Amedeo Mugellini

Sexual activity in hypertensive men treated with valsartan or carvedilol : A crossover study

The aim of this study was to compare the effect of antihypertensive treatment with valsartan or cavedilol on sexual activity in hypertensive men who were never treated for hypertension. A total of 160 newly diagnosed hypertensive men (diastolic blood pressure [DBP] > or = 95 mm Hg and < 110 mm Hg), aged 40 to 49 years, all married and without any previous sexual disfunction, were enrolled. After a 4-week placebo period, the patients were divided into two groups: a) 120 patients were randomized to receive carvedilol 50 mg once daily or valsartan 80 mg once daily for 16 weeks according to a double-blind, cross-over design; after another 4-week placebo period, patients were crossed over to the alternative regimen for a further 16 weeks; b) 40 patients were treated with placebo according to a single-blind design for 16 weeks. At the screening visit and every 4 weeks thereafter, blood pressure (BP) was evaluated and patients were interviewed by a questionnaire about their sexual activity. Blood pressure was significantly lowered by both treatments, with a 48% of normalization with valsartan and 45% with carvedilol. During the first month of therapy, sexual activity (assessed as number of sexual intercourse episodes per month) declined with both drugs as compared with baseline, although the decrease was statistically significant in the carvedilol (from 8.2 to 4.4 sexual intercourse episodes, P < .01) but not in the valsartan-treated patients (from 8.3 to 6.6 sexual intercourse episodes, not significant). Ongoing with the treatment the sexual activity further worsened with carvedilol (3.7 sexual intercourse episodes per month) while fully recovered and also improved with valsartan (10.2 sexual intercourse episodes per month). The results were confirmed by the cross-over. Erectile dysfunction was a complaint of 15 patients with carvedilol (13.5%), one patient with valsartan (0.9%), and one patient in the placebo group. These findings suggest that carvedilol induces a chronic worsening of sexual activity, whereas valsartan not only does not significantly worsen sexual activity but may even improve it.

Effects of a Restricted Sleep Regimen on Ambulatory Blood Pressure Monitoring in Normotensive Subjects

The influence of sleep deprivation during the first part of the night on 24-h ambulatory blood pressure monitoring (ABPM) was studied in 18 normotensive subjects. They underwent two ABPM, one week apart: during the first, they slept from 11 PM to 7 AM, and during the second, from 2 AM to 7 AM. The main differences were observed at dawn, before awakening, when SBP and DBP significantly decreased (P < .01) in the restricted sleep regimen, and during the morning after the recovery sleep, when SBP and HR significantly increased (P < .05). The explanation for these findings is not obvious. We suppose that the decrease in SBP and DBP at dawn might be due to a reorganization of the sleep phases in the restricted sleep regimen, whereas the increase in SBP and HR after awakening might be due to a greater sympathetic activation, as though sleep deprivation was a stressful condition.

ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients.

The aim of this study was to compare the effects of the angiotensin-converting enzyme (ACE) inhibitor perindopril and the angiotensin II antagonist losartan on insulin sensitivity and plasma fibrinogen in overweight hypertensive patients. Twenty-eight overweight mild to moderate [diastolic blood pressure (DBP) >90 and <110 mm Hg] hypertensives aged 43-64 years, after a 4-week placebo period, were randomized to perindopril, 4 mg o.d., or losartan, 50 mg o.d., for 6 weeks. Then, after a new placebo period, patients were crossed to the alternative regimen for further 6 weeks. At the end of the placebo and of the treatment periods, blood pressure was measured, plasma fibrinogen was evaluated, and insulin sensitivity was assessed by the euglycemic, hyperinsulinemic clamp technique. Glucose infusion rate (GIR) during the last 30 min of clamp and total glucose requirement (TGR) were evaluated. Both perindopril and losartan reduced SBP (by a mean of 20.2 mm Hg, p < 0.001 vs. placebo; and 15.8 mm Hg, p = 0.002 vs. placebo, respectively) and DBP (by a mean of 15.2 mm Hg, p = 0.001 vs. placebo, and 11.8 mm Hg, p = 0.01 vs. placebo respectively), with no difference between the two treatments. GIR was significantly increased by perindopril (+2.91 mg/min/kg, p = 0.042 vs. placebo), but not by losartan (+0.28 mg/min/kg, NS). TGR was not modified by losartan but was increased by perindopril (+9.3 g, p = 0.042 vs. placebo). Plasma fibrinogen levels were reduced by perindopril (-53.4 mg/dl, p = 0.022 vs. placebo) but not by losartan (-16.8 mg/dl, NS). The perindopril-induced decrease in fibrinogen was correlated with the increase in GIR (r = 0.39; p < 0.01). These findings suggest that fibrinogen decrease produced by the ACE inhibitor is related to its action on insulin sensitivity, which seems to be dependent not on angiotensin II blockade but rather on other mechanisms.

