Biomedical subjects

Roberto Fogari

Publications and source records attributed to Roberto Fogari.

At least 19 recordsLinked to original sources

PubMed2006

Effects of amlodipine-atorvastatin combination on inflammation markers and insulin sensitivity in normocholesterolemic obese hypertensive patients.

OBJECTIVE: The objective of this study was to assess the effect of amlodipine-atorvastatin combination on plasma interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and insulin sensitivity in normocholesterolemic obese hypertensive patients. MATERIALS AND METHODS: After a 4-week placebo wash-out period, 50 normocholesterolemic [total cholesterol (TC) <5.2 mmol/L], obese (BMI >/=30 kg/m(2)) hypertensive patients (DBP >90 and <105 mm Hg and SBP >140 and <180 mm Hg) were randomly treated with amlodipine (10 mg) or with amlodipine (10 mg) plus atorvastatin (20 mg) according to a cross-over design; each treatment had a 12-week duration. At the end of the placebo and of each treatment period, blood pressure (BP), TNF-alpha, IL-6, insulin resistance (IR) by homeostasis model assessment of IR index (HOMA-IR) and TC were evaluated. RESULTS: Amlodipine monotherapy decreased both SBP (-17.1 mm Hg, p=0.008 vs. placebo) and DBP (-14.3 mm Hg, p=0.008) as well as TNF-alpha (from 3.66+/-1.6 to 3.09+/-1.1 pg/ml, p=0.045) and HOMA-IR (from 4.58+/-0.7 to 3.88+/-0.6, p=0.007). The amlodipine-atorvastatin combination produced a decrease in SBP (-22.5 mm Hg, p=0.0007 vs. placebo, p=0.039 vs. amlodipine), DBP (-17.7 mm Hg, p=0.0007 vs. placebo; p=0.04 vs. amlodipine), TNF-alpha (2.59+/-0.9 pg/mL, p=0.007 vs. placebo and p=0.038 vs. amlodipine) and HOMA-IR (2.86+/-0.4, p=0.0008 vs. placebo and p=0.007 vs. amlodipine). The combination reduced IL-6 (from 7.93+/-1.9 to 5.59+/-1.2 pg/mL, p=0.008 vs. placebo and p=0.007 vs. amlodipine) and TC (from 4.3+/-0.5 to 3.6+/-0.4 mmol/L, p=0.008 vs. placebo and vs. amlodipine). HOMA-IR changes significantly correlated with TNF-alpha changes (r=0.38, p<0.05) during combination but not during amlodipine monotherapy. In normocholesterolemic, obese hypertensive patients, the amlodipine-atorvastatin combination decreased inflammatory markers and IR more than amlodipine monotherapy and produced a greater SBP and DBP reduction.

Adult↗

PubMed2006

Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL.

N-terminal natriuretic peptide type B (NT-proBNP) is a marker of cardiac dysfunction in light chain amyloidosis (AL) and a powerful prognostic determinant. Serum NT-proBNP and circulating free light chains (FLCs) were measured at enrollment and after 3 cycles of chemotherapy in 51 patients with cardiac AL. In patients (n = 22, 43%) in whom FLCs decreased by more than 50% (hematologic response), NT-proBNP concentration decreased by a median of 48%, whereas in the remaining patients it increased by 47% (P = .01). The reduction of NT-proBNP was greater in patients (n = 9) in whom amyloidogenic FLCs disappeared at immunofixation (median 53%), than in the remaining responding patients (median 31%, P = .04). Left ventricular wall thickness decreased by at least 2 mm in 3 of 20 patients in whom NT-proBNP improved. Fifteen patients died. Thirteen of them, in whom NT-proBNP and FLCs did not improve, died after a median of 1.8 months. The decrease of FLCs translates into a simultaneous decrease of NT-proBNP and improved survival. Patients in whom chemotherapy fails to induce such a decrease are at risk of early death. Cardiac function in AL can rapidly improve due to a reduction of the circulating amyloidogenic precursor, despite the amount of cardiac amyloid deposits remaining apparently unaltered, as measured by echocardiography.

Adult↗

PubMed2006

Antihypertensive drugs and fibrinolytic function.

