Annachiara Nuzzo

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 <or=4.5%) was greater than the combined event rate noted in the other 2 tertiles (women in the lower tertile accounted for 51 events [56.6% of total events]). When added to age and other conventional cardiovascular risk factors (smoking habits, presence of hypercholesterolemia, history of diabetes, hypertension), FMD contributed significantly to the model predicting cardiovascular events (likelihood ratio chi-square change: 10.22; p < 0.0001). CONCLUSIONS In post-menopausal women, the knowledge of FMD provided incremental prognostic information regarding the risk of developing cardiovascular events.

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/m2.7). 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.

Influence of body mass index on extent of coronary atherosclerosis and cardiac events in a cohort of patients at risk of coronary artery disease

BACKGROUND AND AIM To estimate if a meaningful relationship exists between body mass index (BMI) and the entity of coronary atherosclerosis, coronary events and mortality in a cohort of consecutive patients with suspected coronary artery disease (CAD). METHODS AND RESULTS In this prospective study, we enrolled 1299 consecutive patients (905 [69.7%] males) who had undergone coronary angiography. Our sample consisted of 477 patients (36.8%) of normal weight; 567 (43.6%) overweight and 255 (19.6%) obese, according to the WHO classification. Conventional cardiovascular risk factors, BMI, endothelial function and subclinical inflammation were studied. Different angiographic CAD scores were used to quantify coronary atherosclerotic burden. In overweight and obese patients, respect to normal weight population, there is a higher prevalence of hypertension, hypercholesterolemia and diabetes mellitus, but BMI was not significantly associated with greater extent of coronary atherosclerosis. At follow-up (mean: 40; range: 24-82 months) obese and overweight patients showed a higher incidence of coronary events compared to the normal weight population (74.9% [obese] versus 62.7% [overweight] versus 53.2% [normal weight]; adjusted relative risk [obese versus overweight]: 1.08 [95% confidence interval: 1.02-1.23]; P<0.05; and adjusted RR [obese versus normal weight]: 1.17 [95% CI: 1.10-1.42], P<0.01). Mortality from cardiac events was not significant within the categories. The Cox regression model showed flow mediated dilation (P<0.0001), high-sensitive C reactive protein (P=0.022) and BMI (P=0.045) as independent predictors of acute coronary events. CONCLUSION BMI is not associated with the extent of coronary atherosclerosis and mortality. The higher incidence of coronary events in obese subjects is only partly explained by conventional associated risk factors. Impaired endothelial function and sub-clinical inflammation could be involved in this association but BMI itself is related to cardiovascular events suggesting that other unknown (or not considered) pathways are involved.

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.

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.

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.

Endothelial dysfunction in postmenopausal women and hypertension.

The endothelium is a major regulator of homeostasis and exerts a number of vasoprotective effects, such as vasodilation, inhibition of inflammatory responses and suppression of smooth muscle cell growth. Dysfunction of the endothelium thus causes reduction or abolition of these vasoprotective effects. Factors that lead to endothelial dysfunction (ED) include a reduction in nitric oxide (NO) production, increased oxidative stress and a decrease in NO bioavailability, whereas endothelium-derived contracting factors are increased. This imbalance leads to an impairment of endothelium-dependent vasodilation, which represents the functional characteristic of ED. Moreover, ED also comprises a specific state of ‘endothelial activation’, which is characterized by a proinflammatory, proliferative and procoagulatory milieu that favors all stages of atherogenesis [1,2]. Hence, ED it is considered a systemic disorder and a key variable in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk-factor burden but, rather, may be regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual. ED reflects a vascular phenotype prone to atherogenesis, and may therefore serve as a marker of the inherent atherosclerotic risk in an individual. In line with this hypothesis, dysfunction of either the coronary or peripheral vascular endothelium was shown to constitute an independent predictor of cardiovascular events, providing valuable prognostic information additional to that derived from conventional risk-factor assessment [3].

Impairment of functional integrity of the vasculature is not changed in patients starting abacavir

Abstracts of the Ninth International Congress on Drug Therapy in HIV Infection Meeting abstracts – A single PDF containing all abstracts in this Supplement is available here . http://www.biomedcentral.com/content/pdf/1758-2652-11-S1-info.pdf