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Biomedical subjects

Giuseppe M C Rosano

Publications and source records attributed to Giuseppe M C Rosano.

At least 19 recordsLinked to original sources
PubMed2006

Effect of free fatty acid inhibition on silent and symptomatic myocardial ischemia in diabetic patients with coronary artery disease.

OBJECTIVE: Free fatty acid inhibition with trimetazidine (TMZ) improves myocardial metabolism and myocardial ischemia in patients with coronary artery disease (CAD). Because of its effect on myocardial glucose utilization TMZ may represent a therapeutic option in diabetic patients with CAD. Aim of the present study was to evaluate whether the metabolic effect of TMZ may improve episodes of myocardial ischemia in diabetic patients with CAD. RESEARCH DESIGN AND METHODS: We assessed the effect of TMZ on 24 h ambulatory ECG monitoring (AEM) in 30 patients (22 males and 8 females, mean (SE) age 67+/-6.5 years) with NIDDM and ischemic cardiomyopathy. Patients were randomized to receive on top of standard therapy either TMZ (20 mg, tds) or placebo (tds) and were evaluated at baseline and after 6 months. RESULTS: Patients randomized to TMZ or placebo were comparable regarding demographic data, distribution of CAD, and glicated haemoglobin levels. TMZ significantly reduced the number of episodes of transient myocardial ischemia (-24% compared to baseline, p<0.01; -27% compared to placebo, p<0.01), and Total Ischemic Burden (-28% compared to baseline, p<0.01; -29% compared to placebo, p<0.01). TMZ also significantly reduced the number of silent episodes of myocardial ischemia (-42% compared to baseline and -39% compared to placebo, p<0.01) and the time of silent myocardial ischemia/24 h (-37% compared to baseline and -35% compared to placebo, p<0.01). No significant changes in heart rate were detected between baseline, placebo and TMZ evaluations. CONCLUSIONS: TMZ is effective in reducing silent and symptomatic episodes of transient myocardial ischemia in diabetic patients with CAD on standard anti-anginal therapy.

Aged↗
PubMed2006

Metabolic therapy for patients with diabetes mellitus and coronary artery disease.

Patients with diabetes mellitus and ischemic heart disease more frequently develop heart failure and have a greater amount of myocardial ischemia, often silent, compared with patients without diabetes. Furthermore, patients with coronary artery disease (CAD) and diabetes or insulin resistance have altered myocardial metabolism and accelerated and diffuse atherogenesis with involvement of distal coronary segments that causes chronic hypoperfusion and hibernation. Therefore, in patients with diabetes and CAD, the ischemic metabolic changes are heightened by the metabolic changes in patients with diabetes. An important metabolic alteration in patients with diabetes is the increase in free fatty acid (FFA) concentrations and the increased skeletal muscle and myocardial FFA uptake and oxidation. The increased uptake and utilization of FFA and the reduced utilization of glucose as a source of energy during stress and ischemia contribute to the increased susceptibility of diabetic hearts to myocardial ischemia and to a greater decrease of myocardial performance for a given amount of ischemia compared with nondiabetic hearts. A therapeutic approach aimed at an improvement in cardiac metabolism through manipulations of the use of metabolic substrates should result in an improvement in myocardial ischemia and left ventricular (LV) function. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, increases cardiac resistance to ischemia, and therefore reduces the decrease of LV function caused by chronic hypoperfusion and repetitive episodes of myocardial ischemia in patients with and without diabetes. Thus, modulation of myocardial FFA metabolism should be the key target for metabolic interventions in patients with CAD with and without diabetes. In patients with diabetes, the effects of modulation of FFA metabolism should be even greater compared with those observed in patients without diabetes. Because of its effect on cardiac metabolism at rest and its effects on myocardial ischemia and LV function, trimetazidine should always be considered for the treatment of patients with diabetes with CAD with or without LV dysfunction.

Coronary Disease↗
PubMed2006

Acute administration of 17beta-estradiol reduces endothelin-1 release during pacing-induced ischemia.

