Non-calcified Coronary Plaque Burden Research Articles

A Multiomic Analysis to Identify Drivers of Subclinical Vascular Disease in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) increases cardiovascular disease (CVD) risk, and this is not explained by traditional risk factors. Characterization of blood immunologic signatures that associate with subclinical CVD and predict its progression has been challenging and may help identify subgroups at risk. Patients with SLE (n = 77) and healthy controls (HCs) (n = 27) underwent assessments of arterial stiffness, vascular wall inflammation, and coronary atherosclerosis burden with cardio-ankle vascular index (CAVI); fluorodeoxyglucose-positron emission tomography/computed tomography (CT) (target-to-background ratio [TBR]); and coronary CT angiography. Whole blood bulk RNA sequencing was performed in a subset of study participants (HC n = 10, SLE n = 20). In a partially overlapping subset (HC n = 24, SLE n = 64), serum inflammatory protein biomarkers were quantified with an Olink platform. CAVI, TBR, and noncalcified coronary plaque burden (NCB) were increased in patients with SLE compared to HCs. When comparing patients with SLE with high CAVI scores to those with low CAVI scores or to HCs, there was a down-regulation of genes in pathways involved in the cell cycle and differentially regulated pathways related to metabolism. Distinct serum proteins associated with increased CAVI (CCL23, colony-stimulating factor 1, latency-activating peptide transforming growth factor β1, interleukin 33 [IL-33], CD8A, and IL-12B), NCB (monocyte chemotactic protein 4 and FMS-like tyrosine kinase 3 ligand [Flt3L]), and TBR (CD5, IL-1α, AXIN1, cystatin D [CST5], and tumor necrosis factor receptor superfamily 9; P < 0.05). Blood gene expression patterns and serum proteins that associate with worse vascular phenotypes suggest dysregulated immune and metabolic pathways linked to premature CVD. Cytokines and chemokines identified in associations with arterial stiffness, inflammation, and NCB in SLE may allow for characterization of new CVD biomarkers in lupus.

Body mass components affecting low-attenuation noncalcified coronary plaque burden

Abstract Funding Acknowledgements Type of funding sources: Public hospital(s). Main funding source(s): National Institute of Cardiology in Warsaw, Poland Background Weight control is a major risk modifier for coronary artery disease. However, the effect exerted by individual body mass components on coronary plaque may not be uniform. Low-attenuation noncalcified plaque (LAP) has been recently identified as an independent predictor of cardiovascular outcomes [1]. Purpose To determine the relationship between changes in body mass composition and LAP burden. Methods 89 participants of Dietary Intervention to Stop Coronary Atherosclerosis in Computed Tomography (DISCO-CT) were enrolled into the analysis (40% women, mean age 60±7.7 years). Patients with non-obstructive (stenosis&amp;lt;70%) coronary atherosclerosis confirmed in coronary computed tomography angiography (CCTA) and qualified to conservative treatment were randomized (1:1) to intensive diet and lifestyle intervention atop optimal medical therapy (OMT) versus OMT alone over 66.8±13.7 months [2]. Body mass (BM) and body mass components including total body fat (TBF), skeletal muscle mass (SMM), visceral cell mass (VCM), and extracellular mass (ECM) were measured at baseline and follow-up (InBody S10 analyser, South Korea). LAP burden was defined as the volume of coronary plaque &amp;lt;30 Hounsfield units divided by the vessel volume, and expressed in %. Changes in body components were compared with changes in LAP measured in serial CCTA scans (QAngioCT, Medis Medical Imaging Systems, the Netherlands). Results Reduction in BM was significantly higher in the experimental (∆BM=-3.6±4.9 kg) vs control arm (∆BM=-1.4±2.9 kg; p = 0.016) and so was the reduction in TBF (∆TBF=-4.2±5.3 kg vs ∆TBF=0.2±4.3 kg, respectively; p&amp;lt;0.001). SMM increased by 0.4±2.6 kg in the experimental arm and decreased by 1.0±2.1 kg in the control arm (p = 0.006). No significant interarm differences were observed for changes in VCM and ECM. Reduction in LAP was higher in the experimental vs control arm (∆LAP=-0.42±1.4% vs ∆LAP=-0.03±0.45%, respectively; p = 0.078). In the entire study population, a significant positive correlation between LAP reduction and BM reduction was revealed (r=0.45, p&amp;lt;0.001). Multivariate regression model incorporating the investigated body mass components identified TBF as the only component associated with LAP reduction (table). Conclusions Body mass reduction may decrease LAP burden due to body fat reduction.

