Left atrial appendage thrombosis in a patient with Friedreich Ataxia-related cardiomyopathy, left ventricular systolic dysfunction, and atrial fibrillation.

Friedreich ataxia is the most common form of hereditary ataxia. Heart involvement in Friedreich ataxia is common and can include increased left ventricular wall thickness, atrial fibrillation, and in the later stages, a reduction of left ventricular ejection fraction. We present the case of a 45-year-old man with a history of paroxysmal atrial fibrillation and a congestive heart failure, hypertension, age ⩾ 75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years, and female sex (CHA2DS2-VASc) score of only 1 (because of reduced left ventricular ejection fraction) who presented with pneumonia and was also found to have atrial fibrillation with a rapid ventricular response. Despite already being on long-term therapy with a non-vitamin K-antagonist oral anticoagulant, a transesophageal echocardiogram showed a mobile floating thrombus in the left atrial appendage. In accordance with previous necropsy evidence of thrombosis and thromboembolism in Friedreich ataxia subjects who likely have had only non-sex-related CHA2DS2-VASc score ⩽1, this case suggests that the risk of thromboembolism in Friedreich ataxia subjects with atrial fibrillation may not be adequately predicted by the sole CHA2DS2-VASc score.

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.

Hypertension alone or related to the metabolic syndrome in postmenopausal women.

Cardiovascular risk is poorly perceived by women, especially during the peri- and postmenopausal period when susceptibility to cardiovascular events increases. Nevertheless in Europe, 55% of women versus 43% of men currently die of cardiovascular disease. Blood pressure is one of the most powerful and accurate determinants of cardiovascular status and risk. Despite its importance, hypertension is often underestimated and undiagnosed, especially in women. Various mechanisms are implicated to play a role in the blood pressure increase in women at the time of menopause. Hypertension can be considered an isolated disease, more typical of elderly women, or part of the metabolic syndrome, more frequent in early postmenopausal women. The metabolic syndrome, a clustering of lipid and nonlipid cardiovascular risk factors, is estimated to affect approximately 20-30% of the middle-aged population and its prevalence appears to be increasing in the worldwide population.

Metabolic disorders induced by highly active antiretroviral therapy and their relationship with vascular remodeling of the brachial artery in a population of HIV-infected patients.

Antiretroviral therapy has positively modified the natural history of HIV infection; but this treatment can induce metabolic abnormalities, including dyslipidemia, fat redistribution, high blood pressure, and insulin resistance. The metabolic syndrome, a clustering of the metabolic disorders, is frequently detected among HIV patients, especially those on antiretroviral treatment. All the arteries can modify their diameter in response to a chronic injury. This process, defined vascular remodeling, was demonstrated for the brachial artery. It is well known that the diameter of the brachial artery was correlated with the number of the elements of the metabolic syndrome and was associated with the severity of coronary artery disease. On this basis, we postulate that brachial arterial enlargement may be a process potentially correlated with the metabolic disorders induced by antiretroviral therapy. We tested this hypothesis in a large population of HIV-infected patients in which we measured brachial artery diameter, as an indicator of artery remodeling, by noninvasive, ultrasonographic technique. Our population consisted of 570 patients, with a mean age of 46.3 +/- 7.1 years. All the patients were chronically treated with highly active antiretroviral therapy. Brachial artery diameter was correlated with insulin resistance, evaluated by the homeostasis model assessment of insulin resistance index (r = 0.18, P < .0001). There was a significant linear increase in brachial artery diameter as the number of components of the metabolic syndrome increased: brachial artery diameter for those with 0, 1, 2, 3, or + characteristics was 39.3 +/- 7.2, 41.0 +/- 6.8, 42.0 +/- 7.3, and 43.8 +/- 7.9 mm, respectively (P < .001 for trend). In multivariable logistic regression analysis, brachial artery diameter was independently correlated with the presence of metabolic syndrome. Our results are in line with the hypothesis that, among HIV-infected patients chronically treated with antiretroviral therapy, those with a larger brachial artery diameter are at high risk for metabolic disorders, including a more severe insulin resistance and the presence of metabolic syndrome.

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

Sildenafil improves endothelial function in patients with pulmonary hypertension.

BACKGROUND: Sildenafil has been shown to be effective in the treatment of pulmonary hypertension, and has favourable effects on endothelial function. Our hypothesis is that a part of the beneficial effects of sildenafil in patients with pulmonary hypertension is due to the improvement of the endothelial function. METHODS: Nine patients (seven females, age 67+/-9 years) with thromboembolic pulmonary hypertension were treated with sildenafil, at a mean dose of 150+/-75 mg/die. At baseline and after 6 months all patients underwent: right-heart catheterization, 6-min walking distance, and a study of endothelial function, including the measure of the flow-mediated vasodilation of the brachial artery, and the dosage of plasma levels of endothelin-1 and von Willebrand factor. RESULTS: During follow-up we found a significant reduction of mean pulmonary artery pressure and arteriolar resistances. Accordingly, the functional capacity improved (an average of+37 m). Sildenafil improved endothelial-dependent vasodilation and reduced plasma concentrations of endothelin-1 (from 4.5+/-0.6 to 3.1+/-0.7 pg/mL; p<0.0001) and von Willebrand factor (from 183.1+/-10.1 to 149.1+/-17.6 mU/mL; p<0.0001). CONCLUSION: Improvement of the endothelial function may represents one of the mechanisms able to explain the favourable effects sildenafil has shown in patients with pulmonary 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.

Gender differences in diagnostic procedures.

This review examines the contribution of the literature to the controversial issue of diagnostic procedures in women affected by coronary artery disease (CAD), on which a large number of papers have been published. It has been reported that cerebro- and cardiovascular diseases represent the first cause of death in the New as well as in the Old World, Italy included. Some studies are conditioned by bias; one of these is the Framingham study, in which angina was reported and defined only clinically and for a relatively young age range, as a benign condition in women. Angiographic studies, such as the CASS, considered a super elected group of women referred to the hemodynamic laboratory for chest pain, which in the female gender often has atypical characteristics. In our opinion, it is mandatory to take into account: 1) what chest pain really means in women; 2) the fact that there are gender differences: women have a different biological and hormonal status, lifestyle, and perception of the disease; 3) that there is a different approach of the physicians to a woman with possible or suspected CAD. We suggest, therefore, a more peculiar and individualized diagnostic approach to women suspected as having CAD. This approach should also take the pre-test probability of disease into consideration. The first investigational step we recommend is the exercise ECG test; should this be unfeasible or not interpretable, an imaging and/or pharmacological stress test is advisable. In case of positive first test results, coronary angiography should be performed.