KDIGO classification in Japanese clinical practice. Method This study was a cohort study using data collated from the RWD database which includes electronic medical records and claims data from approximately 200 medical institutions across Japan since 2000. Subjects aged ≥18 years with two or more consecutive results of eGFR &amp;lt;90 mL/min/1.73 m2 at least 90 days apart within a 360-day period were included, and those received renal replacement therapy (RRT; dialysis or renal transplantation) before the index date was excluded. The index date was defined as the date of the second eGFR measurement &amp;lt;90 mL/min/1.73 m2 between January 2004 and December 2020. Patients were categorized into KDIGO classification G2-G5 based on their eGFR values and A1-A3 based on urine protein test (quantitative test and urine dipstick) results and into `no urine protein data` if no urine protein test was available. The primary endpoint was MACE that was defined as a composite of myocardial infarction, stroke, heart failure hospitalization, and in-hospital death. The secondary endpoint was renal outcomes defined as a composite of RRT, eGFR decline &amp;gt;50%, eGFR &amp;lt;15 mL/min/1.73 m2, diagnosis of CKD stage 5, and in-hospital death, and was analyzed in the group excluding patients with eGFR &amp;lt;15 mL/min/1.73 m2 or with diagnosis of stage 5 CKD on or before the index date. The risk of MACE and renal outcomes were evaluated using the cox proportional hazards model with G2A1 as a reference. Sensitivity analyses were performed for the population excluding those without urine protein data and for the population with quantitative urine protein test results. Results This study included 543,606 patients who met the criteria. Mean age was 61.6 ± 15.3 years, and 50.1% was male. Of those, 222,246 (40.9%) had no urine protein data. Tables 1 and 2 show hazard ratio (HR) for MACE and renal outcomes, respectively. HR (95% confidence interval) for MACE was 1.17 (1.12-1.21) in G2A2 and 1.16 (1.12-1.20) in G3aA1, showing significantly increased risk in early stages of CKD, and continued to increase as disease advances to 2.83 (2.54-3.15) in G5A3. HR for renal outcomes was similarly significantly increased in early stages of CKD, and further increased to 19.96 (18.62-21.40) in G4A3. Results of two sensitivity analyses, excluding subjects with no urine protein data (n = 321,360, 59.1% of overall population) shown in Table 3 and 4, and excluding patients with no quantitative data (n = 36,615, 6.7% of overall population) showed similar trends, supporting the robustness of primary findings. Conclusion This study is the first to demonstrate the applicability of the KDIGO risk classification in assessing the risk of cardiovascular events, including heart failure, and renal outcomes in Japan. Risk of events was increased from early stages of CKD (G3aA1 and G2A2), suggesting the importance of early diagnosis and therapeutic intervention through appropriate testing. These findings may contribute to better management of people with CKD.

#3106 The prevalence and degree of hyperkalaemia in adult patients with chronic kidney disease, in Durban, South Africa

Abstract Background and Aims Hyperkalaemia is a known risk factor for the development of cardiac rhythm disturbances and sudden cardiac death. The presence of chronic kidney disease (CKD) is also an independent risk factor for cardiovascular complications. The prevalence of hyperkalaemia in patients with CKD has previously varied widely between studies. The prevalence of hyperkalaemia in the patients attending the renal clinic at Inkosi Albert Luthuli Central Hospital (IALCH) has not been previously determined. This study aimed to discover the prevalence of hyperkalaemia in patients attending the renal clinic at IALCH, as well as the degree of severity amongst the patients in whom hyperkalaemia was present. Demographic and other variables were also assessed for an association with hyperkalaemia. Method A retrospective review of outpatients attending the renal clinic at IALCH from 1 October 2016 until 30 September 2017. Demographic and clinical characteristics were retrieved and descriptive statistical methods and logistic regression analysis were performed. Results The study consisted of 200 patients, of whom the majority were female (n=120, 60%). The prevalence of hyperkalaemia amongst these patients was found to be 16%. In those with stage 3 CKD, the prevalence of hyperkalaemia was 7.69%. In those with stage 4 CKD, the prevalence of hyperkalaemia was 20.5% and in those with stage 5 CKD the prevalence was 17.3%. There were no statistically significant associations between hyperkalaemia and demographic variables, nor with dietician intervention. There was a significant association with the use of sodium polystyrene sulfonate. Conclusion CKD is a growing burden in the developing world. With CKD comes metabolic and other derangements, including electrolyte abnormalities as well as increased cardiovascular risk. Hyperkalaemia is associated with worsening CKD. In addition, hyperkalaemia puts patients at risk of cardiac dysrhythmias and sudden cardiac death. Pharmacological measures to manage CVD risk should be weighed up against the risk of hyperkalaemia related complications. Potassium lowering agents should be considered to allow for optimal CVD management in the setting of hyperkalaemia in CKD.