Impaired fibrinolytic function, characterized by increased plasminogen activator inhibitor type 1 (PAI-1) levels and decreased tissue plasminogen activator (t-PA) activity, has been found in patients with hypertension and may account in part for the increased risk of atherosclerosis and its clinical complications in these patients. Failure to correct this prothrombotic state may be one of the possible reasons for the disappointing effect of antihypertensive treatment on the incidence of coronary events. In this regard, data from the literature indicate that different antihypertensive drugs may vary in their influence on fibrinolysis. Scarce and conflicting data exist regarding the effects of diuretics and beta-blockers on the fibrinolytic system. Angiotensin-converting enzyme (ACE) inhibitors (ACE-I) have generally been shown to improve the fibrinolytic balance by reducing plasma PAI-1 levels, calcium channel blockers (CCB) have been reported to increase t-PA activity, and angiotensin receptor blockers (ARB) seem to be neutral in their effect. Interesting data have been reported about the positive impact on fibrinolysis of combining an ACE-I with a CCB, which resulted in a decrease of PAI-1 caused by ACE inhibition, and an increase in t-PA resulting from calcium channel blockade. The positive effect of ACE-I on the fibrinolytic system has been related to: 1) inhibition of angiotensin II, which stimulates PAI-1 expression; 2) inhibition of degradation of bradykinin, a potent stimulus for tPA production; and 3) improvement of insulin sensitivity. The mechanisms underlying the CCB effect on t-PA are less clear, but a direct action of CCB on vascular endothelium has been reported to play a major role. The greater improvement in the fibrinolytic balance because of the combined action of ACE inhibition and Ca antagonism represents a further indication to the use of combinations of ACE-I and CCB in the treatment of hypertension.

Adrenergic Antagonists↗

PubMed2006

Losartan and prevention of atrial fibrillation recurrence in hypertensive patients.

The aim of the study was to evaluate the effect of losartan as compared with amlodipine, both associated with amiodarone, in preventing the recurrence of atrial fibrillation (AF) in hypertensive patients with a history of recent paroxysmal atrial fibrillation. Two hundred and fifty mild hypertensive (SBP > 140 mm Hg and/or DBP > 90 < 100 mm Hg) outpatients in sinus rhythm but with at least two ECG-documented episodes of symptomatic atrial fibrillation in the previous 6 months and in treatment with amiodarone were randomized to losartan or amlodipine and were followed up for 1 year. Clinic blood pressure (BP) and a 24-hour ECG was evaluated every month; the patients were asked to report any episode of symptomatic atrial fibrillation and to perform an ECG as early as possible. Two hundred and thirteen patients completed the study, 107 in the losartan group and 106 in the amlodipine group. After 12 months the SBP/DBP mean values were significantly reduced by both losartan (from 151.4/95.6 to 135.5/83.7 mm Hg, P < 0.001 versus baseline) and amlodipine (from 152.3/96.5 to 135.2/83.4 mm Hg, P < 0.001 versus baseline), with no difference between the two treatments. At least one ECG-documented episode of atrial fibrillation was reported in 13% of the patients treated with losartan and in 39% of the patients treated with amlodipine. The use of losartan in combination with amiodarone seems more effective than amlodipine/amiodarone combination in preventing new episodes of atrial fibrillation in hypertensive patients with recurrent atrial fibrillation. This might be related to possible favorable impact of angiotensin II receptor blockers (ARB) on the atrial electrical and structural remodeling in this type of patients.

Adult↗

PubMed2006

Effect of doxazosin on C-reactive protein plasma levels and on nitric oxide in patients with hypertension.

Inflammation has been hypothesized to play a role in the development of hypertension. The high-sensitivity C-reactive protein (hs-CRP) is a well-studied marker of systemic inflammation that has a predictive power with regard to the development of hypertension. This study was designed to test the hypothesis that hs-CRP plasma levels are altered in hypertension. Moreover, the study was to assess whether chronic antihypertensive treatment with doxazosin would normalize hs-CRP and nitrites/nitrates. We measured plasma levels of hs-CRP and nitrites/nitrates in 44 normotensive subjects and in 44 patients with hypertension before and after doxazosin therapy for 4 months. hs-CRP plasma levels were significantly higher (P < 0.007) in untreated hypertensive group compared to controls. Significant decrease was observed for hs-CRP (P < 0.05) in hypertensive patients after antihypertensive treatment. Nitrites/nitrates were significantly lower (P < 0.0001) in the untreated hypertensive group compared to controls. A significant increase was observed for nitrites/nitrates (P < 0.05) in hypertensive patients after antihypertensive treatment. These results suggest that doxazosin treatment exerts anti-inflammatory effects in addition to its antihypertensive properties in hypertensive patients.

