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International audience; Background: Prior analyses suggest an association between formula-based plasma volume (PV) estimates and outcomes in heart failure (HF). We assessed the association between estimated PV status by the Duarte-ePV and Kaplan Hakim (KH-ePVS) formulas, and in-hospital and postdischarge clinical outcomes, in the ASCEND-HF trial.Methods and results: The KH-ePVS and Duarte-ePV were calculated on admission. We assessed associations with in-hospital worsening HF, 30-day composite cardiovascular mortality or HF rehospitalization and 180-day all-cause mortality. There were 6373 (89.2%), and 6354 (89.0%) patients who had necessary characteristics to calculate KH-ePVS and Duarte-ePV, respectively. There was no association between PV by either formula with in-hospital worsening HF. KH-ePVS showed a weak correlation with N-terminal prohormone BNP, and with measures of decongestion such as body weight change and urine output (r < 0.3 for all). Duarte-ePV was trending toward an association with worse 30-day (adjusted odds ratio 1.07, 95% confidence interval [CI] 1.00-1.15, P = .058), but not 180-day outcomes (adjusted hazard ratio 1.03, 95% CI 0.97-1.09, P = .289). A continuous KH-ePVS of >0 (per 10-unit increase) was associated with improved 30-day outcomes (adjusted odds ratio 0.75, 95% CI 0.62-0.91, P = .004). The continuous KH-ePVS was not associated with 180-day outcomes (adjusted hazard ratio 1.05, 95% CI 0.98-1.12, P = .139).Conclusions: Baseline PV estimates had a weak association with in-hospital measures of decongestion. The Duarte-ePV trended toward an association with early clinical outcomes in decompensated HF, and may improve risk stratification in HF.

Pulmonary embolism (PE) is a major cause of cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA) is increasingly recognized in the aging population, especially with the rising obesity epidemic. The impact of OSA on inpatient mortality in PE is not well understood. We used the Nationwide Inpatient Sample databases from 2005 to 2016 to identify 755,532 acute PE patients (age≥18 years). Among these, 61,050 (8.1%) were OSA+. Temporal trends in length of stay, inpatient mortality, and its association with OSA in PE patients were analyzed. The proportion of PE patients who were OSA+ increased from 2005 to 2016. OSA+ PE patients were younger and predominantly men. Despite a higher prevalence of traditional risk factors for inpatient mortality in OSA+ patients, OSA was associated with a lower risk of mortality in PE patients (odds ratio, 95% confidence interval; p : unadjusted 0.56, 0.53–0.58; p

Background: Psoriasis, a chronic inflammatory disease associated with an accelerated risk of myocardial infarction, provides an ideal human model to study inflammatory atherogenesis in vivo. We hypothesized that the increased cardiovascular risk observed in psoriasis would be partially attributable to an elevated subclinical coronary artery disease burden composed of noncalcified plaques with high-risk features. However, inadequate efforts have been made to directly measure coronary artery disease in this vulnerable population. As such, we sought to compare total coronary plaque burden and noncalcified coronary plaque burden (NCB) and high-risk plaque (HRP) prevalence between patients with psoriasis (n=105), patients with hyperlipidemia eligible for statin therapy under National Cholesterol Education Program-Adult Treatment Panel III guidelines (n=100) who were ≈10 years older, and healthy volunteers without psoriasis (n=25). Methods: Patients underwent coronary computed-tomography angiography for total coronary plaque burden and NCB quantification and HRP identification, defined as low attenuation (1.10), and spotty calcification. A consecutive sample of the first 50 patients with psoriasis was scanned again 1 year after therapy. Results: Despite being younger and at lower traditional risk than patients with hyperlipidemia, patients with psoriasis had increased NCB (mean±SD: 1.18±0.33 versus 1.11±0.32, P =0.02) and similar HRP prevalence ( P =0.58). Furthermore, compared to healthy volunteers, patients with psoriasis had increased total coronary plaque burden (1.22±0.31 versus 1.04±0.22, P =0.001), NCB (1.18±0.33 versus 1.03±0.21, P =0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1–31.7; P =0.03). Last, among patients with psoriasis followed for 1 year, improvement in psoriasis severity was associated with improvement in total coronary plaque burden (β=0.45, 0.23–0.67; P P Conclusions: Patients with psoriasis had greater NCB and increased HRP prevalence than healthy volunteers. In addition, patients with psoriasis had elevated NCB and equivalent HRP prevalence as older patients with hyperlipidemia. Last, modulation of target organ inflammation (eg, skin) was associated with an improvement in NCB at 1 year, suggesting that control of remote sites of inflammation may translate into reduced coronary artery disease risk.