845 HDL composition, particle number and size is associated with non-calcified coronary plaque in psoriasis

There is an evolving appreciation that high-density lipoproteins (HDL) is highly heterogeneous in both composition and function. With the advent of advanced lipid-testing techniques that allow for the quantitation and recovery of individual particle populations, we are beginning to connect the functionality of HDL subspecies with chronic inflammatory diseases. Psoriasis (PSO), provides a reliable human model to study how HDL composition may relate to non-calcified coronary plaque burden (NCB). We hypothesized that HDL composition would directly associate with NCB beyond traditional cardiovascular risk factors.

Determinants of Non-calcified Low-Attenuation Coronary Plaque Burden in Patients Without Known Coronary Artery Disease: A Coronary CT Angiography Study

BackgroundAlthough epicardial adipose tissue (EAT) is associated with coronary artery disease (CAD), it is unclear whether EAT volume (EAV) can be used to diagnose high-risk coronary plaque burden associated with coronary events. This study aimed to investigate (1) the prognostic impact of low-attenuation non-calcified coronary plaque (LAP) burden on patient level analysis, and (2) the association of EAV with LAP volume in patients without known CAD undergoing coronary computed tomography angiography (CCTA).Materials and MethodsThis retrospective study consisted of 376 patients (male, 57%; mean age, 65.2 ± 13 years) without known CAD undergoing CCTA. Percent LAP volume (%LAP, <30 HU) was calculated as the LAP volume divided by the vessel volume. EAT was defined as adipose tissue with a CT attenuation value ranging from −250 to −30 HU within the pericardial sac. The primary endpoint was a composite event of death, non-fatal myocardial infarction, and unstable angina and worsening symptoms requiring unplanned coronary revascularization >3 months after CCTA. The determinants of %LAP (Q4) were analyzed using a multivariable logistic regression model.ResultsDuring the follow-up period (mean, 2.2 ± 0.9 years), the primary endpoint was observed in 17 patients (4.5%). The independent predictors of the primary endpoint were %LAP (Q4) (hazard ratio [HR], 3.05; 95% confidence interval [CI], 1.09–8.54; p = 0.033] in the Cox proportional hazard model adjusted by CAD-RADS category. Cox proportional hazard ratio analysis demonstrated that %LAP (Q4) was a predictor of the primary endpoint, independnet of CAD severity, Suita score, EAV, or CACS. The independent determinants of %LAP (Q4) were CACS ≥218.3 (p < 0.0001) and EAV ≥125.3 ml (p < 0.0001). The addition of EAV to CACS significantly improved the area under the curve (AUC) to identify %LAP (Q4) than CACS alone (AUC, EAV + CACS vs. CACS alone: 0.728 vs. 0.637; p = 0.013).ConclusionsCCTA-based assessment of EAV, CACS, and LAP could help improve personalized cardiac risk management by administering patient-suited therapy.

Multimodality molecular imaging: Gaining insights into the mechanisms linking chronic stress to cardiovascular disease

Positron emission tomography (PET) imaging can yield unique mechanistic insights into the pathophysiology of atherosclerosis. 18F-fluorodeoxyglucose (18F-FDG), a radiolabeled glucose analog, is retained by cells in proportion to their glycolytic activity. While 18F-FDG accumulates within several cell types in the arterial wall, its retention correlates with macrophage content, providing an index of arterial inflammation (ArtI) which predicts subsequent cardiovascular disease (CVD) events. Furthermore, 18F-FDG-PET imaging allows the simultaneous assessment of metabolic activity in several tissues (e.g., brain, bone marrow) and is performed in conjunction with cross-sectional imaging that enables multi-organ structural assessments. Accordingly, 18F-FDG-PET/computed tomography (CT) imaging facilitates evaluation of disease pathways that span multiple organ systems. Within this paradigm, 18F-FDG-PET/CT imaging has been implemented to study the mechanism linking chronic stress to CVD. To evaluate this, stress-associated neural activity can be quantified (as metabolic activity of the amygdala (AmygA)), while leukopoietic activity, ArtI, and coronary plaque burden are assessed concurrently. Such simultaneous quantification of tissue structures and activities enables the evaluation of multi-organ pathways with the aid of mediation analysis. Using this approach, multi-system 18F-FDG-PET/CT imaging studies have demonstrated that chronically heightened stress-associated neurobiological activity promotes leukopoietic activity and systemic inflammation. This in turn fuels more ArtI and greater non-calcified coronary plaque burden, which result in more CVD events. Subsequent studies have revealed that common stressors, such as chronic noise exposure and income disparities, drive the front end of this pathway to increase CVD risk. Hence, multi-tissue multimodality imaging serves as a powerful tool to uncover complex disease mechanisms.

