The role of NETosis in heart failure.

The hallmark of heart failure (HF) is structural myocardial remodeling including cardiomyocyte hypertrophy, fibrosis, cardiomyocyte cell death, and a low-grade aseptic inflammation. The initiation and maintenance of persistent chronic low-grade inflammation in HF are not fully understood. Oxidative stress-mediated neutrophil extracellular traps (NETs) are the main immune defense mechanism against external bacterial infections. Furthermore, NETs play important roles in noninfectious diseases. In the settings of myocardial infarction, myocarditis, or cardiomyopathies, neutrophils infiltrate the cardiac tissue and undergo NETosis that further aggravate the inflammation. A number of stimuli may cause NETosis that is a form of programmed cell death of neutrophils that is different from apoptosis of these cells. Whether NETosis is directly involved in the pathogenesis and development of HF is still unclear. In this review, we analyzed the mechanisms and markers of NETosis, especially placing the accent on the activation of the neutrophil-specific myeloperoxidase (MPO), elastase (NE), and peptidylarginine deiminase 4 (PAD4). These conclusions are supported by the recent genetic and pharmacological studies which demonstrated that MPO, NE, and PAD4 inhibitors are effective at least in the settings of post-myocardial infarction adverse remodeling, cardiac valve diseases, cardiomyopathies, and decompensated left ventricular hypertrophy whose deterioration can lead to HF. This is essential for understanding NETosis as a contributor to pathophysiology of HF and developments of new therapies of HF.

Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1.

The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7-9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel-Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.

Association of endothelial function and lower extremity perfusion in peripheral artery disease.

Background: The current study aims to investigate the association between endothelial function and lower extremity perfusion in patients with peripheral artery disease (PAD). Patients and methods: In total 229 patients with PAD (Rutherford stage 0-3) were enrolled in the current study. Endothelial function was assessed by measuring flow-mediated dilation (FMD) and endothelial cell proliferation capacity (ECPC). Lower extremity perfusion was assessed by measuring oscillometry-based ankle brachial index (oABI) and pulse wave index (PWI). In addition, carotid intima-media-thickness (cIMT) was also measured as a surrogate marker for atherosclerosis. Correlations between FMD, ECPC, oABI, PWI, and cIMT were analysed using Pearson correlation coefficient. The relationship between the above variables and the severity of PAD was investigated using ordinal logistic regression analysis. Results: Correlation analysis showed that FMD negatively associated with PWI (r = -0.183, p = 0.005), ECPC positively associated with oABI (r = 0.162, p = 0.014), and oABI negatively associated with PWI (r = -0.264, p < 0.001). Ordinal logistic regression analysis showed that ECPC (ß = -0.009, p = 0.048), oABI (ß = -5.290, p < 0.001), and age (ß = -0.058, p = 0.002) negatively associated with the PAD Rutherford stages. In addition, PWI (ß = 0.006, p < 0.001), cIMT (ß = 18.363, p = 0.043) positively associated with the PAD Rutherford stages. Conclusions: Endothelial function significantly associates with lower extremity perfusion in patients with PAD, and both are related to the severity of PAD.

Essential Polyunsaturated Fatty Acids in Blood from Patients with and without Catheter-Proven Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of death worldwide. Statins reduce morbidity and mortality of CAD. Intake of n-3 polyunsaturated fatty acid (n-3 PUFAs), particularly eicosapentaenoic acid (EPA), is associated with reduced morbidity and mortality in patients with CAD. Previous data indicate that a higher conversion of precursor fatty acids (FAs) to arachidonic acid (AA) is associated with increased CAD prevalence. Our study explored the FA composition in blood to assess n-3 PUFA levels from patients with and without CAD. We analyzed blood samples from 273 patients undergoing cardiac catheterization. Patients were stratified according to clinically relevant CAD (n = 192) and those without (n = 81). FA analysis in full blood was performed by gas chromatography. Indicating increased formation of AA from precursors, the ratio of dihomo-gamma-linolenic acid (DGLA) to AA, the delta-5 desaturase index (D5D index) was higher in CAD patients. CAD patients had significantly lower levels of omega-6 polyunsaturated FAs (n-6 PUFA) and n-3 PUFA, particularly EPA, in the blood. Thus, our study supports a role of increased EPA levels for cardioprotection.

