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Prevalence and predictors of metabolic syndrome among Congolese pre- and postmenopausal women M. J. Muchanga Sifa*,†, F. B. Lepira‡, A. L. Longo‡, E. K. Sumaili‡, J. R. Makulo‡, E. P. Mbelambela**, R. Tozin*, N. R. Ngatu† and N. Suganuma† *Department of Gynecology and Obstetrics, Kinshasa University Hospital, Kinshasa, Democratic Republic of the Congo; †Department of Environmental Medicine, Kochi Medical School, Kochi University, Kochi, Japan; ‡Department of Internal Medicine, Kinshasa University Hospital, Kinshasa, Democratic Republic of the Congo; **Akram Medical Center, Kinshasa, Democratic Republic of the Congo Key words: METABOLIC SYNDROME, PREDICTORS, BLACK WOMEN, MENOPAUSE
ABSTRACT Objectives This study aimed to determine the prevalence and predictors of metabolic syndrome (MetS) among Congolese pre- and postmenopausal women. Methods In total, 200 women (100 premenopausal and 100 postmenopausal) were interviewed and underwent clinical and biological investigations searching for lipid and non-lipid cardiovascular risk factors. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria were used to define MetS. Multivariate logistic regression analysis was used to evaluate predictors of MetS. Results There were significant differences between the two groups in terms of age, plasma cholesterol, high density lipoprotein cholesterol and triglyceride levels. MetS was present in 20% and 10% of postmenopausal and premenopausal women (p ⫽ 0.07), respectively. The MetS components hypertension, elevated plasma glucose and triglycerides were more frequently observed in post- vs. premenopausal women with MetS. Menopause (adjusted odds ratio (aOR) 2.49; 95% confidence interval (CI) 1.05–5.95), overweight (aOR 6.35; 95% CI 1.66–24.23) and obesity (aOR 14.29; 95% CI: 3.84–53.06) emerged as the main independent predictors of MetS. Conclusion This study showed that MetS is common among Congolese postmenopausal women; menopause and weight gain emerged as its main predictors. This suggests that an integrated therapeutic approach combining hormone replacement therapy and lifestyle change in postmenopausal women should be considered.
INTRODUCTION Cardiovascular disease is the largest single cause of death in women world-wide, accounting for one-third of all deaths1. Although the incidence of cardiovascular disease in women increases during the transition from premenopause to postmenopause, the mechanism by which menopause exerts its effects on the cardiovascular system is not yet well understood2–5. The metabolic syndrome (MetS), whose frequency also increases during the transition from premenopause to postmenopause6,7, might explain the excess cardiovascular morbidity and mortality in postmenopausal women2,6,8.
Whereas the prevalence of MetS and its individual components such as hypertension in Western societies is higher in men aged 30–45 years than in women of similar age, it increases in older women to similar levels or higher than in men2,9. Whether this is related to ovarian senescence and the subsequent change in hormonal milieu or caused by menopause-associated increase in age and body mass index (BMI) is still debated2,10. Cross-sectional and longitudinal studies have explored this issue with conflicting results6. Although many studies have reported an association between menopause and MetS, a number of other studies have reported no association, and a few studies have even reported a low prevalence
Correspondence: Dr M. J. Muchanga Sifa, Department of Environmental Medicine, Kochi Medical School, Oko-cho, Nankoku-city, Kochi prefecture, Japan; E-mail: [email protected] ORIGINAL ARTICLE © 2014 International Menopause Society DOI: 10.3109/13697137.2013.856403
Received 16-09-2013 Revised 03-10-2013 Accepted 14-10-2013
Metabolic syndrome in Congolese women of MetS during menopause6. Several studies linking MetS to menopause have found it to be explained by age or BMI or by a combination of both6. Some studies reported that the increased risk of menopause-related MetS could not be attributed solely to age2. Therefore, further studies aimed to clarify this issue are awaited. The clarification of this issue is of utmost public health importance since approximately 95% of women in industrialized countries spend more than one-third of their life in menopause (WHO) and, in 2030, there will be one billion two hundred million menopausal women11. Sub-Saharan Africa, like other regions of the developing world, is experiencing an epidemic of cardiovascular disease that is thought to be driven by the ever-growing incidence of obesity, hypertension and diabetes, all components of MetS12. With the improvement of life expectancy in Sub-Saharan Africa, a substantial proportion of women will spend an important portion of their life in menopause, with a potential increase in cardiovascular risk13,14. Unfortunately, few studies are devoted to the relationship between menopause and cardiovascular disease or its surrogate markers such as MetS15,16. In the Democratic Republic of the Congo, few studies conducted on menopause have targeted other aspects than cardiovascular risk17,18. Furthermore, studies on MetS involved populations other than postmenopausal women19,20. To fill out this gap, the present study was aimed to evaluate the prevalence and predictors of MetS in postmenopausal women seen in outpatient Gynecology Clinics in comparison to premenopausal women. To our best knowledge, this is the first study that investigates the relationship between MetS components and menopause in both pre- and postmenopausal Central African women.
Muchanga et al. that period, 311 women aged 40–60 years old came to the clinics for various gynecologic and obstetric problems. A total of 111 women with past medical history of hysterectomy, those under hormone replacement therapy and pregnant women were excluded. At the first visit, an interview was conducted; information regarding lifestyle (self-reported physical activity, alcohol consumption and smoking habit), menses characteristics, duration of menopause, family and past medical history of diabetes, cardiovascular disease, hypertension and current antihypertensive medication was collected. At the second visit, a physical examination was performed; adiposity was estimated with the use of BMI and waist circumference. Seated blood pressure was measured at the left arm from each subject with the help of an Omron M1 digital electronic blood pressure/pulse monitor (OMRON Corporation, Tokyo, Japan) after 5 min of relaxation; three blood pressure measurements were taken and averaged for analysis. Pulse pressure was calculated as systolic blood pressure minus diastolic blood pressure. The following measurements were taken from all patients after 12-h fasting: total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, and glucose. Cholesterol (Cholesterol Test Kit, Wybenga & Pileggi-One Step Method, Span Diagnostics Ltd) and triglycerides (Triglycerides Test, enzymatic GPO-PAP method, Span Diagnostics Ltd) were measured using enzymatic methods. Low density lipoprotein (LDL) cholesterol was calculated according to Friedewald22. The Combur test was used to assess dipstick proteinuria.
