Cardiovascular diseases (CVD) are the leading cause of death worldwide. Therefore, it is essential to understand their relationship and prevalence in different diseases that may present specific risk factors for them. The objective of this document is to analyze the specific prevalence of CVD in patients with inflammatory bowel disease (IBD), describing the presence of classical and non-classical cardiovascular risk factors in these patients. Additionally, we will detail the pathophysiology of atherosclerosis in this patient group and the different methods used to assess cardiovascular risk, including the use of risk calculators in clinical practice and different ways to assess subclinical atherosclerosis and endothelial dysfunction. Furthermore, we will describe the potential influence of medication used for managing patients with IBD on cardiovascular risk, as well as the potential influence of commonly used drugs for managing CVD on the course of IBD. The document provides comments and evidence-based recommendations based on available evidence and expert opinion. An interdisciplinary group of gastroenterologists specialized in IBD management, along with a consulting cardiologist for this type of patients, participated in the development of these recommendations by the Spanish Group of Work on Crohn's Disease and Ulcerative Colitis (GETECCU).

Immune checkpoint inhibitors (ICIs) might increase the risk of major adverse cardiovascular events (MACEs). This study aimed to evaluate the risk of MACE in patients with melanoma after ICI initiation.

We conducted a before-after cohort study using claims data from Optum's deidentified Clinformatics Data Mart Database. We included adult patients with melanoma who received any approved ICI between 2011 and 2021 with a minimum of 12 months of observable data before ICI. The main outcome was time to first MACE (myocardial infarction, coronary revascularization, stroke, heart failure hospitalization) and rate of MACE before and after ICI, ascertained using International Classification of Diseases, 9th/10th Revision diagnostic codes. Hazard ratio (HR) and incidence rate ratio (IRR) were calculated.

We identified 4024 patients with ICI-treated melanoma. Mean age was 67.4 years (SD 14.1), 36% were women; 3066 (76.2%) received monotherapy and 958 (23.8%) combination immunotherapy. A total of 160 (4%) patients had a MACE before ICI and 224 (5.6%) after ICI (HR, 1.76; 95% CI, 1.47-2.12). MACE rate in the year before ICI was 56.16 per 1000 person-years compared with 80.91 per 1000 person-years the year after ICI (IRR, 1.44; 95% CI, 1.21-1.72). Ten cases of myocarditis were observed after ICI, 50% of them had a MACE. Risk factors associated with MACE after ICI were prior MACE, other cardiovascular conditions, hypertension, and older age. Glucocorticoid use was not associated with MACE.

Our results suggest that ICI might increase the risk of MACE in patients with melanoma during the first year after ICI.

To evaluate the risk of heart failure (HF) in patients with immune-mediated inflammatory diseases (IMIDs) compared to the general population with and without diabetes mellitus (DM).

A population-based cohort study was conducted in patients with rheumatoid arthritis (RA), radiographic axial spondyloarthritis (r-axSpA), psoriatic arthritis, and psoriasis (PsO) in Ontario from 2011 until 2019. The study outcome was first hospitalization for HF. Incidence rates of HF were calculated for each cohort. Hazard ratios (HRs) for HF were calculated using Cox proportional hazard models. The etiology of HF was descriptively classified into mutually exclusive groups based on comorbidities during HF hospitalization.

A total of 243,061 patients with IMID, 748,517 with DM, and 8,278,934 non-IMID, non-DM controls were analyzed. The crude incidence rate for HF in IMID was 2.70 per 1000 person-years, with the highest rate in RA and lowest in r-axSpA. The risk of being hospitalized for HF was higher in IMID compared with non-IMID comparators (HR 1.34, 95% CI 1.30-1.38). This risk was highest among patients with RA (HR 1.61, 95% CI 1.54-1.68) and lowest in PsO (HR 1.09, 95% CI 1.03-1.15). In comparison, the risk of HF hospitalization in patients with DM was higher (HR 2.19, 95% CI 2.16-2.21). The most common antecedent comorbidity associated with HF in all patients with IMID was ischemic heart disease. In patients with IMID without DM, atrial fibrillation had a similar effect as ischemic heart disease.

The risk of HF hospitalization is increased in patients with IMID compared to the general population.

Non-traditional cardiovascular risk factors (RFs) are increasingly emerging as important modifiers of cardiovascular risk (CVR), offering insights beyond traditional metrics like hypertension, diabetes, and dyslipidemia. These include novel biomarkers, chronic conditions (e.g., chronic kidney disease and chronic obstructive pulmonary disease), environmental exposures, chronic inflammation, infections, psychosocial factors, and sex-specific conditions, all of which influence the prediction, management, and outcomes of cardiovascular disease (CVD). These additional RFs may impact on CVD prediction and add valid information during tailored patient assessment and management. Therefore, a careful assessment of both traditional and non-traditional cardiovascular RFs, with a personalized treatment, could dramatically reduce the total CVD burden. Nevertheless, further research is needed to precisely estimate the magnitude of their impact as risk and prognosis modifiers in order to be included in future risk charts. This review provides a critical analysis of non-traditional RFs, their pathophysiological mechanisms, and their implications for personalized care. Integrating these factors into CVR assessment can reclassify patient risk categories, optimize therapeutic strategies, and improve prognosis. However, further research is needed to refine their inclusion in risk charts and evaluate their impact on public health outcomes. A tailored, multidisciplinary approach is essential to reduce the burden of CVD and associated mortality.

To determine the incidence rate (IR) and predictors of myocardial infarction (MI) in patients with antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV) as well as to estimate the IR ratio (IRR) of MI in AAV versus the background population.

325 patients diagnosed with AAV 1997-2016 in Skåne, Sweden were included. Data were collected from the time of AAV diagnosis, and each patient was grouped with 10 age-matched and sex-matched reference subjects from the background population. MI after AAV diagnosis was identified using Swedish Web-System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies and the Skåne Healthcare Register, and IR of first MI calculated. The IRR was computed by dividing the IR for 282 AAV patients by the corresponding rate in the 2763 reference subjects. Predictors of MI were analysed using Cox regression.

