Parity as predictor of early hypertension during menopausal transition.

OBJECTIVES: Studies regarding the effects of parity on blood pressure in later life produced conflicting results. The aim of our study is to analyse whether parity influences the prevalence of hypertension in perimenopausal and postmenopausal women. METHODS: One thousand perimenopausal and postmenopausal women (mean age 55.2 ±â€Š5.4 years) were enrolled with a median follow-up of 63.0 months. The study sample consisted of patients who self-referred, in 1998-2009, to the BenEssere Donna Clinic, dedicated to menopause-related disorders. RESULTS: One hundred and twenty-two (12.2%) women were nulliparous and 878 (87.8%) had at least one child. Thirty-four (27.9%) women among nulliparous and 326 (37.1%) among parous were hypertensive at baseline (P = 0.046) and 812 women (81.2%) were in their postmenopausal period. Univariate analysis showed that women with one or more children were at higher risk of being hypertensive [odds ratio (OR): 1.529; 95% confidence interval (CI): 1.006-2.324; P = 0.047]. Likewise, multivariate analysis revealed that parity (OR: 2.907; 95% CI: 1.290-6.547; P = 0.010), BMI (OR: 1.097; 95% CI: 1.048-1.149; P < 0.001) and family history of hypertension (OR: 3.623; 95% CI: 2.231-5.883; P < 0.001) were independently related to hypertension at baseline. In a subanalysis of 640 initially normotensive women, 109 (17.0%) patients developed hypertension after follow-up, without a statistically significant association with parity (13.6% in nulliparous versus 17.6% in parous; P = 0.362). Consistently, parity showed no relationship with the incidence of hypertension during follow-up (OR: 1.350; 95% CI: 0.707-2.579; P = 0.363). CONCLUSION: For the first time in a population of White perimenopausal and postmenopausal women, parity was demonstrated to be independently associated with early hypertension during menopausal transition. Conversely, postmenopausal hypertension was not related with parity.

Effects of antihypertensive treatment on endothelial function in postmenopausal hypertensive women. A significant role for aldosterone inhibition.

INTRODUCTION: Endothelial dysfunction is a well-demonstrated independent predictor of cardiovascular events in hypertensive postmenopausal women. Accordingly, it is plausible that improving endothelial function could represent an adjunctive target for antihypertensive treatment. The aim of our study was to evaluate the effect of pharmacologic treatment on endothelial function in the specific population of hypertensive postmenopausal women. METHODS: A total of 320 consecutive hypertensive postmenopausal women underwent a high-resolution ultrasound study of the brachial artery at baseline and after six months, while 'optimal' control of blood pressure (maintenance of blood pressure values below 140/90 mmHg at all follow-up visits) was achieved using antihypertensive therapy. Endothelial function was measured as flow-mediated dilation, using ultrasound method. RESULTS: After six months of treatment, flow-mediated dilatation (FMD) had significantly improved in the majority of patients (n = 257 [80.3% of the entire population]; FMD = 8.1 ± 1.0% at baseline vs. 10.6 ± 1.5% after follow-up; p < 0.001), but it had not changed or worsened in others (n = 63 [19.7%]; FMD = 8.2 ± 1.2% at baseline vs. 7.6 ± 1.0% after six months; p = ns). Improvement of endothelial function, at multivariate analysis, resulted independently associated with the use of aldosterone inhibitors (odds ratio = 2.15; 95% confidence interval: 1.55-2.75; p = 0.001). CONCLUSIONS: This study demonstrates that a significant improvement in endothelial function may be obtained after six months of an optimal antihypertensive therapy. Among all hypertensive postmenopausal women that achieved an optimal control of blood pressure during follow-up, the use of drugs that inhibit aldosterone receptors was associated with an improvement of endothelial function, beyond the 'optimal' blood pressure control.

Endothelial function affects early carotid atherosclerosis progression in hypertensive postmenopausal women.

OBJECTIVES: Endothelial dysfunction is known to be associated with atherosclerosis progression and cardiovascular events. Limited information exists regarding the importance of this topic in hypertensive postmenopausal women. In this particular population the influence of endothelial dysfunction on cardio-vascular end cerebro-vascular events is well demonstrated. Therefore, we investigated, in a prospective study, the influence of endothelial-dependent vasodilation on carotid intima-media thickness (IMT) progression in our population of hypertensive postmenopausal women. METHODS: In addition to common risk factors and pharmacological therapy, we measured carotid IMT and flow-mediated dilation (FMD) of the brachial artery at baseline and after 1 year of follow-up. RESULTS: Baseline and follow-up data were available for 618 hypertensive postmenopausal women with an age of 55 ± 8 years. The mean IMT at baseline was 754 ± 161 µm [interquartile range (IQR) from 600 to 838 µm]. The mean FMD at baseline was 5.8 ± 3.9% (IQR from 3.2 to 8.2%). There was a significant correlation between baseline FMD and carotid IMT (r = -0.16; P = 0.003). Mean IMT progression resulted in 103 µm (range from -250 to 567 µm; IQR from 0 to 200 µm) per year. Baseline FMD, FMD change and the amount of SBP reduction during follow-up remained the independent predictors of IMT progression in multivariable analysis. CONCLUSIONS: In this prospective study we observed a significant interaction between baseline FMD, FMD change during follow-up and IMT progression in our population of hypertensive postmenopausal women. These results are in accordance with the suggestion that endothelial dysfunction is associated with enhanced atherosclerosis development. This hypothesis could provide a pathophysiological explanation for the increase in cardio-vascular and cerebro-vascular episodes recorded in hypertensive postmenopausal women with endothelial dysfunction.