Definition of MetS and menopause PATIENTS AND METHODS Participants and study design This was a cross-sectional study conducted from January through June 2010 at the Department of Gynecology and Obstetrics, University of Kinshasa Hospital, and Akram Medical Center in Kinshasa. A total of 200 (100 premenopausal and 100 postmenopausal women) adult (40–60 years) Congolese women took part in the study. We hypothesized that postmenopausal women are more likely to develop MetS than premenopausal women and we expected to have 20% of premenopausal women with MetS. According to the study conducted by Cho and colleagues, postmenopausal women had an increased risk of MetS (odds ratio 2.93)21. The sample size of 200 used in our study was sufficient to test all the study hypotheses at the 5% level of significance with a power of 80% (β ⫽ 0.80). A convenience sampling procedure by consecutive and stratified recruitment was used to select the subjects. We planned to collect 100 post- and 100 premenopausal women. We started the recruitment for both the groups at the same time. It took 4 months to reach 100 postmenopausal women and 2 more months to reach 100 premenopausal women. During
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MetS was defined according to National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATPIII) criteria as the presence of three of the following: blood pressure ⬎ 130/85 mmHg, waist circumference ⬎ 88 cm in women and ⫺ ⬎ 102 cm in men (central obesity), triglycerides ⫺ ⬎ 1.69 mmol/l, HDL cholesterol ⬍ 1.30 mmol/l in women and ⬍ 1.04 mmol/l in men, glucose ⫺ ⬎ 6.11 mmol/l23. Women were defined as postmenopausal if they reported their last menses to be at least 12 months prior to this study, and premenopausal if they had had an unchanged or irregular menstrual pattern24.
Ethical consideration All patients provided written informed consent and the study was approved by the Research and Ethics committee of the Faculty of Medicine, University of Kinshasa.
Statistical analysis Data were expressed as mean ⫹ ⫺ standard deviation or relative frequency in percent. The distribution of serum lipids being positively skewed, a non-parametric test (Mann–Whitney)
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Table 1 Clinical characteristics of the study population as a whole and according to menses characteristics. Data are given as mean ⫹ ⫺ standard deviation or relative frequency in percent Whole group (n ⫽ 200)
Characteristic Age (years) Married Education Family history of diabetes mellitus Family history of hypertension Family history of cardiovascular disease, Diabetes mellitus Hypertension Cardiovascular disease Physical activity Menopause duration (years) Body mass index (kg/m2) Waist circumference (cm) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Pulse pressure (mmHg) Heart rate (beats/min)
49 ⫹ ⫺6 88.5% 75% 21% 33% 3% 4.5% 23% 4% 18% – 27 ⫹ ⫺7 89 ⫹ ⫺ 14 123 ⫹ ⫺ 30 78 ⫹ ⫺ 14 45 ⫹ ⫺ 12 80 ⫹ ⫺8
Postmenopause (n ⫽ 100) 53 ⫹ ⫺4 89% 72% 23% 47% 2% 6% 27% 3% 16% 6⫹ ⫺5 27 ⫹ ⫺6 90 ⫹ ⫺ 14 126 ⫹ ⫺ 19 80 ⫹ ⫺ 13 46 ⫹ ⫺ 12 80 ⫹ ⫺9
Premenopause (n ⫽ 100) 44 ⫹ ⫺ 3*** 88% 78% 17% 19% 1% 3% 19%* 1% 20% – 27 ⫹ ⫺8 88 ⫹ ⫺ 14 120 ⫹ ⫺ 24 76 ⫹ ⫺ 15 45 ⫹ ⫺ 13 81 ⫹ ⫺8
*, p ⬍ ⫺ 0.05; ***, p ⬍ ⫺ 0.001
was used for these variables. χ2 and Student t-tests were performed to compare normally distributed categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to evaluate the relative contribution of menopause to the risk of MetS after adjusting for age, BMI, smoking, alcohol intake, and duration of menopause. A p value ⬍ ⫺ 0.05 defined the statistical significance. All statistical analyses were performed with SPSS for Windows version 17.0 at the Division of Nephrology, Department of Internal Medicine, University of Kinshasa Hospital.