Prognostic properties of biomarkers in COVID-19 infection and concomitant chronic coronary syndromes

Background. The novel coronavirus disease 2019 (COVID-19), caused by a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become an unprecedented challenge for the health care system and has taken a leading position among infectious diseases due to the rapid spread and development of complications from various body systems. The problem of cardiac comorbidity in COVID-19 has several aspects: the impact of concomitant cardiovascular diseases on the incidence of a new viral infection, its severity and risk of mortality, as well as possible side effects of a number of drugs traditionally used to treat certain types of cardiovascular diseases. SARS-CoV-2 is not only a pneumonia pathogen, but also causes serious systemic consequences. Patients with cardiovascular diseases and risk factors for cardiovascular complications, such as hypertension and coronary heart disease, are more exposed to fatal consequences of COVID-19. In addition, a significant proportion of patients develop COVID-associated myocardial injury, which significantly increases the risk of in-hospital mortality. The purpose of the study was to investigate the prognostic role of individual biomarkers in patients with COVID-19-associated pneumonia on the background of chronic coronary syndromes. Materials and methods. This study was defined as an open-label, non-randomized, controlled, comparative one in parallel groups. 124 patients with COVID-19-associated pneumonia were selected upon admission, including 92 participants with a history of chronic coronary syndromes. Results. The study showed that elevated levels of biomarkers such as proinflammatory cytokine interleukin-6, iron-storage protein ferritin, serum angiotensin-converting enzyme-2, ketone body beta-hydroxybutyric acid, and fibrin breakdown product D-dimer may be associated with a more severe course of pneumonia caused by COVID-19 infection. Thus, these biomarkers had good prognostic value in predicting severe disease and death in patients with chronic coronary syndromes during hospitalization. Conclusions. The study confirms that an increase in the level of proinflammatory biomarkers is a predictor for the development of a severe coronavirus infection.

The Relationship Between Egg Consumption and Risk of Type 2 Diabetes in the Shahrekord Cohort Study

Background and aims: Diabetes is a common non-communicable and metabolic disease, and its prevalence is predicted to double by 2045. It is also a significant risk factor for cardiovascular complications and mortality. The study investigated the association between egg consumption and the prevalence of type 2 diabetes (T2D) in a cohort of Iranian adults. Methods: This study compared 261 cases of T2D with 261 controls matched for age and features and assessed their dietary intake using a food frequency questionnaire. The inclusion criterion involved the absence of concurrent chronic diseases apart from T2D. Results: Based on the results, the participants’ average age was 53.32 years, with a slightly higher proportion of females in both groups. Logistic regression analysis revealed that increased consumption of eggs is associated with a diminished risk of developing T2D (P=0.01). Conclusion: The study suggests that egg consumption may have beneficial effects on glucose metabolism and insulin sensitivity, and regional and genetic differences may influence the relationship between egg consumption and T2D. It calls for further longitudinal and interventional studies to confirm the findings.

