Publications by authors named "Justin A Rodante"

25 Publications

  • Page 1 of 1

Subclinical Liver Disease is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

J Invest Dermatol 2021 Jul 19. Epub 2021 Jul 19.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n=76 psoriasis participants and 76 controls), non-alcoholic fatty liver disease (NAFLD), assessed by the sonographic hepatorenal index (SHRI), was more prevalent in psoriasis than controls (61% vs 45%; p=.04). Psoriasis participants with NAFLD had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than psoriasis without NAFLD (61% vs 23%; p=.006) and controls with NAFLD (61% vs 32%; p<.05). SHRI was a determinant of subclinical atherosclerosis in psoriasis (OR, 3.5; p=.01). In the United States cohort, (n=162 psoriasis participants who underwent positron emission tomography and coronary CT angiography), those with high hepatic F-FDG uptake had higher noncalcified (1.3 (0.49 mm) vs 1.0 (0.40 mm)), fibrofatty (0.23 (0.15 mm) vs 0.11 (0.087 mm)), and lipid rich necrotic core (4.3 (2.3 mm) vs 3.0 (1.7 mm)) coronary burden (all p<.001,). Hepatic F-FDG uptake associated with noncalcified (β=0.28; p<.001), fibrofatty (β=0.49; p<.001) and lipid rich necrotic core (β=0.28; p=.003) burden. These results demonstrate the downstream cardiovascular effects of subclinical liver disease in psoriasis.
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http://dx.doi.org/10.1016/j.jid.2021.05.034DOI Listing
July 2021

Nanotomography of lesional skin using electron microscopy reveals cytosolic release of nuclear DNA in psoriasis.

JAAD Case Rep 2021 Mar 6;9:9-14. Epub 2021 Jan 6.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.

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http://dx.doi.org/10.1016/j.jdcr.2020.12.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868746PMC
March 2021

Association of neutrophil-to-lymphocyte ratio with non-calcified coronary artery burden in psoriasis: Findings from an observational cohort study.

J Cardiovasc Comput Tomogr 2021 Jul-Aug;15(4):372-379. Epub 2020 Dec 28.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background: Inflammation in the form of elevated high-sensitivity c-reactive protein (hs-CRP) has been shown to be critical in the development of atherothrombosis. Psoriasis, a chronic inflammatory skin disease, is associated with high systemic-inflammation, elevated neutrophil-to-lymphocyte ratio (NLR) and accelerated non-calcified coronary artery burden (NCB) by coronary computed tomography angiography (CCTA). We hypothesized that NLR would associate with early, rupture-prone atherosclerosis assessed as NCB independent of hs-CRP.

Methods: 316 consecutive psoriasis participants were recruited with 233 having one-year follow-up as part of a prospective, observational cohort study design. CCTA scans were performed to assess NCB in all three major epicardial coronary arteries.

Results: Patients with above average NLR (>mean: 2.29 ​± ​1.21) were older (mean ​± ​SD; 52.0 ​± ​12.8 vs. 47.9 ​± ​12.6, p ​= ​0.002), had higher hs-CRP (med. IQR: 2.3 (0.9-7.3) vs. 1.4 (0.7-3.2), p ​= ​0.001) and had higher NCB (mean ​± ​SD; 1.21 ​± ​0.58 vs. 1.13 ​± ​0.49, p ​= ​0.018) when compared to patients with below average NLR. NLR associated with psoriasis area severity index score (β ​= ​0.14, p ​= ​0.017), hs-CRP (β ​= ​0.16, p ​= ​0.005), as well as NCB independent of traditional risk factors, body mass index, statin use and hs-CRP (β ​= ​0.08, p ​= ​0.009). One year of biologic therapy for psoriasis was associated with a reduction in NLR (-14.5%, p ​< ​0.001), and this change in NLR associated with change in NCB in fully adjusted models and beyond hs-CRP (β ​= ​0.17, p ​= ​0.002).

