Impaired Nitric Oxide Mediated Endothelium‐Dependent Vasodilation with Suboptimal LDL Cholesterol

Abstract

Plasma low-density lipoprotein cholesterol (LDL-C) is a risk factor for cardiovascular disease (CVD). Recent data suggest LDL-C in the borderline high range (130–159 mg/dL) is associated with impaired endothelial vasodilation. We determined: 1) whether the impairment in vasodilator function is due to reduced nitric oxide (NO) bioavailability; and 2) if the magnitude of impairment is similar to clinically high LDL-C (≥160 mg/dL). Fifty middle-aged and older adults without overt CVD were studied: 20 optimal LDL-C (<130 mg/dL; age 56±1 yr); 20 borderline high LDL-C (55±1 yr); and 10 high LDL-C (54±2 yr). Forearm blood flow (FBF; plethysmography) was determined in response to intraarterial doses of acetylcholine (ACh), sodium nitroprusside (SNP) and ACh + NO blockade (L-NMMA). FBF to ACh was blunted (~20%; P<0.05) in the borderline (4.4±0.2 to 12.2±0.8 mL/100 ML tissue/min) and high (4.3±0.3 to 12.0±0.5) vs optimal (4.4±0.2 to 14.3±0.5) LDL-C group. There was no difference in the vasodilator response between the borderline and high groups. L-NMMA reduced the FBF response to ACh ~30% (P<0.05) in the optimal LDL-C group; there was no significant effect on FBF in either the borderline high or high LDL-C groups. In summary, NO-mediated endothelium-dependent vasodilation is impaired with borderline high LDL-C. Of note, the degree of impairment in vasodilation with borderline high LDL-C is similar to that with high LDL-C.