Adult↗

PubMed2006

Synergistic effect of doxazosin and acarbose in improving metabolic control in patients with impaired glucose tolerance.

OBJECTIVE: The aim of this study was to evaluate if the expected improvement in glucose and lipid metabolism obtainable with doxazosin is or is not synergistic with standard antihyperglycaemic treatment using the alpha-glucosidase inhibitor acarbose. METHODS: Patients in this randomised, controlled, double-blind clinical trial were enrolled, evaluated and followed up at three Italian centres. We evaluated 107 patients (53 males and 54 females) with impaired glucose tolerance (IGT) as determined by oral glucose tolerance tests (OGTTs). All patients took a fixed dose of acarbose 150 mg/day for 3 months, after which they were titrated up to 300 mg/day for the next 3 months. In addition, patients were randomised to either placebo (53 patients: 27 males and 26 females, aged 50 +/- 4 [mean +/- SD] years) or doxazosin 4 mg/day (54 patients: 26 males and 28 females, aged 51 +/- 5 years) for the entire 6-month treatment period. Parameters evaluated during the 6-month treatment period included body mass index (BMI), glycaemic control (glycosylated haemoglobin [HbA(1c)], fasting plasma [FPG] and post-prandial plasma [PPG] glucose, fasting plasma [FPI] and post-prandial plasma [PPI] insulin levels, homeostasis model assessment [HOMA]-index [insulin resistance]), lipid profile (total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], and triglycerides [TG]), and systolic (SBP) and diastolic (DBP) blood pressure. RESULTS: Significant reductions in BMI, HbA(1c), FPG and PPG compared with baseline were observed after 6 months in both groups (p < 0.05). A significant decrease in FPI was obtained after 6 months (p < 0.05) in the doxazosin group compared with baseline, and this difference was also significant (p < 0.05) compared with the placebo group. Similarly, a significant decrease in HOMA-index was observed at 6 months (p < 0.05) compared with baseline in the doxazosin group, and this difference was also significant (p < 0.05) compared with the placebo group. Significant decreases in TC, LDL-C, HDL-C and TG (p < 0.05) were observed in the doxazosin group after 6 months compared with baseline values. Significant decreases in SBP and DBP were also observed at 3 months in the doxazosin group compared with baseline (p < 0.05), and these differences were significant (p < 0.05) compared with placebo. Furthermore, significant decreases in SBP and DBP were observed at 6 months (p < 0.01) in the doxazosin group compared with baseline, and these differences were also significant (p < 0.01) compared with placebo. All patients who completed an OGTT at 6 months (96 patients) were restored to normal glucose tolerance status. CONCLUSION: In patients with IGT, doxazosin given in combination with acarbose seemed to improve glycaemic and lipid control compared with placebo, with the benefits observed appearing to extend beyond those expected from improvements in blood pressure. Patients in this study also benefited from acarbose therapy, which restored all patients from IGT to normal glucose tolerance status.

Acarbose↗

PubMed2005

Sympathectomy or doxazosin, but not propranolol, blunt myocardial interstitial fibrosis in pressure-overload hypertrophy.

The adaptive changes that develop in the pressure-overloaded left ventricular (LV) myocardium include cardiomyocyte hypertrophy and interstitial fibrosis. Although the former is known to depend to a sizeable extent on sympathetic (over)activity, little information exists whether the same applies to the latter, ie, whether excess catecholamine exposure contributes to the imbalance between collagen deposition by fibroblasts and degradation by matrix metalloproteases (MMPs), eventually leading to LV collagen accumulation. Sprague-Dawley rats were subjected to abdominal aortic banding (B) or sham operation (S) and treated with beta-blockade (Bb, oral propranolol, 40 mg/kg per day), chemical sympathectomy (Sx, 6-hydroxydopamine, 150 mg/kg intraperitoneal twice per week) or vehicle (Vh). Ten weeks later, systolic blood pressure, LV weight, collagen abundance (computer-aided histology), zymographic matrix metalloproteinase (MMP)-2 activity and its specific tissue inhibitor concentration (TIMP-2) were measured. Both sympathectomy and beta-blockade failed to attenuate the banding-induced blood pressure elevation but significantly attenuated the attendant LV hypertrophy. As expected, pressure-overload hypertrophy was associated with interstitial fibrosis (collagen: 4.37+/-1.23% BVh versus 1.23+/-0.44% SVh, P<0.05), which was abolished by sympathectomy (2.55+/-1.31%, P=not significant versus SSx) but left unchanged by beta-blockade (4.11+/-1.23%, P<0.05 versus both SBb and BSx). beta-blockade, but not sympathectomy, was also associated with an increased TIMP-2/MMP-2 ratio (P<0.05), indicating reduced interstitial collagenolytic activity. In separate groups of banded and sham-operated rats, treatment with the alpha-receptor blocker doxazosin (10 mg/kg per day) displayed similar antifibrotic and biochemical effects as sympathectomy. Thus in the course of experimental pressure overload, the sympathetic nervous system plays a major pro-fibrotic role, which is mediated via alpha-adrenergic but not beta-adrenergic receptors.