Obesity may associate with greater cardiovascular risk in adults with congenital heart disease (ACHD) than in the general population. As ACHD often have exercise limitations, they may be uniquely predisposed to obesity. Nevertheless, obesity prevalence in ACHD, compared with the general population, has not been quantified in a large US cohort. Hence, we sought to determine the prevalence of obesity (30 ≤ body mass index40) and morbid obesity (body mass index ≥40), in a large cohort of ACHD, compared with matched controls. Retrospective analysis was thus performed on all ACHD seen in an academic system in 2013. CHD severity was classified as simple, complex, or unclassified, using recently published criteria. A control group without CHD was randomly generated matching for age, gender, and race/ethnicity; 1,451 ACHD met inclusion criteria; 59.5% of ACHD were overweight to morbidly obese. Compared with controls, ACHD had similar prevalence of overweight (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.89 to 1.22, p = 0.63) and obesity (OR 0.96, 95% CI 0.81 to 1.15, p = 0.69) but lower prevalence of morbid obesity (OR 0.24, 95% CI 0.16 to 0.34, p0.001). These relationships were not attenuated by adjustment for CHD severity. In conclusion, ACHD are at equal risk as their matched peers to be overweight and obese. This is the largest study of obesity in US ACHD and the highest reported obesity prevalence in ACHD to date. As obesity is associated with significant cardiovascular risk, our findings indicate a need for improved lifestyle counseling in patients with CHD of all ages.

IMPORTANCE: Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis. OBJECTIVE: To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. DESIGN, SETTING, AND PARTICIPANTS: In a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year. EXPOSURES: Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURES: Coronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. RESULTS: Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age- and sex-matched controls (median, 210.3 [IQR, 110.9-336.2] vs 83.7 [IQR, 40.1-151.0]; P 50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 160.0-648.8] vs median, 224.2 [IQR, 149.1 - 427.4]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02). CONCLUSIONS AND RELEVANCE: Soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory atherogenesis in psoriasis.

Background: Women comprise approximately one-third of the advanced heart failure population but may receive fewer advanced heart failure therapies including left ventricular assist devices (LVADs). During the early pulsatile-flow device era, women had higher post-LVAD mortality and increased complications. However, knowledge about these differences in the continuous-flow device era is limited. Therefore, we sought to explore temporal trends in LVAD utilization and post-LVAD mortality by sex. Methods and Results: Patients with LVAD implantation from 2004 to 2016 were identified using the Nationwide Inpatient Sample. Trends in LVAD utilization and post-LVAD inpatient mortality were compared by sex and device era. Although LVADs are being increasingly utilized for patients with advanced systolic heart failure, women continue to represent a smaller proportion of LVAD recipients—25.8% in 2004 to 21.9% in 2016 ( P for trend, 0.91). Women had increased inpatient mortality after LVAD implantation compared with men in the pulsatile-flow era (46.9% versus 31.1%, P P =0.27; P for interaction=0.0002). Inpatient mortality decreased for both sexes over time after LVAD, with a sharp fall in 2008 to 2009. Female sex was independently associated with increased post-LVAD inpatient mortality beyond adjustment for demographics and risk factors during the pulsatile-flow era (odds ratio, 2.13; 95% CI, 1.45–3.10; P P =0.16). Conclusions: Although utilization of LVAD therapy increased over time for both sexes, LVAD implantation remains stably lower in women, which may suggest a potential underutilization of this potentially life-saving therapy. Prospective studies are needed to confirm these findings.

Introduction: Heart failure with reduced ejection fraction (HFrEF) may be associated with unique metabolic derangements in patients with type 2 diabetes (T2DM). However, whether such derangements are associated with clinical outcomes remains unclear. Purpose: 1) To determine metabolic pathways that are dysregulated in high-risk HFrEF with and without T2DM. 2) To identify metabolomic signatures which may be differentially associated with clinical outcomes in HFrEF patients with T2DM. Methods: The FIGHT trial studied the effect of liraglutide on clinical stability in individuals with advanced HFrEF. Forty-five metabolites were quantified in 254 baseline plasma samples from the trial (T2DM: n=147, non-T2DM: n=107) using tandem flow injection mass spectrometry. Principal component analysis (PCA) was used to reduce the high number of correlated metabolites into uncorrelated factors. Linear regression was used to evaluate the association of T2DM with PCA-derived factor levels. Cox proportional hazards models, stratified by T2DM status, were used to test for time to mortality or HF hospitalization. Results: Patients with T2DM were older, had higher BMI, and were more likely to have CAD, but had similar gender composition and severity of HF, as compared with non-T2DM patients. PCA identified 13 metabolite factors grouping in biologically consistent pathways. T2DM status was associated with two factors, one composed of the short chain dicarboxyl-acylcarnitine, C6-DC, and the long-chain acylcarnitine C22 (β= -0.325, p=0.016), and one composed of aspartic acid/asparagine (β= -0.373, p=0.008), in fully adjusted models. The same C6-DC, C22 factor was associated with time to mortality or HF hospitalization beyond adjustment for sex, race, liraglutide exposure, baseline age, systolic blood pressure, creatinine, BMI, NT-pro-BNP, and liver function (T2DM: HR 1.573, p=0.007; Non-T2DM: HR 1.302, p=0.103). Conclusions: Amongst patients with high-risk HFrEF, those with T2DM had differential levels of a short chain dicarboxyl- and long-chain acylcarnitine, which were associated with adverse clinical outcomes. Such metabolites might serve as potential targets for diagnostic or therapeutic interventions in diabetic HFrEF.

