Metabolic disturbances after acute vascular events: a comparative study of acute coronary syndrome and ischaemic atherothrombotic stroke.

OBJECTIVE: This pilot study aimed to compare metabolic disturbances, particularly insulin resistance (IR) and cardiovascular risk factors (CRFs), following two types of acute vascular atherothrombotic disease events: ischaemic atherothrombotic stroke (AS); and acute coronary syndrome (ACS). DESIGN AND METHODS: A total of 110 non-diabetic patients presenting with either AS (n=55) or ACS (n=55) were included in our prospective comparative study, and matched for age and gender. IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR) method, and each patient's personal and family history were also recorded. RESULTS: IR was significantly higher in the ACS vs AS group (HOMA-IR index 2.17±1.90 vs 1.50±0.81, respectively; P=0.03). The AS group had a significantly higher prevalence of personal history of hypertension (51% vs 31%; P=0.03), while current smoking was more prevalent in the ACS group (30% vs 18%; P=0.04). There were no significant differences between the two groups as regards any other CRFs. CONCLUSION: The distribution of CRFs varied depending on the vascular event, and metabolic disturbances differed according to the atherothrombotic disease. IR was greater after ACS than AS.

Effects of candesartan cilexetil on carotid remodeling in hypertensive diabetic patients: the MITEC study.

In hypertension and diabetes, early structural changes of the arterial wall precede or support atherosclerosis. There is evidence that some antihypertensive drugs exert an antiathero-sclerotic effect. Over 36 months, we investigated the effect of candesartan cilexetil (CC) on the common carotid intima-media thickness (IMT) vs amlodipine besylate (AML) in patients with type 2 diabetes and mild to moderate essential hypertension. After a 4-week wash-out period, 209 patients were randomized to either CC 8 mg or AML 5 mg once daily for a minimum of 1 month, after which, if BP was not normalized, the dosage was doubled, followed by the addition of hydrochlorothiazide 12.5 mg if necessary. No significant differences were observed between the two groups for change in IMT at M12 (-0.001 vs -0.027 mm/year for CC and AML respectively, p = 0.425), at M24 (-0.033 vs -0.019 mm per year respectively, p = 0.442), and at the last visit (-0.016 vs -0.039 mm per year respectively, p = 0.549). Within the group, comparisons did not show a significant difference in changes in IMT from baseline to the three visits. At the last visit, IMT regression was observed in 52.2% of patients receiving CC and in 51.3% of those receiving AML (p = 0.908). The augmentation in carotid lumen diameter from baseline was statistically greater in the AML group at the last visit (p = 0.034). BP variations during the study were similar in the two groups. The results of this study show that CC and AML treatments may alter identically the natural progression of carotid IMT in hypertensive type 2 diabetic patients.

[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.

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).

A placebo-controlled comparison of the efficacy and tolerability of candesartan cilexetil, 8 mg, and losartan, 50 mg, as monotherapy in patients with essential hypertension, using 36-h ambulatory blood pressure monitoring.

This double-blind, randomised, controlled study compared the efficacy of candesartan cilexetil 8 mg (n = 87) and losartan 50 mg (n = 89), once daily for 6 weeks, relative to placebo (n = 80) in patients with mild-to-moderate essential hypertension (diastolic blood pressure (DBP): 95-115 mmHg). Ambulatory BP measurements were done every 15 min over 36 h. At the end of the 6-week treatment, the mean change in DBP between the baseline and the 0-24-h period after the last dose of study medication was greater in patients receiving candesartan cilexetil 8 mg (-7.3 mmHg +/- 6.9 mmHg) compared with losartan 50 mg (-5.1 mmHg +/- 4.9 mmHg) (p < 0.05) or placebo (0.3 mmHg +/- 6.5 mmHg) (p < 0.001). The mean change in systolic BP (SBP) during this time was greater in patients receiving candesartan cilexetil 8 mg (-10.8 mmHg +/- 11.3 mmHg), or losartan 50 mg (-8.8 mmHg +/- 8.9 mmHg) than placebo (1.2 mmHg +/- 9.9 mmHg) (p < 0.001). Candesartan cilexetil 8 mg was associated with a greater reduction in DBP and SBP, relative to placebo, when compared with losartan 50 mg, during both daytime and night-time, and between 12 and 24 h after dosing (p < 0.001). Both active treatments were well tolerated. In patients with mild-to-moderate essential hypertension, candesartan cilexetil 8 mg therefore had greater, more consistent antihypertensive efficacy throughout the day and the night, and long-lasting efficacy after the last dose, compared with losartan 50 mg. This greater efficacy is maintained with an excellent tolerability associated with members of the angiotensin Il type 1-receptor blocker class.

[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.

Validation of the AGILIS ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults.

