Self-monitoring of Blood Pressure in Patients With Hypertension-Related Multi-morbidity: Systematic Review and Individual Patient Data Meta-analysis.

BACKGROUND: Studies have shown that self-monitoring of blood pressure (BP) is effective when combined with co-interventions, but its efficacy varies in the presence of some co-morbidities. This study examined whether self-monitoring can reduce clinic BP in patients with hypertension-related co-morbidity. METHODS: A systematic review was conducted of articles published in Medline, Embase, and the Cochrane Library up to January 2018. Randomized controlled trials of self-monitoring of BP were selected and individual patient data (IPD) were requested. Contributing studies were prospectively categorized by whether they examined a low/high-intensity co-intervention. Change in BP and likelihood of uncontrolled BP at 12 months were examined according to number and type of hypertension-related co-morbidity in a one-stage IPD meta-analysis. RESULTS: A total of 22 trials were eligible, 16 of which were able to provide IPD for the primary outcome, including 6,522 (89%) participants with follow-up data. Self-monitoring was associated with reduced clinic systolic BP compared to usual care at 12-month follow-up, regardless of the number of hypertension-related co-morbidities (-3.12 mm Hg, [95% confidence intervals -4.78, -1.46 mm Hg]; P value for interaction with number of morbidities = 0.260). Intense interventions were more effective than low-intensity interventions in patients with obesity (P < 0.001 for all outcomes), and possibly stroke (P < 0.004 for BP control outcome only), but this effect was not observed in patients with coronary heart disease, diabetes, or chronic kidney disease. CONCLUSIONS: Self-monitoring lowers BP regardless of the number of hypertension-related co-morbidities, but may only be effective in conditions such obesity or stroke when combined with high-intensity co-interventions.

Frovatriptan vs. other triptans for the acute treatment of oral contraceptive-induced menstrual migraine: pooled analysis of three double-blind, randomized, crossover, multicenter studies.

Oral contraceptive-induced menstrual migraine (OCMM) is a particularly severe form of migraine triggered by the cyclic hormone withdrawal. To review the efficacy of frovatriptan vs. other triptans, in the acute treatment of OCMM through a pooled analysis of three individual randomized Italian studies. With or without aura migraineurs were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). All studies had a multicenter, randomized, double-blind, crossover design. After treating 1-3 episodes of migraine in 3 months with the first treatment, patients switched to the other treatment for the next 3 months. In this analysis, the subset of 35 of the 280 women of the intention-to-treat population taking combined oral contraceptives and experiencing a migraine attack during the withdrawal phase, were analyzed. The proportion of pain free and pain relief at 2 h were 25 and 51 % with frovatriptan and 28 and 48 % with comparators (p = NS). At 24 h, 71 and 83 % of frovatriptan-treated patients and 60 and 76 % of comparator-treated patients were pain free (p < 0.05 between treatments) and had pain relief (p = NS), respectively. Relapse at 24 and 48 h was significantly (p < 0.05) lower with frovatriptan (17 and 21 %) than with the comparators (27 and 31 %). Our results suggest that, due to its sustained antimigraine effect, frovatriptan may be particularly suitable for the management of OCMM than other triptans.

Efficacy of frovatriptan and other triptans in the treatment of acute migraine of hypertensive and normotensive subjects: a review of randomized studies.

Migraine might be associated with high blood pressure (BP), which can cause more severe and more difficult to treat forms of headache. To evaluate the efficacy of frovatriptan and other triptans in the acute treatment of migraine, in patients classified according to a history of arterial hypertension, enrolled in three randomized, double-blind, crossover, Italian studies. Migraineurs with or without aura were randomized to frovatriptan 2.5 mg or rizatriptan 10 mg (study 1), frovatriptan 2.5 mg or zolmitriptan 2.5 mg (study 2), frovatriptan 2.5 mg or almotriptan 12.5 mg (study 3). After treating up to three episodes of migraine in 3 months with the first treatment, patients switched to the alternate treatment for the next 3 months. The present analysis assessed triptan efficacy in 60 subjects with a history of treated or untreated essential arterial hypertension (HT) and in 286 normotensive (NT) subjects. During the study, migraine attacks with aura were significantly more prevalent in HT subjects (21 vs. 13 % NT, p < 0.001). The proportion of pain free at 2 h did not significantly differ between HTs and NTs for either frovatriptan (25 vs. 26 %) or the comparators (33 vs. 32 %). Pain relief was achieved in significantly (p < 0.05) fewer episodes in HT subjects for both frovatriptan (41 vs. 52 % NT) and the comparators (48 vs. 58 %). Relapses at 48 h were similarly low in HTs and NTs with frovatriptan (29 vs. 31 %), while they were significantly (p < 0.05) larger in HTs (62 %) than in NTs (44 %) with comparators. No BP or heart rate increment was observed during the study in HT subjects. No difference in tolerability was reported between HTs and NTs. In conclusion, HT individuals tend to be less responsive than NT migraineurs to triptan therapy. However, frovatriptan, in contrast to other triptans, seems to have a sustained antimigraine effect in both HT and NT patients.

