Association of eNOS Glu298Asp gene polymorphism with circadian blood pressure rhythm.

Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).

[Diagnosis and post-operative evolution of patients operated for adrenal adenoma (Conn syndrome). A 12-years retrospective study]. / Diagnostic et évolution postopératoire des patients opérés d'un adénome de Conn. Etude rétrospective sur 12 ans.

The prevalence and characteristics of patients operated for adrenal adenoma (Conn syndrome) as well as their post-operative arterial pressure evolution are varying through literature. Our aim was to report the Grenoble University Hospital experience. From 1993 to 2005, 24 patients (mean age = 46 +/-11 years) presented the biological criteria of primary hyperaldosteronism and benefited from adrenalectomy with confirmation of adrenal adenoma. All had an uncontrolled hypertension, refractory in 42% of cases, with a hypokaliemia (mean = 2.65 +/- 0.47 mmol/l). All adenomas measured more than 10 mm in scanner imaging. After a mean post-operative follow-up of 46 +/- 43 months, 70% of them were normotensive, with (45%) or without (25%) anti-hypertensive therapy. the post-operative kaliemia was normal in all cases. Only 25% had post-operative hormonal dosages for control. Post-operative spontaneous normotensive patients had, at the diagnosis of adrenal adenoma, a more recent and non-refractory hypertension, with a lower number of antihypertensive drugs, a better response to spirinolactone and higher aldosterone plasmatic levels. Two lessons can be taken from this study: 1) Whether 70% of patients operated for adrenal adenoma are normotensive (with or without treatement) post-operatively, only 25% are definitely cured after 4 years. Factors associated to a post-operative cure highlight the interest of an ealy diagnosis. 2) There is probably an underdiagnosis of adrenal adenoma (Conn syndrome) because neither adenomas with normokaliemia, nor adenomas <10 mm in scanner imaging have ever been diagnosed or at least, sent to surgery.

Is "isolated home" hypertension as opposed to "isolated office" hypertension a sign of greater cardiovascular risk?

BACKGROUND: The SHEAF (Self-Measurement of Blood Pressure at Home in the Elderly: Assessment and Follow-up) study is an observational study (from February 1998 to early 2002) designed to determine whether home blood pressure (BP) measurement has a greater cardiovascular prognostic value than office BP measurement among elderly (> or =60 years) French patients with hypertension. The objective of this present work is to describe the baseline characteristics of the treated patients in the SHEAF study from February 1998 to March 1999, placing special emphasis on "isolated office" and "isolated home" hypertension. METHODS: Baseline office BP measurement was assessed using a mercury sphygmomanometer. Home BP measurement was performed over a 4-day period. A 140/90-mm Hg threshold was chosen to define office hypertension, and a 135/85-mm Hg threshold to define home hypertension. RESULTS: Of the 5211 hypertensive patients in the SHEAF study with a valid home BP measurement, 4939 received treatment with at least 1 antihypertensive drug. Patients with isolated office hypertension represented 12.5% of this population, while patients with isolated home hypertension represented 10.8%. The characteristics of the patients with isolated office hypertension were similar to those of patients with controlled hypertension. However, patients with isolated office hypertension had fewer previous cardiovascular complications. In contrast, rates of cardiovascular risk factors and history of cardiovascular disease in patients with isolated home hypertension resembled those in patients with uncontrolled hypertension. CONCLUSIONS: This retrospective analysis suggests that patients with isolated home hypertension belong to a high-risk subgroup. The 3-year follow-up of these patients will provide prospective data about the cardiovascular prognosis of these subgroups.

[The best of hypertension in 2004]. / L'essentiel de 2004 en hypertension artérielle.