37 patients (11%) with AAV suffered an initial MI, yielding an IR of 1.6/100 person-years of follow-up (95% CI 1.2 to 2.2). The highest rate was recorded in the 3 months following AAV diagnosis, at 11.8/100 person-years (95% CI 6.2 to 22.7). The IRR of MI in AAV/reference was 1.9 (95% CI 1.3 to 2.8), highest in patients with myeloperoxidase-ANCA+disease (IRR 2.5, 95% CI 1.5 to 4.3) and those with high disease activity at diagnosis (2.1, 95% CI 1.3 to 3.3). Age at AAV diagnosis independently predicted MI.

The MI IR is greater in individuals diagnosed with AAV compared with background population, especially those with more severe disease, and highest in the 3 months following diagnosis. Age at diagnosis is the single independent predictor of MI in AAV in this study.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired hematopoietic stem cell disease that mainly occurs in young adults and is characterized by bone marrow failure, persistent intravascular hemolysis and thrombosis, all of which can cause severe end-organ damage, increase the risk of early death, and cause a severe disease burden in patients. In China, based on the historic reasons, glucocorticoids are still routinely used in many places. However, the effects of glucocorticoids on PNH hemolysis are uncertain. Evidence-based medical data and clinical benefits for glucocorticoid on PNH are missing, but the long-term use of glucocorticoids significantly increases the risk of adverse reactions in patients. Since PNH needs a lifelong follow-up and management, long-term glucocorticoid therapy will unavoidably seriously damage the health of patients. Therefore, glucocorticoids are not recommended for the treatment of PNH, either from domestic or overseas guidelines, or expert consensus. In this article, the limitations and challenges of glucocorticoids in the treatment of PNH were expounded upon, in order to encourage more effective and safe strategies to be accepted in China.

Background and Objectives: Sepsis still represents a syndrome with a high mortality. A timely sepsis diagnosis and an early intervention are crucial for the disease outcomes. Sepsis-associated acute kidney injury (SA-AKI) is highly prevalent but often diagnosed late. We aimed to investigate whether serum interleukin-6 (IL-6) and leukocyte cell population data (CPD) could be adequate biomarkers for the prediction of survival and SA-AKI development. Materials and Methods: We conducted a prospective observational study in a medical intensive care unit of a tertiary hospital centre in Zagreb, Croatia from June 2020 to October 2023. Adult patients with newly diagnosed sepsis were included and classified as immunocompetent or immunocompromised. Blood samples were collected upon admission. Results: A total of 150 patients were included in the study. Ninety-six (64%) patients were immunocompetent and fifty-four (36%) were immunocompromised. The median SOFA score was 8 (6-11). SA-AKI was diagnosed in 108 (72%) patients. ICU and hospital mortality was 27.3% and 37.3%, with no significant difference between groups. Significantly higher serum IL-6 levels were noted in the immunocompromised group, while neutrophil granularity intensity was higher in the immunocompetent group. According to logistic regression analyses, elevated IL-6 levels predicted a lethal ICU outcome, while elevated IL-6 levels and neutrophil reactivity intensity were predictors of SA-AKI development. A cluster analysis revealed two patient groups with different IL-6 concentrations, and further studies indicated that the group with higher IL-6 values had significantly higher SA-AKI occurrence and increased lethal outcomes. Conclusions: An early serum IL-6 measurement regardless of the patients' immune status indicates disease severity. Its measurement in the early phase of disease presentation, potentially in the emergency department, might facilitate ICU admission. Further research is warranted in the field of leukocyte CDP application.

Patients with adrenal insufficiency (AI) are known to have a higher cardiovascular risk (CVR) than the normal population. In particular arteriosclerosis, coronary heart disease, arterial hypertension, hyperlipoproteinemia as well as metabolic disturbances contribute to the increased morbidity and mortality. Aim of this study was to evaluate known CVR factors along with the quality of care by the treating physicians.

To this end the medical records of AI patients were screened for CVR factors and the treatment initiated was documented. In addition, a questionnaire evaluating CVR factors was analyzed if available.

In total, 327 AI patients were included in the study. At least 298 of these patients were found to have one or more CVR factors. Ninety-one patients were diagnosed with arterial hypertension, of these 40 patients (44%) still showed increased blood pressure (BP) values. Of all AI patients, about 25% (n = 83) did not have measurements to calculate their BMI, even though obesity is known as a major risk factor for cardiovascular events. Out of 46 patients with diabetes, one-quarter still had increased HbA1c values. Regarding hyperlipoproteinemia, only 2% of AI patients achieved normal lipid values across all parameters (n = 8). Interestingly, at least one lipid variable was untested in 150 patients (46%).

Our study demonstrates (1) the high rate of CVR factors in AI patients, leading to increased morbidity and eventually mortality, (2) AI patients are inadequately monitored and treated for CVR factors, (3) treating physicians should be aware of this risk to minimize complications where possible.

Cardiovascular disease (CVD) is a major cause of death in Korea, and studies have reported that asthma can have a negative impact on CVD. This study aimed to identify the association between asthma and CVD, including the current status, treatment status, and duration of asthma in Korean adults.

The Korea National Health and Nutrition Examination Survey (2016-2021) was used, and 34,384 adults aged 19 years or older were included. Exposures were asthma-related characteristics, and outcomes were hypertension, ischemic heart disease, and stroke. The association between asthma characteristics and CVD was analyzed using the chi-square test and multiple logistic regression analysis.

The asthma diagnosis experience rate of the population was 3.1%; 1.6% were currently suffering from asthma, 1.0% were receiving asthma treatment, 0.6% were receiving regular medication, and 1.5% had a disease duration of 11 years or more. The CVD diagnosis rates in the population were 20.2% for hypertension, 2.3% for ischemic heart disease, and 1.8% for stroke. Compared to those who had no asthma diagnosis, those who had been diagnosed with asthma (OR = 2.06, 95% CI = 1.47-2.87), received asthma treatment (OR = 1.93, 95% CI = 1.22-3.04), and had a long duration of asthma (OR = 3.54, 95% CI = 1.71-7.33) had a significantly higher risk of ischemic heart disease. However, hypertension and stroke were not significantly correlated with asthma-related characteristics.

Asthma diagnosis and asthma-related characteristics were associated with an increased risk of ischemic heart disease. Our study suggests that research on risk assessment and management of CVD in patients with asthma would be needed.

