Faculty Bibliography

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.

PURPOSE OF REVIEW/OBJECTIVE:Psoriasis is an immune-mediated pro-inflammatory skin condition that is associated with an increase in risk factors for cardiovascular disease, risk of ischemic heart disease, and cardiovascular death. Despite this, traditional modifiable atherosclerotic cardiovascular disease (ASCVD) risk factors are underdiagnosed and undertreated in patients with psoriasis. RECENT FINDINGS/RESULTS:At a cellular level, psoriasis and atherosclerosis are driven by a host of shared inflammatory pathways, such as pro-inflammatory cytokines (TNF, IL-6), immune cells, and platelets which act synergistically to drive endothelial damage and atherosclerosis progression. SUMMARY/CONCLUSIONS:Optimal prevention of cardiovascular disease in psoriasis centers around modifying known risk factors for the development of ASCVD and emerging data highlight the promise of treating inflammation to further decrease the risk of ASCVD.

PURPOSE OF REVIEW/OBJECTIVE:Outcome benefits for HMG-CoA reductase inhibitor (statin) use in the prevention of atherosclerotic cardiovascular disease (ASCVD) are well established and yet, statins remain underutilized with only half of eligible individuals receiving them among certain vulnerable populations. This review critically examines available data to provide a summary of the current evidence for statin use in select populations. RECENT FINDINGS/RESULTS:Lipid management can be more complex in patients with chronic kidney disease (CKD), organ transplants, metabolic dysfunction associated with steatotic liver disease (MASLD), and human immunodeficiency virus (HIV). Statins are generally safe and effective to reduce the burden of ASCVD among these highly heterogeneous groups of patients and should be considered with careful attention to their concomitant disease state. Herein, we focus on appropriate statin use in these challenging to treat conditions, their relationship with increased ASCVD risk, and approaches to statin use for ASCVD risk reduction. Although further research is needed to define optimal therapy in select high risk groups for ASCVD prevention, statins are proven to be clinically efficacious, safe, and cost-effective for ASCVD prevention, warranting greater efforts to increase their use.

BACKGROUND:Lipoprotein(a) [Lp(a)] is a driver of residual cardiovascular risk. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) decrease Lp(a) with significant heterogeneity in response. We investigated contributors to the heterogeneous response. METHODS:CHOlesterol Reduction and Residual Risk in Diabetes (CHORD) was a prospective study examining lipid lowering in participants with a low-density lipoprotein cholesterol (LDL-C) >100 mg/dL with and without diabetes (DM) on lipid lowering therapy (LLT) for 30-days with evolocumab 140 mg every 14 days combined with either atorvastatin 80 mg or ezetimibe 10 mg daily. Lp(a) level was measured by immunoturbidometry, and the apolipoprotein (a) [apo(a)] isoform size was measured by denaturing agarose gel electrophoresis and western blotting. We examined the change in Lp(a) levels from baseline to 30 days. RESULTS:Among 150 participants (mean age 50 years, 58% female, 50% non-White, 17% Hispanic, 50% DM), median (interquartile range) Lp(a) was 27.5 (8-75) mg/dL at baseline and 23 (3-68) mg/dL at 30 days, leading to a 10% (0-36) median reduction (P < 0.001). Among 73 (49%) participants with Lp(a) ≥30 mg/dL at baseline, there was a 15% (3-25) median reduction in Lp(a) (P < 0.001). While baseline Lp(a) level was not correlated with change in Lp(a) (r = 0.04, P = 0.59), apo(a) size directly correlated with Lp(a) reduction (P < 0.001). After adjustment for age, sex, race/ethnicity, DM, and type of LLT, apo(a) size remained positively associated with a reduction in Lp(a) (Beta 0.95, 95% confidence interval, 0.93-0.97, P < 0.001). CONCLUSION/CONCLUSIONS:Our data demonstrate variation in Lp(a) reduction with potent LLT. Change in Lp(a) was strongly associated with apo(a) isoform size.