Multiscale Biology of Cardiovascular Risk in Psoriasis: Protocol for a Case-Control Study.

BACKGROUND: Patients with psoriasis have increased risk of cardiovascular disease (CVD) independent of traditional risk factors. The molecular mechanisms underlying the psoriasis-CVD connection are not fully understood. Advances in high-throughput molecular profiling technologies and computational analysis techniques offer new opportunities to improve the understanding of disease connections. OBJECTIVE: We aim to characterize the complexity of cardiovascular risk in patients with psoriasis by integrating deep phenotypic data with systems biology techniques to perform comprehensive multiomic analyses and construct network models of the two interacting diseases. METHODS: The study aims to include 120 adult patients with psoriasis (60 with prior atherosclerotic CVD and 60 without CVD). Half of the patients are already receiving systemic antipsoriatic treatment. All patients complete a questionnaire, and a medical interview is conducted to collect medical history and information on, for example, socioeconomics, mental health, diet, and physical exercise. Participants are examined clinically with assessment of the Psoriasis Area and Severity Index and undergo imaging by transthoracic echocardiography, 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), and carotid artery ultrasonography. Skin swabs are collected for analysis of microbiome metagenomics; skin biopsies and blood samples are collected for transcriptomic profiling by RNA sequencing; skin biopsies are collected for immunohistochemistry; plasma samples are collected for analyses of proteomics, lipidomics, and metabolomics; blood samples are collected for high-dimensional mass cytometry; and feces samples are collected for gut microbiome metagenomics. Bioinformatics and systems biology techniques are utilized to analyze the multiomic data and to integrate data into a network model of CVD in patients with psoriasis. RESULTS: Recruitment was completed in September 2020. Preliminary results of 18F-FDG-PET/CT data have recently been published, where vascular inflammation was reduced in the ascending aorta (P=.046) and aortic arch (P=.04) in patients treated with statins and was positively associated with inflammation in the visceral adipose tissue (P<.001), subcutaneous adipose tissue (P=.007), pericardial adipose tissue (P<.001), spleen (P=.001), and bone marrow (P<.001). CONCLUSIONS: This systems biology approach with integration of multiomics and clinical data in patients with psoriasis with or without CVD is likely to provide novel insights into the biological mechanisms underlying these diseases and their interplay that can impact future treatment. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/28669.

Association between Vascular Inflammation and Inflammation in Adipose Tissue, Spleen, and Bone Marrow in Patients with Psoriasis.

Psoriasis is associated with atherosclerotic cardiovascular disease (CVD) with significant overlap of inflammatory pathways. A link between vascular inflammation and inflammation in multiple adipose tissue types, spleen, and bone marrow may exist. Therefore, we investigated these associations using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) in patients with psoriasis (n = 83) where half had established CVD. Carotid ultrasound imaging was also performed. Inflammation was measured by FDG uptake in the aorta, visceral- (VAT), subcutaneous- (SAT), and pericardial (PAT) adipose tissues, and spleen and bone marrow, respectively. Vascular inflammation was associated with FDG uptakes in all adipose tissues, including VAT (ß = 0.26; p < 0.001), SAT (ß = 0.28; p < 0.001), PAT (ß = 0.24; p < 0.001), spleen (ß = 1.35; p = 0.001), and bone marrow (ß = 1.14; p < 0.001). Adjustments for age, sex, body mass index, and high sensitivity C-reactive protein did not change the results. These associations were generally preserved in the patients without prior CVD. No associations were observed between vascular inflammation and carotid intima-media thickness or presence of carotid plaques, respectively. The results suggest an inflammatory link between vascular and adipose tissues, spleen, and bone marrow in patients with psoriasis.

YKL-40: a new biomarker in cardiovascular disease?

