Prior studies linked higher blood phytoestrogen (phytoE) levels of daidzein to beneficial lipoprotein profiles, and higher genistein levels related to worse coronary microvascular dysfunction in women with suspected ischemic heart disease (IHD). However, relationships to adverse outcomes remain unclear. We investigated the associations between eight serum phytoE and major adverse cardiac events (MACE) including myocardial infarction, stroke, hospitalization for heart failure and angina, cardiovascular and all-cause mortality, in women undergoing functional coronary angiography (FCA) for suspected ischemia.
We evaluated 143 women enrolled in the Women’s Ischemia Syndrome Evaluation (1996–2001) for serum phytoE levels and 10-year outcomes. Median follow-up duration was 6.08 years (range 0.01–8.16) for time to MACE and 9.11 years (range 0.01–11.08 years) for time to death. Kaplan–Meier plots were analyzed and Cox regression models adjusted for age, body mass index, hypertension, diabetes, dyslipidemia and tobacco use.
The median age was 54.7 (range 20.6–76.1) years and BMI was 29.3 (range 18.4–57.2). Of the cohort, 80.4% had nonobstructive coronary artery disease, 56% had hypertension, 22.4% had diabetes, 58.1% had dyslipidemia and 59.4% of the women used tobacco. Each unit decrease in log glycitin was associated with increased MACE hazard (HR 1.97, 95% [CI 1.23, 3.14], p = 0.005). Glycitin absence was associated with earlier angina hospitalization (log rank p = 0.05). After 6 years, MACE increased with each unit decrease in log genistein (HR 6.17, 95% [CI 1.81, 20.8], p = 0.0036). Other phytoE did not show statistically significant associations with outcomes.
Among women with suspected IHD undergoing clinically indicated invasive FCA, low serum glycitin was associated with increased MACE and earlier angina hospitalization, while low genistein was associated with increased MACE after 6 years. Future studies are needed regarding phytoE, nutrition, outcomes and possibly supplementation.
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This work was supported by contracts from the National Heart, Lung and Blood Institutes nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, grants U0164829, U01 HL649141, U01 HL649241, K23HL127262, T32HL69751, R01 HL090957, 1R03AG032631 from the National Institute on Aging, GCRC grant MO1-RR00425 from the National Center for Research Resources, the National Center for Advancing Translational Sciences Grant UL1TR000124, and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, and QMED, Inc., Laurence Harbor, NJ, the Edythe L. Broad and the Constance Austin Women’s Heart Research Fellowships, Cedars-Sinai Medical Center, Los Angeles, California, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, The Society for Women’s Health Research (SWHR), Washington, D.C., the Linda Joy Pollin Women’s Heart Health Program, the Erika Glazer Women’s Heart Health Project, and the Adelson Family Foundation, Cedars-Sinai Medical Center, Los Angeles, California.
Conflict of interest
CNBM reports personal fees from iRhythm, other from Sanofi, other from Abbott Diagnostics, during the conduct of the study. CJP reports grants from NIH/NHLBI, during the conduct of the study; grants from NIH/NCATS, grants from BioCardia BC-14-001-02; Mesoblast, Inc. MSB-MPC-CHF001; Ventrix, Inc.; Athersys Inc. AMI MultiStem; Verily Life Sciences LLC-Project Baseline OSMB; Ironwood MSB-MPC-CHF00-DMC, Imbria Pharmaceuticals Inc.; Milestone Pharmaceuticals Inc.; Caladrius Biosciences, Inc.; Gatorade Trust; and McJunkin Family Foundation, outside the submitted work. The other authors declare they have no actual or potential competing financial interests.
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Barsky, L., Cook-Wiens, G., Doyle, M. et al. Phytoestrogen blood levels and adverse outcomes in women with suspected ischemic heart disease. Eur J Clin Nutr (2020). https://doi.org/10.1038/s41430-020-00800-6