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Biomedical subjects

G M Rosano

Publications and source records attributed to G M Rosano.

At least 19 recordsLinked to original sources
PubMed2006

Managing cardiovascular risk in menopausal women.

Blood pressure control and prevention of glucose intolerance are primary factors in overcoming the increased cardiovascular risks in menopausal women. This heightened risk may partially be explained by the metabolic syndrome - a precursor of type 2 diabetes - in which the renin-angiotensin-aldosterone system may play a pivotal role. Once diabetes occurs, the cardiovascular risk is considerably greater in postmenopausal women than in men - especially if hypertension is also present. An additional risk factor, weight gain, is common in postmenopausal women not treated with hormone replacement therapy. Rigorous control of blood pressure has been shown to be particularly beneficial in women with metabolic syndrome; a reduction in blood pressure can reduce the mortality rate of ischemic stroke. The administration of hormone replacement therapy can also reduce the likelihood of coronary heart disease in postmenopausal women; therefore therapy should be started early in the menopausal transition to maximize cardiovascular protection. As such, an ideal hormone replacement therapy that can overcome hypertension, prevent body weight gain and control serum triglycerides offers an important advance in cardiovascular risk management during the menopause.

Age Factors↗
PubMed2001

Effect of estradiol valerate alone or in association with cyproterone acetate upon vascular function of postmenopausal women at increased risk for cardiovascular disease.

OBJECTIVES: a large body of evidence has been accumulated suggesting that impairment of vascular endothelial function is an initial step in the development of atherosclerosis. Recent studies have shown that estrogen replacement therapy in postmenopausal women (PMW) improves endothelium-dependent, flow-mediated dilatation (FMD) while the cyclical adjunct of a progestin may reverse this effect. METHODS: the purpose of this study was to evaluate endothelium-dependent, FMD in the brachial artery and the plasma levels of Endothelin-1 in menopausal females treated with estradiol valerate with and without cyclical cyproterone acetate in 20 PMW (mean age 64+/-6 years) with more than one risk factor for coronary artery disease. After a baseline evaluation, PMW entered a double-blinded, placebo controlled single cross-over study and were randomized to receive either estradiol valerate (2 mg) for 21 days or estradiol valerate (2 mg) for 11 days and estradiol valerate (2 mg) and cyproterone acetate (1 mg) for 10 days. Patients were crossed-over the complementary treatment 7 days after completing the first treatment phase. The study of forearm blood flow was repeated at the end of each treatment period. RESULTS: estradiol valerate significantly increased FMD as compared with baseline (12+/-3 vs. 7+/-4%, P<0.01) the adjunct of cyproterone acetate did not affect the effect of estradiol valerate upon FMD (12+/-3 vs. 11+/-4%, P=NS). Similarly reactive hyperemic flow increased after estradiol valerate alone (24%) or in association with cyproterone acetate (24%) compared with baseline. Plasma levels of Endothelin-1 were significantly reduced by estradiol valerate alone or in association with cyproterone acetate. CONCLUSIONS: in conclusion hormone replacement therapy with estradiol valerate and cyproterone acetate improves endothelial function and reduces plasma levels of Endothelin-1 in PMW at risk of coronary artery disease. These effects may be relevant for cardioprotection.

Brachial Artery↗
PubMed2001

Anti-ischemic effect of chronic oestrogen replacement therapy alone or in combination with medroxyprogesterone acetate in different replacement schemes.

BACKGROUND: Oestrogen replacement therapy in postmenopausal women has a protective effect upon the cardiovascular system and improves exercise-induced myocardial ischemia. Although in hormone replacement schemes progestins are required to reduce the likelihood of uterine malignancies, little is known on the cardiovascular effect of progestins. The purpose of this study was to evaluate the effect of oestrogen replacement alone and two different estrogen-progestin replacement therapy schemes upon exercise induced myocardial ischemia. MATERIAL AND METHOD: The study population included 18 female menopausal patients with coronary artery disease. After a baseline exercise test patients received conjugated equine estrogens (CEE) 0.625 mg alone for 30 days when they underwent a second exercise test and were randomized to receive in a cross-over design medroxyprogesterone acetate (MPA) either in continuous combined therapy (2.5 mg/daily) for 28 days or in cyclical therapy (10 mg o.d. from day 16 to day 28). RESULTS: After CEE alone two patients with a previously positive exercise test showed a negative exercise test. CEE increased time to 1 mm ST compared to baseline (352+/-185 vs 265+/-133 s, P<0.01). In the 2 pts in whom the exercise test was negative after CEE the test remained negative during continuous combined MPA therapy while become positive during cyclical MPA. CEE+continuous combined MPA increased both time to 1 mm ST and exercise time compared to baseline (386+/-165 vs 265+/-133 s, P<0.01 and 545+/-198 vs 465+/-186 s, P<0.05, respectively). No difference was found between baseline and CEE+cyclical MPA in either time to 1 mm ST or exercise time (268+/-164 vs 265+/-133 s, P=NS and 455+/-223 vs 465+/-186 s, P=NS, respectively). CONCLUSION: Continuous combined therapy with CEE+MPA improves exercise-induced myocardial ischemia in female patients with coronary artery disease while the beneficial effect of CEE is reduced by cyclical therapy.

