The journal of nutrition, health & aging

, Volume 16, Issue 4, pp 383–388 | Cite as

Prospective observational study of isoflavone and the risk of stroke recurrence: Potential clinical implications beyond vascular function

  • Y. -H. Chan
  • K. -K. Lau
  • K. -H. Yiu
  • C. -W. Siu
  • H. -T. Chan
  • S. -W. Li
  • S. Tam
  • T. -H. Lam
  • C. -P. Lau
  • Hung-Fat TseEmail author
JNHA: Clinical Trials and Aging



Whether isoflavone has any effect on recurrent cardiovascular events is unknown.


To investigate the relations between isoflavone intake and the risk of stroke recurrence.

Subjects and Methods

We recruited 127 consecutive patients with prior history of atherothrombolic/ hemorrhagic stroke (mean age: 67 ± 11 years, 69% male) and prospectively followed up for a mean duration of 30 months. Stroke recurrence and major adverse cardiovascular events (MACE) were documented. Brachial flow-mediated dilatation (FMD) was measured using high-resolution ultrasound. Isoflavone intake was estimated using a validated food frequency questionnaire.


Median isoflavone intake was 6.9 (range: 2.1–14.5) mg/day. Isoflavone intake was independently associated with increased FMD (Pearson R=0.23, p=0.012). At 30 months, there were 10 stroke recurrence and 12 MACE. Kaplan-Meier analysis showed that patients with isoflavone intake higher than median value had significantly longer median stroke recurrence-free survival time (19.0 [range: 10.4–27.6] mth versus 5.0 [range: 4.1–5.9] mth, p=0.021) and MACE-free survival time (19.0 [range: 10.4–27.6] mth versus 4.0 [range: 2.4–5.6] mth, p=0.013). Using multivariate cox regression, higher isoflavone intake was an independent predictor for lower risk of stroke recurrence (hazards ratio 0.18 [95%CI: 0.03–0.95], risk reduction 82%, p=0.043) and MACE (hazards ratio 0.16 [95%CI: 0.03–0.84], risk reduction 84%, p=0.030).


Higher isoflavone intake in stroke patients was associated with prolonged recurrence-free survival, and reduced risk of stroke recurrence and MACE, independent of baseline vascular.function. Whether isoflavone may confer clinically significant secondary protection in stroke patients should be further investigated in a randomized controlled trial.

