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Objective Increased left ventricular (LV) mass is an important precursor to heart failure. Inflammation plays an important role in increasing LV mass. However, the contribution of subclinical coronary artery disease (CAD) to the inflammation-LV mass relationship is unknown. In subjects with psoriasis, a chronic inflammatory skin disease, we evaluated if systemic inflammation assessed by plasma glycoprotein A (GlycA) associated with LV mass measured on coronary CT angiography (CCTA). Additionally, we analyzed whether this relationship was mediated by early CAD assessed as noncalcified coronary burden (NCB). Methods We performed an observational longitudinal study of 213 subjects with psoriasis free of known cardiovascular disease, 189 of whom were followed over one year. All participants had GlycA measurements by nuclear magnetic resonance spectroscopy and LV mass and NCB quantified by CCTA. Results The cohort had a mean age of 50.3 (±12.9) years and 59% were male. There was moderate psoriasis severity and low cardiovascular risk. LV mass increased by GlycA tertiles [1st tertile:24.6 g/m 2.7 (3.8), 2nd tertile:25.5 g/m 2.7 (3.8), 3rd tertile:27.7 g/m 2.7 (5.5), p <0.001]. Both GlycA (β=0.24, p = 0.001) and NCB (β=0.50, p <0.001) associated with LV mass in models adjusted for age, sex, hypertension, hypertension therapy, lipid therapy, biologic therapy for psoriasis, waist:hip ratio, psoriasis disease duration and severity. In multivariable-adjusted mediation analyses, NCB accounted for 32% of the GlycA-LV mass relationship. Finally, over one year, change in NCB independently associated with change in LV mass (β=0.25, p = 0.002). Conclusions Both systemic inflammation and coronary artery NCB were associated with LV mass beyond cardiovascular risk factors in psoriasis. Furthermore, a substantial proportion of the inflammatory-LV mass relationship was mediated by NCB. These findings underscore the possible contribution of early coronary artery disease to the relationship between systemic inflammation and LV mass.

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Background Psoriasis is a common chronic inflammatory condition associated with an increased risk of obesity and higher coronary atherosclerosis burden by coronary computed tomography angiography (CCTA). Prior studies have shown that the ability to expand subcutaneous adipose tissue (SAT) may serve to identify individuals at a lower risk of atherosclerotic cardiovascular disease. However, the relationship between abdominal SAT and high-risk subclinical coronary artery disease requires exploration. Purpose To characterize the relationship between abdominal SAT volume measured on low-dose computed tomography, and coronary artery disease assessed as noncalcified and lipid-rich necrotic core burden by CCTA in psoriasis. Methods We performed a cross-sectional study of 232 participants with psoriasis and without known cardiovascular disease. All participants underwent CCTA to characterize coronary artery disease burden and low dose abdominal computed tomography to quantify subcutaneous adipose tissue volumes. Fat depot volumes were first adjusted in a sex specific manner for each participant's body mass index in a linear regression model. The residual values from the sex stratified linear regression models were used for analyses. Coronary artery disease burden was quantified in the three main coronary arteries (QAngio, Medis, The Netherlands) and averaged. Analyses were performed with StataIC 16 (Stata Corp., College Station, TX, USA). Results Of the 232 participants, 92 (40%) were women and the average age was 50 years. In women, there was a positive correlation between abdominal SAT and systemic inflammation as assessed by hs-CRP (r=0.30; p=0.004) and GlycA (r=0.29; p=0.007) as well as total cholesterol (r=0.24; p=0.02) and LDL cholesterol (r=0.22; p=0.04). In men, abdominal SAT correlated with hs-CRP (r=0.18; p=0.04) and insulin resistance as assessed by the homeostatic model for insulin resistance (r=0.17; p=0.04). In models fully adjusted for traditional cardiovascular risk factors, abdominal SAT volume negatively associated with noncalcified and lipid-rich necrotic core burden in men (β=−0.17; p=0.03, β=−0.21; p=0.02, respectively), but not women (β=−0.04; p=0.72, β=0.05; p=0.68, respectively) with psoriasis (Table). Conclusions In psoriasis, for a given body mass index, abdominal SAT negatively associated with coronary atherosclerosis burden in men. The observed sex-specific effects on subclinical coronary artery disease warrant further study of abdominal SAT in states of chronic inflammation. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): National Heart, Lung and Blood Institute Intramural Research Program in Bethesda, Maryland

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 <.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< .001) and its individual components of waist circumference (β=0.33; p <.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.

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