phytoestrogens and Coronary-Artery-Disease

Cardiovascular diseases remain the leading cause of morbidity and mortality among postmenopausal women in western societies. There are still no specific and highly efficient methods of preservation of women's vascular health in modern preventive medicine. For many years physicians have assumed that hormone replacement therapy prevents the development of atherosclerosis in menopausal women. However, the results of the largest international trials involving thousands of women have completely destroyed this hope. The modern perspective for the development of effective and safe drugs to enhance the quality of life and to prevent atherosclerosis progression in postmenopausal women may be the use of phytoestrogens, the substances of plant origin possessing estrogen- like effects, and possibly providing anti-atherosclerotic and anti-climacteric action. Phytoestrogens are often considered as a possible alternative to hormone replacement therapy, since they are believed to alleviate some symptoms of menopause. However, until now there is no exact evidence to consider phytoestrogens as the substances that protect women from atherosclerosis. It should be noted that the data from clinical studies with inconsistent results are mainly inconsistent per se, as most of the studies have serious limitations due to the study design and the participants' compliance. Nevertheless, there is a substantial evidence that phytoestrogens have the potential to address several conditions and diseases associated with the menopausal transition. Phytoestrogens, at least, can potentially reduce atherosclerosis and atherosclerosis-related diseases through multiple mechanisms, by regulating serum lipid metabolism, arterial vessels, cytokine levels, and coagulation/fibrinolysis system. However, a skepticism exists concerning the true potential of phytoestrogens to beneficially modify these processes. An analysis of findings from supplementing the diet with phytoestrogens has failed, in general, to confirm them as the agents responsible for beneficial cardiovascular effects. Fortunalely, now there is a growing interest to the use of phytoestrogens for primary prevention of cardiovascular disease in postmenopausal women. Clinical and epidemiologic data indicate that phytoestrogens possess anti-atherosclerotic effects and may be used to prevent and treat cardiovascular diseases, and that adding phytoestrogens to the diet can contribute to the health of postmenopausal women. This review discusse

Topics: Coronary Artery Disease; Dietary Supplements; Female; Humans; Phytoestrogens; Phytotherapy; Postmenopause; Women's Health

HRT may act preventively to reduce morbidity and mortality from cardiovascular disease in primary prevention. The development of SERMs adds a new, exciting, and promising therapeutic option to this field, as does the enhanced availability of soy phytoestrogen products. Although clinical trial data are incomplete, epidemiologic studies suggest that HRT raises HDL-C and triglyceride levels and lowers LDL-C levels. In addition, HRT lowers levels of Lp(a). These changes account for up to 50% of the cardiovascular risk reduction observed with HRT. In contrast, SERMs have less uniform effects. Both SERMs and phytoestrogens are less potent than HRT but have greater tissue selectivity. Although further study is needed, current information suggests that SERMs and phytoestrogens have significant potential to reduce CAD risk and may be a viable alternative to HRT for modest lowering of lipid levels. Phytoestrogens may be particularly useful for reducing CAD risk in men because they do not cause the side effects associated with estrogen. Additional clinical trials are necessary to determine whether the favorable lipid effects associated with HRT, SERMs, and phytoestrogens are linked to protection against cardiovascular disease. Nonetheless, physicians should consider the use of HRT, SERMs, and phytoestrogens for lowering lipid levels and reducing cardiovascular risk in women.

Topics: Aged; Cholesterol, HDL; Coronary Artery Disease; Estrogens; Estrogens, Non-Steroidal; Female; Hormone Replacement Therapy; Humans; Isoflavones; Lipid Metabolism; Middle Aged; Phytoestrogens; Plant Preparations; Postmenopause; Risk Factors; Selective Estrogen Receptor Modulators; Triglycerides

