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Clinic-ambulatory blood pressure (BP) difference is influenced by patients- and device-related factors and inadequate clinic-BP measurement. We investigated whether nonadherence to antihypertensive medications may also influence this difference in a post hoc analysis of the DENERHTN trial (Renal Denervation for Hypertension). We pooled the data of 77 out of 106 evaluable patients with apparent resistant hypertension who received a standardized antihypertensive treatment and had both ambulatory BP and drug-screening results available at baseline after 1 month of standardized triple therapy and at 6 months on a median of 5 antihypertensive drugs. After drug assay samplings on study visits, patients took their antihypertensive treatment under supervision immediately after the start of the ambulatory BP recording, and supine clinic BP was measured 24 hours post-dosing; both allowed to calculate the clinic minus daytime ambulatory systolic BP (SBP) difference (clinic-SBP–day-SBP). A total of 29 (37.7%) were found nonadherent to medications at baseline and 38 (49.4%) at 6 months. At baseline, the mean clinic-SBP–day-SBP difference in the nonadherent group was 12.7 mm Hg (95% CI, 7.8–17.7 mm Hg, P P =0.947). Similar observations were made at 6 months. Using receiver operating characteristics curves, we found that a 6 mm Hg cutoff of clinic-SBP–day-SBP difference had 67% sensitivity and 69% specificity to predict nonadherence to the triple therapy at baseline. In conclusion, a large clinic-SBP–day-SBP difference may help discriminating between adherence and nonadherence to treatment in patients with resistant hypertension. Clinical Trial Registration— URL: https://www.clinicaltrials.gov . Unique identifier: NCT01570777.

Resume Objectifs Cette etude avait pour objectifs : (1) de mesurer l’observance des hommes et des femmes ayant une hypertension arterielle (HTA) non controlee, et (2) d’identifier, dans chaque sexe, les facteurs associes a la non-observance aux anti-HTA. Patients et methodes Les medecins generalistes (MG) devaient inclure les deux premiers patients des 2 sexes ayant une HTA non controlee sous traitement. L’observance etait estimee par le MG et avec l’auto-questionnaire (AQ) du Comite francais de lutte contre l’HTA. Les facteurs associes a la non-observance selon l’AQ ont ete selectionnes par analyse de regression logistique en pas a pas type stepwise , analyse realisee independamment chez les hommes et chez les femmes. Resultats Au total, 1630 hommes et 1612 femmes ont ete inclus dans l’analyse. L’observance au traitement etait significativement meilleure chez les femmes ou quand elle etait estimee par les MG. Le manque de motivation etait le premier facteur associe a une mauvaise observance dans les deux sexes. Considerer l’HTA comme une simple anomalie et non comme une maladie pouvant conduire a des troubles cardiaques ou cerebraux etait le deuxieme parametre commun aux deux sexes. Les autres facteurs communs etaient : rencontrer des difficultes financieres a faire face a ses besoins dans le mois et l’absence d’un depistage regulier du cancer du colon. Conclusion L’observance au traitement est meilleure chez les femmes hypertendues non controlees. La mauvaise observance est principalement associee a des facteurs non cliniques. Le manque de motivation est l’element le plus important.

High blood pressure is a frequent pathology with many cardiovascular complications. As highlighted in guidelines, the therapeutic management of hypertension relies on non-pharmacological measures, which are diet and regular physical activity, but both patients and physicians are reluctant to physical activity prescription. To acquire the conviction that physical activity is beneficial, necessary and possible, we can take into account some fundamental and clinical studies, as well as the feedback of our clinical practice. Physical inactivity is a major risk factor for cardiovascular morbidity and mortality, and hypertension contributes to increase this risk. Conversely, regular practice of physical activity decreases very significantly the risk by up to 60%. The acute blood pressure changes during exercise and post-exercise hypotension differs according to the dynamic component (endurance or aerobic and/or strength exercises), but the repetition of the sessions leads to the chronic hypotensive benefit of physical activity. Moreover, physical activity prescription must take into account the assessment of global cardiovascular risk, the control of the hypertension, and the opportunities and desires of the patient in order to promote good adherence and beneficial lifestyle change.

