[Hypertension: Who to treat, to what extent and how?] / Hypertension artérielle : qui traiter, jusqu'où et comment ?

Hypertension is the modifiable risk factor causing the largest loss in healthy life-years. The risk of cardiovascular events increases exponentially with the level of blood pressure (BP), starting from 115mmHg for systolic BP. Out-of-office BP measurements (self-measurements or ambulatory BP measurements) are now preferred for the diagnosis and follow up. In the absence of a preferred indication, antihypertensive treatment is based on thiazide diuretics, calcium channel blockers, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. These treatments are associated with a significant reduction in morbidity and mortality in people with office BP ≥ 140/90mmHg (self-measurements ≥ 135/85mmHg). For people at high cardiovascular risk, especially those with a history of cardiovascular disease, starting the treatment for an office BP ≥ 130/80mmHg is also beneficial (self-measurements ≥ 130/80mmHg as well). It is now common to start treatment with half-dose dual therapy, which is more effective and better tolerated than full-dose monotherapy. The clinical effect is assessed at 4 weeks and intensification, if required, is then usually done by switching to the same dual therapy at full-dose for both components.

Interactions of radiation therapy with common and innovative systemic treatments: Antidiabetic treatments, antihypertensives, lipid-lowering medications, immunosuppressive medications and other radiosensitizing methods.

The invention and approval of innovative anticancer therapies in the last decade have revolutionized oncology treatment. Radiotherapy is one of the three traditional pillars in oncology treatment with surgery and systemic therapies. Some standard-of-care combinations of chemoradiotherapy widened the therapeutic window of radiation, while some other chemotherapies such as gemcitabine caused unacceptable toxicities when combined with radiation in lung cancers. Fast-paced progress are specially focused on immunotherapies, targeted-therapies, anti-angiogenic treatment, DNA repair inhibitors, hormonotherapy and cell cycle inhibitors. New anticancer therapeutic arsenals provided new possibilities of combined oncological treatments. The interactions of the radiotherapy with other systemic treatments, such as non-anticancer immunomodulatory/immunosuppressive medications are sometimes overlooked even though they could offer a real therapeutic benefit. In this review, we summarize the new opportunities and the risks of historical and novel combined therapies with radiation: non-anticancer immunomodulatory/immunosuppressive drugs, systemic reoxygenation, new therapies such as nanoparticles and SMAC mimetics. Key biological mechanisms, pre-clinical and available clinical data will be provided to demonstrate the promising opportunities in the years to come.

Effects of oleuropein on rat's atria and thoracic aorta: a study of antihypertensive mechanisms.

Oleuropein (OLE) is the main bioactive ingredient in the leaves of the olive plant Olea europaea L. (Oleaceae), which has proven beneficial due to the antiinflammatory, antiatherogenic, anticancer, antimicrobial, and antiviral effects. This study aimed to investigate the antihypertensive and vasodilator potential of OLE by analyzing its acute effects on spontaneous atrial contractions and vasomotor responses of the isolated thoracic aorta in rats. We showed that the application of OLE induces negative chronotropic and inotropic effects on the heart. OLE also causes mild aortic vasodilation given that the maximal reduction in tension of intact aortic rings precontracted with phenylephrine was approximately 30%. This vasodilation is likely dependent on the nitric oxide released from the endothelium based on the effect obtained on denuded and phenylephrine precontracted aortic rings and responses reordered following vasoconstriction induced by high concentrations of K+ and heparin. Our findings provide a basis for further testing of OLE cardiovascular effects, which may lead to subsequent clinical research for its application in the treatment of hypertension and heart disease.

[Assessment for antihypertensive drug intake: How, where and when?] / Pourquoi, comment et où dose-t-on les antihypertenseurs en 2019 ?