BACKGROUND: We evaluated the clinical validity of the AGILIS ambulatory blood pressure monitor according to the European Society of Hypertension International Protocol. METHODS: The blood pressure (BP) was measured at the same arm by two certified observers using two mercury columns and a double stethoscope, then by the volunteer with the automatic device, these measurements were done seven times sequentially using 33 volunteers. For the randomization of the patient, one ABPM measure was compared to the mean of three manual measures. Then, we had three ABPM measures and four manual measures. Each ABPM measure, being compared to two manual measures. Blood pressure readings and recordings were blinded. Position of the subjects was standardized. RESULTS: Phase 1: To pass phase 1, the device had to have at least 25 of the 45 measurements within 5 mmHg, 35 within 10 mmHg or 40 within 15 mmHg of the comparative observer measurements. The AGILIS monitor had 35 measurements lying within 5 mmHg, 42 within 10 mmHg and 45 within 15 mmHg for systolic BP (SBP), 35 within 5 mmHg, 44 within 10 mmHg and 45 within 15 mmHg for diastolic BP (DBP). It passed the criteria for SBP and DBP. Phase 2: To pass phase 2.1, a device must have at least 60 of 99 measurements within 5 mmHg, 75 within 10 mmHg and 90 within 15 mmHg of the comparative observer measurements, and in addition must also have either 65 within 5 mmHg and 80 within 10 mmHg, or 65 within 5 mmHg and 95 within 15 mmHg, or 80 within 10 mmHg and 95 within 15 mmHg. The AGILIS monitor had 78 measurements within 5 mmHg, 91 within 10 mmHg and 96 within 15 mmHg for SBP; and 70 measurements within 5 mmHg, 92 within 10 mmHg and 96 within 15 mmHg for DBP. It passed the criteria for SBP and DBP. For phase 2.2 using the AGILIS monitor, 27 subjects had at least two of the differences within 5 mmHg and none had any differences within 5 mmHg for SBP; 27 subjects had at least two of the differences within 5 mmHg and three subjects had no differences within 5 mmHg for DBP. The results are in concordance with the requested criteria for phase 2.2. CONCLUSION: Thus the AGILIS device fulfils the validation criteria of the international protocol.

Structural and functional abnormalities of large arteries in the Turner syndrome.

OBJECTIVE: To analyse the structural and functional abnormalities in the large arteries in women with the Turner syndrome. METHODS: Aortic stiffness (assessed by means of the carotid femoral pulse wave velocity), level of amplification of the carotid pressure wave (by applanation tonometry), and carotid remodelling (by high resolution ultrasound) were studied in women with the Turner syndrome. Clinical and ambulatory blood pressures were taken into account in the analysis. Thus, 24 patients with the Turner syndrome and 25 healthy female subjects matched for age were studied. RESULTS: Women with the Turner syndrome had a higher augmentation index than the controls (Turner, mean (SD) 0.04 (0.14) v controls, -0.14 (0.13), p < 0.001) but a lower peripheral pulse pressure (39 (8) mm Hg v 47 (11) mm Hg, p = 0.010 in the clinic; 44 (5) mm Hg v 47 (6) mm Hg, p = 0.036 during the 24 hour ambulatory recording). The luminal diameter of the common carotid artery and the carotid-femoral pulse wave velocity were similar in the two groups, whereas carotid intima-media thickness tended to be higher in women with the Turner syndrome (0.53 (0.06) mm v 0.50 (0.05) mm, p = 0.06). After correction for body surface area, carotid intima-media thickness and pulse wave velocity were higher in women with the Turner syndrome. CONCLUSIONS: Vascular abnormalities observed in the Turner syndrome are implicated in the origin of the cardiovascular complications that occur in this syndrome. These abnormalities are morphological but also functional. An increase in the augmentation index can be explained in part by the short height of these patients.

[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.

Detection of masked hypertension by home blood pressure measurement: is the number of measurements an important issue?

BACKGROUND: Office blood pressure (OBP) and home blood pressure (HBP) enable the identification of patients with masked hypertension. Masked hypertension is defined by normal OBP and high HBP and is known as a pejorative cardiovascular risk factor. OBJECTIVE: The objective was to evaluate in the SHEAF study the influence of the number of office or home blood pressure measurements on the classification of patients as masked hypertensives. METHODS: Patients with OBP <140/90 mmHg (mean of six values: three measurements at two separate visits, V1 and V2) and HBP >135/85 mmHg (mean of all valid measurements performed over a 4-day period) were the masked hypertensive reference group. The consistency of the classification was evaluated by using five definitions of HBP values (mean of the 3, 6, 9, 12 and 15 first measurements) and two definitions of OBP values (mean of three measurements at V1 and mean of three measurements at V2). RESULTS: Among the 4939 treated hypertensives included in the SHEAF study, 463 (9.4%) were classified as masked hypertensives (reference group). By decreasing the number of office or home measurements, the prevalence of masked hypertension ranged from 8.9-12.1%. The sensitivity of the classification ranged from 94-69% therefore 6-31% of the masked hypertensives were not detected. The specificity ranged from 98-94% therefore 1-6% of patients were wrongly classified as masked hypertensives. CONCLUSION: A limited number of home and office BP measurements allowed the detection of masked hypertension with a high specificity and a low sensitivity. A sufficient number of measurements (three measurements at two visits for OBP and three measurements in the morning and in the evening over 2 days for HBP) are required to diagnose masked hypertension.