Contextualising the association of socioeconomic deprivation with hospitalisation rates of myocardial infarction in a rural area in eastern Germany.

INTRODUCTION: Evidence on the association of socioeconomic deprivation with occurrence of acute myocardial infarction (AMI) is available from international studies and urban settings in western Germany. This study aimed to assess this association based on small geographical areas in a rural setting in eastern Germany. METHODS: This study used routine data of all patients with AMI who were treated in the Hospital Brandenburg in the city of Brandenburg, Germany, between May 2019 and May 2020. Hospitalisation rates of AMI were calculated for postal code regions that were located within the catchment area of the Hospital Brandenburg. Poisson regression was used to compare hospitalisation rates in areas with medium socioeconomic deprivation to areas with high deprivation, controlling for age group, sex and period (before or during COVID-19 pandemic). Publicly available social, infrastructure and healthcare-related features were mapped to characterise the study region. RESULTS: In total, 265 cases of AMI were registered in the study area, which comprised 116,126 inhabitants. The city of Brandenburg was characterised by the highest level of socioeconomic deprivation, while neighbouring areas showed a rural settlement structure and medium levels of deprivation. The number of general practitioners per 10 000 inhabitants did not differ between both areas. The adjusted rate ratio comparing hospitalisations due to AMI in areas with medium socioeconomic deprivation to areas with high socioeconomic deprivation was 0.71 (95%CI 0.56-0.91, p=0.01). CONCLUSION: This study adds evidence about the association of socioeconomic deprivation and AMI occurrence from a rural area in eastern Germany. Further research about the relationship of socioeconomic deprivation and cardiovascular health is needed from heterogeneous contexts.

Feasibility of non-invasive measurement of central blood pressure and arterial stiffness in shock.

BACKGROUND: Patients in haemodynamic shock are in need for an intensive care treatment. Invasive haemodynamic monitoring is state of the art for these patients. However, evolved, non-invasive blood pressure monitoring devices offer advanced functions like the assessment of central blood pressure and arterial stiffness. We analysed the feasibility of two oscillometric blood pressure devices in patients with shock. METHODS: We performed a monocentre prospective study, enrolling 57 patients admitted to the intensive care unit (ICU), due to septic and/or cardiogenic shock. We assessed invasive and non-invasive peripheral and central blood pressure <24 hours and 48 hours after admission on the ICU. Additional haemodynamic parameters such as pulse wave velocity (PWV), augmentation pressure and augmentation index were obtained through Mobil-o-Graph PWA (IEM) and SphygmoCor XCEL (AtCor Medical). RESULTS: A complete haemodynamic assessment was successful in all patients (48) with the Mobil-o-Graph 24 hours PWA and in 29 patients with the SphygmoCor XCEL (P = .001), when cases of death or device malfunction were excluded. Reasons for failure were severe peripheral artery disease, haemodynamic instability, oedema and agitation. Invasive blood pressure showed a sufficient correlation with both devices; however, large differences between invasive and non-invasive techniques were recorded in Bland-Altmann analysis (P < .05 for all parameters). PWV differed between the two devices. CONCLUSION: Non-invasive peripheral blood pressure measurement remains a rescue technique. However, non-invasive assessment of arterial stiffness and central blood pressure is possible in patients with septic or cardiogenic shock. Further studies are required to assess their clinical significance for patients in shock.

Secondary Prevention of Potentially Life-Threatening Arrhythmia Using Implantable Cardioverter Defibrillators in Patients with Biopsy-Proven Viral Myocarditis and Preserved Ejection Fraction.