Background Subjects with Systemic Lupus Erythematosus (SLE) display an increased risk of atherosclerotic cardiovascular disease (CVD) that is not explained by Framingham Risk. This study sought to investigate the utility of nuclear magnetic resonance (NMR) spectroscopy measurements of serum lipoprotein particle counts and size and glycoprotein acetylation (GlycA) to predict coronary atherosclerosis in SLE. Methods Coronary plaque burden was assessed in SLE subjects and healthy controls using coronary CT angiography. Lipoproteins and GlycA were quantified by NMR spectroscopy. Results SLE subjects displayed statistically significant decreases in high-density lipoprotein (HDL) particle counts and increased very low density lipoprotein (VLDL) particle counts compared to controls. Non-calcified coronary plaque burden (NCB) negatively associated with HDL subsets, whereas it positively associated with VLDL particle counts in multivariate adjusted models. GlycA was significantly increased in SLE sera compared to controls. In contrast to high-sensitivity C-reactive protein, elevations in GlycA in SLE significantly associated with NCB and insulin resistance. Conclusions SLE patients display a proatherogenic lipoprotein profile that may significantly contribute to the development of premature CVD. The results demonstrate that NMR measures of GlycA and lipoprotein profiles, beyond what is captured in routine clinical laboratory tests for lipids, could be a useful tool in assessing CVD risk in SLE patients.

Introduction: Psoriasis (PSO), a chronic inflammatory disease associated with increased prevalence of both stress and coronary artery disease, provides a model to study the role of perceived stress in cardiovascular (CV) disease. While stress perception quantified as resting amygdala activity (RAA) is associated with CV events, its association psoriasis severity as well subclinical CV indices is not well known. We thus, sought to look into the relationship between RAA, psoriasis area severity index (PASI) score and Non-calcified burden (NCB) in PSO. Methods: 150 consecutive PSO patients and 58 healthy volunteers (HV) underwent 18-FDG PET/CT and CCTA scans (Toshiba, 320-detector row) to quantify RAA and NCB respectively. Skin disease severity was assessed as PASI score, RAA as target-to-background ratio (Osirix) and NCB using prior published methods (QAngio). The relationship between them was analyzed using multivariable regressions (STATA 12). Results: Despite older age, both PSO & HV were at low CV risk by traditional risk score. RAA was higher in PSO compared to HV (Table 1). Moreover, PASI score correlated positively with RAA in treatment naïve psoriasis patients (β=0.22, p=0.03). Furthermore, RAA associated with NCB (β=0.27, p Conclusion: In conclusion, PSO skin disease severity relates to amygdalar activity by 18-FDG PET/CT suggesting the role of chronic inflammatory disease like PSO in triggering perceived psychological stress. Moreover, there is a direct association between amygdalar activity and coronary plaque burden suggesting a role for perceived stress in subclinical CV disease in these patients. Larger studies are needed to confirm these findings.

BACKGROUND. Systemic lupus erythematosus (SLE) is associated with enhanced risk of atherosclerotic cardiovascular disease not explained by Framingham risk score (FRS). Immune dysregulation associated to a distinct subset of lupus proinflammatory neutrophils (low density granulocytes; LDGs) may play key roles in conferring enhanced CV risk. This study assessed if lupus LDGs are associated with in vivo vascular dysfunction and inflammation and coronary plaque. METHODS. SLE subjects and healthy controls underwent multimodal phenotyping of vascular disease by quantifying vascular inflammation (18F-fluorodeoxyglucose–PET/CT [18F-FDG–PET/CT]), arterial dysfunction (EndoPAT and cardio-ankle vascular index), and coronary plaque burden (coronary CT angiography). LDGs were quantified by flow cytometry. Cholesterol efflux capacity was measured in high-density lipoprotein–exposed (HDL-exposed) radioactively labeled cell lines. Whole blood RNA sequencing was performed to assess associations between transcriptomic profiles and vascular phenotype. RESULTS. Vascular inflammation, arterial stiffness, and noncalcified plaque burden (NCB) were increased in SLE compared with controls even after adjustment for traditional risk factors. In SLE, NCB directly associated with LDGs and associated negatively with cholesterol efflux capacity in fully adjusted models. A neutrophil gene signature reflective of the most upregulated genes in lupus LDGs associated with vascular inflammation and NCB. CONCLUSION. Individuals with SLE demonstrate vascular inflammation, arterial dysfunction, and NCB, which may explain the higher reported risk for acute coronary syndromes. The association of LDGs and neutrophil genes with vascular disease supports the hypothesis that distinct neutrophil subsets contribute to vascular damage and unstable coronary plaque in SLE. Results also support previous observations that neutrophils may disrupt HDL function and thereby promote atherogenesis. TRIAL REGISTRATION. Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00001372","term_id":"NCT00001372"}}NCT00001372 FUNDING. Intramural Research Program NIAMS/NIH (ZIA {"type":"entrez-nucleotide","attrs":{"text":"AR041199","term_id":"5961695","term_text":"AR041199"}}AR041199) and Lupus Research Institute

