Low density lipoprotein cholesterol and coronary microvascular dysfunction in hypercholesterolemia

OBJECTIVES The present study evaluates the impact of total cholesterol (TC) and its subfractions on coronary flow reserve (CFR), an index of the integrated function of the coronary circulation, in asymptomatic subjects. BACKGROUND Endothelial dysfunction of the coronary microcirculation has been reported in asymptomatic subjects with hypercholesterolemia. METHODS Using oxygen-15-labeled water and positron emission tomography, myocardial blood flow (MBF, in ml/min per g) was measured at rest and during intravenous adenosine (140 μg/kg body weight per min) in 80 asymptomatic nonsmoking men: group 1 (n = 61; age 45 ± 7 years) had normal TC (≤6.5 mmol/liter or ≤250 mg/dl) and group 2 (n = 19; age 48 ± 10 years) had elevated TC. RESULTS Total cholesterol were 5.1 ± 0.8 and 7.2 ± 0.7 mmol/liter in groups 1 and 2 (p < 0.0005), respectively; low density lipoprotein (LDL) cholesterol levels were 3.2 ± 0.8 and 4.9 ± 0.7 mmol/liter (p < 0.0005); high density lipoprotein (HDL) cholesterol levels were 1.1 ± 0.3 and 1.0 ± 0.4 mmol/liter (p = NS); and triglyceride levels were 1.8 ± 1.3 and 3.0 ± 1.8 mmol/liter (p < 0.005). Groups 1 and 2 did not differ with regard to MBF at rest (0.87 ± 0.14 vs. 0.84 ± 0.14), MBF during adenosine (3.63 ± 1.02 vs. 3.30 ± 0.86) or CFR (4.23 ± 1.29 vs. 3.95 ± 0.93). A significant but weak correlation was found between CFR and HDL in group 1 (r = 0.29, p < 0.05), but not in group 2. In contrast, a significant inverse correlation between LDL and CFR was found in group 2 (r = −0.61, p < 0.05), but not in group 1. CONCLUSIONS Low density lipoprotein cholesterol but not TC correlated inversely with CFR in hypercholesterolemic subjects. Thus, LDL-induced coronary microvascular dysfunction could play an important role in the pathogenesis of coronary artery disease and its complications.