Technological innovation can drive scientific inquiry by allowing researchers to answer questions that were once out of reach. Eukaryotic mRNA synthesis was not so long ago thought of as a deterministic, sequential process in which transcriptional regulators and general transcription factors assemble in an orderly fashion into chromatin to, ultimately, activate RNA polymerase II. Advances in fluorescence microscopy techniques have revealed a much more complex scenario, wherein transcriptional regulators dynamically engage with chromatin in a more stochastic, probabilistic way. In this review, we will concentrate on what fluorescence fluctuation methods have taught us about the journey of transcription factors within live cells. Specifically, we summarized how these techniques have contributed to reshaping our understanding of the mechanism(s) of action of the glucocorticoid receptor, a ligand-regulated transcription factor involved in many physiological and pathological processes. This receptor regulates a variety of gene networks in a context-specific manner and its activity can be quickly and easily controlled by the addition of specific ligands. Thus, it is widely used as a model to study the mechanisms of transcription factors through live-cell imaging.

Inflammation has been widely recognized as one of the major pathophysiological drivers of the development of atrial fibrillation (AF), which works in tandem with other risk factors of AF including obesity, diabetes, hypertension, and heart failure (HF). Our current understanding of the role of inflammation in the natural history of AF remains elusive; however, several key players, including the NLRP3 (NLR family pyrin domain containing 3) inflammasome, have been acknowledged to be heavily influential on chronic inflammation in the atrial myocardium, which leads to fibrosis and eventual degradation of its electrical function. Nevertheless, our current methods of pharmacological modalities with reported immunomodulatory properties, including well-established classes of drugs e.g., drugs targeting the renin-angiotensin-aldosterone system (RAAS), statins, and vitamin D, have proven effective in reducing the overall risk of developing AF, the onset of postoperative atrial fibrillation (POAF), and reducing overall mortality among patients with AF. This might bring hope for further progress in developing new treatment modalities targeting cellular checkpoints of the NLRP3 inflammasome pathway, or revisiting other well-known anti-inflammatory drugs e.g., colchicine, vitamin C, nonsteroidal anti-inflammatory drugs (NSAIDs), glucocorticosteroids, and antimalarial drugs. In our review, we aim to find relevant upstream anti-inflammatory treatment methods for the management of AF and present the most current real-world evidence of their clinical utility.

To evaluate the incidence and risk of cardiovascular disease (CVD) among Korean patients with systemic lupus erythematosus (SLE) comparing them to diabetes patients and the general population. This nationwide cohort study focused on incident SLE patients aged over 40 years, matched with diabetes patients and the general population (1:4:4 ratio). CVD was defined as ischaemic heart disease, ischaemic stroke, and cardiac arrest. Incidence rate and incidence rate ratio (IRR) of CVD were calculated using generalised estimating equation models. The Fine-Gray model assessed risk factors for CVD in both SLE and diabetes patients. The study included 4272 incident SLE patients, 17,003 diabetes patients, and 17,088 from the general population. SLE patients had higher CVD risk compared to the general population, with adjusted IRRs of 1.99 for overall CVD. Diabetes patients showed increased CVD risk, but to a lesser extent, with an IRR of 1.39. SLE patients aged 40-59 years displayed a significantly elevated CVD risk. Advanced age, male gender, and current use of glucocorticoids, immunosuppressive, and anti-platelet agents were associated with increased CVD risk in SLE patients. SLE patients have a higher risk of CVD compared to the general population, more so than diabetes patients.

Whether inhaled corticosteroids (ICSs) reduce major adverse cardiovascular events (MACEs) in people with chronic obstructive pulmonary disease (COPD) is debated.

To establish, within people with COPD, (1) whether ICS reduced MACE rates (acute coronary syndrome (ACS), heart failure (HF), ischaemic strokes or cardiovascular-specific death) compared with long-acting bronchodilators; and (2) whether drug class, incident usership or patient cardiovascular history influenced the ICS-MACE relationship.

We conducted a cohort study including patients with COPD in England, using Clinical Practice Research Datalink Aurum data, linked with Hospital Episode Statistics and Office of National Statistics death data, between 1 January 2010 and 31 December 2019. We implemented Cox proportional hazard regressions, adjusting for time interactions or using propensity score-adjusted models, as necessary. Our exposures included prescriptions of any ICS (vs any long-acting bronchodilators) and triple therapy (vs combination long-acting bronchodilators), determined during the year prior to follow-up. The outcomes of interest were MACE collectively and individual MACE subtypes.

Among 113 353 people with COPD (mean age 67.9 years old, 53.3% male), ICS prescription was not associated with MACE (adjusted HR (95% CI)=0.98 (0.95, 1.02), p=0.41) but was associated with reduced HF, specifically, until year 6 of follow-up (average adjusted HR (95% CI)=0.91 (0.86, 0.96), p<0.001). HF reduction was driven by the ICS group containing mometasone furoate, beclomethasone, budesonide or ciclesonide (HR (95% CI)=0.89 (0.84, 0.94), p<0.001). Incident ICS use was associated with increased ACS (HR (95% CI)=1.27 (1.09, 1.47), p<0.001) but was not sustained beyond incident use. There was no association between triple therapy and MACE. Results did not differ by cardiovascular history.

ICS did not reduce MACE, except HF, likely by reducing misclassified COPD exacerbations.

Giant cell arteritis (GCA) is a large-vessel vasculitis that mainly affects women over fifty. GCA usually involves branches from the external carotid arteries, causing symptoms such as headaches, scalp tenderness, and jaw claudication. The most severe complication is ophthalmologic involvement, including acute anterior ischemic optic neuropathy and, less frequently, central retinal artery occlusion with a risk of permanent blindness. Approximately 40% of patients may have involvement of the aorta or its branches, which has a poor prognosis, although this is often asymptomatic at diagnosis. Diagnosis is largely based on imaging techniques such as FDG-PET combined with CT, CT angiography, or MRI angiography of the aorta and its branches. Polymyalgia rheumatica is associated with GCA in 30-50% of cases but may also occur independently. Treatment must be initiated urgently in the presence of ophthalmologic signs or when GCA is strongly suspected to prevent vision loss. The gold standard to confirm the diagnosis is temporal artery biopsy. However, Doppler ultrasound and vascular imaging are also reliable diagnostic techniques. Initially, high doses of corticosteroids like prednisone (40-80mg per day) are the mainstay of treatment. Tocilizumab can be discussed in combination with prednisone for corticosteroid sparing. Long-term management is essential, including monitoring for disease recurrence and corticosteroid-related side effects. General practitioners play a crucial role in early diagnosis, directing patients to specialized centres, and in managing ongoing treatment in collaboration with specialists. This collaboration is essential to address potential long-term complications such as cardiovascular events. They can occur five to ten years after the diagnosis of GCA even when the disease is no longer active, meaning that vigilant follow-up is required due to the patients' age and status.