Abstract P221: Metabolic Syndrome And Its Factors Associate With Non-calcified Coronary Plaque Burden In Chronic Inflammation: Results From A Prospective Observational Study

Introduction: Psoriasis is a common, inflammatory skin disease associated with systemic inflammation and heightened risk of cardiovascular diseases (CVD). Population studies have shown that psoriasis is associated with metabolic syndrome (MetSyn) and its individual components. However, the impact of MetSyn on early atherosclerosis in chronic inflammatory diseases assessed as non-calcified coronary plaque burden (NCB) by coronary computed CT angiography (CCTA) is not known. Hypothesis: We hypothesized that those with MetSyn in psoriasis would have increased NCB compared to non-MetSyn and that MetSyn and its components would associate with NCB in fully adjusted models. Methods: The cohort consisted of 336 psoriasis patients free of cardiovascular disease, of which 326 had adequate data to classify MetSyn based on the International Diabetes Federation criteria (waist circumference, triglycerides, HDL cholesterol, blood pressure and fasting glucose). Of these, 260 had quantitative CCTA data available for analyses (Stata 16). Results: Of the 260 patients, 80 had MetSyn (31%). The MetSyn group had increased cardiometabolic disease and more adverse coronary characteristics including higher non-calcified ( p &lt;.001) and high-risk plaque ( p =.02) (Table) . In fully adjusted models for Framingham risk score, lipid lowering therapy and biologic use, MetSyn (β=0.31; p&lt; .001) and its individual components of waist circumference (β=0.33; p &lt;.001), triglycerides (β=0.17; p =.005), blood pressure (β=0.18; p =.005) and fasting glucose (β=0.17; p =.009) associated with NCB. Conclusions: MetSyn and its components were associated with NCB in psoriasis suggesting that early atherosclerosis is importantly impacted by poor cardiometabolic health. Components of MetSyn should be assessed in psoriasis patients and patients educated about this heightened risk of CVD associated with MetSyn.

Association between the systemic treatment of psoriasis and cardiovascular risk.

Association between the systemic treatment of psoriasis and cardiovascular risk.

Abstract 16281: Non-calcified Coronary Plaque Burden is Related to Epicardial Adipose Tissue and Peri-coronary Adipose Tissue Attenuation in Heart Failure With Preserved Ejection Fraction

Introduction: Coronary inflammation may be a factor in developing heart failure with preserved ejection fraction (HFpEF). Epicardial fat volume (EFV) measured using non-contrast computed tomography (CT) and pericoronary adipose tissue (PCAT) attenuation on coronary CT angiography (CCTA) are considered to be inflammatory mediators, which play an important role in the development of coronary plaque. Hypothesis: We hypothesize that there is an interrelationship between these measures in HFpEF and no obstructive coronary artery disease (CAD). Methods: 28 subjects with HFpEF (European Society of Cardiology criteria), with coronary CCTA-documented absence of obstructive CAD. Non-calcified plaque (NCP), low-density non-calcified plaque (LDNCP), PCAT attenuation were quantified using semi-automated software and EFV was quantified using QFAT software. PCAT attenuation in Hounsfield Units (HU) was measured in a standardized 40 mm segment around the proximal right coronary artery. Statistical analysis was performed using Spearman correlation and multivariable regression models adjusted for age, BMI, EFV, and PCAT tested relations to NCP burden. Results: Overall, the mean age of 64.8±12 years, 74% women, BMI 29.3±4, total cholesterol 162±41mg/dl, LDL 85±29 mg/dl, HDL 55±14 mg/dl, systolic BP 132±22mmHg, diastolic BP 77±12mmHg, EFV 139±73 cm 3 and, PCAT attenuation -78±8 HU. Mean total NCP burden 34±13%, total LDNCP burden 3±1.8 %, and coronary calcium score (CCS) 414±920. EFV and PCAT attenuation correlated with the coronary risk markers including CCS and NCP burden variables (Table). In multivariable analysis, age and PCAT (β±SE=0.43±0.2, p=0.04, 0.64±0.3, p=0.03 per 1%-change in NCP burden respectively) were related to NCP burden. Conclusions: EFV and PCAT attenuation are associated with non-calcified plaque burden and may play an important role in the pathophysiological process of HFpEF. Further studies are needed to further understand these findings.