BACKGROUND: Arrhythmia and sudden cardiac death (SCD) are known complications of acute viral myocarditis, regardless of ejection fraction (EF) at presentation. Whether such complications confer long-term risk is unknown, especially in those who present with preserved left ventricular (LV) function. No guidelines exist to the long-term reduction of arrhythmic death in such patients. METHOD: In this retrospective study, we analyzed the long-term results of implantable cardioverter defibrillator (ICD) treatment in patients after an acute phase of myocarditis with life-threatening arrhythmia. RESULTS: We identified 51 patients who had ICDs implanted following life-threatening arrhythmia presentation of confirmed acute viral myocarditis, despite preserved LVEF. Overall, 72.5% of patients had a clinical history of chest pain and viral infection with fever. Viral myocarditis was confirmed by cardiac magnetic resonance imaging (all had late enhancement) plus endomyocardial biopsies (most frequent were Epstein-Barr virus 29.4%, adenovirus 17.6%, and Coxsackie 17.6%), and 88.2% were discharged on anti-arrhythmic drugs. Overall, 12 patients (23.5%) required ICD intervention within the first 3 months, a further 7 patients (37.3% overall) between 3 and 12 months, and a further 12 patients (60.8% overall) until 58 months. During the follow-up, 3 of 51 patients (5.9%) died-deaths were due to cardiac events (n = 1), fatal infection (n = 1), and car accidents (n = 1). Of the 31 patients who had ventricular tachycardias after the acute phase of myocarditis, 11 needed radiofrequency ablation due to a high number of events or electrical storm. No baseline variables were identified that would serve as a basis for risk stratification. CONCLUSION: Malignant arrhythmic events due to viral myocarditis are potential predictors of future SCD in patients not only with a reduced but also with a preserved EF.

The impact of blood pressure variability and pulse pressure on graft survival and mortality after kidney transplantation.

BACKGROUND: Blood pressure variability and pulse pressure are strong and independent predictors of cardiovascular morbidity and mortality in the general population. So far, there are no data on the impact of blood pressure variability on mortality and graft survival after renal transplantation. METHODS: We performed a retrospective analysis of 877 patients who underwent kidney transplantation between 1997 and 2011 in two transplant centers in Germany (Berlin and Bochum) with a follow-up of 12-266 months. Visit-to-visit blood pressure variability over the first 12 months after transplantation (3 visits) and during the first 120 months after transplantation (7 visits) was calculated as the coefficient of variation (CV = standard deviation (SD)/mean blood pressure). Patient and graft survival was defined as composite endpoint. RESULTS: Cumulative survival was significantly higher for those patients with lower systolic blood pressure and pulse pressure within both the first 12 months and the 120 months posttransplant. After adjustment of data for gender, age, body mass index, and coronary artery disease, the cumulative incidence of the combined endpoint did not significantly differ between patients with lower vs higher CV (12 months CV hazard ratio (HR) (95% CI) = 0.90 (0.66-1.23), P = 0.51; 120 months CV HR (95% CI) = 0.92 (0.67-1.26), P = 0.60). A lower systolic blood pressure remained highly predictive for better survival in adjusted analyses. CONCLUSION: Visit-to-visit blood pressure variability is not associated with mortality or graft loss after kidney transplantation in this retrospective analysis. In analogy to the general population, however, there is an inverse relationship of survival and pulse pressure as a marker of arterial stiffness.

Prognostic Value of Urinary Calprotectin, NGAL and KIM-1 in Chronic Kidney Disease.

BACKGROUND/AIMS: Urinary biomarkers like neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) do not only allow an early diagnosis of acute kidney injury, but also provide prognostic information in this setting. The present prospective study investigates, whether the urinary biomarkers NGAL, KIM-1 and calprotectin have prognostic information in chronic kidney disease (CKD) as well. METHODS: Urinary calprotectin, NGAL and KIM-1 concentrations were assessed in a study population of 143 patients with stable CKD comprising diabetic and hypertensive nephropathy, glomerulonephritis/vasculitis, and autosomal dominant polycystic kidney disease. An eGFR fluctuation > 5ml/min/1.73m2 in the past 12 months was defined as an exclusion criterion in order to exclude cases with acute on chronic kidney injury. Renal function was monitored for a median follow-up of 37 months. RESULTS: In the overall study population, all the three biomarkers failed to predict DeGFR and DACR from baseline to follow-up in linear regression analysis adjusted for age, gender, and baseline eGFR. Contrarily, baseline ACR was significantly associated with DeGFR (p< 0.001). In the subgroup of patients with vasculitis and glomerulonephritis, all the three biomarkers were significantly associated with DeGFR, with calprotectin having the highest regression coefficient. CONCLUSION: In contrast to the traditional biomarker "albuminuria", neither the inflammatory biomarker calprotectin, nor the tubular biomarkers NGAL and KIM-1, provide robust prognostic information on the loss or renal function in a heterogeneous CKD population. All of them, however, are candidate prognostic biomarkers in primarily inflammatory renal diseases.

Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD) MRI.