Oxidative stress and baroreflex sensitivity in healthy subjects and patients with mild-to-moderate hypertension.

Decreased baroreflex sensitivity (BRS) is a prognostic marker in essential hypertension. Animal experiments suggest that decreased BRS is related to increased oxidative stress. Our study was aimed at testing whether oxidative stress, estimated by isoprostane 15-F(2t)-IsoP urinary levels, is correlated to BRS variation in healthy subjects as well as in patients suffering from essential hypertension. Urinary 15-F(2t)-IsoP levels and BRS were evaluated in two groups of subjects: healthy volunteers (n=64) and patients with untreated mild-to-moderate hypertension (n=33). Data were analysed in 61 and 31 subjects, respectively, BRS analysis being impossible in three and two subjects, respectively. 15-F(2t)-IsoP levels were measured using gas chromatography/mass spectrometry. BRS was measured using the sequence method [PS+/RR+ and PS-/RR-] and crossspectral analysis (CSP) (MF gain) at rest, lying down. No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and BRS (sequence method and CSP) in either healthy controls or hypertensive patients. Our study shows that oxidative stress is not involved in interindividual variations of BRS in healthy subjects and patients suffering from mild-to-moderate hypertensionJournal of Human Hypertension (2004) 18, 517-521. doi:10.1038/sj.jhh.1001684 Published online 12 February 2004

Pulse pressure responses in patients treated with Valsartan and hydrochlorothiazide combination therapy.

In a randomized, double-blind, parallel-group study of middle-aged and elderly patients, we examined the effects of treatment with the angiotensin receptor blocker valsartan (Val) in combination with hydrochlorothiazide (HCTZ) on pulse pressure (PP). After a 2-week washout period, patients entered a 4-week single-blind Val 160 mg once daily run-in period before randomization to one of three treatment groups: Val 160 mg (n = 666), Val 160 mg/HCTZ 12.5 mg (n = 670) or Val 160 mg/HCTZ 25 mg (n = 666), once daily for eight weeks. Sitting PP at baseline was similar in all groups. From baseline to randomization, Val monotherapy reduced PP by 4.7 +/- 10.2 mmHg (mean +/- SD). At the end of the study, overall reductions in PP were 6.7 mmHg for Val 160/HCTZ 12.5 and 7.5 mmHg for Val 160/HCTZ 25. Val monotherapy reduced PP in mild-to-moderate hypertensive patients. Val combined with HCTZ provides an additional dose-related reduction in PP.

[Estimation of the number of patients treated for hypertension, diabetes or hyperlipidemia in France: FLAHS study 2002]. / Estimation du nombre des sujets traités pour une hypertension, un diabète ou une hyperlipidémie en France: étude FLAHS 2002.

The study used a cross-sectional survey of the general population living in metropolitan France in April 2002. A national sample of 5,000 adults, representative of the French population, 15 years of age or older, received at their home a questionnaire mailed by SOFRES medical. The sample was designed to provide estimates of the prevalence of hypertension in the general population and in persons older than 60 years of age, a subgroup on which prevalence of treated cardiovascular risk factors is unknown in France. The questionnaire included questions related to diagnosis of hypertension, awareness of their usual BP, current SBP/DBP values, prescribed medicine for hypertension dyslipidemia and diabetes. In FLAHS 2002, a number of 3,499 (70%) questionnaires were suitable for analysis. Estimates of prevalence were standardized by the direct method to the age distribution of the French population given by the 1999 national French census (INSEE 2000). Analysis on 2,363 subjects older than 35 years and indicates that 35% are currently treated for one or more risk factor. Overall, 8,036,000 received antihypertensive medication, 1,877,000 were treated for diabetes and 6,074,000 for dyslipidemia. Prevalence of treated hypertension increased with age from from 4.2% (35-44 years) to 51.8% (> 75 years) and 70% of treated hypertensives were older than 60 years. Subjects treated for two risk factors were 3,201,000 and those treated for three risk factors were 640,000. The FLAHS 2002 represents the best available data to estimate the prevalence of treated patients for a cardiovascular risk factor in the general French population. Thirty-five percent of the population 35 years of age or older representing around 11 millions persons were taking medications for the treatment of hypertension, diabetes or dyslipidemia in France.