Association between atherogenic index of plasma and carotid intima-media thickness in a cohort of Mediterranean women.

The association between early atherosclerosis (IMT) and Atherogenic index of plasma (AIP), a marker of atherogenicity (log triglycerides/HDL Cholesterol) was evaluated in a population-based cohort study in women, aged 30-69, living in the metropolitan area of Naples, Southern Italy (Progetto ATENA). Serum cholesterol, HDL-cholesterol, LDL-cholesterol, Triglyceride, Insulin, HOMA, Apo B, hs-CPR were measured in 390 menopausal women, as a part of 5.062 participants of the cohort. Women in the second and third tertile of AIP showed an increased common carotid intima-media thickness compared with those in the first tertile: II vs I tertile (O.R. = 2.24, p = 0.007), III vs I tertile (O.R. = 2.29, p = 0.005), adjusted for age and Systolic pressure or II vs I tertile (O.R. = 2.19, p = 0.014), III vs I tertile (O.R. = 2.13, p = 0.026), adjusted for age, Systolic pressure, Body mass index and Apo B. Women in the second and third tertile of AIP compared to those in the first tertile, showed an OR of 2.14 (p = 0.016) and 1.99 (p = 0.033) respectively, of having elevates level of IMT, adjusted for traditional cardiovascular risk factor (age, Systolic Pressure, BMI, LDL Cholesterol, Diabetes diagnosis). This finding shows that in this group of menopausal women increased IMT is associated with elevated AIP independently of age and different cardiovascular risk factors. These results are in line with the hypothesis that AIP may be an useful clinical tools to give additional information in the risk assessment for atherosclerotic disease, in particular in postmenopausal women.

Plasma creatinine levels, estimated glomerular filtration rate and carotid intima media thickness in middle-aged women: a population based cohort study.

BACKGROUND AND AIM: The relationships between high Creatinine (Cr) levels or low estimated Glomerular Filtration Rate (eGFR) and common carotid Intima Media thickness (IMT) have been evaluated in a population-based cohort study in women, aged 30-69 (Progetto ATENA). METHODS AND RESULTS: Serum Cr and eGFR were measured in 310 women, as a part of 5.062. In this group carotid ultrasound examination (B-Mode imaging) was performed and mean max IMT was calculated. Women were classified by Cr levels >1 mg/dL or eGFR < 56 ml/min. Women with Cr > 1 mg/dL (90th percentile of creatinine distribution) or eGFR less than 56 ml/min (5th percentile of eGFR distribution) had relatively more carotid plaques as compared to the rest of the cohort. Multivariate logistic analysis, after adjustment for age, demonstrated a significant association between Cr (>1 mg/dL) and IMT (≥1.2 mm): OR 4.12 (C.I 1.22-13.86), p = 0.022; or eGFR (<56 ml/min) and IMT (≥1.2 mm): OR 4.31 (C.I 1.27-14.66), p = 0.019. CONCLUSIONS: These findings on an independent relationship between Cr and common carotid plaques in this population of middle aged women, independently of age, suggest the value of screening for early carotid disease in asymptomatic middle aged-women with mild renal insufficiency, in order to predict those at relatively higher risk for future cardiovascular events.

Obesity, overweight, and weight gain over adult life are main determinants of elevated hs-CRP in a cohort of Mediterranean women.

