Depression and Subclinical Vascular Diseases in Psoriasis

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1 Depression and Subclinical Vascular Diseases in Psoriasis Nehal N. Mehta, MD MSCE FAHA Section Chief, Inflammation and Cardiometabolic Diseases National Heart, Lung, and Blood Institute, USA Lasker Clinical Scholar Investigator National Institutes of Health, USA Clinical Professor of Medicine

2 Case Review: History 44 previously healthy female with psoriasis for 5 years cardiovascular evaluation Self-referred Been feeling down and slow recently

3 Case Review: History PMH: untreated psoriasis Medications: none Fhx: none SHx: + tobacco of about ½ PPD ROS: no complaints

4 Case Review: Examination VS: 144/89; 84 bpm (reg); 96%; height: 61 inches; weight: 214lbsàBMI 32 waist: 36 inches; hip: 35 inchesà WHR ~1.0 Neck: JVP at 6 cm H 2 0, no carotid bruits Lungs: clear bilaterally CV: RRR, normal S1/S2, no murmurs, rubs or gallops Abd: No HSM or pulsatile liver Ext: No edema bilateral lower extremities Vascular: Pulses 2+ in both UE and LE Skin: plaque psoriasis on trunk, elbows, knees and scalp; estimated ~9% BSA

5 Case Review: Laboratory Data Lipids: TC: 186 (4.8 mmol/l) LDL: 129 (3.6 mmol/l) TG s: 144 (4.4 mmol/l) HDL: 45 (1.14 mmol/l) Chemistry: Fasting Glc 106 (2.8 mmol/l)

6 Case Summary 44 female with untreated moderate psoriasis + tobacco use + high blood pressure BMI of 32 (obese) feeling down consistent with possible depression

7 What about inflammation associated with her psoriasis?

8 Inflammation matters in CV Disease Libby, P and Ridker P. Am J of Medicine (6) 9-16.

9 Inflammation: critical in atherosclerosis 1 & Messenger Inflamm. Chemokines IL-1 TNF-a IL-6 IL-18 MCP-1 Cellular Adhesion Molecules sicam svcam sselectins sesam Acute (& chronic) Phase Reactants hs-crp, SAA, Lp-PLA2, WBC Plaque Destabilization MMPs IL-18 MPO Plaque Rupture CD40L Endothelial Fxn EPCs Stary, et al. Circulation. 1995;92:

10 CV Disease in Psoriasis Severe Psoriasis 50% increased risk of mortality 5 years of life lost Outcome Hazard Ratio (adjusted for CV risk factors) MI Stroke CV Death MACE Figure. Abuabara K, et al. Br J Dermatol Sep;163(3): Gelfand, JM et al. JAMA. 2006;296: Gelfand, JM et al. J Invest Dermatol.2009; 129: Mehta, NN et al. Eur Heart J. 2010;31: Mehta, NN et al. Am Journal Of Medicine. 2011; 776: 1-7.

11 Key Immune Factors in Psoriasis Initiation Perpetuation Natural killer T cell Plasmacytoid dendritic cell Keratinocyte TNF-α IFN-γ IFN-α Macrophage TNF-α IL-1β IL-6 TNF-α Activation Myeloid dendritic cell IL-12 IL-23 Modified from: Nestle FO, et al. N Engl J Med 2009;361: Th1 cell Th17 cell TNF-α IFN-γ Keratinocyte IL-17A IL-17F IL-22 Hypothetical model based in part on non-clinical data Antimicrobial peptides IL-1β IL-6 TNF-α S100 CXCL8 CXCL9 CXCL10 CXCL11 CCL20

12 Cell mediated inflammation drives CVDSlide courtesy of James DeLemos, MD Lumen Area of detail Lipid core Fibrous cap Media Vulnerable Plaque Lumen Lipid core T lymphocyte Macrophage foam cell (tissue factor + ) Stable Plaque Activated intimal SMC (HLA-DR + ) Normal medial SMC Libby. Circulation. 1995;91:

13 What about inflammation associated with her psoriasis? What about her mood and feeling slow?

14 Depression and Anxiety in Psoriasis Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM, Archives of Dermatology, 2010

15 Depression and Anxiety in Psoriasis Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM, Archives of Dermatology, 2010

16 MI, Stroke and CV Death are increased in acute depression in psoriasis Egeberg, A. Acta Derm Venereol Feb;96(2):218-21

17 Linking Psoriasis and Mood Disorders Connor CJ, Liu V, Fiedorowicz JG. Dermatology Research and Practice, 2015

18 Conceptual Framework Depression/Anxiety Psoriasis IL-1β, IL-2, IL-6, TNF-α, PGE2, CRP Inflammation IL-6, TNF-α, GM-CSF, IL-17 Cardiovascular Disease

19 Can we utilize subclinical vascular diseases to understand this relationship?

20 Vascular imaging in psoriasis: How do we approach it? CT Coronary Angiography (CCTA) Estimates direct coronary artery plaque burden FDG PET-CT & FDG PET-MR Estimates inflammatory burden and functional consequences

21 FDG PET/CT A Novel Biomarker 18-Fluorodeoxyglucose (FDG) is taken up by cells in proportion to their metabolic activity Biomarker for macrophages in early atherosclerotic plaques recent dataàsmoothmuscle or endothelial cells Visualizes and quantifies vascular inflammation in vivo as Standardized Uptake Value (SUV) Demonstrates functional and anatomical data

22 FDG PET CT Image Quantification:

23 Vascular Inflammation Associates with Future CVD Events in Non-Psoriasis Figueroa et al JACC Imaging 2013

24 Coronary Computed Tomography Angiography (CCTA) Axial images and 3D rendering diagonal branches Video provided by: Karen Rodriguez, Dr. David Bluemke

25 CCTA Analytical Approach Total Volume Lumen Volume - = Plaque Volume Plaque volume = (Artery volume) (Lumen volume) Plaque Index = Sum of all plaque volumes of segment Length of segment

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27 Study Design Cross-sectional, observational; nested cohort study Hypothesis: Subclinical atherosclerosis, as measured by FDG PET/CT and CCTA, will be increased in patients with psoriasis and comorbid depression and/or anxiety as compared to patients with psoriasis alone.

28 Methods 1 patient randomly dropped 40 PSO patients with reported comorbid depression and/or anxiety 159 patients prospectively enrolled in cohort study 41 patients reported history of depression or anxiety on baseline survey 40 PSO patients reporting no history of comorbid psychiatric illness matched by age and sex

29 Study Sample

30 Self-reported depression increases vascular inflammation in psoriasis Aberra, T from Mehta Lab NHLBI. Atherosclerosis Aug;251:

31 Self-reported depression is associated with higher coronary plaque burden Aberra, T from Mehta Lab NHLBI. Atherosclerosis Aug;251:

32 Non-calcified plaque à acute myocardial infarction

33 Limitations/Future Directions Sample size Cross-sectional Limited characterization of psychiatric diagnoses Mechanism??

34 Conclusions Self reported depression in psoriasis was associated with increased vascular diseases. Better risk stratification of psoriasis patients by understanding the impact of psychiatric illness on early CV disease may be warranted. Early identification and intervention may contribute to reducing the burden of cardiovascular diseases.

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