OBJECTIVES: To assess whether acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in female menopausal patients with coronary artery disease. BACKGROUND: Endothelin-1 is a potent vasoactive peptide which plays a pathogenetic role in myocardial ischemia and adverse clinical events in patients with coronary artery disease. Estrogens decrease plasma levels of endothelin-1 and improve stress-induced myocardial ischemia in menopausal women with coronary artery disease. METHODS: Twenty-two postmenopausal women with angiographically proven coronary artery entered a randomized, double blinded, placebo-controlled study. Patients were sampled into the coronary sinus and aorta for endothelin-1 at baseline and after incremental pacing. After baseline study, patients were randomized to receive either sublingual 17beta-estradiol (1 mg) or placebo and underwent the sampling protocol 20 min thereafter. RESULTS: 17Beta-estradiol but not placebo improved the time of onset of myocardial ischemia during pacing. The coronary sinus plasma levels of endothelin-1 were significantly reduced by estradiol administration but not by placebo, at each step of pacing protocol. The maximum reduction of endothelin-1 was noted at peak pacing (-0.18 ng/l; -0.09, -0.3; 95% CI). No changes in endothelin-1 were noted in patients allocated to placebo (-0.002 ng/l; -0.06, -0.01; 95% CI). Similarly, aorto-coronary sinus difference of endothelin-1 was significantly influenced by 17beta-estradiol administration but not by placebo. CONCLUSION: Acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease. This result may be related to the anti-ischemic or to a primary direct effect of the hormone upon myocyte release of the peptide, and may contribute to its anti-ischemic effect. CONDENSED ABSTRACT: To assess effect of acute 17beta-estradiol administration on pacing-induced cardiac release of endothelin-1, we studied 22 female menopausal patients with coronary artery diseases. In a randomized, double-blinded, placebo-controlled study, patients were randomized to receive either sublingual 17beta-estradiol (1 mg) or placebo. Aortic and coronary sinus plasma endothelin-1 levels were evaluated at baseline, during incremental atrial pacing, and at peak pacing before and after the sublingual administration of either 17beta-estradiol or placebo. The time to the onset of myocardial ischemia during pacing was significantly increased by 17beta-estradiol vs. placebo. Moreover, coronary sinus endothelin-1 levels at peak pacing and aortic-coronary sinus changes were significantly improved by the administration of 17beta-estradiol but not by placebo. Acute administration of 17beta-estradiol reduces pacing-induced cardiac release of endothelin-1 in postmenopausal women with coronary artery disease.

Blood Pressure↗
PubMed2006

Effect of estradiol 17beta upon coronary artery vasoconstrictor response to methylergometrine maleate in female menopausal patients.

BACKGROUND: Estrogens produce several beneficial effects upon the cardiovascular system. Amongst these, an endothelium-independent effect has been convincingly demonstrated only in vitro, while there is no evidence for such an effect in vivo. The aim of the present study was to evaluate the effect of acute administration of estradiol 17beta upon coronary artery reactivity to methylergometrine in 16 menopausal patients with coronary artery disease. METHODS: Sixteen menopausal patients underwent coronary angiography at rest and after incremental doses of methylergometrine (intracoronary 2, 10, 30 microg) before and 20 min after either intracoronary estradiol 17beta (20 ng/mL at 1 mL/min for 20 min; 8 patients) or placebo (Dextrose 5%, 1 mL/min; 8 patients). RESULTS AND CONCLUSIONS: No significant differences were observed in baseline coronary artery diameter or area between the 2 groups. No significant differences in the degree of coronary artery constriction were observed after either estradiol 17beta or placebo at submaximal doses of methylergometrine. However, the degree of coronary artery constriction after maximal doses of methylergometrine was significantly attenuated by estradiol 17beta compared to placebo (change in diameter: -0.9+/-4.5% vs. -19+/-6%, p<0.001; change in area: -3.2+/-9% vs. -32.2+/-10%, p<0.001). Estradiol 17beta reduces coronary artery constriction following methylergometrine administration in menopausal patients with coronary artery disease. This effect may be related to the calcium-antagonist properties of the ovarian hormone.

