Chronic Cardiovascular Disease Research Articles

Association between chronic kidney disease and cardiovascular disease risk factors in elderly: results from the first phase of Fasa and Shahedieh cohort studies

Association between chronic kidney disease and cardiovascular disease risk factors in elderly: results from the first phase of Fasa and Shahedieh cohort studies

Abstract 4138559: Cystatin C Predicts Cardiovascular Events in Patients With Coronary Artery Disease Both Among Patients With and Among Those Without Type 2 Diabetes

Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD). We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM. During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p<0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p<0.001). We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.

Chemokine receptor CXCR7 antagonism ameliorates cardiac and renal fibrosis induced by mineralocorticoid excess

Cardiorenal fibrosis is a common feature of chronic cardiovascular disease and recent data suggests that cytokines and chemokines may also drive fibrosis. Here we tested the hypothesis that CXCR7, a highly conserved chemokine receptor, contributes to cardiac and renal fibrosis. We generated an anti-mouse CXCR7-specific monoclonal antibody (CXCR7 mAb) and tested its anti-fibrotic actions in cardiorenal fibrosis induced using the deoxycorticosterone acetate/uni-nephrectomy (DOCA-UNX) model. CXCR7 mAb treatment (10 mg/kg, twice weekly for 6 weeks) significantly attenuated the development of cardiac and renal fibrosis, and reduced fibrotic and inflammatory gene expression levels, in the absence of an effect on blood pressure. Immunohistochemical analysis demonstrated an increase in the vascular expression of CXCR7 in DOCA-UNX-treated mice. This study demonstrated that a CXCR7 mediated pathway plays a significant role in cardiac and renal fibrosis induced by DOCA-UNX treatment. Accordingly, antagonism of CXCR7 may provide a therapeutic opportunity to mitigate against fibrosis in the setting of mineralocorticoid excess.

Insertable Biomaterial-Based Multianalyte Barcode Sensor toward Continuous Monitoring of Glucose and Oxygen.

Chronic diseases, including diabetes, cardiovascular diseases, and microvascular complications, contribute significantly to global morbidity and mortality. Current monitoring tools such as glucometers and continuous glucose monitors only measure one analyte; multiplexing technologies offer a promising approach for monitoring multiple biomarkers, enabling the management of comorbidities and providing more comprehensive disease insights. In this work, we describe a miniaturized optical "barcode" sensor with high biocompatibility for the continuous monitoring of glucose and oxygen. This enzymatic sensor relies on oxygen consumption in proportion to local glucose levels and the phosphorescence reporting of tissue oxygen with a lifetime-based probe. The sensor was specifically designed to operate in a tissue environment with low levels of dissolved oxygen. The barcode sensor consists of a poly(ethylene glycol) diacrylate (PEGDA) hydrogel with four discrete compartments separately filled with glucose- or oxygen-sensing phosphorescent microparticles. We evaluated the response of the barcode hydrogels to fluctuating glucose levels over the physiological range under low oxygen conditions, demonstrating the controlled tuning of dynamic range and sensitivity. Moreover, the barcode sensor exhibited remarkable storage stability over 12 weeks, along with full reversibility and excellent reproducibility (∼6% variability in the phosphorescence lifetime) over nearly 50 devices. Electron beam sterilization had a negligible effect on the glucose response of the barcode sensors. Furthermore, our investigation revealed minimal phosphorescence lifetime changes in oxygen compartments while exhibiting increased lifetime in glucose-responsive compartments when subjected to alternating glucose concentrations (0 and 200 mg/dL), showcasing the sensor's multianalyte sensing capabilities without crosstalk between compartments. Additionally, the evaluation of chronic tissue response to sensors inserted in pigs revealed the appropriate biocompatibility of the barcodes as well as excellent material stability over many months. These findings support further development of similar technologies for introducing optical assays for multiple biomarkers that can provide continuous or on-demand feedback to individuals to manage chronic conditions.

