Patient compliance in the treatment of arterial hypertension.
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Biomedical subjects
Publications and source records attributed to J M Mallion.
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F2-isoprostanes are stable lipid peroxidation products of arachidonic acid and their quantification provides a novel approach to the assessment of oxidative stress in vivo. F2-isoprostanes are present in increased amounts in adult hypercholesterolemia, but no data exist concerning children. We investigated urinary isoprostaglandin F2, type III production as an index of lipid peroxidation in 15 children presenting with type IIa hypercholesterolemia (serum total cholesterol, 290 [SD +/- 70] mg/dl; low-density lipoprotein cholesterol, 210 [SD +/- 90] mg/dl) compared with 15 sex- and age-paired control children (serum total cholesterol, 160 [SD +/- 20] mg/dl). Urinary levels of isoprostaglandin F2alpha type III were measured by gas chromatography mass spectrometry. Urinary concentrations did not differ significantly in hypercholesterolemic children compared with control children (84.7 [SD +/- 37] vs. 96 [SD +/- 35] pmol/mmol creatinine, respectively). No significant correlation was found with total cholesterol, low-density-lipoprotein and high-density-lipoprotein cholesterol, and apolipoprotein B and A1 serum levels. F2-isoprostane urinary levels in children with type IIa hypercholesterolemia do not differ from those of age- and sex-matched control children and are not correlated to blood lipid parameters, suggesting that hypercholesterolemia is not associated with increased lipid peroxidation in childhood.
BACKGROUND: Many studies have shown definite but weak correlations between 24h blood pressure and left ventricular mass in hypertension. OBJECTIVE: The present study applied an original multivariate analysis of parameters from ambulatory blood pressure monitoring to predict left ventricular mass in hypertension. METHODS: Two hundred untreated hypertensive subjects (age=51+/-13 years, clinic blood pressure=163/98mmHg) had echocardiography and 24h recording of blood pressure. Data from 102 subjects were used to construct a mathematical model for prediction of left ventricular mass. The remaining 98 subjects were used to validate the model. RESULTS: The model included age, weight, height, 24h systolic blood pressure, heart rate over 24h, standard deviations of systolic blood pressure and of heart rate over 24h. Using this model, we explained 63% of the variance of left ventricular mass. Moreover, the model was validated for the correlation (r=0.70) between measured and the estimated left ventricular mass. CONCLUSIONS: Systolic blood pressure, heart rate and their standard deviations over 24h contribute to left ventricular mass in hypertensive subjects. Thus, it is important to take into account not only blood pressure but also heart rate in clinical studies.
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Patent foramen ovale is frequently associated with embolic cerebrovascular accidents. The diagnosis of patent foramen ovale is easier since the advent of transesophageal echocardiography. However, this method is semi-invasive and is not readily available in all units. Contrast transcranial Doppler ultrasound enables the detection of the passage of a contrast material injected into a peripheral vein to the cerebral circulation across an orifice which is most often a patent foramen ovale. Contrast transcranial Doppler ultrasound may facilitate, with a high sensitivity and specificity, the diagnosis of a patent foramen ovale when a transesophageal echo is not possible. However, transesophageal echocardiography remains the preferred test especially in the young since other potentially embolic sources, such as a thrombus in the left atrium, may be demonstrable.
OBJECTIVE: To study the influence of position changes on 24-h ambulatory blood pressure (ABP) in normotensive or mildly hypertensive normoalbuminuric patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: A cross-sectional evaluation of patients was staged according to the duration of diabetes (DD) and the presence of microangiopathy. We recruited 37 patients (30 men and 7 women), aged 38 +/- 12 years, who were normotensive or mildly hypertensive (diastolic blood pressure [DBP] <105 mmHg) and free of antihypertensive treatment and microalbuminuria. They were included according to DD (group 1, <5 years; group 2, > or =10 years). An additional group of seven diabetic patients with microalbuminuria and mild untreated hypertension was also investigated. We recorded 24-h ambulatory blood pressure every 15 min with a position sensor, which allowed for the discrimination between standing or supine/sitting position in the patient. RESULTS: Mean daytime (10:00 A.M. to 8:00 P.M.) ABP in supine/sitting position did not significantly differ between groups 1 and 2. However, standing ambulatory systolic blood pressure (ASBP) and ambulatory DBP (ADBP) were significantly higher than supine/sitting ASBP and ADBP in group 1 (DeltaSBP 4 +/- 5, DeltaDPB 4 +/- 6 mmHg, P < 0.01) but not in group 2 (DeltaSBP 2 +/- 8, DeltaDBP 2 +/- 4 mmHg, P = NS). Patients free of microangiopathy presented with significantly higher ABP in standing position than in sitting/lying position, whereas patients with retinopathy and/or nephropathy exhibited no significant increase of ABP during standing. CONCLUSION: The monitoring of position during ambulatory measurement of blood pressure in type 1 diabetic patients shows different patterns in relation to disease duration and the presence of microangiopathy.