BACKGROUND/OBJECTIVES: Body mass index (BMI), waist circumference (WC), body weight modification, and rate of weight increase over 10 years were evaluated in relation to high-sensitive C-reactive protein (hs-CRP) to assess the association of cross-sectional or longitudinal estimates of obesity/overweight with levels of circulating CRP, a well established and standardized marker of low-grade inflammation, in relation to cardiovascular risk. SUBJECTS: This study included a subgroup of 390 menopausal women participating in a large currently ongoing epidemiological study (Progetto Atena; N=5062). RESULTS: At the final visit, women in the third tertile of BMI, compared with those in the first tertile, showed the following odds ratio (OR) of having high hs-CRP values: III vs I tertile OR, 3.55; 95% confidence interval, 1.94-6.49, P<0.001, adjusted for age, and metabolic syndrome. Similar results were obtained when we evaluated women in the third tertile of WC, or those in the highest group of estimated weight increase, relative to their weight at age 20 years or in the group of highest rate of weight increase over 10 years of observation (weight at the final visit-weight at the baseline visit divided by time in months between visits). CONCLUSIONS: The independent relations between different markers of overweight/obesity and elevated hs-CRP consistently indicate that high (above 1.5 mg l(-1), median) hs-CRP is a major biochemical counterpart of cross-sectional or longitudinal estimates of increased adipose tissue mass.

Menstrual cycle length, serum lipids and lipoproteins in a cohort of Italian Mediterranean women: findings from Progetto ATENA.

BACKGROUND AND AIMS: Clinical studies suggest that menstrual irregularities are associated with metabolic and hormonal abnormalities, insulin resistance and a hyperestrogenic/hyperandrogenic imbalance, that may influence the risk of cardiovascular disease. METHODS AND RESULTS: The association of these abnormalities with the metabolic syndrome suggests that information on lipid patterns at different menstrual cycle length may be of interest in identifying women at higher cardiovascular risk. The association of lipid patterns with menstrual cycle length was evaluated in a cohort of 5062 women participating in the Progetto ATENA Study. Questions were administered to the participants about their cycle lengths at different periods of time over their reproductive life. The period between 20 and 50 years was investigated: normal cycle length was defined as short (30 days). Perimenopausal women were excluded and variables adjusted for age, BMI and menopausal status. In 4434 participants serum triglycerides were found to increase with an increased number of days in the menstrual cycle: 106 mg/dl in the short cycle pattern (21-26 days); 113 mg/dl in the medium cycle pattern (27-29 days); and 116 mg/dl in the long cycle pattern (30-31 days), whereas total and LDL cholesterol were found to be higher and HDL was lower in women with longer cycles, but the difference was not statistically significant. The results were very similar when the same adjusted analysis was restricted to a subgroup of 3823 women with a stable cycle length over the fourth and the fifth decade of life. CONCLUSIONS: These results suggest that cycle length may be a marker of higher cardiovascular risk due to associated metabolic and hormonal patterns.

Carotid artery wall hypertrophy in children with metabolic syndrome.

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6+/-2.6 years; range 6-14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl(-1), fasting triglyceride concentration >100 mg dl(-1), fasting high-density lipoprotein cholesterol concentration <50 mg dl(-1) for females or <45 mg dl(-1) for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima-media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima-media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83+/-1.86 mm(2) [mean+/-s.d.] compared with the control group: 7.77+/-1.72 mm(2), P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.

Impaired endothelium-dependent vascular reactivity in patients with familial combined hyperlipidaemia.

BACKGROUND: Familial combined hyperlipidaemia (FCHL) is associated with a markedly increased risk of premature coronary artery disease. This study was designed to evaluate whether preclinical atherosclerotic functional abnormalities are detectable in the arteries of patients with FCHL. METHODS: 60 subjects were recruited for the study: 30 probands of families with FCHL (mean (standard deviation (SD)) age 48 (10) years, 77% men), defined by fasting total plasma cholesterol or triglyceride concentration >250 mg/dl (>6.5 mmol/l cholesterol, >2.8 mmol/l triglyceride) and by the occurrence of multiple lipoprotein phenotypes within a family, and 30 age-matched and sex-matched healthy controls. All subjects underwent high-resolution B-mode ultrasound examination and the brachial arterial reactivity, a marker of endothelial function, was measured by a semiautomated computerised program. Lipid profile, resting blood pressure, body mass index (BMI), smoking status, insulin and homocysteine levels were also determined. RESULTS: Compared with controls, patients with FCHL had significantly higher BMI, diastolic blood pressure and insulin levels. No difference was observed in baseline brachial diameter between the two groups (mean (SD) 3.45 (0.51) mm for FCHL v 3.60 (0.63) mm for controls; p = 0.17). In response to flow increase, the arteries of the controls dilated (mean (SD) 8.9% (4.9%), range 2.3-20.8%), whereas in the patients with FCHL, brachial arterial reactivity was significantly impaired (5.5% (2.5%), range 0-10.1%; p = 0.002). In multivariate linear regression analysis, apolipoprotein B and BMI were independent determinants of brachial artery response to reactive hyperaemia. CONCLUSIONS: The findings of our study suggest that vascular reactivity is impaired in the arteries of patients with FCHL.

Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy.

BACKGROUND AND AIM: Obesity in children may lead to insulin resistance and impaired glucose regulation over time. The aim of this study was to investigate the insulin resistance status and the frequency of impaired glucose regulation in obese children and adolescents from the Campania region (Southern Italy), where the prevalence of obesity is among the highest in Europe. METHODS AND RESULTS: We studied 100 (62 male) Italian obese children and adolescents (mean age 10.1+/-2.7 years) and 50 (27 male) normal weight healthy subjects (mean age 10.2+/-2.7 years). Anthropometric measures and biochemical tests were performed in all subjects. In obese patients an oral glucose tolerance test was also performed. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) index. A cut-off HOMA level of >2.5 in children and >4.0 in adolescents was used to identify an insulin-resistance status. Insulin resistance was found in 40.8% of obese children and 41.2% of obese adolescents, whereas it was found in 3.0% of normal children and none of the 17 normal adolescents (p<0.0001 and p<0.002, respectively). None of the subjects had impaired fasting glucose or diabetes, while 4 obese patients had impaired glucose tolerance (4%). CONCLUSIONS: Impaired glucose tolerance is still rare whereas insulin-resistance is already detectable in more than 40% of obese children and adolescents in Southern Italy. Our observations confirm that metabolic risk factors can be found at a very early age and strengthen the case for implementing programmes for prevention and treatment of childhood obesity.

Nutrition and prevention of ischemic stroke: present knowledge, limitations and future perspectives.

Stroke, particularly ischemic stroke, has a major impact on public health due to its high incidence, prevalence and rate of subsequent disability in Italy as in most industrialised countries. Apart from age, many modifiable factors, such as hypertension, smoking, diabetes, dyslipidemia, obesity, physical inactivity, alcohol abuse and hyperhomocysteinemia, have been recognised as playing a role in the pathogenesis of this disease. While appropriate pharmacological therapy has proven effective in the prevention of stroke in particular categories of patients, most of the above mentioned predisposing conditions are amenable to be affected by nutrition. Unequivocal demonstration of a protective or adverse role of single foods and nutrients against the risk of stroke has been however difficult to achieve due to confounding by biological variability, methodological inadequacies in the assessment of individual nutritional habits and difficulty to carry out long-term randomised controlled trials in the nutritional area. Notwithstanding, in several cases, causal relationships could be inferred from case-control and cohort studies in the presence of plausible and reproducible associations, evidence of dose-dependent effects and consistency in the results of different studies. The aim of this paper was to review present knowledge and highlight limitations and future perspectives about the role of nutrition in the prevention of ischemic stroke.

Citizens and family doctors facing awareness and management of traditional cardiovascular risk factors: results from the Global Cardiovascular Risk Reduction Project (Help Your Heart Stay Young Study).