Inflammation as a shared mechanism of chronic stressrelated disorders with potential novel therapeutic targets.

Stress is a subjective experience that varies across individuals depending on their sensitivity, resilience, and length of exposure to stressors. Stress may be categorised as acute (positive stress) or chronic (negative stress). Acute stress is advantageous for the human body, but chronic stress results in changes in cardiovascular, neuroendocrine, autonomic, and immunological functions, eventually causing different illnesses. The specific process relating stress to chronic stress associated diseases is still a topic of continuing debate. Inflammation has been recognised as a new and fascinating physiological mechanism that connects chronic stress and its associated illnesses. This article explored the relationships between chronic stress, inflammation, and chronic illnesses, including depression, cancer, and cardiovascular disease. This article also emphasises on various possible therapeutic targets for the management of chronic stressrelated illnesses by targeting inflammation, namely lipoxins and alpha7 nicotinic receptors. These therapeutic targets may be useful in developing new and safe therapies for the management of chronic stressrelated dysfunctions.

Hypnotic-based intervention for people with non-communicable diseases : A scoping review

This scoping study aimed to explore the use of hypnotic-based interventions for individuals with Non-Communicable Diseases (NCDs). Four research questions were addressed: the types of hypnosis-based interventions, the types of NCDs studied, the targeted outcomes, and the evidence of effectiveness. Using Arksey and O'Malley's framework, a systematic search of databases (Cochrane Library, Google Scholar, Scopus, PubMed) was conducted from March to April 2021. Studies published in English between 2001 and 2021, employing Randomized Controlled Trials (RCTs), were included. Out of 6,382 unique records, 11 primary studies met the inclusion criteria, encompassing 589 participants across four NCD subgroups: diabetes, chronic respiratory diseases, cancer, and cardiovascular diseases. Five types of hypnotic interventions were identified: mindfulness, relaxation, self-hypnosis, hypnotherapy, and cognitive behavior therapy plus hypnosis. The outcomes assessed included pain, fatigue, anxiety, sleep quality, dyspnoea, emotion, panic, and quality of life. While the results suggest that hypnotic-based interventions hold promise as supportive therapy for NCD patients, especially in addressing psychological symptoms, the evidence remains inconclusive. Further research is needed to establish the overall effectiveness of hypnosis in this context. Nonetheless, these findings highlight the potential of hypnosis to complement medical treatments for NCDs.

Chronic kidney disease and cardiovascular disease: is there a connection?

Chronic kidney disease represents an increasing health burden worldwide. Chronic kidney disease and cardiovascular disease are closely interlinked, with dysfunction in one organ often causing dysfunction in the other, ultimately leading to the failure of both. Patients with end-stage renal disease are at significantly higher risk of mortality due to cardiovascular complications. Shared risk factors for both chronic kidney disease and cardiovascular disease include age, hypertension, diabetes mellitus, dyslipidemia, tobacco use, family history, and male gender. This review focuses on whether early-stage chronic kidney disease serves as an important risk factor for the presence, severity, and progression of cardiovascular disease.

Cardiovascular Risks With SGLT2 Inhibitors in Clinical Practice Among Patients With Type 2 Diabetes