Metabolic syndrome affects cardiovascular risk profile and response to treatment in hypertensive postmenopausal women.

Metabolic syndrome is increasingly recognized as an important cardiovascular risk factor in hypertension, but its influence on the cardiovascular risk profile in hypertensive postmenopausal women has not been studied. The aim of the present study was to investigate the impact of metabolic syndrome on the cardiovascular risk profile and the response to treatment. We enrolled 350 hypertensive postmenopausal women, 55+/-6 years of age (range 47 to 60 years of age). Patients were divided into 2 groups according to the presence of metabolic syndrome. Compared with those without, women with metabolic syndrome had higher waist circumference, body mass index, and levels of glucose, triglycerides, and HDL cholesterol, as would be expected, based on definition. In addition, patients with metabolic syndrome had a cardiovascular risk profile less favorable, characterized by a significantly higher highly sensitive C-reactive protein (2.2+/-0.6 versus 1.7+/-0.7 ng/L; P<0.01), a more compromised endothelial function (flow-mediated vasodilation 2.4+/-2.2 versus 4.4+/-2.5%; P=0.01), and a significantly higher left ventricular mass (44+/-15 versus 41+/-16 g/m(2.7)). Also, antihypertensive treatment induced a more modest improvement of both endothelial dysfunction and subclinical inflammation in women with metabolic syndrome. The results of our study show that in postmenopausal women, there are 2 different forms of hypertension: that which is isolated, and that which is associated with metabolic syndrome. This last form is related to a more severe risk profile, and response to therapy is less favorable.

Prognostic role of flow-mediated dilation and cardiac risk factors in post-menopausal women.

OBJECTIVES: The aim of this study was to examine the association between brachial artery flow-mediated dilation (FMD) and cardiovascular events in a cohort of initially asymptomatic post-menopausal women, with adjustment for the presence of the major cardiovascular risk factors. BACKGROUND: Conventional major cardiovascular risk factors (cigarette smoking, hypercholesterolemia, hypertension, and diabetes) fail to explain nearly 50% of cardiovascular events. Defining the magnitude of future risk for the development of clinical events is a major focus of effective primary prevention. Evaluation of endothelial function, utilizing the noninvasive measurement of the brachial artery FMD, may serve as a screening tool to individualize high-risk patients. METHODS: We conducted a prospective study on 2,264 post-menopausal women, age 54 +/- 6 years. The length of the follow-up was 45 +/- 13 months (range 6 to 65 months). RESULTS: During observation, 90 major events were recorded. Risk-adjusted relative risk values resulted 1.0, 1.33 (95% confidence interval [CI] 1.09 to 4.09), and 4.42 (95% CI 2.97 to 8.01) for women in the higher, intermediate, and lower tertile of FMD, respectively (p < 0.0001 for trend). The event rate for women in the lower tertile (FMD

Type 2 diabetes mellitus is a risk factor for the development of hypertension in postmenopausal women.

OBJECTIVE: Hypertension and type 2 diabetes mellitus are common diseases that are frequently found concomitantly in postmenopausal women. These findings suggest a close and/or synergistic nature in the relationship between the two disease processes; however, no prospective data exist on the incidence rate of hypertension in postmenopausal women with type 2 diabetes mellitus. METHODS: The present study assessed the risk of developing hypertension in 840 postmenopausal women: 102 women (12.1% of the cohort) with type 2 diabetes mellitus and 738 (87.9%) free of diabetes. The mean +/- SD follow-up was 3.2 +/- 0.9 years (range 0.5-6.0 years). RESULTS: The incidence rate (cases of hypertension per 100 person-years) was 1.1 for the group of women without diabetes versus 5.6 in women with diabetes (P < 0.0001). Compared with the non-diabetic group, women with type 2 diabetes mellitus had a statistically significant higher risk of developing hypertension. The relative risks for women with diabetes was 5.09 [crude: 95% confidence interval (CI) = 3.52-7.36; P < 0.0001]; 3.43 (adjusted for body mass index and waist circumference: 95% CI = 2.25-5.14; P < 0.001); and 2.95 (adjusted for all potential confounders: 95% CI = 1.86-4.32; P < 0.01). CONCLUSION: In our prospective study, on the incidence of hypertension, the presence of type 2 diabetes was found to be a potent independent risk determinant. This suggests that postmenopausal women affected by type 2 diabetes mellitus comprise a population at high risk for the subsequent development of hypertension.

