Systemic Inflammation and Metabolic Syndrome in Cardiac Allograft Vasculopathy

Abstract

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). 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. 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. 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.