Cardiovascular disease (CVD) can be recurrent during type 2 diabetes (T2D) progression in this aging population. The effectiveness of sodium-glucose cotransporter 2 inhibitor (SGLT2i) therapy on total (ie, first and subsequent) CVD among patients with T2D in clinical practice remains uncertain. To analyze the comparative association of SGLT2i vs dipeptidyl peptidase 4 inhibitor (DPP4i) therapy with total CVD among patients with T2D in clinical practice. This retrospective cohort study used electronic medical records at the National Cheng Kung University Hospital, a leading medical center in Taiwan, from 2015 through 2021. Adult patients with T2D who initiated first use of the study drugs from 2016 through 2019, with up to 6 years of follow-up, were identified. The primary outcomes included total composite CVD events and individual CVD subtypes (ie, atrial fibrillation, coronary heart disease, heart failure, stroke, myocardial infarction, and transient ischemic attack). A shared frailty model analysis was used to assess the association of treatment with repeat CVD events. Data from patients at high risk for CVD recurrence were further analyzed. Data were analyzed from September 1, 2022, to December 31, 2023. Overall, 8384 patients with T2D were identified (mean [SD] age, 63.7 [12.4] years; 4645 [55.4%] male). A total of 1632 propensity score-matched pairs of SGLT2i (mean [SD] age, 57.8 [12.0] years; 673 [41.2%] female and 959 [58.8%] male) and DPP4i (mean [SD] age, 58.2 [12.9] years; 655 [40.1%] female and 977 [59.9%] male) users were included. SGLT2i was associated with reduced total CVD risk vs DPP4i therapy (hazard ratio [HR], 0.82 [95% CI, 0.69-0.98]) but not the first CVD event (with the use of SGLT2i therapy were more prominent for patients at high risk of CVD (ie, HR, 0.70 [95% CI, 0.62-0.80] for individuals with estimated glomerular filtration rate lower than 60 mL/min/1.73 m2; HR, 0.70 [95% CI, 0.64-0.78]; for individuals having any diabetes-related complications; and HR, 0.72 [95% CI, 0.65-0.80] for individuals with a history of CVD) compared with the overall cohort. Among patients at high risk of CVD, greater reduced total CVD burden associated with SGLT2i therapy was observed for women vs men (eg, HR, 0.59 [95% CI, 0.49-0.72] in the subgroup with CVD history). In this cohort study of patients with T2D, the use of SGLT2is vs DPP4is was associated with reduced total cardiovascular burden, suggesting that long-term use of this therapy may optimize treatment benefit among patients with chronic CVD. The SGLT2i-associated benefit among patients with high risk of CVD encourages the prioritization of SGLT2i use for these vulnerable individuals.

Role of Sex and Early Life Stress Experience on Porcine Cardiac and Brain Tissue Expression of the Oxytocin and H2S Systems

Early life stress (ELS) significantly increases the risk of chronic cardiovascular diseases and may cause neuroinflammation. This post hoc study, based on the material available from a previous study showing elevated “serum brain injury markers” in male control animals, examines the effect of sex and/or ELS on the cerebral and cardiac expression of the H2S and oxytocin systems. Following approval by the Regional Council of Tübingen, a randomized controlled study was conducted on 12 sexually mature, uncastrated German Large White swine of both sexes. The control animals were separated from their mothers at 28–35 days, while the ELS group was separated at day 21. At 20–24 weeks, animals underwent anesthesia, ventilation, and surgical instrumentation. An immunohistochemical analysis of oxytocin, its receptor, and the H2S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase was performed on hypothalamic, prefrontal cortex, and myocardial tissue samples. Data are expressed as the % of positive tissue staining, and differences between groups were tested using a two-way ANOVA. The results showed no significant differences in the oxytocin and H2S systems between groups; however, sex influenced the oxytocin system, and ELS affected the oxytocin and H2S systems in a sex-specific manner. No immunohistochemical correlate to the elevated “serum brain injury markers” in male controls was identified.

Cost-effectiveness of semaglutide for secondary prevention of cardiovascular disease in the United States

