Alexander V Sorokin1, Kazuhiko Kotani2, Youssef A Elnabawi1, Amit K Dey1, Aparna P Sajja1, Shingo Yamada3, Masashi Ueda4, Charlotte L Harrington1, Yvonne Baumer1, Justin A Rodante1, Joel M Gelfand5,6, Marcus Y Chen1, Aditya A Joshi1, Martin P Playford1, Alan T Remaley7, Nehal N Mehta1. 1. 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. 2. Department of Clinical Laboratory Medicine, Jichi Medical University, Shimotsuke-City, Tochigi, Japan (K.K.). 3. Shino-Test Corporation, Sagamihara, Japan (S.Y.). 4. Hokenkagaku-West, Co, Ltd, Kyoto-City, Japan (M.U.). 5. Department of Dermatology, Perelman School of Medicine (J.M.G.). 6. Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia (J.M.G.). 7. Section of Lipoprotein Metabolism, Translational Vascular Medicine Branch (A.T.R.), National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
Abstract
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.
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.
Authors: Charlotte L Harrington; Amit K Dey; Raza Yunus; Aditya A Joshi; Nehal N Mehta Journal: Am J Physiol Heart Circ Physiol Date: 2017-03-03 Impact factor: 4.733
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Authors: Amit K Dey; Ranjitha Gaddipati; Youssef A Elnabawi; Emily Ongstad; Aditya Goyal; Jonathan H Chung; Heather L Teague; Justin A Rodante; Aparna A Sajja; Alexander V Sorokin; Sundus S Lateef; Milena Aksentijevich; Harry Choi; Aarthi S Reddy; Nevin J Varghese; Jacob Groenendyk; Agastya D Belur; Leonard Genovese; Joshua P Rivers; Joseph Lerman; Mohammad Tarek Kabbany; Charlotte Harrington; Jenis Ortiz; Noor Khalil; Andrew Keel; Yvonne Baumer; Marcus Y Chen; David A Bluemke; Aditya A Joshi; Mariana J Kaplan; Alan T Remaley; Martin P Playford; Sotirios K Karathanasis; Joel M Gelfand; Ruchi Gupta; Nehal N Mehta Journal: JAMA Dermatol Date: 2020-02-01 Impact factor: 10.282
Authors: Milena Aksentijevich; Sundus S Lateef; Paula Anzenberg; Amit K Dey; Nehal N Mehta Journal: Trends Cardiovasc Med Date: 2019-11-20 Impact factor: 6.677
Authors: Di Yan; Andrew Blauvelt; Amit K Dey; Rachel S Golpanian; Samuel T Hwang; Nehal N Mehta; Bridget Myers; Zhen-Rui Shi; Gil Yosipovitch; Stacie Bell; Wilson Liao Journal: J Invest Dermatol Date: 2021-04-19 Impact factor: 7.590