TY - JOUR
T1 - Discordant effects of rosiglitazone on novel inflammatory biomarkers
AU - Gada, Elan
AU - Owens, Andrew W.
AU - Gore, M. Odette
AU - See, Raphael
AU - Abdullah, Shuaib M
AU - Ayers, Colby R.
AU - Rohatgi, Anand K
AU - Khera, Amit
AU - de Lemos, James A
AU - McGuire, Darren K
N1 - Funding Information:
Grant support was provided by GlaxoSmithKline; Biosite, Inc. ; and the Donald W. Reynolds Foundation and supported in part by grant UL1TR000451 from the National Center for Advancing Translational Sciences, National Institutes of Health . The authors are solely responsible for the design and conduct of this study, all study analyses, the drafting and editing of the manuscript, and its final contents.
Funding Information:
Dr de Lemos has received significant grant support from Biosite, Roche Diagnostics, and Abbott Labs and modest consulting fees from Biosite and Tethys-Bioscience. Dr McGuire has received significant grant support from Biosite and GlaxoSmithKline; significant research support from Merck, AstraZeneca, Eli Lilly, Bristol Myers Squibb, Takeda, Orexigen, Boehringer Ingelheim, Daiichi Sankyo, F. Hoffmann LaRoche, and Genentech; and modest consulting fees from Regeneron, Sanofi Aventis, Genentech, F. Hoffmann LaRoche, Daiichi Sankyo, Tethys-Bioscience, Boehringer Ingelheim, and Janssen.
PY - 2013/4
Y1 - 2013/4
N2 - Background Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). Methods Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. Results Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P =.002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P =.01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P =.02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P =.003) and hs-CRP (0.42 vs 0.31 ng/mL, P =.02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P =.046). Conclusion Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.
AB - Background Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin β receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). Methods Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. Results Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin β receptor (1.7 vs 2.4 ng/mL, P =.002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P =.01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P =.02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P =.003) and hs-CRP (0.42 vs 0.31 ng/mL, P =.02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P =.046). Conclusion Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.
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U2 - 10.1016/j.ahj.2013.01.006
DO - 10.1016/j.ahj.2013.01.006
M3 - Article
C2 - 23537979
AN - SCOPUS:84875476553
SN - 0002-8703
VL - 165
SP - 609
EP - 614
JO - American heart journal
JF - American heart journal
IS - 4
ER -