Long-term Effect of a Dietary Education Program on Postmenopausal Cardiovascular Risk and Metabolic Syndrome: The Brisighella Heart Study

Introduction

Loss of ovarian function and subsequent decline of endogenous estrogens are associated with cardiovascular disease (CVD) risk and increased mortality rate after menopause. ¹ In fact, menopause appears to exacerbate many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction, and vascular inflammation. ² Recent evidence, however, suggests that this observation could be more related to the increasing mean age of women and to conventional risk factors than to a primary role of menopause itself in inducing CVD. ³ In any case, CVD is the leading cause of mortality and morbidity in women after the age of 50 in most developed countries, and the majority of risk factors are known and potentially reversible. ⁴

Because incorrect dietary habits seem to be one of the strongest predictors of cardiovascular mortality in women, ⁵ various studies have tried to identify which type of dietary pattern or nutrient could be associated with the lowest incidence of CVD. It has been shown that moderate alcohol, ⁶ nut, ⁷ isoflavone ⁸ or flavonoid ⁹ consumption and low fat intake ¹⁰ are associated with risk reduction in the population. A global education intervention on diet and lifestyle may be the most effective preventive means, as it has been postulated that up to 77% of events can be prevented in such patients. ¹¹ Others have suggested that an unfocused preventive intervention is not useful because it has only modest effects on CVD risk factors in postmenopausal women. ¹⁰ Overall, the available but inconclusive data support the hypothesis that the earlier the intervention, the better the preventive results; that is, if the intervention begins before menopause, the prevention effect could be greater. ¹² Moreover, dietary patterns begun before menopause influence subclinical atherogenesis in the subsequent period, ¹³ further supporting an early dietary intervention in premenopausal women.

In this context, we have evaluated whether a nutritional education intervention on a general population cohort is able to balance negative metabolic effects of incident menopause in a large sample of perimenopausal women.

Materials and Methods

The Brisighella Heart Study is a prospective, population-based longitudinal epidemiological cohort study involving 2939 randomly selected subjects, aged 14–84 years, free of known CVD at enrollment, residing in the northern Italian rural town of Brisighella. The study was initiated in 1972 by Prof. G. Descovich. ¹⁴ Subjects were clinically evaluated at baseline and every 4 years after enrollment with clinical and laboratory data, in addition to the assessment of medical outcomes. In 1986, the study became part of the World Health Organization (WHO) European Risk Factors Co-ordinated Analysis (ERICA), ¹⁵ and in 1990, it became part of the Risk Factors and Life Expectancy (RIFLE) Project. ¹⁶ Throughout the duration of the study, all-cause mortality and morbidity, as well as the prevalence of cardiovascular risk factors, were recorded. ^17,18 The study design included an update of the database every 3 months with regard to fatal and nonfatal new events, and every 4 years, a complete medical checkup, including a nutritional habits record and fasting blood sample, ^17,18 was performed. From 1986 to 1988, several programs further evaluated efficacy, cost, and reliability of primary and secondary cardiovascular prevention, including school-age and general population nutritional education programs and general practitioner training about therapeutic guidelines. ¹⁹ Physical activity and nutritional habits were recorded throughout the study and encoded as previously reported. ¹⁴ With regard to the nutritional education program, from 1986 to 1989, a Nutritional Information Center was opened in Brisighella, and four registered dietitians provided study participants with nutritional advice aimed at reducing daily intake of animal fat and cholesterol. The center was open 3 days per week, and access was free (no charge or appointment necessary). All Brisighella families were informed about the program by mail in the form of brochures on nutritional guidelines and with informative posters.

As described in the literature, ¹⁴ people were invited to (1) substitute whole fat milk and yoghurt with low-fat products, (2) substitute saturated fat-rich meat with white meat and fish and limit meat consumption to less than four times per week, (3) consume fresh cheese and limit its consumption to less than twice per week, considering cheese as a substitute for meat, (4) limit egg consumption (as cooked eggs or as a component of noodles and pastry, (5) increase vegetable consumption, (6) limit sugar intake and fruit consumption to less than 300 g/day in cases of hypertriglyceridemia or hyperglycemia, and (7) consume extravirgin olive oil and non transesterified margarines instead of butter and animal fats. Since 1986, approximately 2200 citizens have come to the Nutritional Center; at least 0.7 person for every Brisighella family participated in the program from 1986 to 1989. Overall, compliance with the project was adequate and widely described elsewhere. In short, as shown by the modification in cholesterol and fatty acid intake and the mean cholesterol and triglyceride blood level of the subjects, ¹⁴ adherence to the diet suggestions was very good during the program and for 3 years after the end of the program and appeared homogeneous in different subgroups of the population (adults, elderly, men, women). ¹⁹

The Brisighella Heart Study protocol and its substudies were approved by the Ethical Board of the University of Bologna, and all volunteers gave signed consent to participation in the study.