Taking into account all the risk factors and blood pressure levels, as indicated by several American and European recommendations available since 1997, is a leading strategy to reduce mortality and morbidity of hypertensive patients. The aim of this study was to quantify how, in 1999. French practitioners applied recommendations on hypertension (HTN), diabetes and hypercholesterolemia in recently diagnosed hypertensive patients and to evaluate whether or not the recommended targets were met. 1639 French GPs and cardiologists included 5831 recently diagnosed (7.5 +/- 3.6 months) hypertensives (57 +/- 12 years of age, M/F = 55/45%). Initial BP was 173 +/- 15/99 +/- 9 mmHg. 56% had no concomitant disease, 36% had either diabetes, dyslipidemia or coronary heart disease, 8% had at least two concomitant diseases. At the time of the study corresponding to 6.3 +/- 3.8 months after initiation of diet and/or medical treatment, their BP was 148 +/- 17/86 +/- 11 mmHg (-25/-19 mmHg). At that time only 37% of patients with stage 2 HTN were encouraged to adopt lifestyle modifications without any medical treatment as recommended by the JNC VI. Among these hypertensives, measurement of plasma cholesterol was performed in only 61%, HDL-C/LDL-C in 26% and blood glucose in 51%. In the patients with dyslipidemia, LDL-C was measured in only 47%. In the 677 diabetic patients only 27% had a glycated hemoglobin measurement. The percentage of patients reaching target BP was 59% as regard DBP < 90 mmHg, 25% as regard SBP < 140 mmHg, and 23% reached both target values of BP. In addition, 30% of patients with dyslipidemia reached the target LDL-C as defined by French recommendations (ANAES 1996) and 30% of the diabetic patients reached the target value for glycemia recommended by ADA (1997). In 1999 in France, a minority of patients reaches the national or international recommended target values for blood pressure, glycemia and plasma LDL-cholesterol. In spite of that, French practitioners do not implement all the available diagnostic tools to improve the treatment of metabolic disorders in hypertensive patients. As a conclusion, to improve the prognosis of hypertensive patients, it is mandatory to raise the awareness of physicians about multiple risk factor management and help them implement the recommendations in their daily practice.
OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.
BACKGROUND: Epidemiological studies have shown that increased arterial stiffness and wave reflections, major determinants of systolic and pulse pressure, are associated with morbidity and mortality. Therapeutic trials based on cardiovascular mortality have recently shown that reduction of systolic blood pressure (SBP) requires normalization of both large-artery stiffness and wave reflections. AIMS: To compare the antihypertensive effects of the very-low-dose combination of perindopril (2 mg) and indapamide (0.625 mg) (one or two tablets per day) with the beta-blocking agent atenolol (50 mg; one or two tablets per day) in order to determine whether the combination decreased SBP and pulse pressure more than did atenolol, and whether this decrease occurred in relation to a reduction in arterial stiffness [aortic pulse wave velocity (PWV)] or a decrease in the intensity of, or delay in, wave reflections (augmentation index, measured by applanation tonometry) or a combination of both. MATERIAL AND METHODS: This was a double-blind randomized study in 471 individuals with essential hypertension followed for 12 months. Arterial pressure was measured in the brachial artery (mercury sphygmomanometer) and in the carotid artery (applanation tonometry). RESULTS: For the same reduction in diastolic blood pressure (DBP), the combination of perindopril and indapamide decreased brachial SBP and pulse pressure significantly more than did atenolol (adjusted differences between groups -6.2 +/- 1.5 and -5.5 +/- 1.0 mmHg, respectively; P < 0.001). This difference was even more pronounced for the carotid than for the brachial artery. Whereas both antihypertensive agents similarly decreased PWV, only the combination significantly attenuated wave reflections. CONCLUSION: Normalization of SBP, pulse pressure and arterial function--a haemodynamic profile known to improve survival significantly in hypertensive populations at high cardiovascular risk--was achieved to a greater extent with a very-low-dose combination of perindopril and indapamide than with atenolol.