Conclusion: NLR associated with psoriasis severity, hs-CRP and NCB at baseline. Biologic therapy reduced NLR over time and this change in NLR associated with the change in NCB at one-year. Taken together, these findings suggest that NLR may capture psoriasis patients at higher risk of NCB due to residual inflammation not fully captured by hs-CRP.
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http://dx.doi.org/10.1016/j.jcct.2020.12.006DOI Listing
December 2020

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

J Am Acad Dermatol 2021 May 3;84(5):1329-1338. Epub 2021 Feb 3.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Background: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome.

Objective: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis.

Methods: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria.

Results: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (β = .31; P < .001) and its individual factors of waist circumference (β = .33; P < .001), triglyceride levels (β = .17; P = .005), blood pressure (β = .18; P = .005), and fasting glucose (β = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden.

Limitations: Observational nature with limited ability to control for confounders.

Conclusions: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.
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http://dx.doi.org/10.1016/j.jaad.2020.12.044DOI Listing
May 2021

Association Among Noncalcified Coronary Burden, Fractional Flow Reserve, and Myocardial Injury in Psoriasis.

J Am Heart Assoc 2020 11 10;9(22):e017417. Epub 2020 Nov 10.

National Heart, Lung, and Blood Institute National Institutes of Health Bethesda MD.

Background Myocardial infarction and premature death have been observed in patients with psoriasis. Although inflammation-driven accelerated atherosclerosis has been proposed as a mechanism, the relationship between subclinical noncalcified coronary burden (NCB), functional coronary flow impairment, and myocardial injury is unclear. Methods and Results In an ongoing longitudinal cohort study, 202 consecutive patients with psoriasis (168 at 1 year) underwent coronary computed tomography angiography to identify coronary plaque, quantify NCB, and calculate coronary fractional flow reserve by computed tomography. Serum high-sensitivity troponin-T (hs-cTn-T) was measured using a fifth-generation assay. Overall, patients were middle-aged, predominantly male, and low cardiovascular risk. A higher than median NCB associated with a positive hs-cTn-T (fully adjusted model [odds ratio (OR), 1.72; 95% CI, 1.10-2.69, =0.018]) at baseline. Additionally, patients with a higher than median baseline NCB had higher odds of positive hs-cTn-T at 1 year in fully adjusted analyses (adjusted OR, 2.36; 95% CI, 1.47-3.79, <0.001). Higher NCB was associated with a higher frequency of fractional flow reserve by computed tomography ≤0.80 (36.11% versus 25.11%, Pearson χ=6.84, =0.009, unadjusted OR, 2.09; 95% CI, 1.36-3.22, <0.001) and higher frequency of a positive hs-cTn-T (54.36% versus 27.54%, Pearson χ=32.23, <0.001) in adjusted models (OR, 2.63; 95% CI, 1.56-4.42, <0.001). Conclusions NCB was associated with hs-cTn-T at baseline as well as at 1 year. Furthermore, patients with high NCB had higher prevalence of fractional flow reserve by computed tomography ≤0.80 and a >2- fold higher odds of positive hs-cTn-T. These findings underscore the importance of early vascular disease in driving myocardial injury, and support conduct of myocardial perfusion studies to better understand these findings.
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http://dx.doi.org/10.1161/JAHA.119.017417DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7763703PMC
November 2020

Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

JCI Insight 2020 11 19;5(22). Epub 2020 Nov 19.

National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (β = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (β = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (β = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.
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http://dx.doi.org/10.1172/jci.insight.142534DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7710282PMC
November 2020

Treatment of Psoriasis With Biologic Therapy Is Associated With Improvement of Coronary Artery Plaque Lipid-Rich Necrotic Core: Results From a Prospective, Observational Study.

