Faculty Bibliography

BACKGROUND:Cardiometabolic risk factors diabetes, obesity, and hypertension are highly prevalent and contribute to increased cardiovascular disease (CVD). Endothelial dysfunction precedes CVD development. The current study aimed to investigate the EC transcriptome among individuals with varying degree of cardiometabolic risk. METHODS:Adult participants without CVD and various degrees of cardiometabolic risk factor burden (hypertension, diabetes, obesity) were included. Participants underwent brachial vein EC harvesting followed by RNA sequencing. To evaluate the association between cardiometabolic comorbidity burden and outcome transcripts we performed linear regression with multivariable models, adjusting for age, sex, and race/ethnicity. RESULTS:A total of 18 individuals were included in the present analysis (mean age 47 ± 14, 44% female, and 61% White adults). Endothelial cell RNA sequencing revealed 588 differentially expressed transcripts (p-adj <0.05) with excellent discrimination in unsupervised hierarchical clustering analysis. Gene ontology enrichment analysis revealed upregulated pathways associated with T-cell activation (NES = 2.22, p<0.001), leukocyte differentiation (NES= 2.16, p<0.001), leukocyte migration (NES= 2.12, p<0.001), regulation of cell-cell adhesion (NES= 1.91, p=0.006). Downregulated pathways of interest included endothelial cell proliferation (NES= -1.68, p=0.03) and response to interleukin-1 (NES= -1.61, p=0.04). Upregulated genes included VCAM1, CEACAM1, ADAM 17, and CD99L2, all with a log-2-fold change >3 and p-adj <0.05. These genes demonstrated a graded increase in mean normalized counts with increasing number of risk factors. CONCLUSIONS:We demonstrate a proinflammatory and pro-adhesive EC transcriptome associated with increased cardiometabolic risk factor burden offering insight into a potential mechanism linking these risk factors with the development of CVD.

IMPORTANCE/UNASSIGNED:Janus kinase (JAK) inhibitors are an effective treatment option for patients with certain skin-related conditions, such as atopic dermatitis, alopecia areata, and vitiligo, but there is a current US Food and Drug Administration (FDA) boxed warning label for oral and topical JAK inhibitors regarding increased risk of major adverse cardiovascular events (MACE), venous thromboembolism (VTE), serious infections, malignant neoplasm, and death. However, this boxed warning was precipitated by results of the Oral Rheumatoid Arthritis Trial (ORAL) Surveillance study, which only included patients with rheumatoid arthritis, and the same association may not be observed in dermatologic conditions. OBJECTIVE/UNASSIGNED:To determine the risk of all-cause mortality, MACE, and VTE with JAK inhibitors in patients with dermatologic conditions. DATA SOURCES/UNASSIGNED:PubMed and ClinicalTrials.gov were searched from database inception to April 1, 2023. STUDY SELECTION/UNASSIGNED:This review included phase 3 randomized clinical trials with a placebo/active comparator group of JAK inhibitors used for a dermatologic indication with FDA approval or pending approval or with European Union or Japanese approval. Studies without a comparison group, case reports, observational studies, and review articles were excluded. DATA EXTRACTION AND SYNTHESIS/UNASSIGNED:This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Adverse events using odds ratios (ORs) and 95% CIs were calculated using a random-effects model and the DerSimonian-Laird method. Studies were screened, data abstracted, and quality assessed by 2 independent authors. The protocol was prospectively registered with PROSPERO. MAIN OUTCOMES AND MEASURES/UNASSIGNED:Primary outcomes were a composite of adjudicated MACE and all-cause mortality, and VTE. RESULTS/UNASSIGNED:The analysis included 35 randomized clinical trials with 20 651 patients (mean [SD] age, 38.5 [10.1] years; male, 54%) and a mean (SD) follow-up time of 4.9 (2.68) months. Findings did not show a significant difference between JAK inhibitors and placebo/active comparator in composite MACE and all-cause mortality (OR, 0.83; 95% CI, 0.44-1.57) or VTE (OR, 0.52; 95% CI, 0.26-1.04). CONCLUSIONS AND RELEVANCE/UNASSIGNED:In this systematic review and meta-analysis, use of JAK inhibitors was not associated with increased risk of all-cause mortality, MACE, and VTE compared to the placebo/active comparator groups. Additional trials with long-term follow-up are needed to better understand the safety risks of JAK inhibitors used for dermatologic indications.

Immune-mediated systemic inflammatory conditions (IMIDs) are associated with an increased risk of atherosclerosis and adverse cardiovascular (CV) events secondary to pathogenic inflammation and derangements in the innate and adaptive immune responses inherent to the underlying rheumatic diseases. As the intersection of cardio-rheumatology continues to expand, a multi-disciplinary approach must be considered to optimize clinical outcomes and long-term survival. This review will highlight acute cardiac manifestations of systemic inflammatory diseases and propose a clinically relevant framework for diagnosis, management, and the role of integrated multimodality imaging.