BACKGROUND/AIMS: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. METHODS: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. RESULTS: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each), whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each). CONCLUSION: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na+-K+-2Cl- transporter by furosemide.

Urinary biomarkers for the differentiation of prerenal and intrinsic pediatric acute kidney injury.

BACKGROUND: Urinary calprotectin and neutrophil gelatinase-associated lipocalin (NGAL) have recently been identified as promising biomarkers for the differentiation of prerenal and intrinsic acute kidney injury (AKI) in adults. In the study reported here we examined the diagnostic accuracy of calprotectin, NGAL, and kidney injury molecule 1 (KIM-1) in pediatric patients. METHODS: Urinary calprotectin, NGAL, and KIM-1 concentrations were assessed in a study population of 139 pediatric subjects including 39 patients with intrinsic AKI, 14 with prerenal AKI, and 86 non-AKI subjects. RESULTS: Median urinary calprotectin and NGAL concentrations were higher in patients with intrinsic AKI than in those with prerenal AKI (calprotectin by 22-fold, NGAL by 9-fold). Receiver operating characteristic (ROC) curve analyses for the differentiation of intrinsic and prerenal AKI resulted in an area under the curve (AUC) of 0.90 [95 % confidence interval (CI) 0.81-0.98] for calprotectin and 0.73 (95 % CI 0.58-0.87) for NGAL. Median urinary KIM-1 concentrations were not significantly different between patients with prerenal AKI and those with intrinsic disease (P = 0.98; AUC 0.50, 95 % CI, 0.35-0.65). The AUC for the fractional excretion of sodium (FENa) and proteinuria was 0.78 (95 % CI 0.63-0.92) and 0.77 (CI 0.65-0.90), respectively. CONCLUSIONS: Urinary calprotectin outperforms NGAL, KIM-1, FENa, and proteinuria as a biomarker for the differentiation of prerenal and intrinsic AKI in pediatric patients with a high diagnostic accuracy.

Urinary calprotectin: a new diagnostic marker in urothelial carcinoma of the bladder.

PURPOSE: Recently, a proteomic study of sera from patients with bladder cancer identified S100A8 and S100A9 as tumor-associated proteins. The present cross-sectional study investigates whether calprotectin, the heterodimer of S100A8/S100A9 may serve as a urinary biomarker for the detection of urothelial bladder cancer. METHODS: Urinary calprotectin concentrations were assessed in a population of 181 subjects including 46 cases of bladder cancer. 41 cases of renal cell cancer, 54 cases of prostate cancer, and 40 healthy subjects served as control. Acute kidney injury, urinary tract infection, previous BCG-treatment and secondary transurethral resection of the bladder tumor were defined as exclusion criteria. Assessment was performed by enzyme-linked immunosorbent assay and immunohistochemistry detecting calprotectin. RESULTS: Median calprotectin concentrations (ng/ml) were significantly higher in patients with bladder cancer than in healthy controls (522.3 vs. 51.0, p < 0.001), renal cell cancer (90.4, p < 0.001), and prostate cancer (71.8, p < 0.001). In urothelial carcinoma prominent immunostaining occurred in a subset of tumor cells and in infiltrating myeloid cells. Receiver operating characteristic analysis provided an area under the curve of 0.88 for the differentiation of bladder cancer and healthy control. A cut-off value of 140 ng/ml (determined by Youden's index) resulted in sensitivity and specificity values of 80.4 and 92.5 %. Low grade tumors were associated with significantly lower calprotectin concentrations than high grade tumors (351.9 vs. 1635.2 ng/ml, p = 0.004). CONCLUSIONS: Urothelial malignancies are associated with highly increased concentrations of calprotecin in the urine. In absence of renal failure and pyuria, calprotectin constitutes a promising biomarker for the detection of bladder cancer.

Differential impact of belatacept and cyclosporine A on central aortic blood pressure and arterial stiffness after renal transplantation.