Adrenergic alpha-Antagonists↗

PubMed2005

Effect of successful hypertension control by manidipine or lisinopril on albuminuria and left ventricular mass in diabetic hypertensive patients with microalbuminuria.

OBJECTIVE: The aim of this open-labelled, randomised, parallel-group study was to evaluate the effect of long-term monotherapy with manidipine or lisinopril on albumin excretion rate (AER) and left ventricular mass index (LVMI) in hypertensive patients with type-2 diabetes and microalbuminuria. METHODS: After a 4-week wash-out period, 174 patients with essential hypertension [diastolic blood pressure (DBP) >80 mmHg and <100 mmHg], type-2 diabetes and microalbuminuria were randomised to manidipine 10 mg o.d. or lisinopril 10 mg o.d.; after 8 weeks, the dose was doubled in non-responders (DBP >80 mmHg); after 3 months, treatment was discontinued in the non-responder patients and in those complaining of side effects; the remaining 121 patients continued their therapy with manidipine or lisinopril, and 99 completed the 2-year study. At the end of the wash-out period, of the titration period and after 6, 12, 18 and 24 months of treatment, BP was measured, AER, creatinine clearance, glycosylated haemoglobin (HbA1c) and body mass index (BMI) were evaluated and an echocardiographic evaluation was performed. RESULTS: The 99 patients who completed the study were statistically analysed according to a per-protocol evaluation. Manidipine and lisinopril significantly reduced systolic blood pressure (SBP) and DBP levels (at 24 months, --22.3/15.5 mmHg, P<0.001 versus baseline and --21.4/15.7 mmHg, P<0.01 versus baseline, respectively). Both drugs provided a significant decrease in AER, but it was significantly more pronounced with lisinopril (at 24 weeks, --37.2 mg/24 h, P<0.001 versus baseline) than with manidipine (--29.9 mg/24 h, P<0.05 versus baseline) and became evident earlier in the lisinopril group (after 3 months versus 6 months of treatment). Manidipine produced a greater reduction of LVMI than lisinopril (--14.9 g/m(2) versus --10.8 g/m(2) at 24 months). The effect was more pronounced in patients with left ventricular hypertrophy at baseline (--19.8 g/m(2) versus --12.8 g/m(2), P<0.05). CONCLUSION: These data suggest that, despite similar BP lowering, non-haemodynamic factors play an important role in the pharmacological reduction of AER and LVMI in diabetic hypertensive patients.

Aged↗

PubMed2005

Matrix metalloproteinase 2 may be a marker of microangiopathy in children and adolescents with type 1 diabetes mellitus.

Matrix metalloproteinases (MMPs) 2 and 9 are responsible for extracellular matrix breakdown and their abnormal circulating levels may pre-date clinical evidence of diabetic angiopathy. We detected by ELISA, plasma MMP-2 and MMP-9 levels and associated activity in 25 children and adolescents with T1DM. Thirteen male and 12 female patients were evaluated at the clinical diagnosis and onset of T1DM and again at a 5-year follow-up. Twelve patients had developed microangiopathic complications at the follow-up evaluation. MMP-2 and MMP-9 levels and activity were detected in samples obtained at T1DM diagnosis and at the 5-year follow-up. As controls, 19 healthy subjects who were the same age as the patients were also evaluated at baseline and again after 5 years. MMP-2 levels and activity were significantly higher in the patients than in the controls at disease onset. This was particularly evident when patients who developed microangiopathic complications were compared to controls and patients without complications. At the 5-year follow-up, a significant increase in MMP-2 levels and a significant decrease in MMP-2 activity were found only in the control group compared to the baseline levels. MMP-2 levels and activity were higher in patients with microangiopathy. MMP-9 levels and activity were increased in all groups compared to baseline levels. MMP-9 levels were lower in patients with microangiopathy compared to controls, but no difference was found between the two patient groups. It is well known that MMP-9 is an index of the severity and stability of macroangiopathy while our results allow us to postulate that MMP-2 may be a marker of microangiopathy.