Restless legs syndrome is not associated with migraine with aura: a clinical study.

Based on recent data about the association between restless legs syndrome (RLS) and migraine, we performed an observational study on the occurrence of RLS in patients affected by "pure" migraine with aura (pMA). We recruited 63 patients (33 females and 30 males) affected by MA without other types of primary headache among all patients referred in five Italian headache centers in a 1-year period. The prevalence of RLS in pMA patients (9.5%) is similar to that observed in Italian headache-free subjects (8.3%). No significant differences were found between pMA patients with and without RLS about clinical features of MA attacks and systemic and psychiatric diseases were investigated. Moreover, no association appeared between RLS and familial cases of MA. Differently from migraine without aura, our data do not confirm the existence of an association between RLS and MA, not even when a genetic factor is involved.

Circadian blood pressure profile in patients with active Cushing's disease and after long-term cure.

Hypertension is a major feature of Cushing's disease, with the attendant increase in the rate of cardiovascular events. The circadian blood pressure profile also impacts cardiovascular risk and a few studies have shown that patients with Cushing's syndrome do not present the expected nocturnal blood pressure decrease and, further, that this alteration persists in short-range disease remission. These studies were performed by conventional discontinuous ambulatory pressure monitoring, a technique not devoid of limitations. Aim of our study was the assessment of blood pressure and heart rate profile by beat-to-beat noninvasive monitoring in twelve patients with active Cushing's disease (9 women and 3 men, age 33.3+/-2.36 years) and the assessment of its possible changes at short- (<1 year) and long-term (2-3 years) follow-up after curative surgery. No nocturnal blood pressure dipping (i.e., decrease by 10% of daytime values) was observed in 50% of patients both during active hypercortisolism and within 1 year from surgery. Recovery of blood pressure dipping profile was detected at long-term follow-up in a minority of patients. Daytime heart rate was higher in patients with active Cushing's disease and decreased over time after cure. In conclusion, patients with Cushing's disease present absent nocturnal blood pressure dipping and abnormal heart rate values which do not resolve after short-term remission of hypercortisolism and show only partial improvement in the long run. These findings identify additional cardiovascular risk factors for patients cured of Cushing's disease.

Frovatriptan for the prevention of postdural puncture headache.

Efficacy of 5-day treatment with oral frovatriptan 2.5 mg/die for the prophylaxis of post-dural puncture headache (PDPH) was tested in 50 in-patients. A mild headache occurred in 7 (14%) patients for a total of 9 days (p < 0.01 vs. no-PDPH). Most episodes of PDPH occurred in the first days of treatment (only 1 patient had headache at dismissal): 5 patients had only 1 episode, while 2 had headache for 2 consecutive days. No other symptoms were recorded. Occurrence of PDPH in a subgroup of 6 (12%) patients previously submitted to a diagnostic lumbar puncture was also examined: 4 of them reported a PDPH on the previous lumbar puncture in absence of triptans. In only 1 of these 4 patients PDPH recurred under treatment with frovatriptan. In conclusion, our non-randomized open-label study suggests efficacy of oral frovatriptan for PDPH prevention. These results need to be confirmed in a randomized, controlled, double-blind study.

Mechanisms underlying the impairment in orthostatic tolerance after nocturnal recumbency in patients with autonomic failure.