BACKGROUND AND AIM: The numerous guidelines and multiple approaches to managing cardiovascular risk factors have reduced the number of fatal events but not the incidence of cardiovascular disease (CVD). One rarely explored aspect is the extent to which individuals perceive their own risk in relation to their education and history of CVD. Furthermore, Italy has a State-based Health System, in which family doctors (FDs) may be an extremely useful and relatively low cost resource for risk management, but the degree of their involvement in individual CVD risk management has not been previously assessed. METHODS AND RESULTS: The Department of Clinical and Experimental Medicine of Federico II University, Naples, Italy, and the Neapolitan Section of the Italian Society of Family Doctors (SIMG), developed an epidemiological survey to evaluate the level and awareness of CVD risk in subjects in the urban area of Naples, and the degree of involvement of FDs in CVD risk management. During a period of a few months, the subjects who visited their FDs were invited to respond to a standard self-explanatory questionnaire, and the FDs were required to provide quantitative information concerning the CVD risk factors of each enrolled subject from their databases in order to assess global CVD risk. The data included cholesterol and blood pressure (BP) levels, and had to be collected within six months of the visit; if the date were missing, the fact was recorded. The present analysis was based on data concerning the 5,687 subjects who had entered the study by January 2002, 7.6% of whom reported CVD (myocardial infarction (MI), stroke, angina, cerebral transient ischemic attack: CD+) and 92.4% did not (CVD-). MI was the most frequent CVD, and 18% of the CVD+ cases reported more than one non-fatal cardiovascular event. On average, the CVD+ subjects were older and more often men. After adjusting for age and FD, they also had a higher body mass index (BMI) and prevalence of obesity, higher self-reported BP, a lower education level, and more often referred high cholesterol levels, hypertension and diabetes. On the contrary, the proportion of smokers was higher in the CVD- group. Among the subjects who declared that they did not have a high cholesterol level, 11% reported recent values of > 200 mg/dL. The FDs of 36% of the cases were unable to assess the individual global CV risk level using quantitative data from their electronic databases. The most frequently missing information was the level of total cholesterol. Missing data were more frequent in the CVD- than the CVD+ subjects, regardless of age and FD. CONCLUSIONS: The results of our study suggest that the awareness of CVD risk among subjects is somewhat vague. The FDs were generally able to provide a quantitative assessment of CVD risk in their patients. CVD risk prevention programmes may be more successful if they stress knowledge and awareness in the population, and stimulate FDs to undertake more stringent quantitative assessments of CVD risk factors.

Site-specific atherosclerotic plaques in the carotid arteries of middle-aged women from southern Italy: associations with traditional risk factors and oxidation markers.

BACKGROUND AND PURPOSE: Studies on cardiovascular disease have preferentially involved men because of the lower frequency of the disease in preelderly women. The aim of this analysis was to examine, with the use of a standardized ultrasound protocol, a cohort of women to differentiate early atherosclerotic lesions in different carotid segments in relation to traditional (lipoprotein abnormalities, high blood pressure, cigarette smoking) and nontraditional (oxidation markers) cardiovascular risk factors. METHODS: More than 5000 clinically healthy, middle-aged women (n=5062; age range, 30 to 69 years) living in the area of Naples in southern Italy participated in the Progetto Atena, a population-based study on the etiology of cardiovascular disease and cancer in the female population. A subsample of 310 participants underwent high-resolution B-mode ultrasound to assess intima-media thickness of common carotid artery and carotid bifurcation. RESULTS: Early atherosclerotic plaques (intima-media thickness >1.2 mm) were detected within the common carotid arteries in 37 women, in the carotid bifurcations in 77 women, and in both sites in 91 women. After age adjustment, common carotid plaques were found to be associated with higher systolic blood pressure (143 versus 138 mm Hg; P<0.05) and higher body mass index (29 versus 27 kg/m(2); P<0.01), while lesions at the carotid bifurcations were associated with higher LDL cholesterol (4.3 versus 3.8 mmol/L; P<0.01) and with smoking habit. Multivariate odds ratios for the presence of common carotid plaques were related to antibodies against oxidized LDL (odds ratio, 2.72; 95% CI, 1.46 to 5.07), and those for plaques at the bifurcation were related to lipid peroxides (odds ratio, 1.90; 95% CI, 1.04 to 3.47), and both relationships were independent of age, LDL cholesterol concentrations, body mass index, smoking habit, and systolic blood pressure. CONCLUSIONS: In a cohort of clinically healthy, middle-aged women, we found a site-specific association of traditional risk factors and oxidation markers with early atherosclerotic lesions in arterial segments differing in geometry, shear stress, extracellular matrix composition, and cell type populations.