The role of pulse pressure (PP) in cardiovascular remodelling was studied in 61 never treated hypertensive subjects who were selected on the criteria of ambulatory blood pressure (BP) monitoring (mean BP over 24 h: 147 +/- 14/96 +/- 10 mm Hg). Echocardiography and carotid ultrasonography were performed and the vascular images analysed using a specific automatic measuring program. Thirty percent of subjects had left ventricular hypertrophy (LVH). Left ventricular mass index (LVMI) was related to the clinic (r = 0.35) and ambulatory (r = 0.41 over 24 h, r = 0.38 daytime and r = 0.42 night-time) PP and to the systolic BP. PP was higher when there was LVH. Vascular thickening was found in 6.6% of subjects (carotid intima-media thickness (IMT) >/=1.0 mm). Among the BP parameters, IMT and cross-sectional area (CSA) were related only to the clinic PP (r = 0.27, r = 0.29 respectively) and to the ambulatory PP (over 24 h: r= 0.29, r = 0.28; daytime: r = 0.22, r = 0.23; night-time: r = 0.32, r = 0.30). In men, the relationship between CSA and PP (clinic and over 24 h) was independent of age. A total of 16.7% of subjects with LVH had intima-media thickening in contrast to 2.3% in the group without LVH. LVMI was related to the CSA (r = 0.37) and to the IMT (r = 0.31). However, after multivariate analysis taking into account the PP, relationships between IMT or CSA and LVMI disappeared. Our data showed that the PP was the most important BP parameter in the development of cardiac and arterial remodelling in hypertension. Journal of Human Hypertension (2000) 14, 23-30.
Candesartan is one of the first angiotensin II receptor antagonists (AIIRAs) to be developed. It binds tightly to and dissociates slowly from the angiotensin subtype 1 (AT1) receptor in vitro. These binding characteristics differ from those of losartan, which demonstrates lower affinity and faster dissociation from the AT1 receptor. Candesartan causes long-lasting antagonism of the vascular contractile response to angiotensin II compared with irbesartan, losartan or the active metabolite of losartan - EXP-3174. While there are relatively few distinctions that can be made between the AIIRAs in terms of their pharmacokinetic profiles, the antagonistic potency of candesartan cilexetil at the AT1 receptor over 24 h clearly differentiates it from other members of its class. These differences are reflected in the antihypertensive efficacy and duration of action of candesartan in clinical trials.
This multicenter, double-blind, parallel-group study was designed to assess the efficacy and the safety of fixed low dose combination perindopril 2 mg/indapamide 0.625 mg (Per/Ind) versus atenolol 50 mg (Ate). After a 4-week placebo run-in, 446 hypertensive patients (mean age : 55.8 +/- 11.0 years) were randomised to receive Per/Ind or Ate for 12 weeks. The primary outcome measures were the changes in trough supine systolic and diastolic blood pressure (sSBP, sDBP) between baseline and the last observation. Equivalence was assessed in an intention-to-treat analysis using a two one-sided tests procedure. Per/Ind and Ate decreased sSBP by -20.5 mmHg and -20.1 mmHg, respectively; the 90% confidence interval [-2.3; 1.5] of the intertreatment difference (-0.4 mmHg) fell within the predefined equivalence interval [-8; +8 mmHg]. Similarly, the sDBP decreased by -15.1 mmHg (Per/Ind) and -16.2 mmHg (Ate) with an intertreatment difference of 1.1 mmHg whose 90% confidence interval [-0.1; 2.2 mmHg] fell within the predefined equivalence interval [-4; +4 mmHg]; thus antihypertensive efficacy of Per/Ind and Ate were equivalent (P <0.001). In patients older than 65, Per/Ind induces a statistically greater decrease in sSBP than Ate (P <0.05). Per/Ind was well tolerated. Further controlled studies are needed to confirm these results on a long-term period.