Circ Cardiovasc Imaging 2020 09 15;13(9):e011199. Epub 2020 Sep 15.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD (H.C., D.E.U., A.K.D., K.M.A., M.A., J.A.R., Y.A.E., A.R., A.K., J.E.-A., H.T., M.P.P., W.Z., M.Y.C., N.N.M.).

Background: Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy.

Methods: Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year.

Results: Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (β [standardized β]=0.12 [95% CI, 0.00-0.15]; =0.045), and psoriasis severity (β=0.13 [95% CI, 0.01-0.26]; =0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm; 3.12 [1.99-4.66] versus 2.97 [1.84-4.35]; =0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82-4.60] versus 3.34 [2.04-4.74]; =0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, -0.22 mm versus 0.14 mm, =0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (β=-0.09 [95% CI, -0.01 to -0.18]; =0.033).

Conclusions: LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.
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http://dx.doi.org/10.1161/CIRCIMAGING.120.011199DOI Listing
September 2020

Relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease in psoriasis: Findings from a longitudinal observational cohort study.

Atherosclerosis 2020 10 29;310:37-44. Epub 2020 Jul 29.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background And Aims: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis.

Methods: Consecutive psoriasis patients (n = 275 at baseline and n = 205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods.

Results: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (β = 0.17, p = 0.01), GlycA (a systemic marker of inflammation, β = 0.49, p < 0.001), amygdalar activity (β = 0.30, p < 0.001), and NCB (β = 0.39; p < 0.001). Moreover, NCB associated with amygdalar activity in participants with high allostatic load score (β = 0.27; p < 0.001) but not in those with low allostatic load score (β = 0.07; p = 0.34). Finally, in patients with an improvement in allostatic load score at one year, there was an 8% reduction in amygdalar FDG uptake (p < 0.001) and a 6% reduction in NCB (p = 0.02).

Conclusions: In psoriasis, allostatic load score represents physiological dysregulation and may capture pathways by which chronic stress-related neural activity associates with coronary artery disease, emphasizing the need to further study stress-induced physiological dysregulation in inflammatory disease states.
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http://dx.doi.org/10.1016/j.atherosclerosis.2020.07.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7587126PMC
October 2020

Hyperlipidaemia and IFNgamma/TNFalpha Synergism are associated with cholesterol crystal formation in Endothelial cells partly through modulation of Lysosomal pH and Cholesterol homeostasis.

EBioMedicine 2020 Sep 6;59:102876. Epub 2020 Jul 6.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, 10 Center Drive, Bethesda, MD 20892, USA. Electronic address:

Background: Inflammation plays an important role in the development of cardiovascular disease (CVD). Patients with chronic inflammation diseases have high levels of inflammation and early fatal myocardial infarction due to early, unstable coronary plaques. Cholesterol crystals (CC) play a key role in atherogenesis. However, the underlying mechanisms of endothelial cell (EC)-derived CC formation are not well understood in chronic inflammation.

Methods: We utilized a combination of a mouse psoriasis model (K14-Rac1V12 mouse model) and human psoriasis patients to study the effect of inflammatory cytokines on CC formation in ECs. Lysosomal pH, alterations in lipid load and inflammatory proteins were evaluated as potential mechanisms linking inflammatory cytokines to CC formation. Coronary CT angiography was performed (n = 224) to characterize potential IFNγ and TNFα synergism on vascular diseases in vivo.

Findings: We detected CC presence in the aorta of K14-Rac1V12 mice on chow diet. IFNγ and TNFα were found to synergistically increase LDL-induced CC formation by almost 2-fold. There was an increase in lysosomal pH accompanied by a 28% loss in pH-dependent lysosomal signal and altered vATPaseV1E1 expression patterns. In parallel, we found that LDL+IFNγ/TNFα treatments increased free cholesterol content within EC and led to a decrease in SOAT-1 expression, an enzyme critically involved cholesterol homeostasis. Finally, the product of IFNγ and TNFα positively associated with early non-calcified coronary burden in patients with psoriasis (n = 224; β = 0.28, p < 0.001).