In April 2023, over 30 experts and advocates from four countries met in Rome, Italy to discuss unmet needs in endocrine and bone health care for individuals with Duchenne muscular dystrophy (DMD). Despite recent advances in muscle-targeted therapy, long-term glucocorticoids (GC) remain the backbone of treatment for the foreseeable future. This affirms the need to intensify efforts that will mitigate serious complications of GC therapy, including unexpected mortality due to fat embolism syndrome following bone injury and also unrecognized adrenal suppression, early loss of ambulation linked to excess weight and/or fragility fracture, adverse cardiometabolic effects of GC, the psychosocial impact of profound growth and pubertal delay/hypogonadism, and the burden to families arising from monitoring and treating endocrine and skeletal complications of GC therapy. Delegates discussed: 1. The impact of GC therapy on the heart, 2. Predictors of fragility fractures and experience with intravenous and oral bisphosphonates plus teriparatide, 3. The effect of hormonal therapy on muscle-bone health, 4. Adrenal suppression, 5. Weight management, 6. Puberty, sexuality, fertility and gender identity, 7. The impact of early GC initiation, 8. Emerging knowledge about vamorolone (a novel dissociative steroid) and its effects on muscle, bone and endocrine health, and 9. Experiences implementing an endocrine-bone health management strategy nation-wide (in the UK). At the conclusion of the meeting, it was agreed that an endocrine-bone working group should be struck to continue the narrative, following which the International OPTIMIZE DMD Consortium was ignited to move the dial in these important areas.

Morphological and functional cardiac involvement is rarely described in patients with inflammatory bowel disease (IBD) but there is evidence that they have an increased risk of cardiovascular (CV) events despite the lower prevalence of traditional CV risk factors.

Our systematic review and meta-analysis examined the relationship between IBD and cardiac function, namely the incidence of heart failure (HF) and subclinical echocardiographic changes.

Two medical databases, PubMed and Scopus, were systematically searched up to September 2022 to identify all studies reporting HF and/or echocardiographic changes in IBD patients.

The qualitative analysis comprised a total of 18 studies (14 retrospective and 4 prospective studies) involving 59,838 patients. IBD was associated with subtle systolic and diastolic alterations, vascular dysfunction, increased risk for HF hospitalizations, and globally worse CV outcomes. Nine studies were included in the meta-analysis. In the IBD population, we found statistically significant reduced early to late diastolic transmitral flow (E/A), higher E to early diastolic mitral annular tissue velocity (E/e'), and decreased global longitudinal strain. Increased left atrial diameter and area were also present in IBD patients but no statistical significance was reached. Inter-atrial and right intra-atrial conduction delays were observed.

The IBD population has an increased risk for left ventricular and atrial dysfunction, vascular changes, arrhythmias, and HF hospitalization. Screening with sensitive imaging like speckle tracking echocardiography could identify early subclinical changes. IBD is in fact a CV risk factor and tight inflammation control may reduce CV risk.

Despite their beneficial actions as immunosuppressants, glucocorticoids (GC) have devastating effects on the musculoskeletal and cardiac systems, as long-term treated patients exhibit high incidence of falls, bone fractures, and cardiovascular events. Herein, we show that GC upregulate simultaneously in bone, skeletal muscle, and the heart the expression of E3 ubiquitin ligases (atrogenes), known to stimulate the proteasomal degradation of proteins. Activation of vitamin D receptor (VDR) signaling with the VDR ligands calcitriol or eldecalcitol prevented GC-induced atrogene upregulation in vivo and ex vivo in bone/muscle organ cultures and preserved tissue structure/mass and function of the 3 tissues in vivo. Direct pharmacologic inhibition of the proteasome with carfilzomib also conferred musculoskeletal protection. Genetic loss of the atrogene MuRF1-mediated protein ubiquitination in ΔRING mice afforded temporary or sustained protection from GC excess in bone or skeletal and heart muscle. We concluded that the atrogene pathway downstream of MuRF1 underlies GC action in bone, muscle, and the heart, and it can be pharmacologically or genetically targeted to confer protection against the damaging actions of GC simultaneously in the 3 tissues.

Introduction: Inflammation is a significant contributor to cardiovascular disease (CVD) in people with HIV (PWH), who face twice the risk of CVD compared to the general population. The presence of co-existing rheumatic disease (RD) may further exacerbate inflammation and increase the incidence of CVD events in this population. Methods: We conducted a retrospective cohort study using electronic health record (EHR) data from the Veterans Affairs Medical Center in Atlanta, covering the period from 2000 to 2019. A total of 5000 patients aged 20-87 years who were diagnosed with HIV and receiving care at the Atlanta VAMC between 2000 and 2019 were eligible for this analysis. This study included 3930 veterans with HIV and assessed the impact of rheumatic disease therapies (RDTs) on CVD outcomes. The primary outcome was the first occurrence of a CVD event. Results: Rheumatic disease was significantly associated with an increased risk of CVD events (OR = 2.67; p < 0.001). Additionally, exposure to multiple RDTs (aHR = 2.121, p = 0.047), NSAIDs (aHR = 1.694, p = 0.003), glucocorticoids (aHR = 2.332, p < 0.0001), and hypouricemic agents and colchicine (aHR = 3.445, p < 0.0001) were all significantly associated with increased CVD events. Conclusions: The co-existence of HIV infection and rheumatic disease, along with the use of RDTs, may amplify the risk of CVD events in PWH. These findings underscore the need for further investigation into the relationship between RD, RDTs, and CVD risk in larger, controlled studies, given the potential implications for treatment decisions in this patient population. A limitation of our study is that due to its retrospective design, we could not examine the impact of the sequential use of RDT groups and RD severity on CVD events.

TAVI-related complications, such as conduction disturbances, vascular complications or death may be related to increased inflammatory response. The aim of this study was to elucidate the efficacy and safety of the systemic glucocorticoid therapy regarding the adverse events after TAVI deployment.