Adolescent↗

PubMed2005

Effect of telmisartan/hydrochlorothiazide combination versus nifedipine GITS on ambulatory blood pressure and sympathetic activation.

BACKGROUND: This study compares the effects of telmisartan hydrochlorothiazide (HCTZ) combination versus nifedipine GITS on ambulatory blood pressure (BP) and sympathetic activity, in patients with mild-to-moderate hypertension. METHODS: One hundred twenty-four outpatients with sitting diastolic BP > or =95 mmHg and <110 mm Hg were randomized to telmisartan 80 mg/HCTZ 12.5 mg daily (n = 62) or nifedipine GITS 60 mg daily (n = 62) for 12 weeks, according to a prospective, open-label, blind end point, parallel-group design. At the end of a 2-week washout period and after 12 weeks of active treatment, 24-h noninvasive ambulatory BP monitoring (ABPM) was performed, clinic BP and heart rate were measured, and plasma norepinephrine and cardiovascular responses to mental stress induced by the color word test were assessed. RESULTS: Both treatments reduced ambulatory and clinic BP. However, the drug combination had an antihypertensive efficacy significantly greater than nifedipine GITS, as shown by the 24-h (P < .001), daytime (P < .001), and night-time (P < .01) ambulatory BP monitoring values, as well as by the clinic BP at trough (P < .05). The trough-to-peak ratio was similar, but the smoothness index was significantly higher with the combination for both systolic and diastolic BP (P < .05). A significant increase in plasma norepinephrine levels in resting conditions was observed with nifedipine GITS (+20%) but not with telmisartan/HCTZ combination. The color word test produced a greater increase in plasma norepinephrine and heart rate values in the patients treated with nifedipine GITS than in those treated with the combination. CONCLUSIONS: These results suggest that the telmisartan 80 mg/HCTZ 12.5 mg combination provided a more sustained and homogeneous BP control than nifedipine GITS 60 mg, without producing sympathetic activation.

Adult↗

PubMed2005

Long-term effects of glimepiride or rosiglitazone in combination with metformin on blood pressure control in type 2 diabetic patients affected by the metabolic syndrome: a 12-month, double-blind, randomized clinical trial.

BACKGROUND: Some evidence suggests that antihyperglycemic drugs might have a small but clinically significant beneficial effect on blood pressure in patients with diabetes mellitus. Based on a literature search, few direct comparisons of different antihyperglycemic treatments on blood pressure have been reported. OBJECTIVES: The primary aim of the present study was to compare the effect of long-term (12-month) combination treatment with glimepiride or rosiglitazone plus metformin on blood pressure in patients with type 2 diabetes mellitus (DM-2) and the metabolic syndrome. Secondary end points were glycemic control and improvement in insulin sensitivity. METHODS: This randomized, double-blind study was conducted at 2 centers in Italy. Patients aged > or =18 years with DM-2 and the metabolic syndrome and poor glycemic control (insulin resistance) with monotherapy with the maximum tolerated dose of an antihyperglycemic agent (eg, a sulfonylurea, metformin) were enrolled. All patients received 12 months of oral treatment with metformin 500 mg TID plus glimepiride 2 mg QD (G + M) or rosiglitazone 4 mg QD (R + M). Blood pressure, heart rate (HR), and body mass index (BMI); plasma levels of fasting and postprandial glucose and insulin (FPG, PPG, FPI, and PPI, respectively) and glycosylated hemoglobin (HbA(1c)); and homeostasis model assessment (HOMA) index were determined at 0 (baseline), 3, 6, 9, and 12 months of treatment. Adverse effects (AEs) were assessed using spontaneous reporting, patient interview, and laboratory analysis. RESULTS: Ninety-nine patients were enrolled in the study; 95 completed it (48 men, 47 women; mean age, 54 years [range, 47-58 years]; G + M, 47 patients; R + M, 48 patients). Four patients did not complete the study due to noncompliance (2 patients in the R + M group), protocol violation (1 patient in the G + M group), and loss to follow-up (1 patient in the G + M group). Mean blood pressure values were not significantly improved in the G + M group at any time point, whereas these values were significantly improved at 12 months in the R + M group. Mean BMI, HbA(1c), FPG, and PPG were significantly decreased from baseline in both groups at 12 months (all, P < or = 0.05). Mean FPI, PPI, and HOMA index were significantly improved at 12 months only in the R + M group (all, P < or = 0.05 vs baseline); these changes were not found in the G + M group. No significant changes in HR were found. Headache and flatulence were reported in both groups (G + M, 2 patients each; R + M, 1 and 2 patients, respectively), but these AEs were mild and transient. In the R + M group, liver enzyme levels were increased to 1.5-fold the upper limit of normal in 3 patients, but were normalized by study end. CONCLUSIONS: In this study in patients with DM-2 and the metabolic syndrome, long-term (12-month) combination treatment with R + M, but not G + M, was associated with a significant improvement in blood pressure control. Improvements in glycemic control and insulin resistance-related parameters were found at 9 months with R + M, compared with 12 months with G + M. Both treatments were well tolerated.