In the present study, we have assessed in patients with neurogenic orthostatic hypotension the haemodynamics underlying the reduced tolerance to standing after prolonged recumbency at night. In 10 patients with neurogenic orthostatic hypotension (age 33-68 years), of which seven were being treated with fludrocortisone and/or sleeping in the 12 degrees head-up tilt position, 24 h continuous non-invasive finger blood pressure was recorded by a Portapres device. Beat-to-beat blood pressure, heart rate, stroke volume, cardiac output and total peripheral vascular resistance obtained by pulse contour analysis were assessed during 5 min of standing in the evening (at 22.30 hours) and in the morning (at 06.30 hours). On average, the inverse of the normal 24 h blood pressure profile was found, with a large diversity in blood pressure profiles among patients. Supine blood pressure values were similar, but standing blood pressure values were lower in the morning than in the evening (P<0.01). This resulted from larger falls in stroke volume and cardiac output upon standing in the morning compared with the evening, while total peripheral resistance did not change. There was no relationship between the decrease in body weight during the night (mean 0.9 kg; range 0.2-1.6 kg) and the evening-morning difference in standing blood pressure. We conclude that, in patients with neurogenic orthostatic hypotension, the impaired tolerance to standing in the morning is due to larger falls in stroke volume and cardiac output. Not only nocturnal polyuria, but also a redistribution of body fluid, are likely mechanisms underlying the pronounced decreases in stroke volume and cardiac output after prolonged recumbency at night.

A smooth blood pressure control is obtained over 24 h by delapril in mild to moderate essential hypertensives.

OBJECTIVE: To assess the homogeneity of the antihypertensive effect of delapril over 24 h. DESIGN AND METHODS: After 2 weeks of placebo 50 mild to moderate essential hypertensives (age 54+/-5 years) were subjected to 8 weeks of treatment with delapril 30 mg once daily. At the end of each period, blood pressure (BP) was assessed by conventional sphygmomanometry (clinic or CBP) and ambulatory (A) BP monitoring. Twenty-four-hour means, trough-to-peak ratio (T/P) and smoothness index (SI, the ratio between the average of the 24-h BP changes after T and its standard deviation) were calculated for systolic (S) and diastolic (D) BP. RESULTS: CBP and ABP were significantly reduced by treatment. Pulse pressure (PP, the SBP-DBP difference) was also significantly (p < 0.01) reduced by delapril (5.7+/-6.2 and 3.3+/-3.8 mmHg, CPP and APP). The median T/P was higher (0.51 and 0.62, SBP and DBP) in the 43 responders at trough than in the whole group (0.44 and 0.51). The SI was similarly high in the whole group (1.3+/-0.6 and 1.4+/-0.6, SBP and DBP) and in the responders (1.4+/-0.5 and 1.5+/-0.6). CONCLUSIONS: Delapril effectively and smoothly reduces BP over 24 h, this effect being evident also on PP, a parameter with a relevant prognostic value.

Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study.

BACKGROUND AND AIMS: The Hypertension Optimal Treatment (HOT) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg, there can be a further reduction of cardiovascular events, particularly myocardial infarction, with no evidence of a J-shaped curve at lower pressures. Office measurement, however, gives no information about blood pressure outside the office. This paper describes a HOT substudy in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring. METHODS: The mean age of the substudy population was 62 +/- 7 years. Substudy patients were treated for a median period of 2 years. All received the dihydropyridine calcium antagonist felodipine, while some also received an ACE-inhibitor, a beta-blocker or a diuretic. Average 24 h, day and night ambulatory blood pressure values were computed at baseline (n = 277) and during treatment (n = 347): 112 patients had been randomized to a target office diastolic blood pressure

Relation between blood pressure variability and carotid artery damage in hypertension: baseline data from the European Lacidipine Study on Atherosclerosis (ELSA).

