Isoflavones and cardiovascular disease

Abstract

The specific profile of estrogens on cardiovascular risk, with limiting action on atherogenesis but a less clear protection on cardiovascular episodes, might be improved by other agonists of the estrogen receptor, such as isoflavones. By using a systematic search based on the electronic Medline database plus a hand-search of reference lists of selected review papers, we reviewed the rapidly growing body of experimental and clinical data that, on average, follow a pattern of benefit rather similar to estrogens. Experimental models have used endothelial and vascular smooth muscle cells, isolated arteries, and live animals, including monkeys. The clinical evidence arises from studies on the lipid profile and lipid oxidation, insulin resistance, hemostasis, changes in the inflammatory factors, and indicators of endothelial function, including metabolites of nitric oxide and prostacyclin. There are not randomized trials investigating the action of isoflavones on the incidence of clinical episodes, but a few recent, well-designed studies have suggested the association of the ingestion of isoflavones with a reduction in the atherosclerotic burden, as indicated by the measurement of the intima-media thickness in carotid vessels.

Introduction

There is a debate on whether menopause per se adds some cardiovascular risk. The demonstrated sensitivity of the vasculature to sexual hormones is one important argument at the base of the discussion. While natural menopause seems to only exert some indirect actions, such as the increase in the waist-hip ratio [1], [2] or slight lipid changes [3], the sudden loss of ovarian function, as determined by surgical menopause has been more clearly involved in the increase of cardiovascular risk and cardiovascular mortality [4], [5].

This debated relationship, together with a series of experimental and clinical data showing an action of ovarian hormones on biological factors implicated in atherogenesis, is at the base of the huge interest deployed on the role of ovarian hormones on cardiovascular risk.

The interest on this topic would be much less whether the relevance of cardiovascular disease (CVD) was only minor within the context of the health of women. Contrary to common beliefs, CVD is the leading cause of mortality and morbidity in women. The epidemiological weight of the disease is unequally divided into its two main forms, coronary heart disease (CHD) and cerebrovascular disease, which includes stroke and transient ischemic attacks. In the USA, a 47% of deaths from CVD in women has been assigned to CHD and a 19% to stroke [6]. The figures are very similar in Europe [7], and the World Health Organisation estimates that CVD will be the first cause of death in developing countries by 2010 [8].

The actual consensus on the modulatory capacity of estrogens on cardiovascular risk is underneath the interest generated by isoflavones in this regard. Isoflavones bind to estrogen receptors (ER) and are capable of activating their specific cellular pathways with a concrete profile, which does not totally overlap that of estrogens. Given the wide use of isoflavones by women around the menopause, it is very important to gain knowledge on their effect concerning cardiovascular risk. Should any net beneficial effect be confirmed, the support for their widespread use would be strengthened. This article will review the main evidences obtained on the effects of isoflavones on the cardiovascular system at both the experimental and the clinical level. We sought peer reviewed, full-length basic and clinical articles published using a PubMed search strategy with the terms (cardiovascular disease OR coronary heart disease OR cerebrovascular disease OR atherosclerosis OR hemostasis OR thrombosis) AND isoflavones. There was no date restriction, but only articles in English were chosen. This search was further supplemented by a hand-search of reference lists of selected review papers. After crossing–cleaning the reference lists some 750 articles were selected. One author (García-Pérez) separated experimental from clinical studies and extracted the data from the selected articles. Among the clinical studies, epidemiological surveys and controlled studies were reviewed. The data from clinical trials were further assessed by another author (AC), who used a protocol in which the characteristics of the subjects, the type of intervention, and the methodology used to obtain the results were evaluated.