Background and Purpose There is evidence that an allelic variation in
the angiotensin-converting enzyme (ACE) gene may confer an increased r
isk of vascular disease. The roles of the ACE insertion/deletion polym
orphism and circulating ACE levels are unknown in cerebrovascular dise
ase. Methods We studied an insertion/deletion polymorphism within intr
on 16 of the ACE gene by polymerase chain reaction and plasma ACE acti
vity in 467 cases of stroke, the pathological type of which was establ
ished by cranial CT, and 231 control subjects. ACE genotype and activi
ty were related to stroke type and mortality at 4 weeks and 3 months.
Results No difference in genotype frequency was observed between all s
ubjects with stroke and control subjects or between control subjects a
nd subjects with cerebral infarction or cerebral hemorrhage. Plasma AC
E activity was significantly lower in stroke patients at presentation
(64.1 IU/L) than in control subjects (79.6 IU/L; P<.0001). Twenty-one
patients (4.5%) with cerebral infarction died within 4 weeks and 56 pa
tients (12%) within 3 months. These patients had significantly lower p
lasma ACE activity than patients who survived. There was some evidence
that risk of death within 4 weeks increased with the number of D alle
les (P=.02). Among survivors, plasma ACE activity showed a mean increa
se of 6.9 IU/L (95% confidence interval, 3.0 to 10.8) between levels a
t presentation and at 3 months (73.6 IU/L), the latter being similar t
o ACE activity in control subjects. Conclusions Low ACE activity at st
roke presentation and possession of the D allele may be associated wit
h increased risk of early death from acute cerebral infarction.