The use of "snus" (smokeless tobacco) can be detrimental to health. Snus delivers rapidly high doses of nicotine which can lead to addiction. The use of snus increases the risk of myocardial infarction and stroke. Nicotine substitution therapy as well as bupropion and varenicline reduce withdrawal symptoms and tobacco craving during snus cessation. However, they have been shown not to assist in long-term abstinence. Information concerning potential cardiovascular hazards of snus must be incorporated into health educational programs in order to discourage its use. Snus is not a recommended product to help stop smoking.

The aim of this study was (1) to measure adherence in males and females with uncontrolled hypertension, and (2) to identify factors associated with non-adherence to antihypertensive medication.Each general practitioner (GP) should include the first two male and the first two female patients with uncontrolled treated hypertension. Adherence to antihypertensive treatment was estimated by the GP and using the French League Against High blood pressure (FLAH) self-administered questionnaire. A stepwise logistic regression analysis was used to identify factors associated with non-adherence on the FLAH scale, independently in males and in females.A total of 1630 males and 1612 females were included in the analysis. Adherence to treatment was significantly better in females or when estimated by the GP. Lack of motivation was the first factor associated with poor adherence in both sexes. Considering hypertension as a simple anomaly and not a disease that can lead to cardiac or cerebral disorders was the second common parameter in both sexes. Other common factors were: having monthly periods of financial difficulties in facing his/her needs and absence of regular screening for colon cancer.Adherence to treatment is better in uncontrolled hypertensive females. Poor adherence is mainly associated with non-clinical factors. The lack of motivation is the most important element.

Correspondance : Jacques Blacher Unite hypertension arterielle, prevention et therapeutique cardiovasculaire Centre de diagnostic et de therapeutique Hotel-Dieu, AP-HP 1, place du Parvis Notre-Dame 75181 Paris cedex 4 jacques.blacher@htd.aphp.fr Membres du groupe de travail : Jacques Amar, Athanase Benetos, Jacques Blacher (redacteur), Guillaume Bobrie, Bernard Chamontin, Xavier Girerd, Jean-Michel Halimi, Daniel Herpin, Claire Mounier-Vehier, Jean-Jacques Mourad, Jean Ribstein, Bruno Schnebert, Bernard Vaisse.

This multicentre study was aimed at comparing the trough effect of telmisartan and perindopril on diastolic blood pressure (DBP), using self blood pressure measurement (SBPM). A second objective was to compare the data obtained from SBPM with those provided by automatic office BP measurement. A total of 441 mild-to-moderate hypertensive patients were randomised to receive either telmisartan 40 mg or perindopril 4 mg for a period of 12 weeks. Patients whose clinic DBP remained higher than or equal to 90 mmHg at the end of the 6th week (W6) were given a double-dose regimen. Office BP and SBPM were performed at baseline (W0), at W6 and at week 12 (W12), both with the same automatic device. A greater diminution of trough DBP was obtained with telmisartan (-6.6+/-6.7 mmHg) than with perindopril (-5.1+/-7.0 mmHg; P=0.018). Regarding clinic BP, the same results were observed. Doubling dose was significantly less frequent with telmisartan (41%; n=85) than with perindopril (55%; n=115, P=0.005). Mean values of SBPM were lower than office BP values, with a difference of a greater importance at W0 than at W12: 6.6 vs 4.7 mmHg for systolic blood pressure (P

Background : Acetylsalicylic acid, or aspirin, is widely used in secondary prevention of coronary artery diseases, but the inhibition of platelet aggregation is not uniform in all individuals. Objective : To investigate the prevalence of aspirin resistance at rest and during exercise in coronary artery disease patients. Materials and methods : Fifty patients with stable coronary artery disease were prospectively studied. All patients received aspirin (75–300 mg/day for >1 month) and no other antiplatelet therapy. Aspirin resistance was studied, at rest and immediately after a stress test, using the standardized platelet function analyzer (PFA-100®, Dade-Behring). Aspirin resistance was defined as a normal collagen/epinephrine closure time ( Results : Ten patients (20%) were aspirin-resistant at rest. Out of the 40 patients who were aspirin-sensitive at rest, 9 (22%) were aspirin-resistant immediately after the exercise stress test. There were no differences in aspirin sensitivity regarding gender, age, diabetes, hypertension, dyslipidemia, platelet count, medical treatment or number of the coronary arteries involved. Conclusions : Aspirin resistance is detected, at rest, in 20% of our patients with stable coronary artery disease. Aspirin treatment does not seem to protect against exercise-induced platelet activation in 22% of such patients, despite aspirin sensitivity at rest.