Aged↗
PubMed2006

Impairment of physical exercise capacity in healthy postmenopausal women.

BACKGROUND: Healthy postmenopausal women reveal a series of peripheral vascular abnormalities, whose possible consequences on exercise performance has not been yet elucidated. METHODS: We studied the response to strenuous exercise in 25 postmenopausal women (mean age 50 +/- 3 years) without cardiovascular risk factors or disease through an integrative cardiopulmonary test. RESULTS: In comparison with 25 premenopausal subjects matched for age and biophysical characteristics, postmenopausal women showed a lower maximal workload (P < .01) and maximum VO2 (P < .01), an early anaerobic threshold (P < .05), and a lower ratio between increase of VO2 consumption and work rate (P < .01). CONCLUSIONS: Our results suggest that menopause could represent an important concomitant cause in determining an impairment of exercise capacity. The set of cardiopulmonary abnormalities found in the present study seems to identify the peripheral circulation as the limiting system in postmenopausal women experiencing exercise intolerance. Finally, present findings are in favor of an early introduction of postmenopausal hormone replacement therapy.

Anaerobic Threshold↗
PubMed2005

Interleukin-6 and flow-mediated dilatation as markers of increased vascular inflammation in women receiving hormone therapy.

OBJECTIVE: The lack of a beneficial long-term cardiovascular effect of hormone therapy and the early incidence of cardiovascular adverse events observed in recent randomized studies have been related to a heightened inflammatory effect of hormone therapy. DESIGN: We evaluated the effect of different postmenopause therapies on inflammatory markers and endothelial function in 205 postmenopausal women before and after therapy. RESULTS: all postmenopausal women, estrogens alone increased plasma levels of C-reactive protein (CRP) but decreased all other markers of inflammation including interleukin-6 (IL-6) (CRP: +75% +/- 11%, intracellular adhesion molecule: -21% +/- 4%, vascular cell adhesion molecule: -15% +/- 6%, E-selectin: -18% +/- 4%, s-thrombomodulin -10.5% +/- 3.7%, IL-6 -14% +/- 6%; percent changes, P < 0.01 compared with baseline). Raloxifene and tibolone did not significantly affect the overall inflammatory milieu. In a minority of patients, estrogen-progestogen associations and tibolone increased IL-6 levels and induced unfavorable changes on inflammation markers (CRP: +93% +/- 8%, intracellular adhesion molecule: -3% +/- 2%, vascular cell adhesion molecule: -5% +/- 2%, E-selectin: +6% +/- 2%, s-thrombomodulin: +5% +/- 2%, IL-6: +12% +/- 4%; percent changes compared with baseline). Patients with increased IL-6 levels were older and had a longer time since menopause. In all patients except those with increased IL-6 levels, hormone therapy improved endothelial function, whereas tibolone and raloxifene did not significantly change endothelial function compared with baseline. A worsening of endothelial function was detected in patients with increased IL-6 levels during therapy. CONCLUSIONS: Postmenopausal hormone therapy is associated with decreased vascular inflammation; however, in patients with a longer time since menopause, postmenopause hormone therapy may increase inflammation and worsen endothelial function. These unfavorable vascular effects may be detected by an elevation in IL-6 levels and by a lack of improvement in endothelial function.