Interpretation: Our results provide evidence that IFNγ and TNFα accelerate CC formation in endothelial cells in part by altering lysosomal pH and free cholesterol load. These changes promote early atherogenesis and contribute to understanding the burden of CVD in psoriasis.

Funding: Funding was provided by the Intramural Research Program at NIH (NNM) and the National Psoriasis Foundation (NNM and YB).
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http://dx.doi.org/10.1016/j.ebiom.2020.102876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502673PMC
September 2020

Association Between Soluble Lectinlike Oxidized Low-Density Lipoprotein Receptor-1 and Coronary Artery Disease in Psoriasis.

JAMA Dermatol 2020 02;156(2):151-157

National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.

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 < .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >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.
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http://dx.doi.org/10.1001/jamadermatol.2019.3595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6902165PMC
February 2020

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

Atherosclerosis 2019 10 17;289:44-50. Epub 2019 Aug 17.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

Background And Aims: 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)D) 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)D in psoriasis may perform better than 25(OH)D in capturing cardiovascular risk.

Methods: 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)D and 25(OH)D were measured by chemiluminescence (LIAISON XL DIaSorin, Stillwater, MN).

Results: 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)D 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)D, 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)D, 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).

Conclusions: In conclusion, we demonstrate that low 1,25(OH)D 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)D may better capture the cardiometabolic risk associated with vitamin D deficient states.
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http://dx.doi.org/10.1016/j.atherosclerosis.2019.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7428835PMC
October 2019

Association of Biologic Therapy With Coronary Inflammation in Patients With Psoriasis as Assessed by Perivascular Fat Attenuation Index.

JAMA Cardiol 2019 09;4(9):885-891

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Importance: Psoriasis is a chronic inflammatory skin disease associated with increased coronary plaque burden and cardiovascular events. Biologic therapy for psoriasis has been found to be favorably associated with luminal coronary plaque, but it is unclear whether these associations are attributable to direct anti-inflammatory effects on the coronary arteries.

Objective: To investigate the association of biologic therapy with coronary inflammation in patients with psoriasis using the perivascular fat attenuation index (FAI), a novel imaging biomarker that assesses coronary inflammation by mapping spatial changes of perivascular fat composition via coronary computed tomography angiography (CCTA).

Design, Setting, And Participants: This prospective cohort study performed from January 1, 2013, through March 31, 2019, analyzed changes in FAI in patients with moderate to severe psoriasis who underwent CCTA at baseline and at 1 year and were not receiving biologic psoriasis therapy at baseline.

Exposures: Biologic therapy for psoriasis.

Main Outcomes And Measures: Perivascular FAI mapping was performed based on an established method by a reader blinded to patient demographics, visit, and treatment status.

Results: Of the 134 patients (mean [SD] age, 51.1 [12.1] years; 84 [62.5%] male), most had low cardiovascular risk by traditional risk scores (median 10-year Framingham Risk Score, 3% [interquartile range, 1%-7%]) and moderate to severe skin disease. Of these patients, 82 received biologic psoriasis therapy (anti-tumor necrosis factor α, anti-interleukin [IL] 12/23, or anti-IL-17) for 1 year, and 52 did not receive any biologic therapy and were given topical or light therapy (control group). At baseline, 46 patients (27 in the treated group and 19 in the untreated group) had a focal coronary atherosclerotic plaque. Biologic therapy was associated with a significant decrease in FAI at 1 year (median FAI -71.22 HU [interquartile range (IQR), -75.85 to -68.11 HU] at baseline vs -76.09 HU [IQR, -80.08 to -70.37 HU] at 1 year; P < .001) concurrent with skin disease improvement (median PASI, 7.7 [IQR, 3.2-12.5] at baseline vs 3.2 [IQR, 1.8-5.7] at 1 year; P < .001), whereas no change in FAI was noted in those not receiving biologic therapy (median FAI, -71.98 [IQR, -77.36 to -65.64] at baseline vs -72.66 [IQR, -78.21 to -67.44] at 1 year; P = .39). The associations with FAI were independent of the presence of coronary plaque and were consistent among patients receiving different biologic agents, including anti-tumor necrosis factor α (median FAI, -71.25 [IQR, -75.86 to -66.89] at baseline vs -75.49 [IQR, -79.12 to -68.58] at 1 year; P < .001) and anti-IL-12/23 or anti-IL-17 therapy (median FAI, -71.18 [IQR, -75.85 to -68.80] at baseline vs -76.92 [IQR, -81.16 to -71.67] at 1 year; P < .001).

