Evolution of serum atherogenic risk in liver transplant recipients: Role of lipoproteins and metabolic and inflammatory markers.

ABSTRACT

Although cardiovascular disease (CVD) is the leading cause of long-term mortality in liver transplant recipients (LTRs), the role of recently identified biomarkers of CVD risk in liver transplantation is unknown. We aimed to evaluate an extensive CVD risk profile in LTRs. Markers of CVD risk in 65 LTRs with no known history of diabetes mellitus (DM), dyslipidemia, or ischemic heart disease were compared to age-, sex-, and body mass index (BMI)-matched controls with no chronic medical disease. LTRs on corticosteroids or those with graft cirrhosis (GC) were excluded. The effect of calcineurin inhibitors on the CVD risk profile was separately analyzed in LTRs receiving either tacrolimus (Tac) or cyclosporine A (CsA). To evaluate the impact of GC, a comparison was made between LTRs with and without GC. Non-DM LTRs were matched to controls with respect to age, sex, and BMI. LTRs had similar serum high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and total cholesterol in comparison with BMI-matched controls. Proatherogenic small-dense (sd) LDL-C (33.6 ± 14 versus 25.9 ± 9.9 mg/dL; P < 0.001) and %sdLDL-C (30% ± 10% versus 26.4% ± 9%; P = 0.02) were significantly higher in LTRs. In comparison with controls, LTRs had higher apolipoprotein B (apoB; 98 ± 37 versus 88 ± 24 mg/dL; P < 0.01), very low density lipoprotein-particle concentration (VLDL-P; 7.7 ± 6.7 nmol/L versus 3.2 ± 9.1 nmol/L; P < 0.001), and VLDL size (51.1 ± 6.6 versus 46.5 ± 6.9 nm; P < 0.001). In LTRs, VLDL size and VLDL-P were directly related to serum CsA levels (r = 0.53, P = 0.09, and r = 0.63, P < 0.01, respectively) but not to Tac levels. In comparison with controls, LTRs had significantly lower total serum high-density lipoprotein-particle concentration. In comparison with those with preserved graft function, LTRs with GC had lower levels of serum atherogenic markers characterized by low sdLDL-C, apoB, triglycerides, LDL-C, and total cholesterol. In conclusion, LTRs have a proatherogenic lipoprotein profile that is not captured with a traditional lipid panel, and this suggests that a detailed serum atherogenic profile is needed to truly assess CVD risk in LTRs.