RESULTS Clinical and biological parameters of the study population according to characteristics of menses are summarized in
Tables 1 and 2. A total of 200 (100 postmenopausal and 100 premenopausal) adult women (mean age 49 ⫹ ⫺ 6 years) were examined. Compared to premenopausal women, postmenopausal women had higher proportions of subjects with hypertension and, on average, higher levels of total cholesterol (5.59 ⫹ ⫺ 1.11 vs. 5.29 ⫹ ⫺ 1.11 mmol/l; p ⫽ 0.05), HDL cholesterol (1.59 ⫹ 0.33 vs. 1.47 ⫹ ⫺ ⫺ 0.30 mmol/l; p ⫽ 0.01) and triglycerides (1.49 ⫹ 1.05 vs. 1.08 ⫹ ⫺ ⫺ 0.57 mmol/l; p ⫽ 0.0007). Differences in other variables of interest did not reach the level of statistical significance (Tables 1 and 2). Overall, 15% of the study population met the NCEP–ATPIII criteria for MetS. According to menses characteristics, MetS was present in 20% and 10% of postmenopausal and premenopausal women, respectively; however, the observed difference was not statistically significant (p ⫽ 0.07). The prevalence of individual components of MetS in the subgroup of women with MetS are depicted in Table 3. In
Table 2 Biological characteristics of the study population as a whole and according to menses characteristics. Data are given as mean ⫹ ⫺ standard deviation or relative frequency in percent Characteristic Total cholesterol (mmol/l) LDL cholesterol (mmol/l) HDL cholesterol (mmol/l) Triglycerides (mmol/l) Glucose (mmol/l) Proteinuria
Whole group (n ⫽ 200)
Postmenopause (n ⫽ 100)
Premenopause (n ⫽ 100)
5.44 ⫹ ⫺ 1.12 3.65 ⫹ ⫺ 0.81 1.53 ⫹ ⫺ 0.32 1.29 ⫹ ⫺ 0.87 5.35 ⫹ ⫺ 2.01 36%
5.59 ⫹ ⫺ 1.11 3.50 ⫹ ⫺ 0.31 1.59 ⫹ ⫺ 0.33 1.49 ⫹ ⫺ 1.05 5.45 ⫹ ⫺ 1.69 40%
5.29 ⫹ ⫺ 1.11* 3.59 ⫹ ⫺ 0.29 1.47 ⫹ ⫺ 0.33** 1.08 ⫹ ⫺ 0.57*** 5.25 ⫹ ⫺ 2.29 32%
HDL, high density lipoprotein; LDL, low density lipoprotein *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01; ***, p ⬍ ⫺ 0.001
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Table 3 Individual components of the metabolic syndrome (MetS) among pre- and postmenopausal women with MetS. Data are expressed as n (relative frequency in percent) MetS components Impaired fasting plasma glucose High triglycerides High blood pressure Central obesity Low HDL cholesterol
Postmenopause (n ⫽ 20) 13 10 20 12 5
(72.23%) (76.92%) (66.67%) (46.16%) (38.46%)
Premenopause (n ⫽ 10) 5 (27.77%)** 3 (23.08%)** 10 (33.33%)* 14 (53.85%) 8 (61.54%)
Total (n ⫽ 30) 18 13 30 26 13
(100%) (100%) (100%) (100%) (100%)
HDL, high density lipoprotein *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01
postmenopausal women with MetS, elevated plasma glucose and triglycerides, high blood pressure, central obesity and low HDL cholesterol as individual components of the MetS were observed in 72.23%, 76.92%, 66.67%, 46.15% and 38.46% of women, respectively. Compared to premenopausal women with MetS, a significantly higher proportion of postmenopausal women with MetS had elevated plasma glucose levels (72.23% vs. 27.77%; p ⫽ 0.01), triglycerides (76.92% vs. 23.08%; p ⫽ 0.01) and hypertension (66.67% vs. 33.33%; p ⫽ 0.02). In the univariate analysis, predictors of MetS were menopause, overweight, family history of diabetes mellitus, family history of cardiovascular disease, and family history of hypertension (Table 4). However, after adjusting for age, BMI, smoking, alcohol intake and duration of menopause, menopause, overweight and obesity emerged as the main predictors of the risk of MetS. The risk of MetS was 2- (adjusted odds ratio (aOR) 2.49; 95% confidence interval (CI) 1.05–5.95), 6- (aOR 6.35; 95% CI 1.66–24.23) and 14-fold (aOR 14.29; 95% CI 3.84–53.06) greater in postmenopausal, overweight and obese women in comparison to their counterparts (Table 5).
DISCUSSION The present study aimed to evaluate the prevalence of MetS and determine its predictors in Congolese postmenopausal women. The key findings are as follows. First, postmenopausal women had, on average, higher levels of total cholesterol, HDL cholesterol and triglycerides than premenopausal women; second, the frequency of MetS tended to be higher in post- than premenopausal women; third, high blood pressure, elevated plasma glucose and triglycerides were individual components of MetS most frequently seen in postmenopausal women with MetS in comparison with their premenopausal counterparts; fourth, menopause, overweight and obesity emerged as the main independent predictors of MetS. Higher levels of total cholesterol and triglycerides observed in postmenopausal women in the present study corroborate with previous reports on abnormal lipid profile in this category of women7. Elevated levels of cholesterol, triglycerides, fibrinogen and lipoprotein(a) have already been observed following menopause25. Indeed, in a longitudinal study of 541 initially premenopausal women aged 42–50 years, greater changes in blood lipid levels were seen in those women who underwent menopause than in those who did not26. While age
Table 4 Univariate analyses of predictors of metabolic syndrome (MetS) according to menses characteristics. Data are expressed as n (relative frequency in percent) Variable Married vs. not Postmenopause vs. premenopause Family history of diabetes mellitus vs. not Body mass index (kg/m2) 18–24.9 25–29.9 ⬎ 30 ⫺ Alcohol intake vs. not Education: elementary vs. high school or higher Physical activity vs. not Family history of cardiovascular diseases vs. not Family history of hypertension vs. not
MetS
Odds ratio
25 (83.3%) 20 (66.7%) 11 (36.7%)
0.592 2.250 2.596
3 11 16 6 3 24 2 19
(10%) (36.7%) (53.3%) (20%) (10%) (80%) (6.7%) (63.3%)
5.500 14.400 1.078 0.339 0.857 6.000 2.188
95% confidence interval 0.202–1.739 0.994–5.092* 1.122–6.004*
1.466–20.63* 3.915–52.96*** 0.407–2.855 0.098–1.173 0.322–2.278 0.812–44.35 0.981–4.879*
*, p ⬍ ⫺ 0.05; ***, p ⬍ ⫺ 0.001
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Table 5 Independent predictors of metabolic syndrome (MetS) calculated by stepwise logistic regression according to menses characteristics Regression coefficient β
Odds ratio (standard error)
Menopausal status†
0.991
2.50 (0.44)
Body mass index (kg/m2) Normal (18–24.9) Overweight (25–29.9) Obese (⫺ ⬎ 30)
1 (ref) 1.848 2.659
1 6.35 (0.68) 13.29 (0.67)
Variable
95% confidence interval 1.04–5.95*
– 1.66–24.23** 3.84–53.06***
† *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01; ***, p ⬍ ⫺ 0.001; , postmenopausal vs. premenopausal