Among the major developments of the year 2004 in the knowledge of hypertension, a special part should be dedicated to the venue in Paris of the Fourteenth meeting of the European Society of Hypertension last June. Beside major progress observed in basic science, namely signaling pathways involved in the regulation of smooth muscle tone, growth and inflammation, at the cross-road of hypertension, diabetes, and metabolic syndrome, large clinical trials have afforded strong evidence for the usefulness of lowering blood pressure in various diseases associated with hypertension. Despite these advances, the percentage of treated hypertensive patients who reach the BP goal (<140/90 mmHg) is too low (about 30%). Thus urges the need for adapting therapeutic strategies. The ESH meeting gave the opportunity to gather a large body of evidence for a better therapeutic approach, in order to control BP in a larger number of hypertensive patients.

[Significance of the exercise test in hypertensives]. / Intérêt de l'épreuve d'effort chez l'hypertendu.

The presence of hypertension is responsible for an increase in cardiovascular morbidity and mortality. The significance of evaluating variations of blood pressure on exercise in actual or potential hypertensives warrants further consideration. The modes of physiological blood pressure variation on effort and the practical methods of performing an exercise test are well documented and have been the subject of guidelines. Within this framework must be included dynamic exercise tests on ergometric bicycles or with treadmills. From numerous studies it is now possible to better define the predictive and prognostic values of the various modes of blood pressure changes with exercise. Blood pressure measurement on exercise represents an additional investigation in cardiovascular morbidity and mortality (coronary or cerebrovascular events). The diagnostic applications of this exercise measurement reveal these prognostic data, and exercise blood pressure measurement is to be recommended in subjects who experience regular significant physical effort.

[Use of home blood pressure devices in France in 2004]. / Utilisation des appareils d'automesure tensionnelle en France en 2004. Enquête FLAHS 2004.

OBJECTIVE: To estimate the number of devices for home blood pressure measurements in the French population in 2004 and to evaluate the use of these apparatus. METHODS: The French League Against Hypertension Survey 2004 (FLAHS-2004) was performed cross-sectionally on 3707 subjects, part of a sample of 5476 subjects selected as being representative of the French metropolitan population for age (35 years and above), gender, socioeconomic status, and place of living. Subjects who declare to take an antihypertensive medication were classified as treated hypertensive patients. A questionnaire evaluating the condition of use of HBP device was given. RESULTS: In 2004, 24% of the French population above the age of 35 years was treated for hypertension, corresponding to an estimate of 7.5 million of subjects. 25% of treated hypertensives and 12% of untreated subjects had a tensiometer. A total of 4 millions of BP devices are owned in the general population with 43% by treated hypertensive patients. 67% of BP devices are wrist cuff. Medical doctors recommended home blood pressure monitoring in only 12% of subjects. CONCLUSION: In 2004, the number of subjects treated for hypertension is 1/4 of the general population over the age of 35 years in France. In this group of subjects, 1/4 possessed a tensiometer but in only 10% medical doctor recommended the use of home blood pressure monitoring.

[Changes in life style and drug therapy for treatment of hypertension in France between 2002 and 2004]. / Evolution dans l'utilisation des traitements non médicamenteux et médicamenteux pour le traitement de l'hypertension artérielle en France. Enquête FLAHS 2004.

OBJECTIVES: To estimate changes in life style and drug therapy for treatment of hypertension in France between 2002 and 2004. METHODS: The French League Against Hypertension Survey 2004 (FLAHS-2004) was performed cross-sectionally on 3 707 subjects, part of a sample of 5476 subjects selected as being representative of the French metropolitan population for age (35 years and above), gender, socioeconomic status, and place of living. Subjects who declare to take an antihypertensive medication were classified as treated hypertensive patients. A questionnaire evaluating changes in life style during the last year (physical activities, quality of food consumption, smoking, and alcohol habits) was auto-administered. RESULTS: In 2004, 24% of the French population above the age of 35 years was treated for hypertension, corresponding to an estimate of 7.5 million of subjects. The two most frequent prescribed drugs are: fixed-dose combination drugs and beta-blockers in patients aged less than 75 years, and calcium antagonist and fixed-dose combination drugs in patients aged more than 75 years. Hypertensive subjects experienced: a weight loss of more than 3 kg in 11% vs 9%* in the general population, an increased in fruits and vegetables consumption in 41% vs 34%*, a decreased in cheese (21 vs 17%*), pork-butchery (46 vs 34%*) and alcohol consumption (23 vs 18%*) [*p < 0.01]. On the other hand, the percentage of subjects who increased their physical activities was low and not different in the two groups (7 vs 9%). CONCLUSION: Changes in life style were more often applied by the subjects treated for hypertension that by the general population. The dominating place that occupies today fixed-dose combination drugs indicates a change of the therapeutic practices.

