Prospective Study on Usual Dietary Phytoestrogen Intake and Cardiovascular Disease Risk in Western Women

BACKGROUND: Phytoestrogens have been suggested to lower cardiovascular disease risk, but existing research focused on non-Western high intake levels and on risk factors. We investigated whether habitual low phytoestrogen intake is associated with manifest cardiovascular disease risk. METHODS AND RESULTS: Between 1993 and 1997, 16,165 women 49 to 70 years old and free from cardiovascular disease were enrolled in the Dutch Prospect-EPIC cohort (European Prospective study Into Cancer and nutrition) and followed up for a median period of 75 months. At enrollment, women filled in questionnaires on chronic disease risk factors and nutrition. Intake of phytoestrogens was estimated using the food frequency questionnaire covering regular dietary intake of 178 food items in the year before enrollment. Cox regression analysis was used to estimate hazard ratios of cardiovascular disease for quartiles of phytoestrogen intake adjusted for age at intake, body mass index, smoking, physical activity, hypertension, hypercholesterolemia, use of hormone replacement therapy, menopausal status, and intake of total energy, total fiber, vegetables, fruit, and alcohol. In total, 372 women experienced a coronary event (CHD) (International Classification of Diseases, Ninth Revision, Clinical Modification ICD-9, 410 to 414, 427.5) and 147 women a cerebrovascular event (CVD) (ICD-9, 430 to 438) during follow-up. Overall, neither isoflavones nor lignans were associated with decreased cardiovascular disease risk. When stratifying for ever versus never smokers, CHD risk decreased with increasing lignan intake for ever smokers. CONCLUSIONS: Our results do not support the presence of a protective effect of higher intake of phytoestrogens in low doses on cardiovascular disease risk, although a small risk reduction with higher lignan intake cannot be excluded for smokers.