IMPACT OF DIET , PHYSICAL ACTIVITY , LIPID STATUS AND GLYCOREGULATION IN ESTIMATION OF SCORE ( SYSTEMATIC CORONARY RISK EVALUATION ) FOR TEN YEARS IN POSTMENOPAUSAL WOMEN

Th e incidence of cardiovascular diseases (CVD) in women, although lower than in men, increases dramatically after the menopause. Diabetes mellitus is a more powerful predictor of CHD risk and prognosis in women than in men. Th e aim of this study was to promote diet and physical activity (PA) regimen in order to decrease coronary risk in next years in postmenopausal women with impaired glucose tolerance. Methodological approach of this research is to compare data gathered trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters of  examinees, regarding the glycoregulation, lipid status, body mass indexes, incidence of hypertension, uric acid and fi brinogen level. Th e SCORE ( Systematic Coronary Risk Evaluation) assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal CVD events over a ten-year period. It was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women after proposed diet/PA regimen. In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level bellow . Th e risk of  and above was not documented after diet/physical activity regimen. Th e prevalence of the atherogenic lipid markers at the beginning and the end of the assay decreased for all investigated lipid parameters in the group of pre-menopausal women what was more than in postmenopausal ones. Presented data indicate that dietary regimen and physical activity are crucial factors in CVD prevention throughout menopause and beyond. Behavioral changes aimed at decreasing food intake and increasing energy expenditure, should be implemented in pre-menopausal period of life.


Introduction
Significant advances in knowledge in interventions aimed to prevent female-specifi c cardiovascular disease (CVD) were pointed out after the first recommendations for preventive cardiology in  ().Despite research-based gains in the treatment of CVD, it remains the leading risk factor of women in the United States and developed parts of the world.In the United States alone, more than one half million women die of CVD each year, or approximately  death every minute, exceeding the number of deaths in men.Coronary heart disease (CHD) accounts for the majority of CVD deaths in women, disproportionately afflicting racial and ethnic minorities, and is a prime target for prevention (,).Because CHD is often fatal, nearly two thirds of women who die suddenly have no previously recognized symptoms, it is essential to make a specifi c approach in preventing CHD (,).The incidence of myocardial infarction (MI) in women, increases dramatically after the menopause.Risk factors such as smoking and dyslipidemia may be particularly important ().Lifestyle intervention reduces the risk of progression from impaired glucose tolerance (IGT) to type  diabetes.It is widely assumed that current advice regarding physical activity and dietary modifi cation is suffi cient to reduce the risk of type  diabetes.It is presumably mediated via an improvement in insulin sensitivity.It appears that once abnormal glucose levels have developed, signifi cant metabolic dysfunction has already occurred, and there is less chance of improving insulin sensitivity (,).According to the guidelines of the National Cholesterol Education Program (NCEP)() and a scientific statement from the American Heart Association (AHA) and American College of Cardiology (ACC) (), the primary cardiovascular risk factors in women are: personal history of CHD; Age over ; dyslipidemia: high LDL and/or low HDL; family history of premature CHD and diabetes mellitus; smoking; hypertension and peripheral vascular disease.Their assessment should be an important component of periodic health examinations.Elevated triglycerides, obesity and a sedentary lifestyle, while not considered primary risk factors in the NCEP guidelines, are also highly associated with coronary risk and assessment is recommended by the AHA/ ACC guidelines (, ).Diabetes mellitus carries greater prognostic information in women than any of the other traditional cardiac risk factors and is confi rmed to be the most important predictor for CHD in women ().Menopause is defi ned, for statistical and epidemiologic purposes, as the absence of menses for  year.Menopause is adult-onset ovarian failure, with the loss of estrogens, progesterone, and ovarian androgens.Th e loss of estrogens can lead to vasomotor symptoms, sleep disturbances, mood alteration, depression, urinary tract and vaginal atrophy, and increased health risks for several chronic disorders, including osteoporosis, cardiovascular disease, and loss of cognitive function.Although the pathophysiological changes associated with estrogen defi ciency in postmenopausal women are relatively well understood, the eff ects of the absence of progesterone and decrease of androgens are not fully appreciated ().
In the current study we tried to determine the impact of lipid status, glycoregulation body weight and hypertension as a risk of fatal CVD among postmenopausal women.The possible influence of lifestyle changes, such as six months physical activity and diet regimen, on coronary risk changes were assessed.Th e SCORE ( Systematic Coronary Risk Evaluation) risk assessment system is derived from a large dataset of prospective European studies and predicts any kind of fatal atherosclerotic end-point i.e. fatal CVD events over a tenyear period.Using SCORE it is now possible to produce risk charts tailored for individual countries which may provide reliable national mortality informations.