Conclusions And Relevance: In this study, biologic therapy for moderate to severe psoriasis was associated with reduced coronary inflammation assessed by perivascular FAI. This finding suggests that perivascular FAI measured by CCTA may be used to track response to interventions for coronary artery disease.
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http://dx.doi.org/10.1001/jamacardio.2019.2589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669789PMC
September 2019

Early effects of roflumilast on insulin sensitivity in adults with prediabetes and overweight/obesity involve age-associated fat mass loss - results of an exploratory study.

Diabetes Metab Syndr Obes 2019 27;12:743-759. Epub 2019 May 27.

Laboratory of Obesity and Aging Research NHLBI, National Institutes of Health, Bethesda, MD 20892, USA,

Purpose: Roflumilast (Daliresp, Daxas) is a FDA-approved phosphodiesterase 4 (PDE4) inhibitor for the treatment of moderate-to-severe chronic obstructive pulmonary disease. In mice and in limited human studies, this oral medication can cause weight loss and improve insulin sensitivity. We set out to determine the mechanism of its effect on insulin sensitivity.

Patients And Methods: Eight adults with overweight/obesity and prediabetes received roflumilast for 6 weeks. Before and after roflumilast, subjects underwent tests of insulin sensitivity, mixed meal test, body composition, markers of inflammation, and mitochondria function. Dietary intake and physical activity were also assessed. Our primary outcome was the change in peripheral insulin sensitivity, as assessed by the hyper-insulinemic euglycemic clamp.

Results: This study was underpowered for the primary outcome. Pre- and post-roflumilast mean peripheral insulin sensitivity were 48.7 and 70.0 mg/g fat free mass/minute, respectively, (-value=0.18), respectively. Among the mixed meal variables, roflumilast altered glucagon-like peptide 1 (GLP-1) hormone the most, although the average effect was not statistically significant (=0.18). Roflumilast induced a trend toward significance in 1) decreased energy intake (from 11,095 KJ to 8,4555 KJ, =0.07), 2) decreased fat mass (from 34.53 to 32.97 kg, =0.06), 3) decreased total and LDL cholesterol (=0.06 for both variables), and 4) increased plasma free fatty acids (from 0.40 to 0.50 mEq/L, =0.09) The interval changes in adiposity and free fatty acid were significantly associated with the subject's age (-value range= <0.001 to 0.02 for the correlations). Inflammatory and adhesion markers, though unchanged, significantly correlated with one another and with incretin hormones only after roflumilast.

Conclusion: We demonstrate, for the first time in humans, increasing percentage of fat mass loss from roflumilast with increasing age in adults with prediabetes and overweight/obesity. We also demonstrate novel associations among roflumilast-induced changes in incretin hormones, inflammatory markers, peripheral insulin sensitivity, and adiposity. We conclude that roflumilast's early effects on insulin sensitivity is indirect and likely mediated through roflumilast's prioritization of lipid over glucose handling.

Clinical Trials Registration: NCT01862029.
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http://dx.doi.org/10.2147/DMSO.S182953DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542328PMC
May 2019

Neutrophil Subsets, Platelets, and Vascular Disease in Psoriasis.

