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

Abstract

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.

Keywords: Adipose tissue; Atherosclerosis; Cardiology; Inflammation; Obesity.

Conflict of interest statement

Conflict of interest: NNM has served as a consultant for and received grants and/or other payments from Amgen, Lilly, and Leo Pharma and as a principal investigator and/or investigator for and received grants and/or research funding from AbbVie, Celgene, Janssen Pharmaceuticals Inc., and Novartis. JMG served as a consultant for and received honoraria from Bristol-Myers Squibb, Boehringer Ingelheim, Janssen Biologics, Novartis, UCB (DSMB), Sanofi, and Pfizer Inc.; receives research grants (to the Trustees of the University of Pennsylvania) from Abbvie, Boehringer Ingelheim, Janssen, Novartis, Celgene, Ortho Dermatologics, and Pfizer Inc.; and received payment for continuing medical education work related to psoriasis that was supported indirectly by Lilly, Ortho Dermatologics, and Novartis. JMG is a co–patent holder of resiquimod as for treatment of cutaneous T cell lymphoma (AU2014203896B2). JMG is a Deputy Editor for the Journal of Investigative Dermatology and receives honoraria from the Society for Investigative Dermatology.

Figures

Figure 1. Systemic effects of visceral adiposity in psoriasis.

(A) Psoriasis is associated with increased lipoprotein dysfunction, such as increased production of triglyceride-rich large VLDL particles. (B) High visceral adiposity is associated with greater systemic inflammation. (C) Furthermore, psoriasis is associated with traditional risk factors for atherosclerotic vascular disease. (D) Visceral adiposity increases cardiometabolic risk through associations with traditional risk factors, markers of lipid dysfunction, and systemic inflammation — contributing overall to increased noncalcified coronary artery burden, a marker of early coronary artery disease. CETP, cholesterylester transfer protein; CM, chylomicron; HDL, high density lipoprotein; HL, hepatic lipase; IDL, intermediate-density lipoprotein; LDL, low-density lipoprotein; LPL, lipoprotein lipase; TG, triglyceride; VLDL, very low-density lipoprotein.

Figure 2. Visceral adiposity and noncalcified coronary artery burden in psoriasis.

(A) Axial abdominal CT of a patient with psoriasis with high VAT volume (VAT, 32,767 cc3) for quantification of visceral (blue) and subcutaneous (red) adiposity. (B) CCTA showing the proximal left anterior descending artery (LAD) of the same patient, with the lumen (yellow) and the outer walls (orange) (LAD noncalcified coronary artery burden, 1.04 mm2) shown. (C) Axial abdominal CT of an age- and sex-matched patient with psoriasis with low VAT (VAT, 13,900 cc3) for quantification of visceral (blue) and subcutaneous (red) adiposity. (D) CCTA showing the LAD of the same patient, with the lumen (yellow) and the outer wall (orange) (LAD noncalcified coronary artery burden: 0.84 mm2) shown.

Figure 3. Relationship of visceral adiposity with lipid, metabolic, and inflammatory parameters.

Fitted regression plot with data scatter showing the relationship of visceral adiposity with (A) lipid (large VLDL particle number), (B) metabolic (homeostatic model assessment of insulin resistance [HOMA-IR]), and (C) inflammatory (GlycA) parameters in psoriasis. The shaded regions represent the lower and upper 95% CIs for the fitted regression plot.

Figure 4. Relationship of adiposity with noncalcified coronary plaque burden in psoriasis.

Fitted regression plot showing the relationship of (A) visceral, (B) subcutaneous, and (C) total adiposity with noncalcified coronary plaque burden. The shaded regions represent the lower and upper 95% CIs for the fitted regression plot.

Figure 5. Recruitment and follow-up scheme.

A total of 288 patients with psoriasis were examined at baseline. Of those, 237 consecutive psoriasis patients had quantitative data from CCTA scans at baseline. 176 patients were followed at 1 year and 50 were followed at 4 years.