Abstract Background In the SELECT trial, semaglutide produced a 20% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke in individuals with overweight or obesity who did not have diabetes but had established pre-existing cardiovascular disease (CVD). Cost is an important barrier to widespread uptake of semaglutide, particularly in the US, and the cost-effectiveness for the secondary prevention of CVD is uncertain. Purpose To evaluate the cost-effectiveness of semaglutide vs. no obesity treatment for the secondary prevention of CVD from a US healthcare sector perspective. Methods The CVD Policy Model is an established, validated simulation model of fatal and non-fatal CVD outcomes and costs in the US population. Using data from the National Health and Nutrition Examination Survey, we created a nationally representative cohort of SELECT-eligible individuals (age ≥45, BMI ≥27kg/m2, no diabetes, pre-existing CVD). Healthcare costs associated with acute and chronic CVD were estimated from national survey and claims data and inflated to 2023 US dollars. The simulated control arm received usual care; the intervention arm received weekly semaglutide 2.4mg injections (assuming 8% discontinuation, which occurs year one). We reproduced the effectiveness of semaglutide based on results of the SELECT trial primary cardiovascular composite endpoint (non-fatal MI, non-fatal strokes and CVD death). The base case assumed 7% of patients receiving semaglutide developed injection-site reactions. Monthly cost of semaglutide was assumed to be $717 (US price net of rebates and discounts), but this was varied in sensitivity analyses. The analysis adopted a health system perspective over lifetime horizon. Results Approximately 4.7 million US adults would meet SELECT trial eligibility criteria. Over a lifetime horizon, semaglutide is projected to avert 538,000 major adverse cardiovascular events (241,000 nonfatal MIs; 80,000 nonfatal stokes, and 217,000 cardiovascular deaths) at an incremental cost of $613 billion. The incremental cost effectiveness ratio for semaglutide was $443,000 per quality-adjusted life year (QALY) gained. In order to meet cost-effectiveness thresholds of $50,000/QALY, $100,000/QALY, $150,000/QALY, drug costs would have to decline 90%, 79%, and 69% respectively. In sensitivity analyses, lowering drug cost to the current UK price (~ $220 per patient per month) would improve the incremental cost-effectiveness of semaglutide to <$150,000 per QALY gained, a potential upper threshold for cost-effectiveness in the US. Conclusion Widespread uptake of semaglutide in the SELECT-eligible U.S. population would prevent a large number of cardiovascular events, but its use would be low economic value at current US prices. Lowering prices in line with those in Europe (e.g., monthly price from $717 to $223) would make the therapy cost-effective at a threshold of $150,000 per QALY gained.

Longitudinal and cross-sectional associations of NT-proBNP with kidney function and chronic kidney disease: results from KORA cohort studies

Abstract Background Chronic kidney disease (CKD) and cardiovascular disease (CVD) exhibit a bidirectional and complex relationship, and share common risk factors and mechanisms of disease development. Thus, important CVD-related biomarkers, such as N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), may serve as a biomarker for CKD development. Purpose We aimed to investigate the cross-sectional and longitudinal associations of NT-proBNP with kidney function and CKD in data from two population-based cohort studies. Methods We included 5854 men and women, aged 25-74 years, from the Cooperative Health Research in the Region of Augsburg (KORA) cohort studies S3 and S4, and their 1-2 subsequent follow-up surveys, with a median follow-up time of 9.4 and 13.4 years, respectively. Kidney function was assessed by 3 estimated glomerular filtration rate (eGFR) assessments, calculated using creatinine (eGFRcr), cystatin C, and combined creatinine and cystatin C. Serum NT-proBNP was logarithmically transformed followed by Z-score standardization and categorized into 4 groups (G1-4), <48.6, 48.6-125, 125-300, and ≥300 pg/ml. In cross-sectional analysis, linear regression and logistic regression were used to estimate β/odds ratio (OR) and their 95% confidence intervals (CIs) of continuous eGFR or prevalent CKD. For longitudinal analysis of repeated eGFR measurements during follow-up (5854 participants, 11870 observations), linear mixed-effects models were used. For incident CKD associations, interval-censored Cox regression models were performed in participants free of CKD at baseline. Results In cross-sectional analyses, higher NT-proBNP levels were associated with lower eGFR and higher prevalence of CKD across all 3 eGFR assessments. For example, results based on eGFRcr showed that the fully-adjusted β (95% CIs) for per 1 SD increase in log-transformed NT-proBNP were -1.03 (-1.42, -0.64) and -7.01 (-8.93, -5.09) 60 ml/min/1.73m2 for G4 compared to G1, respectively. Corresponding OR (95% CIs) were 2.22 (1.81, 2.74) and 13.8 (5.76, 36.4), respectively. In longitudinal analyses, participants with higher baseline NT-proBNP had a faster decline in eGFR during follow-up. The fully-adjusted β (95% CIs) for 5-year eGFRcr decline were -0.67 (-0.87, -0.47) per 1 SD increase, and -0.37 (-0.79, 0.05), -1.53 (-2.18, -0.88), -4.24 (-5.57, -2.90) 60 ml/min/1.73m2/year for G2-4. Higher NT-proBNP levels were associated with higher incident CKD risks. For associations with incident creatinine-based CKD, hazard ratio (95% CIs) were 1.16 (1.00, 1.33) per 1 SD increase and 1.03 (0.77, 1.38), 1.07 (0.75, 1.52), and 1.81 (1.07, 3.04) for G2-4. Conclusions We found associations of higher NT-proBNP with lower kidney function and higher CKD prevalence. Moreover, higher baseline NT-proBNP levels were associated with faster kidney function decline and higher incident CKD risks. Our findings indicate the potential utility of NT-proBNP as a biomarker of kidney health.Figure 1.Cross-sectional associationsFigure 2.Longitudinal associations