L-arginine improves post-ischemic vasodilation in coronary heart disease patients taking vasodilating drugs.

BACKGROUND: The hypothesis that intravenous L-arginine infusion improves the vasodilatory response to ischemia in the resistance vessels of human lower limbs in relatively young coronary heart disease patients taking vasodilating drugs was tested. METHODS: Twenty patients with onset of symptoms of coronary artery disease before age 50, operated for aortocoronary bypass and taking vasodilating drugs, were compared with 20 control subjects of comparable age and gender; neither group included heavy smokers (>10 cigarettes/day). Blood flow in the lower limbs was measured noninvasively with strain-gauge plethysmography, both at rest and during a reactive hyperemia test. Intravenous infusion of L-arginine was performed in nine coronary heart disease patients and in nine control subjects. RESULTS: Resting blood flow to the lower limbs was 2.3 mL/min/100 mL in control subjects vs 3.4 mL/min/100 mL in patients (difference not statistically significant). Peak blood flow measured after a 3-minute arterial occlusion was 24.0 mL/min/100 mL in control subjects vs 20.3 mL/min/100 mL in coronary heart disease patients (P<0.05). Peripheral minimal vascular resistances were 4.28 and 5.46 peripheral resistances units (p.r.u.) in control subjects and patients, respectively (P<0.05). Intravenous infusion of L-arginine was followed by increased resting blood flow in cases and controls (P=0.009), with a parallel reduction in peripheral resting vascular resistances (P=0.009). Coronary heart disease patients showed increased peak blood flow (P=0.04) and reduced minimal vascular resistances (P=0.02), whereas no statistically significant changes in these parameters were detectable in control subjects. Intravenous glucose infusion, leading to increased serum insulin concentration, did not modify any hemodynamic parameter. CONCLUSIONS: Hemodynamic responses in the skeletal muscle are impaired during a reactive hyperemia test in relatively young coronary heart disease patients taking vasodilating drugs. Intravenous L-arginine infusion corrects the impaired vasodilatory response of the lower limbs to an acute increase in flow following a cuff thigh occlusion.

LDL receptor cDNA sequence analysis in familial hypercholesterolemia patients: 5 novel mutations with high prevalence in families originating from southern Italy.

We screened a group of patients from southern Italy with clinically diagnosed familial hypercholesterolemia (FH) for mutations of the LDL receptor (LDLR) gene. RNA from each proband was analysed by RT-PCR followed by complete cDNA sequencing. Among 51 unrelated FH families we detected 17 mutations affecting the coding region of the LDLR gene. Five of these mutations, designated R395P, L783fsinsG, IVS15-3C>A, IVS3+5G>A, and 1698-1704delCACCCTAinsGCCCAAT (ITL545MPN), have not yet been reported in the literature. Interestingly, the novel IVS15-3C>A splicing mutation was detected in 20% of our unrelated FH families, suggesting an unusually high prevalence in our local population. Hum Mutat 17:433, 2001.

Systolic and pulse blood pressures (but not diastolic blood pressure and serum cholesterol) are associated with alterations in carotid intima-media thickness in the moderately hypercholesterolaemic hypertensive patients of the Plaque Hypertension Lipid Lowering Italian Study. PHYLLIS study group.