For this study, we evaluated modification of cardiovascular risk factors in two groups of nondiabetic women who experienced menopause during the 1984–1985 population survey and after the nutritional education program was carried out on the whole population during the 1991–1992 population survey. We excluded those who began or increased antihypertensive and antihyperlipidemic drugs or began hormone replacement therapy (HRT) during the observation period. Patients who started treatment during the nutrition education program were excluded, as they took different drugs and at different dosages with antihypertensive or antihypercholesterolemic effects that were not comparable. Overall, however, a similar number of subjects began therapy in both groups of women. Menopause was self-defined by the interviewed patients as the moment when menstruation definitively stopped. Based on the study design, women who experienced menopause a maximum of 4 years before or after the nutritional program were acceptable. The baseline basal characteristics of the two groups of women are described in Table 1.

After identifying a normality distribution tested by the Kolmogorv-Smirnov test of body mass index (BMI), blood pressure, and lipid parameters, comparison was made with a paired t test before and after menopause in each group and with an unpaired t test between groups before and after menopause. The prevalence of metabolic syndrome, as defined by the National Cholesterol Education Program Adult Treatment Panel III guidelines, ²⁰ was calculated and compared by a chi-square test. A p level <0.05 was accepted as significant for each test.

Results

The mean dietary changes observed before and after the nutritional education program in premenopausal and postmenopausal groups are summarized in Table 2. Before the interventional period, women within 4 years of menopause experienced a significant increase in BMI, systolic blood pressure, total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides (for all, p < 0.01), and a significant decrease in high-density lipoprotein cholesterol (HDL-C) (p < 0.001). After the interventional period, women within 4 years of menopause experienced a significant reduction only in triglyceride plasma level (p < 0.001). No significant difference in any group was noted with regard to diastolic blood pressure and fasting plasma glucose.

Comparing the modification in the studied parameters between the two groups of women, we observed that the changes in BMI (t = 19.12, 561 DF, p < 0.001), systolic blood pressure (t = 13.73, 561 DF, p < 0.001), total cholesterol (t = 147.41, 561 DF, p < 0.001), LDL-C (t = 78.64, 561 DF, p < 0.001), HDL-C (t = 45.62, 561 DF, p < 0.001), and triglycerides (t = 81.36, 561 DF, p < 0.001) differed significantly (Table 3). The preintervention group experienced worsening in all parameters after menopause; there was no change in the intervention group. Again, no significant differences were observed with regard to diastolic blood pressure and fasting plasma glucose. The prevalence of metabolic syndrome was 73 of 301 (24.2%) and 99 of 301 (35.9%) (z = 2.35, p = 0.018), respectively, before and after menopause in the preintervention group, and it was 66 of 262 (25.2%) and 68 of 262 (25.9%) (z = 0.16, p = 0,871), respectively, before and after menopause in the intervention group (Table 3).

Discussion

Women comprise 55% of the total world population. This percentage is set to steadily increase over the next three decades, and in Europe, there are now approximately 3 women for every 2 men over the age of 65. All of these data confirm the importance of prevention specific to women. ²¹ However, available evidence on effective preventive treatment for postmenopausal women is not conclusive, and each individual case is left to clinical judgment. ²² The challenge of finding common guidelines is mainly related to the need to simultaneously reduce the health risk of multiple disease processes, for example, CVD, osteoporosis, and cancer specific to elderly women. ²³ In particular, a diet to reduce cholesterol intake could potentially increase the osteoporosis risk as a result of lowering the protein and calcium intake by elimination of dairy products from the diet. ²⁴

In our study, a nutritional education intervention involving a general population was effective in decreasing the independent cardiovascular risk factors of increasing BMI, systolic blood pressure, and LDL-cholesterolemia associated with menopause. This effect has been achieved without reducing the dietary intake of essential nutrients such as potassium, magnesium, and phosphorus. ¹⁹ Although concordant studies with previously produced data, our study is unique. Most previous research tested educational programs in postmenopausal women ^25,26 (and more rarely on premenopausal women ^27,28 ) in the setting of randomized clinical trials. These were mainly focused on evaluation of a specific intervention on a single parameter. In contrast, our results were obtained in the setting of a program involving a general population cohort (among them, premenopausal women) using rigid protocols and strict monitoring.

Another condition that significantly influences CVD risk in aging women is the increased prevalence of metabolic syndrome occurring with menopause. ²⁹ We also observed in our preintervention group that metabolic syndrome prevalence increased from 24% to 33% after menopause; the nutritional intervention was associated with a nonsignificant increase in the metabolic syndrome prevalence from 25% to 26% after the beginning of the menopausal period. These results supported the hypothesis linking diet-induced metabolic changes with a reduction in body weight. ^30,31

Our study has some relevant limitations, including the length of time between sequential population surveys and the lack of a systematic screening for atherosclerosis by Doppler ultrasound or other diagnostic techniques. As stated previously, however, a particular characteristic of this study was to involve a large cohort of premenopausal women followed during the transition to a postmenopausal state in the setting of a nutritional intervention in a whole population cohort. Therefore, exclusion from the analysis of women who began antihypertensive or antihyperlipidemic treatment during the observation period and those who were treated with HRT strengthens the value of the observed results. Another limitation is that menopause age is based on patient self-reporting of menstruation cessation and not on specific laboratory parameters.

Conclusions

In our epidemiological study, we found that a nutritional education program aimed at improving the cardiovascular risk profile of a whole village population is associated with prevention of increases in systolic blood pressure, BMI, and cholesterolemia associated with menopause. A similar result was observed with regard to the prevalence of metabolic syndrome.