Serum active 1,25(OH)2D, but not inactive 25(OH)D vitamin D levels are associated with cardiometabolic and cardiovascular disease risk in psoriasis

Background and aimsVitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk. MethodsConsecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN). ResultsThe psoriasis cohort was middle-aged (mean ± SD: 49.6 ± 13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2–10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)2D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (β = − 0.43, p = 0.026 and β = −0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)2D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (β = −0.19, p = 0.01). Finally, we found that serum 1,25(OH)2D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (β = −0.18, p = 0.03). ConclusionsIn conclusion, we demonstrate that low 1,25(OH)2D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)2D may better capture the cardiometabolic risk associated with vitamin D deficient states.

Association of lipoprotein subfractions and glycoprotein acetylation with coronary plaque burden in SLE

ObjectiveSubjects with SLE display an enhanced risk of atherosclerotic cardiovascular disease (CVD) that is not explained by Framingham risk. This study sought to investigate the utility of nuclear MR (NMR)...

APPLICATION OF MACHINE LEARNING TO DETERMINE TOP PREDICTORS OF NON-CALCIFIED CORONARY PLAQUE BURDEN IN PSORIASIS

Psoriasis, a chronic systemic inflammatory disease, is associated with elevated non-calcified coronary plaque burden (NCB) and increased cardiovascular (CV) events. In this study, we used machine learning (ML) as a tool to determine the top predictors of NCB, which is prone to rupture and cause

SOLUBLE LECTIN-LIKE OXIDIZED LOW-DENSITY LIPOPROTEIN RECEPTOR-1 IS ASSOCIATED WITH SUBCLINICAL CORONARY ARTERY DISEASES IN PSORIASIS

Psoriasis (PSO), a chronic inflammatory skin disease is associated with increased non-calcified coronary plaque burden (NCB) as well as heightened MI. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a scavenger receptor for oxidized LDL, is critical in the development of NCB. We

CORONARY PLAQUE BURDEN IS ASSOCIATED WITH CHOLESTEROL EFFLUX CAPACITY PARTIALLY MEDIATED BY THE HEMATOPOIETIC SYSTEM IN PSORIASIS

Psoriasis, a chronic inflammatory skin disease, is associated with heightened FDG-uptake in the bone marrow (BM) by FDG/PET-CT concomitant with increased non-calcified coronary plaque burden (NCB) by CCTA. Additionally, psoriasis patients have reduced cholesterol efflux capacity (CEC), which in turn

Coronary artery plaque characteristics and treatment with biologic therapy in severe psoriasis: results from a prospective observational study.