Cystatin C predicts cardiovascular events in patients with coronary artery disease both among patients with and among those without type 2 diabetes

Abstract Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD). We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM. During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p<0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p<0.001). We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.

The role of cardiopulmonary rehabilitation in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients

Abstract Introduction Coronavirus disease-19 (COVID-19) is predominantly a respiratory disease, but simultaneous cardiovascular impairment has been documented, even in the post-acute phase. Subclinical right ventricular (RV) dysfunction is often described and mainly attributed to parenchymal lung damage (ARDS) or pulmonary vascular complications such as pulmonary embolism. Cardiopulmonary rehabilitation programs play an integral part in the long-term management of chronic cardiovascular and pulmonary diseases and lately have been proven useful in managing post-COVID-19 sequelae. Purpose The aim of this study is to assess the impact of a post-COVID-19 rehabilitation program in the recovery of right ventricular function and right ventricular-pulmonary artery coupling in convalescent COVID-19 patients. Methods 40 convalescent COVID-19 patients were evaluated one and three months after the acute phase of the disease. 30 subjects participated in a 3-month cardiopulmonary rehabilitation program (study group) and 10 did not (control group). Right ventricular function echocardiographic parameters (right ventricular global longitudinal strain (RVGLS) and pulmonary artery systolic pressure (PASP)) were evaluated and right ventricular-arterial coupling (RVAC) was estimated via the RVGLS/PASP ratio. Results A total of 40 patients were included in this study, of whom 30 underwent cardiopulmonary rehabilitation. There were no major differences in the prevalence of cardiovascular risk factors between the two groups. When examining right ventricular parameters at baseline, RVGLS (Rehabilitation: -23.1 (4.1) % vs. No rehabilitation: -23.0 (4.7) %, p=0.94) and PASP (Rehabilitation: 28 (6) mmHg vs. No rehabilitation: 25 (4) mmHg, p=0.08) did not differ statistically between the two groups. RVAC was also similar at baseline (Rehabilitation: -0.96 (0.28) %/mmHg vs. No rehabilitation: -0.86 (0.27) %/mmHg, p=0.30). At follow-up, patients who underwent cardiopulmonary rehabilitation exhibited a significant improvement in RVGLS (from Τ0: -23.1 (4.2) % to T1: -24.3 (4) %, p<0.001), PASP (from T0: 28 (6) mmHg to T1: 27 (5) mmHg, p=0.016), and RVAC (from T0: -0.86 (0.27) %/mmHg to T1: -0.93 (0.26) %/mmHg, p<0.001). In the no rehabilitation group, RVGLS (from T0: -23.0 (4.7) % to T1: -23.2 (4.4) %, p=0.19), PASP (from T0: 25 (4) mmHg to T1: 25 (4) mmHg, p=0.17), and RVAC (from T0: -0.96 (0.28) %/mmHg to T1: -0.96 (0.27) %/mmHg, p=0.60) were not significantly altered at follow-up. We detected a statistically significant interaction of intervention with RVGLS (p=0.024) and RVAC (p=0.012) (Figure 1). Conclusion Subclinical right ventricular dysfunction is present in convalescent COVID-19 patients. Cardiopulmonary rehabilitation can accelerate the improvement of RVAC by mediating both the RV afterload reduction (PASP) and improving RV function.Figure 1