Patients and Methods
Patients and clinical examination: Methodological approach was examined trough prospective and retrospective analysis of anamnestic data, clinical research, diagnostic tests and biochemical parameters.Research was conducted at the Clinic for endocrinology Faculty of medicine Niš and Institute for prevention, treatment and rehabilitation of rheumatic and cardiovascular diseases Niška Banja Faculty of Medicine Niš and at the Center for medical biochemistry University Clinical Center Niš.Th e research study involved  examinees.All examinees were followed at least  moths.Examined groups were formed based on next criteria: presence of hyperlipidemia, menopause, as absents of regular menstrual bleeding in one whole year, values of glucose and other risk factors.Individuals were divided into  groups: I: postmenopausal women with hyperlipoproteinemia and glycoregulation disorder (N=); II premenopausal women with hyperlipoproteinemia and glycoregulation disorders (N=); Clinical evaluation at the beginning of research included precise anamnestic data based on a questionnaire designed by Institute for prevention, treatment and rehabilitation of rheumatic and cardiovascular diseases Niška Banja, anthropometric  ().Biochemical analyses: Standard methods for determining lipids and lipoproteins, fibrinogen, uric acid and glucose in blood were used.On the basis of clinical examination and biochemical analyses, the atherogenic ratio, calculation of atherogenic phenotype, lipid levels of risk, glycoregulation, risk factor of non lipid origin and absolute ten year risk for nonfatal cardiovascular event were determined ().After clinical examination, the examinees received recommendation for physical activities and diet.Control was done after third and sixth month.Total cholesterol (TC) was determined by enzyme color test (PAP method) ().Triglycerides (TG) were determined by enzyme color test, modifi ed PAP reaction-PAP (GPO) ().Very low density lipoprotein cholesterol (VLDL-C) was calculated indirectly trough its formula VLDL-C= TG/, ().High-density lipoprotein cholesterol (HDL-C) was determined by enzyme color test (PAP method), ().Low-density lipoprotein cholesterol (LDL-C) was calculated indirectly trough its formula LDL-C = TC -TG / , -HDL-C ().
All reagents were purchased from the Randox Company, estimated on the Synchron CX, Beckman analyzer.
Glucose was determined by GOD-PAP method on Synchron CX, Beckman analyzer ().Uric acid was determined by enzyme color test, with modifi ed Trinder, PAP method, measured on the Synchron CX, Beckman analyzer ().Fibrinogen was determined by turbidimetric method ().Oral glucose tolerance test oGTT was preformed in the morning after  hours abstinent from food intake.The patients were taking  grams of glucose dissolved in  ml of water with le mon.Blood for determining glucose was taken before and , ,  and  minute after orally taken glucose ().
Diet: Food and energy intake were adjusted for achiev- Since this chart predicts fatal events the threshold for being at high risk is defi ned as ≥, instead of the previous ≥ in charts using a composite coronary endpoint ().

Results
Postmenopausal women with hyperlipoproteinemia and glycoregulation disordes: Assay had  individuals age behalf with , ± , who had positive family history of cardiovascular disease (CVD) risk ().Among them,  were smokers.Non lipid risk factors have noted signifi cant reduction after  month carried out diet and physical activity in the BMI, systolic and diastolic blood pressure and waist circumference.In this group a trend of a signifi cant decrease of fasting plasma glucose and h-post load glucose after six months therapy was documented (Table ).Only fi brinogen was not signifi cantly changed.After six months of diet/physical activity regimen, the atherogenic lipid profi le (TC, LDL-C, TG) was signifi cantly decreased, while HDL cholesterol tended to be higher (Table ).
Pre-menopausal women with hyperlipoproteinemia and glycoregulation disorders: Assay had  individuals age , ± , year,  had positive family history of CVD.Among them,  were smokers.Non lipid risk factors have noted signifi cant reduction after  month carried out diet and physical activity in the BMI, systolic and diastolic blood pressure and waist circumference.Only fi brinogen and uric acid level remained unchanged (Table ).
In this group a highly signifi cant decrease of fasting plasma glucose and h-post load glucose after six months therapy was documented as well ( months of diet/physical activity regimen exerted benefi t on the atherogenic lipid profi le (TC, LDL-C, TG), did not change signifi cantly VLDL cholesterol, while HDL cholesterol tended to be higher (Table ).By estimating SCORE it was documented that the then year risk of fatal CVD exerted a shift toward the lower percent value in postmenopausal women.It was mainly due to the increased number of examinees with SCORE being .Th e risk of  and above was not documented after diet/physical activity regimen (Figure ).By estimating the prevalence of atherogenic lipid markers it was documented that TC decrease was amongst the most important predictive factors for decreasing atherogenic risk in this population (  ning and the end of the assay was decreased for all investigated lipid parameters in this group of women (Figure ).