OBJECTIVE: We have assessed the influence of gender and age on the main outcome results of the Hypertension Optimal Treatment (HOT) study. DESIGN AND INTERVENTIONS: The aims of the HOT study were to study the relationship between three levels of target office diastolic blood pressure (BP) (< or = 90, < or = 85 or < or = 80 mmHg) and cardiovascular (CV) events in hypertensive patients, and to examine the effects of 75 mg acetylsalicylic acid (ASA) daily versus placebo. SETTING: Outpatient clinical trial in 26 countries. PATIENTS: A total of 18790 patients (mean age 61.5 years, range 50-80) were randomized and followed for an average of 3.8 years until 71051 patient-years and 683 events had occurred. MAIN OUTCOME MEASURES: CV death, myocardial infarction (MI) and stroke. RESULTS: There were significantly fewer MIs in those in the lower diastolic BP target groups (3.0 versus 1.2 and 1.7 MIs/1000 patient-years, P for trend = 0.034) in women (n = 8883), whereas the similar but smaller trend (4.1 versus 4.1 and 3.4 MIs/1000 patient-years) was not statistically significant in men nor in the subgroup analysis of younger and older subjects. The effect of ASA on preventing MI was not influenced by age < 65 years (P= 0.02) or age > or = 65 years (P = 0.04) but was influenced by gender (P = 0.38 in women and P = 0.001 in men, lowered by 42% corresponding to a reduction from 5.0 to 2.9 MIs/1000 patient-years). CONCLUSIONS: The data of this HOT study sub-analysis suggest somewhat differentiated optimal gender- and age-dependent effects of anti-hypertensive and anti-platelet therapies; lowering of diastolic BP to about 80 mmHg in hypertensive women and, in addition, the administration of 75 mg of ASA to well-treated hypertensive men appear to effectively reduce the most common cardiovascular complication, i.e. myocardial infarction, in patients with essential hypertension.
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OBJECTIVE: To evaluate the physiological variations in arterial blood pressure in normotensive subjects during activity and in relation to the sitting or lying position. METHODS: The subjects were 30 healthy volunteers who were normotensive and receiving no treatment. Blood pressure was measured using the validated monitor Diasys Integra (NOVACOR SA, Rueil-Malmaison, France) with an integral position sensor. Blood pressure was recorded every 15min over a 24h period, additional measurements being made in the first, third and sixth minutes after standing up. RESULTS: During the active period (1000-2000h), 53% of the measures were made in the standing position. Over this period, the values of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were significantly elevated in the standing position in comparison to the sitting position. The difference was of the order of 5mmHg for the SBP, 3.5mmHg for the DBP and 9beats/min for the heart rate. The SBP, DBP and heart rate measured in the first, third and sixth minutes after standing up were not significantly different. CONCLUSION: When measuring the blood pressure and heart rate in ambulatory patients, it seems justified to evaluate the patient's position during monitoring in order to achieve a better reproducibility and also to uncover any problems of blood pressure control with positional change, as could exist in patients with autonomic dysfunction. This might also aid in evaluating antihypertensive treatment and also any deleterious hypotensive effects.
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The goal of the SHEAF study is to determine whether self blood pressure measurement (SBPM) has a better cardiovascular prognostic value than office blood pressure (OBP) among French elderly (> or = 60 y) hypertensive patients (pts) followed-up by general practitioners. Baseline SBPM was performed over a 4-day period: every day a series of 3 consecutive measurements was requested in the morning (8:00 am) and in the evening (8:00 pm), using a validated device OMRON 705 CP. Measurements performed out of predefined morning and evening time (outside the 4:00-12:00 am range or the 4:00-12:00 pm range) were discarded as well as aberrant values. Pts were included in the study only if they exhibited at least 15 valid measurements with at least 6 in the morning and 6 in the evening. 5,649 pts were selected. 186 pts were excluded for age < 60 years. Thus SBPM analysis was performed for 5,463 pts: 2,687 men (49%) and 2,776 women (51%) aged 70 +/- 7 years. Only 252 pts (5%) were excluded for non valid SBPM (207 pts < 15 measurements, 106 pts < 6 measurements in the morning and 205 pts < 6 measurements in the evening). 5,211 pts (95%) with valid SBPM were included. The distribution of pts according to the number of measurements performed is the following: [table: see text] The number of measurements performed in the morning is highly related to the number of measurements performed in the evening. None of the following variables is significantly associated with the poor compliance of measurement protocol: age, gender, CV history, CV risk factors, hypertension duration. In a large cohort of elderly hypertensive living in the community, SBPM is easily performed both in the morning and in the evening by most of the pts. If the SHEAF study demonstrates the prognostic value of SBPM, this would provide the basis for the use of this measurement method by a majority of elderly hypertensives.