Lipoprotein(a) [Lp(a)] is a novel risk factor for atherosclerosis, whose role in multiracial populations has been debated. We recently demonstrated a significant association of elevated levels of Lp(a) carried in particles containing small apolipoprotein(a) [apo(a)] isoforms with coronary artery disease in African American and white men. To extend these findings, we investigated the associations between Lp(a) levels, apo(a) size, and maximum internal carotid artery plaque thickness (MPT) in a randomly selected elderly multiethnic population (173 men and 253 women, consisting of 135 African Americans, 146 Hispanics, and 145 whites; mean age 70.5+/-11.4 years). Lp(a) levels were not associated with MPT. Among white men, MPT was associated with a small apo(a) isoform size (P=0.03) as well as with the amount of Lp(a) carrying the small apo(a) size (P=0.04), and the latter showed a borderline association in African American men (P=0.07). Among white women, but not in Hispanic or African American women, MPT was associated with the amount of Lp(a) carrying a small apo(a) isoform size (P<0.01). For all patients, the amount of Lp(a) carrying the small apo(a) size was associated with carotid atherosclerosis when there was control for age, sex, ethnicity, high density lipoprotein cholesterol, low density lipoprotein cholesterol, triglycerides, diabetes mellitus, hypertension, waist-to-hip ratio, and current smoking status (P=0.03). This association was significant for all men (P=0.03) and for white women (P=0.007). The results suggest that molecular properties of apo(a) are important in determining the atherogenicity of Lp(a).