Renin-angiotensin-aldosterone system in brain infarction and vascular death.
The renin-angiotensin-aldosterone system has functions that may contribute to brain infarction (BI). In 459 matched pairs of white patients and control subjects, we measured plasma angiotensin-converting enzyme (ACE) levels, seven polymorphisms (angiotensinogen T174M and M235T, ACE I/D and 4656 2/3CT repeat [rpt], angiotensin II type 1 receptor A1166C and A153G, and aldosterone synthase CYP11B2), and evaluated 5-year poststroke mortality. Mean plasma ACE levels (+/-standard error) were significantly greater in patients than control subjects (37.5 +/- 0.9 vs 33.9 +/- 0.9), in patients with lacunar stroke, and in patients with no previous vascular (cerebrovascular or cardiovascular) history. The risk for BI increased with tertiles of plasma ACE, without an interaction with hypertension. After adjustments, the association disappeared except among patients with cardioembolic BI and those without previous vascular events. Among the polymorphisms, there was a weak association of BI with angiotensin II type 1 receptor 1166C, a weak protective effect with angiotensinogen 174M, and a strong association of angiotensinogen 235T with 5-year vascular mortality. These results suggest that renin-angiotensin-aldosterone system activity and genes contribute to cerebrovascular disease and poststroke vascular death in white patients.
Brenner
David
D
Department of Neurology and Stroke Centre, Bichat University Hospital and Medical School, Denis Diderot University, Paris, France.
Labreuche
Julien
J
Poirier
Odette
O
Cambien
François
F
Amarenco
Pierre
P
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000808:Angiotensinogen / Q000097:blood / Q000235:genetics; D020520:Brain Infarction / Q000235:genetics* / Q000401:mortality*; D016022:Case-Control Studies; D019405:Cytochrome P-450 CYP11B2 / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011110:Polymorphism, Genetic; D044140:Receptor, Angiotensin, Type 1 / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*
D044140:Receptor, Angiotensin, Type 1; D000808:Angiotensinogen; D019405:Cytochrome P-450 CYP11B2; D007703:Peptidyl-Dipeptidase A