Journal of Hypertension and Cardiology
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Research Article | Open Access
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  • Late Age at Menarche Increased Common Carotid Artery Intima-Media Thickness in Overweight and Obese Women

    Pietro Scicchitano 1     Giulia Frasso 1     Mariangela Carbone 1     Michele Moncelli 1     Rosa Carbonara 1     Franco Silvestris 2     Giovanni De Pergola 2     Marco M. Ciccone 1      

    1Section of Cardiovascular Diseases, Department of Emergency and Organ Transplantation, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare, 70124 Bari, Italy

    2Clinical Nutrition Unit, Internal Medicine IV, Department of Internal Medicine and Clinical Oncology, University of Bari, School of Medicine, Policlinico, Piazza Giulio Cesare 11, 70124 Bari, Italy

    Abstract

    Objective:

    To determine whether age at menarche is an independent predictor of common carotid artery intima-media thickness in overweight and obese adult women.

    Methods:

    403 overweight and obese women, aged 18–72 years, were evaluated. We examined the associations among common carotid artery intima-media thickness (CCA-IMT), age at menarche, body mass index, central fat accumulation (indirectly measured by waist circumference), and other well-known cardiovascular risk factors (blood pressure; fasting serum insulin, glucose and lipids concentrations; insulin resistance (estimated by homeostasis model assessment for insulin resistance)).

    Results:

    CCA-IMT was significantly and positively correlated with age (r=0.632, p<0.001), age of menarche (r=0.156, p<0.01), waist circumference (r=0.110, p<0.05), systolic (r=0.292, p<0.001) and diastolic (r=0.183, p<0.001) blood pressure, fasting blood glucose (r=0.265, p<0.001), triglycerides (r=0.204, p<0.001) and total cholesterol (r=0.396, p<0.001) levels. Conversely, CCA-IMT was negatively associated with high-density lipoprotein cholesterol (r=-0.111, p<0.05).

    Age at menarche was associated with CCA-IMT (r=0.156, p<0.01), age (r=0.110, p<0.05) and waist circumference (r=0.121, p<0.05). Multiple linear analysis showed that only age and age at menarche maintained an independent positive relationship with the CCA-IMT.

    Conclusions:

    Age at menarche is positively associated with CCA-IMT, independently of common cardiovascular risk factors (adverse glucose and lipid levels, higher blood pressure,insulin resistance, body fatness and central body fat). Late age at menarche can be considered as an independent cardiovascular risk factor in obese subjects.

    Received 20 Nov 2012; Accepted 20 Jan 2013; Published 26 Nov 2013;

    Academic Editor:Prasenjit Guchhait, Assistant Professor, Thrombosis Research Division, Cardiovascular Research Section. Department of Medicine Baylor College of Medicine. Huston. USA

    Checked for plagiarism: Yes

    Review by: Single-blind

    Copyright©  2013 Pietro Scicchitano, et al.

    License
    Creative Commons License    This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    Competing interests

    The authors have declared that no competing interests exist.

    Citation:

    Pietro Scicchitano, Giulia Frasso, Mariangela Carbone, Michele Moncelli, Rosa Carbonara et al. (2013) Late Age at Menarche Increased Common Carotid Artery Intima-Media Thickness in Overweight and Obese Women. Journal of Hypertension and Cardiology - 1(2):1-10.
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    DOI10.14302/issn.2329-9487.jhc-12-154

    Introduction

    Age at menarche is a key maturity indicator of female development. It reflects population health1. Several studies showed a reduction in the mean age at menarche 1, 2, 3, 4, 5, 6, influenced by variables such as genetic factors, race, body mass index, nutrition, geography, socioeconomic status, maternal menarche age, maternal age at birth and sleep time6, 7, 8, 9, 10, 11. Girls with earlier age at menarche demonstrate worse cardiovascular risk factor in adulthood than those with later age at menarche12, 13, 14, 15, 16, 17, 18, 19. By contrast, the JACC study showed that women with age at menarche > 17 years had higher risk of mortality due to stroke events as compared to women with age at menarche < 13 years, even though late menarche was not associated with risk of mortality from coronary heart disease20.