CARDIOVASCULAR COMPLICATIONS IN PATIENTS ON RENAL REPLACEMENT THERAPY

Introduction. A progressive decrease in the rate of glomerular filtration is an independent risk factor for cardiovascular complications, as well as a marker of an unfavorable prognosis of cardiovascular diseases. Cardiovascular complications arising against the background of end-stage renal failure are the main cause of mortality in patients undergoing renal replacement therapy.&#x0D; The aim of the study was to determine the features and prevalence of cardiovascular complications in patients undergoing renal replacement therapy.&#x0D; Materials and methods. A retrospective study was conducted of 114 medical records of nephrology patients who were treated in the center of nephrology and dialysis of Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky. Patients were divided into three groups: two experimental and one control group. The first experimental group consisted of 44 (38.6%) patients who were on RRT by the method of programmed hemodialysis. The second experimental group consisted of 21 (18.4%) patients who were also undergoing RRT, but by the method of peritoneal dialysis. The control group consisted of 49 (43.0%) patients with CKD stages I-II. Analysis of laboratory data of traditional risk factors for cardiovascular complications (lipidogram), as well as non-traditional ones (level of calcium and phosphorus) was carried out. The frequency of cardiovascular complications in patients on renal replacement therapy was studied.&#x0D; Results. A statistically significant difference was found between the indicators of the atherogenicity index in the groups GD1 with CG1 (р=0.001) and GD2 with CG2 (р=0.031), PD1 and CG1 (р=0.005) and PD2 with CG2 (р=0.027). When analyzing the correlations between indicators of mineral metabolism in the experimental and control groups, it was found that weak and medium inverse correlations were observed in the experimental groups (GD1: -0.4703, GD2: -0.3219, PD1: -0,2146, PD2: -0.2784, respectively), while in the control groups a direct weak correlation was found (CG1 0.1975, CG2 0.2031, respectively). Chronic heart failure was detected in 75.0% of patients in the GD1 group, in 66.6% – in GD2, and in 100.0% of PD1 and PD2 patients. Valve calcification was observed in 35.0%, 29.1%, 33.3%, and 20.0%, respectively.&#x0D; Conclusions. Studying the features of cardiovascular complications, control of risk factors, which in any case occur in patients on dialysis therapy, is one of the main directions of controlling the underlying disease, reducing the risk of dangerous cardiovascular complications, prolonging life expectancy and its quality.

Renal function and cardiovascular risk in overweight patients

Background. Currently, in most countries of the world, there is a tendency for an annual increase in the proportion of overweight people (OW). Studies performed in various age groups and devoted to the relationship of OW with the functional state of the kidneys show contradictory results.The aim: to study the functional state of the kidneys and the prevalence of risk factors for cardiovascular complications in OW, taking into account gender differences.Patients and Methods. A cross–sectional single-center study was conducted with the participation of 154 patients (73 men and 81 women) with body mass index (BMI) 25.0–29.9 kg/m2), whose average age was 53.9±12.6 years. Anthropometric and biochemical parameters were evaluated in all patients, the functional state of the kidneys (according to serum creatinine and cystatin C) was studied, and an analysis of cardiovascular risk factors was carried out.Results. Analysis of excretory renal function by cystatin C showed that in most of the examined individuals, regardless of gender, there was a decrease in eGFR to CKD stages 2 and 3a. OW among men was statistically significantly more often associated with hypertriglyceridemia (32.8 %), tachycardia (38.3 %) and atherosclerotic lesion of the carotid arteries (24.6 %). In the subgroup of women with ischemic heart disease, the average age, the content of low-density lipoproteins, the double product index, the frequency of hypercholesterolemia, dyslipidemia and hypertrophy of the left ventricle (LVH), mainly of the eccentric type, were significantly higher, and the hemoglobin content and the number of red blood cells were significantly lower. Significant correlations of eGFR with concentrations of hemoglobin and C-reactive protein, as well as with the value of the left ventricular myocardial mass index (LVMI) were found in men with ischemic heart disease. Correlations of eGFR with the levels of systolic, mean, pulse and central blood pressure, index of functional changes, LDL-C, triglycerides, hemoglobin, fibrinogen, metabolic index, as well as LVMI were found in women with ischemic heart disease. The value of LVH in women was significantly associated with the level of central blood pressure, cystatin C, LDL, hemolobin, fibrinogen, metabolic index, and eGFR. In the general sample of patients with ischemic heart disease, the content of serum cystatin C was positively correlated with LVH and inversely with eGFR calculated by cystatin C. There was a weak negative relationship between the level of central arterial pressure and eGFR by cystatin C.Conclusion. Evaluation of excretory renal function, according to cystatin C and serum creatinine, in individuals with ISM has a higher diagnostic value than evaluation using methods based on the use of serum creatinine alone. In males, the presence of OW is associated with tachycardia, hypertriglyceridemia, a significant decrease in GFR and an increase in the frequency of atherosclerotic changes in the carotid arteries. The following cardiovascular risk factors are associated in women with ischemic heart disease: old age, anemia, increased fibrinogen concentration, dyslipidemia, increased values of the double product index, metabolic index and index of functional changes, as well as hemodynamic and LVH parameters.