We appreciate the correspondence brought forward by both groups, who positively support our study,1 and facilitate further fruitful discussion of this study. In response to Drs Jin-shan and Xue-bin, we agree that there is an increase in cardiovascular risk factors in psoriasis. We adjusted for traditional cardiovascular risk factors and body mass index in our study. Our results suggest an independent association of psoriasis with increased subclinical coronary artery disease. Furthermore, we emphasize that high-risk plaque formation in psoriasis is likely multifactorial, and related to a complex interplay between keratinocytes, immune cells, vascular endothelial cells, lipoproteins, oxidative stress, and genetic factors. Therefore, as suggested, we advocate for more in vitro mechanistic studies that use primary human psoriatic skin, and murine models, as well, that recapitulate the human disease state. Only after these careful laboratory-based efforts coupled with a rigorous, randomized controlled cardiovascular outcomes study …

Purpose Women comprise over half of the heart failure (HF) population but less commonly receive advanced HF therapies such as left ventricular assist devices (LVAD). Women had higher mortality rates and increased postoperative complications after LVADs during the early pulsatile flow (PF) era and in large registries in the continuous flow (CF) era. Whether these disparities and complication rates persist over time and how they may impact LVAD utilization in women in the CF era is unknown. Methods We utilized the National Inpatient Sample from 2004 to 2016 to identify patients with LVAD placement. Temporal trends in LVAD utilization and post-LVAD inpatient mortality were compared by gender and between PF (before 2009) and CF (2009 and after) era. Results The absolute number of LVAD implants increased for both genders (Fig 1A) over time but the percentage of women overall receiving LVAD remained stably low compared to men over time (less than 30% of total implants; Fig 1B&C). Baseline characteristics including comorbidity profiles, post-LVAD complications and inpatient outcomes are summarized (Table 1). Despite fewer comorbidities, women had higher mortality post LVAD in the PF era (p Conclusion Although overall LVAD implants increased for both genders from 2004 to 2016, LVAD utilization remained comparatively low in women. Disparately increased inpatient mortality in women post-LVAD during the PF era did not remain during the CF era. Prospective studies need to confirm our findings of post-LVAD outcomes between genders. However, our results suggest potential underutilization of LVAD in women with advanced HF in the CF LVAD era.

Inflammation is critical in the development of atherosclerosis. Psoriasis is a chronic inflammatory skin disease that is associated with increased vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography in vivo and future cardiovascular events. It provides a human model to understand the effect of treating inflammation in a target organ (eg, the skin) on vascular diseases.To investigate the association between change in skin disease severity and change in vascular inflammation at 1 year and to characterize the impact of 1 year of anti-tumor necrosis factor therapy on vascular inflammation.In this prospective cohort study, 220 participants from outpatient practices were recruited at the US National Institutes of Health. A total of 115 consecutively recruited patients with psoriasis were followed up at 1 year. The study was conducted from January 1, 2013, through October 31, 2016, with data analyzed in November 2016.Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score.Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography.Among the 115 patients, the mean (SD) age at 1-year follow-up was 50.8 (12.8) years and 68 were men (59%). The cohort had a low cardiovascular risk by Framingham risk score and mild-to-moderate psoriasis, with a median PASI score of 5.2 (interquartile range, 3.0-8.9). At follow-up, the total cohort had a median improvement in PASI score of 33%, with use of topical therapy (60%), biological therapy (66%, mostly anti-tumor necrosis factor) and phototherapy (15%) (P .001). Moreover, improvement in PASI score was associated with improvement in target-to-background ratio of 6%, mainly driven by those with higher responses in PASI score (P .001). This association persisted beyond traditional risk factors (β = 0.19; 95% CI, 0.012-0.375; P = .03) and was the strongest in those initiated with anti-tumor necrosis factor therapy (β = 0.79; 95% CI, 0.269-1.311; P = .03).Improvement in psoriasis skin disease severity was associated with improvement in aortic vascular inflammation by 18fluorodeoxyglucose positron emission tomography/computed tomography, with greater improvement in aortic vascular inflammation observed in those who had higher than 75% reduction in skin disease severity. These findings suggest that controlling remote target organ inflammation (eg, in the skin) may improve vascular diseases; however, randomized clinical trials are needed to confirm these findings.