Tubulointerstitial injury in proteinuric chronic kidney diseases.

Proteinuria is an independent risk factor for chronic kidney disease progression and cardiovascular diseases. Apart from its prognostic role, the load of proteins that pass across the disrupted glomerular capillary wall trigger multiple pathophysiologic processes. These include, among others, intratubular complement activation and excessive proximal tubular reabsorption of filtered proteins, especially albumin and albumin-bound free fatty acids, which can set off several pathways of cellular damage. The activation of these pathways can cause apoptosis of proximal tubular cells and paracrine effects that incite the development of interstitial inflammation and fibrosis, ultimately leading to irreversible kidney injury. In this review, we provide a comprehensive overview of the current understanding on the mechanisms underlying the tubular toxicity of ultrafiltered proteins in the setting of proteinuric chronic kidney diseases. The acquired knowledge is expected to be instrumental for the development of novel therapeutic classes of medications to be tested on top of standard of care with optimized renin-angiotensin-aldosterone blockade and sodium-glucose cotransporter-2 inhibition, in order to further improve the clinical outcomes of patients with proteinuric chronic kidney diseases.

Artificial intelligence-enabled electrocardiogram for left ventricular diastolic dysfunction and long-term risk of new-onset atrial fibrillation

Abstract Background Heart failure (HF) and atrial fibrillation (AF) are intertwined, sharing common risk factors and influencing each other in a reciprocal manner. While left ventricular diastolic dysfunction (LVDD) stands as a hallmark of HF's hemodynamic profile, its direct correlation with heightened AF risk remains uncertain. Our recent validation of an artificial intelligence-enabled electrocardiogram (AI-ECG) algorithm for LVDD detection has opened new avenues. Yet, whether AI-ECG-detected LVDD correlates with long-term AF risk remains unexplored. Methods We performed a retrospective study among all patients with a comprehensive LVDD assessment from the test population of the AI-ECG LVDD study between September 2001 and June 2022. Patients with prior documented AF according to health records or previous ECG were excluded. Patients were classified by AI-ECG as normal diastolic function (DF), grade 1 (G1), grade 2 (G2), or grade 3 (G3) LVDD. We assessed the risk of AF across AI-ECG LVDD grade, with normal DF as reference, with competing risk models. Results Of 97,023 patients free of AF at baseline, 63,533 (65.4%), 10,776 (11.1%), 18,940 (19.5%), and 3,774 (3.9%) were classified as normal DF, G1-LVDD, G2-LVDD, and G3-LVDD, respectively. Worse AI-ECG LVDD was associated with older age, lower left ventricular ejection fraction (LVEF), and higher rates of HF, diabetes, hypertension, chronic pulmonary disease, renal failure, and cardiovascular disease (p-of-trend<0.001 for all). Over a median follow-up of 4.8 years (interquartile range 1.8-9.2 years), new-onset AF occurred in 6,795 (7.0%) patients. In multivariable survival analysis, adjusted to multiple risk factors including LVEF and clinical HF, G2 and G3 LVDD, representing patients with high filling pressures, were independently associated with a higher AF-risk [G2-LVDD: adjusted hazard ratio (aHR) 1.64 (95% confidence interval (95%CI) 1.52-1.73), G3-LVDD: aHR 2.24 (95%CI 2.02-2.48)]. Conclusion The AI-ECG LVDD algorithm independently predicts long-term AF risk, regardless of LVEF and clinical HF status, highlighting its potential for identifying high-risk populations and guiding proactive monitoring and management.

