Modulation of Vascular Endothelial Function by Low-Density Lipoprotein Cholesterol With Aging: Influence of Habitual Exercise

Abstract

Aging is associated with reduced endothelium-dependent dilation (EDD) and increased risk for cardiovascular disease (CVD), but the mechanisms are incompletely understood. Clinically elevated plasma low-density lipoprotein cholesterol (LDL-C) is associated with impaired EDD. The purpose of this study was to determine whether circulating LDL-C within the "normal" range modulates EDD in healthy older adults and whether young age or habitual aerobic exercise protects against this adverse effect. In 83 healthy men with optimal/near optimal LDL-C (<130 mg/dl) or borderline high LDL-C (130-159 mg/dl), EDD (brachial artery flow-mediated dilation, FMD), and endothelium-independent dilation (sublingual glyceryl trinitrate, GTN) were assessed. FMD was 35% lower in older nonexercising men with borderline high LDL-C vs. optimal/near optimal LDL-C (3.1 +/- 0.5 vs. 4.8 +/- 0.4%Delta, P < 0.05), whereas the GTN response did not differ (P = 0.86). In contrast, FMD was similar between groups of young nonexercising men and between groups of older exercising men differing in LDL-C (P = 0.89-0.95). FMD was inversely related to LDL-C among the older nonexercising men (r = -0.43, P < 0.001), whereas there was no relation in the other groups (P > 0.05). Borderline high plasma LDL-C is associated with impaired EDD in older sedentary men, but not in young sedentary or older exercising men. Thus, modest elevations in plasma LDL-C within the normal range may contribute to the increased risk of CVD in sedentary older men by exacerbating vascular endothelial dysfunction, whereas resistance to this adverse influence may help explain the enhanced endothelial function and reduced CVD risk associated with young age and regular aerobic exercise.