may contribute to altered lipid metabolism, menopause itself through estrogen deficiency and associated morphological changes may play a significant role26. These findings support the general consensus that menopause, whether natural or surgical, is associated with a less desirable lipid profile25. In the present study, higher HDL cholesterol levels were observed in older Congolese postmenopausal women in comparison with younger premenopausal ones. Although most studies have reported low HDL cholesterol levels in post- than premenopausal women, there are some previous researches that have also observed higher levels of this lipoprotein in postmenopausal Korean, Iranian and American women27–29. However, the mechanisms underlying increased HDL cholesterol levels in menopause are not yet fully understood28. One of the proposed mechanisms is age-induced changes in the HDL cholesterol profile27. In women, HDL cholesterol levels increase progressively to the sixth decade, and then decrease28. Therefore, age may influence HDL cholesterol levels, leading to discrepancy among studies27. Several reports that considered the age of subjects showed similar or even higher HDL cholesterol levels in postmenopausal women compared to premenopausal ones27. In the Atherosclerosis Risk in Communities and Framingham Heart Study, significant differences in HDL cholesterol levels were not observed between pre- and postmenopausal women in the fixed age intervals30. Our study showed a higher frequency of MetS in post- than premenopausal women; however, the difference did not reach statistical significance. This finding also corroborates with previous studies reporting a progressive increase in the prevalence or incidence of MetS during the transition from pre- to postmenopause2,15,31–35. The mechanisms underlying the increased prevalence or incidence of MetS during the transition from pre- to postmenopause are not yet well elucidated. It has been suggested that the hormonal dysregulation occurring during the menopausal transition may play a key role in the initiation of pathobiological changes such as adverse lipid profile and atherosclerotic plaques that will increase risk of cardiovascular disease during the postmenopausal period36. Some studies, however, attributed these pathobiological changes to the aging process and associated weight gain with subsequent insulin resistance30,37,38. To reconcile these opposed opinions, a combination of hormonal dysregulation and aging effects on lipid metabolism and the cardiovascular system has
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been evoked37; Matthews and colleagues have shown that triglycerides increased with age but total cholesterol, LDL cholesterol and apolipoprotein B increased specifically with menopausal status39. Furthermore there is experimental evidence from intervention studies using hormone replacement therapies and ovariectomy, and correlations of circulating hormones levels with disease risk, which indicate that the decrease in estrogen levels is central to the development of age-related diseases40. There is considerable evidence that only physiological hormone replacement therapies delay the onset, halt the progression and even reverse the course of age-related diseases41,42. Individual MetS components more frequently seen in postthan premenopausal women with MetS were high blood pressure, elevated plasma glucose and triglycerides. These findings are in agreement with a report by Heidari and colleagues who found that, except for high blood pressure and elevated triglycerides, there was no significant difference between pre- and postmenopausal women when MetS components were considered31. They concluded that, in contrast to the claims regarding the role of waist circumference in the occurrence of MetS during the menopausal transition, the presence of MetS could be independent of abdominal adiposity31. Furthermore, Lejskova and colleagues reported in menopausal women an increase in the clustered incidence of MetS components at the expense of isolated incidence43. Of note, some MetS components such as hypertension and diabetes have been reported to carry a greater risk for cardiovascular disease in women43,44. In Congolese women, menopause, overweight and obesity emerged as the main predictors of the risk of MetS as a surrogate marker of cardiovascular risk. Although many risk factors contribute to cardiovascular disease in women, menopause appears for some authors as the strongest one45. Previous studies found that MetS risk increased progressively up to 14 years since menopause before declining21,46,47. The mechanism underlying this increased risk remains a subject of controversy. Menopause-induced hormonal dysregulation and subsequent weight gain were evoked as responsible for the clustering of MetS risk factors43,46. The association of obesity with the risk of MetS in menopause has already been reported47,48. Indeed, Kim and colleagues showed that, compared to normal weight, overweight and obesity were associated with 6- and 14-fold greater risk of MetS, respectively46.
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Metabolic syndrome in Congolese women In some studies, this increased risk was attributable to the aging process associated with menopause31,38,43,48. Given the fact that there is an increasing prevalence of obesity, diabetes, hypertension (9–15%, 7–12% and 10–28% increase within two decades, respectively) and chronic renal diseases with renal failure in the Congolese population and the inaccessibility to hemodialysis by the majority of patients (only 8% of patients have access to hemodialysis) because of financial reasons, there is a necessity for early detection and treatment of risk factors49.
Muchanga et al. menopause was defined on the basis of self-reported menstrual bleeding characteristics without hormone measurements. However, NHANES demonstrated that this menstrually defined measure of menopause correlates strongly with hormone measurements50. In conclusion, the present study has shown that MetS is common among Congolese postmenopausal women, and that hypertension, elevated plasma glucose and serum triglycerides are the MetS components more frequently encountered among postmenopausal women in comparison to their premenopausal counterparts. Menopause itself, overweight and obesity emerged as the main predictors of MetS.
Limitations The stratified cross-sectional design of the present work precludes clear establishment of a causal relationship between MetS and associated risk factors. A longitudinal study would be more appropriate for this question. Furthermore,
Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
University of Kinshasa.
