This is a nice study that indicates tertiary prevention (treatment) of artherosclerosis is sometimes
geared towards immediate lowering of risk, not using IMT as a measure to do so. Perhaps L-arginine
can also decrease the progression of strokes when they first occur. Endothelial function is a better
indicator of risk reduction within a few weeks time than IMT. Current theory suggests that
endothelial dysfunction starts first, and then the intima-media complex becomes ill over time. Many
nutritional and lifestyle issues are shown to immediately impact the endothelium, and its function
is measured by ultrasound.
Cerebrovasc Dis. 2004 [Epub ahead of print]. Epub 2003 Dec 23.
L-Arginine-Mediated Vasoreactivity in Patients with a Risk of Stroke.
Zimmermann C, Wimmer M, Haberl RL.
Department of Neurology, Krankenhaus Munchen-Harlaching, Munchen, Germany.
OBJECTIVES:L-arginine is the substrate for nitric oxide (NO) production and has been shown to induce
an endothelium-dependent increase in cerebral blood flow in humans. We studied the hypothesis that
L-arginine-mediated vasoreactivity is impaired in patients with cardiovascular risk factors and a
risk of stroke. METHODS: 55 patients with cardiovascular risk factors (mean age 63.0 +/- 8.5 years)
were included in the study. 45 of them had a history of previous minor stroke or transient ischemic
attack (TIA) while 10 patients had cardiovascular risk factors but no previous cerebral ischemic
event. Endothelium-dependent changes in cerebral blood flow during the infusion of 30 g L-arginine
were assessed by continuous transcranial Doppler sonography of both middle cerebral arteries, intima-
media thickness (IMT) of the common carotid artery, by Duplex sonography. Associations between risk
factors, IMT, L-arginine reactivity and previous cerebrovascular events were analyzed by stepwise
multiple linear regression analysis and patient groups were compared. RESULTS: Normal young
volunteers showed an L-arginine-mediated increase in mean flow velocity of 22 +/- 8%; L-arginine
reactivity of the 55 patients was 28 +/- 10%. Patients with a history of stroke or TIA had
significantly higher flow velocity responses to L-arginine (29 +/- 10%) than patients with
cardiovascular risk factors but no previous cerebrovascular event (21 +/- 8%, p < 0.05). Stepwise
multiple linear regression analysis showed a significant association of enhanced L-arginine
reactivity with previous stroke/TIA (p < 0.001) and elevated fibrinogen levels (p < 0.05) but not
with age, IMT, hypertension, cholesterol or other risk factors. The same regression model showed an
association between IMT and previous stroke/TIA (p < 0.001) and serum cholesterol levels (p < 0.05)
but not L-arginine reactivity. CONCLUSIONS: L-arginine reactivity of the cerebral vessels may be
assessed by Doppler sonography and was enhanced in patients with a history of stroke or TIA. It was
independent of IMT of the carotid arteries. We conclude that enhanced L-arginine reactivity is a
potential marker for cerebral endothelial dysfunction and an independent indicator for an increased
risk of stroke. Copyright 2004 S. Karger AG, Basel
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