Relationship of serum inflammatory biomarkers with plaque inflammation assessed by FDG PET/CT: the dal-PLAQUE study

Abstract

Objectives: This study sought to longitudinally investigate the relationship between a broad spectrum of serum inflammatory biomarkers and plaque inflammation assessed by (18)F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT).

Background: Both plaque inflammation and serum biomarkers of inflammation are associated with atherothrombotic events; however, the relationship between them is unclear.

Methods: We conducted a post hoc analysis of the dal-PLAQUE (A Randomized Placebo-Controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors), a randomized, placebo-controlled study of dalcetrapib, a cholesteryl ester transfer protein inhibitor, in 130 patients with coronary heart disease, or coronary heart disease risk equivalents on stable lipid-lowering therapy. Baseline and change after 3-month follow-up in inflammatory biomarker levels and baseline and change after 3-month follow-up in aorta and carotid (18)F-FDG PET/CT (mean maximum target-to-background ratio of the most diseased segment [TBRmds]) were analyzed.

Results: Baseline myeloperoxidase positively correlated with baseline carotid TBRmds (rho = 0.25, p = 0.02). This correlation remained at the 3-month follow-up and was independent of traditional cardiovascular disease risk factors. Baseline lipoprotein-associated phospholipase A2 mass correlated with aorta TBRmds (rho = 0.21, p = 0.03). However, this correlation disappeared at the 3-month follow-up and was not independent of cardiovascular disease risk factors. There was no association between change from baseline in myeloperoxidase or lipoprotein-associated phospholipase A2 mass and change from baseline in aorta and carotid TBRmds. Baseline and change from baseline in high sensitivity C-reactive protein, interleukin 6, soluble P-selectin, soluble E-selectin, soluble intracellular adhesion molecule 1, soluble vascular cell adhesion molecule 1, and matrix-metalloproteinase 3 and 9 did not correlate with baseline or change from baseline in carotid or aorta TBRmds.

Conclusions: Our data show that, in patients with coronary heart disease or at high risk of coronary heart disease on stable lipid-lowering therapy, circulating myeloperoxidase levels are associated with carotid plaque inflammation. (A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease [CHD] Including Patients With Other CHD Risk Factors [dal-PLAQUE]; NCT00655473).

Keywords: (18)F-FDG PET/CT; IL-6; Lp-PLA(2); MMP; MPO; TBR(mds); atherosclerosis; fluorodeoxyglucose F 18 positron emission tomography; fluorodeoxyglucose F 18 positron emission tomography/computed tomography; high-sensitivity C-reactive protein; hsCRP; inflammatory biomarkers; interleukin 6; lipoprotein-associated phospholipase A(2); matrix metalloproteinase; myeloperoxidase; sE-selectin; sICAM; sP-selectin; sVCAM; soluble E-selectin; soluble P-selectin; soluble intracellular adhesion molecule; soluble vascular cell adhesion molecule; target-to-background ratio of the most diseased segment.

Conflict of interest statement

Conflict of Interest Disclosures: RD has nothing to disclose. VM receives consulting fees from Tursiop Inc. MW received honoraria from F. Hoffmann-La Roche Ltd. DK and GS are employees of F. Hoffmann-La Roche Ltd. VF has nothing to disclose. JHFR received honoraria from F. Hoffmann-La Roche Ltd. AT received honoraria from F. Hoffmann-La Roche Ltd, Bristol-Myers Squibb and Novartis, and research grants from Merck, Bristol-Myers Squibb, Genentech, GlaxoSmithKline and VBL Therapeutics. MEF received honoraria from F. Hoffmann-La Roche Ltd and acted as a consultant to Genentech. ZAF received research grants from F. Hoffmann-La Roche Ltd, GlaxoSmithKline, Merck, VBL Therapeutics, Novartis, Bristol-Myers Squibb, and Via Pharmaceuticals, and honoraria from F. Hoffmann-La Roche Ltd. F. Hoffmann-La Roche Ltd funded the dal-PLAQUE study and provided third-party editorial support through Prime Healthcare for the preparation of the manuscript.

Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. Carotid TBRmds Values at Baseline and 3 Months’ Follow-Up for Baseline MPO Quartiles

Higher baseline MPO values were associated with higher baseline carotid TBRmds values, and this relation remained present at 3 months’ follow-up. p-values are for the comparison between the lowest and highest quartiles. Adj P = p-values adjusted for age, gender, body mass index, low density lipoprotein cholesterol, high density lipoprotein cholesterol, hypertension, diabetes mellitus, history of coronary heart disease, and current smoking; MPO = myeloperoxidase; TBRmds = mean maximum most diseased segment target-to-background ratio.

Figure 2. Aortic TBRmds Values at Baseline and 3 Months’ Follow-Up for Baseline Lp-PLA2 Mass Quartiles

Although there is a trend towards higher baseline aorta TBRmds in higher baseline Lp-PLA2 mass quartiles, this relation is not independent of other risk factors and the relation disappears after 3 months’ follow up. p-values are for the comparison between the lowest and highest quartiles. Adj P = p-values adjusted for age, gender, body mass index, low density lipoprotein cholesterol, high density lipoprotein cholesterol, hypertension, diabetes mellitus, history of coronary heart disease, and current smoking; Lp-PLA2 = lipoprotein-associated phospholipase A2; TBRmds = mean maximum most diseased segment target-to-background ratio.