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Muchanga et al. 39. Matthews KA, Crawford SL, Chae CU, et al. Are changes in cardiovascular disease risk factors in midlife women due to chronological aging or the menopausal transition? J Am Coll Cardiol 2009;54:2366–73 40. Atwood CS, Bowen RL. The reproductive-cell cycle theory of aging: An update. Exp Gerontol 2011;46:100–7 41. Santen RJ, Allred DC, Ardoin SP, et al. Postmenopausal hormone therapy: an Endocrine Society scientific statement. J Clin Endocrinol Metab 95(7 Suppl 1):s1–66 42. Nilsen J, Morales A, Brinton RD. Medroxyprogesterone acetate exacerbates glutamate excitotoxicity. Gynecol Endocrinol 2006; 22:355–61 43. Lejskova M, Alusik S, Suchanek M, Zecova S, Pitha J. Menopause: clustering of metabolic syndrome components and population changes in insulin resistance. Climacteric 2011;14:83–91 44. Nuzzo A, Rossi R, Modena MG. Hypertension alone or related to metabolic syndrome in postmenopausal women. Expert Cardiovasc Ther 2010;8:1541–8 45. Bozkurt B. Where do we currently stand with advice on HRT for women. Methodist Debakey Cardiovasc J 2010;6:21–5 46. Kim HM, Park J, Ryu SY, Kim J. The effect of menopause on the metabolic syndrome among Korean women. Diabetes Care 2007;30:701–6 47. Ruan X, Jin J, Hua L, et al. The prevalence of metabolic syndrome in Chinese postmenopausal women and the optimum body composition indices to predict it. Menopause 2010;17:566–70 48. Teede HJ, Lombart C, Deeks AA. Obesity, metabolic complications and menopause: an opportunity for prevention. Climacteric 2010;13:203–9 49. Sumaili EK, Krzesinski JM, Ohen EP, et al. Epidemiology of chronic kidney disease in the Democratic Republic of Congo: Review of cross-sectional studies from Kinshasa, the capital of the Democratic Republic of the Congo. Nephrologie et Therapeutique 2010;6:232–9 50. Cooper GS, Baird DD, Darden FR. Measures of menstrual status in relation to demographic, reproductive, and behavioral characteristics in a population-based study of women aged 35–49 years. Am J Epidemiol 2001;153:1159–65
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Prevalence and predictors of metabolic syndrome among Congolese pre- and postmenopausal women M. J. Muchanga Sifa*,†, F. B. Lepira‡, A. L. Longo‡, E. K. Sumaili‡, J. R. Makulo‡, E. P. Mbelambela**, R. Tozin*, N. R. Ngatu† and N. Suganuma† *Department of Gynecology and Obstetrics, Kinshasa University Hospital, Kinshasa, Democratic Republic of the Congo; †Department of Environmental Medicine, Kochi Medical School, Kochi University, Kochi, Japan; ‡Department of Internal Medicine, Kinshasa University Hospital, Kinshasa, Democratic Republic of the Congo; **Akram Medical Center, Kinshasa, Democratic Republic of the Congo Key words: METABOLIC SYNDROME, PREDICTORS, BLACK WOMEN, MENOPAUSE
ABSTRACT Objectives This study aimed to determine the prevalence and predictors of metabolic syndrome (MetS) among Congolese pre- and postmenopausal women. Methods In total, 200 women (100 premenopausal and 100 postmenopausal) were interviewed and underwent clinical and biological investigations searching for lipid and non-lipid cardiovascular risk factors. National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATPIII) criteria were used to define MetS. Multivariate logistic regression analysis was used to evaluate predictors of MetS. Results There were significant differences between the two groups in terms of age, plasma cholesterol, high density lipoprotein cholesterol and triglyceride levels. MetS was present in 20% and 10% of postmenopausal and premenopausal women (p ⫽ 0.07), respectively. The MetS components hypertension, elevated plasma glucose and triglycerides were more frequently observed in post- vs. premenopausal women with MetS. Menopause (adjusted odds ratio (aOR) 2.49; 95% confidence interval (CI) 1.05–5.95), overweight (aOR 6.35; 95% CI 1.66–24.23) and obesity (aOR 14.29; 95% CI: 3.84–53.06) emerged as the main independent predictors of MetS. Conclusion This study showed that MetS is common among Congolese postmenopausal women; menopause and weight gain emerged as its main predictors. This suggests that an integrated therapeutic approach combining hormone replacement therapy and lifestyle change in postmenopausal women should be considered.
INTRODUCTION Cardiovascular disease is the largest single cause of death in women world-wide, accounting for one-third of all deaths1. Although the incidence of cardiovascular disease in women increases during the transition from premenopause to postmenopause, the mechanism by which menopause exerts its effects on the cardiovascular system is not yet well understood2–5. The metabolic syndrome (MetS), whose frequency also increases during the transition from premenopause to postmenopause6,7, might explain the excess cardiovascular morbidity and mortality in postmenopausal women2,6,8.
Whereas the prevalence of MetS and its individual components such as hypertension in Western societies is higher in men aged 30–45 years than in women of similar age, it increases in older women to similar levels or higher than in men2,9. Whether this is related to ovarian senescence and the subsequent change in hormonal milieu or caused by menopause-associated increase in age and body mass index (BMI) is still debated2,10. Cross-sectional and longitudinal studies have explored this issue with conflicting results6. Although many studies have reported an association between menopause and MetS, a number of other studies have reported no association, and a few studies have even reported a low prevalence
Correspondence: Dr M. J. Muchanga Sifa, Department of Environmental Medicine, Kochi Medical School, Oko-cho, Nankoku-city, Kochi prefecture, Japan; E-mail: [email protected] ORIGINAL ARTICLE © 2014 International Menopause Society DOI: 10.3109/13697137.2013.856403
Received 16-09-2013 Revised 03-10-2013 Accepted 14-10-2013
Metabolic syndrome in Congolese women of MetS during menopause6. Several studies linking MetS to menopause have found it to be explained by age or BMI or by a combination of both6. Some studies reported that the increased risk of menopause-related MetS could not be attributed solely to age2. Therefore, further studies aimed to clarify this issue are awaited. The clarification of this issue is of utmost public health importance since approximately 95% of women in industrialized countries spend more than one-third of their life in menopause (WHO) and, in 2030, there will be one billion two hundred million menopausal women11. Sub-Saharan Africa, like other regions of the developing world, is experiencing an epidemic of cardiovascular disease that is thought to be driven by the ever-growing incidence of obesity, hypertension and diabetes, all components of MetS12. With the improvement of life expectancy in Sub-Saharan Africa, a substantial proportion of women will spend an important portion of their life in menopause, with a potential increase in cardiovascular risk13,14. Unfortunately, few studies are devoted to the relationship between menopause and cardiovascular disease or its surrogate markers such as MetS15,16. In the Democratic Republic of the Congo, few studies conducted on menopause have targeted other aspects than cardiovascular risk17,18. Furthermore, studies on MetS involved populations other than postmenopausal women19,20. To fill out this gap, the present study was aimed to evaluate the prevalence and predictors of MetS in postmenopausal women seen in outpatient Gynecology Clinics in comparison to premenopausal women. To our best knowledge, this is the first study that investigates the relationship between MetS components and menopause in both pre- and postmenopausal Central African women.
