Is a blood chemical that inhibits nitric oxide associated with damage to the brain’s small blood vessels?

Details

Endothelial dysfunction—impaired function of the lining of blood vessels—may play a causal role in cerebral small vessel disease (SVD). Asymmetric dimethylarginine (ADMA), a circulating, naturally produced inhibitor of nitric oxide, has been implicated in endothelial dysfunction, particularly in hyperhomocysteinemia, a known risk factor for SVD. The researchers investigated whether ADMA was elevated in SVD, correlated with disease severity, and interacted with homocysteine.

In this observational patient–control comparison, ADMA and homocysteine levels were measured in 47 consecutive patients with symptomatic SVD and 38 controls. SVD was graded using the severity of leukoaraiosis (white matter changes) and the number of lacunar infarcts.

Mean ADMA was higher in patients with SVD than in controls: 0.814 (SD 0.145) versus 0.747 (SD 0.184) micromol/L, with P=0.014 after adjustment for age, gender, vascular risk factors, and creatinine clearance. The abstract describes additional adjustment for homocysteine as having only a small effect on this relationship; the resulting P value was 0.055.

Mean homocysteine was also higher in SVD patients than in controls: 15.14 (SD 5.59) versus 12.49 (SD 4.15) micromol/L; P=0.035. Leukoaraiosis grade correlated positively with both ADMA (P=0.026) and homocysteine (P=0.003). Lacunar infarct grade correlated with homocysteine (P=0.017), but not with ADMA.

The authors concluded that ADMA is independently associated with SVD and correlates with leukoaraiosis severity.