Analysis of Variance↗

PubMed2005

Fixed combination of manidipine and delapril in the treatment of mild to moderate essential hypertension: evaluation by 24-hour ambulatory blood pressure monitoring.

This present study assessed the antihypertensive efficacy of the fixed combination of manidipine and delapril by ambulatory blood pressure monitoring in patients with hypertension inadequately controlled by monotherapy with either component. After a 2-week placebo period, 55 mild to moderate hypertensive patients were randomized to manidipine 20 mg o.d. or delapril 30 mg b.i.d. for 4 weeks. After this period, 30 patients, aged 30-76 years (18 males and 12 females) whose diastolic blood pressure was not adequately controlled (> or = 90 mmHg) by monotherapy were treated with the fixed combination of manidipine 10 mg plus delapril 30 mg o.d. for 8 weeks. A 24-h ambulatory blood pressure monitoring recording was performed at the end of the placebo washout, of the monotherapy and of the combination therapy. Blood pressure control over the 24 h was quantified by the trough-to-peak ratio and the smoothness index. As compared to placebo, the fixed combination of manidipine and delapril produced a statistically significant (p<0.01) decrease in sitting clinic (18 +/- 9/14 +/- 5 mmHg) and 24-h blood pressure (12 +/- 7/10 +/- 5 mmHg) without affecting heart rate. This reduction was greater than that observed with single components. At the end of the 8-week combination treatment period, the rate of normalilized patients was 73%. Treatment with the fixed combination was associated with a positively high smoothness index (1.2 +/- 0.7/13.8 +/- 0.8) and with a relatively good trough-to-peak ratio (0.46/0.60). The combination of manidipine and delapril produced significant and smooth reductions in blood pressure values, which persisted over the 24-h dosing interval. These results support the use of fixed manidipine-delapril combination in the treatment of mild to moderate hypertensive patients inadequately controlled by monotherapy.

Adult↗

PubMed2005

Effect of manidipine as compared to atenolol on platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus.

This study was done to evaluate the effect of treatment with manidipine as compared with atenolol on thrombin-mediated platelet aggregation in elderly patients with isolated systolic hypertension and type II diabetes mellitus. After a 2-week washout placebo period, 60 elderly patients (aged 65-80 years) with isolated systolic hypertension (SBP > 140 mm Hg and DBP < 90 mm Hg) were randomly assigned to manidipine 10 mg or atenolol 50 mg 6-week treatment according to a double-blind, crossover design. Thirty patients had a concomitant well-controlled type 2 diabetes mellitus (HbA1c < or = 6.5%). At the end of the washout and of each treatment period, blood pressure (BP) (by mercury sphygmomanometer) and platelet aggregation (by Born-type aggregometer) were evaluated. Blood samples were collected using sodium citrate as anticoagulant, and platelet aggregation was induced by 2 different concentrations of ADP and collagen. Manidipine and atenolol produced a significant BP reduction in both diabetic and nondiabetic patients, with no difference between treatments. Despite the similar BP effect, in diabetic patients manidipine produced a significant reduction in platelet aggregation induced by both doses of either ADP or collagen. In nondiabetic hypertensives, manidipine inhibited platelet aggregation only at the highest doses of both inducers. The difference in the platelet inhibitory effect of manidipine between diabetic and nondiabetic subjects was statistically significant (P < 0.05) at both inducer concentrations. No changes in platelet aggregation were observed in the atenolol group. These data indicate that, unlike atenolol, manidipine inhibits platelet aggregation in elderly hypertensive patients, expecially in those with associated type II diabetes mellitus. The clinical impact of this positive effect in terms of prevention of cardiovascular complications in these high-risk patients remains to be clarified.