Aged↗
PubMed2001

Time course and determinants of left ventricular function recovery after primary angioplasty in patients with acute myocardial infarction.

OBJECTIVES: We sought to evaluate the importance of time in relation to treatment, time course and determinants of recovery of left ventricular (LV) function in patients with acute myocardial infarction (AMI) undergoing primary percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: Myocardial salvage has been shown to be dependent on the time elapsed from the onset of AMI to reperfusion. METHODS: Left ventricular function was evaluated at hospital admission, after angioplasty, at 24 h and 6 months by both echocardiography and angiography and at 1, 7, 30, 90 and 180 days by echocardiography in 101 consecutive patients. RESULTS: Patients were allocated to three groups according to interval between symptom onset and angioplasty: <2 h (group A), 2 to 4 h (group B) and >4 h (group C). Patients in groups A and B showed a progressive improvement of LV function between day 7 and day 90, which became statistically significant at day 30 (p < 0.01). No LV function changes were noted in group C patients. Thrombolysis In Myocardial Infarction (TIMI) flow grade <3 at 24 h was not associated with any significant change in LV volume and function during the six-month follow-up period. Restenosis, when associated with TIMI flow grade 3 in the infarct-related vessel, did not influence LV function. Flow grade <3 of the infarct-related artery was not associated with any improvement of cardiac events independently from the time to treatment at the initial procedure. CONCLUSIONS: Patients undergoing primary PTCA for AMI have a good recovery of LV function if TIMI flow grade 3 is restored within 4 h. Coronary angioplasty limits further remodeling of the LV in patients treated after 4 h.

Angioplasty, Balloon, Coronary↗
PubMed2001

How progestins influence the cardiovascular effect of hormone replacement therapy.

Hormone replacement therapy aims to protect against osteoporosis and alleviate fastidious menopausal symptoms such as hot flushes, depression, sleep disturbances and vaginal dryness. In view of the acknowledgement of estrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, hormone replacement therapy may also be proposed as a substantial beneficial cardioprotective agent. The effects of progestins on lipoprotein profile and vasomotor tone are dependent on the chemical structure and the scheme of administration of progestins, with androgenic progestins and cyclical therapy having a potential detrimental effect. Prospective primary and secondary prevention studies, however, suggest that the adjunct of non-androgenic progestins to estrogen therapy is at least as effective as estrogen replacement therapy in reducing cardiovascular mortality and morbidity. Data from recent randomized secondary prevention studies have to be viewed with caution.

Animals↗
PubMed2001

Can menopause be considered an independent risk factor for cardiovascular disease?

Following the menopause, women develop coronary artery disease at the same rate as men. The best documented change observed in the risk factors linked to ovarian exhaustion is an alteration in lipid composition. More recent studies, however, suggest that the increased cardiovascular morbidity and mortality after menopause cannot be fully explained by changes in plasma lipoproteins, and support the concept that ovarian hormone deprivation has a widespread impact on the cardiovascular system, with a direct harmful effect on vessel-wall physiology. After the menopause, subjects free from cardiovascular diseases show vascular hyperactivity and a poor vasodilator reserve; the rate of increase in the incidence of arterial hypertension in women is higher than that observed among males of the same age; altogether, cardiovascular diseases become the number one cause of death among women. A large number of mechanistic studies have shown that estrogens, through either direct or genomic-dependent activities, produce beneficial effects on the factors controlling blood flow and plaque formation. Nevertheless, results from recent randomized clinical trials are challenging the belief that postmenopausal hormone therapy protects against coronary artery disease.

Arteriosclerosis↗
PubMed2001

Effect of sildenafil citrate upon myocardial ischemia in patients with chronic stable angina in therapy with beta-blockers.