BACKGROUND: Baseline data from the European Lacidipine Study on Atherosclerosis (ELSA) have shown that carotid intima-media thickness (IMT) is not related to diastolic blood pressure (BP), but that it is related to clinic systolic (S) or pulse pressure (PP) and more so to their 24 h average values. The aim of the present study was to determine whether IMT independently relates to additional information obtained through ambulatory BP, in particular to SBP or PP variability. METHODS AND RESULTS: In 1663 hypertensive patients, after a wash-out period from antihypertensive treatment (mean age 56.2 +/- 7.65 years), IMT was assessed from 12 different carotid sites. Ambulatory BP measurements were performed every 15 min (day) and every 20 min (night). IMT values were positively related to 24 h, day and night average SBP and PP. There was some relationship of IMT with day-night or clinic-day SBP and PP differences. The most important finding, however, was that IMT values were related with 24 h SBP or PP standard deviation (P < 0.001), a measure of overall SBP or PP variability. The relationship was seen also by multiple regression analysis, the standard deviation for SBP or PP only following age and 24 h average SBP or PP in accounting for IMT values. CONCLUSIONS: This is the first demonstration from a large database that not only average 24 h PP and SBP values, but also 24 h BP fluctuations, are associated with, and possibly determinants of, the alterations of large artery structure in hypertension.

Efficacy, tolerability, and impact on quality of life of long-term treatment with manidipine or amlodipine in patients with essential hypertension.

This double-blind, multicenter trial compared antihypertensive efficacy, tolerability, and impact on quality of life of manidipine and amlodipine in patients with mild-to-moderate essential hypertension. Patients were randomly assigned to 48 weeks of once-daily manidipine, 10-20 mg, or amlodipine, 5-10 mg. Patients who did not respond to treatment after 12 weeks were also given enalapril, 10-20 mg, for the study's duration. The main efficacy end point was equivalence in sitting systolic (SiSBP) and diastolic (SiDBP) blood pressure reduction between the two drugs after 8 weeks (per protocol analysis). An intention-to-treat (ITT) analysis was performed in all patients with at least one efficacy determination during treatment. Quality of life was assessed by the "Subjective Symptoms Assessment Profile" (SSA-P) and "General Well-being Schedule" (GWBS), after 12 weeks of treatment. SiSBP reduction after 8 weeks was equivalent for manidipine (15.2 mm Hg, n = 227) and amlodipine (17.0 mm Hg, n = 219). The corresponding figure for SiDBP was 11.3 mm Hg for manidipine and 12.3 mm Hg for amlodipine. In the larger ITT population SiDBP was similarly and significantly reduced by manidipine (from 102 +/- 5 to 88 +/- 9 mm Hg, n = 241) and amlodipine (from 101 +/- 5 to 87 +/- 8 mm Hg, n = 240). Similar results were observed for SiSBP and standing SBP and DBP. Neither drug changed sitting or standing heart rate compared with baseline. SSA-P scores improved with manidipine but not amlodipine. GWBS total and partial scores increased more with manidipine than with amlodipine. Safety profile favored manidipine, which was associated with significantly less ankle edema than was amlodipine. This study shows for the first time that long-term treatment with the long-acting calcium channel blocker manidipine is as effective as treatment with amlodipine, has a better tolerability profile, and induces greater improvement in quality of life than amlodipine.

Comparison of candesartan versus enalapril in essential hypertension. Italian Candesartan Study Group.

BACKGROUND: The objective of this study was to compare the antihypertensive efficacy and tolerability of candesartan cilexetil (CC) with that of enalapril (E) and placebo (P) in hypertensives by clinic and ambulatory blood pressure (BP). PROCEDURES: The study was an Italian multicenter, randomized, double-blind, parallel group trial including 227 mild to moderate essential hypertensives (age range, 18 to 70 years). After 4 weeks of P, patients were randomized to 8 weeks of treatment with P or CC (4 mg) or E (10 mg) once daily, which was eventually increased to 8 mg and 20 mg once daily in nonresponders. At the end of each study phase, trough BP was measured by conventional sphygmomanometry and ambulatory BP was monitored over 24 h by a Spacelabs device. Analysis of 24-h BP profile included calculation of 24-h, daytime, nighttime, and hourly average values. RESULTS: In the 178 patients evaluable per protocol, at the end of 8 weeks of treatment, trough systolic (S) and diastolic (D) BP were similarly reduced by both active treatments (13 +/- 12 and 10 +/- 7 mm Hg for CC and 14 +/- 12 and 10 +/- 7 mm Hg for E) and significantly more by both treatments than by P (6 +/- 11 and 7 +/- 8 mm Hg, P < .01 v CC and E). In the 85 patients with valid 24-h recordings reduction in 24-h BP was again similar for the two active groups. The antihypertensive effect was still evident during h 23 and 24 after the last dose for both active treatments (8 +/- 20 v 5 +/- 18 mm Hg for SBP and 4 +/- 12 v 6 +/- 13 mm Hg for DBP, CC v E, respectively) but not for P. Heart rate was not significantly modified by either active treatment. The incidence of adverse events was greater in the E than in the CC group. CONCLUSIONS: Our study provides evidence that CC at a dose of 4 to 8 mg is as effective as E at a dose of 10 to 20 mg over 24 h, but is better tolerated than E.