Introduction: Psoriasis (PSO), a chronic inflammatory disease associates with increased metabolic and cardiovascular (CV) risk. Dysglycemia may contribute to the increased risk of CV disease observed in psoriasis. Therefore, the aim of this study was to characterize whether dysglycemia assessed by hemoglobin A1c (HbA1c) is associated with subclinical coronary artery disease in psoriasis. Hypothesis: We hypothesized that total burden (TB) of coronary artery plaque and non-calcified burden (NCB) would be associated with HbA1c values in psoriasis independent of cardiovascular risk factors. Methods: Consecutive psoriasis patients (n=103) and age and sex matched controls (n=42) underwent CCTA (Toshiba, 320-detector row) for coronary plaque characterization. TB and NCB were quantified using QAngio (Medis, The Netherlands). Fasting blood samples were collected on the same day to get HbA1c values. The relationship of HbA1c with TB and NCB was analyzed using multivariable regression models (STATA 12). Results: PSO patients were middle-aged, predominantly male, had a low CV risk by FRS and had mild to moderate skin disease (Table 1). HbA1c levels were elevated in psoriasis compared to controls (P=0.007). Furthermore, total (P=0.02) and non-calcified (P=0.04) burden were elevated in psoriasis as compared to controls. HbA1c directly associated with TB ( β =0.21; P=0.001) and NCB ( β =0.18; P=0.004); a relationship which persisted beyond CV risk factors (TB and NCB: β =0.22; P=0.01). Conclusions: HbA1c was associated with total and non-calcified burden in psoriasis population independent of CV risk factors. These findings underscore the importance of screening for glycemic abnormalities to mitigate CV disease risk in patients with psoriasis.

Background: Psoriasis (PSO), a chronic inflammatory disease associated with increased cardiovascular (CV) risk, provides a reliable human model to study inflammatory atherogenesis. PSO has been known to be associated with cardiometabolic dysfunction including adipose tissue dysfunction. Recently, visceral adiposity (VAT) was shown to be associated with increased CV events, but whether VAT is associated with subclinical atherosclerosis as assessed by coronary plaque burden has not been characterized. Hypothesis: We hypothesized that VAT volume by CT is associated with total burden (TB) and more specifically with non-calcified burden (NCB) by CCTA. Methods: Consecutive PSO patients (N=68) underwent CT scans to measure abdominal adiposity. VAT volume was quantified from the level of the diaphragm to the pubic symphysis and reported in volume. Coronary plaque characterization was performed by CCTA (Toshiba 30 slice) via QAngio CT software (Medis, The Netherlands). The relationship of VAT with TB and NCB was analyzed using unadjusted and adjusted multivariable regression models (STATA 12). Results: The cohort was middle-aged, predominantly male, at low CV risk by FRS with mild to moderate PSO by skin disease severity (Table 1). VAT volume associated with both TB (beta coefficient= 0.49, p-value Conclusions: Directly quantified VAT directly associated with TB and NCB independent of cardiovascular risk factors. These findings suggest that adipose tissue dysfunction may in part contribute to the high CV events observed in psoriasis and support efforts to provide weight control as a strategy to reduce CV disease in psoriasis.

Introduction: Cholesterol efflux capacity (CEC), a measure of high density lipoprotein (HDL) function, has been shown to be associated with future cardiovascular (CV) events. Lipid rich plaque is associated with higher plaque rupture and future CV events, and can be readily phenotyped by coronary CT angiography (CCTA). Whether CEC associates with lipid rich plaque is not known. Hypothesis: We hypothesize that CEC associates with lipid rich plaque in those at risk for myocardial infarction (MI). Methods: Consecutively recruited patients (N=94) underwent CCTA (Toshiba 320 slice) to assess plaque burden within the coronary arteries by QAngio CT (Medis, The Netherlands); history was obtained and statin use was recorded. CEC was measured using an ex vivo validated assay. Results: The study population mean age was 61 and had normal cholesterol, HDL, low density lipoprotein (LDL), and triglyceride levels (Table 1). CEC was 1.03 ± 0.17 while total plaque and lipid rich plaque were 1.05 (0.79-1.37) mm 2 and 1.00 (0.77-1.33) mm 2 , respectively. Lipid rich plaque inversely associated with CEC beyond adjustment for age, gender, systolic blood pressure, statin treatment, total cholesterol, LDL, and HDL (β= -0.18, p=0.002). Conclusion: CEC associated with lipid rich plaque independent of CV risk factors to provide additional risk stratification in those at risk for MI and early atherogenesis. Clinical Implications: My study will help cardiovascular clinicians to better understand that HDL function may capture additional CV risk in those at risk for future MI.