Discussion
Menopause is often associated with weight gain.Th e early postmenopausal years are associated with accelerated weight gain.Evidence for this comes from a Swedish study that assessed BMI in a cross-sectional sample of adult population - years of age ().Women exhibit a sharp increase in obesity between the ages  and .Th ere is also evidence suggesting that menopause is associated with changes in body composition and fat distribution.Th e proportion of android (upper-body) fat to gynoid (lower-body) fat deposition is greater in postmenopausal than in pre-menopausal women.In the Iowa Women's Study, which followed over   postmenopausal women, the difference between the two sites of fat deposition became clear ().Th e estrogen has an eff ect on the form of obesity, its defi ciency leads women to attain the metabolic syndrome of overweight/ obese men.Both overall and cardiovascular mortality correlated better with abdominal adiposity, as assessed by the waist hip ratio, than with BMI (a more general measure of adiposity).Th e hormone replacement therapy has been shown to decrease the shift from gynoid to android fat deposition after menopause ().A comparison of middle-aged female twins found that among environmental factors infl uencing total and abdominal fat mass, physical activity (PA) had the strongest eff ect.Th e postmenopausal years have been associated with lower levels of PA, leading to a lower energy expenditure and greater abdominal adiposity in this time of life.Among women aged -, only half reported doing any regular PA, while only about one quarter report high intensity exercise ().Th erefore, insuffi cient PA can be an important factor in postmenopausal weight gain.It was documented that the type  diabetes mellitus can be prevented or delayed through lifestyle interventions, because this disease has a prolonged pre-diabetic phase.
Patients with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have a risk for diabetes.Among other risk factors for diabetes are body mass index (BMI) greater than  kg per m, sedentary lifestyle, hypertension, dyslipidemia, history of gestational diabetes or large-for-gestational-age infant, and polycystic ovary syndrome ().Up to now,  potentially relevant studies were occupied with the relation between physical activity and glucose tolerance ().A great number of patients with IGT have shown success for lifestyle interventions in delaying or preventing the development of diabetes.Th ere is a strong evidence that a well structured program of diet and exercise may reduce the risk of progression to type  diabetes in patients with IGT.It was shown that the risk of diabetes was reduced by approximately  with changes in physical activity levels.Th e contribution of physical activity independent of dietary or weight loss changes to the prevention of type  diabetes in people with pre-diabetes is equivocal.Moderate exercise on a regular, long-term basis has several eff ects on muscle function that lead to more effi cient use of energy.Th ese changes include increases in the quantity of mitochondrial enzymes and the number of "slow-twitch" muscle fi bers, and the development of new muscle capillaries.Th ere is also increased translocation of insulin-responsive glucose transporters (GLUT) from intracellular stores to the cell surface.GLUT promotes glucose uptake, which probably explains the overall increase in insulin sensitivity ().Th e Finnish Twin Cohort study of almost  same sex twin pairs found an odds ratio for death of , in occasional exercisers and , in conditioning exercisers compared with their sedentary twins ().A benefi t from light to moderate exercise has been also shown for Healthy ; the benefi t is again related to the duration of exercise ().
Virtually identical fi ndings were noted in a review of over , postmenopausal women in the Women's Health Initiative Observational Study in which prolonged sitting predicted an increase in cardiovascular risk () tions were made in men, a similar cardiovascular benefi t from fi tness has been found in women and across different ethnic groups ().Th e Nurses' Health study of , women between  to  years of age found that brisk walking or vigorous exercise was inversely related to the risk of a coronary event; in a multivariate analysis, women in increasing quintile groups for energy expenditure had age-adjusted relative risks for coronary events of ,; ,; , and ,, indicating a graded benefi t from exercise.Sedentary women who became active in mid life or later had a lower incidence of coronary events compared to those who remained inactive ().
Prolonged exercise programs cause a greater decrease in abdominal fat.This is important because subjects with abdominal obesity are at increased cardiovascular risk.Exercise reduces serum triglycerides and increases serum HDL-cholesterol, with variable eff ects on total cholesterol, LDL-cholesterol and VLDL-cholesterol ().The risk of cardiovascular diseases increases continuously as blood pressure (BP) rises from levels that are considered to be within the normal range.The decision to start treatment, however, depends not only on the level of blood pressure, but also on an assessment of total cardiovascular risk and the presence or absence of target organ damage (,.The institution of a regular exercise regimen (such as jogging two miles or riding a bicycle for  minutes) can, within four weeks, lower the BP by as much as  to  mmHg in patients with essential hypertension ().

