Faculty Bibliography

BACKGROUNDPlatelets are increasingly recognized as active participants in immune signaling and systemic inflammation. Upon activation, platelets form monocyte platelet aggregates (MPA) representing the crossroads of thrombosis and inflammation. We hypothesized that platelet transcriptomics could capture this thromboinflammatory axis and identify individuals at elevated cardiovascular risk.METHODS: MPA levels, defined as CD14+CD61+ cells, were measured using flow cytometry at 2 time points, 4 weeks apart, in healthy individualsPlatelets were isolated and sequenced. Individuals were categorized as MPAhi or MPAlo based on consistently high or low MPA levels across time points.RESULTSAmong 149 participants (median age 52 years, 57% female, 50% non-White), MPAhi individuals exhibited increased expression of platelet activation markers P-selectin (P < 0.001), PAC-1 (P = 0.021), and CD40L (P < 0.001) and enriched immune signaling pathways. Informed by MPA levels and derived from the platelet transcriptome, we developed a 42-gene thromboinflammation platelet signature (TIPS), which correlated with MPA levels in multiple cohorts and was reproducible over time. TIPS was elevated in patients with COVID-19 (P = 0.0002) and myocardial infarction (Padj = 0.008), and as in predicted future cardiovascular events in patients who underwent lower extremity revascularization after a median follow-up of 18 months (adjusted for age, sex, race, and ethnicity [adjHR] 1.55, P = 0.006). Notably, TIPS was modifiable by ticagrelor (P = 0.002) but not aspirin.CONCLUSIONThese findings establish MPA as a biomarker of thromboinflammation and introduce TIPS, a platelet RNA signature, that captures thromboinflammation and provides a promising tool for cardiovascular risk stratification and a potential therapeutic target.TRIAL REGISTRATIONNCT04369664FUNDINGNIH R35HL144993, NIH R01HL139909, and AHA 16SFRN2873002 to JSB, DFG Walter-Benjamin-Programme 537070747 to AB.

There is a growing body of evidence supporting the safety and utility of interleukin-1 inhibitors for treatment of recurrent pericarditis. This therapy has not been investigated specifically as related to postpericardiotomy syndrome or after thoracic organ transplantation. We report on rilonacept use for treatment of recurrent pericarditis in 4 patients after lung or heart transplantation, describing the clinical presentation, infectious complications, and outcomes of these cases. Our single-center experience of this highly comorbid patient population highlights the major considerations of interleukin-1 inhibitor use within these patients, particularly as related to infectious complications and immunosuppression management.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with an increased risk of vascular dysfunction and cardiovascular disease. We validate our previously developed Systemic Lupus Erythematosus Activity Platelet-Gene Expression Signature (SLAP-GES) score and investigate its relationship with platelet activity and vascular health. SLAP-GES was associated with the SLE Disease Activity Index (Padj < 0.001) and consistent over time (r = 0.76; P = 9 × 10^-5). Moreover, SLAP-GES was associated increased platelet aggregation in response to submaximal epinephrine (P = 0.084), leukocyte platelet aggregates (P = 0.014), and neutrophil platelet aggregates (P = 0.043). SLAP-GES was also associated with impaired glycocalyx (P = 0.011) and brachial artery flow-mediated dilation (P = 0.045). Altogether, SLAP-GES is associated with SLE disease activity, platelet activity, and impaired vascular health.

BACKGROUND:Recurrent pericarditis (RP) guidelines recommend second-line corticosteroids after aspirin/nonsteroidal anti-inflammatory drugs/colchicine, but complications of protracted use underscore the importance of corticosteroid-sparing strategies. OBJECTIVES/OBJECTIVE:Given clinical trial evidence supporting interleukin (IL)-1 pathway inhibition and US Food and Drug Administration approval of rilonacept in RP, the objective was to assess temporal trends in corticosteroid-sparing treatment of RP in a multicenter registry. METHODS:RESONANCE (REgiStry Of the NAtural history of recurreNt periCarditis in pEdiatric and adult patients; NCT04687358) combines retrospective and prospective data from clinical practice into a single observation period. Patients receiving treatment for idiopathic and postprocedural RP were included. Demographics and treatment intensifications were quantified. RESULTS:Of 313 patients with aspirin/nonsteroidal anti-inflammatory drugs/colchicine treatment (median disease duration 1.9 years; 1 preenrollment recurrence), 44% (n = 138) intensified treatment. Before rilonacept approval in RP, 71% (n = 10) of patients intensified to corticosteroids for second-line therapy, and 29% (n = 4) intensified to IL-1 pathway inhibition. After rilonacept approval, the proportion of patients intensifying to second-line IL-1 pathway inhibition increased to 64% by 2023 (n = 27; rilonacept: 57%, anakinra: 7%), whereas the proportion of patients intensifying to corticosteroids decreased to 33% (n = 14), P = 0.02. Approximately 59% (n = 35) of second-line corticosteroid initiators later transitioned to IL-1 pathway inhibition. In patients starting second-line IL-1 pathway inhibition, 5% (n = 3, rilonacept) and 25% (n = 4, anakinra) subsequently used corticosteroids for >30 days. CONCLUSIONS:In RESONANCE, IL-1 pathway inhibition increasingly replaced corticosteroids as second-line therapy. Most patients starting corticosteroids transitioned to IL-1 pathway inhibition; few transitioned from second-line IL-1 pathway inhibition to long-term corticosteroids. These findings may inform treatment algorithms and patient-provider decision-making.

Patients with psoriasis (PsO) and psoriatic arthritis (PsA) are at significantly increased risk for cardiovascular (CV) disease, attributed to chronic systemic inflammation and a high burden of cardiometabolic comorbidities. Despite this, CV risk factors in this population are frequently underdiagnosed and undertreated. This consensus document, developed by the Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN), provides practical recommendations for dermatologists, rheumatologists, and primary care physicians to improve CV risk assessment and management in PsO and PsA. Key recommendations include conducting baseline CV risk assessments at diagnosis-particularly for patients with moderate-to-severe PsO, PsA, or those requiring biologic therapy-and routine screening for hypertension, diabetes, dyslipidemia, smoking, obesity, and metabolic syndrome. The use of biomarkers such as high-sensitivity C-reactive protein and lipoprotein(a) may help refine risk stratification. Patients at elevated risk should be referred to their primary care provider or a cardiologist for further evaluation and may require additional imaging, including coronary artery calcium scoring. Lifestyle counseling on diet, exercise, weight management, and smoking cessation is essential. Pharmacologic strategies, such as earlier initiation of statins and consideration of glucagon-like peptide-1 (GLP-1) receptor agonists, are encouraged when clinically appropriate. Systemic inflammation should be reduced using anti-inflammatory therapies, although outcome data remain mixed. Clinicians must carefully assess the risks and benefits of NSAIDs, corticosteroids, and Janus kinase (JAK) inhibitors. This document aims to bridge existing gaps in interdisciplinary care and facilitate earlier, more aggressive CV risk management in psoriatic disease, aligning with current cardiology and dermatology guidelines to reduce morbidity and mortality.