PMID- 17403721
OWN - NLM
STAT- MEDLINE
DCOM- 20071207
LR  - 20220409
IS  - 0195-668X (Print)
IS  - 0195-668X (Linking)
VI  - 28
IP  - 7
DP  - 2007 Apr
TI  - Synergistic relationship between hyperglycaemia and inflammation with respect to 
      clinical outcomes in non-ST-elevation acute coronary syndromes: analyses from 
      OPUS-TIMI 16 and TACTICS-TIMI 18.
PG  - 806-13
AB  - AIMS: To investigate the relationship between diabetes and inflammation and the 
      potentially synergistic relationship between hyperglycaemia and inflammation on 
      clinical outcomes in non ST-elevation ACS. METHODS AND RESULTS: The principal 
      analysis was conducted in 2200 patients in OPUS-TIMI 16 with C-reactive protein 
      data available and then validated in the invasive arm of TACTICS-TIMI 18 (n = 
      929). In addition, two further inflammatory markers [monocyte chemoattractant 
      protein-1 (MCP-1) and von Willebrand factor (vWF)] were assessed in OPUS-TIMI 16. 
      Diabetic patients had higher C-reactive protein and MCP-1 levels vs. non-diabetic 
      patients in OPUS-TIMI 16 (9 vs. 7.8 mg/L, P = 0.002, and 190.6 vs. 170.8 pg/mL, P 
      = 0.04, respectively), higher C-reactive protein levels in TACTICS-TIMI 18 (6.6 
      vs. 5.2 mg/L, P = 0.0005), and as expected higher glucose levels in both trials. 
      Stratifying by the median C-reactive protein and diabetes in OPUS-TIMI 16, 
      diabetic patients with C-reactive protein greater than or equal to the median 
      were the highest risk group vs. non-diabetic patients with C-reactive protein 
      less than the median (adjusted HR 1.63, 95% CI 1.20-2.23, P = 0.002). 
      Directionally, similar findings were observed for MCP-1 and vWF in OPUS-TIMI 16 
      and for C-reactive protein in TACTICS-TIMI 18. After adjustment for diabetes, the 
      risk associated with a 1 mmol/L increase in glucose was greater among those with 
      a C-reactive protein greater than or equal to the median (HR 1.07, 95% CI 
      1.03-1.11) vs. those with a C-reactive protein less than the median (HR 1.02, 95% 
      CI 0.97-1.06). After multivariable adjustment, the synergistic relationship 
      between glucose and C-reactive protein and clinical outcomes remained 
      statistically significant (P = 0.01). A similar pattern was observed in 
      TACTICS-TIMI 18. CONCLUSION: Among ACS patients, diabetes was associated with 
      both greater inflammation and higher glucose levels and patients with both 
      hyperglycaemia and inflammation had worse outcomes. Better control of both 
      inflammation and hyperglycaemia should be assessed in future ACS trials as a 
      means to reduce the cardiovascular risk among diabetics.
FAU - Ray, Kausik K
AU  - Ray KK
AD  - The TIMI Study Group and Cardiovascular Division, Department of Medicine, Brigham 
      and Women's Hospital, Harvard Medical School, 350 Longwood Avenue, Boston, MA 
      02115, USA.
FAU - Cannon, Christopher P
AU  - Cannon CP
FAU - Morrow, David A
AU  - Morrow DA
FAU - Kirtane, Ajay J
AU  - Kirtane AJ
FAU - Buros, Jacqueline
AU  - Buros J
FAU - Rifai, Nader
AU  - Rifai N
FAU - McCabe, Carolyn H
AU  - McCabe CH
FAU - Gibson, C Michael
AU  - Gibson CM
FAU - Braunwald, Eugene
AU  - Braunwald E
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070402
PL  - England
TA  - Eur Heart J
JT  - European heart journal
JID - 8006263
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Pyrrolidines)
RN  - 0 (von Willebrand Factor)
RN  - 9007-41-4 (C-Reactive Protein)
RN  - FGJ53JS7PT (orbofiban)
RN  - OF5P57N2ZX (Alanine)
SB  - IM
MH  - Aged
MH  - Alanine/therapeutic use
MH  - Biomarkers/metabolism
MH  - Blood Glucose/metabolism
MH  - C-Reactive Protein/metabolism
MH  - Chemokine CCL2/metabolism
MH  - Diabetic Angiopathies/drug therapy/*etiology/metabolism
MH  - Female
MH  - Humans
MH  - Hyperglycemia/*complications/drug therapy/metabolism
MH  - Hypoglycemic Agents/therapeutic use
MH  - Male
MH  - Middle Aged
MH  - Myocardial Ischemia/*etiology/metabolism
MH  - Myocarditis/*complications/metabolism
MH  - Pyrrolidines/therapeutic use
MH  - von Willebrand Factor/metabolism
EDAT- 2007/04/04 09:00
MHDA- 2007/12/08 09:00
CRDT- 2007/04/04 09:00
PHST- 2007/04/04 09:00 [pubmed]
PHST- 2007/12/08 09:00 [medline]
PHST- 2007/04/04 09:00 [entrez]
AID - ehm010 [pii]
AID - 10.1093/eurheartj/ehm010 [doi]
PST - ppublish
SO  - Eur Heart J. 2007 Apr;28(7):806-13. doi: 10.1093/eurheartj/ehm010. Epub 2007 Apr 
      2.