Muchanga et al. that period, 311 women aged 40–60 years old came to the clinics for various gynecologic and obstetric problems. A total of 111 women with past medical history of hysterectomy, those under hormone replacement therapy and pregnant women were excluded. At the first visit, an interview was conducted; information regarding lifestyle (self-reported physical activity, alcohol consumption and smoking habit), menses characteristics, duration of menopause, family and past medical history of diabetes, cardiovascular disease, hypertension and current antihypertensive medication was collected. At the second visit, a physical examination was performed; adiposity was estimated with the use of BMI and waist circumference. Seated blood pressure was measured at the left arm from each subject with the help of an Omron M1 digital electronic blood pressure/pulse monitor (OMRON Corporation, Tokyo, Japan) after 5 min of relaxation; three blood pressure measurements were taken and averaged for analysis. Pulse pressure was calculated as systolic blood pressure minus diastolic blood pressure. The following measurements were taken from all patients after 12-h fasting: total cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, and glucose. Cholesterol (Cholesterol Test Kit, Wybenga & Pileggi-One Step Method, Span Diagnostics Ltd) and triglycerides (Triglycerides Test, enzymatic GPO-PAP method, Span Diagnostics Ltd) were measured using enzymatic methods. Low density lipoprotein (LDL) cholesterol was calculated according to Friedewald22. The Combur test was used to assess dipstick proteinuria.
Definition of MetS and menopause PATIENTS AND METHODS Participants and study design This was a cross-sectional study conducted from January through June 2010 at the Department of Gynecology and Obstetrics, University of Kinshasa Hospital, and Akram Medical Center in Kinshasa. A total of 200 (100 premenopausal and 100 postmenopausal women) adult (40–60 years) Congolese women took part in the study. We hypothesized that postmenopausal women are more likely to develop MetS than premenopausal women and we expected to have 20% of premenopausal women with MetS. According to the study conducted by Cho and colleagues, postmenopausal women had an increased risk of MetS (odds ratio 2.93)21. The sample size of 200 used in our study was sufficient to test all the study hypotheses at the 5% level of significance with a power of 80% (β ⫽ 0.80). A convenience sampling procedure by consecutive and stratified recruitment was used to select the subjects. We planned to collect 100 post- and 100 premenopausal women. We started the recruitment for both the groups at the same time. It took 4 months to reach 100 postmenopausal women and 2 more months to reach 100 premenopausal women. During
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MetS was defined according to National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATPIII) criteria as the presence of three of the following: blood pressure ⬎ 130/85 mmHg, waist circumference ⬎ 88 cm in women and ⫺ ⬎ 102 cm in men (central obesity), triglycerides ⫺ ⬎ 1.69 mmol/l, HDL cholesterol ⬍ 1.30 mmol/l in women and ⬍ 1.04 mmol/l in men, glucose ⫺ ⬎ 6.11 mmol/l23. Women were defined as postmenopausal if they reported their last menses to be at least 12 months prior to this study, and premenopausal if they had had an unchanged or irregular menstrual pattern24.
Ethical consideration All patients provided written informed consent and the study was approved by the Research and Ethics committee of the Faculty of Medicine, University of Kinshasa.
Statistical analysis Data were expressed as mean ⫹ ⫺ standard deviation or relative frequency in percent. The distribution of serum lipids being positively skewed, a non-parametric test (Mann–Whitney)
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Table 1 Clinical characteristics of the study population as a whole and according to menses characteristics. Data are given as mean ⫹ ⫺ standard deviation or relative frequency in percent Whole group (n ⫽ 200)
Characteristic Age (years) Married Education Family history of diabetes mellitus Family history of hypertension Family history of cardiovascular disease, Diabetes mellitus Hypertension Cardiovascular disease Physical activity Menopause duration (years) Body mass index (kg/m2) Waist circumference (cm) Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Pulse pressure (mmHg) Heart rate (beats/min)
49 ⫹ ⫺6 88.5% 75% 21% 33% 3% 4.5% 23% 4% 18% – 27 ⫹ ⫺7 89 ⫹ ⫺ 14 123 ⫹ ⫺ 30 78 ⫹ ⫺ 14 45 ⫹ ⫺ 12 80 ⫹ ⫺8
Postmenopause (n ⫽ 100) 53 ⫹ ⫺4 89% 72% 23% 47% 2% 6% 27% 3% 16% 6⫹ ⫺5 27 ⫹ ⫺6 90 ⫹ ⫺ 14 126 ⫹ ⫺ 19 80 ⫹ ⫺ 13 46 ⫹ ⫺ 12 80 ⫹ ⫺9
Premenopause (n ⫽ 100) 44 ⫹ ⫺ 3*** 88% 78% 17% 19% 1% 3% 19%* 1% 20% – 27 ⫹ ⫺8 88 ⫹ ⫺ 14 120 ⫹ ⫺ 24 76 ⫹ ⫺ 15 45 ⫹ ⫺ 13 81 ⫹ ⫺8
*, p ⬍ ⫺ 0.05; ***, p ⬍ ⫺ 0.001
was used for these variables. χ2 and Student t-tests were performed to compare normally distributed categorical and continuous variables, respectively. Multivariate logistic regression analysis was performed to evaluate the relative contribution of menopause to the risk of MetS after adjusting for age, BMI, smoking, alcohol intake, and duration of menopause. A p value ⬍ ⫺ 0.05 defined the statistical significance. All statistical analyses were performed with SPSS for Windows version 17.0 at the Division of Nephrology, Department of Internal Medicine, University of Kinshasa Hospital.
