Background and Purpose— Endothelial dysfunction may play a causal role in cerebral small vessel disease (SVD). Asymmetric dimethylarginine (ADMA), a circulating endogenous inhibitor of nitric oxide, has been implicated in endothelial dysfunction, particularly in hyperhomocystinemia, a known risk factor for SVD. We determined if ADMA was elevated in SVD, correlated with disease severity, and interacted with homocysteine.

Methods— ADMA and homocysteine levels were determined in 47 consecutive symptomatic SVD patients and 38 controls. SVD was graded by leukoariosis severity and number of lacunar infarcts.

Results— Mean (and SD) ADMA was higher in SVD patients compared with controls (0.814 [0.145] versus 0.747 [0.184] μmol/L; P=0.014) after controlling for age, gender, vascular risk factors, and creatinine clearance. Additionally controlling for homocysteine had only a small effect on this relationship (P=0.055). Mean homocysteine was higher in SVD cases compared with controls (15.14 [5.59] versus 12.49 [4.15] μmol/L; P=0.035). Leukoariosis grade correlated positively with ADMA (P=0.026) and homocysteine (P=0.003). Lacunar grade correlated with homocysteine (P=0.017), but not ADMA.

Conclusions— ADMA is independently associated with SVD and correlates with leukoariosis severity.