There is strong evidence from both human and nonhuman primate studies supporting the conclusion that estrogen deficiency increases the progression of atherosclerosis. More controversial is the conclusion that postmenopausal estrogen replacement inhibits the progression of atherosclerosis. Estrogen treatment of older women (>65 years) with pre-existing coronary artery atherosclerosis had no beneficial effects. In contrast, estrogen treatment of younger postmenopausal women or monkeys in the early stages of atherosclerosis progression has marked beneficial effects. Whether progestogens attenuate the cardiovascular benefits of estrogen replacement therapy has been controversial for more than a decade. Current evidence from studies of both monkeys and women suggest little or no attenuation of estrogen benefits for coronary artery atherosclerosis. Lack of compliance with estrogen replacement therapy, usually because of fear of breast cancer, remains a major problem. Future regimens may overcome that fear by the co-administration of a breast cancer preventive agent (i.e., selective estrogen receptor modulators, phytoestrogens) with low dose estrogen.

Topics: Aged; Aging; Animals; Coronary Artery Disease; Endothelium, Vascular; Estrogen Replacement Therapy; Estrogens, Non-Steroidal; Female; Humans; Inflammation; Isoflavones; Lipids; Macaca; Male; Middle Aged; Models, Animal; Phytoestrogens; Plant Preparations; Progestins; Raloxifene Hydrochloride; Selective Estrogen Receptor Modulators

To observe the effect of daidzein on serum inflammatory factors of senile patients with coronary heart disease (CHD).. Forty senile patients with CHD were randomly assigned into the control group and the daidzein group, 20 in each group. Patients in both groups were treated with conventional medicine, while those in the daidzein group were given daidzein Tablets additionally for 6 weeks. The levels of resting heart rate (RHR), blood pressure (BP), fasting plasma glucose (FPG), blood lipids and inflammatory factors, including hsCRP, IL-6 and TNF-alpha, were measured before and after treatment.. In the control group, the levels of RHR, BP and hsCRP changed after conventional medicinal treatment (P < 0.05 or P < 0.01) but other parameters unchanged (P > 0.05). While in the daidzein group, all the parameters measured were decreased in different degrees after 6 weeks treatment (P < 0.05 or P < 0.01), and also showed significant difference as compared with those in the control group respectively (P < 0.05 or P < 0.01).. Daidzein can effectively decrease the levels serum inflammatory factors in senile patients with CHD, the fact proved that isoflavone has anti-inflammatory effect in patients with coronary atherosclerosis.

Topics: Aged; C-Reactive Protein; Coronary Artery Disease; Female; Humans; Interleukin-6; Isoflavones; Male; Middle Aged; Phytoestrogens; Tumor Necrosis Factor-alpha

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.

Topics: Adult; Aged; Coronary Angiography; Coronary Artery Disease; Female; Humans; Ischemia; Middle Aged; Myocardial Ischemia; Phytoestrogens; Prognosis; Risk Factors; Young Adult

Topics: Breast Neoplasms; Climacteric; Complementary Therapies; Coronary Artery Disease; Female; Hormone Replacement Therapy; Hot Flashes; Humans; Life Style; Osteoporosis, Postmenopausal; Phytoestrogens; Risk Factors; Thrombosis

Soy phytoestrogens are popular, but information on their coronary effects in patients with suspected ischemic heart disease is limited. Accordingly, we investigated the relationship between blood phytoestrogen levels and coronary reactivity in women with suspected myocardial ischemia referred for coronary angiography.. Coronary flow velocity reserve (CFVR) and volumetric flow reserve (VFR) to adenosine (ADO) and nitroglycerin (NTG) (nonendothelial-dependent responses) and acetylcholine (ACH) (endothelial-dependent response) were assessed in 106 women from the Women's Ischemia Syndrome Evaluation (WISE). Blood phytoestrogen (daidzein and genistein) and estrogen (estradiol) levels were correlated with coronary reactivity measures.. Participants were mostly postmenopausal (79%), mean age 56 years, and 24% had obstructive coronary artery disease (CAD) at angiography. Genistein blood levels were negatively correlated with nonendothelial-dependent coronary flow responses. The highest genistein tertile (>6.1 ng/mL) had a CFVR of 2.1 +/- 0.5 (mean +/- SD) and VFRADO of 1.0 +/- 0.6, and both were significantly (p= 0.0001) lower compared with the other genistein tertiles combined. Similar associations were noted for CFVR(NTG) and VFR(NTG) (p = 0.03 and p = 0.01, respectively). The highest genistein tertile was associated with lower CFVR(ACH) compared with the other tertiles (p = 0.03). In multivariable modeling, blood genistein levels were significant independent predictors of coronary flow responses to ADO. There were no significant correlations between coronary reactivity variables and daidzein or endogenous estrogen.. In women with suspected myocardial ischemia, higher genistein blood levels are associated with impaired nonendothelial-dependent and endothelial-dependent coronary microvascular function.