Risk factors and prediction models for cardiovascular complications of hypertension in older adults with machine learning: A cross-sectional study

BackgroundHypertension has emerged as a chronic disease prevalent worldwide that may cause severe cardiovascular complications, particularly in older patients. However, there is a paucity of studies that use risk factors and prediction models for cardiovascular complications associated with hypertension in older adults. ObjectivesTo identify the risk factors and develop prediction models for cardiovascular complications among older patients with hypertension. MethodsA convenience sample of 476 older patients with hypertension was recruited from a university-affiliated hospital in China. Demographic data, clinical physiological indicators, regulatory emotional self-efficacy, medication adherence, and lifestyle information were collected from participants. Binary logistic regression analysis was performed to screen for preliminary risk factors associated with cardiovascular complications. Two machine learning methods, Back-Propagation neural network, and random forest were applied to develop prediction models for cardiovascular complications among the study cohort. The sensitivity, specificity, accuracy, receiver operating characteristic curve, and area under the curve (AUC) values were used to assess the performance of the prediction models. ResultsBinary logistic regression identified nine risk factors for cardiovascular complications among older patients with hypertension. The machine learning models displayed excellent performance in predicting cardiovascular complications, with the random forest model (AUC 0.954) outperforming the Back-Propagation neural network model (AUC 0.811), as confirmed by model comparison analysis. The sensitivity, specificity and accuracy of the Back-Propagation neural network model compared to the random forest model were 74.2% vs. 86.5%, 75.2% vs. 94.3%, and 74.7% vs. 90.4%, respectively. ConclusionThe machine learning methods employed in this study demonstrated feasibility in predicting cardiovascular complications among older patients with hypertension, with the random forest model based on nine risk factors exhibiting excellent prediction performance. These models could be used to identify high-risk populations and suggest early interventions aimed at preventing cardiovascular complications in such cohorts.

Cardiac Implications of Adenotonsillar Hypertrophy and Obstructive Sleep Apnea in Pediatric Patients: A Comprehensive Systematic Review.

This review investigates the relationship between pediatric obstructive sleep apnea, often associated with adenotonsillar hypertrophy, and cardiovascular health, particularly pulmonary hypertension. We conducted a comprehensive literature search using electronic databases, including Medline Pub-Med, Scopus, and the Web of Science. The study analyzed a total of 230 articles and screened 48 articles, with 20 included in the final analysis, involving 2429 children. The PRISMA flowchart visually illustrates the selection process, and the ROBINS-E and -I tools help ensure the reliability and validity of the evidence produced by these studies. These studies explored various aspects, including the severity of obstructive sleep apnea, cardiac anomalies, cardiac stress markers, risk factors for pulmonary hypertension, and the impact of adenoidectomy and tonsillectomy on cardiac function. The research found that adenotonsillar hypertrophy and obstructive sleep apnea are significant risk factors for cardiovascular complications, especially pulmonary hypertension, in children. Adenoidectomy and tonsillectomy may provide effective treatments. Following adenoidectomy in relation to obstructive sleep apnea, there appears to be a reduction in mean pulmonary artery pressure during echocardiographic examination. However, the efficacy of these procedures can vary based on the severity of obstructive sleep apnea and individual cardiac conditions. The study also identified concerns regarding data bias. The authors emphasize the need for well-designed clinical studies, including both healthy patients with adenotonsillar hypertrophy and vulnerable children with genetic disorders, to ensure that clinical decisions are based on solid scientific evidence.

A Retrospective Clinical Study on Cardiovascular Complications from Colorectal Cancer.

