Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

TY - JOUR

T1 - Low plasma arginine:asymmetric dimethyl arginine ratios predict mortality after intracranial aneurysm rupture

AU - Staalsø, Jonatan Myrup

AU - Bergström, Anita

AU - Edsen, Troels

AU - Weikop, Pia

AU - Romner, Bertil

AU - Olsen, Niels Vidiendal

PY - 2013/5

Y1 - 2013/5

N2 - BACKGROUND-: Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients. METHODS-: One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale. RESULTS-: Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003). CONCLUSIONS-: This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.

AB - BACKGROUND-: Asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases, predicts mortality in cardiovascular disease and has been linked to cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). In this prospective study, we assessed whether circulating ADMA, arginine:ADMA ratio, and nitrite/nitrate levels were associated with survival and cerebral vasospasm in SAH patients. METHODS-: One hundred and eleven patients were observed day 1 to 15 after SAH, with serial measurements of transcranial Doppler flow velocities (VMCA) and plasma biomarkers. Clinical status was assessed by the World Federation of Neurosurgical Societies grading scale. RESULTS-: Overall 30-day mortality was 18%, but differed between patients grouped by low, midrange, and high arginine:ADMA ratio in the first week after SAH. Mortality rates were 14/37, 1/37, and 5/37 in the 3 groups, respectively (P-logrank=0.0003). Cox regression showed that low versus midrange or high arginine:ADMA was associated with a hazard ratio of 4.1 independent of World Federation of Neurosurgical Societies grade (95% confidence interval, 1.5-10.9; P=0.006). ADMA or arginine:ADMA had no association to VMCA, but there was an inverse relationship between VMCA and nitrite/nitrate levels (P<0.0001). The NOS3 894G/G genotype was associated with 15% lower VMCA (P=0.01). ATbG-NOS3 haplotype homozygosity was associated with up to 64% higher nitrite/nitrate levels (P=0.003). CONCLUSIONS-: This study suggests that plasma arginine:ADMA ratios predict mortality after SAH. Both clinical and physiological measures of changes in cerebral hemodynamics are coupled to the nitric oxide system.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Aneurysm, Ruptured

KW - Arginine

KW - Biological Markers

KW - Blood Flow Velocity

KW - Female

KW - Humans

KW - Intracranial Aneurysm

KW - Male

KW - Middle Aged

KW - Predictive Value of Tests

KW - Prospective Studies

KW - Vasospasm, Intracranial

U2 - 10.1161/STROKEAHA.111.000605

DO - 10.1161/STROKEAHA.111.000605

M3 - Journal article

C2 - 23463757

SN - 0039-2499

VL - 44

SP - 1273

EP - 1281

JO - Stroke

JF - Stroke

IS - 5

ER -