Endothelial-dependent vasodilation and incidence of type 2 diabetes in a population of healthy postmenopausal women.

OBJECTIVE: Both postmenopausal state and diabetes are associated with endothelial dysfunction and are well-known risk factors for atherosclerosis. However, the relationship of endothelium-dependent vasodilation and diabetes has never been prospectively evaluated. This study provided the opportunity to assess the association between endothelial vasodilation function and the incidence of diabetes in a cohort of apparently healthy postmenopausal women. RESEARCH DESIGN AND METHODS: We conducted a prospective cohort study that began in 1997 with 840 apparently healthy, nonobese, postmenopausal women, aged 53 +/- 6 years, initially with normal glucose tolerance at the oral glucose tolerance test. All participants were followed up for a mean period of 3.9 +/- 0.7 years (range 0.5-6.9). Endothelial function was measured as flow-mediated dilation (FMD) of the brachial artery, using high-resolution ultrasound. RESULTS: There were no significant differences in demographic, blood pressure, and biochemical profiles among each tertile group at baseline or at follow-up review. During follow-up, 102 women developed type 2 diabetes. The adjusted relative risk (RR) for women with FMD /=5.6 (highest tertile reference). Each 1-unit decrease of FMD was associated with a significant 32% (22-48%) increase in the multiple-adjusted RR of incident diabetes. CONCLUSIONS: These prospective data indicate a significant increase in the RR of diabetes with each unit decrease of FMD. This could suggest that an impaired endothelial function may play a fundamental role in diabetogenesis in postmenopausal women.

Flow-mediated vasodilation and the risk of developing hypertension in healthy postmenopausal women.

OBJECTIVES: This study provided the opportunity to assess the relationship between endothelial vasomotor function and incidence of hypertension in a cohort of postmenopausal women. BACKGROUND: Both menopause and hypertension are associated with endothelial dysfunction and are well-known risk factors for atherosclerotic-related disease. METHODS: We conducted a prospective cohort study that began in 1996 on 952 apparently healthy postmenopausal women, age 53 +/- 5 years (range 44 to 60 years), with initially normal levels of blood pressure and no history of hypertension. All participants were followed up for a mean period of 3.6 +/- 0.7 years (range 0.5 to 6.9 years). Endothelial function was measured as flow-mediated dilation of the brachial artery using high-resolution ultrasound. RESULTS: During follow-up 112 women developed hypertension. The adjusted relative risk for women with flow-mediated dilation of 3.5 or less (lowest quartile) was 5.77 (95% confidence interval 4.34 to 8.10) versus women with flow-mediated dilation of 5.5 or greater (highest quartile, referent). Each one-unit decrease of flow-mediated dilation was associated with a significant 16% (95% confidence interval 12% to 33%) increase in the multiple-adjusted relative risk of incident hypertension. CONCLUSIONS: These prospective data indicate a significant increase in the relative risk of hypertension with each unit decrease of flow-mediated dilation that is independent of age and baseline systolic and diastolic pressure values. This could suggest that an impaired endothelial vasomotor function precedes and predicts the future development of hypertension in postmenopausal women.

Transdermal 17-beta-estradiol and risk of developing type 2 diabetes in a population of healthy, nonobese postmenopausal women.

OBJECTIVE: Various observational and randomized studies have demonstrated a reduction in the incidence of type 2 diabetes in postmenopausal women who received estrogen orally. No studies have been performed on the incidence of type 2 diabetes in postmenopausal women treated with transdermal 17-beta-estradiol. The purpose of our study was to assess the influence of transdermal 17-beta-estradiol on the incidence of type 2 diabetes in a population of healthy, nonobese postmenopausal women. RESEARCH DESIGN AND METHODS: Between January 1998 and December 2002, 673 healthy, nonobese postmenopausal women (mean age 54 +/- 5 years) were enrolled: 144 (21.4%) of these took transdermal 17-beta-estradiol and 529 (78.6%) had never taken hormones during their postmenopausal period. Final elaboration of the data took place in July 2003, with a mean follow-up of 3.7 +/- 0.7 years (ranging from 0.5 to 5 years). RESULTS: Type 2 diabetes developed in 60 patients during the follow-up period, which is the equivalent of 22 cases per 1,000 women-years. In the "hormones nonusers" group, diabetes developed in 10% (54 of 529 women; equivalent of 26.5 cases/1,000 women-years), whereas in the "hormones users" group, diabetes developed in 4.16% (6 of 144 women; equivalent of 12.1 cases/1,000 women-years). Transdermal 17-beta-estradiol emerged as a treatment that significantly reduced the risk of developing diabetes (RR 2.19, 95% CI 1.79-3.56; P=0.006). CONCLUSIONS: Our results suggest a significant reduction in the incidence of type 2 diabetes in our population of nonobese, healthy postmenopausal women who used transdermal 17-beta-estradiol. This could suggest that, in some women, the estrogen deficiency that occurs after menopause could represent a fundamental step in the process of diabetogenesis.