Aged↗

PubMed2005

Effects of doxazosin and irbesartan on blood pressure and metabolic control in patients with type 2 diabetes and hypertension.

The objective of this trial was to compare the metabolic effects of long-term treatment with doxazosin to those of irbesartan in patients with type 2 diabetes and hypertension. We evaluated 96 hypertensive diabetic patients who were randomized to 12 months of double-blind treatment with doxazosin 4 mg/d or irbesartan 300 mg/d. At the end of the study, systolic and diastolic blood pressure (SBP and DBP) were significantly reduced from 152 to 140 mm Hg and from 97 to 87 mm Hg, respectively, with doxazosin (P < 0.01). SBP and DBP were reduced from 150 to 134 mm Hg and from 94 to 83 mm Hg, respectively, with irbesartan (P < 0.01). Irbesartan had significantly better antihypertensive efficacy than doxazosin (P < 0.05). Doxazosin had the greatest effect on glucose metabolism and lipid parameters, with significant (P </= 0.05) reductions observed at study end compared with baseline in glycosylated hemoglobin, fasting plasma glucose, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and Homeostasis Model Assessment Index. In conclusion, both doxazosin and irbesartan reduced BP during long-term treatment, but not to recommended levels, and doxazosin had the more beneficial effect on glucose metabolism and lipid profile.

Adult↗

PubMed2005

Decreased plasma levels of soluble receptor for advanced glycation end-products in patients with essential hypertension.

OBJECTIVES: Advanced glycation end-products (AGE) may cause vascular stiffening by forming crosslinks through the collagen molecule or by interaction with their cellular transductional receptor (RAGE). A secreted isoform of RAGE, termed soluble RAGE (sRAGE), may contribute to the removal/detoxification of AGE by acting as a decoy. Here we studied the plasma sRAGE levels in hypertensive and normotensive human subjects. We also investigated the relationship between blood pressure parameters and plasma sRAGE concentrations. DESIGN: A cross-sectional case-control study. SETTING AND PARTICIPANTS: The outpatient clinic of a university teaching hospital. Participants were 147 never-treated patients with essential hypertension (87 men and 60 women, aged 50 +/- 10 years) and 177 normotensive controls (118 men and 59 women, aged 49 +/- 10 years). MAIN OUTCOME MEASURES: Plasma sRAGE levels determined by enzyme-linked immunosorbent assay, systolic blood pressure (SBP), diastolic blood pressure, pulse pressure (PP) and mean arterial pressure. RESULTS: The plasma concentration of sRAGE [median (interquartile range)] was 1206 (879-1658) pg/ml in hypertensive subjects and 1359 (999-2198) pg/ml in normotensive controls (P = 0.002). Simple correlation analysis revealed that log-transformed sRAGE levels were inversely correlated with SBP (r = -0.11; P < 0.001) and PP (r = -0.23; P < 0.001). Forward-selection multiple regression analysis revealed that log-transformed sRAGE levels were determined more strongly by PP (F = 3.127, P < 0.001). CONCLUSIONS: Plasma sRAGE levels are decreased in patients with essential hypertension and are inversely related to PP. Our results raise the possibility that sRAGE may play a role in arterial stiffening and its complications.

Adult↗

PubMed2005

Comparison of the effects of valsartan and felodipine on plasma leptin and insulin sensitivity in hypertensive obese patients.