The authors reviewed some of the most relevant studies dedicated to the assessment of the effects of the antihypertensive drugs on the stress-induced cardiovascular changes. The rises in both blood pressure and heart rate turned out not to be significantly altered by calcium channel blockers, ACE inhibitors, moxonidine, nor beta-blockers, whereas they seemed to be slightly blunted by alpha-blocking drugs. However, since baseline blood pressure was significantly lower in treated hypertensives than in placebo-given patients, all antihypertensive drugs eventually resulted in a lower blood pressure level during stress, as compared with untreated patients. Regarding white coat effect, which has to be considered as a very particular stress, it appeared to be lowered to the same extent by placebo and antihypertensive drugs; moreover, its changes were not associated with any clinical beneficial effect.

High blood pressure is a frequent pathology with many cardiovascular complications. As highlighted in guidelines, the therapeutic management of hypertension relies on non-pharmacological measures, which are diet and regular physical activity, but both patients and physicians are reluctant to physical activity prescription. To acquire the conviction that physical activity is beneficial, necessary and possible, we can take into account some fundamental and clinical studies, as well as the feedback of our clinical practice. Physical inactivity is a major risk factor for cardiovascular morbidity and mortality, and hypertension contributes to increase this risk. Conversely, regular practice of physical activity decreases very significantly the risk by up to 60%. The acute blood pressure changes during exercise and post-exercise hypotension differs according to the dynamic component (endurance or aerobic and/or strength exercises), but the repetition of the sessions leads to the chronic hypotensive benefit of physical activity. Moreover, physical activity prescription must take into account the assessment of global cardiovascular risk, the control of the hypertension, and the opportunities and desires of the patient in order to promote good adherence and beneficial lifestyle change.

Resume La variabilite intra-individuelle de la pression arterielle est tres grande : elle tient a des phenomenes biologiques spontanes (systeme sympathique, mouvements respiratoires) ou induits (stress physiques et psychosensoriels), mais aussi a des facteurs technologiques lies a l'appareil de mesure ou au medecin. Les statisticiens ont quantifie l'importance de la variabilite tensionnelle : une variation de 35 mmHg pour la systolique et de 17 mmHg pour la diastolique, entre deux consultations, a 95 chances sur 100 de n'etre due qu'a la variabilite spontanee des chiffres tensionnels. Par ailleurs, si l'on selectionne un groupe d'hypertendus dont la pression arterielle systolique moyenne est de 160 mmHg, la simple regression vers la moyenne doit faire attendre lors d'une mesure ulterieure, une diminution spontanee moyenne de 9 mmHg. Le praticien doit donc s'attacher a gerer au mieux l'imprecision qui entoure la mesure de la pression arterielle. Il a pour cela, a sa disposition, trois moyens essentiels : l'appreciation du contexte clinique (le moindre signe de souffrance viscerale authentifie la realite de l'HTA et justifie la mise en place d'un traitement pharmacologique actif) ; le respect rigoureux des recommandations editees pour la mesure clinique de la pression arterielle (les sources d'erreur sont aujourd'hui bien repertoriees et souvent faciles a corriger) ; enfin, les methodes de mesure “sophistiquees” (automesure, enregistrement automatique ambulatoire ou semi-ambulatoire, epreuve d'effort) peuvent dans certaines circonstances, apporter un complement d'informations tres utiles.

