Better understanding of the mechanisms through which homocysteine causes atherosclerosis may enable identification of more targeted and effective therapies to reduce the risk of stroke in patients with elevated homo- cysteine levels. Hyperhomocysteinemia: Recommendation 1. The use of the B complex vitamins, cobalamin (B12 ), ), and folic acid might be considered for the prevention of ischemic stroke in patients with hyperhomocysteinemia, but its effectiveness is not well established (Class IIb; Level of Evidence B). Elevated Lp(a) Lp(a) is an LDL particle in which apolipoprotein B-100 is covalently linked to the glycoprotein apoprotein(a). The structure and chemical properties of this lipoprotein particle are similar to those of LDL. Lp(a) contributes to athero- genesis in experimental models797 and is associated with an increased risk for coronary artery disease.798,799 Apoprotein(a) also has structural homology to plasminogen but does not possess its enzymatic activity. Thus, it may inhibit fibrino- lysis, binding to the catalytic complex of plasminogen, tis- sue plasminogen activator, and fibrin, thereby contributing Meschia et al Guidelines for the Primary Prevention of Stroke 3793 Some, but not all, population-based epidemiological stud- ies have found that Lp(a) is associated with an increased risk In the Physicians Health Study, which com- prised primarily healthy, white, middle-aged men, there was no association between baseline plasma concentration of Lp(a) and future risk of stroke.804 In the CHS, the risk of stroke was increased 3-fold (RR, 3.00; 95% CI, 1.59 5.65) in older men whose Lp(a) levels were in the highest quintile compared with men with levels in the lowest quintile but not older women.801 In the ARIC study, the incidence of ischemic stroke was sig- nificantly increased in individuals with higher Lp(a) levels after adjustment for age, sex, and CVD risk factors, and this associa- tion was stronger in blacks than in whites. 