JACC Basic Transl Sci 2019 Feb 25;4(1):1-14. Epub 2019 Feb 25.

Systemic Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland.

Psoriasis is an inflammatory skin disease associated with increased cardiovascular risk and serves as a reliable model 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.
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http://dx.doi.org/10.1016/j.jacbts.2018.10.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6390681PMC
February 2019

Association Between Oxidation-Modified Lipoproteins and Coronary Plaque in Psoriasis.

Circ Res 2018 11;123(11):1244-1254

From the Section of Inflammation and Cardiometabolic Diseases, Cardiovascular Branch, (A.V.S., Y.A.E., A.K.D., A.P.S., C.L.H., Y.B., J.A.R., M.Y.C., A.A.J., M.P.P., N.N.M.), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.

Rationale: Psoriasis is a systemic inflammatory skin disease associated with cardiovascular disease and lipid dysfunction. However, traditional lipid parameters have limited prognostic value, whereas assessing oxidation-modified lipids in this inflammatory driven condition may capture additional risk. Recently, a study showed that psoriasis was associated with increased lipid-rich coronary plaques; therefore, investigating potential relationships with oxidation-modified lipids may speed understanding of increased cardiovascular disease in psoriasis.

Objective: To understand whether oxidation-modified lipids associate with traditional lipid phenotypes, cardiometabolic disease biomarkers, and total coronary plaque, with focus on noncalcified burden (NCB) by coronary computed tomographic angiography in psoriasis.

Methods And Results: Psoriasis subjects and controls (n=252) had profiling for oxidation-modified LDL (low-density lipoprotein), HDL (high-density lipoprotein), Lp(a) (lipoprotein[a]), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy, and PON-1 (paraoxonase-1) activity. Blinded coronary computed tomographic angiography coronary artery disease characterization included total burden, NCB, and dense-calcified burden. Compared with healthy volunteers, psoriasis subjects were older (mean age, 50.1), had increased body mass index, and homeostatic model assessment of insulin resistance. Psoriasis subjects had increase in oxidized Lp(a), Lp(a), and oxidized HDL (oxHDL; P <0.05 for all) with significant association of oxidized LDL (β=0.10; P=0.020) and oxHDL (β=-0.11; P=0.007) with NCB. Moreover, psoriasis subjects expressed significantly higher PON-1 (kU/µL) activity compared with healthy volunteers (8.55±3.21 versus 6.24±3.82; P=0.01). Finally, psoriasis treatment was associated with a reduction in oxHDL (U/mL; 203.79±88.40 versus 116.36±85.03; P<0.001) and with a concomitant decrease in NCB at 1 year (1.04±0.44 versus 0.95±0.32; P=0.03).

Conclusions: Traditional lipids did not capture risk of lipid-rich plaque as assessed by NCB, whereas assaying oxidation-modification of lipids revealed significant association with oxidized LDL and oxHDL. The PON-1 activity was increased in psoriasis suggesting possible compensatory antioxidative effect. Psoriasis treatment was associated with a reduction in oxHDL. These findings support performance of larger studies to understand oxidation-modified lipids in inflammatory states.
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http://dx.doi.org/10.1161/CIRCRESAHA.118.313608DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345554PMC
November 2018

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

JACC Cardiovasc Imaging 2020 02 15;13(2 Pt 1):465-477. Epub 2018 Nov 15.

Section of Inflammation and Cardiometabolic Diseases, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Objectives: This 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.

Background: PSO 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.

Methods: A 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.

Results: The 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.

Conclusions: In 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.
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http://dx.doi.org/10.1016/j.jcmg.2018.08.038DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6506409PMC
February 2020

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

JAMA Cardiol 2018 10;3(10):949-956

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Importance: 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.

Objective: To assess the association between aortic VI and CAD indices, including TB, NCB, luminal stenosis, and HRP prevalence, in psoriasis.

Design, Setting, And Participants: 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.