The importance of blood pressure variability in hypertension.

Use of ambulatory blood pressure monitoring (ABPM) techniques has revealed that blood pressure is characterized by a considerable degree of variability over a 24 h period as a result, not only of the well-known fluctuations that occur between wakefulness and sleep, but also of the minute-to-minute changes induced by a variety of behavioural conditions. The degree of these variations is also influenced by neural mechanisms responsible for cardiovascular regulation, such as the arterial baroreflex. Blood pressure variability increases with age and blood pressure values, and its magnitude has been shown to correlate independently with the target-organ damage of hypertension. This has stimulated both the development of antihypertensive drugs able to reduce blood pressure homogeneously over 24 h, and recent proposals to develop more accurate indices, such as the smoothness index, to quantify the distribution of the antihypertensive effect over the entire day and night. Despite the important information that ABPM can provide concerning daily-life blood pressure variations and their modification by treatment, international guidelines suggest that it should not yet be used routinely in daily practice, but rather reserved for selected patients.

Antihypertensive efficacy of manidipine and enalapril in hypertensive diabetic patients.

Recent studies showed that in diabetic hypertensive patients, administration of angiotensin-converting enzyme (ACE)-inhibitors or calcium antagonists can effectively lower blood pressure (BP) and prevent diabetes-related cardiovascular complications with no adverse metabolic effects. We sought to assess the antihypertensive and metabolic effects of the new dihydropyridine calcium antagonist manidipine (M) in patients with diabetes mellitus and essential hypertension as compared with the ACE inhibitor enalapril (E). After 3 weeks of placebo, 101 (62 men; age range, 34-72 years) hypertensives with type II diabetes mellitus were randomized to M 10-20 mg or E 10-20 mg, od, for 24 weeks. At the end of the placebo period and the active-treatment phase, BP was measured with a mercury sphygmomanometer (office, O) and over the 24 h by ambulatory (A) monitoring. ABP recordings were analyzed to obtain 24-h, day (6 a.m. to midnight), and night (midnight to 6 a.m.) average systolic (S) and diastolic (D) BP and heart rate (HR) values. Homogeneity of the antihypertensive effect over the 24 h was assessed by the smoothness index [SI: i.e., the ratio between the average of the 24 hourly BP changes after treatment and the corresponding standard deviation (the higher the SI, the more uniform is the BP control by treatment over the 24 h]. The O SBP and DBP were significantly (p < 0.01) and similarly reduced by M (16 +/- 10 and 13 +/- 6 mm Hg, n = 49) and E (15 +/- 10 and 13 +/- 6 mm Hg, n = 45). The percentage of patients whose O DBP was reduced < or = 85 mm Hg (i.e., the value indicated to be the optimal DBP goal in diabetic hypertensives) was similar for M (37%) and E (40%). The reduction of 24-h BP also was similar between M (n = 38) and E (n = 38) for both drugs (systolic, 6 +/- 11 and 8 +/- 10 mm Hg; diastolic, 5 +/- 8 and 5 +/- 7; NS, M vs. E). The antihypertensive effect was distributed in a similar homogeneous fashion throughout the dosing interval, as shown by the similar SI values (M, 0.6 +/- 1.2 for SBP and 0.6 +/- 0.9 for DBP; E, 0.6 +/- 0.8 for SBP and 0.5 +/- 0.7 for DBP; NS, M vs. E). O and A HR were unchanged by either treatment. Markers of glucose and lipid metabolism and renal function were not significantly modified by treatment both with M and with E. In the diabetic hypertensives, M was as effective and metabolically neutral as the ACE-inhibitor E.

