Roberto Fogari

Ambulatory Blood Pressure Is Superior to Clinic Blood Pressure in Predicting Treatment-Induced Regression of Left Ventricular Hypertrophy

Background In cross-sectional studies, ambulatory blood pressure (ABP) correlates more closely than clinic BP with the organ damage of hypertension. Whether ABP predicts development or regression o...

Effects of insufficient sleep on blood pressure in hypertensive patients A 24-h study

The influence of acute sleep deprivation during the first part of the night on 24-h blood pressure monitoring (ABPM) was studied in 36 never-treated mild to moderate hypertensive patients. According to a crossover design, they were randomized to have either sleep deprivation or a full nights sleep 1 week apart, during which they were monitored with ABPM. Urine samples for analysis of nocturnal urinary excretion of norepinephrine were collected. During the sleep-deprivation day, both mean 24-h blood pressure and mean 24-h heart rate were higher in comparison with those recorded during the routine workday, the difference being more pronounced during the nighttime (P < .01). Urinary excretion of norepinephrine showed a significant increase at night during sleep deprivation (P < .05). Blood pressure and heart rate significantly increased in the morning after a sleep-insufficient night (P < .05). These data suggest that lack of sleep in hypertensive patients may increase sympathetic nervous activity during the night and the following morning, leading to increased blood pressure and heart rate. This situation might represent an increased risk for both target organ damage and acute cardiovascular diseases.

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.

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.

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.

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: A comparative study of the efficacy and safety against amlodipine

To compare the antihypertensive efficacy of a new angiotensin II antagonist, valsartan, with a reference therapy, amlodipine.

Dynamic Interactions Between Musical, Cardiovascular, and Cerebral Rhythms in Humans

Background— Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. Methods and Results— Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccinis “Turandot”) or orchestral (Beethovens 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdis arias “Va pensiero” and “Libiam nei lieti calici”), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded. Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases. Vocal and orchestral crescendos produced significant (P=0.05 or better) correlations between cardiovascular or respiratory signals and music profile, particularly skin vasoconstriction and blood pressures, proportional to crescendo, in contrast to uniform emphasis, which induced skin vasodilation and reduction in blood pressures. Correlations were significant both in individual and group-averaged signals. Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables. No qualitative differences in recorded measurements were seen between musicians and nonmusicians. Conclusions— Music emphasis and rhythmic phrases are tracked consistently by physiological variables. Autonomic responses are synchronized with music, which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases.

Valsartan, a new angiotensin II antagonist for the treatment of essential hypertension: efficacy and safety compared with placebo and enalapril.

Objective To compare the antihypertensive efficacy and systemic tolerability of valsartan, a new angiotensin II receptor antagonist, with placebo and with an angiotensin converting enzyme (ACE) inhibitor, enalapril. Design A total of 348 adult outpatients with mild-to-moderate uncomplicated essential hypertension participated in this double-blind, parallel, study. Patients were allocated randomly in a ratio of 2:2:1 to receive 80mg valsartan once a day, 20 mg enalapril once a day, or placebo for 8 weeks in general practice. Patients were assessed at 4 and 8 weeks of therapy. Main outcome measures The primary efficacy variable was the change from baseline in mean sitting diastolic blood pressure (SDBP) after 8 weeks of therapy. Secondary variables included the change in sitting systolic blood pressure (SSBP) and response rates at 8 weeks. Results Valsartan and enalapril produced statistically significant reductions in diastolic and systolic blood pressures compared with placebo. Similar falls were found in both of the active treatment groups with mean changes in SDBP at 8 weeks of — 9.5mmHg for valsartan and — 9.4mmHg for enalapril ( 4.5mmHg for placebo). No significant differences between valsartan and enalapril were found for reductions in SDBP or SSBP. Response rates at 8 weeks were significantly greater for valsartan (54%) and enalapril (58%) than for placebo (20%), with no significant difference between the two active treatments. Both valsartan and enalapril demonstrated a consistent a nti hypertensive effect over time, with 90% of patients with a response at 4 weeks responding at 8 weeks. Both of the treatments were tolerated well. Although the incidence of coughing was generally low in the study, more cases were reported with enalapril (three) than with valsartan (one) or placebo (none). Conclusions The data show 80 mg valsartan once a day to be as effective as 20 mg enalapril once a day in the treatment of mild-to-moderate hypertension. Valsartan is tolerated well and does not appear to be associated with any increase in the incidence of coughing.

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.