Subclinical inflammation and prothrombotic state in heart transplant recipients: impact of cyclosporin microemulsion vs. tacrolimus.
BACKGROUND
Subclinical inflammation is related to adverse events in patients with coronary artery disease. In the present study, we determined the changes in hemostatic parameters and inflammatory markers in a large cohort of dyslipidemic cardiac transplant recipients compared with dyslipidemic healthy controls, and the effect of cyclosporin microemulsion (CsA) vs. tacrolimus immunoprophylaxis on these parameters.


METHODS
Stable cardiac transplant recipients (n=129) aged 56.7+/-10.1 years, 79+/-42 months postcardiac transplantation, and 26 mildly dyslipidemic healthy control subjects had serum measurements for lipids and lipoproteins, hemostatic parameters, and selected inflammatory markers. Transplant recipients were randomized to either continuation of CsA maintenance or conversion to tacrolimus immunoprophylaxis and were reassessed after six months.


RESULTS
CsA-maintained cardiac transplant recipients exhibited a significant elevation in Factor VIII, Von Willebrand factor, fibrinogen and PAI-I compared with healthy control subjects (all P<0.05). Similarly, cardiac transplant patients yielded a significantly elevated C-reactive protein (CRP) (4.11+/-6.25 [transplant group (TX)] vs. 2.09+/-2.21 mg/L [control group (CTL)]; P=0.0195), and homocysteine (19.2+/-8.8 [TX] vs. 9.70+/-2.45 microM [CTL]; P<0.001). VCAM, ICAM, E- and P-selectins were also significantly higher in transplant patients than in controls (all P<0.05). The conversion from CsA to tacrolimus resulted in a significant decrease in uric acid, total- and LDL-cholesterol, apolipoprotein B, creatinine, and homocysteine levels (all P<0.05).


CONCLUSIONS
Stable long-term CsA-maintained cardiac transplant patients exhibit a significant and general increase in hemostatic parameters and markers for subclinical inflammation. Tacrolimus conversion improved the patient lipid profile and decreased serum creatinine, uric acid, and homocysteine without any significant effect on the other markers.
White
Michel
M
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada. michel.white@icm-mhi.org
Ross
Heather
H
Haddad
Haissam
H
LeBlanc
Marie-Hélène
MH
Racine
Normand
N
Pflugfelder
Peter
P
Giannetti
Nadia
N
Davies
Ross
R
Azevedo
Eduardo
E
Isaac
Debra
D
Burton
Jeffrey
J
Ferguson
Ralph
R
Genest
Jacques
J
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002097:C-Reactive Protein / Q000032:analysis; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000453:epidemiology; D004655:Emulsions; D016027:Heart Transplantation / Q000276:immunology*; D006487:Hemostasis; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation / Q000453:epidemiology*; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology; D016559:Tacrolimus / Q000627:therapeutic use*; D013927:Thrombosis / Q000453:epidemiology*
D015415:Biomarkers; D004655:Emulsions; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D002097:C-Reactive Protein; D016559:Tacrolimus