Rosario Rossi

Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women

OBJECTIVES ; The aim of the present study was to assess whether optimized antihypertensive treatment is effective in modifying endothelial function and whether an improvement in flow-mediated vasodilation (FMD) in response to treatment, as an expression of reversible endothelial dysfunction, could predict a more favorable prognosis in a population of postmenopausal women. BACKGROUND Hypertensive postmenopausal women have been shown to have abnormal endothelium-dependent vascular function. However, FMD may change over time, according to antihypertensive treatment; the prognostic value of these changes has not been investigated. METHODS A total of 400 consecutive postmenopausal women with mild-to-moderate hypertension and impaired FMD underwent ultrasonography of the brachial artery at baseline and after six months, while optimal control of blood pressure was achieved using antihypertensive therapy. They were then followed up for a mean period of 67 months (range 57 to 78). Endothelial function was measured as FMD of the brachial artery, using high-resolution ultrasound. RESULTS After six months of treatment, FMD had not changed (< or = 10% relative to baseline) in 150 (37.5%) of 400 women (group 1), whereas it had significantly improved (>10% relative to baseline) in the remaining 250 women (62.5%) (group 2). During follow-up, we noticed 32 events (3.50 per 100 person-years) in group 1 and 15 events (0.51 per 100 person-years) in group 2 (p < 0.0001). CONCLUSIONS This study demonstrates that a significant improvement in endothelial function may be obtained after six months of antihypertensive therapy and clearly identifies patients who possibly have a more favorable prognosis.

A randomised trial of target-vessel versus multi-vessel revascularisation in ST-elevation myocardial infarction: major adverse cardiac events during long-term follow-up

Background Few reports described outcomes of complete compared with infarct-related artery (IRA)-only revascularisation in patients with ST-elevation myocardial infarction (STEMI) and multivessel coronary artery disease (CAD). Moreover, no studies have compared the simultaneous treatment of non-IRA with the IRA treatment followed by an elective procedure for the other lesions (staged revascularisation). Methods The outcomes of 214 consecutive patients with STEMI and multivessel CAD undergoing primary angioplasty were studied. Before the first angioplasty patients were randomly assigned to three different strategies: culprit vessel angioplasty-only (COR group); staged revascularisation (SR group) and simultaneous treatment of non-IRA (CR group). Results During a mean follow-up of 2.5 years, 42 (50.0%) patients in the COR group experienced at least one major adverse cardiac event (MACE), 13 (20.0%) in the SR group and 15 (23.1%) in the CR group, p<0.001. Inhospital death, repeat revascularisation and re-hospitalisation occurred more frequently in the COR group (all p<0.05), whereas there was no significant difference in re-infarction among the three groups. Survival free of MACE was significantly reduced in the COR group but was similar in the CR and SR groups. Conclusions Culprit vessel-only angioplasty was associated with the highest rate of long-term MACE compared with multivessel treatment. Patients scheduled for staged revascularisation experienced a similar rate of MACE to patients undergoing complete simultaneous treatment of non-IRA.

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.

Coronary Aging in HIV-Infected Patients

BACKGROUND Human immunodeficiency virus (HIV)-infected patients often demonstrate accelerated aging processes. We investigated whether the vascular age of a cohort of stable HIV-infected patients receiving antiretroviral therapy (ART) was increased and sought out predictors of increased vascular age. METHODS In this cross-sectional study, 400 HIV-infected patients (mean age, 48 years) attending a cardiometabolic clinic underwent cardiac computed tomography imaging to identify coronary artery calcium (CAC). Vascular age was estimated on the basis of the extent of CAC by means of previously published equations. RESULTS Increased vascular age was observed in 162 patients (40.5%), with an average increase of 15 years (range, 1-43 years) over the chronological age. In univariable analyses, chronological age, male sex, systolic blood pressure, duration of ART, fasting glucose level, fasting serum triglyceride level, total cholesterol level, low-density and high-density lipoprotein cholesterol levels, hypertension, and the presence of the metabolic syndrome were associated with increased vascular age. In multivariable linear regression analyses, current CD4+ cell count was the only predictor of increased vascular age (beta = 0.51; P = .005). CONCLUSIONS Increased vascular age is frequent among HIV-infected patients and appears to be associated with CD4+ cell count. If these findings were to be confirmed in prospective trials, a positive response to ART with an increase in CD4+ cell count may become a marker of increased risk of atherosclerosis development.

Reduction of scatter radiation during transradial percutaneous coronary angiography: A randomized trial using a lead-free radiation shield†

Background: Occupational radiation exposure is a growing problem due to the increasing number and complexity of interventional procedures performed. Radial artery access has reduced the number of complications at the price of longer procedure duration. Radpad® scatter protection is a sterile, disposable bismuth‐barium radiation shield drape that should be able to decrease the dose of operator radiation during diagnostic and interventional procedures. Such radiation shield has never been tested in a randomized study in humans.

