Severity, predictors and clinical correlates of Post-COVID syndrome (PCS) in Germany: A prospective, multi-centre, population-based cohort study.

Background: Post-COVID syndrome (PCS) is an important sequela of COVID-19, characterised by symptom persistence for >3 months, post-acute symptom development, and worsening of pre-existing comorbidities. The causes and public health impact of PCS are still unclear, not least for the lack of efficient means to assess the presence and severity of PCS.

Methods: COVIDOM is a population-based cohort study of polymerase chain reaction (PCR) confirmed cases of SARS-CoV-2 infection, recruited through public health authorities in three German regions (Kiel, Berlin, Würzburg) between November 15, 2020 and September 29, 2021.

Systematic Evaluation of Pleiotropy Identifies 6 Further Loci Associated With Coronary Artery Disease.

Background: Genome-wide association studies have so far identified 56 loci associated with risk of coronary artery disease (CAD). Many CAD loci show pleiotropy; that is, they are also associated with other diseases or traits.

Objectives: This study sought to systematically test if genetic variants identified for non-CAD diseases/traits also associate with CAD and to undertake a comprehensive analysis of the extent of pleiotropy of all CAD loci.

Coding Variation in ANGPTL4, LPL, and SVEP1 and the Risk of Coronary Disease.

Background: The discovery of low-frequency coding variants affecting the risk of coronary artery disease has facilitated the identification of therapeutic targets.

Methods: Through DNA genotyping, we tested 54,003 coding-sequence variants covering 13,715 human genes in up to 72,868 patients with coronary artery disease and 120,770 controls who did not have coronary artery disease. Through DNA sequencing, we studied the effects of loss-of-function mutations in selected genes.

A genome-wide association study identifies 6p21 as novel risk locus for dilated cardiomyopathy.

Aims: Dilated cardiomyopathy (DCM) is one of the leading causes for cardiac transplantations and accounts for up to one-third of all heart failure cases. Since extrinsic and monogenic causes explain only a fraction of all cases, common genetic variants are suspected to contribute to the pathogenesis of DCM, its age of onset, and clinical progression. By a large-scale case-control genome-wide association study we aimed here to identify novel genetic risk loci for DCM.

The large non-coding RNA ANRIL, which is associated with atherosclerosis, periodontitis and several forms of cancer, regulates ADIPOR1, VAMP3 and C11ORF10.

The long non-coding RNA ANRIL is the best replicated genetic risk locus of coronary artery disease (CAD) and periodontitis (PD), and is independently associated with a variety of other immune-mediated and metabolic disorders and several forms of cancer. Recent studies showed a correlation of decreased concentrations of proximal ANRIL transcripts with homozygous carriership of the CAD and PD main risk alleles. To elucidate the relation of these transcripts to disease manifestation, we constructed a short hairpin RNA in a stable inducible knock-down system of T-Rex 293 HEK cell lines, specifically targeting the proximal transcripts EU741058 and DQ485454.

Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: a collaborative meta-analysis.

Objectives: This study sought to ascertain the relationship of 9p21 locus with: 1) angiographic coronary artery disease (CAD) burden; and 2) myocardial infarction (MI) in individuals with underlying CAD.

Background: Chromosome 9p21 variants have been robustly associated with coronary heart disease, but questions remain on the mechanism of risk, specifically whether the locus contributes to coronary atheroma burden or plaque instability.

Methods: We established a collaboration of 21 studies consisting of 33,673 subjects with information on both CAD (clinical or angiographic) and MI status along with 9p21 genotype.

Large-scale association analysis identifies new risk loci for coronary artery disease.

Coronary artery disease (CAD) is the commonest cause of death. Here, we report an association analysis in 63,746 CAD cases and 130,681 controls identifying 15 loci reaching genome-wide significance, taking the number of susceptibility loci for CAD to 46, and a further 104 independent variants (r(2) < 0.2) strongly associated with CAD at a 5% false discovery rate (FDR).