The use of biologic therapy has increased over the past decade well beyond primary autoimmune diseases. Indeed, a recent trial using an anti-IL-1beta antibody reduced second myocardial infarction (MI) in those who have had MI. Psoriasis is a chronic inflammatory disease often treated with biologics when severe, is associated with increased risk of MI, in part driven by high-risk coronary plaque phenotypes by coronary computed tomography angiography (CCTA). We hypothesized that we would observe a reduction in inflammatory-driven phenotypes of coronary plaque, including non-calcified coronary plaque burden and lipid-rich necrotic core in those treated with biologic therapy after one-year compared with non-biologic therapy. In a prospective, observational study, 290 participants were recruited from 1 January 2013 through 31 October 2018 with 215 completing one-year follow-up. Of the 238, 121 consecutive participants who were biologic treatment naïve at baseline were included. A blinded reader (blinded to patient demographics, visit and treatment) quantified total coronary plaque burden and plaque subcomponents (calcified and non-calcified) in the three main coronary vessels >2 mm using dedicated software (QAngio, Medis, Netherlands). Psoriasis patients were middle-aged [mean (standard deviation) age, 50.5 (12.1) years], mostly male (n = 70, 58%) with low cardiovascular risk by Framingham score [median (interquartile range, IQR), 3 (1-6)] and had moderate to severe skin disease at baseline [median (IQR) Psoriasis Area Severity Index, PASI, 8.6 (5.3-14.0)]. Biologic therapy was associated with a 6% reduction in non-calcified plaque burden (P = 0.005) reduction in necrotic core (P = 0.03), with no effect on fibrous burden (P = 0.71). Decrease in non-calcified plaque burden in the biologic treated group was significant compared with slow plaque progression in non-biologic treated (Δ, -0.07 mm2 vs. 0.06 mm2; P = 0.02) and associated with biologic treatment beyond adjustment for traditional cardiovascular risk factors (β = 0.20, P = 0.02). In this observational study, we demonstrate that biologic therapy in severe psoriasis was associated with favourable modulation of coronary plaque indices by CCTA. These findings highlight the importance of systemic inflammation in coronary artery disease and support the conduct of larger, randomized trials.

Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis

Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliablemodel to study inflammatory atherogenesis. Because neutrophils are implicated in atherosclerosis development, this study reports that the interaction among low-density granulocytes, a subset of neutrophils, and platelets is associated with a noncalcified coronary plaque burden assessed by coronary computed tomography angiography. Because early atherosclerotic noncalcified burden can lead to fatal myocardial infarction, the low-density granulocyte-platelet interaction may play a crucial target for clinical intervention.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in Psoriasis: A Prospective Cohort Study

ObjectivesThis study hypothesized that there is an association between chronic stress (as indexed by resting amygdalar activity [AmygA]), hematopoietic system activity (HMPA), and subclinical cardiovascular indexes (aortic vascular inflammation [VI] and noncalcified coronary plaque burden [NCB]) in psoriasis (PSO). The study also hypothesized that treatment of PSO would improve these parameters. BackgroundPSO is a stress-related chronic inflammatory condition that is associated with increased prevalence of subclinical cardiovascular disease (CVD). In individuals without PSO, stress has been linked to CVD through a serial biological pathway that involves the amygdala, hematopoietic tissues, and atherosclerotic plaques. MethodsA total of 164 consecutive patients with PSO and 47 healthy volunteers underwent 18-fluorodeoxyglucose positron emission tomography/computed tomography scans for assessment of AmygA, HMPA, and VI, as well as coronary computed tomography angiography scans for quantifying NCB. Furthermore, a consecutive subset of 30 patients with severe PSO (Psoriasis Area Severity Index Score >10) were followed at 1 year to assess the relationship between skin disease improvement and AmygA, HMPA, VI, and NCB. ResultsThe PSO cohort was middle-aged (mean age: 50 years), had low cardiovascular risk (Framingham risk score: median: 3) and had mild to moderate PSO activity (median Psoriasis Area Severity Index Score: 5.6). AmygA was higher in patients with PSO compared to volunteer participants. AmygA was associated with HMPA (bone marrow activity: β = 0.20, p = 0.01) and subclinical CVD (VI: β = 0.31, p < 0.001; NCB: β = 0.27, p < 0.001) The AmygA−CVD association was in part mediated by HMPA (VI: 20.9%, NCB: 36.7%). Following 1 year of PSO treatment in those with severe disease, improvement in skin disease was accompanied by a reduction in AmygA, bone marrow activity, and VI, with no progression of NCB. ConclusionsIn PSO, a chronic inflammatory disease state, AmygA, which is a manifestation of chronic stress, substantially contributes to the risk of subclinical CVD. Additional studies that use psychometric measures of stress are required to explore therapeutic impact.