Exposures: Aortic VI assessed by 18F-FDG PET/CT.

Main Outcomes And Measures: Primary outcome: TB and NCB. Secondary outcomes: luminal stenosis and HRP.

Results: 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.

Conclusions And Relevance: 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.
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http://dx.doi.org/10.1001/jamacardio.2018.2769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6233814PMC
October 2018

Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis.

JCI Insight 2018 01 11;3(1). Epub 2018 Jan 11.

Section of Inflammation and Cardiometabolic Diseases and.

Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12-/+/Srb1-/-/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis.
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http://dx.doi.org/10.1172/jci.insight.97179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5821196PMC
January 2018

Visceral Adiposity in Psoriasis is Associated With Vascular Inflammation by F-Fluorodeoxyglucose Positron-Emission Tomography/Computed Tomography Beyond Cardiometabolic Disease Risk Factors in an Observational Cohort Study.

JACC Cardiovasc Imaging 2018 02 18;11(2 Pt 2):349-357. Epub 2017 Oct 18.

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Electronic address:

Objectives: The authors sought to examine the relationship between visceral adipose tissue (VAT) and vascular inflammation (VI) by F-Fluorodeoxyglucose (F-FDG) positron-emission tomography (PET)/computed tomography (CT) in psoriasis (PSO). Furthermore, we evaluated whether treatment of PSO modulated VAT and VI.

Background: PSO, a chronic inflammatory skin disease, is associated with VI by F-FDG PET/CT and increased cardiometabolic risk including adipose tissue dysregulation. Recently, VI was associated with future cardiovascular events; however, the relationship of visceral and subcutaneous adiposity with VI in PSO has yet to be evaluated.

Methods: Consecutive PSO patients (N = 77) underwent F-FDG PET/CT scans to measure VI and abdominal adiposity. A subset of PSO patients with severe skin disease was scanned at 1 year following PSO treatment (N = 13).

Results: The cohort was middle aged (51.8 ± 12.6 years), predominantly male (n = 44, 57%), had low cardiovascular risk by Framingham 10-year risk (median 4 years [interquartile range (IQR): 2 to 7 years]), and mild-to-moderate skin disease (5.2 [IQR: 3.0 to 8.5]). PSO disease severity associated with VAT (β = 0.33; p = 0.004) beyond SAT (β = 0.30; p = 0.005). VAT (β = 0.55; p < 0.001), but not SAT (β = 0.15; p = 0.11), associated with VI beyond cardiovascular risk factors. We followed a subset of severe PSO patients treated aggressively for PSO and observed improvement in PSO severity and VAT, which was associated with an improvement in VI at 1 year beyond cardiovascular risk factors (β = 0.53; p = 0.049).

Conclusions: Volume-based CT measurement of VAT may capture metabolic risk associated with VI compared to subcutaneous adipose tissue in PSO. PSO treatment associated with a decrease in VAT as well as decrease in VI suggesting VAT as a relevant biomarker related to VI in PSO.
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http://dx.doi.org/10.1016/j.jcmg.2017.08.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5803350PMC
February 2018

Association Between Skin and Aortic Vascular Inflammation in Patients With Psoriasis: A Case-Cohort Study Using Positron Emission Tomography/Computed Tomography.

JAMA Cardiol 2017 09;2(9):1013-1018

National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland.

Importance: 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.

Objective: 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.

Design, Setting, And Participants: 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.

Exposure: Skin inflammation measured as Psoriasis Area and Severity Index (PASI) score.

Main Outcomes And Measures: Vascular inflammation assessed as target-to-background ratio by 18fluorodeoxyglucose positron emission tomography/computed tomography.

Results: 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).

Conclusions And Relevance: 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.
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http://dx.doi.org/10.1001/jamacardio.2017.1213DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5815046PMC
September 2017

Coronary Plaque Characterization in Psoriasis Reveals High-Risk Features That Improve After Treatment in a Prospective Observational Study.

