Monocyte-to-High-Density Lipoprotein Ratio Is Associated with Systemic Inflammation, Insulin Resistance, and Coronary Subclinical Atherosclerosis in Psoriasis: Results from 2 Observational Cohorts.

Systemic inflammation or insulin resistance drive atherosclerosis. However, they are difficult to capture for assessing cardiovascular risk in clinical settings. The monocyte-to-high-density lipoprotein ratio (MHR) is an accessible biomarker that integrates inflammatory and metabolic information and has been associated with poorer cardiovascular outcomes. Our aim was to evaluate the association of MHR with the presence of subclinical atherosclerosis in patients with psoriasis. The study involved a European and an American cohort including 405 patients with the disease. Subclinical atherosclerosis was assessed by coronary computed tomography angiography. First, MHR correlated with insulin resistance through homeostatic model assessment for insulin resistance, with high-sensitivity CRP and with 18F-fluorodeoxyglucose uptake in spleen, liver, and bone marrow by positron emission tomography/computed tomography. MHR was associated with both the presence of coronary plaques >50% of the artery lumen and noncalcified coronary burden, beyond traditional cardiovascular risk factors (P < .05). In a noncalcified coronary burden prediction model accounting for cardiovascular risk factors, statins, and biologic treatment, MHR added value (area under the curve base model = 0.72 vs area under the curve base model plus MHR = 0.76, P = .04) within the American cohort. These results suggests that MHR may detect patients with psoriasis who have subclinical burden of cardiovascular disease and warrant more aggressive measures to reduce lifetime adverse cardiovascular outcomes.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study.

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP): protocol for an observational, single-centre, prospective cohort study.

INTRODUCTION: Life expectancy of patients with psoriasis is reduced by 4-5 years due to cardiovascular disease with an increased risk of myocardial infarction at an earlier age compared with the general population. This increased risk is independent of traditional cardiovascular risk factors and higher in moderate-to-severe forms of psoriasis. Inflammation may play a key role in the development of atherosclerosis in these patients. METHODS AND ANALYSIS: A prospective cohort study, Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP), was initiated in January 2020 to investigate the presence and progression of subclinical atherosclerosis in patients with psoriasis. 120 patients aged 30-65 years and eligible for biological treatment have been recruited at Hospital Ramón y Cajal in Madrid, Spain. Patients undergo a baseline visit, and 1-year follow-up visit after starting biological therapy. Each visit includes: assessment of cardiovascular risk factors, screening for subclinical atherosclerosis by two-dimensional/three-dimensional ultrasound of carotid and femoral arteries, cardiac CT of coronary arteries and blood sampling. All baseline visits were completed by December 2022, and the remaining follow-up visits will be concluded by the end of 2023. The EDSAP study aims to identify new molecular and imaging markers associated with the presence of atherosclerosis and its progression in a chronic inflammatory state such as psoriasis. This has the potential to: (1) help improve primary cardiovascular prevention strategies in these patients; (2) understand the effect of biological drugs on the cardiovascular system; and (3) serve as a model for understanding atherosclerosis in other chronic inflammatory diseases. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of the Hospital Ramón y Cajal in Madrid. We will present our findings at national and international congresses, and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05858099.

Genetic Influence on Treatment Response in Psoriasis: New Insights into Personalized Medicine.

Psoriasis is a chronic inflammatory disease with an established genetic background. The HLA-Cw*06 allele and different polymorphisms in genes involved in inflammatory responses and keratinocyte proliferation have been associated with the development of the disease. Despite the effectiveness and safety of psoriasis treatment, a significant percentage of patients still do not achieve adequate disease control. Pharmacogenetic and pharmacogenomic studies on how genetic variations affect drug efficacy and toxicity could provide important clues in this respect. This comprehensive review assessed the available evidence for the role that those different genetic variations may play in the response to psoriasis treatment. One hundred fourteen articles were included in this qualitative synthesis. VDR gene polymorphisms may influence the response to topical vitamin D analogs and phototherapy. Variations affecting the ABC transporter seem to play a role in methotrexate and cyclosporine outcomes. Several single-nucleotide polymorphisms affecting different genes are involved with anti-TNF-α response modulation (TNF-α, TNFRSF1A, TNFRSF1B, TNFAIP3, FCGR2A, FCGR3A, IL-17F, IL-17R, and IL-23R, among others) with conflicting results. HLA-Cw*06 has been the most extensively studied allele, although it has only been robustly related to the response to ustekinumab. However, further research is needed to firmly establish the usefulness of these genetic biomarkers in clinical practice.

Cardiovascular Screening Practices and Statin Prescription Habits in Patients with Psoriasis among Dermatologists, Rheumatologists and Primary Care Physicians.

Patients with psoriasis have a higher prevalence of cardiovascular risk factors. This study evaluated cardiovascular screening practices and statin prescribing habits among dermatologists, rheumatologists and primary care physicians (PCPs) through an online questionnaire, which was distributed through the Spanish scientific societies of the above-mentioned specialties. A total of 299 physicians (103 dermatologists, 94 rheumatologists and 102 PCPs) responded to the questionnaire. Of these, 74.6% reported screening for smoking, 37.8% for hypertension, 80.3% for dyslipidaemia, and 79.6% for diabetes mellitus. Notably, only 28.4% performed global screening, defined as screening for smoking, hypertension, dyslipidaemia, and diabetes mellitus by the same physician, and 24.4% reported calculating 10-year cardiovascular disease (CVD) risk, probably reflecting a lack of comprehensive cardiovascular risk assessment in these patients. This study also identified unmet needs for awareness of cardiovascular comorbidities in psoriasis and corresponding screening and treatment recommendations among PCPs. Of PCPs, 61.2% reported not being aware of the association between psoriasis and CVD and/or not being aware of its screening recommendations, and 67.6% did not consider psoriasis as a risk-enhancing factor when deciding on statin prescription. Thirteen dermatologists (12.6%) and 35 rheumatologists (37.2%) reported prescribing statins. Among those who do not prescribe, 49.7% would be willing to start their prescription.