Association Between Aortic Vascular Inflammation and Coronary Artery Plaque Characteristics in Psoriasis

Inflammation is critical to atherosclerosis. Psoriasis, a chronic inflammatory disease associated with early cardiovascular events and increased aortic vascular inflammation (VI), provides a model to study the process of early atherogenesis. Fludeoxyglucose F 18 positron emission tomography/computed tomography (18F-FDG PET/CT) helps quantify aortic VI, and coronary computed tomography angiography provides coronary artery disease (CAD) assessment through evaluation of total plaque burden (TB) and noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP). To our knowledge, association between aortic VI and broad CAD indices has not yet been assessed in a chronic inflammatory disease state. Such a study may provide information regarding the utility of aortic VI in capturing early CAD. To assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis. In a cross-sectional cohort study at the National Institutes of Health, 215 consecutive patients with psoriasis were recruited from surrounding outpatient dermatology practices. All patients underwent 18F-FDG PET/CT for aortic VI assessment, and 190 of 215 patients underwent coronary computed tomography angiography to characterize CAD. The study was conducted between January 1, 2013, and May 31, 2017. Data were analyzed in March 2018. Aortic VI assessed by 18F-FDG PET/CT. Primary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP. Among 215 patients with psoriasis (mean [SD] age, 50.4 [12.6] years; 126 men [59%]), patients with increased aortic VI had increased TB (standardized β = 0.48; P < .001), and higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71-7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42-6.47; P = .004). The aortic VI and TB association was primarily driven by NCB (β = 0.49; P < .001), whereas the aortic VI and HRP association was driven by low-attenuation plaque (OR, 5.63; 95% CI, 1.96-16.19; P = .001). All associations of aortic VI remained significant after adjustment for cardiovascular risk factors: aortic VI and TB (β = 0.23; P < .001), NCB (β = 0.24; P < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40-8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08-6.83; P = .03). No association was found between aortic VI and dense-calcified coronary plaque burden. Aortic VI is associated with broad CAD indices, suggesting that aortic VI may be a surrogate for early CAD. Larger prospective studies need to assess these associations longitudinally and examine treatment effects on these outcomes.

P 161 – Correlation between patient reported outcome measures and objective clinical findings in the knee arthroplasty population

Vitamin D exists as an inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream, which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting cardiovascular disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. Psoriasis, a chronic inflammatory disease, is a vitamin D deficient state and is associated with increased cardiovascular disease risk. While serum 25(OH)D is routinely measured, we hypothesized that measurement of 1,25(OH)2D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk.Consecutive psoriasis patients (N = 122) at baseline underwent FDG PET/CT and CCTA scans to measure visceral adipose volume, aortic vascular uptake of FDG, and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN).The psoriasis cohort was middle-aged (mean ± SD: 49.6 ± 13.0), predominantly male (n = 71, 58%), in majority Caucasians (n = 98, 80%), and had moderate-to-severe skin disease [psoriasis area severity index score, PASI score, med. (IQR): 5.5 (3.2–10.7)], with almost one-fourth of the cohort on biologic psoriasis therapy for skin disease management (n = 32, 27%) at baseline. Interestingly, serum levels of 1,25(OH)2D but not 25(OH)D were found to be inversely associated with visceral adipose, a marker of cardiometabolic risk in fully adjusted models (β = − 0.43, p = 0.026 and β = −0.26 p = 0.13). Similarly, we found an inverse relationship between 1,25(OH)2D, but not 25(OH)D, and aortic vascular uptake of FDG independent of traditional risk factors (β = −0.19, p = 0.01). Finally, we found that serum 1,25(OH)2D, but not 25(OH)D, was inversely associated with non-calcified coronary plaque burden, as measured by CCTA independent of traditional risk factors (β = −0.18, p = 0.03).In conclusion, we demonstrate that low 1,25(OH)2D levels were associated with visceral adipose volume, vascular uptake of FDG and coronary plaque burden independent of traditional risk factors, suggesting that 1,25(OH)2D may better capture the cardiometabolic risk associated with vitamin D deficient states.