To investigate the incidence and risk factors of cardiovascular complications amongst patients with colorectal cancer (CRC). A retrospective cohort study was conducted on 2085 patients diagnosed with CRC in two tertiary hospitals in China between 2015 and 2020. The patients' medical records were reviewed to identify cardiovascular complications, including myocardial infarction, heart failure, stroke, hypertension, coronary heart disease, heart failure, and arrhythmia. The incidence rate of cardiovascular complications was calculated, and Cox proportional hazards regression analysis was used to identify risk factors. Of the 2085 CRC patients, 329 (15.8%) experienced cardiovascular complications during the follow-up period, with an incidence rate of 17.4 cases per 1000 person-years. The risk was significantly higher in patients who were older than 60 years (adjusted hazard ratio [HR] 2.04, 95% confidence interval [CI] 1.22-3.41), had a higher level of low-density lipoprotein cholesterol (LDL-C) (adjusted HR 2.32, 95% CI 1.31-4.10), had higher levels of serum C-reactive protein (CRP) (adjusted HR 1.57, 95% CI 1.21-2.04), or who underwent chemotherapy or radiotherapy. CRC patients with cardiovascular complications had significantly higher levels of oxidative stress markers, including malondialdehyde (MDA) (5.8 ± 1.2 μmol/L vs. 3.4 ± 0.9 μmol/L, p < 0.001), lower levels of superoxide dismutase (SOD) (85.2 ± 15.6 U/mg protein vs. 112.5 ± 21.3 U/mg protein, p < 0.001), and lower levels of glutathione peroxidase (GPx) (15.6 ± 3.2 U/mg protein vs. 20.4 ± 4.1 U/mg protein, p < 0.001) compared to those without complications. A progressive increase was observed in the proportion of CRC patients with cardiovascular complications over time, rising from 10% in the first year to 38% by the tenth year of follow-up. Cardiovascular complications pose a high risk in CRC patients, particularly amongst older patients and those with higher levels of LDL-C or CRP. Regular monitoring of cardiovascular function should be considered in the management of patients with CRC.

Clonal Hematopoiesis-Related Mutations Are Associated with Favorable Clinical Benefit Following Luspatercept Treatment in Patients with Lower-Risk Myelodysplastic Syndromes: A Subgroup Analysis from the Phase 3 COMMANDS Trial

Introduction: Clonal hematopoiesis of indeterminate potential (CHIP) is a common age-related condition arising from somatic mutations in hematopoietic stem cells that leads to mutant cell clonal progeny in the blood (variant allele frequency [VAF] &amp;gt; 2%) and is found in 10%-30% of people &amp;gt; 70 years of age. CHIP-related mutations (eg, DNA methyltransferase 3 alpha [ DNMT3A], tet methylcytosine dioxygenase 2 [ TET2], ASXL transcriptional regulator 1 [ ASXL1], splicing factor 3b subunit 1 [ SF3B1]) are associated with increased inflammation and elevated risk of developing hematologic malignancies, including myelodysplastic syndromes (MDS)/acute myeloid leukemia, and are an independent risk factor for cardiovascular complications. Recently, patients with MDS were reported to have high rates of cardiovascular co-morbidities including elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiovascular and all-cause mortality. Currently, no treatments targeting CHIP mutations or associated complications are available. Luspatercept is currently approved for anemia in adult patients with lower-risk MDS (LR-MDS) with ring sideroblasts who require red blood cell (RBC) transfusions (≥ 2 RBC units/8 weeks) after erythropoiesis-stimulating agent (ESA) treatment failure. Recently, the phase 3 COMMANDS trial (NCT03682536) reported superiority of luspatercept over ESAs in reducing transfusion burden in ESA-naive patients with LR-MDS. Aims: We investigated the association between the most frequent CHIP-related mutations ( DNMT3A, TET2, ASXL1, SF3B1) and clinical outcomes in patients treated with luspatercept from the COMMANDS trial. Methods: Genomic DNA was isolated from bone marrow (BM) mononuclear cells, and 36 myeloid-specific somatic gene mutations were identified by targeted next-generation sequencing (400X; sensitivity 3%; Munich Leukemia Laboratory information system) at baseline. Hematologic parameters (eg, hemoglobin [Hb], complete blood counts), transcriptome data (bulk BM RNA sequencing [RNA-Seq] data) and cytokines/chemokines (peripheral blood) were assessed at baseline and week 24. Results: Overall, 145 patients in the luspatercept arm of the COMMANDS trial were included in the current analyses, of whom 85% (123/145) (Figure 1A) had the most frequent CHIP-related mutations (eg, DNMT3A, TET2, ASXL1, and SF3B1) with a VAF of 3%-50%. Modest positive correlations were observed between DNMT3A, TET2 and SF3B1 baseline VAF and monocyte percentage ( P = 0.024, P = 0.015, and P = 0.005, respectively). Baseline Hb levels were lower in patients with frequent CHIP-related mutations than in those with less frequent/other somatic mutations. Luspatercept treatment significantly reduced anemia from baseline in patients with CHIP-related mutations (primary endpoint response 62%; n/N = 76/123). Concomitant with the Hb increase (∆ = +1.0 mg/dL; P &amp;lt; 0.001), we observed improvements in other cell counts, including white blood cell counts (∆ = +0.7 × 10 9 cells/L; P = 0.01). In addition, luspatercept treatment in patients with CHIP-related mutations was associated with downregulation of inflammatory gene signatures (Figure 1B) and proinflammatory cytokines/chemokines, including hepcidin (∆ = −43.9 ng/mL; P &amp;lt; 0.001). Furthermore, we observed upregulation of an anti-inflammatory regulator (growth/differentiation factor 15) following treatment. Most importantly, significant downregulation of NT-proBNP levels (∆ = −330 pg/mL; P &amp;lt; 0.05) was observed in patients with LR-MDS who received luspatercept. Conclusions: This retrospective subgroup analysis of patients in the COMMANDS trial with the most frequent CHIP-related mutations ( DNMT3A, TET2, ASXL1 and SF3B1) demonstrated novel effects of luspatercept in clonal hematopoiesis-related consequences including improvements in anemia, cytopenias, and reduced inflammation. Most importantly, NT-proBNP and elevated hepcidin levels were significantly downregulated in responders following luspatercept treatment. These results warrant evaluation of luspatercept in patients with high-risk CHIP mutations including clonal cytopenia of undetermined significance and patients with anemia of inflammation.