Age Factors↗
PubMed2005

Metabolic effect of telmisartan and losartan in hypertensive patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome is a cluster of common cardiovascular risk factors that includes hypertension and insulin resistance. Hypertension and diabetes mellitus are frequent comorbidities and, like metabolic syndrome, increase the risk of cardiovascular events. Telmisartan, an antihypertensive agent with evidence of partial peroxisome proliferator-activated receptor activity-gamma (PPARgamma) activity, may improve insulin sensitivity and lipid profile in patients with metabolic syndrome. METHODS: In a double-blind, parallel-group, randomized study, patients with World Health Organization criteria for metabolic syndrome received once-daily doses of telmisartan (80 mg, n = 20) or losartan (50 mg, n = 20) for 3 months. At baseline and end of treatment, fasting and postprandial plasma glucose, insulin sensitivity, glycosylated haemoglobin (HBA1c) and 24-hour mean systolic and diastolic blood pressures were determined. RESULTS: Telmisartan, but not losartan, significantly (p < 0.05) reduced free plasma glucose, free plasma insulin, homeostasis model assessment of insulin resistance and HbAic. Following treatment, plasma glucose and insulin were reduced during the oral glucose tolerance test by telmisartan, but not by losartan. Telmisartan also significantly reduced 24-hour mean systolic blood pressure (p < 0.05) and diastolic blood pressure (p < 0.05) compared with losartan. CONCLUSION: As well as providing superior 24-hour blood pressure control, telmisartan, unlike losartan, displayed insulin-sensitizing activity, which may be explained by its partial PPARgamma activity.

Journal Article↗
PubMed2005

Value of C-reactive protein levels and IL-6 in predicting events levels in women at increased cardiovascular risk.

BACKGROUND: Elevated C-reactive protein (CRP) levels due to of heightened vascular inflammatory state in vascular conditions are often associated with elevated interleukin-6 (IL-6) levels since during inflammation CRP production in the liver is induced by IL-6. It has been suggested that CRP may be a predictors of unfavourable outcome in postmenopausal women (PMW) receiving hormone replacement therapy. Because of the possible metabolic effect of hormone replacement therapy (HRT) on CRP, the relative predictive importance of CRP and IL-6 levels in PMW receiving HRT remains to be elucidated. METHODS: We measured plasma levels of CRP and IL-6 levels in 346 consecutive PMW (mean age 66+/-9 years) with cardiovascular risk >20 in 10 years followed during a 36 month period. Women underwent measurement of inflammatory cytokines at baseline and were allocated to two groups according to the willingness to take hormone replacement therapy. All women underwent a further measurement of CRP and IL-6 at 3 and 6 months. Health status was assessed by out patient visits and hospital charts. RESULTS: During 1 year follow up, three patient died, four had a major cardiovascular event, three had a unstable angina, two had a transient ischemic attack and two patients underwent PTCA. PMW with events had higher CRP levels compared with patients with no events (1.9+/-0.61 versus 1.43+/-0.21, P<0.05) but still within the limits of normal. Also baseline IL-6 plasma levels were significantly higher in PMW with events than in those without events (0.87+/-0.23 versus 0.54+/-0.18, P <0.05). The increase in CRP and IL-6 with HRT was significantly higher in patients with events than in those with no events (CRP: 81+/-12 % versus 76+/-21%, P<0.05; IL-6 9+/-3 % versus -14+/-7%, P<0.05). In a stepwise multivariate analysis, IL-6 levels resulted a stronger predictor of outcome than CRP. CRP levels were predictors of future events only after removal of IL-6 levels and presence of cardiovascular symptoms from the analysis. CRP levels were associated with an unfavourable outcome only when IL-6 levels were also elevated. The increase in CRP with HRT during follow up was not associated to an increased event rate. CONCLUSION: Our study showed that CRP levels are increased in PMW receiving HRT. Elevated IL-6 levels may identify those PMW at increased 1 year risk. CRP levels predict events only when they are coupled with elevated IL-6 levels.

Aged↗
PubMed2005

Different effect of hormone replacement therapy, DHEAS and tibolone on endothelial function in postmenopausal women with increased cardiovascular risk.