We conducted a systemic search of PubMed, a reference list of relevant articles, and Medline. The main efficacy outcomes of interest were all-cause death, cardiac and non-cardiac death, permanent pacemaker implantation (PPM), new left bundle branch block (LBBB), stroke, and myocardial infarction (MI). Safety endpoints were major vascular complications, major bleeding events, and cardiac tamponade.

A total of 7 studies including data from 3439 patients with a median follow-up was 30 days. Systemic glucocorticoid compared to the control group were associated with an increased risk of non-cardiac death (Relative Risk [RR] 5.90 95%CI [2.95; 11.80], P<0.001) major vascular complications (RR 1.78, 95%CI [1.22 - 2.61], P=0.003) and cardiac tamponade (RR 3.42, 95%CI [1.69 - 6.92], P<0.001). However, there were no differences in all-cause death, cardiac death, new LBBB, stroke, MI, or major bleeding events (all P values >0.05).

Glucocorticoid therapy before the TAVI procedure was associated with an increase in non-cardiac death, major vascular events and cardiac tamponade. There were no differences in the risk of all-cause death, cardiac death, PPM or LBBB, stroke, or MI.

Rheumatoid arthritis (RA) is the most common form of autoimmune inflammatory arthritis and is associated with various comorbidities including cardiovascular disease (CVD). This scoping review summarizes the current evidence on longitudinal cohort studies assessing potential factors associated with the incidence of cardiovascular events among patients with RA.

Scopus, PubMed, Ovid MEDLINE and Cochrane databases were used to identify longitudinal cohort studies investigating the incidence of CVD among RA patients. Using predetermined inclusion and exclusion criteria, two reviewers screened and extracted the relevant studies independently to map the existing literature on this topic. The extracted data included study characteristics, demographics, comorbidities, behavioural and RA-related factors.

Thirty-three research papers were included with a mean follow-up duration of 7.8 years. The sample size of the studies ranged from 182 to 4,311,022 subjects, the mean age from 46.1 to 72.3 years, and on average, 34.6% of the participants were male. The following factors were reported to be associated with a higher incidence of CVD in RA patients: older age, male sex, co-morbid hypertension, diabetes, and/or dyslipidemia, the presence of rheumatoid factor (RF) and/or acute phase reactants. Among RA treatments, glucocorticoids were shown to increase CVD incidence while DMARDs, especially methotrexate, were associated with a lower incidence of CVD.

This review offers a comprehensive summary of the current literature reporting on risk factors for CVD incidence among RA patients. Future research should focus on the less studied factors, including socioeconomic status, physical inactivity, alcohol consumption, sleep habits and dietary patterns as well as some RA-related factors such as anti-citrullinated protein antibodies and functional impairment.

Iatrogenic adrenal insufficiency (IAI) is the most common form of adrenal insufficiency in adult patients, although its overall exact prevalence remains unclear. IAI is associated with adverse clinical outcomes, including adrenal crisis, impaired quality of life and increased mortality; therefore, it is imperative that clinicians maintain a high index of suspicion in patients at risk of IAI to facilitate timely diagnosis and appropriate management. Herein, we review the major causes, clinical consequences, diagnosis and care of patients with IAI. The management of IAI, particularly glucocorticoid-induced (or tertiary) adrenal insufficiency, can be particularly challenging, and the provision of adequate glucocorticoid replacement must be balanced against minimizing the cardiometabolic effects of excess glucocorticoid exposure and optimizing recovery of the hypothalamic-pituitary-adrenal axis. We review current treatment strategies and their limitations and discuss developments in optimizing treatment of IAI. This comprehensive Review aims to aid clinicians in identifying who is at risk of IAI, how to approach screening of at-risk populations and how to treat patients with IAI, with a focus on emergency management and prevention of an adrenal crisis.

While glucocorticoid (GC) treatment initiated for COVID-19 reduces mortality, it is unclear whether GC treatment prior to COVID-19 affects mortality. Long-term GC use raises infection and thromboembolic risks. We investigated if patients with oral GC use prior to COVID-19 had increased mortality overall and by selected causes.

Population-based observational cohort study.

Population-based register data in Sweden.

All patients infected with COVID-19 in Sweden from January 2020 to November 2021 (n=1 200 153).

Any prior oral GC use was defined as ≥1 GC prescription during 12 months before index. High exposure was defined as ≥2 GC prescriptions with a cumulative prednisolone dose ≥750 mg or equivalent during 6 months before index. GC users were compared with COVID-19 patients who had not received GCs within 12 months before index. We used Cox proportional hazard models and 1:2 propensity score matching to estimate HRs and 95% CIs, controlling for the same confounders in all analyses.

3378 deaths occurred in subjects with any prior GC exposure (n=48 806; 6.9%) and 14 850 among non-exposed (n=1 151 347; 1.3%). Both high (HR 1.98, 95% CI 1.87 to 2.09) and any exposure (1.58, 1.52 to 1.65) to GCs were associated with overall death. Deaths from pulmonary embolism, sepsis and COVID-19 were associated with high GC exposure and, similarly but weaker, with any exposure. High exposure to GCs was associated with increased deaths caused by stroke and myocardial infarction.

Patients on oral GC treatment prior to COVID-19 have increased mortality, particularly from pulmonary embolism, sepsis and COVID-19.

IgE has been known for mediating endothelial cell dysfunction and mast cell (MC) activation to fuel asthma-aggravated high-fat diet-induced atherosclerosis. However, it remains unclear for the mechanism of asthma-mediated atherosclerosis, especially the potential involvement of IgE in the exacerbation of asthma-mediated atherosclerosis with a standard laboratory diet, and the cross talk between endothelial cells and MCs.

Asthma-mediated atherosclerosis mice models under a standard laboratory diet and FcεR1 knock-out mice were used to determine the role of IgE-FcεR1 signaling in asthma-mediated atherosclerosis, which was assessed by Oil Red O staining and immunohistochemistry. Various in vitro assays including nanoparticle tracking analysis and transmission electron microscopy were used to evaluate exosome characteristics. Immunofluorescence and fluorescent in situ hybridization approaches were used to evaluate the effect and mechanism of MC-secreted exosomes encapsulated circular RNA CDR1as (cerebellar degeneration-related 1 antisense) on endothelial cells in vivo and in vitro. Finally, cohort studies examined the plasma CDR1as levels in patients with atherosclerosis with or without allergies.

