European Heart Journal Advance Access originally published online on September 23, 2008
European Heart Journal 2008 29(22):2800-2807; doi:10.1093/eurheartj/ehn409
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Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke
1 Cardiology Division, Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong, People’s Republic of China
2 Department of Medicine, Tung Wah Hospital, Hong Kong, People’s Republic of China
3 Department of Nursing Studies, The University of Hong Kong, Hong Kong, People’s Republic of China
4 Department of Clinical Biochemistry Unit, Queen Mary Hospital, Hong Kong, People’s Republic of China
5 Li Ka Shing Faculty of Medicine, Research Centre of Heart, Brain, Hormone and Healthy Ageing, The University of Hong Kong, Hong Kong, People’s Republic of China
Received 16 April 2008; revised 26 July 2008; accepted 21 August 2008; online publish-ahead-of-print 23 September 2008.
* Corresponding author. Tel: +852 2855 3598, Fax: +852 2818 6304, Email: hftse{at}hkucc.hku.hk
See page 2710 for the editorial comment on this article (doi:10.1093/eurheartj/ehn468)
Aims: To investigate the effect of oral isoflavone supplement on vascular endothelial function in patients with established cardiovascular disease.
Methods and results: A randomized, double-blinded, placebo-controlled trial was performed to determine the effects of isoflavone supplement (80 mg/day, n = 50) vs. placebo (n = 52) for 12 weeks on brachial flow-mediated dilatation (FMD) in patients with prior ischaemic stroke. Compared with controls, FMD at 12 weeks was significantly greater in isoflavone-treated patients [treatment effect 1.0%, 95% confidence interval (95% CI) 0.1–2.0, P = 0.035]. Adjusted for baseline differences in FMD, isoflavone treatment was independently associated with significantly less impairment of FMD at 12 weeks (odds ratio 0.32, 95% CI 0.13–0.80, P = 0.014). The absolute treatment effect of isoflavone on brachial FMD was inversely related to baseline FMD (r = –0.51, P < 0.001), suggesting that vasoprotective effect of isoflavone was more pronounced in patients with more severe endothelial dysfunction. Moreover, isoflavone treatment for 12 weeks resulted in a significant decrease in serum high-sensitivity (hs)-C-reactive protein level (treatment effect –1.7 mg/L, 95% CI –3.3 to –0.1, P = 0.033). Nevertheless, isoflavone did not have any significant treatment effects on nitroglycerin-mediated dilatation, blood pressure, heart rate, serum levels of fasting glucose and insulin, haemoglobin A1c, and oxidative stress as determined by serum superoxide dismutase, 8-isoprostane, and malondialdehyde (all P > 0.05).
Conclusion: This study demonstrated that 12 week isoflavone treatment reduced serum hs-C-reactive protein and improved brachial FMD in patients with clinically manifest atherosclerosis, thus reversing their endothelial dysfunction status. These findings may have important implication for the use of isoflavone for secondary prevention in patients with cardiovascular disease, on top of conventional interventions.
Key Words: Isoflavone • Endothelial dysfunction • C-reactive protein
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