    Atherosclerosis is accelerated in obese, and above all central obese subjects as shown by higher common carotid artery intima media thickness21, 22, 23, 24, 25, 26. Common carotid artery intima media thickness is a well-established early marker of asymptomatic atherosclerosis and precedes the development of plaque and stenosis in the arterial wall27, 28. Central obesity is associated with early carotid intima-media thickening independently of other risk factors21, 23, 25, 26; even leptin, a protein quite exclusively produced by adipose tissue, is independently associated with the common carotid artery intima-media thickness21.

    To the best of our knowledge, no study has previously examined in a population of overweight and/or obese subjects whether the common carotid artery intima-media thickness in adulthood is influenced by earlier or later age at menarche, independently of common cardiovascular risk factors. Study aim is to find the relationship between carotid vasculature alterations and age at menarche in an obese/overweight female population.

    Methods

    Subject Population

    We consecutively recruited 403 euthyroid apparently healthy overweight and obese women at the Outpatient Clinic Nutrition Unit, Policlinico di Bari, Bari, Italy. They were referred to the Outpatient Clinic due to their increased weight and/or to be educated to have correct food and lifestyle habits.

    Exclusion criteria were: smokers, subjects taking any kind of drugs, patients known to be affected by thyroid dysfunction, endocrinological diseases, diabetes mellitus, stable and drug-treated hypertension, stroke, transient ischemic attack, angina pectoris, myocardial infarction, claudicatio intermittens, congenital heart disease or electrocardiographic abnormalities. Furthermore, overweight/obese patients were only included in our study.

    Hypertension was defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure > 90 mmHg, or antihypertensive drugs use29; hypercholesterolemia was defined according to NCEP ATP III criteria30 (total-cholesterol > 220 mg/dl or the use of lipid-lowering drug(s)); diabetes as fasting blood sugar > 126 mg/dl in at least two determinations, or blood sugar during 75 gr oral glucose tolerance test > 200 mg/dl, or the use of antidiabetic drug(s)31.

    According to the above exclusion criteria, 403 women, aged 18–72 years (mean age 38.5 ± 12.5 years old), were enrolled. All subjects gave their written informed consent before enrolment, which was performed in agreement with Helsinki Declaration. The study was approved by the Institutional Review Board of Bari University General Hospital.

    All patients showed normal fasting blood glucose levels (see table 1).

    Table 1. General, anthropometric, and metabolic parameters in women under study.
    N=403
    Age (years) 38.5 ± 12.5
    Age of menarche (years) 11.9 ± 1.6
    Body mass index (kg/m2) 34.8 ± 6.7
    Waist circumference (cm) 107.1 ± 14.8
    Systolic blood pressure (mmHg) 121.1 ± 12.4
    Diastolic blood pressure (mmHg) 78.0 ± 8.3
    Fasting insulin (μ UI/ml) 24.4 ± 14.6
    Fasting blood glucose (mg/dl) 91 ± 11
    HOMAIR 5.61 ± 3.81
    Triglycerides (mg/dl) 90.7 ± 47.0
    Total cholesterol (mg/ml) 189.6 ± 37.1
    HDL cholesterol (mg/dl) 49.6 ± 11.0

    The data are expressed as mean values ± standard deviation. HDL: high-density lipoprotein; HOMAIR: homeostasis model assessment for insulin resistance.

    All study subjects were judged to be in good health on the basis of physical examination, medical history, routine blood examinations, urinalysis and electrocardiogram.