Asthma mice with a standard laboratory diet showed increased atherosclerotic lesions and inflammatory infiltration depending on IgE-FcεR1 signal. FcεR1 knockout mice and blockage of IgE-FcεR1 signaling with IgE monoclonal antibody, omalizumab, all significantly alleviated asthma-mediated atherosclerosis and vascular inflammatory remodeling. Anti-inflammation with dexamethasone and stabilization of MC with cromolyn partially alleviated atherosclerotic lesions and mitigated the inflammatory infiltration in arteries. Mechanistically, IgE stimulation upregulates MC CDR1as expression in exosomes and upregulates the endothelial cell adhesive factors VCAM-1 (vascular cell adhesion molecule-1) and ICAM-1 (intercellular adhesion molecule-1) via the CDR1as-FUS (fused in sarcoma)-phos-p65 axis. Knockdown of CDR1as in vivo significantly decreased the endothelial adhesion function and mitigated asthma-mediated atherosclerosis. Furthermore, a cohort study indicated higher plasma CDR1as levels in patients with atherosclerosis with allergies than in patients with atherosclerosis and healthy controls.

Exosomes from IgE-stimulated MCs aggravated atherosclerosis through circular RNA CDR1as-mediated endothelial dysfunction, providing a novel insight into asthma-mediated atherosclerosis and potential diagnostic and therapeutic targets.

The immunosuppressive effects of corticosteroid (CS) injections have come under more scrutiny during the coronavirus disease 2019 (COVID-19) pandemic. The aim of the study was to explore any relationship between joint/epidural CS injection and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) polymerase chain reaction (PCR) positivity.

A retrospective chart review was conducted on patients 18 years or over who received at least one joint or epidural CS injection by physiatrists in a tertiary care center between January 1, 2020, and December 31, 2021. This cohort of patients was then compared to a control group who did not receive any CS injection during this time period.

A total of 766 patients were identified in the CS injection group and 1546 patients in the control group. Overall, 12.27% of patients turned SARS-CoV-2 PCR positive in the CS injection group, which was similar to 11.90% in the control group (p = 0.797). But 3-month SARS-CoV-2 PCR positivity rate showed a statistically significant higher rate among the CS injection group (3.30% in the CS injection group vs. 2.10% in the control group; p = 0.027). In multivariate regression analysis, after adjusting both groups for Charlson Comorbidity Index (CCI), there was statistically significant higher SARS-CoV-2 PCR positivity rate in the CS injection group (p = 0.024). However, after adjusting both groups for age and total number of comorbidities, there was no difference between the groups in regard to SARS-CoV-2 PCR positivity rate (p = 0.081). In the subgroup analysis of only COVID-19 vaccinated patients, there was an increased 3-month SARS-CoV-2 PCR positivity rate among patients with severe comorbidities in the CS injection group (p = 0.036).

The study was not conclusive on the effect of joint or epidural CS injection on SARS-CoV-2 PCR positivity rate, although adjusted analysis suggests higher 3-month SARS-CoV-2 PCR positivity rate after CS injection in patients with severe comorbidities with significant disease burden when compared to controls.

Cushing's Syndrome (CS) is associated with increased cardiovascular morbidity and mortality. In endogenous CS, cardiovascular mortality remains increased for up to 15 years post remission of hypercortisolism. Similarly, patients with exogenous CS have 4-fold increased incidence of cardiovascular events, regardless of pre-existing cardiovascular disease (CVD).

To present the pathophysiology, prognosis, clinical and imaging phenotype of cardiac disease in CS.

A Pubmed search for cardiac disease in CS over the last 20 years was conducted using combinations of relevant terms. Preclinical and clinical studies, as well as review papers reporting on subclinical heart failure (HF), cardiomyopathy, coronary heart disease (CHD), and cardiovascular imaging were selected.

Cardiac disease in CS is associated with direct mineralocorticoid and glucocorticoid receptor activation, increased responsiveness to angiotensin II, ectopic epicardial adiposity, arterial stiffness and endothelial dysfunction, as well as with diabetes mellitus, hypertension, hyperlipidemia, obesity and prothrombotic diathesis. Subclinical HF and cardiomyopathy are principally related to direct glucocorticoid (GC) effects and markedly improve or regress post hypercortisolism remission. In contrast, CHD is related to both direct GC effects and CS comorbidities and persists post cure. In patients without clinical evidence of CVD, echocardiography and cardiac magnetic resonance (CMR) imaging reveal left ventricular hypertrophy, fibrosis, diastolic and systolic dysfunction, with the latter being underestimated by echocardiography. Finally, coronary microvascular disease is encountered in one third of cases.

Cardiovascular imaging is crucial in evaluation of cardiac involvement in CS. CMR superiority in terms of reproducibility, operator independency, unrestricted field of view and capability of tissue characterisation makes this modality ideal for future studies.

Anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) is a rare, multisystem, autoimmune disease characterised by microvascular inflammation. Over the past 20 years, advances in immunological management have improved short-term patient outcomes. Longer-term patient outcomes remain poor with cardiovascular disease now the leading cause of death in AAV. Here, we examine the potential pathways that contribute to the increased risk of cardiovascular disease in AAV and the current evidence to manage this risk.

The incidence of cardiovascular disease in AAV exceeds that expected by traditional risk factors alone, suggesting a contribution from disease-specific factors. Similarly, it is unclear how different immunosuppressive therapies contribute to and modify cardiovascular risk, and there is a paucity of data examining the efficacy of traditional cardioprotective medications in AAV. There is a lack of evidence-based cardiovascular risk assessment tools and cardioprotective therapies in patients with AAV which should be addressed to improve long-term outcomes.

Even as immune checkpoint inhibitors (ICIs) have transformed the lifespan of many patients, they may also trigger acceleration of long-term cardiovascular disease. Our review aims to examine the current landscape of research on ICI-mediated atherosclerosis and address key questions regarding its pathogenesis and impact on patient management.

Preclinical mouse models suggest that T cell dysregulation and proatherogenic cytokine production are key contributors to plaque development after checkpoint inhibition. Clinical data also highlight the significant burden of atherosclerotic cardiovascular disease (ASCVD) in patients on immunotherapy, although the value of proactively preventing and treating ASCVD in this population remains an open area of inquiry. Current treatment options include dietary/lifestyle modification and traditional medications to manage hypertension, hyperlipidemia, and diabetes risk factors; no current targeted therapies exist.

