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

Aditya A Joshi; Joseph B Lerman; Tsion M Aberra; Mehdi Afshar; Heather L Teague; Justin A Rodante; Parasuram Krishnamoorthy; Qimin Ng; Tarek Z Aridi; Taufiq Salahuddin; Balaji Natarajan; Benjamin N Lockshin; Mark A Ahlman; Marcus Y Chen; Daniel J Rader; Muredach P Reilly; Alan T Remaley; David A Bluemke; Martin P Playford; Joel M Gelfand; Nehal N Mehta

doi:10.1161/CIRCRESAHA.116.309637

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

Circ Res. 2016 Nov 11;119(11):1242-1253. doi: 10.1161/CIRCRESAHA.116.309637. Epub 2016 Sep 21.

Authors

Aditya A Joshi¹, Joseph B Lerman¹, Tsion M Aberra¹, Mehdi Afshar¹, Heather L Teague¹, Justin A Rodante¹, Parasuram Krishnamoorthy¹, Qimin Ng¹, Tarek Z Aridi¹, Taufiq Salahuddin¹, Balaji Natarajan¹, Benjamin N Lockshin¹, Mark A Ahlman¹, Marcus Y Chen¹, Daniel J Rader¹, Muredach P Reilly¹, Alan T Remaley¹, David A Bluemke¹, Martin P Playford¹, Joel M Gelfand¹, Nehal N Mehta²

Affiliations

¹ 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.).
² 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.). nehal.mehta@nih.gov.

Abstract

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.

Keywords: cardiovascular disease; coronary artery disease; inflammation; psoriasis; risk factors.

MeSH terms

Adult
Biomarkers / blood
Cardiovascular Diseases / blood*
Cardiovascular Diseases / diagnosis*
Cardiovascular Diseases / epidemiology
Cohort Studies
Cross-Sectional Studies
Female
Humans
Inflammation / blood
Inflammation / diagnosis
Inflammation Mediators / blood*
Male
Middle Aged
Psoriasis / blood*
Psoriasis / diagnosis*
Psoriasis / epidemiology
Risk Factors

Substances

Biomarkers
Inflammation Mediators

Abstract

MeSH terms

Substances

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