Key words

Recurrent stroke isoflavone diet secondary prevention vascular function 


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  1. 1.
    Donnan GA, Fisher M, Macleod M, Davis SM. Stroke. Lancet 2008;371(9624):1612–1623.PubMedCrossRefGoogle Scholar
  2. 2.
    Samsa GP, Bian J, Lipscomb J, Matchar DB. Epidemiology of recurrent cerebral infarction: a medicare claims-based comparison of first and recurrent strokes on 2-year survival and cost. Stroke 1999;30(2):338–349.PubMedCrossRefGoogle Scholar
  3. 3.
    Hankey GJ. Secondary prevention of recurrent stroke. Stroke 2005;36(2):218–221.PubMedCrossRefGoogle Scholar
  4. 4.
    Hackam DG, Spence JD. Combining multiple approaches for the secondary prevention of vascular events after stroke: a quantitative modeling study. Stroke 2007;38(6):1881–1885.PubMedCrossRefGoogle Scholar
  5. 5.
    Vanharanta M, Voutilainen S, Lakka TA, van der Lee M, Adlercreutz H, Salonen JT. Risk of acute coronaiy events according to serum concentrations of enterolactone: a prospective population-based case-control study. Lancet 1999;354(9196):2112–2115.PubMedCrossRefGoogle Scholar
  6. 6.
    Bazzano LA, He J, Ogden LG, Loria C, Vupputuri S, Myers L, Whelton PK. Legume consumption and risk of coronary heart disease in US men and women: NILANES I Epidemiologic Follow-up Study. Arch Intern Med 2001;161(21):2573–2578.PubMedCrossRefGoogle Scholar
  7. 7.
    He FJ, Nowson CA, MacGregor GA. Fruit and vegetable consumption and stroke: meta-analysis of cohort studies. Lancet 2006;367(9507):320–326.PubMedCrossRefGoogle Scholar
  8. 8.
    Taubert D, Roesen R, Lehmann C, Jung N, Schomig E. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA 2007;298(1):49–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Heiss C, Kleinbongard P, Dejam A, Perre S, Schroeter H, Sies H, Kelm M. Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers. J Am Coll Cardiol 2005;46(7):1276–1283.PubMedCrossRefGoogle Scholar
  10. 10.
    Anthony MS. Phytoestrogens and cardiovascular disease: where’s the meat? Arterioscler Thromb Vasc Biol 2002;22(8):1245–1247.PubMedCrossRefGoogle Scholar
  11. 11.
    Sacks FM, Lichtenstein A. Van Horn L, Harris W, Kris-Etherton P, Winston M. Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee. Circulation 2006;113(7):1034–1044.PubMedCrossRefGoogle Scholar
  12. 12.
    Trifiletti A, Gaudio A, Lasco A, Atteritano M, Scamardi R, Pizzoleo MA, Morabito N, Frisina N. Haemostatic effects of phytoestrogen genistein in postmenopausal women. Thromb Res 2008.Google Scholar
  13. 13.
    Chan YH, Lau KK, Yiu KH, Li SW, Chan HT, Tarn S, Shu XO, Lau CP, Tse HF. Isoflavone intake in persons at high risk of cardiovascular events: implications for vascular endothelial function and the carotid atherosclerotic burden. Am J Clin Nutr 2007;86(4):938–945.PubMedGoogle Scholar
  14. 14.
    Chan YH, Lau KK, Yin KH, Li SW, Chan HT, Fong DY, Tam S, Lau CP, Tse HP. Reduction of C-reactive protein with isoflavone supplement reverses endothelial dysfunction in patients with ischaemic stroke. Eur Heart J 2008;29(22);2800–2807.PubMedCrossRefGoogle Scholar
  15. 15.
    Kokubo Y, Tso H, Tshibara J, Okada K, Inoue M, Tsugane S. Association of dietary intake of soy, beans, and isoflavones with risk of cerebral and myocardial infarctions in Japanese populations: the Japan Public Health Center-based (JPHC) study cohort I. Circulation 2007;116(22):2553–2562.PubMedCrossRefGoogle Scholar
  16. 16.
    Adams H, Adams R, Del Zoppo G, Goldstein LB. Guidelines for the early management of patients with ischemic stroke: 2005 guidelines update a scientific statement from the Stroke Council of the American Heart Association/American Stroke Association. Stroke 2005;36(4):916–923.PubMedCrossRefGoogle Scholar
  17. 17.
    Zhang X, Shu XO, Li H, Yang G, Li Q, Gao YT, Zheng W. Prospective cohort study of soy food consumption and risk of bone fracture among postmenopausal women. Arch Intern Med 2005;165(16):1890–1895.PubMedCrossRefGoogle Scholar