Lipodystrophy and anti-retroviral therapy as predictors of sub-clinical atherosclerosis in human immunodeficiency virus infected subjects

BACKGROUND AND OBJECTIVE Although anti-retroviral therapy (ART) prolonged survival in HIV-infected persons, an increase in cardiovascular disease has also been observed. A frequent complication of ART is the development of lipodystrophy (LD) with its multiple phenotypes that may be associated with cardiovascular disease. We assessed the contribution of chronic HIV infection, ART use and LD to the presence of sub-clinical atherosclerosis as evaluated by coronary artery calcium (CAC) imaging. METHODS Observational cross-sectional study of 372 HIV-infected patients receiving ART who attended a cardiometabolic clinic (48.2+/-8-year old; 74% men). All patients underwent CAC surveillance with computed tomography and the Agatston score was used to quantitate CAC. Presence of CAC was defined as a score >10. Multivariable logistic regression was used to evaluate associations between HIV clinical factors, ART and LD with the presence of CAC. FINDINGS CAC was found in 134 patients (36%) with a median CAC score of 50 (range 10; 1243). Lipoatrophy alone (OR 3.82, 95% CI: 1.11; 13.1), fat accumulation alone (OR 7.65, 95% CI: 1.71; 37.17) and mixed lipodystrophy phenotypes (OR 4.36, 95% CI: 1.26; 15.01) were strongly associated with presence of CAC after adjusting for age, sex, hypertension and cumulative exposure to ART. CONCLUSION CAC is common among long-term ART users. The association between CAC and LD underscores the potential atherosclerosis risk inherent with ART and the need to undertake routine cardiovascular surveillance in patients treated with these drugs.

Menopause and cardiovascular risk.

Menopause is not a disease, but a physiologic phase of a womans life, due to the changes of their hormonal status. Fastidious symptoms may be associated with changes in the metabolism together with new cardiovascular risk factors, particularly aggressive for the female cardiovascular system, unprepared because of the protection due to the fertile period. Changes of the lipid profile, obesity, hypertension, glucose intolerance and diabetes mellitus may intervene as severe risk factors. Cardiovascular disease represents therefore the most frequent cause of mortality and morbidity also in the female gender more than cancer either in the United States as in Europe. The risks related to post-menopause are mainly due to the abrupt interruption of estrogen, which has indirect protective effects on lipid, glycidic metabolism and direct effects on vessel function. They have, in fact, vasodilator action due to nitric oxide release, calcium-antagonist like action and an antiproliferative effect on smooth muscle cells. Post-menopause is also frequently associated with hypertension, the most frequent related factor to coronary artery disease. Hypertension is due to increased body mass index, with insulin-resistance, sodium retention, increased blood viscosity and estrogen deficiency with increased smooth muscle cell proliferation which determines an increase in systemic vascular resistance. Age and estrogen deficiency are together the most important cause of cardiovascular risk in post-menopause. The discovery of alpha and recently beta estrogen receptors on coronary female vessels unaffected by atherosclerosis either during pre and post-menopause phase are possible key of interpretation of pathophysiology of coronary artery disease in women, with important therapeutic consequence.

Effects of transdermal 17β-estradiol on left ventricular anatomy and performance in hypertensive women

To reduce cardiovascular complications, antihypertensive therapy should not only normalize blood pressure but also induce a regression of structural abnormalities, which are the expression of end-organ damage. We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of left ventricular anatomy and systolic performance in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 169 postmenopausal women with mild or moderate hypertension. Eighty-six patients (group 1) received transdermal 17beta-estradiol (50 microg/d) and norethisterone acetate (2.5 mg/d, orally), and 83 patients (group 2) received placebo. At baseline, all women underwent M-mode and 2-D echocardiogram, which was repeated after 6, 12, and 18 months of follow-up. After 18 months of treatment, we observed a significant decrease in left ventricular diastolic septal and posterior wall thickness and mass in both groups. Furthermore, after 18 months, left ventricular mass was significantly less than in the estrogen-treated group. No significant modifications were observed in left ventricular systolic and diastolic dimensions or in systolic performance, as expressed by left ventricular fractional shortening. In conclusion, transdermal 17beta-estradiol, which is associated with antihypertensive therapy, may contribute in the reduction of left ventricular mass in hypertensive postmenopausal women.

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.

Double-blind randomized placebo-controlled study of transdermal estrogen replacement therapy on hypertensive postmenopausal women

We investigated the effects of transdermal 17beta-estradiol, combined with standard antihypertensive therapy, on the modification of the cardiovascular risk profile in hypertensive postmenopausal women. In a randomized, double-blind, placebo-controlled study, we enrolled 200 postmenopausal women with mild to moderate hypertension. Patients received 17beta-estradiol (50 microg/day, transdermal) and norethisterone acetate (2.5 mg/ day, orally) or placebo. At baseline serum total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, glucose, and fibrinogen plasma levels were measured and all subjects underwent complete M-mode and 2-D echocardiograms, which were repeated after 6, 12, and 18 months of hormonal replacement therapy. Compared with placebo, all values decreased significantly except for HDL cholesterol. In both groups, no modifications were observed in echocardiographic parameters, except for left ventricular mean diastolic and systolic wall thickness and left ventricular mass index, which showed a significant decrease in both groups. The reduction was greater in the treated group; the percentage of patients with left ventricular hypertrophy was 46% before randomization and 17.2% after 18 months of treatment (P < .0001), whereas in group II the percentage was 48% at baseline and 31.5% after 18 months (P < .05). In conclusion, transdermal 17beta-estradiol, associated with antihypertensive therapy, may contribute to the reduction of cardiovascular risk profile in hypertensive postmenopausal women.