The main objective of this study was to identify significant contributors to cardiometabolic risk in primarily normal and overweight (BMI < 30) healthy postmenopausal women. In agreement with our hypothesis, androidal fat mass was the strongest and most consistent predictor of all cardiometabolic outcomes (except for Hcy) examined in this study. Our participants, as a group, showed no significant changes in body composition measurements, including androidal fat mass, during the course of the study. It should be noted, however, that the women were instructed to maintain their weight throughout the course of the study by following their usual diet and physical activity patterns, and hence, we did not expect to document overall or androidal fat mass change from baseline to 36 months. Similarly, with the exception of insulin, none of the cardiometabolic risk factors changed significantly between baseline and the time of final assessment (either 12
mo or 36
mo). Nevertheless, strong associations between androidal fat and cardiometabolic risk factors suggested that even a small increase in androidal fat mass may have considerable health consequences. Indeed, Biggs et al. [16
] reported that the incidence of type 2 diabetes was 70% higher (a hazard ratio of 1.7) in adults 65 years of age and older who gained at least 10
cm in waist circumference over several years compared with those who remained within 2
cm of their baseline waist circumference. Although the Biggs's study did not specifically target postmenopausal women, it provided some insight into the magnitude of the impact of central adiposity on the incidence of type 2 diabetes.
Certain factors such as duration of menopause, isoflavone treatment, and diet quality that are recognized in the literature as influential with respect to cardiovascular health did not emerge as significant predictors of the cardiometabolic outcomes examined in this study. Some of our findings are consistent with previous reports. For instance, DeNino et al. [17
] found that the relationship between age and blood lipids in nonobese women was abolished after controlling for visceral fat. Similarly, in our study, TLMP did not emerge in any model (except for fibrinogen) as a significant covariate, because time point took precedence over TLMP. Results also suggested that androidal fat mass in combination with other factors predominated in these cardiometabolic risk models. On the other hand, our findings for isoflavone treatment and dietary quality conflict with some of the previously published reports. The lowering effect of soy protein rich in isoflavones on blood lipids/lipoproteins, albeit modest (≤6% reduction), has been documented [18
]. The effect is more profound in hypercholesterolemic individuals and in males. Similarly, the effect of diet quality on CVD outcomes is well known: a healthier diet (high in fiber and low in fat and sodium) is associated with a lower risk of CVD [20
]. We included both a HEI score as a measure of diet quality and isoflavone treatment in our analysis. None of the models retained either covariate. The lack of association between HEI and cardiometabolic outcomes in our study could be in part explained by a majority of women who had relatively healthy diets (median HEI of 67 out of 100). Very few studies have examined the association between HEI and cardiometabolic outcomes with mixed results. For instance, Kant and Graubard [22
] reported that HEI emerged as a negative predictor of serum Hcy, CRP and plasma glucose (P
< .05), whereas Fung and colleagues [23
] did not find an association between HEI and CRP. In a recent study of 125 multiethnic overweight and obese women in early postpartum, the HEI scores were negatively associated with LDL-C and total cholesterol and positively related to HDL-C after adjustment for energy intake, body weight, and lactation status [24
Based on the results of our study, HEI does not appear to be a predictor of cardiometabolic risk factors. On the other hand, the effects of dietary factors as well as isoflavone treatment on cardiometabolic outcomes may be mediated by androidal fat mass. We previously reported that soy isoflavone treatment for 12 months did not exert an effect on body composition, including androidal fat, in our sample of women [25
]. With respect to diet, Fox et al. [26
] determined that premenopausal women who participated in a 24 week diet and/or exercise program showed reductions in weight (~
kg) and total percentage body fat (although it remained greater than 35% for all groups), but no significant improvements in blood lipids, glucose, or insulin concentrations. Further analysis revealed a lack of change in the waist-to-hip ratio, which in turn indicated that body fat distribution was not influenced by the intervention. To summarize, dietary interventions that are not sufficiently potent to reduce androidal fat mass are not likely to produce changes in cardiometabolic outcomes.
In addition to androidal fat mass, the other most common independent predictors of cardiometabolic outcomes in our study included time and site. Although concentrations of HDL-C and glucose did not change significantly during the study, both analytes showed an upward trend from baseline to 36
mo. The effect of time could be related to biological and/or behavioral factors that were not included in our models. In fact, TLMP was no longer significant when time was included, indicating that time was more important than TLMP. The site variable also emerged as a significant covariate in all models: compared with women at ISU, women at UCD had lower concentrations of triacylglycerol, HDL-C, glucose, insulin, HOMA, CRP, and fibrinogen and higher concentrations of LDL-C and uric acid. The site effect may be in part explained by baseline characteristics: ISU women were slightly (albeit not significantly) heavier and younger compared with UCD women. It is also quite possible that the site effect was due to some inherent differences between the two geographic locations. We did not document a relationship between androidal fat mass, as well as other factors, and Hcy likely because the women in our study were well below the clinical cut-off of 15, and Hcy values did not indicate great variability.
Some of the strengths of our study were that we followed a relatively large number of women and monitored longitudinal changes (baseline to 12 or 36
mo) in cardiometabolic risk factors. Limitations were that these women were free-living (both a strength and limitation), lacked ethnic diversity, and underwent infrequent measurements (yearly). Women in this study were mainly nonobese based upon the BMI definition. However, BMI does not adequately reflect body composition. Thus, some of our women may have been identified as obese using other criteria, such as percentage body fat (35–40% = overweight, >40% = obese [27
]). In conclusion, although cardiometabolic outcomes examined in this study were not affected by isoflavone treatment, each outcome (except for Hcy) had a strong, significant association with androidal fat mass. Thus, even small changes in androidal fat are likely to alter the cardiometabolic profile in healthy postmenopausal women.