title: Emerging Cardiovascular Disease Biomarkers and Incident Diabetes Mellitus Risk in Statin-Treated Patients With Coronary Artery Disease (from the Treating to New Targets [TNT] Study).
abstract: Whether biomarkers associated with cardiovascular disease risk also predict incident diabetes mellitus (DM) is unknown. Our objective was to determine if a panel of 18 biomarkers previously associated with risk of cardiovascular disease also predicts incident DM in statin-treated patients with coronary artery disease (CAD). The Treating to New Targets (TNT) study is a randomized trial that compared the efficacy of high (80 mg) versus low (10 mg) dose atorvastatin for the secondary prevention of coronary heart disease events. Fasting plasma levels of standard lipids and of 18 emerging CAD risk biomarkers were obtained after an 8-week run-in period on atorvastatin 10 mg in a random sample of 1,424 TNT patients. After exclusion of patients with DM at baseline (n = 253), 101 patients developed DM during the median follow-up of 4.9 years. Patients with incident DM had lower levels of total and high-molecular weight adiponectin, lipoprotein-associated phospholipase A2 (Lp-PLA2), soluble receptor of advanced glycation end products, and vitamin D compared with patients without incident DM. In contrast, insulin, soluble CD40 ligand, and soluble intercellular adhesion molecule-1 levels were higher in patients with incident DM compared with those without. Plasma levels of C-reactive protein, cystatin C, lipoprotein(a), monocyte chemotactic protein-1, matrix metalloproteinase-9, myeloperoxidase, neopterin, N-terminal fragment of pro-B-type natriuretic peptide, osteopontin, and soluble vascular cell adhesion molecule-1 were comparable in patients with and without incident DM. After multivariate adjustment, total and high-molecular weight adiponectin as well as Lp-PLA2 were negatively associated with incident DM. Results of this study suggest that plasma lipids and some emerging CAD risk biomarkers, such as adiponectin and Lp-PLA2, may be useful for predicting incident DM in statin-treated patients with stable CAD.
authors.affiliation: Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada; Département de médicine, Faculté de medicine, Université Laval, Québec, Canada. Electronic address: benoit.arsenault@criucpq.ulaval.ca.
authors.forename: Benoit J
authors.initials: BJ
authors.lastname: Arsenault
authors.affiliation: Division of Cardiology, University of California, San Francisco, San Francisco, California.
authors.forename: Payal
authors.initials: P
authors.lastname: Kohli
authors.affiliation: Laboratoire Inserm U1188, Université de la Réunion, Sainte-Clotilde, France.
authors.forename: Gilles
authors.initials: G
authors.lastname: Lambert
authors.affiliation: Pfizer, New York, New York.
authors.forename: David A
authors.initials: DA
authors.lastname: DeMicco
authors.affiliation: Pfizer, New York, New York.
authors.forename: Rachel
authors.initials: R
authors.lastname: Laskey
authors.affiliation: Pfizer, New York, New York.
authors.forename: Michael M
authors.initials: MM
authors.lastname: Messig
authors.affiliation: Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: John J P
authors.initials: JJ
authors.lastname: Kastelein
authors.affiliation: Division of Cardiology, University of California, San Francisco, San Francisco, California.
authors.forename: David D
authors.initials: DD
authors.lastname: Waters
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000097:blood; D052242:Adiponectin / Q000097:blood; D000368:Aged; D000069059:Atorvastatin / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D023201:CD40 Ligand / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood; D018932:Chemokine CCL2 / Q000097:blood; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D055316:Cystatin C / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D007328:Insulin / Q000097:blood; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D015999:Multivariate Analysis; D020097:Natriuretic Peptide, Brain / Q000097:blood; D019798:Neopterin / Q000097:blood; D053495:Osteopontin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D009195:Peroxidase / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood; D012307:Risk Factors; D055502:Secondary Prevention; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D014807:Vitamin D / Q000097:blood
chemical_list: C499918:ADIPOQ protein, human; C000593871:AGER protein, human; D052242:Adiponectin; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D055316:Cystatin C; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C573420:ICAM1 protein, human; D007328:Insulin; D017270:Lipoprotein(a); D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D019010:Vascular Cell Adhesion Molecule-1; C109794:pro-brain natriuretic peptide (1-76); D053495:Osteopontin; D020097:Natriuretic Peptide, Brain; D018799:Intercellular Adhesion Molecule-1; D014807:Vitamin D; D023201:CD40 Ligand; D019798:Neopterin; D002097:C-Reactive Protein; D000069059:Atorvastatin; D009195:Peroxidase; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9