ПОЛИМОРФИЗМ RS247616 ГЕНА CETP У ПАЦИЕНТОВ С ХРОНИЧЕСКОЙ СЕРДЕЧНОЙ НЕДОСТАТОЧНОСТЬЮ И ИШЕМИЧЕСКОЙ БОЛЕЗНЬЮ СЕРДЦА: ОСОБЕННОСТИ ЛИПИДНОГО ОБМЕНА И ЭФФЕКТИВНОСТИ ТЕРАПИИ СТАТИНАМИ

Abstract. Introduction. Dyslipidemia is a modifiable risk factor for cardiovascular complications in patients with chronic ischemia-induced heart failure. Being the best-known class of drugs, statins effectively reduce cardiovascular mortality in all age groups. Effectiveness of using lipid-lowering drugs is determined by some factors, including genetic ones. Polymorphism rs247616 of the CETP (cholesterol ester transfer protein) gene is associated with changing high-density lipoprotein levels in blood serum. Aim. To analyze the clinical parameters and effectiveness of lipid-lowering therapy in stable chronic ischemia-induced heart failure patients with the rs247616 polymorphism of the CETP gene. Materials and Methods. We examined 517 patients with chronic ischemia-induced heart failure, aged 66.4±10.4 years, of both sexes. A genetic control of 118 conditionally healthy individuals was included. We analyzed the allele frequency of the CETP rs247616 occurrences, clinical characteristics, statin administration frequency, dose range, and achieving the lipid metabolism goals, including in relation to the genotype. Results and Discussion. Statins were prescribed to 28.8% of patients with chronic heart failure, with 42.3% receiving the minimum dosage and 35.6% receiving the average therapeutic dosage. Frequency of TT-genotype and T allele of the CETP rs247616 was higher in patients with chronic heart failure compared with controls (13.2% and 10.2%, p=0.026, 35% and 26.7%, p=0.014). It was found that CC-genotype has a protective effect against the development of chronic heart failure (CC vs CT+TT, OR=0.57, 95%CI:0.38-0.86). In patients with CC-genotype chronic heart failure, a lower level of high-density lipoproteins was observed (1.12±0.37 and 1.25±0.37 mmol/l, p=0.012), as compared to the carriers of T allele (CT+TT). Percentage of individuals with total cholesterol levels below 4.5 mmol/l (33.3%, 29.7%, and 37.5%) and triglyceride levels &lt; 1.7 mmol/l (36.5%, 25%, and 37.5%) did not differ between CC-, CT-, and TT-genotypes, respectively. There is a trend towards an increase in the proportion of the carriers of T allele and TT-genotype with low-density lipoprotein levels &lt; 1.8 mmol/l (30.8%, 45.5%, and 50%) and non-high-density lipoproteins levels&lt;2.6 mmol/l (29.4%, 31.2%, and 50%). Conclusions. Effectiveness of statin therapy is low: 38.1 % of patients had the total cholesterol levels &lt; 4.5 mmol/l, 11% had low-density lipoprotein levels &lt;1.8 mmol/l, 50.6% had triglyceride levels &lt;1.7 mmol/l, and 12.2% of patients had non-high-density lipoprotein levels &lt;2.6 mmol/l. Protective effect of CC-genotype was found regarding the genesis of chronic heart failure.