    Free thyroid hormones and thyroid-stimulating hormone (< 4.0 mUI/ml) were in the normal range in all subjects. None of patients were receiving any kind of medication (including oral contraceptives for pre-menopausal women and hormone replacement therapy for post-menopausal women) when they entered the study. Moreover, none of them had been involved into intensive or competitive physical activity prior to the enrollment. During the testing period, all subjects were asked to keep their normal mixed diet and not to perform any sporting activity.

    Questionnaire-Based Interview

    A questionnaire-based interview was adopted in order to collect information on the participants’ occupations, physical activity, smoking habit, cardiovascular diseases history, women’s periods and reproductive history, including age at menarche.

    Measurements of the Common Carotid Artery Intima-Media Thickness

    Determinations of common carotid artery intima-media thickness were performed as previously described21, 26, 32. Briefly, measurements were obtained from the far wall of the distal common carotid arteries (immediately proximal to the carotid bulb). This location was chosen a priori because of its demonstrated reproducibility, compared with measurements of common carotid artery intima-media thickness at other sites32. The mean value for the bilateral measurement had been reported.

    Allstudies were performed on a single ultrasound machine (Hewlett Packard Sonos 1500B) using a linear-array 8.0 MHz scan head with standardized image settings, including resolution mode, depth of field, gain, and transmit focus. Ultrasound study was performed in a standard fashion by an examiner who was specifically trained to perform the prescribed study examination. All sonograms were obtained with the patient in the supine position and the head turned slightly to the contralateral side. Each ultrasound examination was performed as an independent study, without any knowledge of the patients’ cardiovascular risk factors. The near-field (intimal-luminal surface) and far-field (medial-adventitial) arterial wall borders were manually traced for measurement of minimal and maximal common carotid artery intima-media thickness.

    Anthropometric Measurements and General Data

    Weight was measured to the nearest kg. Height was determined to the nearest cm. Body mass index was calculated as the weight (kg) divided by the square of height (m) in order to identify obese and/or overweight subjects (overweight: 25 < body mass index < 30 kg/m2; obesity: body mass index > 30 kg/m2). Waist circumference was measured at the narrowest part of the abdomen, i.e., at the natural indentation between the 10th rib and the iliac crest (minimum waist). It is related to the presence of abdominal obesity (waist circumference > 88cm for women and > 102 cm for men)33.

    Blood pressure was recorded on at least three different occasions, using a mercury manometer with an appropriate cuff size.

    Hormonal and Metabolic Parameters

    Blood samples were drawn between 08:00h and 09:00 h after an overnight fast. Serum insulin concentrations were measured by radioimmunoassay (Behring, Scoppitto, Italy) and intra- and interassay coefficients of variation were 3.7% and 7.5% respectively.

    Plasma glucose levels were determined by the glucose-oxidase method (Sclavo, Siena, Italy). Plasma lipids (triglycerides, total cholesterol and high-density lipoprotein (HDL)-cholesterol) were determined by an automatic colorimetric method (Hitachi; Boehringer Mannheim, Mannheim, Germany). Insulin resistance was assessed by using the homeostasis model assessment (HOMAIR)34.

    Statistics

    Results are presented as mean and standard deviation for all parameters. Significant relationships between study parameters were evaluated by Pearson’s correlation coefficient. A multiple linear regression analysis was also performed to test the joint effect of different variables on common carotid artery intima-media thickness. All statistical analyses were performed using the STATISTICA 6.0 for Windows, StatSoft Inc. (Tulsa, OK, USA).

    Results

    Table 1 shows general, anthropometric, and metabolic parameters of enrolled women.

    Table 2 shows the associations between age at menarche and all the parameters investigated. Apart from the relationship with common carotid artery intima-media thickness (r=0.156, p<0.01), age of menarche was significantly correlated with age (r=0.110, p<0.05) and waist circumference (r=0.121, p<0.05).