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) spectroscopy measurements of serum lipoprotein particle counts and size and glycoprotein acetylation (GlycA) burden to predict coronary atherosclerosis in SLE.MethodsCoronary plaque burden was assessed in SLE subjects and healthy controls using coronary CT angiography. Lipoproteins and GlycA were quantified by NMR spectroscopy.ResultsSLE subjects displayed statistically significant decreases in high-density lipoprotein (HDL) particle counts and increased very low-density lipoprotein (VLDL) particle counts compared with controls. Non-calcified coronary plaque burden (NCB) negatively associated with HDL subsets whereas it positively associated with VLDL particle counts in multivariate adjusted models. GlycA was significantly increased in SLE sera compared with controls. In contrast to high-sensitivity C reactive protein, elevations in GlycA in SLE significantly associated with NCB and insulin resistance (IR), though the association with NCB was no longer significant after adjusting for prednisone use.ConclusionsPatients with SLE display a proatherogenic lipoprotein profile that may significantly contribute to the development of premature CVD. The results demonstrate that NMR measures of GlycA and lipoprotein profiles, beyond what is captured in routine clinical labs, could be a useful tool in assessing CVD risk in patients with SLE.

Rationale: GlycA, an emerging inflammatory biomarker, predicted cardiovascular events in population-based studies. Psoriasis, an inflammatory disease associated with increased cardiovascular risk, provides a model to study inflammatory biomarkers in cardiovascular disease (CVD). Whether GlycA associates with psoriasis and how it predicts subclinical CVD beyond high-sensitivity C-reactive protein in psoriasis is unknown. Objective: To investigate the relationships between GlycA and psoriasis and between GlycA and subclinical CVD. Methods and Results: Patients with psoriasis and controls (n=412) participated in a 2-stage study. We measured GlycA by nuclear magnetic resonance spectroscopy. National Institutes of Health (NIH) participants underwent 18-F Fluorodeoxyglucose Positron Emission Tomography Computed Tomography (18-FDG PET/CT) scans to assess vascular inflammation (VI) and coronary computed tomographic angiography to quantify coronary artery disease burden. Psoriasis cohorts were young (mean age=47.9), with low cardiovascular risk and moderate skin disease. high-sensitivity C-reactive protein and GlycA were increased in psoriasis compared with controls (GlycA: [PENN: 408.8±75.4 versus 289.4±60.2, P P P P =0.004) associated with GlycA beyond CV risk factors in psoriasis. In receiver operating characteristic analysis, GlycA added value in predicting VI ( P =0.01) and coronary artery disease ( P P P P P Conclusions: GlycA associated with psoriasis severity and subclinical CVD beyond traditional CV risk and high-sensitivity C-reactive protein. Moreover, psoriasis treatment reduced GlycA and VI. These findings support the potential use of GlycA in subclinical CVD risk assessment in psoriasis and potentially other inflammatory diseases.

Background and aims Psoriasis is a chronic inflammatory disorder associated with vascular inflammation, measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and an increased risk of myocardial infarction. Patients with psoriasis are also more likely to suffer from comorbid depression. Whether depression accelerates the development of subclinical atherosclerosis in psoriasis is unknown. Methods Patients were selected from within a larger psoriasis cohort. Those who reported a history of depression (N = 36) on survey were matched by age and gender to patients who reported no history of psychiatric illness (N = 36). Target-to-background ratio from FDG PET/CT was used to assess aortic vascular inflammation and coronary CT angiography scans were analyzed to determine coronary plaque burden. Multivariable linear regression was performed to understand the effect of self-reported depression on vascular inflammation and coronary plaque burden after adjustment for Framingham risk (standardized β reported). Results In unadjusted analyses, vascular inflammation and coronary plaque burden were significantly increased in patients with self-reported depression as compared to patients with psoriasis alone. After adjustment for Framingham Risk Score, vascular inflammation (β = 0.26, p = 0.02), total plaque burden (β = 0.17, p = 0.03), and non-calcified burden (β = 0.17, p = 0.03) were associated with self-reported depression. Conclusions Self-reported depression in psoriasis is associated with increased vascular inflammation and coronary plaque burden. Depression may play an important role in promoting subclinical atherosclerosis beyond traditional cardiovascular risk factors.