The role of triglyceride-glucose index in predicting cardiovascular and metabolic outcomes in patients with type 2 diabetes mellitus

Diabetes mellitus type 2 is a global medical and social problem, which, in terms of population coverage around the world, is becoming a pandemic. The main cause of premature death in patients with type 2 diabetes is diseases of the cardiovascular system. The presence of diabetes is associated with an increase in the risk of developing coronary heart disease by two-four times, and every sixth patient has signs of myocardial infarction in the past. The risk of developing ASCVD in patients with type 2 diabetes is early onset, rapid progression, and asymptomatic course. It is known that patients with type 2 diabetes develop ASCVD 8–10 years earlier than people of the same age group who do not have diabetes. Along with chronic hyperglycemia, an independent risk factor for cardiovascular complications in patients with type 2 diabetes is dyslipidemia, which occurs in 30–40% of patients. Insulin resistance, the state of chronic hyperglycemia, dyslipidemia play a key role in the development of the metabolic syndrome and atherosclerosis. The TyG index and the parameter of non-HDL-C have convincingly established themselves as predictors of the development of CVD, as well as markers reflecting signs of the presence of independent factors of the metabolic syndrome that increase the risk of CVD. Conducted clinical studies have confirmed the predictive value of these parameters in relation to CVD. This review focuses on the pathogenesis, development mechanisms, and methods for correcting lipid disorders that underlie the development of CV complications in patients with type 2 diabetes.

Imaging photoplethysmography quantifies endothelial dysfunction in patients with risk factors for cardiovascular complications

The endothelium plays an important role in the pathogenesis of cardiovascular pathology, so that revealing its dysfunction can predict outcomes of the disease. However, the correct assessment of the endothelial function remains an unsolved problem. Registration of endothelium dependent vasodilation in response to nitric oxide synthesis using available noninvasive technologies does not show sufficient specificity and sensitivity, although it helps to detect its differences in population studies. In this pilot study, we compared the dynamics of microcirculation of the forearm skin and its spectral parameters during mild heating (up to 42 °С) between groups of smokers (n = 17) and non-smokers (n = 21) using imaging photoplethysmography synchronized with electrocardiography. The study included healthy men with similar anthropometric characteristics at the age of 51 ± 8 years and 48 ± 13 years, respectively. During the comparative analysis, no intergroup difference was found in the perfusion increase in either the axon- or endothelial-related phases of the reaction to local hyperemia. However, it was revealed that the power spectral density in the frequency band 0.01–0.02 Hz is significantly smaller in smokers than in non-smokers only during the phase of endothelium induced vasodilation: 4.0 ± 1.1 versus 5.3 ± 1.2 rel.un., respectively (P = 0.005). At the same time, no difference in the spectral power in the same band was observed during the axon-mediated phase, thus indicating high sensitivity and selectivity for assessment of the nitric oxide dependent vascular reactivity. The obtained results can be used for noninvasive evaluation of other cardiometabolic risk factors for early prediction and timely prevention of adverse outcomes by optimizing and intensifying treatment.