Early disturbances of ambulatory blood pressure load in normotensive type I diabetic patients with microalbuminuria.

OBJECTIVE: To compare 24-h ABP in normotensive type 1 diabetic patients with and without microalbuminuria. RESEARCH DESIGN AND METHODS: The study was a retrospective comparison of cases and matched control subjects. The first phase included 35 type 1 diabetic patients, normotensive by OMS criteria. The 23 patients with normoalbuminuria (< 15 micrograms/min) were compared with 12 patients with microalbuminuria (> or = 15 micrograms/min). In the second phase, the 12 microalbuminuric patients were paired by sex- and age-matched with 12 normoalbuminuric patients and 12 nondiabetic healthy control subjects. We measured casual systolic and diastolic BP and HR, 24-h ABP and AHR (recorded with a Spacelabs automatic recorder), and microalbuminuria. RESULTS: No correlation between microalbuminuria and casual BP was observed. Microalbuminuria was correlated significantly with diastolic 24-h APR and nocturnal systolic and diastolic ABP (r = 0.35, 0.38, and 0.33, respectively; P < 0.05) and with AHR during all time periods (24-h, r = 0.46; day, r = 0.39; night, r = 0.39; P < 0.05). Normo- and microalbuminuric patients did not differ in casual BP and HR. However, microalbuminuric patients had a significant increase in systolic 24-h ABP (119.1 +/- 8.2 vs. 113.1 +/- 8.1, P = 0.05), diastolic 24-h ABP (74.9 +/- 7.5 vs. 70.2 +/- 5.7, P = 0.04), nocturnal systolic ABP (112.8 +/- 7.1 vs. 105.8 +/- 7.9, P = 0.01), and AHR during all time periods. The same results were observed when patients were paired by age and sex. CONCLUSIONS: Normotensive microalbuminuric type 1 patients, although strictly comparable with normoalbuminuric patients for casual BP and HR, have an increased ABP and HR, especially during the night. This difference might reflect dysautonomia. Ambulatory measurement of BP and HR is more appropriate than casual measurements in hemodynamic studies of incipient diabetic nephropathies and could be proposed as an interesting tool for an early prediction of diabetic nephropathy.

Variations of ambulatory blood pressure with position in patients with type 1 diabetes: influence of disease duration and microangiopathy in a pilot study.

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.

Home blood pressure: variability, comparison with office readings and proposal for reference values. Groupe de la Mesure, French Society of Hypertension.

PURPOSE: A multicentre study was performed on 390 healthy subjects (210 male, 180 female) to evaluate home blood pressure versus office blood pressure. METHODS: The patients, aged 20-59 years, not on antihypertensive treatment, were not preselected by blood pressure levels. Blood pressure was measured in the doctor's office, using a mercury manometer at the fifth, sixth and seventh minute of rest, and at home by self-measurement using a validated electronic oscillometric device at the fifth, sixth and seventh minute of rest, in the morning and evening, on three consecutive days. RESULTS: The analysis of office and home measurements at the fifth, sixth and seventh minute of rest showed a significant decrease in blood pressure, mostly between the fifth and sixth minute. There was no significant variation in home pressure over the three consecutive days of measurement. Blood pressures were significantly higher in the evening than in the morning; the mean differences were 3 mmHg for systolic and 1.5 mmHg for diastolic blood pressure. Compared with office blood pressure measurement, home measurement provided significantly lower systolic and diastolic blood pressure means. Of the subjects, 78% showed a higher systolic and 69.9% a higher diastolic blood pressure with office measurement than with home measurement. Systolic and diastolic blood pressure differences were non-significantly higher for females than for males and did not differ with age. CONCLUSIONS: The comparison of the office and home measurement distributions allowed us to propose reference values for home blood pressure measurement. These were established by choosing blood pressure at the identical percentile for home measurement as we found for office measurement using the World Health Organization criteria (140/90 and 160/95 mmHg). Using this approach, the upper limit for normotension by home measurement would be 127/83 mmHg and for hypertension 147/86 mmHg. Although this approach has no prognostic value, it could be useful for the interpretation of home blood pressure.