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

Increasing trends in hypertension-related mortality in European Union 27 countries from 2011 to 2019

Abstract Background Arterial Hypertension (HT) is one of the most common chronic cardiovascular disease in adults and a leading cause of disability and mortality worldwide. However, update data regarding the HT-related mortality trends in Europe are lacking. Therefore, we assess the age- and sex- specific trends in HT-related mortality in the 27 European Union Member States (EU-27) between years 2011 and 2029. Methods Data were retrieved from the free publicly available EUROSTAT death certificate database to examine age-adjusted HT-related mortality rates (AAMR) (per 100.000 people) and relative average annual percentage change (AAPC) across all European Union 27 countries (EU27) from 2011 to 2019 using the International Classification of diseases, Tenth Revision (ICD-10) codes I10-I13 and I15. To calculate annual trends in HT-related mortality, we assessed the average annual percent change (AAPC) and relative 95% confidence intervals (CIs) using Joinpoint regression analysis. Results Over the study period, 254.540 HT-related deaths (157,081 males) were listed in EU27. Age-adjusted HT-related death increased from 9.12 to 10.7 per 100,000 people [AAPC: +1.5% (95% CI: 0.8-2.0), p<0.001]. Specifically, the HT-related mortality increased in males [AAPC: +1.8 (95% CI: 0.9-2.6) while decreased in women [AAPC: -1.1 (95% CI: -2.0 to 0.2), p=0.001]. Additionally, the HT-related mortality rates increased in northern [+1.5 (95% CI: 0.7 to 2.3), p<0.001] and eastern [AAPC: +3.9 (95% CI: 2.3 to 5.4), p<0.001] EU-27 states. Conversely, the AAMR plateaued in southern [AAPC: -0.1 (95% ci: 0.6 to 0.7), p=0.96)] and western EU-27 countries [AAPC: 1.0 (95% CI: -0.1 to 2.1, p=0.07] over the same period. Conclusions In EU27, HT-related mortality increased from 2011 to 2019, especially in men. However, significant disparities in HT-related mortality rates still exist between different European regions.

Impact of a new coronavirus infection on the level of inflammatory, haemostasis markers and microcirculatory parameters of patients with arterial hypertension

Relevance. The COVID-19 pandemic and its consequences have significantly affected the health of the population as a whole. Persons who have undergone coronavirus infection against the background of chronic cardiovascular diseases and obesity deserve special attention. Aim. To study and compare the main indicators of carbohydrate and lipid metabolism the level of inflammatory and haemostasis markers, microvascular changes in obesity AH patients and in AH patients with normal body weight 1 month after a new coronavirus infection in moderate to severe form. Materials and methods. The study included 87 patients of both sexes, aged from 18 to 55 years, from which three groups were formed: the first group included people with AH and normal body weight (BMI<25 kg/m²) who had undergone COVID-19 within a month, the second group included people with AH and obesity (BMI≥30 kg/m²) who had undergone COVID-19 within a month, the control group consisted of 20 people with AH and obesity without COVID-19. The parameters of height, weight, waist circumference, and BMI were assessed in all subjects. The parameters of lipid profile, glucose level were determined, inflammatory markers and haemostasis parameters. All participants underwent laser Doppler flowmetry (LDF) on the forearm with constrictor and dilator functional tests, and single-photon emission computed tomography (SPECT) in combination with x-ray computed tomography (SPECT/CT). Results. Patients of groups 1 and 2 naturally differed from each other in anthropometric indicators. Lipid and carbohydrate metabolism rates were also significantly higher in group 2 patients compared to group 1 patients (p < 0.05). The CRP level in the group of people with hypertension and obesity who underwent COVID-19 was significantly higher than in people with hypertension without obesity (p < 0.001) and than in people with hypertension and obesity without a history of COVID-19. When comparing microcirculation parameters by LDF, there was a decrease in tissue hemoperfusion (M), blood flow reserve (RK) in all three groups (p < 0.001), the most pronounced dysfunction of neurogenic and myogenic blood flow regulation was detected in the group of people with hypertension andobesity who underwent COVID-19. Conclusion. The study of microcirculation indicators by LDF method in persons with hypertension and obesity after suffering a coronavirus infection indicates the predominance of the spastic type of microcirculation, which, together with an increase in the levels of inflammatory markers, indicates a higher risk of thrombosis and cardiovascular complications, requiring more careful monitoring and treatment of this group of patients.