Calcineurin inhibitors (CNI) are potent vasoconstrictors and induce an acceleration of arteriosclerosis, thus contributing to the cardiovascular risk after renal transplantation. The study compares the impact of belatacept and cyclosporine A (CsA) on arterial stiffness and central aortic blood pressure. We performed a case-control study in 46 patients (23 on belatacept and 23 on CsA) matched for age, body mass index, time after transplantation, and time on dialysis prior to transplantation. Pulse wave analysis (SphygmoCor, AtCor(®) ) was used to assess central aortic blood pressure, aortic augmentation pressure, and pulse wave velocity (PWV) as a marker of arterial stiffness. Assessment of vascular function was performed after a minimum of 20 months and a median follow-up of 81 months post-transplant. Peripheral systolic and diastolic blood pressure did not significantly differ in the two groups (p > 0.05 each). The central aortic augmentation pressure was higher in the CsA group (12.7 mmHg vs. 7.3 mmHg, p = 0.048). PWV as a measure of arterial stiffness did not differ in the two groups. Thus, belatacept is not associated with a significant difference in arterial stiffness compared to CsA after a median of 81 months post-transplant. It is associated, however, with a lower aortic augmentation pressure, a strong independent cardiovascular risk factor.

Sonographic assessment of spleen size in Turkish migrants with Familial Mediterranean fever in Germany.

OBJECTIVES: Familial Mediterranean fever (FMF) can be associated with splenomegaly. Prospective quantitative data are lacking. We performed a sonographic assessment of spleen size in patients with FMF and healthy control participants to assess its diagnostic value. METHODS: Patients with FMF according to the criteria of Livneh et al (Arthritis Rheum 1997; 40:1879-1885) who were in an asymptomatic interval and control participants were prospectively included in this study in Germany and underwent sonographic measurement of the spleen as well as a structured interview and a physical examination. Patients and controls were Turkish migrants. RESULTS: Thirty-six patients and 27 controls were included. Patients and controls did not differ significantly in age (mean ± SD, 34.8 ± 9.7 versus 33.3 ± 10.0 years, respectively; P = .56), sex, height, weight, or body mass index (26.7 ± 4.7 versus 26.1 ± 4.3 kg/m(2); P = .63). Spleen size was greater in patients than controls in width (4.3 ± 1.0 versus 3.7 ± 0.7 cm; P = .008) and also length (12.1 ± 1.9 versus 10.5 ± 1.4 cm; P = .001). Twenty-six of 36 patients (72.2%) had a history of appendectomy compared to 3 of 27 controls (11.1%; P < .001). The combination of an enlarged spleen (length >11 cm and/or width >4 cm) gave specificity of 100% (95% confidence interval, 87%-100%) and a positive predictive value of 100% (95% confidence interval, 78%-100%) for the diagnosis of FMF in our study. CONCLUSIONS: Spleen size as evaluated by sonography is larger in patients with FMF compared to healthy controls. Most patients with FMF included in this study had undergone appendectomy. Familial Mediterranean fever should be considered as a differential diagnosis in Turkish migrants in Germany if the spleen is enlarged and a history of appendectomy is reported.

Atrial fibrillation in human patients is associated with increased collagen type V and TGFbeta1.

Background and aim: Atrial fibrosis is an important factor in initiating and maintaining atrial fibrillation (AF). Collagen V belongs to fibrillar collagens. There are, however no data on collagen V in AF. The aim of this work was to study the quantity of collagen V and its relationship with the number of fibroblasts and TGF- b 1 expression in patients in sinus rhythm (SR) and in patients with atrial fibrillation (AF). Methods: We used quantitative immuhistochemistry to study collagen V in right and left atrial biopsies obtained from 35 patients in SR, 35 patients with paroxysmal AF (pAF) and 27 patients with chronic, long-standing persistent AF (cAF). In addition, we have quantified the number of vimentin-positive fibroblasts and expression levels of TGF-ß1. Results: Compared to patients in SR, collagen V was increased 1.8- and 3.1-fold in patients with pAF and cAF, respectively. In comparison with SR patients, the number of vimentin-positive cells increased significantly 1.46- and 1.8-fold in pAF and cAF patients, respectively.Compared to SR patients, expression levels of TGF-ß1, expressed as fluorescence units per tissue area, was significantly increased by 77 % and 300 % in patients with pAF and cAF, respectively. Similar to intensity measurements, the number of TGFß1-positive cells per 1 mm2 atrial tissue increased significantly from 35.5 ± 5.5 cells in SR patients to 61.9 ± 12.4 cells in pAF and 131.5 ± 23.5 cells in cAF. In both types of measurements, there was a statistically significant difference between pAF and cAF groups. Conclusions: This is the first study to show that AF is associated with increased expression levels of collagen V and TGF-ß1indicating its role in the pathogenesis of atrial fibrosis. In addition, increases in collagen V correlate with increased number of fibroblasts and TGF-ß1 and are more pronounced in cAF patients than those in pAF patients.