Early identification of high-risk patients is crucial for effective preventive strategies and timely intervention. Future research should focus on refining screening tools, elucidating targetable mechanisms driving ICI atherosclerosis, and evaluating long-term cardiovascular outcomes in cancer survivors who received immunotherapy. Moreover, close collaboration between oncologists and cardiologists is essential to optimize patient outcomes.

The purpose of this study was to evaluate the effects of administration of overnight 1 mg dexamethasone on vascular function in patients with nonfunctioning adrenal adenomas (NFA). Flow-mediated vasodilation (FMD) and nitroglycerine-induced vasodilation (NID) were measured to assess vascular function in 22 patients with NFA who had hypertension and/or diabetes mellitus (DM) and 272 patients without adrenal incidentalomas who had hypertension and/or DM (control patients with hypertension and/or DM). FMD and NID were measured in the morning before and after administration of 1 mg of dexamethasone at 2300 h in 18 patients with NFA. There were no significant differences in FMD and NID between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM (3.4 ± 2.8% vs. 2.9 ± 1.9% and 11.5 ± 5.7% vs. 11.4 ± 4.3%, P = 0.46, and P = 0.99, respectively). There were no significant differences in vascular function between control patients with hypertension and/or DM and patients with NFA who had hypertension and/or DM even after adjustment for cardiovascular risk factors. Overnight 1 mg dexamethasone increased FMD from 2.4 ± 1.9% to 5.3 ± 3.2% (P < 0.01) and increased NID from 12.1 ± 4.2% to 14.0 ± 2.8% (P < 0.01) in patients with NFA. The overnight 1 mg dexamethasone suppression test does not impair FMD and NID in patients with NFA. Decreases in circulating levels of cortisol may improve vascular function.Clinical Trial Registration: This study was approved by principal authorities and ethical issues in Japan (URL for Clinical Trial: http://www.umin.ac.jp/ctr/index.htm Registration Number for Clinical Trial: UMIN000039512).

Musculoskeletal corticosteroid injection (CSI) is a frequently used treatment, considered safe with a low incidence of minor side effects.

To investigate whether the incidence of acute coronary syndrome (ACS) is increased following corticosteroid injection for musculoskeletal conditions.

Data were reviewed from 41,276 patients aged over 40 years and hospitalised with ACS between January 2015 and December 2019. Each ACS case was allocated up to 10 control patients from their primary care clinic, matched for age and sex. The cases and controls were reviewed for orthopaedic or rheumatological consultation including a CSI procedure and occurring prior to the hospital admission date. The incidence of CSI was compared between the case and control groups.

Data from a total of 413,063 patients were reviewed, 41,276 ACS cases and 371,787 controls. The mean age was 68.1, standard deviation (SD) = 13.1, 69.4% male. In the week prior to their hospital admission, 118 ACS patients were treated with CSI compared with 495 patients in the control group; odds ratio (OR) = 1.95 (1.56-2.43). In total, 98% of CSI procedures were carried out by orthopaedic specialists. An association between ACS and prior CSI was strongest in the days immediately prior to hospitalisation: OR = 3.11 (2.10-4.61) for patients who were injected 1 day before ACS. The association between ACS and CSI declined with increasing time between injection and hospital admission: at 90 days OR = 1.08 (0.98-1.18). The association remained robust when cardiovascular risk factors, history of rheumatological disease, and other co-morbidity were taken into consideration.

Musculoskeletal corticosteroid injection appears to substantially increase the risk of acute coronary syndrome.

Oral corticosteroids (OCS) are often prescribed for chronic obstructive pulmonary disease (COPD) exacerbations.

This observational, individually matched historical cohort study used electronic medical records (1987-2019) from the UK Clinical Practice Research Datalink linked to English Hospital Episode Statistics (HES) to evaluate adverse outcomes in patients with COPD who used OCS (OCS cohort) and those not exposed to OCS (non-OCS cohort). Risk of 17 adverse outcomes was estimated using proportional hazard regression.

Of 323,722 patients, 106,775 (33.0%) had COPD-related OCS prescriptions. Of the 106,775 patients in the overall cohort, 58,955 had HES linkage and were eligible for inclusion in the OCS cohort. The individual matching process identified 53,299 pairs of patients to form the OCS and non-OCS cohorts. Median follow-up post-index was 6.9 years (OCS cohort) and 5.4 years (non-OCS cohort). Adjusted risk of multiple adverse outcomes was higher for the OCS cohort versus the non-OCS cohort, including osteoporosis with/without fractures (adjusted hazard ratio [aHR] 1.80; 95% confidence interval [CI] 1.70-1.92), type 2 diabetes mellitus (aHR 1.44; 95% CI 1.37-1.51), cardiovascular/cerebrovascular disease (aHR 1.26; 95% CI 1.21-1.30), and all-cause mortality (aHR 1.04; 95% CI 1.02-1.07). In the OCS cohort, risk of most adverse outcomes increased with increasing categorized cumulative OCS dose. For example, risk of cardiovascular/cerebrovascular disease was 34% higher in the 1.0-<2.5 g group versus the <0.5 g group (HR 1.34; 95% CI 1.26-1.42).

Any OCS use was associated with higher risk of adverse outcomes in patients with COPD, with risk generally increasing with greater cumulative OCS dose.

It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.

To evaluate the synergistic effects created by fine particulate matter (PM2.5) and corticosteroid use on hospitalisation and mortality in older adults at high risk for cardiovascular thromboembolic events (CTEs).

A retrospective cohort study using a US nationwide administrative healthcare claims database.

A 50% random sample of participants with high-risk conditions for CTE from the 2008-2016 Medicare Fee-for-Service population.

Corticosteroid therapy and seasonal-average PM2.5.

Incidences of myocardial infarction or acute coronary syndrome (MI/ACS), ischaemic stroke or transient ischaemic attack, heart failure (HF), venous thromboembolism, atrial fibrillation and all-cause mortality. We assessed additive interactions between PM2.5 and corticosteroids using estimates of the relative excess risk due to interaction (RERI) obtained using marginal structural models for causal inference.

