P. Lusardi

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.

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.

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.

β-Blocker effects on plasma lipids during prolonged treatment of hypertensive patients with hypercholesterolemia

The aim of this study was to compare the effects of long-term monotherapy with four different beta-blockers on plasma lipids in hypercholesterolemic hypertensive patients. We studied 152 subjects with essential hypertension [diastolic blood pressure (DBP) >90 mm Hg], total cholesterol (TC) >240 and <330 mg/dl, and triglycerides (TGs) <300 mg/dl. After a 4-week washout period with placebo, patients were randomized to receive propranolol, 160 mg/day (n = 37), atenolol, 100 mg/day (n = 38), bisoprolol, 10 mg/day (n = 39), or celiprolol, 400 mg/day (n = 38), for 18 months. No cholesterol-reducing drug was allowed. Blood samples for evaluation of TC, low-density lipoprotein cholesterol (LDL-C), HDL cholesterol (HDL-C), and TGs were taken before and after the placebo period and subsequently every 6 months. No beta-blocker worsened TC or LDL-C. Nonselective propranolol caused the most pronounced changes in HDL-C and TGs. Beta1-Selective atenolol produced the same qualitative effects, but to a lesser extent. The more beta1-selective bisoprolol did not affect HDL-C and TGs. Celiprolol significantly improved the lipid profile by significantly decreasing TC, LDL-C, and TGs, and increasing HDL-C. These findings suggest that in hypercholesterolemic hypertensive patients, (a) beta1-selective beta-blockers are likely to adversely affect plasma lipids to a lesser extent than nonselective ones; and (b) celiprolol is able to improve the lipid pattern, which could be because of its peculiar ancillary properties.

Effect of Benazepril plus Amlodipine vs Benazepril Alone on Urinary Albumin Excretion in Hypertensive Patients with Type II Diabetes and Microalbuminuria

SummaryTo compare the effect of the combination of benazepril and amlodipine on urinary albumin excretion (UAE) with that of benazepril alone, 45 patients with hypertension and type II (non-insulin-dependent) diabetes mellitus and microalbuminuria were randomised to receive benazepril 10mg plus amlodipine 5mg once daily, or benazepril monotherapy (10mg once daily), for 6 months. Before and after 3 and 6 months of therapy, sitting blood pressure and heart rate, bodyweight, UAE, plasma creatinine and creatinine clearance, glycosylated haemoglobin and plasma levels of glucose, electrolytes, uric acid and nitrogen were evaluated. Both benazepril alone and benazepril plus amlodipine significantly reduced blood pressure values without affecting heart rate and glucose homeostasis, but combination therapy was more effective in lowering both systolic and diastolic blood pressure. At 3 months, there was a similar reduction in UAE in the patients treated with benazepril alone and in those treated with benazepril plus amlodipine, but at 6 months UAE tended to show a greater decrease with the combination (−24.6%, p < 0.02) than with monotherapy (−19.7%, p < 0.04). Creatinine clearance significantly increased during combination therapy (p < 0.02), but was unchanged during benazepril monotherapy.In conclusion, compared with benazepril monotherapy, benazepril plus amlodipine tended to produce a greater reduction in UAE, and increased creatinine clearance.

Cigarette Smoking and Blood Pressure in a Worker Population: A Cross-Sectional Study

Background Cigarette smoking has been reported to cause an acute increase in blood pressure (BP). Nevertheless, many epidemiological studies have found lower average BP values in smokers than in non-smokers. The aim of this study was to evaluate the possible existence of a systematic difference in BP values between smokers and non-smokers in a worker population. Methods We studied 7109 employees of a metallurgical factory, all men, aged 18–60 years, 3237 non-smokers and 3872 smokers; of the latter, 816 smoked less than 10 cigarettes per day (light smokers), the others smoked 10 or more cigarettes per day. Clinical examination included measures of resting BP (by mercury sphygmomanometer), heart rate (HR) (by pulse palpation), body weight and height. Data were adjusted for age and body mass index (BMI). Four age groups (18–30, >30, >40 and >50 years) and 3 BMI groups (<25, 25–30, >30) were considered. Results In smokers, the adjusted values of systolic BP (SBP) and HR (127.72 mmHg and 75.16 beats/min, respectively) were slightly but significantly higher than in non-smokers (127.1 mmHg, P <0.05 and 72.64 beats/min, P < 0.001), whereas diastolic BP (DBP) was significantly lower (83.37 versus 84.31 mmHg, P < 0.001). Considering the amount of cigarettes smoked, the mean BP values of light smokers were not significantly different from those of subjects smoking 10 or more cigarettes per day, whereas HR mean values were significantly higher in the latter. The prevalence of hypertension (WHO criteria) was similar in smokers and non-smokers in each age group. Conclusions Our data showed slightly but statistically higher SBP and HR, and lower DBP mean values in smokers than in non-smokers; however, the differences in BP, although significant from the statistical point of view, were not of actual clinical significance.

Effects of Amlodipine vs Enalapril on Microalbuminuria in Hypertensive Patients with Type II Diabetes

SummaryThe effects of once-daily amlodipine 10mg or enalapril 20mg on urinary albumin excretion (UAE) were evaluated over 12 months, in a randomised trial of 50 hypertensive patients with type II (non-insulin-dependent) diabetes mellitus and microalbuminuria. Both drugs significantly reduced systolic and diastolic blood pressure without affecting heart rate or glucose homeostasis. UAE was significantly reduced after 3 months of treatment with enalapril, and 6 months of therapy with amlodipine. The percentage reduction in UAE significantly correlated with the decrement in systolic blood pressure and duration of hypertension in both treatment groups. Creatinine clearance was unaffected by enalapril, but was significantly increased by amlodipine. Long term treatment with either amlodipine or enalapril was therefore effective in reducing UAE in hypertensive patients with type II diabetes and microalbuminuria.

Effect of low-dose manidipine on ambulatory blood pressure in very elderly hypertensives

Summary. To evaluate the effect of manidipine 10 mg on 24-hour ambulatory blood pressure (BP) and heart rate (HR) in very elderly hypertensive patients, 54 patients aged 76–89 years (mean age 81.8 years) with systolic blood pressure (SBP) >160 mmHg and diastolic blood pressure (DBP) >90 mmHg were studied. After a 4-week placebo washout period, patients were randomized to receive manidipine 10 mg or placebo, both administered once daily for 8 weeks. Patients were checked after the initial run-in placebo phase and every 4 weeks thereafter. At each visit casual BP and HR were measured. At the end of the placebo period and after 8 weeks of active treatment, noninvasive 24-hour ambulate blood pressure measurement ABPM was performed. Manidipine significantly lowered casual sitting and standing SBP (P <0.001) and DBP (P <0.001) at the trough level. ABPM showed a significant decrease in 24-hour SBP and DBP values (P < 0,001), daytime SBP and DBP (P <0.001), and night-time SBP (P <0.001) and DBP (P <0.005). In addition, ABPM confirmed a consistent antihypertensive activity throughout the 24-hour dosing interval, without effect on the circadian BP profile. The trough/peak ratio was 0.67 for SBP and 0.59 DBP. No statistically significant change in HR was observed. The treatment was well tolerated, and there were no serious side effects. In conclusion, in very elderly hypertensive patients, once-daily administration of manidipine 10 mg was well tolerated and effective in reducing casual as well ambulatory BP.