Effect of valsartan addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients

The aim of this study was to assess the effect of valsartan addition to amlodipine on ankle foot volume (AFV) and pretibial subcutaneous tissue pressure (PSTP), two objective measures of ankle oedema. After a 4-week placebo period, 80 grade 1–2 hypertensive patients (diastolic blood pressure (DBP)>90 mm Hg and <110 systolic blood pressure (SBP)>140 mm Hg) were randomized to amlodipine 10 mg or valsartan 160 mg or amlodipine 10 mg plus valsartan 160 mg for 6 weeks according to an open-label, blinded end point, crossover design. At the end of the placebo period and of each treatment period, blood pressure, AFV and PSTP were evaluated. AFV was measured using the principle of water displacement. PSTP was assessed connecting the subcutaneous pretibial interstitial environment with a water manometer. Both amlodipine and valsartan monotherapy significantly reduced SBP (−16.9 and –14.5 mm Hg, respectively, P<0.01 vs baseline), and DBP (−12.9 and −10.2 mm Hg, respectively, P<0.01 vs baseline) but the reduction was greater with the combination (−22.9 mm Hg for SBP, P<0.01 vs monotherapy; −16.8 mm Hg for DBP, P<0.01 vs monotherapy). Amlodipine monotherapy significantly increased both AFV (+23%, P<0.01 vs baseline) and PSTP (+75.5%, P<0.001 vs baseline) whereas valsartan monotherapy did not influence them. As compared to amlodipine alone, the combination produced a less marked increase in AFV (+6.8%, P<0.01 vs amlodipine) and PSTP (+23.2%, P<0.001 vs amlodipine). Ankle oedema was clinically evident in 24 patients with amlodipine and in six patients with the combination. These results suggest that angiotensin receptor blockers partially counteract the microcirculatory changes responsible for calcium channel blockers induced oedema formation.

Influence of losartan and atenolol on memory function in very elderly hypertensive patients

The aim of this study was to compare the effect of the beta-adrenergic blocker atenolol and the Angiotensin II type 1 (AT1) receptor antagonist losartan on cognitive function in very elderly hypertensive patients. A total of 120 mild to moderate essential hypertensive (DBP >90 and <105 mmHg) patients, aged 75–89 years, were studied. After a 4-week wash-out period on placebo, they were randomized to receive atenolol 50 mg or losartan 50 mg for 24 weeks according to a parallel arm design. At the end of the placebo period and of each active treatment period, BP was measured (by mercury sphygmomanometer, Korotkoff I and V) and cognitive function was evaluated through three different tests (word list memory, word list recall and word list fluency). Both atenolol and losartan were equally effective in reducing SBP (−22.1 and −23.1 mmHg, respectively, P< 0.01 vs baseline) and DBP (−10.3 and −11.2 mmHg, respectively, P< 0.01 vs baseline). Atenolol treatment did not induce significant changes in any test score, whereas losartan significantly increased the score of both the word list memory (+2.2, P<0.05 vs baseline) and the word list recall test (+2.1, P<0.05 vs baseline). The comparison between losartan and atenolol was significant (P<0.05) for both memory tests. These data suggest that in very elderly hypertensive patients, chronic AT1 receptor blockade by losartan could improve cognitive function, in particular immediate and delayed memory.

The effect of L-carnitine on plasma lipoprotein(a) levels in hypercholesterolemic patients with type 2 diabetes mellitus.

BACKGROUND A previous study has demonstrated that L-carnitine reduces plasma lipoprotein(a) (Lp[a]) levels in patients with hypercholesterolemia. OBJECTIVE To test a tolerable Lp(a)-reducing agent in diabetic patients, we assessed the effect of a dietary supplementation of L-carnitine on plasma lipid levels, particularly Lp(a), of patients with type 2 diabetes mellitus (DM) and hypercholesterolemia. METHODS In this 6-month, randomized, double-masked, placebo-controlled clinical trial, patients were enrolled, assessed, and followed up at the Diabetic and Metabolic Diseases Center of the Department of Internal Medicine and Therapeutics at the University of Pavia, Pavia, Italy. All study patients had newly diagnosed type 2 DM that was managed through dietary restriction alone throughout the study, as well as hypercholesterolemia. Patients were randomized to 1 of 2 groups. One group received L-carnitine, one 1-g tablet BID. The other group received a corresponding placebo. We assessed body mass index, fasting plasma glucose, postprandial plasma glucose, glycosylated hemoglobin, fasting plasma insulin, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, apolipoprotein (apo) A-I, apo B, and Lp(a) at baseline and at 1, 3, and 6 months of treatment. RESULTS This study included 94 patients. The treatment group included 24 men and 22 women (mean [SD] age, 52 [6] years). The placebo group included 23 men and 25 women (mean [SD] age, 50 [7] years). The baseline characteristics of the groups did not differ significantly. The mean (SD) body weight, height, and body mass index were 78.2 (5.8) kg, 1.70 (0.04) m, and 27.3 (2.5) kg/m(2), respectively, in the L-carnitine group and 77.6 (6.4) kg, 1.71 (0.05) m, and 26.8 (2.2) kg/m(2), respectively, in the placebo group. In the treatment group, Lp(a) was significantly reduced at 3 and 6 months compared with baseline (P < 0.05) and P < 0.01, respectively). We observed a significant improvement after 6 months (P < 0.05) in the Lp(a) value in patients taking L-carnitine compared with those taking placebo. Between-group differences in other variables did not reach a level of significance at months 3 and 6. No drug-related adverse events were reported or observed. CONCLUSION In this preliminary study, after 3 and 6 months, L-carnitine significantly lowered the plasma Lp(a) level compared with placebo in selected hypercholesterolemic patients with newly diagnosed type 2 DM.

