Systemic inflammation and metabolic syndrome in cardiac allograft vasculopathy.
BACKGROUND
Metabolic syndrome and elevation of inflammatory markers is common in transplant recipients. We investigated the role of insulin resistance and C-reactive protein (CRP) in predicting development of angiographic cardiac allograft vasculopathy (CAV).


METHODS
CRP and lipid profile were measured in 114 cardiac transplant recipients at 4.7 +/- 3.1 years post-transplant. A triglyceride/high-density lipoprotein cholesterol (TG/HDL) ratio of >or=3 was considered a marker of insulin resistance. Ninety-seven patients (mean age +/- SD: 48.2 +/- 16.7 years) subsequently underwent routine coronary angiography at 8.6 +/- 3.2 years post-transplantation. Diagnosis of CAV required the presence of stenosis of >or=40% in any major branch, and/or distal pruning of secondary side branches. Coronary artery stenosis >or=70% was defined as severe.


RESULTS
Eighty-one percent of patients were treated with statins. Low-density lipoprotein (LDL)-cholesterol level was 98 +/- 26 mg/dl at study entry. CRP and TG/HDL were found to be predictors of development of CAV. CAV severity correlated with TG/HDL (p < 0.005), but not with CRP level. Freedom from CAV 5 years after study entry was 9% in patients with TG/HDL >3, CRP >3 mg/liter, as compared with 65% in patients with TG/HDL <3, CRP <3 mg/liter (p = 0.003). The combination of CRP >3 mg/liter and TG/HDL >3 identified a sub-group of patients having a 2.8-fold increased odds ratio for a combined end-point of cardiovascular (CV) events (percutaneous coronary intervention, coronary artery bypass graft, left ventricular ejection fraction <45%) and death (95% confidence interval 0.90 to 8.45, p = 0.07) compared to patients with CRP <3 mg/liter and TG/HDL <3.


CONCLUSIONS
CRP >3 mg/liter and TG/HDL >3 are cumulative risk factors for angiographic CAV and the combined end-point of CV events and death in transplant patients and these patients should be targeted for intervention.
Raichlin
Eugenia R
ER
Division of Cardiovascular Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
McConnell
Joseph P
JP
Lerman
Amir
A
Kremers
Walter K
WK
Edwards
Brooks S
BS
Kushwaha
Sudhir S
SS
Clavell
Alfredo L
AL
Rodeheffer
Richard J
RJ
Frantz
Robert P
RP
D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D016001:Confidence Intervals; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000209:etiology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000209:etiology*; D008875:Middle Aged; D016017:Odds Ratio; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D007328:Insulin; D014280:Triglycerides; D002097:C-Reactive Protein