BACKGROUND: It has been suggested that phosphodiesterase 5 (PDE5) inhibition is potentially hazardous and that it increases the risk of cardiac events in patients with coronary artery disease. This study sought to evaluate whether PDE5 inhibition with sildenafil exerts any effect on exercise-induced myocardial ischemia in patients on beta-blockers. METHODS: Fourteen patients underwent a baseline exercise test off-therapy and were then started on atenolol (100 mg once daily). After a run-in phase of 1 week, patients underwent a second exercise test and were randomized to receive either sildenafil (50 mg) or placebo given in a random order on two different occasions, 2 days apart. Exercise test was repeated 2 hours after the administration of sildenafil or placebo. RESULTS: All patients had a > 1 mm ST-segment depression while off-therapy. Eight patients had a negative exercise test response after atenolol, which was unaltered by the adjunct of either sildenafil or placebo. In the remaining subjects, atenolol significantly prolonged the time to 1 mm ST-segment depression and the exercise time. Sildenafil and placebo did not reverse the beneficial effect of atenolol upon exercise-induced myocardial ischemia. CONCLUSIONS: PDE5 inhibition does not worsen exercise capacity and exercise-induced myocardial ischemia in patients with chronic stable angina whose symptoms and exercise test response are well controlled by beta-blocker therapy.

Adrenergic beta-Antagonists↗
PubMed2000

Acute electrophysiologic effect of estradiol 17beta in menopausal women.

Sixteen postmenopausal women underwent electrophysiologic study before and 20 minutes after the administration of sublingual estradiol 17beta or placebo. Estradiol 17beta significantly affected electrophysiologic parameters, thereby suggesting its role in the development of palpitations in women.

Administration, Sublingual↗
PubMed2000

Cardioprotective effects of ovarian hormones and the HERS in perspective.

The increased population of women in menopause living in the industrialized countries is associated with an increase of diseases which are dependent or facilitated by a state of estrogen deficiency such as cardiovascular and cerebrovascular diseases. Several studies have shown that estrogen replacement therapy reduces the occurrence of coronary and may be of cerebrovascular disease by nearly 50% in treated women compared to non-users. These findings are supported by the evidence that estrogens have a beneficial effect on cholesterol metabolism and deposition, contributing to the inhibition of atherosclerotic plaque formation in arterial walls as well as a direct effect on the vessel wall. Progestins may, in some cases, counteract the beneficial effect of estrogens upon cardiovascular functions. More androgenic progestins may have a detrimental effect upon vascular reactivity while less androgenic progestins seem not to reduce the beneficial effect of estrogens. Of interest, continuous combined administration of hormone replacement therapy seem to be preferable for women with coronary artery disease or for those with increased cardiovascular risk. Case-control and cohort studies have shown that estrogen progestin therapy is associated with a significant reduction of cardiovascular mortality and morbidity. The HERS study has added critical data regarding the cardioprotective effect of hormone replacement therapy in elderly women with proven coronary artery disease. Because of the several methodological and statistical flaws of the HERS study, further studies are warranted to evaluate the effect of hormone replacement therapy on cardiovascular prognosis. Large scale randomized studies will evaluate the effect of estrogen and estrogen-progestin replacement therapy upon cardiovascular events in menopausal women. Until completion of these studies hormone replacement therapy in women with increased cardiovascular risk should be seen with no enthusiasm but also with no fear.

Cardiovascular Diseases↗
PubMed2000

Evidence of a role of endogenous estrogen in the modulation of autonomic nervous system.

We studied heart rate variability in 14 healthy women before and after oophorectomy compared with 14 matched women who underwent hysterectomy with ovarian conservation. Surgical menopause induced a decline in cardiac vagal modulation with a shift toward sympathetic hyperactivity. Recovery of the baseline condition after 3 months of estrogen replacement therapy in oophorectomized women suggests a role of estrogen in the autonomic nervous control of the cardiovascular system.

Cardiovascular System↗
PubMed2000

Natural progesterone, but not medroxyprogesterone acetate, enhances the beneficial effect of estrogen on exercise-induced myocardial ischemia in postmenopausal women.