A variant in the heart-specific fatty acid transport protein 6 is associated with lower fasting and postprandial TAG, blood pressure and left ventricular hypertrophy.

Fatty acid transport protein 6 (FATP6) is primarily expressed in the heart and seems to be involved in cardiac fatty acid uptake. Therefore, we investigated whether a variation in the 5'-untranslated region of the FATP6 gene is associated with features of the metabolic syndrome and signs of myocardial alteration or heart failure. A total of 755 male participants from a Metabolic Intervention Cohort Kiel were genotyped for the FATP6-7T>A polymorphism (rs2526246) and phenotyped for features of the metabolic syndrome.

Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.

We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 × 10⁻⁸ and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.

Genome-wide association study identifies a new locus for coronary artery disease on chromosome 10p11.23.

Aims: Recent genome-wide association (GWA) studies identified 10 chromosomal loci for coronary artery disease (CAD) or myocardial infarction (MI). However, these loci explain only a small proportion of the genetic variability of these pertinent diseases. We sought to identify additional CAD/MI loci by applying a three-stage approach.

Cardiac release and kinetics of cytokines after elective bare metal coronary stenting.

The study was designed to assess the cardiac release kinetics of the cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor-necrosis-factor-α (TNF-α) in patients with significant stenosis of the ramus interventricularis anterior. Ten patients were treated by bare metal stent implantation, 11 patients who underwent a diagnostic coronary angiography without intervention served as a control group. Cytokines paired blood samples were withdrawn from the coronary sinus and a peripheral vein immediately before and 1, 2, 6 h after the intervention.

Intravascular ultrasound study and evidence of pathological coronary flow reserve in patients with isolated coronary artery aneurysms.

Objectives: Isolated coronary artery aneurysms (CA) are defined as non-obstructive lesions with luminal dilation > or =2-fold of normal coronary diameters.

Methods: A coronary sinus study with incremental atrial pacing was performed in 19 patients with bilateral fusiform CA to investigate myocardial ischemia. Intravascular ultrasound was performed to characterize the lesions morphology.

Platelet-activating factor levels of serum and gingival crevicular fluid in nonsmoking patients with periodontitis and/or coronary heart disease.

The purpose of the present study was to investigate systemic and local levels of platelet-activating factor (PAF), a potent proinflammatory mediator implicated in cardiovascular pathophysiology in adult nonsmoking patients with periodontitis with or without coronary heart disease (CHD). Eighty-seven volunteers, 25 periodontitis patients, 19 periodontitis with CHD patients, 19 CHD patients, and 24 healthy controls were included, and periodontal conditions were assessed. Gingival crevicular fluid (GCF) and venous blood were collected, and PAF levels were measured by enzyme-linked immunosorbent assay.

Identification of a shared genetic susceptibility locus for coronary heart disease and periodontitis.

Recent studies indicate a mutual epidemiological relationship between coronary heart disease (CHD) and periodontitis. Both diseases are associated with similar risk factors and are characterized by a chronic inflammatory process. In a candidate-gene association study, we identify an association of a genetic susceptibility locus shared by both diseases.

New susceptibility locus for coronary artery disease on chromosome 3q22.3.

We present a three-stage analysis of genome-wide SNP data in 1,222 German individuals with myocardial infarction and 1,298 controls, in silico replication in three additional genome-wide datasets of coronary artery disease (CAD) and subsequent replication in approximately 25,000 subjects. We identified one new CAD risk locus on 3q22.3 in MRAS (P = 7.

HBEGF, SRA1, and IK: Three cosegregating genes as determinants of cardiomyopathy.

Human dilated cardiomyopathy (DCM), a disorder of the cardiac muscle, causes considerable morbidity and mortality and is one of the major causes of sudden cardiac death. Genetic factors play a role in the etiology and pathogenesis of DCM. Disease-associated genetic variations identified to date have been identified in single families or single sporadic patients and explain a minority of the etiology of DCM.