Impact of the COVID-19 pandemic on hospital admission rates for arterial hypertension and coronary heart disease: a German database study.

Background: During the SARS-CoV-2 pandemic it was speculated that the virus might be associated with a persistent increase of cardiovascular risk. The present study compares pre- and post-pandemic hospital admission rates for hypertension and coronary artery disease. Methods: Systematic multicentric retrospective cohort analysis of 57.795 hospital admissions in an urban region in Germany during two different periods (pre-pandemic 01-06/2019 vs. post-pandemic era 01-06/2023). Information on hospital admissions for arterial hypertension, chronic coronary syndrome, unstable angina pectoris and acute myocardial infarction were extracted from the hospitals data systems. Additionally, six comorbidities and performed coronary interventions were monitored. Results: Compared to the pre-pandemic era, there was no increase in hospitalizations for arterial hypertension (516 vs. 483, -6.8%, p = 0.07) or myocardial infarction (487 vs. 349, -23.8%, p < 0.001), but the total number of patient admissions with chest pain as the presenting symptom increased (chronic coronary syndrome: 759 vs. 943, +24.2%, p < 0.001; unstable angina pectoris: 270 vs. 451, +67.0%, p < 0.001). At the same time, the number of performed coronary angiographies increased, but less patients underwent percutaneous interventions. Patients admitted with chest pain in the post-pandemic era were in general healthier with less comorbidities. Conclusion: The present multicenter cohort study found no evidence for an increase in hospitalizations for arterial hypertension or coronary artery disease after the end of the pandemic. However, further studies with larger sample sizes are needed to confirm our results.

Lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients in non-metropolitan areas of Brandenburg, Germany.

Background and aims: In the non-metropolitan region of Brandenburg (Germany), which is characterized by high rates of cardiovascular diseases and underserved medical care, there is a lack of awareness regarding lipoprotein(a) [Lp(a)] as a risk factor. In addition, data from patients with atherosclerotic cardiovascular disease (ASCVD) in diverse regional backgrounds, including the understudied Brandenburg cohort, and various healthcare statuses remain insufficient. Methods: In this WalkByLab study, Lp(a) levels were monitored in a non-metropolitan cohort (n = 850) in Brandenburg, Germany, comprising 533 patients at high cardiovascular risk and 317 healthy controls. Patients underwent a comprehensive angiological screening, which included blood serum analysis, assessment of medical and family history, cardiovascular risk, and disease status, and evaluation of lifestyle and quality of life. All parameters were evaluated with regard to two groups based on Lp(a) levels: low (<50 mg/dl) and high (≥50 mg/dl). Results: Brandenburg patients with cardiovascular diseases showed higher Lp(a) levels than healthy controls (24.2% vs. 14.8%, p = 0.001). Logistic regression analysis with different characteristics revealed that Lp(a) was an independent risk factor significantly associated with ASCVD (OR 2.26, 95% CI 1.32-3.95, p = 0.003). The high-Lp(a) group showed a higher proportion of patients with coronary artery disease, peripheral artery disease, or cerebrovascular disease compared to the low-Lp(a) group (50% vs. 36.8%; 57.7% vs. 45.8%; 17.6% vs. 9.2%; p = 0.004); also, a higher percentage of patients in the high-Lp(a) group had heart failure (72.8% vs. 53.2%, p = 0.014) and myocardial infarction (24.7% vs. 13.9%, p = 0.001). The high-Lp(a) group exhibited higher rates of statins (63.1% vs. 50.4%, p = 0.003), ezetimibe (14.8% vs. 5.5.%, p = 0.001), and beta-blockers (55.7% vs. 40.7%, p = 0.001) use. Lp(a) levels were found to be independent of physical activity or smoking behavior and did not change over time (12 months). Conclusions: Our study highlights the significance of elevated Lp(a) levels in Brandenburg cardiovascular patients and identifies them as an independent risk factor for ASCVD, which has implications for addressing cardiovascular health of non-metropolitan populations.