Among the 1 936 786 individuals in the high CTE risk cohort (mean age 76.8, 40.0% male, 87.4% white), the mean PM2.5 exposure level was 8.3±2.4 µg/m3 and 37.7% had at least one prescription for a systemic corticosteroid during follow-up. For all outcomes, we observed increases in risk associated with corticosteroid use and with increasing PM2.5 exposure. PM2.5 demonstrated a non-linear relationship with some outcomes. We also observed evidence of an interaction existing between corticosteroid use and PM2.5 for some CTEs. For an increase in PM2.5 from 8 μg/m3 to 12 μg/m3 (a policy-relevant change), the RERI of corticosteroid use and PM2.5 was significant for HF (15.6%, 95% CI 4.0%, 27.3%). Increasing PM2.5 from 5 μg/m3 to 10 μg/m3 yielded significant RERIs for incidences of HF (32.4; 95% CI 14.9%, 49.9%) and MI/ACSs (29.8%; 95% CI 5.5%, 54.0%).

PM2.5 and systemic corticosteroid use were independently associated with increases in CTE hospitalisations. We also found evidence of significant additive interactions between the two exposures for HF and MI/ACSs suggesting synergy between these two exposures.

Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.

Rheumatoid arthritis (RA) is a type of difficult-to-cure arthralgia with a worldwide prevalence. It severely affects people's living standards. For a long time, bee venom has been used to treat RA and has shown good results. Melittin is the main active component of bee venom used for RA treatment, but the molecular mechanism of melittin in RA treatments remains unclear.

Potential melittin and RA targets were obtained from relevant databases, and common targets of melittin and RA were screened. The STRING database was used to build the PPI network and screen the core targets after visualization. The core targets were enriched by Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway. Finally, the binding of melittin to target proteins was evaluated through simulated molecular docking, which verified the reliability of the prediction results of network pharmacology.

In total, 138 melittin targets and 5795 RA targets were obtained from relevant databases, and 90 common targets were obtained through intersection. Eighteen core targets, such as STAT3, AKT1, tumor necrosis factor, and JUN, were screened out. Enrichment analysis results suggested that melittin plays an anti-RA role mainly through tumor necrosis factor, interleukin-17, toll-like receptors, and advanced glycation end products-RAGE signaling pathways, and pathogenic bacterial infection. Molecular docking results suggested that melittin has good docking activity with core target proteins.

RA treatment with melittin is the result of a multi-target and multi-pathway interaction. This study offers a theoretical basis and scientific evidence for further exploring melittin in RA therapy.

Hypercortisolism is a risk factor for adverse cardiovascular and cerebrovascular outcomes, including hypertension, hyperglycemia, and dyslipidemia. It has been suggested that cardiovascular risk increases with increasing steroid use in patients taking oral steroids as immunosuppressive drugs. Cardiomyopathy is often reported to occur concomitantly in patients with Cushing's syndrome. Reports of cases of long-term high-dose glucocorticoid ingestion and concomitant cardiomyopathy are rare. We report a case of cardiomyopathy in a 63-year-old Japanese man. He had refractory bronchial asthma and had been on prednisolone ≥15 mg/day equivalent for >20 years. Echocardiography showed severe left ventricular dilatation, left ventricular systolic dysfunction, and mitral regurgitation. Since other secondary cardiomyopathies were excluded, a diagnosis of glucocorticoid cardiomyopathy was made, cardioprotective drugs were introduced, and the steroid dose was reduced during hospitalization. Four months after the patient's discharge, echocardiography showed normalization of left ventricular systolic function.

Synthetic corticosteroids are widely used due to their anti-inflammatory and immunosuppressant effects. Their use has been associated with venous thromboembolism, but it is unknown whether thromboembolism has a causal relationship with corticosteroid treatment. In a randomised, double-blind, placebo-controlled trial in normal to overweight healthy men, the effect of the corticosteroid prednisolone on haemostasis using either 50 mg prednisolone or matching placebo once daily for ten days was investigated. The primary outcome was a change from baseline in the viscoelastic measurement maximal amplitude of clot in kaolin-activated thromboelastography (TEG). Changes from baseline in other TEG measurements, D-dimer, von Willebrand factor (VWF) antigen, and ristocetin cofactor activity (RCo), antithrombin, protein C, prothrombin, fibrinogen, INR, APTT, and platelet count were secondary outcomes. Thirty-four men participated in this study. Compared to placebo, prednisolone treatment did not affect maximal amplitude of clot (difference -0.77 (95% confidence interval (CI) -2.48, 0.94) mm, p = 0.37, missing: n = 2), but it altered VWF antigen (28%, p = 0.0004), VWF:RCo (19%, p = 0.0006), prothrombin (5%, p = 0.05), protein C (31%, p < 0.0001), antithrombin (5%, p = 0.013), and fibrinogen (-15%, p = 0.004). Thus, prednisolone treatment did not alter TEG-assessed maximal amplitude of clot, despite that it affected prothrombotic markers (increased prothrombin, VWF antigen, VWF:RCo, prothrombin, and decreased fibrinogen) and increased antithrombotic markers (protein C and antithrombin).

Patients with primary Sjögren's syndrome (pSS) are at increased risk of cardiovascular morbidity as compared with the general population.

A retrospective study on 349 Chinese patients with pSS was conducted to identify potential risk factors for cardiovascular events and develop a cardiovascular risk nomogram.

This is a retrospective observational study.

The study included 349 patients who were diagnosed with pSS at Tongji Hospital, School of Medicine, Tongji University, China from January 2010 to March 2022. The least absolute shrinkage and selection operator (LASSO) was used to select features for the cardiovascular risk model. The features selected in LASSO were used to build the cardiovascular risk model in a multivariate logistic regression analysis. C-index, receiver operating characteristic (ROC) curve, calibration plot, and decision curve analysis were used to assess the predictive model. Internal validation was performed by bootstrapping.

Sex, joint pain as an initial symptom, dry mouth, oral ulcers, dental caries, Raynaud's phenomenon, fatigue, diabetes, elevated thyroid-stimulating hormone (TSH) level, and elevated systolic blood pressure were included in the nomogram for the prediction of cardiovascular risk. Our model had good discrimination (C-index: 0.824, 95% confidence interval: 0.712-0.936) and good calibration (C-index in the interval validation: 0.8). Decision curve analysis indicated that our nomogram demonstrated clinical usefulness for intervention in a cardiovascular disease possibility threshold of 3%.

The cardiovascular risk nomogram incorporating sex, initial joint pain, dry mouth, oral ulcer, dental caries, Raynaud's phenomenon, fatigue, diabetes, elevated TSH, and systolic blood pressure could be used in the prediction of cardiovascular risk in patients with pSS and the guidance of further treatment.