RESULTS Clinical and biological parameters of the study population according to characteristics of menses are summarized in
Tables 1 and 2. A total of 200 (100 postmenopausal and 100 premenopausal) adult women (mean age 49 ⫹ ⫺ 6 years) were examined. Compared to premenopausal women, postmenopausal women had higher proportions of subjects with hypertension and, on average, higher levels of total cholesterol (5.59 ⫹ ⫺ 1.11 vs. 5.29 ⫹ ⫺ 1.11 mmol/l; p ⫽ 0.05), HDL cholesterol (1.59 ⫹ 0.33 vs. 1.47 ⫹ ⫺ ⫺ 0.30 mmol/l; p ⫽ 0.01) and triglycerides (1.49 ⫹ 1.05 vs. 1.08 ⫹ ⫺ ⫺ 0.57 mmol/l; p ⫽ 0.0007). Differences in other variables of interest did not reach the level of statistical significance (Tables 1 and 2). Overall, 15% of the study population met the NCEP–ATPIII criteria for MetS. According to menses characteristics, MetS was present in 20% and 10% of postmenopausal and premenopausal women, respectively; however, the observed difference was not statistically significant (p ⫽ 0.07). The prevalence of individual components of MetS in the subgroup of women with MetS are depicted in Table 3. In
Table 2 Biological characteristics of the study population as a whole and according to menses characteristics. Data are given as mean ⫹ ⫺ standard deviation or relative frequency in percent Characteristic Total cholesterol (mmol/l) LDL cholesterol (mmol/l) HDL cholesterol (mmol/l) Triglycerides (mmol/l) Glucose (mmol/l) Proteinuria
Whole group (n ⫽ 200)
Postmenopause (n ⫽ 100)
Premenopause (n ⫽ 100)
5.44 ⫹ ⫺ 1.12 3.65 ⫹ ⫺ 0.81 1.53 ⫹ ⫺ 0.32 1.29 ⫹ ⫺ 0.87 5.35 ⫹ ⫺ 2.01 36%
5.59 ⫹ ⫺ 1.11 3.50 ⫹ ⫺ 0.31 1.59 ⫹ ⫺ 0.33 1.49 ⫹ ⫺ 1.05 5.45 ⫹ ⫺ 1.69 40%
5.29 ⫹ ⫺ 1.11* 3.59 ⫹ ⫺ 0.29 1.47 ⫹ ⫺ 0.33** 1.08 ⫹ ⫺ 0.57*** 5.25 ⫹ ⫺ 2.29 32%
HDL, high density lipoprotein; LDL, low density lipoprotein *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01; ***, p ⬍ ⫺ 0.001
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Table 3 Individual components of the metabolic syndrome (MetS) among pre- and postmenopausal women with MetS. Data are expressed as n (relative frequency in percent) MetS components Impaired fasting plasma glucose High triglycerides High blood pressure Central obesity Low HDL cholesterol
Postmenopause (n ⫽ 20) 13 10 20 12 5
(72.23%) (76.92%) (66.67%) (46.16%) (38.46%)
Premenopause (n ⫽ 10) 5 (27.77%)** 3 (23.08%)** 10 (33.33%)* 14 (53.85%) 8 (61.54%)
Total (n ⫽ 30) 18 13 30 26 13
(100%) (100%) (100%) (100%) (100%)
HDL, high density lipoprotein *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01
postmenopausal women with MetS, elevated plasma glucose and triglycerides, high blood pressure, central obesity and low HDL cholesterol as individual components of the MetS were observed in 72.23%, 76.92%, 66.67%, 46.15% and 38.46% of women, respectively. Compared to premenopausal women with MetS, a significantly higher proportion of postmenopausal women with MetS had elevated plasma glucose levels (72.23% vs. 27.77%; p ⫽ 0.01), triglycerides (76.92% vs. 23.08%; p ⫽ 0.01) and hypertension (66.67% vs. 33.33%; p ⫽ 0.02). In the univariate analysis, predictors of MetS were menopause, overweight, family history of diabetes mellitus, family history of cardiovascular disease, and family history of hypertension (Table 4). However, after adjusting for age, BMI, smoking, alcohol intake and duration of menopause, menopause, overweight and obesity emerged as the main predictors of the risk of MetS. The risk of MetS was 2- (adjusted odds ratio (aOR) 2.49; 95% confidence interval (CI) 1.05–5.95), 6- (aOR 6.35; 95% CI 1.66–24.23) and 14-fold (aOR 14.29; 95% CI 3.84–53.06) greater in postmenopausal, overweight and obese women in comparison to their counterparts (Table 5).
DISCUSSION The present study aimed to evaluate the prevalence of MetS and determine its predictors in Congolese postmenopausal women. The key findings are as follows. First, postmenopausal women had, on average, higher levels of total cholesterol, HDL cholesterol and triglycerides than premenopausal women; second, the frequency of MetS tended to be higher in post- than premenopausal women; third, high blood pressure, elevated plasma glucose and triglycerides were individual components of MetS most frequently seen in postmenopausal women with MetS in comparison with their premenopausal counterparts; fourth, menopause, overweight and obesity emerged as the main independent predictors of MetS. Higher levels of total cholesterol and triglycerides observed in postmenopausal women in the present study corroborate with previous reports on abnormal lipid profile in this category of women7. Elevated levels of cholesterol, triglycerides, fibrinogen and lipoprotein(a) have already been observed following menopause25. Indeed, in a longitudinal study of 541 initially premenopausal women aged 42–50 years, greater changes in blood lipid levels were seen in those women who underwent menopause than in those who did not26. While age
Table 4 Univariate analyses of predictors of metabolic syndrome (MetS) according to menses characteristics. Data are expressed as n (relative frequency in percent) Variable Married vs. not Postmenopause vs. premenopause Family history of diabetes mellitus vs. not Body mass index (kg/m2) 18–24.9 25–29.9 ⬎ 30 ⫺ Alcohol intake vs. not Education: elementary vs. high school or higher Physical activity vs. not Family history of cardiovascular diseases vs. not Family history of hypertension vs. not
MetS
Odds ratio
25 (83.3%) 20 (66.7%) 11 (36.7%)
0.592 2.250 2.596
3 11 16 6 3 24 2 19
(10%) (36.7%) (53.3%) (20%) (10%) (80%) (6.7%) (63.3%)
5.500 14.400 1.078 0.339 0.857 6.000 2.188
95% confidence interval 0.202–1.739 0.994–5.092* 1.122–6.004*
1.466–20.63* 3.915–52.96*** 0.407–2.855 0.098–1.173 0.322–2.278 0.812–44.35 0.981–4.879*
*, p ⬍ ⫺ 0.05; ***, p ⬍ ⫺ 0.001
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Table 5 Independent predictors of metabolic syndrome (MetS) calculated by stepwise logistic regression according to menses characteristics Regression coefficient β
Odds ratio (standard error)
Menopausal status†
0.991
2.50 (0.44)
Body mass index (kg/m2) Normal (18–24.9) Overweight (25–29.9) Obese (⫺ ⬎ 30)
1 (ref) 1.848 2.659
1 6.35 (0.68) 13.29 (0.67)
Variable
95% confidence interval 1.04–5.95*
– 1.66–24.23** 3.84–53.06***
† *, p ⬍ ⫺ 0.05; **, p ⬍ ⫺ 0.01; ***, p ⬍ ⫺ 0.001; , postmenopausal vs. premenopausal