Cardiovascular disease in the form of coronary artery disease is the most common cause of death in western countries. Early treatment with stabilizing drugs and mechanical revascularization by percutaneous coronary intervention or coronary bypass surgery has reduced the mortality significantly. But in spite of improved treatments, many patients are still plagued by a high frequency of angina symptoms, hospitalizations and a poor prognosis. There is a need for new independent or supplementary biomarkers that can help to predict cardiovascular disease and cardiovascular events earlier and more precisely, and thus accompany existing biomarkers in both primary and secondary cardiovascular prevention. One such potential new biomarker is the protein YKL-40. As an independent biomarker in both cardiovascular diseases and noncardiovascular diseases, current evidence suggests YKL-40 to be most useful as a marker of disease severity, prognosis and short survival. However, future studies will evaluate whether YKL-40 can be used for monitoring of the treatment effect in different patient populations with a distinct disease diagnosis. In this article we explore present knowledge on YKL-40 as a biomarker in cardiovascular disease.

Prognostic impact of hs-CRP and IL-6 in patients with persistent atrial fibrillation treated with electrical cardioversion.

OBJECTIVE: The aim of this study was to assess the role of inflammatory processes in the development of atrial fibrillation (AF) and the prognostic impact of inflammatory markers in predicting long-term risk of AF recurrence after electrical cardioversion (CV). METHODS: High-sensitivity C-reactive protein (hs-CRP) and interleukin-6 (IL-6) were measured in 56 patients with persistent AF (lasting mean 128 days (range 14-960), mean age 65 years (34-84)), 19 healthy volunteers and 19 patients with permanent AF. Patients with persistent AF underwent CV. Blood samples were taken prior to CV and after 1, 30 and 180 days. RESULTS: The immediate success rate of CV was 88%, while the total recurrence rate after 180 days was 68%. Patients with permanent AF had significantly higher levels of hs-CRP and IL-6 than patients with persistent AF (p = 0.0011, p<0.001). Patients in sinus rhythm (SR) after 180 days had significantly lower baseline hs-CRP (1.25 mg/L (0.5-2.4) versus 2.0 mg/L (0.9-3.3), p<0.001) and IL-6 (1.96 pg/mL (1.35-2.7) versus 2.75 pg/mL (1.55-3.62), p<0.001) than patients with recurrent AF. Baseline IL-6 was the only independent predictor of recurrent AF (p = 0.04) in a multivariate Cox analysis. Patients in the lowest hs-CRP quartile (<0.8 mg/L) had significantly lower AF recurrence rates after 180 days (50% versus 74% in the other three quartiles combined; p = 0.0069). CONCLUSION: Patients with AF had elevated levels of inflammatory markers. Low hs-CRP and IL-6 prior to CV are associated with a lower risk of AF recurrence after CV.

Prognostic impact of hs-CRP and IL-6 in patients undergoing radiofrequency catheter ablation for atrial fibrillation.

AIM: The aim of this study was to assess the predictive value of inflammatory markers in patients with paroxysmal/persistent atrial fibrillation (AF) treated with radiofrequency (RF) catheter ablation. METHODS: Forty-six consecutive patients, mean age 55 years (range 31 - 81 yrs), with paroxysmal or persistent AF were treated with either segmental or circumferential pulmonary vein isolation ablation technique. All patients presented with sinus rhythm on inclusion. Holter monitoring lasting at least 14 days was performed before ablation and after 3 months. Recurrent symptomatic AF or atrial tachycardia >10 minutes was considered failure and patients were offered a second ablation session. Interleukin-6 and high-sensitivity C-reactive protein were measured prior to ablation and at follow-up visits. RESULTS: After a maximum of two ablations, 19 patients (41%) had SR without recurrence of AF after 12 months. Patients in SR had significantly lower left atrium diameter (p = 0.007) and lower values of both IL-6 (p = 0.007) and hs-CRP (p = 0.018) at baseline before ablation. IL-6 concentration prior to ablation was an independent predictor of recurrent AF (p = 0.027). CONCLUSION: In patients with a history of paroxysmal or persistent AF treated with RF catheter ablation, elevated levels of IL-6 and hs-CRP before ablation are independent predictors of recurrence of AF.