    Table 2. Pearson correlation coefficients of age of menarche with all other parameters in all women under study (n=403)
    r
    CCA-IMT (mm) 0.156**
    Age (years) 0.110*
    Body mass index (kg/m 2 ) 0.091
    Waist circumference (cm) 0.121*
    Systolic blood pressure (mmHg) 0.039
    Diastolic blood pressure (mmHg) -0.017
    Fasting blood glucose (mg/dl) 0.001
    Fasting insulin (μ UI/ml) 0.051
    HOMAIR 0.038
    Triglycerides (mg/ml) 0.060
    Total cholesterol (mg/ml) -0.015
    HDL cholesterol (mg/ml) 0.046

    CCA-IMT: common carotid intima-media thickness; HDL: high-density lipoprotein;
    HOMAIR: homeostasis model assessment for insulin resistance.
    * p < 0.05
    ** p < 0.01
    *** p < 0.001

    Table 3 shows the relationship between common carotid artery intim-media thickness and all the parameters investigated. Common carotid artery intima-media thickness was significantly and positively correlated with age (r=0.632, p<0.001), age at menarche (r=0.156, p<0.01), waist circumference (r=0.110, p<0.05), systolic (r=0.292, p<0.001) and diastolic (r=0.183, p<0.001) blood pressure, fasting blood glucose (r=0.265, p<0.001), triglycerides (r=0.204, p<0.001) and total cholesterol (r=0.396, p<0.001) levels. Conversely, common carotid artery intima-media thickness was negatively associated with HDL cholesterol (r=-0.111, p<0.05).

    Table 3. Pearson correlation coefficients of common carotid intima-media thickness with all other parameters in all women under study (n=403)
    r
    Age of menarche (years) 0.156**
    Age (years) 0.632***
    Body mass index (kg/m 2 ) 0.041
    Waist circumference (cm) 0.110*
    Systolic blood pressure (mmHg) 0.292***
    Diastolic blood pressure (mmHg) 0.183***
    Fasting blood glucose (mg/dl) 0.265***
    Fasting insulin (μ UI/ml) 0.008
    HOMAIR 0.061
    Triglycerides (mg/ml) 0.204***
    Total cholesterol (mg/ml) 0.396***
    HDL cholesterol (mg/ml) -0.111*

    HDL: high-density lipoprotein; HOMAIR: homeostasis model assessment for insulin resistance.
    * p < 0.05
    ** p < 0.01
    *** p < 0.001

    Table 4 shows the results of the multiple linear analysis of different variables in relation to common carotid artery intima-media thickness, considered as the dependent variable (R2=0.406, p<0.001). All parameters showing a significant linear association with common carotid artery intima-media thickness were entered as independent variables in the multiple regression analysis. Only age and age at menarche maintained an independent positive relationship with the common carotid artery intima-media thickness.

    Table 4. Determinants of common carotid intima-media thickness in multiple regression analysis.
    Variable β T (393) P-value
    Age of menarche (years) 0.089 2.264 <0.05
    Age (years) 0.560 11.364 <0.001
    Waist (cm) 0.047 1.114 Ns
    Systolic blood pressure (mmHg) 0.048 0.903 Ns
    Diastolic blood pressure (mmHg) 0.014 -0.281 ns
    Fasting blood glucose (mg/dl) 0.019 0.449 ns
    Triglycerides (mg/dl) -0.004 -0.888 ns
    Total cholesterol (mg/ml) -0.027 1.627 ns
    HDL cholesterol (μ g/24 h) -0.078 -0.593 Ns

    HDL: high-density lipoprotein.

    Discussion

    The present study, performed in a population of healthy euthyroid overweight and obese women, shows a high positive relationship between age at menarche and the common carotid artery intima-media thickness, independently of common cardiovascular risk factors such as glucose, lipids, blood pressure, body mass index, body fat distribution and insulin resistance. This is an important result, since the thickening of the intima and tunica media is considered an early marker of asymptomatic atherosclerosis and precedes the development of plaque and stenosis in the arterial wall27, 28 Nevertheless, the relationship between common carotid intima-media thickness and age at menarche is an almost controversial subject. Literature data offer examples of the opposite results obtained and the different theories produced to explain them.