Arterial mechanics predict cardiovascular risk in hypertension.

Systolic and diastolic blood pressures are the exclusive mechanical factors considered as predictors of cardiovascular risk for members of populations of normotensive and hypertensive subjects. However, if hypertension is considered as a mechanical factor acting on the arterial wall with deleterious consequences, the totality of the blood pressure curve should be considered in order to investigate the risk. The purpose of this review is to show that in addition to systolic and diastolic blood pressures, other hemodynamic indexes with particular relevance for cardiac complications and that originate from pulsatile pressure should be taken into account, namely brachial pulse pressure, pulse pressure amplification, early wave reflections, and pulse wave velocity.

Examination of variability in arterial blood pressure at rest using spectral analysis in hypertensive patients.

INTRODUCTION: We hypothesize that in essential hypertension sympathetic nervous activity is related to the development of left ventricular hypertrophy, which can be regarded as a measure of the severity of hypertension. METHODS: Using spectral analysis, we studied the short-term variability in resting blood pressure and heart rate in essential hypertensive subjects. We measured blood over 10 min using a Finapres in 88 subjects after 20 min rest. We performed echocardiography to evaluate left ventricular hypertrophy and thereby identified three groups: 23 control subjects (group I), 29 hypertensive subjects (World Health Organization criteria) without left ventricular hypertrophy (group II) and 36 hypertensive subjects with left ventricular hypertrophy (group III). None had been treated for hypertension before the study. RESULTS: The variability in blood pressure over a low-frequency period considered to be a marker of sympathetic activity was significantly increased in group II compared with groups I and III (analysis of covariance taking into account blood pressure and age). The variability in heart rate was similar in groups II and III, but both groups had a significantly reduced variability in heart rate compared with group I. CONCLUSION: These data, which examine globally, using a non-invasive method, all neurohormonal factors associated with the development of left ventricular hypertrophy, demonstrate that, in the time course of hypertension, low-frequency oscillations in blood pressure and heart rate are shifted to a lower level, presumably reflecting altered function of the sympathetic nervous system. We suggest that spectral analysis of blood pressure at rest in hypertensive patients can lead to complementary information to single measures of blood pressure and detect differences in the cardiovascular regulatory system.

Clinical value of ambulatory blood pressure monitoring.