Introduction: Recent studies suggest that hsCRP may inaccurately predict coronary heart disease (CHD) in patients with chronic inflammatory disorders. GlycA, a novel inflammatory biomarker measured by nuclear magnetic resonance, was associated with future cardiovascular events in a large cohort study. Whether GlycA predicts CHD beyond hsCRP in chronic inflammatory patients is unknown. Psoriasis (PSO), a chronic inflammatory disease associated with increased cardiovascular risk, provides a clinical human model to assess the utility of GlycA as a risk marker of CHD. Hypothesis: We hypothesized that GlycA would associate with CHD, by total (TB) and non-calcified burden (NCB) assessed by coronary CT angiography, beyond traditional risk factors in PSO. Methods: 151 consecutive PSO patients and 40 controls underwent coronary CT angiography (320 detector row) as part of a large cohort study (NCT01778569). Coronary plaque burden was assessed by QAngio (Medis). We measured GlycA by nuclear magnetic resonance (LabCorp). A physician ascertained clinical parameters. Labs were measured in a certified clinical research facility. Statistical analyses include multivariate regression and ROC modeling. Results: PSO patients were older, at low Framingham risk, but had significant cardiometabolic dysfunction and increased CHD by TB and NCB (Table). While hsCRP significantly associated with CHD in controls, it showed no relationship in PSO. GlycA, however, strongly associated with TB (β=0.14, p=0.01) and NCB (β=0.12, p=0.01) beyond traditional risk factors in PSO. Finally, ROC analyses demonstrated greater AUC for GlycA in predicting TB and NCB (Figure), suggesting GlycA adds incremental value to traditional cardiovascular risk factors. Conclusion: In conclusion, GlycA associates with coronary plaque burden in PSO. Our study suggests a role for GlycA beyond hsCRP in assessing CHD in inflammatory states. Larger prospective studies are needed to confirm these findings.

Introduction: Psoriasis is a chronic inflammatory disorder associated with vascular inflammation (VI), measured by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT), and increased risk of MI. Coronary plaque composition by coronary computed tomography angiography (CCTA) predicts both CV risk and outcomes. Patients with psoriasis are more likely to suffer from comorbid depression and anxiety. Whether these comorbidities may accelerate the development of CVD in psoriasis is not well characterized. Hypothesis: We hypothesized that aortic VI and coronary plaque burden would be increased in patients with psoriasis who have depression and/or anxiety when compared to those with psoriasis who do not. Methods: Psoriasis patients were derived from an ongoing psoriasis study cohort. Patients who reported a history of depression and/or anxiety (n=40) on survey and age- and gender- matched patients who reported no history of psychiatric illness (n=40) were selected. Target-to-background ratio from FDG PET/CT was used to assess aortic VI and CCTA scans were analyzed for coronary plaque composition. Multivariate linear regression was performed to understand the effect of psychiatric diagnoses on VI and plaque burden after adjustment for CV risk factors (standardized β reported). Results: In unadjusted analyses, both aortic VI and coronary plaque burden were higher in psoriasis patients with comorbid depression or anxiety compared to those without (Table 1). After adjustment for Framingham Risk Score, body mass index, and statin use, VI (β=0.24, p=0.02), total plaque burden (β=0.13, p=0.04), and non-calcified burden (β=0.13, p=0.04) were associated with comorbid depression or anxiety. Conclusions: Patients with psoriasis who have comorbid depression or anxiety have increased aortic VI and coronary plaque burden, suggesting that identification of psychiatric diagnoses in psoriasis may be warranted for future CV risk reduction in this high risk population.

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.

Rheumatoid arthritis (RA) is associated with higher incidence of systolic and diastolic heart failure (HF) from both ischemic and non-ischemic etiologies independent of traditional CV risk factors. Although HF is an important contributor to the excess mortality in RA, the burden of acute

Background Psoriasis is associated with risk of cardiovascular (CV) disease (CVD) and a major adverse CV event (MACE). Whether psoriasis duration affects risk of vascular inflammation and MACEs has not been well characterized. Objectives We utilized two resources to understand the effect of psoriasis duration on vascular disease and CV events: (1) a human imaging study and (2) a population-based study of CVD events. Methods First, patients with psoriasis (N = 190) underwent fludeoxyglucose F 18 positron emission tomography/computed tomography (duration effect reported as a β-coefficient). Second, MACE risk was examined by using nationwide registries (adjusted hazard ratios in patients with psoriasis (n = 87,161) versus the general population (n = 4,234,793). Results In the human imaging study, patients were young, of low CV risk by traditional risk scores, and had a high prevalence of cardiometabolic diseases. Vascular inflammation by fludeoxyglucose F 18 positron emission tomography/computed tomography was significantly associated with disease duration (β = 0.171, P = .002). In the population-based study, psoriasis duration had strong relationship with MACE risk (1.0% per additional year of psoriasis duration [hazard ratio, 1.010; 95% confidence interval, 1.007-1.013]). Limitations These studies utilized observational data. Conclusion We found detrimental effects of psoriasis duration on vascular inflammation and MACE, suggesting that cumulative duration of exposure to low-grade chronic inflammation may accelerate vascular disease development and MACEs. Providers should consider inquiring about duration of disease to counsel for heightened CVD risk in psoriasis.