Resume L'hypertrophie ventriculaire gauche (HVG) est frequemment observee chez l'hypertendu. Son depistage ne peut se faire que par l'echocardiogramme qui, sous reserve d'une bonne qualite technique (80% des cas) a une excellente sensibilite (93%) et une excellente specificite (95%). Le plus souvent, l'HVG se presente sous une forme concentrique (rapport h/r superieur a 0,45). Les mecanismes d'apparition de l'HVG chez l'hypertendu sont essentiellement de deux ordres : mecanique et hormonal ; les theories recentes de Weber et Brilla conduiraient a rendre le facteur mecanique responsable de l'hypertrophie myocitaire et les facteurs hormonaux, de la proliferation du tissu de soutien. Bien que correspondant au depart a un processus d'adaptation, l'HVG a des consequences nefastes : troubles du rythme, ischemie myocardique, anomalies de la relaxation ventriculaire gauche. Elle est aujourd'hui classiquement reconnue comme un facteur de risque independant, grevant lourdement le pronostic de l'hypertendu. Il parait donc logique de chercher non seulement a normaliser les chiffres tensionnels, mais aussi a reduire la masse ventriculaire gauche. Les etudes de regression actuellement publiees appellent toutefois un certain nombre de reserves d'ordre methodologique.

The use of "snus" (smokeless tobacco) can be detrimental to health. Snus delivers rapidly high doses of nicotine which can lead to addiction. The use of snus increases the risk of myocardial infarction and stroke. Nicotine substitution therapy as well as bupropion and varenicline reduce withdrawal symptoms and tobacco craving during snus cessation. However, they have been shown not to assist in long-term abstinence. Information concerning potential cardiovascular hazards of snus must be incorporated into health educational programs in order to discourage its use. Snus is not a recommended product to help stop smoking.

The introduction of beryllium as a neutron multiplier in ceramic blankets of thermonuclear fusion reactors may give rise to the following compatibility problems: (i) oxidation of Be by ceramics (lithium aluminate and silicates) or by water vapour; (ii) interaction between beryllium and austenitic and martensitic steels. The studies were done in contact tests under vacuum and in tests under wet sweeping helium. The contact tests under vacuum have revealed that the interaction of beryllium with ceramics seems to be low up to 700°C, the interaction of beryllium with steels is significant and is characterized by the formation of a diffusion layer and of a brittle Be-Fe-Ni compound. With type 316 L austenitic steel, this interaction appears quite large at 600°C whereas it is noticeable only at 700°C with martensitic steels. The experiments carried out with sweeping wet helium at 600°C have evidenced a slight oxidation of beryllium due to water vapour which can be enhanced in the front of uncompletely dehydrated ceramics.

The clinical pharmacological and therapeutic working group was particularly impressed by twelve recent publications relative to its various themes of interest. Two studies were made of the prognostic impact of non-observance of treatment which seems to be associated with an extra-mortality even when the treatment is placebo: the probable explanation is that the non-observance of drug therapy is also associated with the non observance of dietary/life style measures and with cognitive dysfunction associated with more severe cardiac disease. A recent study on n-acetyl-cysteine has rekindled the debate on this substance for preventing nephrotoxicity of radiological contrast used during angioplasty in high risk patients. The risks of AINS drug therapy has been reassessed. The increased risk of myocardial infarction is confirmed with celecoxib but not with "classical" AINS drugs if not prescribed for more than one year and without aspirin. With respect to lipid-lowering drugs, should statins be prescribed to attain a target value of LDL-cholesterol or to attain a given reduction in LDL-cholesterol? The death knell of fibrates has more or less been rung by the results of the FIELD study and the real value of OMEGA-3 drugs should be reassessed by good quality prospective studies. In the domain of hypertension, the recent arrival of aliskiren, the first of the antirenin drugs, is noteworthy although its role in the therapeutic strategy, remains to be defined. Finally, a comment is made on the results of the TROPHY study which suggest value in the possible prevention of hypertension with angiotensin II inhibitors in patients at risk of developing hypertension.

Although the year 2005 has reinforced the therapeutic advances of 2004, with confirmation of certain concepts, the 'coxib affair' has continued to provoke arguments between pharmaceutical companies, licensing agencies as well as patients, some of whom have amalgamated into consumer groups to reject en masse placing any responsibility on the prescribers in favour of an attack on the drug licensing process itself. Among the cardiovascular drugs that will soon be licensed, only ivabradine in stable angina, and remodulin in primary pulmonary arterial hypertension are new. The therapeutic advances in 2005 regarding platelet aggregation and blood coagulation have been significant, in the human, scientific and commercial context, while hypertension has not been ignored. Another new development is the ever more precise notion of the metabolic syndrome, a target of choice for the pharmaceutical industry. The potential range of applications has been widened to include obesity, hypertension, diabetes, HDL cholesterol... The licensing authorities find themselves facing a hurdle to overcome, with novel combinations of drugs (ACE inhibitors, calcium blockers/statins, statins/aspirin, ARA2/calcium blockers...).