    Our findings are apparently in line with the JACC study20 This international research showed that women with age at menarche > 17 years tended to have increased risk of mortality from stroke compared to women with age at menarche < 13 years20. Later menarche would correspond to a shorter period of exposure to estrogens in women, and the positive relationship between age at menarche and the common carotid artery intima-media thickness in adulthood could be explained by an early protective effect of endogenous estrogen on the development of atherosclerosis. Nevertheless, our data are apparently in contrast with previous studies showing that girls with earlier age at menarche tend to have worse cardiovascular risk factor levels in adulthood than those who underwent menarche at a later age12-19.

    Chang et al.35 pointed out that the risk of coronary heart disease mortality was lower in 17, 18 years old at menarche women than that in younger than 17 years at menarche in a population of 3,257 post-menopausal women. Lakshman et al.36 found that early age at menarche (before age 12 years old) induced an increased risk of cardiovascular disease events/mortality and overall mortality in 15,807 women aged 40-79 years old. This relationship was only partly in relation to an increased adiposity37.

    However, our study is not comparable to previous studies, since our patients are overweight and obese women, in contrast with the general population enrolled in previous studies.

    The most consistent evidence relates to higher adult body mass index in women who had earlier menarche on average13, 15-18; moreover, an inverse association of menarcheal age has been reported with blood pressure15, glucose intolerance15, insulin resistance38 and risk of ischemic heart disease and stroke14,20,39. However, none of these studies has demonstrated that earlier menarche is an independent predictor of adverse adult outcomes. The recent Cardiovascular Risk in Young Finns study showed that early menarche is only a risk marker and greater childhood BMI seemed to contribute to earlier age at menarche40. Moreover, all the available studies do not exclude that either earlier or later menarche have an unfavorable effect on the arterial intima-media thickness and the cardiovascular risk.

    Limitations of this study concern the sample characteristics. In particular, the present study was performed in women with a wide range of age, and only in overweight and obese women, enrolled at an Outpatient Clinic Nutrition Unit. Therefore, we cannot exclude that results might be different in the general population not selected according to our exclusion criteria. Furthermore, we did not consider a lean group as control. Furthermore, the research did not reach the same sample size of previous researches. Nevertheless, other literature data consider for example general population, with at least many confounding factors able to influence the overall cardiovascular risk profile of each patient enrolled. On the contrary, our study considered only selected patients who showed an increased BMI, different according to age. These reduced the biases and improved the selection of the population in order to try to understand the real weight of age at menarche in the development of cardiovascular risk. For this reason further evaluations and researches will be developed in order to improve our results.

    conclusions

    In conclusion, the present study shows that later menarche is a predictive factor of arterial thickening in the adult age, independently of common cardiovascular risk factors, in overweight and obese adult women. Further studies are needed in order to confirm or not these results.

