Effect of Lp(a) on the early functional and structural changes of atherosclerosis

Epidemiologic studies have shown a significant, relationship between elevat ed plasma levels of Lp(a) and increased risk of cardiovascular events; howe ver, the mechanisms by which elevated Lp(a) levels produce this increased r isk are not known. To test the hypothesis that high Lp(a) levels might cont ribute to the development of subclinical atherosclerosis, we examined the i nfluence of Lp(a) levels on early functional and structural atherosclerotic vascular changes, mow-mediated (endothelium-dependent) and nitrate-mediate d (smooth muscle-dependent) arterial dilations were measured by high-resolu tion ultrasound in 241 normal healthy subjects (aged 15 to 69 years; 116 me n). In addition, carotid artery intima-media thickness was measured by ultr asound in 71 subjects. Plasma Lp(a) was measured using a 2-sided immunoradi ometric assay (cohort median, 10 mg/dL; interquartile range, 3.9 to 24.4 mg /dL). In these subjects, there were no significant relationships between Lp (a) and arterial endothelial function, smooth muscle responses, or carotid wall thickness (P>0.25). By contrast, other Lipid risk factors, such as LDL -cholesterol and LDL-cholesterol/HDL-cholesterol ratio, were significantly correlated with abnormal arterial function and structure (P less than or eq ual to 0.01). These data suggest that elevated Lp(a) levels do not confer c ardiovascular risk by contributing to the early functional or structural ch anges of atherosclerosis.