  18. 18.
    Xu WH, Zheng W, Xiang YB, Ruan ZX, Cheng JR, Dai Q, Gao YT, Shu XO. Soya food intake and risk of endometrial cancer among Chinese women in Shanghai: population based case-control study. BMJ 2004;328(7451):1285.PubMedCrossRefGoogle Scholar
  19. 19.
    Shu XO, Yang G, Jin F, Liu D, Kushi L, Wen W, Gao IT, Zheng W. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women’s Health Study. Eur J Clin Nutr 2004;58(1):17–23.PubMedCrossRefGoogle Scholar
  20. 20.
    Witike A, Chang A, Froicu M, Harandi OF, Weaver V, August A, Paulson RF, Cantoma MT. Vitamin D receptor expression by the lung micro-environment is required for maximal induction of lung inflammation. Arch Biochem Biophys 2007;460(2):306–313.CrossRefGoogle Scholar
  21. 21.
    Ip MS, Tse HP, Lam B, Tsang KW, Lam WK. Endothelial function in obstructive sleep apnea and response to treatment. Am J Respir Crit Care Med 2004;169(3):34S–53.Google Scholar
  22. 22.
    Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, et al. Prognostic significance of endothelial dysfunction in hypertensive patients. Circulation 2001;104(2):191–196.PubMedGoogle Scholar
  23. 23.
    Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dysfunction. oxidative stress, and risk of cardiovascular events in patients with coronary artery disease. Circulation 2001;104(22):2673–2678.PubMedCrossRefGoogle Scholar
  24. 24.
    Dzau VJ, Antman EM, Black HR, Hayes DL, Manson JE, Plutzky J, Popma JJ, Stevenson W. The cardiovascular disease continuum validated: clinical evidence of improved patient outcomes: part I: Pathophysiology and clinical trial evidence (risk factors through stable coronary artery disease). Circulation 2006;114(25):2850–2870.PubMedCrossRefGoogle Scholar
  25. 25.
    Walker HA, Dean TS, Sanders TA, Jackson G, Ritter JM, Cbowienczyk PJ. The phytoestrogen genistein produces acute nitric oxide-dependent dilation of human forearm vasculature with similar potency to 17beta-estradiol. Circulation 2001;103(2):258–262.PubMedGoogle Scholar
  26. 26.
    Cederroth CR, Vinciguerra M, Gjinovci A, Kuhne F, Klein M, Cederroth M, et al. Dietary phytoestrogens activate AMP-activated protein kinase with improvement in lipid and glucose metabolism. Diabetes 2008;57(5):1176–1185.PubMedCrossRefGoogle Scholar
  27. 27.
    Kerry N, Abbey M. The isoflavone genistein inhibits copper and peroxyl radical mediated low density lipoprotein oxidation in vitro. Atherosclerosis 1998;140(2):341–347.PubMedCrossRefGoogle Scholar
  28. 28.
    Ryan-Borchers TA, Park JS, Chew BP, McGuire MK, Foumier LR, Beerman KA. Soy isoflavones modulate immune function in healthy postmenopausal women. Am J Clin Nutr 2006;83(5):1118–1125.PubMedGoogle Scholar
  29. 29.
    Garrido A, De la Maza MP, Hirsch S, Valladares L. Soy isoflavones affect platelet thromboxane A2 receptor density but not plasma lipids in menopausal women. Maturitas 2006;54(3):270–276.PubMedCrossRefGoogle Scholar
  30. 30.
    Schabath MB, Hernandez LM, Wu X, Pillow PC, Spitz MR. Dietary phytoestrogens and lung cancer risk. JAMA 2005;294(12):1493–1504.PubMedCrossRefGoogle Scholar

Copyright information

© Serdi and Springer Verlag France 2012

Authors and Affiliations

  • Y. -H. Chan
    • 1
  • K. -K. Lau
    • 2
  • K. -H. Yiu
    • 2
  • C. -W. Siu
    • 2
  • H. -T. Chan
    • 2
  • S. -W. Li
    • 3
  • S. Tam
    • 4
  • T. -H. Lam
    • 1
  • C. -P. Lau
    • 2
  • Hung-Fat Tse
    • 2
    • 5
    Email author
  1. 1.School of Public HealthThe University of Hong KongHong KongChina
  2. 2.Cardiology Division, Department of MedicineThe University of Hong Kong, Queen Mary HospitalHong KongChina
  3. 3.Department of MedicineTung Wah HospitalHong KongChina
  4. 4.Department of Clinical Biochemistry UnitQueen Mary HospitalHong KongChina
  5. 5.Department of MedicineThe University of Hong Kong, Queen Mary HospitalHong KongChina

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