Annalisa Zoppi

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.

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.

Effect of Antihypertensive Agents on Quality of Life in the Elderly

Management of hypertension in the elderly should take into account, in particular, the possible negative impact of antihypertensive drugs on the patient’s quality of life, the deterioration of which may result in a loss of independence and reduced treatment compliance. Quality of life is recognised as a multifactorial variable and can be subdivided into different domains (symptomatic well-being, emotional, physical, work-social, cognitive and life satisfaction), which are generally explored by means of specific questionnaires or scales. When evaluating elderly patients with hypertension, it is necessary to pay particular attention to specific domains such as symptomatic well-being, cognitive function, activity and sexual function, which have already been diminished by the age itself and the disease. The results of some large trials that specifically evaluated the quality of life effects of long-term therapy of hypertension in older people (Medical Research Council’s [MRC] Trial of Hypertension in Older Adults, Systolic Hypertension in the Elderly Program [SHEP], Systolic Hypertension in Europe [Syst-Eur], Study on COgnition and Prognosis in the Elderly [SCOPE]) have shown that antihypertensive treatment as a whole either had no negative impact on quality of life, or even produced some improvement. The question whether some classes of antihypertensive agents are more beneficial or harmful than others in terms of quality-of-life effects remains largely unanswered.Results from long-term trials suggest that treatment with diuretics is not associated with adverse effects on quality of life. Nevertheless, chlortalidone and other diuretics have been more often associated with sexual dysfunction in men, including decreased libido, erectile dysfunction and difficult ejaculation, than other drug classes. Nonselective lipophilic β-adrenoceptor antagonists, such as propranolol, have been reported to exert some negative effect on quality of life and have been associated with depression, impairment of memory function and adverse effects such as erectile problems. A less unfavourable impact has been described with β1-adrenoceptor antagonists and those with vasodilating properties. Calcium channel antagonists have generally been associated with a positive effect on quality of life, although some trials have shown high rates of adverse effects and withdrawals, particularly with first-generation dihydropyridines. Concern has also been raised about the potential for adverse cognitive effects associated with the use of calcium channel antagonists, but studies on this topic are not univocal. ACE inhibitors have usually been reported to exert favourable effects on quality of life. These drugs seem to be effective in maintaining, or even improving, cognitive function through mechanisms other than blood pressure control. In addition, a number of studies reported favourable impact of ACE inhibitors on sexual function. Angiotensin II receptor antagonists have been associated with good tolerability and low withdrawal rate. They have been demonstrated not to interfere with or even improve cognitive function as well as sexual performance.Although no class of antihypertensive agents presents a clearly superior effect over the others in terms of quality of life, the current impression is that ACE inhibitors and angiotensin II receptor antagonists may offer some advantage, at least in regard to effects on cognitive function and sexual activity.

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.