Effect of Statins and Renin-Angiotensin-Aldosterone System Inhibitors on IL-6 Levels in COVID-19 Patients.

Background/Objectives: Severe clinical course and mortality from COVID-19 are mostly associated with increased concentrations of IL-6 and IL-10. Findings from clinical trials suggest that both statins and renin-angiotensin-aldosterone system inhibitors (RAASI) might have the potential to reduce unfavorable outcomes in patients with COVID-19. The aim of this study was to evaluate the effect of statins and RAASI on the cytokine concentrations in COVID-19 patients. Methods: SARS-CoV-2 infected patients were enrolled in this study, and demographic, clinical, and routine laboratory data were evaluated. Plasma cytokine levels were measured by multiplex assay. Results: COVID-19 patients with chronic cardiovascular diseases (CVD) had significantly lower median plasma IL-6 levels than COVID-19 patients with no co-morbidities (26 vs. 53 pg/mL, p = 0.021). COVID-19 patients with CVD who were taking statins had significantly lower median concentrations of IL-6 (21 vs. 44 pg/mL, p = 0.027), TNFα (21 vs. 39.5 pg/mL, p = 0.036), and IL-10 (19 vs. 25.5 pg/mL, p = 0.025) compared to COVID-19 patients with no CVD. In a binary logistic regression model, IL-6 was a significant variable, with an odds ratio value of 0.961 (95% CI 0.929-0.995). Regarding RAASI, only plasma IL-6 (22 vs. 44 pg/mL, p = 0.012) levels were found to be significantly lower in COVID-19 patients with CVD consuming these medications compared to patients who did not have any CVD. Conclusions: COVID-19 patients who had chronic cardiovascular co-morbidities and who were administered statins or RAASI had significantly lower concentrations of IL-6 than COVID-19 patients who did not have any co-morbidities. These findings suggest that the use of statins or RAASI may be of value in COVID-19 patients.

The Association of Myocardial Infarction History and Geriatric Syndromes in the Elderly: Data from the Cross-Sectional Study EVKALIPT.

Background/Objectives: In recent decades, the number of patients with chronic cardiovascular diseases (CVDs) has increased, and CVD survivors are more likely to be old and frail and to have multiple comorbidities. A better understanding of geriatric conditions and their prevalence would help improve the management of older patients with CVDs. The main objective of this study is to estimate the association of myocardial infarction (MI) history with geriatric syndromes (GSs) in people 65 years of age and older. Methods: The cross-sectional study EVKALIPT included patients who were 65 years of age and older. All patients underwent a comprehensive geriatric assessment. The presence of MI history was assessed by medical records. Results: A total of 4295 participants were included. The prevalence of MI history was 12.6%. According to univariate regression analysis, MI history was associated with an increase in the odds of 12 GSs by 1.3-2.4 times. Multivariate regression analysis showed that male sex and four GSs (impairment in basic and instrumental activities of daily living, depression, falls) were independently associated with a history of MI, with the odds ratio ranging from 1.28 to 1.86. Conclusions: This study showed the association between MI history and GSs.