Conclusion
Obtained results confi rmed that diet/physical activity regimen has a great impact on delay of possible cardiovascular events in both, postmenopausal and pre-menopausal women.By using SCORE it is now possible to produce risk charts tailored for individual countries that may provide reliable national mortality information available.Practitioners should use total CVD risk estimation when decisions are taken to intensify preventive actions when dietary advice should be more specifi ed, when the physical activity prescription should be more individualized, when drugs should be prescribed, dosages adapted or combinations started to control risk factors.Th ese decisions should usually not be based on the level of any one risk factor alone.Th e data presented above strongly indicate that physical activity is a crucial factor in weight control and disease prevention throughout menopause and beyond.Another action against modern day illnesses is proper nutrition, comprising of fruit, vegetables and grains, with limited fat and salt.Behavioral changes aimed at decreasing food intake and increasing energy expenditure should be implemented in the life.

List of Abbrevations
Figure ).In pre-menopausal women the estimated ten year risk of fatal CVD by SCORE was shifted toward the level bellow .No one was noted to have a risk above  (Figure).Th e prevalence of the atherogenic lipid markers at the begin- RADOVOJ KOCIĆ ET AL.: IMPACT OF DIET, PHYSICAL ACTIVITY, LIPID STATUS AND GLYCOREGULATION IN ESTIMATION OF SCORE SYSTEMATIC CORONARY RISK EVALUATION  FOR TEN YEARS IN POSTMENOPAUSAL WOMEN measurements for calculating Body Mass Index (BMI) and type of obesity, registered blood-pressure (BP), clinical manifestation of dyslipidemias and atherosclerosis, determined diet and other components of life style

TABLE 1 .
Nutrient composition (7) RADOVOJ KOCIĆ ET AL.: IMPACT OF DIET, PHYSICAL ACTIVITY, LIPID STATUS AND GLYCOREGULATION IN ESTIMATION OF SCORE SYSTEMATIC CORONARY RISK EVALUATION  FOR TEN YEARS IN POSTMENOPAUSAL WOMENing an ideal weight.Next types of food should be recommended: fruit and vegetables, products with less fat and fi sh meat.For fat intake the advice was not to precede more than  of total energy intake, for saturated fat to be / of total fat intake.Cholesterol intake should be less than  mg per day (Table.)().
Physical activity: Patients received recommendation for physical activity lasting - min, - times a week or  min every day, the load not to exceed - average of maximal heart rate.Physical activities should start with warm up and then successively cooling.Exercise comprised of various activities such as: driving a bicycle, swimming, fast walking, and housework.Statistical tests: Student's independent t-test (normal distribution); χ-test; Th e Pearson product -moment coeffi cient of correlation (r) was used to assess associations between variables.Estimation of SCORE: Ten year risk of fatal CVD in high risk regions of Europe was estimated according to the guidelines recommending a new model for total risk estimation based on the SCORE (Systematic Coronary Risk Evaluation) system.It predicts any kind of fatal atherosclerotic end-point i.e. fatal CVD events over a ten-year period.In SCORE the following risk factors are integrated: gender, age, smoking, systolic blood pressure and either total cholesterol or the cholesterol/HDL ratio.

Table  )
. A six TABLE3.Lipid parameters and ratio at the beginning and the end of assay for postmenopausal women

TABLE 2 .
Examined non-lipid risk factors at the beginning and the end of assay for postmenopausal women

TABLE 5 .
Lipid parameters and ratio at the beginning and the end of assay for pre-menopausal women

TABLE 4 .
Examined non-lipid risk factors at the beginning and the end of assay for postmenopausal women RADOVOJ KOCIĆ ET AL.: IMPACT OF DIET, PHYSICAL ACTIVITY, LIPID STATUS AND GLYCOREGULATION IN ESTIMATION OF SCORE SYSTEMATIC CORONARY RISK EVALUATION  FOR TEN YEARS IN POSTMENOPAUSAL WOMEN . Exercise training programs increase activity of mitochondrial enzymes, leading to improved muscle energy expenditure, decreased insulin resistance, and a lower rate of progression to overt type  diabetes (,).A number of studies have shown a strong inverse relationship between leisure time activity and energy expenditure, habitual exercise, and fi tness and the risk of coronary disease and death.Although most observa-RADOVOJ KOCIĆ ET AL.: IMPACT OF DIET, PHYSICAL ACTIVITY, LIPID STATUS AND GLYCOREGULATION IN ESTIMATION OF SCORE SYSTEMATIC CORONARY RISK EVALUATION  FOR TEN YEARS IN POSTMENOPAUSAL WOMEN