This review summarizes the evaluation for underlying rheumatic conditions in patients presenting with acute pericarditis, treatment considerations for specific rheumatic conditions, and the role of imaging in diagnosis and monitoring. Pericarditis may be one of the initial presentations of a rheumatic disease or identified in a patient with known rheumatic disease. There is also growing evidence for using anti-inflammatory and immunosuppressive agents for treating recurrent pericarditis, which can overlap with the treatment of rheumatic diseases.

The Psoriasis and Psoriatic Arthritis Clinics Multicenter Advancement Network (PPACMAN) is a nonprofit organization whose mission is to optimize the clinical care of patients with psoriatic disease through multidisciplinary collaboration models. The PPACMAN 2021 Annual Meeting was held virtually on December 11, 2021. In all, 50 stakeholders participated in the meeting including dermatologists, rheumatologists, cardiologists, clinical researchers, patient advocacy representatives, and industry representatives. During the opening session of the meeting, presenters provided an update of several research projects dedicated to predicting and preventing psoriatic arthritis (PsA) such as the Psorcast, PAMPA, HIPPOCRATES, and the ELLIPSS studies. The second session centered around novel approaches to deliver multidisciplinary care in psoriatic disease. PPACMAN leadership introduced its wellness program and invited speakers to discuss new advances in cardiovascular disease, sleep disturbance, mental health problems, and dietary interventions in psoriatic disease. The final session of the meeting focused on how to improve patient engagement in their disease and care.

PURPOSE OF REVIEW/OBJECTIVE:Pericarditis complicates pregnancy planning, pregnancy, or the postpartum period, and the management approach requires special considerations. Here, we aim to summarize the latest research, diagnostic, and treatment strategies. RECENT FINDINGS/RESULTS:Physiologic cardiovascular (CV) adaptations occurring during pregnancy complicate diagnosis, but for most patients, an electrocardiogram (ECG) and transthoracic echocardiogram (TTE) are sufficient to diagnosis pericarditis in the appropriate clinical context. Aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) can be used until 20 weeks gestation as needed. The use of colchicine is encouraged at any time point to reduce the risk of recurrence. Glucocorticoids may be used at the lowest possible dose for the least amount of time throughout pregnancy and breastfeeding. For incessant, recurrent, or refractory pericarditis, or when the above therapies are contraindicated, there may be a consideration of the use of IL-1 inhibition during pregnancy, recognizing the limited data in pregnant patients. Finally, we encourage the use of a multidisciplinary team approach including OB-GYN, cardiology, and rheumatology when available. The diagnosis and treatment of pericarditis in female patients of reproductive age require special considerations. Although highly effective treatment options are available, there is a need for greater data and larger international registries to improve treatment recommendations.

BACKGROUND:Psoriasis is an inflammatory skin disease associated with increased cardiovascular (CV) risk, whose pathogenesis is not fully known. OBJECTIVE:We identified a transcriptomic signature in psoriasis and investigated its association with prevalent and future risk of a CV event to understand the connection between psoriasis and CV disease (CVD). METHODS:Psoriasis patients (n = 37) with a history of moderate-severe skin disease without CVD and 11 matched controls underwent whole blood RNA sequencing. This transcriptomic signature in psoriasis versus controls was evaluated in two CVD cohorts: Women referred for cardiac catheterization with (n = 76) versus without (n = 97) myocardial infarction (MI), and patients with peripheral artery disease (n = 106) followed over 2.5 years for major adverse CV or limb events (MACLE). The association between genes differentially expressed in psoriasis and prevalent and incident CV events was assed. RESULTS:In psoriasis, median age was 44 (IQR; 34-51) years, 49% male and ACC/AHA ASCVD Risk Score of 1.0% (0.6-3.4) with no significant difference versus controls. The median psoriasis area and severity index score (PASI) was 4.0 (IQR 2.9-8.2) with 36% on biologic therapy. Overall, 247 whole blood genes were upregulated and 228 downregulated in psoriasis versus controls (p < 0.05), and 1302 genes positively and 1244 genes negatively correlated with PASI (p < 0.05). Seventy-three genes overlapped between psoriasis prevalence and PASI with key regulators identified as IL-6, IL-1β and interferon gamma. In the CVD cohorts, 50 of 73 genes (68%) identified in psoriasis associated with prevalent MI, and 29 (40%) with incident MACLE. Key regulator transcripts identified in psoriasis and CVD cohorts included SOCS3, BCL3, OSM, PIM2, PIM3 and STAT5A. CONCLUSIONS:A whole blood transcriptomic signature of psoriasis diagnosis and severity associated with prevalent MI and incident MACLE. These data have implications for better understanding the link between psoriasis, systemic inflammation and CVD.