Menopause is associated with an increased cardiovascular risk and with a decrease in endothelial function. Hormone replacement therapy (HRT) improves endothelial function in post-menopausal women (PMW) without established atherosclerosis. New alternative treatments, among which tibolone (T) and DHEAS have been suggested to reduce postmenopausal cardiovascular risk. Although, in vitro animal studies have suggested that T and DHEAS improve endothelial function, their effect in humans has never been tested. The aim of the present study was to compare the effects of HRT (continuous combined 0.625 mg conjugated equine estrogen plus 2.5 mg/d medoxyprogesterone) DHEAS and T on endothelium-dependent flow-mediated vasodilatation (FMD), plasma nitrite, nitrate and endothelin-1 levels in 16 PMW with increased cardiovascular risk in a double-blinded, double-crossover study. Women were randomized and treated for 4 weeks with HRT, T or DHEAS. Brachial artery diameter, FMD, endothelin-1 and plasma nitrite and nitrate levels were measured at baseline and after each treatment phase. Brachial artery diameters remained unchanged after each treatment phase. HRT significantly improved FMD compared to both baseline and to T and DHEAS therapies while no effect of T or DHEAS on FMD was noted. In conclusion, HRT, but neither T nor DHEAS, improves endothelial function and reduces plasma levels of endothelin-1 in PMW at risk of CAD.

Brachial Artery↗
PubMed2005

Postmenopausal hormone replacement therapy increases plasmatic thromboxane beta 2.

OBJECTIVE: This study shows the effect of hormone replacement therapy (HRT), using oral estrogen exclusively or in combination with progestin, on platelet activation in healthy menopaused women. BACKGROUND: Recent evidence from studies of postmenopausal HRT in healthy women demonstrated a short-time increased risk of coronary heart disease. Platelet activation, which generates vasoconstrictory thromboxane A(2) (TxA(2)), has been related to the risk of cardiovascular diseases. METHODS: By means of a placebo-controlled study twenty-seven postmenopausal patients were continuously orally administered estrogen in combination with progestin or estrogen exclusively for an 8-week period. Platelet activation was evaluated by flow cytometric P-selectin expression and by enzyme immunoassay plasmatic TxA(2) (TxB(2)) concentrations. RESULTS: P-selectin binding index changed from 6.3+/-3.6 to 7.0+/-3 in the placebo group (n=10); from 5.9+2.2 to 7.9+/-3.3 in the E+P group (n=8) and from 6.4+2.7 to 7.1+/-1.9 in the E group (n=9). Plasma concentrations of TxB(2) before and after intervention, changed from 1.2+1.2 to 1.5+1.4 (pg/well) in the placebo group; significantly (p=0.005) in the E+P group (n=8), from 0.9+0.3 to 6.1+6.5 (pg/well), and from 1.3+1.5 to 0.8+0.4 (pg/well) in the E group (n=8; mean+standard deviation, basal x therapy, p<0.05). CONCLUSIONS: Healthy menopaused women who were administered estradiol in association with norethisterone continuously had an increase of plasmatic thromboxane, possibly determined by platelet activation, which indicates a higher short-term thrombotic risk. P-selectin expression analyses failed to demonstrate the impact of HRT on platelets.

Aged↗
PubMed2005

Comparison of trimetazidine plus sildenafil to chronic nitrates in the control of myocardial ischemia during sexual activity in patients with coronary artery disease.

A large proportion of patients who have erectile dysfunction also have coronary artery disease (CAD). In these patients, nitrate therapy is a contraindication to the use of sildenafil. To assess whether the metabolic anti-ischemic agent, trimetazidine, is effective in controlling episodes of myocardial ischemia during sexual activity in patients who have CAD and use long-term nitrate therapy, we studied 38 men (57 +/- 6 years of age) who had proved CAD. Patients underwent 24-hour ambulatory electrocardiographic monitoring at baseline, after 1 week of oral nitrate therapy (20 mg 3 times a day), and after 1 week of trimetazidine (20 mg 3 times a day). Patients were asked to engage in >/=1 session of sexual intercourse during each session of ambulatory electrocardiographic monitoring. They were instructed to take sildenafil (100 mg) 1 hour before sexual intercourse performed at baseline and during therapy with trimetazidine and sildenafil or placebo (blinded) during therapy with nitrates. A decrease in total ischemic burden was observed with nitrates and trimetazidine compared with baseline (-3 +/- 1.2 episodes/patient/24 hours vs -5 +/- 1.3 episodes/patient/24 hours and -6 +/- 5 min/patient/24 hours vs -8 +/- 3 min/patient/24 hours, p <0.01 for nitrates and trimetazidine vs baseline). Trimetazidine plus sildenafil was more effective in controlling episodes of myocardial ischemia during sexual activity than nitrates alone (-45 +/- 11% vs -18 +/- 7%, p <0.04). In conclusion, in patients who have CAD, combination therapy with sildenafil and trimetazidine is more effective than nitrate therapy in the control of ischemic episodes during sexual activity, suggesting that long-term nitrate therapy may be safely switched to trimetazidine therapy when therapy for erectile dysfunction is required.