    References

    1.Jones L L, Griffiths P L, Norris S A, Pettifor J M, Cameron N. (2009) Age at menarche and the evidence for a positive secular trend in urban South Africa. , Am J Hum Biol 21, 130-132.
    2.Fredriks A M, S van Buuren, Burgmeijer R J, Meulmeester J F, Beuker R J. (2000) Continuing positive secular growth change in The Netherlands1955–1997. , Pediatr Res 47, 316-323.
    3.Kac G.Auxiliadora de Santa Cruz Coel and G Velasquez-Melendez . (2000)Secular trend in age at menarche for women born. between1920and1979 in Rio de Janeiro,Brazil. Ann Hum Biol.27: 423-428.
    4.Wyshak G. (1983) Secular changes in age at menarche in a sample of US women. , Ann Hum Biol 10, 75-77.
    5.Hwang J Y, Shin C, Frongillo E A, Shin K R, Jo I. (2003) Secular trend in age at menarche for South Korean women born between1920 and 1986:theAnsanstudy. , Ann Hum Biol 30, 434-442.
    6.Cho G J, Park H T, Shin J H, Hur J Y, Kim Y T. (2010) Age at menarche in a Korean population: secular trends and influencing factors. , Eur J Pediatr 169, 89-94.
    7.Ersoy B, Balkan C, Gunay T, Egemen A. (2005) The factors affecting the relation between the menarcheal age of mother and daughter. , Child Care Health Dev 31, 303-308.
    8.Khan A D, Schroeder D G, Martorell R, Haas J D, Rivera J. (1996) Early childhood determinants of age at menarche in rural Guatemala. , Am J Hum Biol 8, 717-723.
    9.Papadimitriou A, Fytanidis G, Douros K, Bakoula C, Nicolaidou P. (2008) Age at menarche in contemporary Greek girls: evidence for levelling-off of the secular trend. , Acta Paediatr 97, 812-815.
    10.Wronka I, Pawlinska-Chmara R. (2005) Menarcheal age and socio-economic factors in Poland. , Ann Hum Biol 32, 630-638.
    11.Ku S Y, Kang J W, Kim H, Kim Y D, Jee B C. (2006) Age at menarche and its influencing factors in North Korean female refugees. , Hum Reprod 21, 833-836.
    12.Demerath E W, Li J, Sun S S, Chumlea W C, Remsberg K E. (2004) Fifty-year trends in serial body mass index during adolescence in girls: the Fels Longitudinal Study. , Am J Clin Nutr 80, 441-446.
    13.Laitinen J, Power C, Jarvelin M R. (2001) Family social class, maternal body mass index, childhood body mass index, and age at menarche as predictors of adult obesity. , Am J Clin Nutr 74, 287-294.
    14.Cooper G S, Ephross S A, Weinberg C R, Baird D D, Whelan E A. (1999) Menstrual and reproductive risk factors for ischemic heart disease. , Epidemiology 10, 255-259.
    15.Remsberg K E, Demerath E W, Schubert C M, Chumlea W C, Sun S S. (2005) Early menarche and the development of cardiovascular disease risk factors in adolescent girls: the Fels Longitudinal Study. , J Clin Endocrinol Metab 90, 2718-2724.
    16.Pierce M B, Leon D A. (2005) Age at menarche and adult BMI in the Aberdeen children of the 1950s cohort study. , Am J Clin Nutr 82, 733-739.
    17.Freedman D S, Khan L K, Serdula M K, Dietz W H, Srinivasan S R. (2003) The relation of menarcheal age to obesity in childhood and adulthood: the Bogalusa Heart Study. , BMC Pediatr 3, 3.
    18.Must A, Naumova E N, Phillips S M, Blum M, Dawson-Hughes B. (2005) Childhood overweight and maturational timing in the development of adult overweight and fatness: the Newton Girls Study and its follow-up. , Pediatrics 116, 620-627.
    19.Power C, Lake J K, Cole T J. (1997) Body mass index and height from childhood to adulthood in the 1958 British born cohort. , Am J Clin Nutr 66, 1094-1101.
    20.Cui R, Iso H, Toyoshima H, Date C, Yamamoto A. (2006) Relationships of age at menarche and menopause, and reproductive year with mortality from cardiovascular disease in Japanese postmenopausal women: the JACC study. , J Epidemiol 16, 177-184.
    21.Ciccone M, Vettor R, Pannacciulli N, Minenna A, Bellacicco M. (2001) Plasma leptin is independently associated with the intima-media thickness of the common carotid artery. , Int J Obesity 25, 805-810.
