Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention.
BACKGROUND
High levels of the soluble fragment of CD40 ligand (sCD40L) have previously been associated with adverse cardiovascular outcomes. CD40L-CD40 interaction has been linked to the pathogenesis of atherothrombotic complications in cardiovascular disease (CVD). We sought to determine whether a "package of care" of intensified multifactorial cardiovascular risk intervention could reduce indices of platelet activation, inflammation, and coagulation in diabetes and whether patients with overt CVD would derive similar benefit compared with those without.


RESULTS
We measured plasma sCD40L, soluble P-selectin (sP-sel, an index of platelet activation), interleukin-6 (IL-6, a proinflammatory cytokine), and tissue factor (TF, an initiator of coagulation) in 97 patients with diabetes mellitus (41 with and 56 without overt CVD) and 39 comparable healthy control subjects. Thirty-six patients with and 32 without overt CVD then participated in a package of care of cardiovascular risk intervention over a period of 1 year. Plasma levels of sCD40L (P<0.001), sP-sel (P<0.001), IL-6 (P=0.001), and TF (P<0.001) were higher in patients with diabetes than in control subjects, with TF levels highest in patients with overt CVD. Multifactorial intervention was associated with significant reductions in sCD40L in both patient groups (both P<0.001), but reductions in sP-sel and TF were seen only in patients without overt CVD. There was no significant change in IL-6 levels in both patient groups.


CONCLUSIONS
Intensive multifactorial risk management can reduce high levels of sCD40L but can only partially correct abnormal platelet activation, inflammation, and coagulation in diabetes, particularly in patients with overt CVD.
Lim
Hoong Sern
HS
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Dudley Road, Birmingham, B18 7QH, England, UK.
Blann
Andrew D
AD
Lip
Gregory Y H
GY
D000368:Aged; D001241:Aspirin / Q000627:therapeutic use; D015415:Biomarkers; D001777:Blood Coagulation; D023201:CD40 Ligand / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology; D015331:Cohort Studies; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood*; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D012308:Risk Management; D013925:Thromboplastin / Q000032:analysis*
D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D015850:Interleukin-6; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D023201:CD40 Ligand; D013925:Thromboplastin; D001241:Aspirin