Small, dense low-density lipoproteins (sLDL-p) by nuclear magnetic resonance (NMR) were recently shown to be a strong predictor of CV events. If this relationship is true in inflammatory states, which modulate lipoprotein structure and function, is unclear. Psoriasis (PSO), a chronic inflammatory

18 Figure 1 *P-value is calculated by comparing baseline and 1-year follow-up values for variables using paired t-test for continuous variables, and Pearson’s chi-squared test for categorical variables. All values are expressed as Mean±SD, unless specified otherwise. PASI: Psoriasis Area Severity Index. 814 J Investig Med 2016;64:800–825 Abstracts group.bmj.com on December 16, 2016 Published by http://jim.bmj.com/ Downloaded from

Psoriasis (PSO), a chronic inflammatory skin disease, is associated with vascular inflammation (VI) by 18-F FDG PET/MRI and an increased risk of MI. Coronary computed tomography angiography (CCTA) characterizes the composition of plaque in coronary heart disease (CHD). We hypothesized that VI in the

Purpose of Study Psoriasis (PSO), a chronic inflammatory disease associated with increased cardiovascular (CV) risk, provides a clinical human model to study inflammatory atherogenesis. While PSO severity is associated with both in vivo vascular disease and future CV risk, the longitudinal impact of PSO severity on coronary disease progression is unknown. We hypothesized that an improvement in PSO severity may lead to a reduction in coronary plaque burden by coronary CT angiography (CCTA). Methods Used Consecutively recruited PSO patients (N=50) underwent CCTA (320 detector row, Toshiba) and cardiometabolic profiling at baseline and 1-year follow-up. Total (TB) and non-calcified (NCB) coronary plaque burden were quantified using QAngio (Medis, Netherlands). PSO severity was measured as the psoriasis area severity index (PASI). The longitudinal change in coronary plaque burden was analyzed with unadjusted and adjusted regression. Summary of Results The cohort had a low Framingham Risk Score and mild to moderate PSO. Patients whose PSO severity improved (ΔPASI −27%; p Conclusions Improvement in PSO severity was associated with improvement in coronary plaque burden by CCTA. Our study suggests that a reduction in skin inflammation may reduce the progression of early, non-calcified coronary plaque. Larger studies are needed to confirm these findings.

Purpose of Study Psoriasis is a chronic inflammatory disorder associated with vascular inflammation (VI), measured by 18-fluorodeoxyglucose positron emission tomography/computed tomography (18-FDG PET/CT), and increased risk of MI. Patients with psoriasis are more likely to have comorbid depression and anxiety. Whether these comorbidities accelerate the development of CVD in psoriasis is unclear. We hypothesized that aortic VI and coronary plaque burden would be increased in patients with psoriasis who have depression and/or anxiety compared to those with psoriasis who do not. Methods Used Patients were prospectively enrolled. Those who reported a history of depression and/or anxiety (n=40) on survey and age- and gender-matched patients who reported no history of psychiatric illness (n=40) were selected. Target-to-Background ratio from 18FDG PET/CT was used to assess aortic VI, and coronary CT angiography scans were analyzed for coronary plaque composition. Summary of Results Both aortic VI and coronary plaque burden were higher in psoriasis patients with comorbid depression or anxiety compared to those without (table 1). After adjustment for Framingham Risk Score, body mass index, and statin use; VI (β=0.24, p=0.02), total plaque burden (β=0.13, p=0.04), and non-calcified burden (β=0.13, p=0.04) were associated with comorbid depression and/or anxiety. Conclusions Patients with psoriasis who have comorbid depression or anxiety have increased aortic VI and coronary plaque burden, suggesting that identification of psychiatric diagnoses in psoriasis may be warranted for future CV risk reduction in this high risk population.

Purpose of Study Psoriasis (PSO), a chronic inflammatory skin disease, is associated with increased CV risk and vascular inflammation (VI). However, the effect of therapeutic lifestyle changes (TLC) including exercise on VI over time is unknown. We hypothesized that TLC would lead to an improvement in VI at 1 year accompanied by improvements in aortic wall characteristics. Methods Used 65 PSO patients, recruited consecutively, underwent FDG PET/CT, phase contrast MRI scans and clinical visits for evaluation of VI, wall characteristics and exercise frequency, at baseline and 1 year follow-up. VI was measured as Target-to-background ratio (TBR), and aortic distensibility (AD) and wall thickness were assessed by commercial software on phase contrast MRI scans. Clinical parameters were ascertained by both survey and provider. Summary of Results VI decreased at 1 year (6.5% decrease in TBR; p Conclusions Our findings suggest that VI improves with TLC. This 6.5% decrease in VI could lead to ∼30% reduction in future adverse events, based on a recent large prospective study. This VI reduction is also associated with improved aortic wall characteristics suggesting that targeting VI as a surrogate marker holds promise to understand the effects of TLC on CV disease.