Oxidized high-density lipoprotein associates with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is the most common heart arrhythmia and considered to be a progressive chronic disease associated with increased morbidity and mortality. Recent data suggest a link between inflammation, oxidative stress, and AF, although the underlying mechanisms are not fully understood. Because oxidized lipoproteins cause structural damage and electrophysiologic changes in cardiomyocytes, it is feasible that the transformation of atheroprotective high-density lipoprotein (HDL) into dysfunctional HDL contributes to the development of AF. OBJECTIVE: The purpose of this study was to determine whether a reduced antioxidant function of HDL is associated with the presence of AF. METHODS: In this multicenter cross-sectional cohort study, we assessed HDL function in sera of 1206 participants. Patients were divided into groups according to the presence of AF (n = 233) or no AF (n = 973). A validated cell-free biochemical assay was used to determine reduced HDL antioxidant function as assessed by increased normalized HDL lipid peroxide content (nHDLox). RESULTS: Participants with AF had a 9% higher mean relative nHDLox compared to persons without AF (P = .025). nHDLox was strongly associated with AF in all models of logistic regression, including the analysis adjusted for age, sex, and risk factors for AF (all P ≤.01). CONCLUSION: Reduced antioxidant HDL function is associated with the presence of AF, which supports growing evidence that impaired lipoprotein function is linked to electrophysiological changes in cardiomyocytes. nHDLox is one of several contributors to the initiation and perpetuation of AF.

Defibrillator exchange in the elderly.

Background: Implantable cardioverter-defibrillator (ICD) therapy in elderly patients is controversial because survival benefits might be attenuated by nonarrhythmic causes of death. Objective: The purpose of this study was to investigate the outcome of septuagenarians and octogenarians after ICD generator exchange (GE). Methods: A total of 506 patients undergoing elective GE were analyzed to determine the incidence of ICD shocks and/or survival after GE. Patients were divided into a septuagenarian group (age 70-79 years) and an octogenarian group (age ≥80 years). The primary endpoint was death from any cause. Secondary endpoints were survival after appropriate ICD shock and death without experiencing ICD shocks after GE ("prior death"). Results: The association of the ICD with all-cause mortality and arrhythmic death was determined for septuagenarians and octogenarians. Comparing both groups, similar left ventricular ejection fraction (35.6% ± 11.2% vs 32.4% ± 8.9%) and baseline prevalence of New York Heart Association functional class III or IV heart failure (17.1% vs 14.7%) were found. During the entire follow-up period of the study, 42.5% of patients in the septuagenarian group died compared to 79% in the octogenarian group (P <.01). Prior death was significantly more frequent in both age groups than were appropriate ICD shocks. Predictors of mortality were common in both groups and included advanced heart failure, peripheral arterial disease, and renal failure. Conclusion: In clinical practice, decision-making for ICD GE among the elderly should be considered carefully for individual patients.

Association of plasma propionate concentration with coronary artery disease in a large cross-sectional study.

Background: Microbiome has been linked to the pathogenesis of coronary artery disease (CAD) but data providing direct evidence for an association of short-chain fatty acids (SCFA) with CAD are lacking. This study aimed to evaluate the role of propionate, the most important SCFA in patients with CAD. Methods: We performed a cross-sectional study enrolling patients admitted for invasive coronary angiography in two university hospitals in Germany. Patients with known or suspected CAD and risk factors for cardiovascular disease were prospectively recruited. Blood sampling was performed after overnight fasting and before invasive procedures. Measurement of propionate was performed by liquid chromatography. Results: The study included 1,253 patients (median [IQR], 67 [58-76] years; 799 men [64%]). A total of 739 had invasively confirmed CAD with at least one coronary artery stenosis ≥50% and 514 had exclusion of CAD. CAD patients had significant lower levels of propionate (median 5.75 µM, IQR, 4.1-7.6) compared to the non-CAD groups 6.53 µM (4.6-8.6, p < 0.001). Multivariate linear regression analysis revealed an odds ratio of 0.94 (CI 0.90-0.98, p = 0.002) for propionate as predictor of CAD. The odds ratio was further decreased to 0.45 (CI 0.31-0.65, p < 0.001) when comparing patients in the lowest quartile of propionate with those with higher levels of propionate. Conclusion: The study provides large-scale in vivo data for the association of propionate to manifest coronary artery disease, independent of other traditional cardiovascular risk factors.