Adult↗
PubMed2005

Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk.

OBJECTIVE: Erectile dysfunction (ED) is often associated with a cluster of risk factors for coronary artery disease and reduced endothelial function. Acute and chronic administration of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, improves endothelial function in patients with ED. Tadalafil (TAD) is a new PDE5 inhibitor with a long half life that allows alternate day administration. Aim of the study was to evaluate whether chronic therapy (4 weeks) with TAD improves endothelial function in patients with increased cardiovascular risk and whether this effect is sustained after discontinuation of therapy. METHODS: We randomized 32 patients with increased cardiovascular risk to receive either TAD 20 mg on alternate days or matching placebo (PLB) for 4 weeks. Patients underwent evaluation of brachial artery flow-mediated dilation (FMD), nitrite/nitrate and endothelin-1 plasma levels at baseline, at the end of treatment period and after two-weeks follow-up. RESULTS: At 4 weeks, FMD was significantly improved by TAD (from 4.2+/-3.2 to 9.3+/-3.7%, p<0.01 vs. baseline), but was not modified by PLB (from 4.1+/-2.8 to 4.0+/-3.4%, p=NS). At 6 weeks the benefit in FMD was sustained in patients that received TAD (9.1+/-3.9% vs. 4.2+/-3.2%, p=0.01 vs. baseline; 9.1+/-3.9% vs. 9.3+/-3.7%, vs. 4 weeks, p=NS) while no changes in FMD were observed in patients randomized to PLB. Also, compared to baseline, a net increase in nitrite/nitrate levels (38.2+/-12.3 vs. 52.6+/-11.7 and 51.1+/-3.1, p<0.05) and a decrease in endothelin-1 levels (3.3+/-0.9 vs. 2.9.+/-0.7 and 2.9+/-0.9, p<0.05) was found both at four and six-weeks after TAD; these changes were inversely correlated as shown by regression analysis (adjusted R2=0.81, p<0.0001). CONCLUSIONS: Chronic therapy with TAD improves endothelial function in patients with increased cardiovascular risk regardless their degree of ED. The benefit of this therapy is sustained for at least two weeks after the discontinuation of therapy. Larger studies are needed in order to assess the possible clinical implications of chronic therapy with TAD.

Aged↗
PubMed2005

Platelet activation status decreases after menopause.