Aim of this study was to compare the effect of valsartan and felodipine on blood pressure (BP), plasma leptin (L), insulin sensitivity and plasma norepinephrine (NE) in obese hypertensive patients. Ninty-six obese patients (body mass index [BMI] > or = 30 kg/m2) with mild to moderate essential hypertension (diastolic blood pressure [DBP] > 90 and < 110 mmHg, as evaluated with an appropriately sized cuff) aged 31-60 years, were randomized to a valsartan (80 mg/day for 16 weeks; n = 48) or felodipine (5 mg/day for 16 weeks; n = 48) treatment group after a 2-week wash-out period. After the first 4 weeks of treatment there was a titration with dose-doubling in non responder patients (DBP > 90 mmHg). At the end of the placebo period and of active treatment period, BP and BMI were evaluated and a venous sample was drawn at the same hour in the morning to evaluate plasma L and NE. Insulin resistance index (HOMA-IR) was calculated. No dietary advice was prescribed. Both valsartan and felodipine significantly decreased BP values (-19.3/15 mmHg and -18.9/13.6 mmHg, respectively p < 0.001 vs. placebo), with no difference between treatments. However, felodipine increased plasma NE (+124 pg/ml, +38.2%, p < 0.05 vs. placebo and < 0.01 vs. valsartan) and had no effect on L, body weight and HOMA-IR index, while valsartan did not modify NE and produced a significant reduction in L (-3.7 ng/ml, -10.1%, p < 0.05 vs. placebo), BMI (-1.7 kg/m2, -4.7%, p < 0.01 vs. placebo) and HOMA-IR index (-1.6, -20%, p < 0.05 vs. placebo). These results suggest that in hypertensive obese subjects, treatment with valsartan might offer an advantage over treatment with felodipine, since valsartan may help to improve obesity-related disorders in addition to lowering BP.

Aged↗

PubMed2005

Serum testosterone levels and arterial blood pressure in the elderly.

The aim of this study was to evaluate the relationship between serum testosterone levels and arterial blood pressure (BP) in the elderly. We studied 356 non-diabetic, non-smoking, non-obese men aged 60 to 80 years and untreated for hypertension. All subjects were evaluated in the morning after an overnight fast. Evaluation included measurements of the following: BP (by mercury sphygmomanometer, Korotkoff I and V), body weight, height and free testosterone (T) plasma levels (by radioimmunoassay). According to the BP values, the subjects were classified as normotensives (NT; n=112; SBP/DBP<140/90 mmHg), systolic and diastolic hypertensives (HT; n=127; SBP/DBP>140/90 mmHg), and isolated systolic hypertensives (ISH; n=117; SBP>140 mmHg and DBP<90 mmHg). T values decreased with increasing age in all 3 groups and was significantly lower in HT (-15%) and ISH men (-21%) than in NT men (p<0.05). In each group, the T levels showed a highly significant negative correlation with BMI (p<0.001). A significant negative correlation was also found between T levels and SBP in NT (r=-0.35, p<0.001), ISH (r=-0.67, p<0.001), and HT (r=-0.19, p<0.05) men, whereas a negative correlation with DBP was observed only in the NT men (r=-0.19, p<0.05). Adjusting for the BMI confirmed a significant difference in plasma T levels between ISH and NT men, but not between HT and NT men. Multiple regression analysis employing BP as a dependent variable confirmed a strong relationship between T levels and SBP in all 3 groups, whereas a significant relationship between T levels and DBP was found only in NT men. In conclusion, although further studies are needed to clarify the relationship between plasma T levels and BP, our findings suggest that in elderly men with ISH, the reduced plasma levels of testosterone might contribute to the increased arterial stiffness typical of these subjects.

Aged↗

PubMed2005

Thiazolidinedione effects on blood pressure in diabetic patients with metabolic syndrome treated with glimepiride.

The aim of our study was to compare the long-term effect of pioglitazone and rosiglitazone on blood pressure control of diabetic patients with metabolic syndrome treated with glimepiride. We evaluated 91 type 2 diabetic patients with metabolic syndrome. All were required to have been diagnosed as diabetic for at least 6 months, and to have failed to achieve glycemic control by dietary changes and the maximum tolerated dose of the oral hypoglycemic agents sulfonylureas or metformin. All patients took a fixed dose of 4 mg/day glimepiride. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) for 12 months in a randomized, double-blind fashion, and evaluated body mass index (BMI), glycemic control, blood pressure and heart rate (HR) throughout the treatment period. A total of 87 patients completed the study and were randomized to receive double-blind treatment with pioglitazone or rosiglitazone. An increase in BMI was observed after 12 months (p < 0.05) in both groups. After 9 and 12 months, there were significant decreases in glycated hemoglobin (HbA(1c)), mean fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), and postprandial plasma insulin (PPI) in both treatment groups (p < 0.05 at 9 months and p < 0.01 at 12 months for all parameters). Furthermore, homeostasis model assessment index (HOMA index) improvement was obtained at 9 and 12 months (p < 0.05 and p < 0.01, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05, respectively) was observed in both groups after 12 months. There were no significant changes in transaminases at any point during the study. We can conclude that the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance.

Blood Glucose↗