Relationship of High-Density Lipoprotein-Associated Arylesterase Activity to Systolic Heart Failure in Patients with and without Type 2 Diabetes

Abstract

High-density lipoprotein (HDL) confers protection against cardiovascular disease partly attributable to its robust anti-oxidant activities, which is largely impaired in diabetic conditions. In this study, we analyzed the anti-oxidant activity of HDL, as represented by the arylesterase activity of paraoxonase 1 (PON1) in HDL particles, in 216 consecutive HF patients with (n = 79) or without (n = 137) type 2 diabetes, and age- and gender-matched 112 diabetic and 189 non-diabetic non-HF controls. We found arylesterase activity was significantly decreased in patients with than without HF, and was further decreased when comorbid with diabetes. After adjusting for conventional risk factors and apolipoprotein A-I levels, arylesterase activity remained correlated positively with left ventricular ejection fraction in diabetic (r = 0.325, P = 0.020) but not non-diabetic patients (r = 0.089, P = 0.415), and negatively with NT-proBNP and NYHA functional class in both subgroups. In regression analyses, a higher risk of HF was observed in diabetic than non-diabetic patients when having low arylesterase activities. In conclusion, our data demonstrate that impaired serum arylesterase activity in patients with HF is further reduced when comorbid with diabetes. The relationship of impaired arylesterase activity to HF is especially enhanced in diabetic patients.

Figure 1

Comparison of serum arylesterase activity among diabetic and non-diabetic patients with or without HF. Diabetic patients tend to have lower arylesterase activity than the non-diabetic controls both in the population with (140.15 ± 45.88 vs. 166.97 ± 49.19 μmol/L/min/mL, P = 0.002) and without HF (179.44 ± 61.40 vs. 199.78 ± 70.51 μmol/L/min/mL, P = 0.005). Serum arylesterase activity is significantly decreased in both diabetic and non-diabetic patients when comorbid with HF. *P < 0.05; **P < 0.01.

Figure 2

Correlation of serum arylesterase activity with pro-BNP, NYHA functional classes and left ventricular ejection fraction (LVEF) in patients with heart failure. Pro-BNP (a) and LVEF (c) were logarithmically transformed before plotting. Open dots and dashed line, non-diabetic subjects (n = 137); closed dots and solid line, patients with type 2 diabetes (n = 79). (b) Shown is arylesterase activity in non-diabetic (open box) and diabetic (box with diagonal lines) patients grouped by different NYHA functional classes. ^**p < 0.01 vs. non-diabetic patients with NYHA II functional class; ^##p < 0.01 vs. diabetic patients with NYHA II functional class; $$p < 0.01 vs. non-diabetic patients with the same NYHA functional class.