Prevalence of Primary Aldosteronism among Unselected Hypertensive Patients: A Prospective Study Based on the Use of an Aldosterone/Renin Ratio above 25 as a Screening Test

Primary aldosteronism (PA) has been considered a rare cause of hypertension. The introduction of the aldosterone/renin ratio (ARR) as a screening test has led to an increase in the detection rate. The aim of this study was to evaluate the prevalence of PA among unselected hypertensive patients by using an ARR >25 as a screening test. We studied 3,000 consecutive unselected hypertensive patients. Blood samples for the determination of plasma renin activity (PRA), aldosterone (ALD) and electrolytes were drawn in the morning, and patients with an ARR >25 underwent intravenous saline infusion as a confirmatory test. Adrenal CT and a dexamethasone suppression test were performed in patients with confirmed PA. Patients with a positive dexamethasone test underwent genetic testing for glucocorticoid-remediable aldosteronism (GRA). Out of 3,000 hypertensives, 684 (22.8%) showed an ARR >25 and 177 of them (5.9% of the whole population) had a positive saline loading test. Only 44 of them (24.8%) were hypokalemic. CT was performed in all the patients with confirmed PA and 53 of them (29.9%) had a solitary adrenal macroadenoma, 112 (63.3%) had bilateral adrenal enlargement and 12 (6.8%) had normal appearing adrenal glands. Of 177 patients given dexamethasone to identify GRA, 8 (4.5%) showed aldosterone suppression but only one (0.1%) tested positive for the chimeric gene. In conclusion, our findings indicate that standardized application of an ARR >25 to unselected hypertensive patients, followed by i.v. saline loading as a confirmatory test, can result in the detection of a large number of patients with PA (5.9% of the studied population), most of whom are normokalemic. Bilateral adrenal hypertrophy represents the more common form of PA.

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.

Sexual Function in Hypertensive Males Treated with Lisinopril or Atenolol A Cross-Over Study

To evaluate the effect of antihypertensive treatment on sexual activity, 90 hypertensive men, aged 40 to 49 years, all married and without history of sexual dysfunction were treated with 100 mg of atenolol or 20 mg of lisinopril for 16 weeks, according to a double-blind, randomized, cross-over design. During the first month of therapy, sexual activity, assessed as number of sexual intercourse episodes per month, significantly declined with both atenolol (from 7.8 +/- 4.3 to 4.5 +/- 2.8, P < .01 v placebo) and lisinopril (from 7.1 +/- 4.0 to 5.0 +/- 2.5, P < .05 v placebo). Ongoing with the treatment, sexual activity tended toward recovery in the lisinopril (7.7 +/- 4.0 sexual intercourse episodes per month, P = NS v placebo), but not in the atenolol group (4.2 +/- 2.8, P < .01 v placebo), with a statistically significant difference between the two drugs (P < .01). The percentage of patients who complained of sexual dysfunction symptoms was significantly higher in the atenolol- than in the lisinopril-treated group (17% v 3%, P < .05). These findings suggest that atenolol induces a chronic worsening of sexual activity, whereas lisinopril causes only a temporary decline.

Long-term effects of ramipril and nitrendipine on albuminuria in hypertensive patients with type II diabetes and impaired renal function.

The aim of this study was to compare the effects of ramipril and nitrendipine chronic treatment on urinary albumin excretion (UAE) in hypertensive patients with type II non-insulin-dependent diabetes mellitus (NIDDM) and impaired renal function. A 2-year, prospective, randomised study was conducted on 51 men with a diastolic blood pressure (DBP) ⩾95 and ⩽105 mm Hg, stable NIDDM, serum creatinine between 1.6 and 3.0 mg/dl and persistent UAE >300 and <2000 mg/24 h. after a 3-month preliminary observation period, during which patients began a low-protein, low-sodium diet, and a subsequent 4-week run-in period on placebo, patients were randomly treated with ramipril 5 mg or nitrendipine 20 mg for 2 years. both drugs similarly reduced bp without affecting glucose homeostasis. in the ramipril group uae significantly decreased after only 3 months of treatment, whereas in the nitrendipine group a significant although lesser reduction in uae was observed only after 1 year. during the second year the uae% change was not statistically different between the two treatments. serum creatinine and creatinine clearance showed no significant change with both drugs. the progression of renal insufficiency as assessed by the rate of reduction of creatinine clearance over the 2 years of the study was similar in the ramipril and the nitrendipine groups. in conclusion both ramipril and nitrendipine were associated with a decrease in uae although such a reduction was earlier and more marked with ramipril. the decline of renal function did not differ significantly between the two treatments.