OBJECTIVE: The aim of the study was to investigate the impact of the climacterium (before and after menopause) on platelet activation. BACKGROUND: Platelet activation has been associated to the risk of cardiovascular disease. There is much speculation about the relationship between platelet function and sex steroids, due to peculiarities of platelet action between the genders, including concerns about the influence of low estradiol status in menopausal women. METHODS: By means of a cross-sectional study design, 37 female patients divided into two groups were compared. Group A consisted of ten women, mean age 43.9 years, in the premenopausal period, with normal estrogen levels; and Group B comprised 27 patients, mean age 53.0 years, who had all reached menopause. Platelet activation markers, namely P-selectin and glycoprotein IIb-IIIa complex (GPIIb-IIIa), were evaluated by flow cytometry with monoclonal antibodies. A binding index was calculated for both parameters (percentage of positive platelets x mean fluorescence of positive platelets). Also, thromboxane A2 was quantified by means of its main plasma metabolite, thromboxane B2, by enzyme immunoassay. RESULTS: P-selectin and GPIIb-IIIa expression results revealed lower platelet activation status after menopause, as there was a decrease in both the percentage of P-selectin+ platelets and of GPIIb-IIIa mean fluorescence of positive platelets, lowering both binding indices. P-selectin binding index differed significantly between Group A (12.3 +/- 3, n = 10) and Group B (6.2 +/- 2.9, n = 27; mean +/- standard deviation (SD), p < 0.001). GPIIb-IIIa binding index also differed significantly between both groups (Group A: 18.8 +/- 2.3, n = 10 vs. Group B: 16.2 +/- 3.1, n = 27; mean +/- SD, p < 0.0018). Plasma concentration of thromboxane B2 was 1.07 +/- 0.5 pg/well before menopause (Group A, n = 10) and 1.9 +/- 4.1 pg/well after menopause (Group B, n = 27), not significantly different (mean +/- SD, baseline x therapy, p = 0.85). CONCLUSIONS: After the menopause, climacteric women--whose estradiol status is low--have a decreased activation platelet status compared with premenopausal women. Nevertheless, further studies on a larger sample are necessary for conclusive data regarding cardiovascular disease.

Adult↗
PubMed2005

Metabolic therapy for the diabetic patients with ischaemic heart disease.

Diabetic patients with ischaemic heart disease have a greater amount of myocardial ischaemia, often silent, and an increased incidence of heart failure compared to nondiabetic patients. This is the result of altered myocardial metabolism and accelerated atherogenesis with involvement of peripheral coronary segments causing chronic hypoperfusion and diffuse hybernation. In patients with diabetes mellitus and myocardial ischaemia, the metabolic changes occurring as a consequence of the mismatch between blood supply and cardiac metabolic requirements are heightened by the diabetic metabolic changes. An important metabolic alteration of diabetes is the increase in free fatty acid concentrations and increased muscular and myocardial free fatty acid uptake and oxidation. This increased uptake and utilization of free fatty acid during stress and ischaemia is responsible for the increased susceptibility of the diabetic heart to myocardial ischaemia and to a greater decrease of myocardial performance for a given amount of ischaemia compared to nondiabetic hearts. Given the metabolic alterations of the diabetic heart at rest and during episodes of myocardial ischaemia, a therapeutic approach aimed at an improvement of cardiac metabolism through manipulations of the utilization of metabolic substrates should result in an improvement of myocardial ischaemia and of left ventricular function. Modulation of myocardial free fatty acid metabolism should be the key target for metabolic interventions in patients with coronary artery disease with and without diabetes. In diabetic patients, the effects of modulation of free fatty acid metabolism should be even greater than those observed in patients without diabetes. The inhibition of FFA oxidation with trimetazidine improves cardiac metabolism at rest, decreases cardiac ischaemia and therefore prevents the decline of left ventricular function due to chronic hypoperfusion and repetitive episodes of myocardial ischaemia. Because of its effect on cardiac metabolism at rest, its effects on myocardial ischaemia and left ventricular function trimetazidine should always be considered for the treatment of diabetic patients with ischaemic heart disease with or without left ventricular dysfunction.

Carbohydrate Metabolism↗
PubMed2004

Effect of hyperuricemia upon endothelial function in patients at increased cardiovascular risk.

The aim of the present study was to evaluate the effect of increased serum uric acid (UA) levels and their therapeutic reduction with allopurinol on endothelium-dependent dilation in subjects with a high cardiovascular (CV) risk but who were free from clinical CV disease. Patients with hyperuricemia had impaired flow-mediated dilation (FMD) compared with matched controls with normal UA levels and elevated CV risk. Three-month therapy with allopurinol improved FMD in hyperuricemic subjects, showing an intrinsic negative effect of elevated UA levels on the arterial wall; conversely, FMD remained unchanged in controls, thus suggesting that the reduction of UA to less than a certain value does not affect endothelial function.