Ambulatory blood pressure monitoring (ABPM) has now become an established clinical tool. It is appropriate to take stock and assess the situation of this technique. UPDATE ON EQUIPMENT: Important improvements in equipment have occurred, with reductions in weight, in awkwardness and in noisiness of the machines, better acceptability and tolerance by the patients, and better reliability. Validation programmes have been proposed and should be referred to. Limitations of the technique persist with intermittent recording in current practice. The reproducibility is limited in the short-term while recording over 24 h is acceptable. DIAGNOSIS AND PROGNOSIS: White-coat effect (WCE) is manifested as a transient elevation in blood pressure during the medical visit The frequency of this phenomenon, the size of the effect, age, sex and level of blood pressure (BP) or the situation of occurrence (general practitioner, specialist or nurse) have been interpreted differently. It does not seem that WCE predicts cardiovascular morbidity or mortality. White-coat hypertension (WCH) is diagnosed on the evidence of abnormal clinical measures of BP and normal ABPM. The latest upper limits of normality by ABPM recommended by the JNCVI are < 135/85 mmHg while patients are awake and < 120/75 mmHg while patients are asleep. If we accept these upper limits of normality in ABPM, WCH does not appear to be a real problem as regards risk factors or end-organ effects. In terms of prognosis, data are limited. Cardiovascular morbidity seems low in WCH but identical to that of hypertensive subjects in these studies. However, further studies are needed to confirm these results. WCH does not appear to benefit from anti-hypertensive treatment. It is obvious that the lower the BP regarded as the limit of normality, the less likely the occurrence of secondary effects of metabolism, or end-organ effects or complications in those classified as hypertensive. 24 HOUR CYCLE: One of the most specific characteristics of ABPM is the possibility of being able to discover modification or alteration of the 24 h cycle of BP. Non-dippers are classically defined as those who show a reduction in BP of less than 10/5 mmHg or 10% between the day (06.00-22.00 h) and the night, or an elevation in BP. In contrast, extreme dippers are those in whom the BP reduction is greater than 20%. CARDIOVASCULAR SYSTEM: The data remain inconclusive with regard to the existence of a consistent relationship between the lack of a nocturnal dip in blood pressure and target organ damage. As regards prognosis, it seems that an inversion of the day-night cycle is of pejorative significance. CEREBROVASCULAR SYSTEM: Almost all studies have shown that non-dippers had a significantly higher frequency of stroke than dippers. In contrast, too great a fall in nocturnal BP may be responsible for more marked cerebral ischaemia. RENAL SYSTEM: Non-dippers have a significantly elevated median urinary excretion of albumin. There is a significant correlation between the systolic BP and nocturnal diastolic BP, and urinary excretion of albumin. Various studies have confirmed the increased frequency of change in the 24 h cycle in hypertensive subjects at the stage of renal failure. DIABETES: BP abnormalities should be considered as markers of an elevated risk in diabetic subjects but cannot be considered at present as predictive of the appearance of micro-albuminuria or other abnormalities. ABPM is thus of interest in type I or type II diabetes both in the initial assessment and in the follow-up and adaptation of treatment. PHARMACO-THERAPEUTIC USES: The introduction of ABPM has truly changed the means and possibilities of approach to the study of the effects of anti-hypertensive medications, with new possibilities of analysis such as trough-peak ratio smoothness index, etc.

Autonomic nervous system activity in dipper and non-dipper essential hypertensive patients. What about sex differences?

OBJECTIVES: To compare the autonomic nervous system activity indexes obtained from photoplethysmography in dipper and non-dipper hypertensive patients and to seek a potential influence of sex on the relation between autonomic nervous system and the nocturnal decrease in blood pressure. METHODS: We studied 245 hypertensive patients, who underwent 24 h ambulatory blood pressure monitoring (ABPM), photoplethysmographic blood pressure recording, and echocardiography. Non-dipping patients were defined as those whose nocturnal decrease in systolic blood pressure (SBP), diastolic blood pressure (DBP), or both was less than 10% of the daytime blood pressure. Spectral powers of SBP, DBP and heart rate were obtained from photoplethysmographic recordings over three main frequency bands: very low frequency (0.005-0.05 Hz), low frequency (0.05-0.14 Hz) and high frequency (0.14-0.40 Hz). RESULTS: Because their ABPM were normal (less than 135/85 mmHg; n = 33), of poor quality (n = 22) or performed at a period too far from the photoplethysmographic recording (n = 17), 66 patients were excluded from the analysis. The remaining 179 patients comprised 117 dippers and 62 non-dippers. The groups did not differ regarding clinical and echocardiographic characteristics, irrespective of sex. Low-frequency spectral powers were significantly lower in non-dippers than in dippers, whatever the signal, whereas high-frequency spectral powers did not differ significantly between the groups. The nocturnal decrease in blood pressure increased with increasing low-frequency spectral powers, but was negatively correlated with high-frequency spectral powers. Multivariate linear regression analysis identified low-frequency spectral power of SBP and clinic DBP as independent factors determining the decrease in blood pressure. After adjustment for all significant covariates, the odds of being a non-dipper did not differ between men and women. CONCLUSION: A non-dipper profile seemed to be associated, in both men and women, with lower low-frequency spectral powers compared with those in dippers, suggesting impaired sympathetic arterial modulation.