OBJECTIVE: The Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95-115 mmHg; systolic blood pressure (SBP) 150-210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14-5.17 mmol/l (160-200 mg/dl) and initial carotid artery alterations (maximum intima-media thickness (IMT) Tmax > or = 1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium-high risk hypertensive patients. METHODS: Patients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean +/- SD) 58.4 +/- 6.7 years, males were 40.2%, current smokers 16.5%, means +/- SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79 +/- 0.67, 4.69 +/- 0.51, 1.37 +/- 0.38, 1.59 +/- 0.64 mmol/l (262.4 +/- 25.8, 181.3 +/- 19.8, 53.0 +/- 14.6, 141.0 +/- 56.7 mg/ dl). Means +/- SD of clinic sitting SBP/DBP were 159.8 +/- 9.0/98.3 +/- 4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean +/- SD 24 h SBP/DBP averages 136.3 +/- 14.1/84.0 +/- 10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax (mean IMT of eight sites at common carotids and bifurcations) was 1.21 +/- 0.17; Mmax (mean of 12 sites also including internal carotids) 1.16 +/- 0.17, and Tmax (single maximum) 1.85 +/- 0.48 mm. RESULTS: Ambulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax (P0.01 -0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement. CONCLUSIONS: Baseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

Non-invasive vascular detection of early signs of atherosclerosis in hypercholesterolemic children: why and how.

Atherosclerosis is a lifelong disease process that begins in childhood and may lead to cardiovascular disease in middle age or later. Non-invasive methods for vascular diagnosis help identify hypercholesterolemic children to treat with dietary or pharmacological intervention on the basis of anatomical or functional markers of arterial pathology. It would be unethical to assess these markers using angiographic or other invasive procedures (such as intravascular ultrasound), but the measurement of intermediate vascular end-points using non-invasive techniques is feasible. We here review the methods and procedures of non-invasive vascular examination that have been demonstrated to be feasible and informative with regard to arterial pathology in hypercholesterolemic children. These include measuring carotid intima-media thickness (IMT) by means of B-mode imaging, Doppler evaluation of the transvalvular aortic pressure gradient, measuring coronary calcium by means of computed tomography, studying the elastic properties of arteries, detecting impaired vasodilation, and measuring arterial remodelling. Suggested operative guidelines could be to measure carotid IMT in all hypercholesterolemic children aged > 10 years. The measurement should be repeated each year if the IMT is in the upper tertile of distribution for that age. A progression in IMT or the development of new lesions during the study could be an indication for more aggressive treatment.

High endogenous estradiol is associated with increased venous distensibility and clinical evidence of varicose veins in menopausal women.

OBJECTIVE: The purpose of this study was to determine if there is an association between elevated sex hormones (ie, serum estradiol, sex hormone binding globulin [SHBG], testosterone) and increased venous distension and clinical evidence of varicose veins in menopausal women. METHODS: Participants were 104 healthy volunteer menopausal women, aged 48 to 65 years, who were not undergoing hormonal treatment. Of these 104, 14 were excluded from analyses because their estradiol levels were compatible with a premenopausal condition (4), because they had missing values for insulin concentration (5), and because they did not show up at venous vessel examination (5). Patients underwent a physical examination to determine the presence of varicose veins; a venous strain-gauge plethysmographic examination to compute instrumental measures of venous distensibility; and laboratory analyses of blood so serum testosterone, estradiol, SHBG, glucose, and insulin could be measured. There were also prevalence ratios and odds ratios used to test the presence of an association between biochemical and instrumental variables. RESULTS: Serum levels of estradiol in the upper tertile of the frequency distribution were significantly associated with clinical evidence of varicose veins (prevalence odds ratios 3.6; 95% CI 1.1-11.6) and with increased lower limb venous distensibility (prevalence odds ratios 4.4; 95% CI 1.2-15.5). No association was found for SHBG and testosterone. CONCLUSIONS: Our finding that high serum levels of estradiol are associated with clinical evidence of varicose veins and instrumental measurements indicating increased venous distensibility in menopausal women suggests that endogenous estrogens may play a role in the development of this very common venous vessel abnormalities.