OBJECTIVES: We sought to compare the effects of estrogen/transvaginal progesterone gel with estrogen/medroxyprogesterone acetate (MPA) on exercise-induced myocardial ischemia in postmenopausal women with coronary artery disease or previous myocardial infarction, or both. BACKGROUND: Estrogen therapy beneficially affects exercise-induced myocardial ischemia in postmenopausal women; however, women with an intact uterus also take progestin to protect against uterine malignancies. The effects of combination estrogen/progestin therapy on myocardial ischemia are unknown. METHODS: Eighteen postmenopausal women (mean +/- SD age 59+/-7 years) were given 17-beta-estradiol in single-blinded manner for four weeks (1 mg/day for three weeks then 2 mg/day for one week). Estradiol (2 mg/day) was then continued, and the patients were randomized (double-blind) for 12 days to either transvaginal progesterone gel (90 mg on alternate days) and oral MPA placebo (10 mg/day), or vice versa. After another two weeks on estradiol alone, the patients crossed over to progestin treatment and repeated the protocol on the opposite treatment. Patients underwent treadmill exercise testing after each estradiol phase and at day 10 of each progestin phase. RESULTS: Exercise time to myocardial ischemia increased after the first estrogen phase as compared with baseline (mean difference with 95% confidence interval [CI]: 72 s [34 to 110], p = 0.001), and was increased by combination estradiol/progesterone therapy as compared with estradiol/MPA therapy (92 s [35 to 149], p = 0.001)). Two patients (11%) were withdrawn while taking estradiol/MPA owing to unstable angina. CONCLUSIONS: Combination estrogen/transvaginal progesterone gel increases exercise time to myocardial ischemia, as compared with estrogen/MPA. These results imply that the choice of progestin in women at higher cardiovascular risk requires careful consideration.

Cross-Over Studies↗
PubMed2000

The relative effects of progesterone and progestins in hormone replacement therapy.

Hormone replacement therapy (HRT) was initially given to protect women against osteoporosis and alleviate menopausal symptoms, such as hot flashes, depression, sleep disturbances, and vaginal dryness. In view of the understanding of oestrogen deficiency as a major trigger for the acceleration of cardiovascular risk after menopause, HRT may also be proposed as a substantial beneficial cardioprotective agent. Progestins, which may be added to oestrogen in combined HRT to reduce the risk of uterine malignancy, have a number of potential adverse effects on the cardiovascular system which could even attenuate the benefit of unopposed oestrogen replacement therapy in post-menopausal women.

Animals↗
PubMed2000

Predictors of long-term clinical outcome in patients undergoing multiple vessel stenting for coronary artery disease.

BACKGROUND: Coronary artery stenting reduces the restenosis rate compared to coronary angioplasty alone. With the increased number of procedures completed with stent placement there has been a parallel increase in the number of procedures performed in patients with multivessel disease and therefore a rise in the number of patients receiving multiple stents. The clinical outcome and the predictors of the outcome of patients receiving multiple stents are not known. METHODS: To evaluate the clinical outcome of patients with multivessel coronary artery disease undergoing multiple stenting we studied 133 consecutive patients who had received > 1 stent in at least two vessels. A total of 375 coronary stents (2.8 stent per patient) were implanted in elective procedure situations. Clinical follow-up was complete in 100%. RESULTS: During follow-up 2 patients (1.5%) died (1 cardiac death), 4 patients (3%) had acute myocardial infarction, 96 patients (72.1%) remained angina-free, and 31 patients (23.3 %) had recurrence of angina. Repeat revascularization procedure was performed in 45 patients (33.8%); 43 patients (32.3%) underwent coronary angioplasty; 2 patients (1.5%) underwent coronary artery bypass grafting. The female gender and the presence of diabetes were significant (p < 0.05) predictors for coronary angioplasty or coronary artery bypass grafting procedures during follow-up. Recurrence of angina was also significantly (p < 0.05) associated with unstable angina at the time of the first procedure as well as diabetes and the female gender. Diabetes, the female gender and unstable angina were highly predictive factors of major adverse cardiac events during follow-up. CONCLUSIONS: Multiple vessel stenting in patients with multivessel coronary artery disease is associated with an acceptable immediate and long-term clinical outcome and could be considered as an alternative therapeutic option in these patients. Predictors of an adverse long-term outcome are the female gender and the presence of diabetes mellitus.

Angioplasty, Balloon, Coronary↗
PubMed1999

The acute effects of sublingual 17beta-estradiol on the cardiovascular system.

The beneficial effects of estrogen in postmenopausal women have been well documented. Cardioprotection by estrogen, which is probably the result of several metabolic alterations, appears after 2 or more years of constant use. However, acute administration of estrogen (intravenous or intracoronary) was found to improve cardiac hemodynamics and function through various non-genomic mechanisms. This article reviews data on the consequences of sublingual administration of estrogen, a non-invasive and simple dosing route which is associated with rapid absorption and prompt cardiovascular reactions. It appears that sublingual estradiol at 1 or 2 mg may improve ischemia and exercise performance in women with coronary artery disease, and augment the aortic and brachial blood flow as a result of vasodilation, whereas larger doses (4 mg) may lead to a decrease in myocardial contractility and aortic blood flow, and a slight drop in blood pressure. More data are needed to evaluate the actual clinical significance of sublingual estradiol in healthy women, in situations when endothelial dysfunction is anticipated (diabetes, hypertension) and in women with diagnosed coronary artery disease.

Absorption↗