Circulation 2017 Jul 8;136(3):263-276. Epub 2017 May 8.

From National Institutes of Health, National Heart, Lung, and Blood Institute, Bethesda, MD (J.B.L., A.A.J., A.C., T.M.A., A.K.D., J.A.R., T.S., J.H.C., A.R., H.L.T., M.P.P., M.Y.C., V.S., D.A.B., N.N.M.); Department of Dermatology, Kaiser Permanente Los Angeles Medical Center, CA (J.J.W.); and DermAssociates, Silver Spring, MD (B.A.L.).

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 (<30 hounsfield units), positive remodeling (>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, =0.02) and similar HRP prevalence (=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, =0.001), NCB (1.18±0.33 versus 1.03±0.21, =0.004), and HRP prevalence beyond traditional risk (odds ratio, 6.0; 95% confidence interval, 1.1-31.7; =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; <0.001) and NCB (β=0.53, 0.32-0.74; <0.001) beyond traditional risk factors.

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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.026859DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534138PMC
July 2017

GlycA Is a Novel Biomarker of Inflammation and Subclinical Cardiovascular Disease in Psoriasis.

Circ Res 2016 Nov 21;119(11):1242-1253. Epub 2016 Sep 21.

From the Cardiovascular and Pulmonary Branch (A.A.J., J.B.L., T.M.A., H.L.T., J.A.R., Q.N., T.Z.A., T.S., B.N., M.Y.C., A.T.R., D.A.B., M.P.P., N.N.M.), Section of Inflammation and Cardiometabolic Diseases (A.A.J., J.B.L., T.M.A., H.L.T., J.A.R., Q.N., T.Z.A., T.S., B.N., A.T.R., M.P.P., N.N.M.), National Heart, Lung, and Blood Institute, Bethesda, MD; Department of Internal Medicine, Allegheny General Hospital, Pittsburgh, PA (A.A.J.); Department of Medicine, McGill University, Montreal, QC, Canada (M.A.); Department of Cardiology, Einstein Institute for Heart and Vascular Health, Albert Einstein Medical Center, Philadelphia, PA (P.K.); Department of Internal Medicine, University of Colorado, Denver (T.S.); Department of Internal Medicine, University of Arizona College of Medicine at South Campus, Tucson (B.N.); Derm Associates, Silver Spring, MD (B.N.L.); Department of Radiology and Imaging Sciences, National Institutes of Health Clinical Research Center, Bethesda, MD (M.A.A.); Perelman School of Medicine (D.J.R.), Department of Dermatology (J.M.G.), and The Center for Clinical Epidemiology and Biostatistics (J.M.G.), University of Pennsylvania, Philadelphia; and Division of Cardiology, Department of Medicine, Irving Institute for Clinical and Translational Research, Columbia University, New York (M.P.R.).

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<0.0001; NIH: 415.8±63.2 versus 346.2±46, P<0.0001]) and demonstrated a dose-response with psoriasis severity. In stage 2, VI (β=0.36, P<0.001) and coronary artery disease (β=0.29, 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<0.01). Finally, initiating anti-tumor necrosis factor therapy (n=16) reduced psoriasis severity (P<0.001), GlycA (463.7±92.5 versus 370.1±78.5, P<0.001) and VI (1.93±0.36 versus 1.76±0.19, P<0.001), whereas GlycA remained associated with VI (β=0.56, P<0.001) post treatment.

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.
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http://dx.doi.org/10.1161/CIRCRESAHA.116.309637DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215065PMC
November 2016

Self-reported depression in psoriasis is associated with subclinical vascular diseases.

Atherosclerosis 2016 08 27;251:219-225. Epub 2016 May 27.

National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA. Electronic address:

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.
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http://dx.doi.org/10.1016/j.atherosclerosis.2016.05.043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5305805PMC
August 2016
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