Effects of individual risk factors on the incidence of cardiovascular events in the treated hypertensive patients of the Hypertension Optimal Treatment Study. HOT Study Group.

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study has provided information about cardiovascular events in 18790 hypertensives, subjected to pronounced blood pressure (BP) lowering for a mean of 3.8 years. The HOT study data have subsequently been analysed after stratification of the patients according to global cardiovascular risk, and it has been found that, despite intensive blood pressure lowering in all risk strata, morbid event rates increased with increasing risk stratum. OBJECTIVES: Previously analysed global risk strata were based on combinations of risk factors. The analyses presented here were intended to provide information on the relative role that the presence of each individual factor may have in increasing cardiovascular risk, despite good BP control. METHODS: Risk ratios (RR) for patients with and those without a risk factor were calculated with 95% confidence intervals (CI) using a Cox proportional hazard model, and adjusted for all variables except the one under examination. RESULTS: For all risk factors considered and for all types of event, RR were always greater than 1, indicating a greater risk in the presence, compared with that in the absence of each factor. The male gender was a statistically significant risk for cardiovascular (CV) events, CV and total mortality and particularly for myocardial infarction (MI); age > or = 65 years for CV events, stroke, CV and particularly total mortality; smoking for all events analysed, but particularly for total mortality (twice higher in smokers than in non-smokers); high serum cholesterol (> 6.8 mmol/l) for CV events, MI and CV mortality; high serum creatinine (> 155 micromol/l) for CV events, stroke, CV and total mortality; diabetes for CV events, stroke, total mortality and particularly CV mortality; and ischaemic heart disease for all events analysed. Adjusted RR were often close to or greater than 2. CONCLUSIONS: Each of the risk factors considered was found to be an important cause of residual risk, despite good BP control. These findings emphasize the importance of addressing other correctable risk factors, e.g. smoking, hypercholesterolaemia and diabetes, as well as rigorous control of blood pressure, and of initiating antihypertensive therapy before cardiovascular and renal damage becomes manifest.

Benefits of electronic pillboxes in evaluating treatment compliance of patients with mild to moderate hypertension.

OBJECTIVE: This study was designed to assess the compliance of hypertensive patients with a once-daily regimen of the angiotensin converting enzyme (ACE) inhibitor trandolapril and to evaluate the antihypertensive efficacy of the drug in relation to the time interval between taking the final dose and measuring the blood pressure (BP). DESIGN: After a 2-week wash-out period, hypertensive patients, recruited by cardiologists, received trandolapril 2 mg once daily in the morning for 4 weeks. METHODS: In order to assess compliance, each patient's supply of trandolapril capsules was presented in a pillbox that incorporated in its lid a microprocessor that recorded the date and time of each occasion that it was opened. BP was measured using validated semi-automatic devices, at the end of both the wash-out and the treatment period. RESULTS: A total of 590 patients entered the study. Compliance data were evaluable for 501 patients. Overall compliance, defined as the ratio of the number of openings recorded to the number of doses prescribed was less than 80, 80-100, and more than 100% in 17, 63 and 20% of patients, respectively. The average number (+/- SD) of missed doses was 4.5 +/- 8 (median 2). The average interval between successive openings was 25 h 07 min mean +/- 13 h (median 24 h). The average number of delayed doses (a delayed dose being defined as the box being opened 25-36 h after the previous occasion) was 5.6 +/- 3 (median 6). Patients living in the Paris area had more forgotten and delayed doses than those living in the provinces (7.9 versus 3.8 forgotten; P<0.0001 and 6.3 versus 5.5 delayed; P<0.005). Doses were forgotten and delayed more often during weekends than on weekdays. The greatest number of delayed doses occurred in those patients under 60 years of age (6.0 versus 5.2; P<0.01). Decreases in systolic blood pressure (SBP and diastolic blood pressure (DBP) were 20.3/12.8 mmHg, for patients whose final drug was taken on the same day as the BP measurement, and 18.9/11.2 mmHg for patients whose final dose was taken on the previous day. CONCLUSIONS: Electronic compliance monitoring allows refined analysis of the behaviour of hypertensive patients. In this study doses were missed and delayed frequently during the first month of treatment, depending on the patient's lifestyle.