Beta-blockers have been considered for decades as effective agents in preventing coronary events in hypertensive patients. Actually, the scrutiny of the available data arises some doubts over the real value of this pharmacological class. In primary prevention, the clinical benefits of beta-blockers are poorly documented: the studies conducted against placebo (MRC, IPPPSH...) did not show any significant differences regarding the rate of coronary events (except within non smokers); moreover, the beneficial effect of propranolol in preventing sudden deaths and silent myocardial infarctions has been reported byjust one retrospective analysis. Likewise in HAPPHY study, the comparison with diuretics did not emphasize a clear superiority of one of both classes; the better effect of metoprolol regarding overall mortality and fatal coronary events was shown in the pecular subset MAPHY, only. Furthermore, in elderly people, HEP, MRC OA and STOP studies did not find any significant effect of beta-blockers in preventing coronary events, as compared with placebo. However, SHEP study, which involved patients older than 60 years with isolated systolic hypertension receiving first a diuretic, then a beta-blocker(atenolol) in 1/4 of the cases, demonstrated a significant reduction versus placebo both in strokes and in coronary events. Finally, in UKPDS, CAPP, LIFE and CONVINCE studies, atenolol turned out to have a similar efficacy as captopril, losartan and verapamil, in preventing ischemic heart disease. Among the numerous published meta-analyses, that of Psaty pointed out the absence of a primary cardioprotective effect by beta-blockers; more recently, that of Carlberg, emphasized atenolol given alone as the first-line drug to fail in significantly reducing coronary events and strokes. In secondary prevention, some more convincing data may be found in the literature, regarding post myocardial infarction patients (meta-analyses of Staessen, 1982, Yusuf, 1985 and Soriano, 1997), as well as those with stable angina (BIP study in diabetics) or silent ischemia (ASIST study: significant reduction in number and duration of ischemic events by atenolol). Moreover, INVEST study recently showed atenolol and verapamil to have an equivalent efficacy in the hypertensive patients with stable coronary artery disease. Last, hypertension should be reminded as resulting in many cases of heart failure, a pathology where beta-blockers have clearly demonstrated their beneficial effects.

Value of systematic dosage of biological markers of inflammation for the prognosis at 12 months of patients undergoing programmed coronary angioplasty Systematic dosage of proteins of inflammation has been suggested for assessing the prognosis of athero-thrombotic diseases. The authors undertook a study of plasma C-reactive protein (CRP) and interleukin 6 (IL-6) for evaluating the prognosis of patients undergoing programmed coronary angioplasty. A prospective monocentric study of 117 patients (65 +/- 8 years) was divided into a control group of 28 patients undergoing coronary angiography (Group 1) and 89 patients undergoing programmed coronary angioplasty (Group 2). Serum IL-6 and CRP levels were measured before arterial puncture and at H12 and H24 after coronary catheterisation. The follow-up period was 12 months. The angioplasty did not significantly increase CRP and IL-6 concentrations compared with coronary angiography. Twenty patients (Group 2) (22%) suffered a cardiovascular event in the 12 months' follow-up. These patients had significantly higher CRP levels at H0, H12 and H24 after coronary angioplasty than those who had uncomplicated outcomes. This was not observed for IL-6 concentrations because of the wide dispersion of the results obtained. Increased CRP concentrations between H0 and H24 was also a good predictive factor independently of high basal CRP levels potentially due to other causes than atheroma. Coronary angioplasty is associated with increased CRP at H0, H12 and H24. These values are correlated with the risk of future events at 6 and 12 months. This information is easily obtained and should help management of these patients.

Atrial remodeling has been demonstrated to be associated with rapid atrial pacing or with hemodynamic overload. It may refer to changes in electrophysiological properties and/or in structure and function. Hemodynamic overload of the atria has been found to be an important pathogenic factor of atrial fibrosis, providing a morphological substrate for atrial fibrillation. This finding could partly account for the high risk of stroke in hypertensive patients. In this respect, a strong involvement of the renin angiotensin system has been suggested by experimental, clinical and epidemiological data. Thus, prevention or even partial regression of atrial remodeling could be reasonably expected from ACE-inhibitors and angiotensin 2-blockers.