Lifelong reduction of LDL-cholesterol related to a common variant in the LDL-receptor gene decreases the risk of coronary artery disease--a Mendelian Randomisation study.

Background: Rare mutations of the low-density lipoprotein receptor gene (LDLR) cause familial hypercholesterolemia, which increases the risk for coronary artery disease (CAD). Less is known about the implications of common genetic variation in the LDLR gene regarding the variability of cholesterol levels and risk of CAD.

Methods: Imputed genotype data at the LDLR locus on 1 644 individuals of a population-based sample were explored for association with LDL-C level.

Standardized quantification of pulmonary fibrosis in histological samples.

The Ashcroft scale for the evaluation of bleomycin-induced lung fibrosis is the analysis of stained histological samples by visual assessment. Based on the knowledge that this procedure is not standardized in animals and results are highly variable, we hypothesized that modification of this method may improve quantification of lung fibrosis in small animals. To prove our hypothesis, we evaluated pulmonary fibrosis in Lewis rats induced by a single intratracheal injection of 0.

Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease.

Background: Recently, genome-wide association studies identified variants on chromosome 9p21.3 as affecting the risk of coronary artery disease (CAD). We investigated the association of this locus with CAD in 7 case-control studies and undertook a meta-analysis.

Inotropic therapy for cardiac low output syndrome: comparison of hemodynamic effects of dopamine/dobutamine versus dopamine/dopexamine.

Objective: To examine the effects of a therapy with dopexamine/dopamine in comparison with a regimen of dobutamine/dopamine on the outcome of patients with profound cardiogenic shock.

Material And Methods: Twenty patients presenting with an acute cardiogenic shock assisted with mechanical ventilation, being refractory to a therapy with dopamine alone were analyzed. After persistence of low cardiac output syndrome (cardiac index <2.

Fungal rDNA signatures in coronary atherosclerotic plaques.

Bacterial DNA has been found in coronary plaques and it has therefore been concluded that bacteria may play a role as trigger factors in the chronic inflammatory process underlying coronary atherosclerosis. However, the microbial spectrum is complex and it is not known whether microorganisms other than bacteria are involved in coronary disease. Fungal 18S rDNA signatures were systematically investigated in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients and controls (unaffected coronary arteries) using clone libraries, denaturating gradient gel analysis (DGGE), in situ hybridization and fluorescence in situ hybridization (FISH).

Role of NOD2/CARD15 in coronary heart disease.

Background: Bacterial DNA has been repeatedly detected in atheromatous lesions of coronary heart disease (CHD) patients. Phylogenetic signatures in the atheroma lesions that are similar to those of bacterial biofilms on human barrier organs, including the respiratory or gastrointestinal tract, raise the question of a defective barrier function in CHD. NOD2 plays a major role in defense against bacterial invasion.

NT-proBNP is not elevated in patients with obstructive sleep apnoea.

Background: N-terminal pro-brain natriuretic peptide (NT-ProBNP) has emerged as an important marker of cardiac stress and may reflect the severity of underlying cardiac dysfunction, which is thought to be associated with obstructive sleep apnoea syndrome (OSAS).

Methods: This study evaluated the plasma concentration of NT-ProBNP in 60 consecutive patients (median age 55.7 years, median body mass index (BMI) 31.

Signal transducer of inflammation gp130 modulates atherosclerosis in mice and man.

Liver-derived acute phase proteins (APPs) emerged as powerful predictors of cardiovascular disease and cardiovascular events, but their functional role in atherosclerosis remains enigmatic. We report that the gp130 receptor, which is a key component of the inflammatory signaling pathway within hepatocytes, influences the risk of atherosclerosis in a hepatocyte-specific gp130 knockout. Mice on an atherosclerosis-prone genetic background exhibit less aortic atherosclerosis (P < 0.