Topics: Acetylcholine; Adenosine; Adult; Aged; Blood Flow Velocity; Coronary Angiography; Coronary Artery Disease; Coronary Vessels; Estradiol; Female; Genistein; Humans; Isoflavones; Middle Aged; Myocardial Ischemia; Nitroglycerin; Phytoestrogens; Predictive Value of Tests

To evaluate the effect of estrogen replacement therapy (ERT) on the functional characteristics of coronary and cerebral arteries in a new rabbit model for postmenopausal vascular function.. Female ovariectomized Watanabe heritable hyperlipidemic (WHHL) rabbits were randomized to treatment for 16 weeks with either 17 beta-estradiol or placebo. The chow used was semi-synthetic, thereby avoiding the influence of phytoestrogens. Ring segments of cerebral and coronary arteries were mounted for isometric tension recordings in myographs. The passive and active length-tension relationships for electromechanical (high potassium), pharmacomechanical (histamine) and combined electro- and pharmacomechanical (high potassium plus histamine) contraction were evaluated.. Treatment with 17 beta-estradiol significantly changed the active length-tension relationship for the electromechanical response in the proximal coronary arteries. No changes were observed for the passive length-tension relationships.. Long-term treatment with 17 beta-estradiol lowered the electromechanical tonus of atherosclerotic coronary arteries proximally, where the atherosclerosis is most developed. This could be one of the mechanisms behind the putative protective effect of hormone replacement therapy against ischemic heart disease. The study presents a promising new animal model for the investigation of postmenopausal coronary and cerebral artery function. The data correspond well with epidemiological observations in postmenopausal women.

Topics: Animal Nutritional Physiological Phenomena; Animals; Brain; Cerebral Arteries; Coronary Artery Disease; Coronary Circulation; Coronary Vessels; Disease Models, Animal; Estradiol; Estrogens, Non-Steroidal; Female; Hyperlipidemias; Isoflavones; Myography; Phytoestrogens; Plant Preparations; Postmenopause; Rabbits; Random Allocation

Experimental evidence was sought concerning whether soy phytoestrogens (SPEs) inhibit postmenopausal atherosclerosis progression/extent and, if so, their effectiveness relative to traditional estrogen replacement therapy. Premenopausal cynomolgus monkeys were fed a moderately atherogenic diet (26 months) to induce atherosclerosis. After ovariectomy, the moderately atherogenic diet was continued, and they were treated (36 months) with a control diet (soy protein depleted of SPEs), a diet containing SPEs in soy protein isolate, or a diet containing SPE-depleted soy protein with conjugated equine estrogens (CEE; Premarin) added. SPE effects on plasma lipids were better than those of CEE (higher high density lipoprotein cholesterol and no increase in triglyceride). Relative to the control group, CEE treatment inhibited (P = 0.0001), and SPE treatment partially inhibited (P = 0.10) the progression of atherosclerosis (common iliac artery atherosclerosis before and after treatment). CEE-treated monkeys had much less coronary artery atherosclerosis than the controls (P = 0.0002), whereas SPE-treated monkeys were intermediate in lesion extent between the controls and the CEE-treated animals (P = 0.02). Both CEE and SPE significantly reduced the extent of common carotid and internal carotid artery atherosclerosis, and the two treatment groups were not significantly different.