The year 2004 was not marked by major pharmacological advances, but by confirmation of previous "evidence". Several innovative drugs for stable angina (ranolazine, ivabradine), some interesting results in acute coronary syndrome (PROVE IT study), some classic concepts (cannabinoid receptors and their antagonists such as rimonabant) applied to novel indications (treatment of obesity), hopes for the "sartans" revived in the light of new evidence (VALUE study), advances in the management of diabetes and hypertension (ASCOT and CARDS studies), nebivolol which is not just a betablocker but also produces the NO radical (is this why it decreased the mortality of heart failure in the elderly in the SENIOR study?). In contrast, although Chronadalate did not live up to expectations for coronary insufficiency, the year was marked above all by the much heralded withdrawal of Vioxx for increasing cardiovascular risk. The old adage: primum non nocere springs to mind.

Stress hyperglycaemia increases the risk of mortality after acute myocardial infarction in diabetic and in non-diabetic patients. We aimed to determine the contribution of admission plasma glucose and HbA(1c) on post-acute myocardial infarction prognosis.Admission plasma glucose and HbA(1c) were simultaneously measured in all patients consecutively hospitalized for acute myocardial infarction. Patient survival was measured on 5 and 28 days after admission. Patients were defined as having 'previously diagnosed diabetes' (personal history of diabetes defined using ADA 1997 criteria), 'no diabetes', those without previously diagnosed diabetes and HbA(1c) below 6.5%, or 'possible diabetes', i.e. those without previously diagnosed diabetes and HbA(1c) above 6.5%.Of the 146 patients included, four had died by day 5 and 14 by day 28. Admission plasma glucose was higher in patients who had died by day 28 (11.7 +/- 5.8 vs. 8.0 +/- 3.3 mmol/l, P = 0.002), whereas HbA(1c) was not (6.4 +/- 1.9 vs. 6.1 +/- 0.8%, NS). Admission plasma glucose was significantly higher in those who had died by day 28 after adjustment on HbA(1c). A multivariate analysis, including sex, age and heart failure prior to acute myocardial infarction, showed that admission plasma glucose concentration was an independent predictor of survival after acute myocardial infarction. Twenty-seven of the patients had previously diagnosed diabetes and 119 had no history of diabetes. Eleven were found to have possible diabetes. Admission plasma glucose was significantly higher in previously diagnosed diabetes (11.1 +/- 5.6) than in the other groups: 7.7 +/- 2.9 in non-diabetes, 8.2 +/- 2.1 in possible diabetes (P0.0001). The relationship between HbA(1c)-adjusted admission plasma glucose and mortality after acute myocardial infarction was also found in the non-diabetes group.Admission plasma glucose, even after adjustment on HbA(1c), is a prognostic factor associated with mortality after acute myocardial infarction. Acute rather than the chronic pre-existing glycometabolic state accounts for the prognosis after acute myocardial infarction.

This year, the writing of "Best of hypertension 2002" was completed by the coordinators of 4 working groups of the French Society of Hypertension, in various domains: (a) the working group on BAroreflex and VARiability (BAVAR): it appeared mandatory to evaluate the influence of calculation methods on the values of spontaneous baroreflex sensitivity, through an european study (The EuroBaVar collaboration study); (b) the working group on Blood Pressure Measurement, was first involved in the establishment of an international protocol for the validation of self blood pressure measurement, then validated, according to this procedure and in collaboration with the French Medicine Agency, several apparatus dedicated to the French market; (c) the working group on epidemiology: after the publication of the IHPAF study (Incidence de l'hypertension dans la population active française), which unmasked the influence of social and professional determinants on blood pressure control, this group settled down ancillary studies in French Indias, the INAPAG study (INcidence de l'hypertension artérielle dans la population Antilles-Guyane), and the PHAPPG study (Prévalence de l'hypertension artérielle dans la population précaire guadeloupéenne); finally (d) the working group for continuous medical education settled down a national diploma, entitled "Hypertension and renal and cardiovascular risk".