Association between high heart rate and high arterial rigidity in normotensive and hypertensive subjects.

BACKGROUND: The dynamic elastic modulus of central arteries is very frequency-dependent Although resting heart rate is a potent independent risk factor for morbidity and mortality both from cardiovascular and from noncardiovascular disease, no link between tachycardia and arterial stiffness has ever been established. OBJECTIVE: To relate arterial stiffness to heart rate in a population with relatively low cardiovascular risk. METHODS: Pulse-wave velocity measurements and high-resolution echo-tracking techniques were used to determine the degree of arterial distension (of carotid and femoral arteries, and terminal aorta) and the velocity of the pulse wave (aorta and upper and lower limbs) at the same time as heart rate, in members of a large population of normotensive and hypertensive subjects in a multicenter study in Paris, Fleury-Merogis and Grenoble (France). RESULTS: A high heart rate was strongly associated with reduced distension and elevated pulse-wave velocity, even after adjustment for age and blood pressure. A high aortic pulse-wave velocity was also negatively associated with a low baroreflex sensitivity. The most significant associations between high heart rate and high arterial rigidity were found for the carotid artery, the thoracic aorta, and the lower limbs, but there was no significant result for the terminal aorta and the arm arteries. CONCLUSION: This study demonstrates that there is a statistically significant positive link between high heart rate and high arterial stiffness measured at the site of central and lower limb arteries. Since an elevated heart rate has been shown to be associated with cardiovascular risk, such findings may be relevant for future cardiovascular studies in epidemiology.

Influence of gender and age on preventing cardiovascular disease by antihypertensive treatment and acetylsalicylic acid. The HOT study. Hypertension Optimal Treatment.

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.

Non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity.

AIM: The objective of this study was to evaluate the relationship between non-invasive ambulatory blood pressure variability and cardiac baroreflex sensitivity in hypertensive patients. SUBJECTS AND METHODS: Ambulatory blood pressure measurements (15-min intervals for 24 h) and continuous blood pressure measurements (Finapres, 20 min at rest after a 10-min resting period) were performed in 123 untreated hypertensives (resting diastolic blood pressure > or = 90 mmHg; 80 males, 43 females; mean +/- SD age 49 +/- 12 years, range 19-73). Fourier series were used to model 24-h blood pressure profiles (four harmonics). Ambulatory blood pressure variability was assessed by determination of the residuals in each 24-h blood pressure profile (measured minus predicted pressures). Resting blood pressure variability was defined as the SD of the mean Finapres value. Baroreflex sensitivity was evaluated by automatic detection of blood pressure and pulse interval sequences of > or = 3 beats when systolic blood pressure and pulse interval sequences changed in the same direction (increase or decrease: 1 mmHg for systolic blood pressure and 4 ms for RR interval), and was assessed as the slope of the regression line for each sequence. RESULTS: Ambulatory systolic blood pressure variability increased with age (r = 0.28*) and systolic pressure (r = 0.44**). Baroreflex sensitivity (increasing systolic pressure/pulse interval) decreased significantly with age (r = -0.48**) and systolic pressure (r = -0.23**), and was significantly related to increased ambulatory blood pressure variability (r = -0.33**). In a multivariate stepwise analysis the relationship between ambulatory blood pressure variability and baroreflex sensitivity (increasing systolic pressure/pulse interval) was statistically independent of age and systolic pressure (R = 0.55, P<0.001); this relationship was not observed with the corresponding decreasing sequence. CONCLUSIONS: This study shows that in uncomplicated hypertension, ambulatory blood pressure variability is related to baroreflex sensitivity independently of the blood pressure level. This finding has prognostic implications for this non-invasive measurement, which needs to be confirmed by large longitudinal studies.