Abstract 197: Active (1,25 OH), but not Inactive (25-OH) Vitamin D levels are inversely associated with aortic Vascular Inflammation, Non-calcified Coronary Plaque Burden and Visceral Adiposity in Psoriasis

Introduction: Psoriasis (PSO), a chronic inflammatory disease associated with increased Cardiovascular (CV) risk provides an ideal model to study the role of vitamin D, a known anti-inflammatory molecule in PSO associated CV disease. Vitamin D exists as inactive 25-hydroxyvitamin D (25(OH)D) in the bloodstream which is converted to active 1,25-dihydroxyvitaminD (1,25(OH)2D) in target tissues. Cohort studies reporting CV disease among individuals with low vitamin D are inconsistent and solely measure 25(OH)D. While serum 25(OH)D is routinely measured , we propose that measurement of 1,25(OH)2D may perform better than 25(OH)D as a surrogate for CV disease. Methods: Consecutive PSO patients (N=122) and healthy controls (N=35) underwent FDG PET/CT and CCTA scans to measure vascular inflammation/ abdominal adiposity volume and coronary plaque burden respectively. Blood levels of both 1,25(OH)2D and 25(OH)D were measured by chemiluminescence (LIASON XL DIaSorin, Stillwater, MN). Results: PSO patients were middle-aged, mostly male, had moderate PSO severity and were at low CV risk by 10-year Framingham risk. PSO patients had lower serum 1,25(OH)2D compared to healthy controls (mean±SEM: 52.4±1.4 pg/ml versus 57.5±2.0, p&lt;0.037) but 25(OH)D was not significantly different (28.7±1.3 versus 27.3±2.2, p=0.30). 1,25(OH)2D, but not 25(OH)D was negatively associated with PASI score beyond adjustment for CV risk factors and systemic/ biological therapy (B=-0.20, p=0.043 vs. B=0.12, p=0.25). Furthermore, serum 1,25(OH)2D but not 25(OH)D was inversely associated with non-calcified coronary burden (B=-0.16, p&lt;0.001 versus B=0.01, p=0.84), vascular inflammation (B=-0.24, p=0.007 versus B=-0.13, p=0.16) and visceral adiposity (B=-0.43, p=0.026 versus B=-0.26, p=0.13) independent of traditional risk factors and statin/PSO therapy. Conclusion: Our data support that active 1,25(OH)2D may more accurately capture cardiometabolic disturbance compared to inactive 25(OH)D in humans.

Abstract P049: Serum Uric Acid Levels Are Associated With Non-Calcified Coronary Plaque Independent of Traditional Cardiovascular Risk Factors in Patients With Psoriasis

Introduction: Serum uric acid (sUA), a known inflammosome-inducer, is associated with prospective risk of coronary artery disease in a dose-dependent fashion. Psoriasis (PSO), a chronic inflammatory disease associated with elevated burden of systemic inflammation and subclinical coronary artery disease, provides a reliable human model to study how sUA may relate to non-calcified coronary plaque burden (NCB) measured by computed coronary tomography angiography (CCTA). Hypothesis: We hypothesized that sUA would directly associate with NCB beyond traditional cardiovascular (CV) risk factors. Methods: 103 consecutive PSO patients and 47 healthy volunteers (HV) underwent CCTA (320 detector row, Toshiba) for coronary plaque burden quantification using QAngio (Medis). PSO severity was assessed by Psoriasis Area Severity Score (PASI) and divided into severe PSO (PASI&gt;10) and mild-moderate PSO (PASI&lt;10). All patients had fasting blood draws for the measurement of sUA at a certified clinical lab. Results: PSO patients were older than HV and had a higher CV risk by Framingham risk score (FRS) (Table 1). We observed a significant trend towards increase in sUA among severe PSO, mild-moderate PSO, and HV groups (mean 6.4, 5.9, 5.4 respectively, p=0.02 for trend). A positive association was observed between sUA and NCB, which was stronger in severe PSO after adjustment for traditional CV risk, alcohol, statins, and systemic/biologic PSO treatment (Severe PSO: β=0.27, p&lt;0.001; Mild-moderate PSO: β=0.18, p=0.03), not significant in HV (β=0.18, p=0.12). Conclusions: sUA is independently associated with NCB in states of chronic inflammation such as PSO, and as such, may potentially serve as a biomarker for subclinical coronary atherosclerosis. However, larger prospective studies of CV outcomes in chronic inflammatory diseases are needed to confirm these results.