Circulating Chemerin Is Associated With Carotid Plaque Instability, Whereas Resistin Is Related to Cerebrovascular Symptomatology.
The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology.



Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594).



Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
Karina
K
Gasbarrino
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
Christos
C
Mantzoros
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
Jessica
J
Gorgui
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
John P
JP
Veinot
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
Chi
C
Lai
From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.). stella.daskalopoulou@mcgill.ca.
Stella S
SS
Daskalopoulou
D052242:Adiponectin / Q000097:blood; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016893:Carotid Stenosis / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000601:surgery; D002561:Cerebrovascular Disorders / Q000175:diagnosis / Q000209:etiology*; D018925:Chemokines / Q000097:blood*; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D020738:Leptin / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016017:Odds Ratio; D058226:Plaque, Atherosclerotic; D011237:Predictive Value of Tests; D011379:Prognosis; D052243:Resistin / Q000097:blood*; D018570:Risk Assessment; D012307:Risk Factors; D012422:Rupture, Spontaneous; D012720:Severity of Illness Index
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; C478630:RARRES2 protein, human; C499624:RETN protein, human; D052243:Resistin
adiponectin; carotid plaque instability; cerebrovascular symptomatology; chemerin; leptin; resistin