Diabetes mellitus and atrial fibrillation-from pathophysiology to treatment.

Type 2 diabetes mellitus (T2DM) is a leading risk factor for cardiovascular complications around the globe and one of the most common medical conditions. Atrial fibrillation (AF) is the most common supraventricular arrhythmia, with a rapidly increasing prevalence. T2DM has been closely associated with the risk of AF development, identified as an independent risk factor. Regarding cardio-vascular complications, both AF and T2DM have been linked with high mortality. The underlying pathophysiology has not been fully determined yet; however, it is multifactorial, including structural, electrical, and autonomic pathways. Novel therapies include pharmaceutical agents in sodium-glucose cotransporter-2 inhibitors, as well as antiarrhythmic strategies, such as cardioversion and ablation. Of interest, glucose-lowering therapies may affect the prevalence of AF. This review presents the current evidence regarding the connection between the two entities, the pathophysiological pathways that link them, and the therapeutic options that exist.

Correlation between GAL-3, Klotho, Calcium and Phosphorus Metabolism Indexes and Cardiovascular Complications in patients with Chronic Kidney Disease.

To investigate the correlation between GAL-3, Klotho, calcium and phosphorus indexes and cardiovascular complications in patients with chronic kidney disease (CKD). This is a retrospective study. Forty patients with CKD and cardiovascular complications admitted to the Affiliated Hospital of Hebei University from February 20, 2022 to February 20, 2023 were selected as the experimental group, and another 40 patients with CKD without cardiovascular complications were selected as the control group. The differences in serum Ca+2, PO- 4, GAL-3 and Klotho levels between the two groups were analyzed, and the correlations between the above indicators levels and creatinine levels were analyzed. The correlation between the above indicators levels and cardiac function classification was analyzed, and analyzed the risk factors of CKD complicated with cardiovascular complications. The levels of Ca+2, PO- 4 and GAL-3 in the experimental group were significantly higher than those in the control group, while the level of Klotho was significantly lower than that in the control group. The levels of Ca+2 and PO- 4 were positively correlated with the level of Creatinine (Cr), while the level of Klotho was negatively correlated with the Cr. The levels of Ca+2 and PO- 4 were positively correlated with cardiac function classification, while the level of Klotho was negatively correlated with cardiac function classification. Logistic regression analysis showed that hypertension, BMI, Cr, Ca+2, PO- 4 and VLDL were risk factors for cardiovascular complications, and Klotho level was a protective factor. A positive correlation can be seen between the levels of Ca+2, PO- 4 and cardiac function classification in patients with CKD. Klotho is a protective factor for cardiovascular diseases.

Serum adiponectin concentrations as a risk factor for cardiovascular complications in type 1 diabetes

AimBy analyzing data from DCCT/EDIC study, we investigated the associations of serum adiponectin concentrations with macrovascular complications and cardiovascular events in T1D. Materials and MethodsAdiponectin concentrations were measured in EDIC year 8. The participants (n = 1040) were divided into four groups by quartiles of adiponectin concentrations. The association of macrovascular complications and cardiovascular events were analyzed by using multivariable regression and Cox proportional hazards models. ResultsHigh adiponectin concentrations were associated with decreased risk of peripheral artery disease represented by ankle brachial index (ORs (95% CI): 0.22 (0.07–0.72), 0.48 (0.18–1.25), and 0.38 (0.14–0.99) in fourth, third, and second quartiles compared with first quartile), with reduced carotid intima-media thickness, and with increased LVEDV index. Moreover, high adiponectin concentrations were also associated with increased risk of any cardiovascular events (HRs (95% CI): 2.59 (1.10–6.06), 2.03 (0.90–4.59), and 1.22 (0.52–2.85)) and major atherosclerotic cardiovascular events (HRs (95% CI): 11.37 (2.04–63.43), 5.68 (1.04–31.07), and 3.76 (0.65–21.77) in fourth, third, and second quartiles compared with first quartile), however, after adjustments with LVEDV index, these associations were diminished. ConclusionsAdiponectin may protect carotid atherosclerosis and peripheral artery disease in T1D. It may be associated with increased cardiovascular events, depending on cardiac structural changes.