doi: 10.1161/01.CIR.0000139385.27259.2c
(Circulation. 2004;110:e37.)
© 2004 American Heart Association, Inc.
Correspondence |
Serum Homocysteine and Endothelial Dysfunction in Circulatory Disorders in Women
Division of Cardiology, Department of Medicine, Wakayama Medical University, Kimiidera 811–1, Wakayama 641–8509, Japan, tsudak{at}mail.wakayama-med.ac.jp
To the Editor:
We read with interest the recent article by Zylberstein and colleagues1 dealing with the relationship between serum total homocysteine (tHcy) level and morbidity and mortality from coronary heart disease in women. The results of their study with the Cox regression analyses demonstrated that for the fifth tHcy quintile (mean value 16.75 µmol/L), relative risk was 1.86 for acute myocardial infarction (AMI) and 5.14 for death due to AMI. In addition, the authors indicated that age-standardized Kaplan-Meier plots for the fifth tHcy quintile versus others showed significant differences both for AMI and for death attributable to AMI. The authors1 proposed that homocysteine in middle-aged women is an independent risk factor for AMI, and in particular mortality due to AMI.
There is evidence that homocysteine might disturb the bioavailability of nitric oxide (NO), which would, at least in part, contribute to the pathophysiology of circulatory disorders in subjects with hyperhomocysteinemia. Stühlinger et al2 examined the relationship among homocysteine, NO, and endothelial function in patients with peripheral arterial disease and demonstrated that experimentally induced hyperhomocysteinemia increased plasma asymmetric dimethylarginine (ADMA; an endogenous NO synthase inhibitor), an effect that was temporally related to a decline in endothelial vasodilator function. This might be an important mechanism for the endothelial dysfunction that occurs in subjects with hyperhomocysteinemia.3 In a study presented earlier,4 we demonstrated that estrogen-induced improvement of membrane fluidity (a reciprocal value of membrane microviscosity) of erythrocytes was counteracted by ADMA, suggesting that ADMA might actively participate in the regulation of rheologic behavior of cell membranes and microcirculation in postmenopausal women. In this context, we speculate that the decreased bioavailability of NO due to ADMA might partially explain the increased risk for coronary heart disease in women with hyperhomocysteinemia. Because the authors1 described that tHcy and other biochemical parameters were analyzed from frozen serum samples of the subjects, we would like to know whether plasma NO metabolite and ADMA levels might be linked to tHcy in the present study of Dr Zylberstein and colleagues. It would be important to assess more precisely the relationships between homocysteine and endothelial function and their contribution to the pathophysiology of circulatory disorders in women.
References
1. Zylberstein DE, Bengtsson C, Björkelund C, et al. Serum homocysteine in relation to mortality and morbidity from coronary heart disease: a 24-year follow-up of the population study of women in Gothenburg. Circulation. 2004; 109: 601–606.
2. Stühlinger MC, Oka RK, Graf EE, et al. Endothelial dysfunction induced by hyperhomocyst(e)inemia: role of asymmetric dimethylarginine. Circulation. 2003; 108: 933–938.
3. Tsuda K, Nishio I, Cooke JP, et al. Asymmetric dimethylarginine and circulatory disorders in postmenopausal women. Circulation. 2004; 109: e35.[Medline] [Order article via Infotrieve]
4. Tsuda K, Kinoshita Y, Kimura K, et al. Electron paramagnetic resonance investigation on modulatory effect of 17ß-estradiol on membrane fluidity of erythrocytes in postmenopausal women. Arterioscler Thromb Vas Biol. 2001; 21: 1306–1312.
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