Ambulatory blood pressure monitoring.

This paper will briefly summarize the available evidence on the diagnostic and prognostic relevance of a number of parameters derived from the analysis of 24 hour ambulatory blood pressure recordings. These parameters include the 24 h average blood pressure values, the difference between daytime and nighttime blood pressure, the difference between clinic blood pressure and daytime average blood pressure as a surrogate measure of the "white coat effect", and 24 hour blood pressure variability as quantified by the standard deviation of the 24 hour average value.

Broad-band spectral analysis of 24 h continuous finger blood pressure: comparison with intra-arterial recordings.

The present study compares the spectral characteristics of 24-h blood pressure variability estimated invasively at the brachial artery level with those estimated by measurement of blood pressure at the finger artery using the non-invasive Portapres device. Broad-band spectra (from 3x10(-5) to 0.5 Hz) were derived from both finger and intra-brachial pressures recorded simultaneously for 24 h in eight normotensive and twelve hypertensive ambulant subjects. At frequencies lower than 0.07 Hz, higher spectral estimates were obtained by Portapres than by intra-brachial measurements. The maximum overestimation occurred in systolic pressure at around 10(-2) Hz, where the amplitude of the oscillations was two times greater when measured by Portapres. A less pronounced overestimation was found for diastolic pressures. The maximum overestimation was greater during daytime than during night-time. At around 0.1 Hz, invasive and non-invasive spectra were similar. At the respiratory frequencies (0.15-0.50 Hz), the power spectra were overestimated by Portapres during daytime, and underestimated at night. These results provide reference information for the correct interpretation of Portapres data in the estimation of 24-h blood pressure spectral power.

The smoothness index: a new, reproducible and clinically relevant measure of the homogeneity of the blood pressure reduction with treatment for hypertension.

OBJECTIVE: To introduce a new method, the smoothness index, for assessing the homogeneity of 24 h blood pressure reduction by antihypertensive treatment and to compare it with the trough : peak ratio; and to assess the ability of both indices to predict a reduction in the left ventricular mass index induced by treatment. PATIENTS AND METHODS: In 174 patients with essential hypertension and left ventricular hypertrophy, enrolled in the Study on Ambulatory Monitoring of Pressure and Lisinopril Evaluation (SAMPLE), aged 20-65 years, we measured clinic blood pressure, 24 h ambulatory blood pressure and the left ventricular mass index (echocardiography) before and after treatment with lisinopril at 20 mg with the addition of 12.5 or 25 mg hydrochlorothiazide as needed to reach a sufficient blood pressure reduction. The following parameters were computed for systolic and diastolic ambulatory blood pressure: (1) hourly and 24 h blood pressure averages (+/- SD) at baseline and after 3 and 12 months of treatment; (2) hourly blood pressure changes from baseline after 3 and 12 months of treatment, and their average (+/- SD) over 24 h; (3) the trough : peak ratio after 3 and 12 months of treatment; and (4) the smoothness index after 3 and 12 months of treatment Similar calculations were also performed at the end of a final study month during which active treatment was withdrawn and placebo was substituted (n = 164). RESULTS: The smoothness index for systolic and diastolic ambulatory blood pressure computed after 3 months of treatment was more closely related to its corresponding values after 12 months of treatment than the trough : peak ratio values computed after the same time periods were (r = 0.68 versus 0.38 for systolic and 0.68 versus 0.42 for diastolic blood pressure, respectively). The smoothness index showed an inverse correlation with the 24 h standard deviation of systolic and diastolic blood pressure (r = -0.25 and -0.16, P < 0.01 and < 0.05, respectively, for 12 months of treatment), while the trough : peak ratio did not (r = -0.01 to -0.12, NS). A treatment-induced reduction in the left ventricular mass index was related to the smoothness index for systolic and diastolic blood pressure (r = -0.35 and -0.32, P< 0.001 with 12 months of treatment), but not to the corresponding trough : peak ratios. CONCLUSIONS: The smoothness index identifies the occurrence of a balanced 24 h blood pressure reduction with treatment and correlates with the favourable effects of treatment on left ventricular hypertrophy better than the commonly used trough : peak ratio.