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Published Online
on July 15, 2004

Stroke. 2004
Published online before print July 15, 2004, doi: 10.1161/01.STR.0000138022.86509.2d
A more recent version of this article appeared on September 1, 2004
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Submitted on February 5, 2004
Revised on June 4, 2004
Accepted on June 22, 2004

Relationship Between Plasma Glutathione Levels and Cardiovascular Disease in a Defined Population. The Hisayama Study

Haruki Shimizu MD*; Yutaka Kiyohara MD; Isao Kato MD; Takanari Kitazono MD; Yumihiro Tanizaki MD; Michiaki Kubo MD; Hirofumi Ueno; Setsuro Ibayashi MD; Masatoshi Fujishima MD; and Mitsuo Iida MD

From the Department of Medicine and Clinical Science (H.S., Y.K., I.K., T.K., Y.T., M.K., S.I., M.F., M.I.), Graduate School of Medical Sciences, Kyushu University; and the Saga Research Institute of Ohtsuka Pharmaceutical Co, Ltd (H.U.).

* To whom correspondence should be addressed. E-mail: haru-sz{at}d7.dion.ne.jp.

Background and Purpose--Glutathione (GSH) appears to have marked antioxidant activities and therefore may prevent cardiovascular disease (CVD). However, there are very few reports on this subject. In a community-based case-control study, we tested the hypothesis that low levels of plasma GSH are closely associated with CVD and its clinical types.

Methods--The association between fasting plasma total GSH (tGSH) levels and CVD were assessed using conditional logistic regression analysis among 134 CVD cases and 435 age- and sex-matched healthy control subjects.

Results--Mean tGSH concentrations were lower in all CVD cases than in the control subjects (3.06 versus 3.71 µmol/L; P=0.0001). Among the CVD types, both the cerebral infarction cases (2.98 versus 3.59 µmol/L; P=0.001) and cerebral hemorrhage cases (2.51 versus 3.43 µmol/L; P=0.0027) had significantly lower tGSH levels than the corresponding control groups had. The same tendency was observed for cases of subarachnoid hemorrhage (3.45 versus 3.83 µmol/L; P=0.36) and myocardial infarction (3.65 versus 3.77 µmol/L; P=0.69), but these differences were not statistically significant. After adjustment for other confounding factors, the risk of CVD was significantly lower in the third (adjusted odds ratio, 041; 95% CI, 0.21 to 0.77) and the fourth quartiles (adjusted odds ratio, 0.25; 95% CI, 0.12 to 0.51) than in the first. This association was most prominent in patients with lacunar infarction or cerebral hemorrhage.

Conclusions--These findings suggest that reduced plasma tGSH levels are a risk factor for CVD, especially for cerebral small vessel disease.


Key words: cardiovascular diseases • lacunar infarction • cerebral hemorrhage • risk factors