may contribute to altered lipid metabolism, menopause itself through estrogen deficiency and associated morphological changes may play a significant role26. These findings support the general consensus that menopause, whether natural or surgical, is associated with a less desirable lipid profile25. In the present study, higher HDL cholesterol levels were observed in older Congolese postmenopausal women in comparison with younger premenopausal ones. Although most studies have reported low HDL cholesterol levels in post- than premenopausal women, there are some previous researches that have also observed higher levels of this lipoprotein in postmenopausal Korean, Iranian and American women27–29. However, the mechanisms underlying increased HDL cholesterol levels in menopause are not yet fully understood28. One of the proposed mechanisms is age-induced changes in the HDL cholesterol profile27. In women, HDL cholesterol levels increase progressively to the sixth decade, and then decrease28. Therefore, age may influence HDL cholesterol levels, leading to discrepancy among studies27. Several reports that considered the age of subjects showed similar or even higher HDL cholesterol levels in postmenopausal women compared to premenopausal ones27. In the Atherosclerosis Risk in Communities and Framingham Heart Study, significant differences in HDL cholesterol levels were not observed between pre- and postmenopausal women in the fixed age intervals30. Our study showed a higher frequency of MetS in post- than premenopausal women; however, the difference did not reach statistical significance. This finding also corroborates with previous studies reporting a progressive increase in the prevalence or incidence of MetS during the transition from pre- to postmenopause2,15,31–35. The mechanisms underlying the increased prevalence or incidence of MetS during the transition from pre- to postmenopause are not yet well elucidated. It has been suggested that the hormonal dysregulation occurring during the menopausal transition may play a key role in the initiation of pathobiological changes such as adverse lipid profile and atherosclerotic plaques that will increase risk of cardiovascular disease during the postmenopausal period36. Some studies, however, attributed these pathobiological changes to the aging process and associated weight gain with subsequent insulin resistance30,37,38. To reconcile these opposed opinions, a combination of hormonal dysregulation and aging effects on lipid metabolism and the cardiovascular system has
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been evoked37; Matthews and colleagues have shown that triglycerides increased with age but total cholesterol, LDL cholesterol and apolipoprotein B increased specifically with menopausal status39. Furthermore there is experimental evidence from intervention studies using hormone replacement therapies and ovariectomy, and correlations of circulating hormones levels with disease risk, which indicate that the decrease in estrogen levels is central to the development of age-related diseases40. There is considerable evidence that only physiological hormone replacement therapies delay the onset, halt the progression and even reverse the course of age-related diseases41,42. Individual MetS components more frequently seen in postthan premenopausal women with MetS were high blood pressure, elevated plasma glucose and triglycerides. These findings are in agreement with a report by Heidari and colleagues who found that, except for high blood pressure and elevated triglycerides, there was no significant difference between pre- and postmenopausal women when MetS components were considered31. They concluded that, in contrast to the claims regarding the role of waist circumference in the occurrence of MetS during the menopausal transition, the presence of MetS could be independent of abdominal adiposity31. Furthermore, Lejskova and colleagues reported in menopausal women an increase in the clustered incidence of MetS components at the expense of isolated incidence43. Of note, some MetS components such as hypertension and diabetes have been reported to carry a greater risk for cardiovascular disease in women43,44. In Congolese women, menopause, overweight and obesity emerged as the main predictors of the risk of MetS as a surrogate marker of cardiovascular risk. Although many risk factors contribute to cardiovascular disease in women, menopause appears for some authors as the strongest one45. Previous studies found that MetS risk increased progressively up to 14 years since menopause before declining21,46,47. The mechanism underlying this increased risk remains a subject of controversy. Menopause-induced hormonal dysregulation and subsequent weight gain were evoked as responsible for the clustering of MetS risk factors43,46. The association of obesity with the risk of MetS in menopause has already been reported47,48. Indeed, Kim and colleagues showed that, compared to normal weight, overweight and obesity were associated with 6- and 14-fold greater risk of MetS, respectively46.
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Metabolic syndrome in Congolese women In some studies, this increased risk was attributable to the aging process associated with menopause31,38,43,48. Given the fact that there is an increasing prevalence of obesity, diabetes, hypertension (9–15%, 7–12% and 10–28% increase within two decades, respectively) and chronic renal diseases with renal failure in the Congolese population and the inaccessibility to hemodialysis by the majority of patients (only 8% of patients have access to hemodialysis) because of financial reasons, there is a necessity for early detection and treatment of risk factors49.
Muchanga et al. menopause was defined on the basis of self-reported menstrual bleeding characteristics without hormone measurements. However, NHANES demonstrated that this menstrually defined measure of menopause correlates strongly with hormone measurements50. In conclusion, the present study has shown that MetS is common among Congolese postmenopausal women, and that hypertension, elevated plasma glucose and serum triglycerides are the MetS components more frequently encountered among postmenopausal women in comparison to their premenopausal counterparts. Menopause itself, overweight and obesity emerged as the main predictors of MetS.
Limitations The stratified cross-sectional design of the present work precludes clear establishment of a causal relationship between MetS and associated risk factors. A longitudinal study would be more appropriate for this question. Furthermore,
Conflict of interest The authors report no confl ict of interest. The authors alone are responsible for the content and writing of this paper. Source of funding
University of Kinshasa.
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