Aged↗
PubMed2004

Menopause induced by oophorectomy reveals a role of ovarian estrogen on the maintenance of pressure homeostasis.

OBJECTIVES: Following spontaneous menopause women show a greater increase in systolic and diastolic blood pressure than men of the same age. The aim of the present study was to assess the effect of acute ovarian hormone withdrawal and replacement on blood pressure and forearm blood flow. METHODS: We studied 18 fertile middle-aged normotensive women (48 +/- 1.5 years, range 46-51 years) 1 week prior and 1 month subsequent to bilateral oophorectomy by means of 24-h blood pressure monitoring and strain-gauge venous occlusion plethysmography. Eighteen subjects who had undergone hysterectomy with ovarian sparing, matched for age and biophysical characteristics, were used as a control group. All women were free from cardiovascular risk factors or disease. RESULTS: Oophorectomy increased the mean values of 24 h (P < 0.001), daytime (P < 0.05), and nighttime (P < 0.01) diastolic blood pressure and nighttime systolic blood pressure (P < 0.01). Blood pressure increase was associated with a rise in forearm vascular resistance (P < 0.01). No significant changes in either blood pressure or forearm vascular resistance values were observed in hysterectomized women. In 16 oophorectomized women a 3-month estrogen replacement therapy (ERT) (17beta-estradiol, 100 mcg/day by transdermal patches) brought blood pressure and forearm vascular resistance values to a level comparable to that recorded before intervention. CONCLUSIONS: Surgically-induced menopause causes an increase in peripheral vascular resistance and blood pressure suggesting a role of ovarian hormones in the homeostatic pressure modulation. Recovery of the baseline condition after ERT suggests that the accelerated increase in blood pressure after menopause is due to ovarian and above all estrogen insufficiency.

Case-Control Studies↗
PubMed2004

Trimetazidine improves left ventricular function and quality of life in elderly patients with coronary artery disease.

AIM: Elderly patients have an increased incidence of ischaemic dilated cardiomyopathy often related to diffuse coronary artery disease. Trimetazidine protects ischaemic myocardium by improving the myocardial energy utilisation during myocardial ischaemia. Aim of the present study was to evaluate the effects of trimetazidine on left ventricular (LV) function in elderly patients with ischaemic heart disease and reduced LV function. METHODS: Forty seven elderly patients (40 males and 7 females, mean age 78+/-3 years) were randomised to receive, in addition to standard therapy, either trimetazidine or placebo and were evaluated by echocardiography at baseline and after 6 months. RESULTS: Trimetazidine and placebo had no effect on either blood pressure or heart rate (SBP 2+/-5 vs 4+/-6 mmHg, DBP -1+/-6 vs 3+/-4 mmHg, HR -3+/-7 vs 5+/-9 bpm, trimetazidine and placebo compared to baseline, respectively). At the end of the study patients randomised to trimetazidine showed a significant greater left ventricular function and smaller left ventricular diastolic and systolic diameters and volume indices compared to patients receiving placebo (LVEF: 34.4+/-2.3% vs 27+/-2.8%, p<0.0001; LVEDD: 58.6+/-1.9 mm vs 64+/-1.7 mm, p<0.0001; LVESD: 44.5+/-1.1 vs 50+/-0.8 mm, p<0.0001). A significant smaller wall motion score index was detected in trimetazidine-treated patients compared to those allocated to placebo (1.24+/-0.12 vs 1.45+/-0.19, p<0.01), the percentage change in LVEF compared to baseline was also significantly greater in trimetazidine-treated patients. Diastolic function significantly improved in the trimetazidine group while it remained unchanged in the placebo group. At follow-up evaluation, patients receiving trimetazidine showed a greater improvement in angina and NYHA class than patients allocated to placebo. Quality of life significantly improved in all patients treated with trimetazidine while remained unchanged in those allocated to placebo. CONCLUSION: In elderly patients with ischaemic cardiomyopathy trimetazidine in addition to standard medical therapy has a beneficial effect on LV systolic and diastolic function, and improves quality of life.

Aged↗