    22.DeMichele M, Panico S, Iannuzzi A, Celentano E, Ciardullo A V. (2002) Association of obesity and central fat distribution with carotid artery wall thickening in middle-aged women. , Stroke 33, 2923-2928.
    23.Lo J, Dolan S E, Kanter J R, Hemphill L C, Connelly J M. (2006) Effects of obesity, body composition, and adiponectin on carotid intima-media thickness in healthy women. , J Clin Endocrinol Metab 91, 1677-1682.
    24.Burke G L, Bertoni A G, Shea S, Tracy R, Watson K E. (2008) The impact of obesity on cardiovascular disease risk factors and subclinical vascular disease. , Arch Intern Med 168, 928-935.
    25.Maher V, O&apos;Dowd M, Carey M, Markham C, Byrne A. (2009) Association of central obesity with early carotid intima-media thickening is independent of that from other risk factors. , Int J Obesity 33, 136-143.
    26.Ciccone M M, G De Pergola, Porcelli M T, Scicchitano P, Caldarola P. (2010) Increased carotid IMT in overweight and obese women affected by Hashimoto&apos;s thyroiditis: an adiposity and autoimmune linkage?. , BMC Cardiovasc Disord 10, 22.
    27.Crouse JR 3rd, Craven T E, Hagaman A P, Bond M G. (1995) Associations of coronary disease with segment specific intimal-medial thickening of the extracranial carotid artery. , Circulation 92, 1141-1147.
    28.Pignoli P, Tremoli E, Poli A, Oreste P, Paoletti R. (1986) Intimal plus medial thickness of the arterial wall: a direct measurement with ultrasound imaging. , Circulation 74, 1399-1406.
    29.Mancia G, G De Backer, Dominiczak A, Cifkova R, Fagard R. (2007) . ESH-ESC Practice Guidelines for the Management of Arterial Hypertension: ESH-ESC Task Force on the Management of Arterial Hypertension. J Hypertens 25, 1751-1762.
    30. (2002) National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation2002; 106, 3143-3421.
    31. (2010) American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care2010;33:S62-69.
    32.Pannacciulli N, G De Pergola, Ciccone M, Rizzon P, Giorgino F. (2003) Effect of family history of type 2 diabetes on the intima-media thickness of the common carotid artery in normal-weight, overweight, and obese glucose tolerant young adults. , Diabetes Care 26, 1230-1234.
    33.MEJ Lean, Han T S, Morrison C E. (1995) Waist circumference as a measure for indicating need for weight management. , BMJ 311, 158-161.
    34.Bonora E, Targher G, Alberiche M, Bonadonna R C, Saggiani F. (2000) Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity: studies in subjects with various degrees of glucose tolerance and insulin sensitivity. , Diabetes Care 23, 57-63.
    35.Chang H S, Odongua N, Ohrr H, Sull J W, Nam C M. (2011) Reproductive risk factors for cardiovascular disease mortality among postmenopausal women in Korea: the Kangwha Cohort Study. , Menopause 18, 1205-1212.
    36.Lakshman R, Forouhi N G, Sharp S J, Luben R, Bingham S A. (2009) Early Age at Menarche Associated with Cardiovascular Disease and Mortality. , J Clin Endocrinol Metab 94, 4953-4960.
    37.Stöckl D, Meisinger C, Peters A, Thorand B, Huth C. (2011) . Age at Menarche and Its Association with the Metabolic Syndrome and Its Components: Results from the KORA F4 Study. PLoS ONE 6:e26076 .
    38.Feng Y, Hong X, Wilker E, Li Z, Zhang W. (2008) Effects of age at menarche, reproductive years, and menopause on metabolic risk factors for cardiovascular diseases. , Atherosclerosis 196, 590-597.
    39.Colditz G A, Willett W C, Stampfer M J, Manson J E, Hennekens C H. (1990) Weight as a risk factor for clinical diabetes in women. , Am J Epidemiol 132, 501-513.
    40.Kivimäki M, Lawlor D A, Smith G D, Elovainio M, Jokela M. (2008) Association of age at menarche with cardiovascular risk factors, vascular structure, and function in adulthood: the Cardiovascular Risk in Young Finns study. , Am J Clin Nutr 87, 1876-1882.