Interplay between systemic inflammation and markers of insulin resistance in cardiovascular prognosis after heart transplantation.
BACKGROUND
Metabolic and immuno-inflammatory risk factors contribute to cardiac allograft vasculopathy (CAV) pathogenesis. Although systemic inflammation, as detected by C-reactive protein (CRP), predicts CAV development, the relationship between CRP and markers of metabolic abnormalities remains unexplored.


METHODS
CRP and the entire metabolic panel were evaluated in 98 consecutive heart transplant recipients at the time of annual coronary angiography, 5.8 years after transplant (range, 1-12 years). A ratio of triglycerides (TG) to high-density lipoproteins (HDL) of 3.0 or more was considered a marker of insulin resistance. CAV prevalence was defined by angiography, and subsequent prognosis was evaluated as incidence of major cardiac adverse events.


RESULTS
CRP was higher in the 34 patients with angiographic CAV than in those without CAV (1.10 +/- 0.20 vs 0.50 +/- 0.05 mg/dl, p < 0.001). Patients with insulin resistance had higher CRP concentrations (p = 0.023) and higher CAV prevalence (p = 0.005). High CRP and a TG/HDL of 3.0 or more were independently associated with an increased likelihood of CAV (odds ratio, > or = 3.9; p = 0.02) and predicted an increased risk of major cardiac adverse events. The combination of high CRP and a TG/HDL of 3.0 or more identified a subgroup of patients having a 4-fold increased risk for CAV and a 3-fold increased risk for major cardiac adverse events compared with patients with low CRP and normal values for metabolic indicators.


CONCLUSIONS
Both CRP and insulin resistance, as estimated by TG/HDL, appear to be strong, synergic risk factors for CAV and for major cardiac adverse events. These findings support the hypothesis that in heart transplant recipients, systemic inflammation may be an important mediator of graft vascular injury associated with metabolic syndrome.
Biadi
Ombretta
O
Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA.
Potena
Luciano
L
Fearon
William F
WF
Luikart
Helen I
HI
Yeung
Alan
A
Ferrara
Rossella
R
Hunt
Sharon A
SA
Mocarski
Edward S
ES
Valantine
Hannah A
HA
D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000209:etiology*; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000209:etiology*; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D014280:Triglycerides / Q000097:blood
D015415:Biomarkers; D008076:Cholesterol, HDL; D014280:Triglycerides; D002097:C-Reactive Protein