Topics: Animals; Arteriosclerosis; Carotid Artery Diseases; Coronary Artery Disease; Disease Progression; Estrogens, Conjugated (USP); Estrogens, Non-Steroidal; Female; Hormones; Horses; Isoflavones; Lipids; Lipoproteins; Macaca fascicularis; Phytoestrogens; Plant Preparations; Postmenopause; Soybean Proteins

The effect of phytoestrogen intake in combination with estrogen replacement therapy (ERT) on atherogenesis is largely unknown. The aim was thus to study the impact of phytoestrogens alone, or combined with oral estrogen, on experimental atherosclerosis in cholesterol-fed rabbits.. Two separate studies were performed in ovariectomized, cholesterol-fed female rabbits. In Study A, 45 rabbits were randomized to either a soy-free diet with or without oral 17 beta-estradiol (E2) 4 mg/day, or a soy-rich diet without any hormone for 14 weeks. In Study B, 100 rabbits were randomized into five groups (oral E2 0.5, 1, 2 or 4 mg/day, or no hormone) based on a soy-rich diet for 30 weeks.. By the end of treatment in Study A, aortic cholesterol content was twice the amount in the group treated with the soy-free diet compared with the soy-rich group and with the soy-free plus E2 group (p < 0.001). In Study B, aortic cholesterol content showed no significant difference between the groups (ANOVA, p = 0.49), but a tendency towards a lower aortic cholesterol content in the E2-treated animals compared with placebo was observed.. Dietary phytoestrogens significantly reduce aortic cholesterol content with a potency comparable to that of ERT, and seem to enhance (although mildly) the antiatherogenic effect of E2 in this model.

Topics: Animals; Aorta; Cholesterol; Chromatography, High Pressure Liquid; Coronary Artery Disease; Diet; Disease Models, Animal; Estradiol; Estrogens, Non-Steroidal; Female; Genistein; Glycine max; Isoflavones; Lipoproteins; Ovariectomy; Phytoestrogens; Plant Preparations; Rabbits; Random Allocation; Uterus

Soy protein, long recognized as having cardiovascular benefits, is a rich source of phytoestrogens (isoflavones). To distinguish the relative contributions of the protein moiety versus the alcohol-extractable phytoestrogens for cardiovascular protection, we studied young male cynomolgus macaques fed a moderately atherogenic diet and randomly assigned to three groups. The groups differed only in the source of dietary protein, which was either casein/lactalbumin (casein, n = 27), soy protein with the phytoestrogens intact (soy+, n = 27), or soy protein with the phytoestrogens mostly extracted (soy-, n = 28). The diets were fed for 14 months. Animals fed soy+ had significantly lower total and LDL plus VLDL cholesterol concentrations compared with the other two groups. They soy+ animals had the highest HDL cholesterol concentrations, the casein group had the lowest, and the soy- group was intermediate. A subset was necropsied for atherosclerosis evaluations (n = 11 per group). Morphometric and angiochemical measures were done to quantify atherosclerosis. Coronary artery atherosclerotic lesions were smallest in the soy+ group (90% less coronary atherosclerosis than the casein group and 50% less than the soy- group), largest in the casein group, and intermediate in the soy- group. The effects of the diets on lesion size and arterial lipid measures of the peripheral arteries were similar to those in the coronary arteries, with greatest prevention of atherogenesis with soy+ and intermediate benefit with soy- relative to casein. We could not determine whether the beneficial effects seen in the soy- group relate to the protein itself or to the remaining traces of phytoestrogens. The beneficial effects of soy protein on atherosclerosis appear to be mediated primarily by the phytoestrogen component. Testicular weights were unaffected by the phytoestrogens.

Topics: Animal Feed; Animals; Blood Vessels; Body Weight; Cholesterol Esters; Coronary Artery Disease; Diet, Atherogenic; Dietary Proteins; Estrogens, Non-Steroidal; Glycine max; Isoflavones; Lipids; Lipoproteins; Macaca fascicularis; Male; Milk Proteins; Organ Size; Phytoestrogens; Plant Preparations; Plant Proteins; Random Allocation; Testis; Testosterone