AIM: Hypertension is a public health problem managed according to therapeutic strategies published in France by the Hauteautoritéde santé (HAS - French Health Authorities). For patients with resistant hypertension, related or not to a non-adherence, prescribers need to be sure the exposure is high enough to achieve the tensional target. Quantitative analysis of antihypertensive drugs in different biological matrices (blood/urine) is one possible solution. However, this involves determining the concentrations observed at standard doses and knowing how to interpret the measured concentrations. It is also necessary to identify medical laboratories that can assay antihypertensive drugs. This was the aim of our work. METHODS: The main antihypertensive drugs recommended by the HAS have been listed. For each of them, we looked for published steady-state plasma/serum concentrations and quantities excreted in the urine at usual dosages. In addition, the elimination half-life and linear pharmacokinetic profile were specified for each antihypertensive agent measured in plasma/serum. Pharmacology-Toxicology laboratories in France likely to carry out assays were identified. The time taken to report the result and the cost of the analysis were also specified. RESULTS: All of the afore-mentioned information has been collected and presented in a table. This can then be used to compare the plasma/serum concentration or the quantity measured in a patient's urine with the values reported in the literature. In cases where the blood sampling times differ between those of the patient and the published data, the patient's measured value is compared to the estimated value based on the published concentrations and pharmacokinetics. CONCLUSION: Interpretation of the plasma/serum/urinary value measured or estimated for an antihypertensive drug is a particularly interesting approach to determine if drug exposure is enough and a possible non-adherence. However, this activity is mostly carried out in hospital centres.

[Resistant hypertension by unadvertised non-compliance detected by psychiatric expertise and drug dosages]. / Hypertension artérielle résistante par inobservance non avouée dépistée par expertise psychiatrique et dosages médicamenteux.

The management of patients with resistant hypertension remains a major challenge in daily clinical practice in order to limit macro and microvascular impact. However, lack of compliance often remains one of the main etiologies of resistant hypertension. Through a clinical case of complex therapeutic non-compliance, we will detail the frequency, the screening and the management of therapeutic non-compliance. Finally, we will specify the contribution of drug dosages and psychological expertise in screening non-observant patients with presumed resistant hypertension.

[Development of a risk calculator for drug compliance in treated hypertensives: The FLAHS Compliance Calculator]. / Mise au point d'un calculateur du risque d'inobservance aux traitements antihypertenseurs chez des hypertendus traités : le calculateur FLAHS Observance.

OBJECTIVE: To investigate the determinants of non-compliance with antihypertensive treatments among participants in the FLAHS 2015 survey and to develop a risk calculator for drug compliance in a hypertensive population. METHODS: The FLAHS surveys are carried out by self-questionnaire sent by mail to individuals from the TNS SOFRES (representative panel of the population living in metropolitan France) sampling frame. In 2015, FLAHS was performed in subjects aged 55years and older. Using the Girerd questionnaire, the "perfect observance" was determined for a score of 0 and "nonobservance" for a score of 1 or higher. A Poisson regression was conducted in univariate and multivariate to estimate risk ratios for each determinant. A non-compliance risk calculator is constructed from multivariate analysis. A Poisson regression was performed in univariate and multivariate to estimate risk ratios. For each sex, a probability table is produced from the equation of the multivariate analysis and then the calculation of a nonobservance probability ratio (PR) using the profile with the best probability as a reference. Each subject is then classified into one of the three classes of risk of non-compliance: low (PR <1.5), high (PR>=2) and intermediate (PR>=1.5 and <2). RESULTS: The survey included 6379 subjects and analysis based on 2370 treated hypertensives. The onset of treatment was less than 2years in 7% of subjects and the median follow-up duration of treatment was 10years. Perfect compliance was observed in 64% of subjects. Independent determinants of non-compliance are: male sex, young age, number of antihypertensive tablet, treatment for a metabolic disease (diabetes, dyslipidemia), presence of other chronic illness, secondary prevention of cardiovascular disease. To get the risk class of nonobservance a web page is available at http://www.comitehta.org/flahs-observance-hta/. CONCLUSION: The development of the FLAHS Compliance Test is a tool whose use is possible during an office visit. Its free availability for French doctor will be one of the actions undertaken as part of the "call for action for adherence in hypertension" proposed by the French League Against Hypertension in 2017.

[Hypertension in the elderly in France: Characteristics of treatments and frequency of cognitive complaint according to the 2014 French League against Hypertension Survey]. / Hypertension artérielle du sujet âgé en France : caractéristiques du traitement et fréquence de la plainte cognitive selon l'enquête FLAHS 2014.

OBJECTIVE: Describe hypertensive patients treated in 2014 in France by age and estimate the degree of cognitive complaint among subjects aged 55 and over. METHOD: French League against Hypertension Survey (FLAHS) was conducted by mail in a representative sample of subjects aged 35 and over living in metropolitan France. Antihypertensive treatment data were obtained by self-administered questionnaire. Among the owners of a self-measurement device, blood pressure was considered to be controlled if the average of three measurements in the morning was below 135/85 mmHg. Cognitive complaint was detected by the cognitive complaint questionnaire (QPC) and analyzed by age and medical history of each subject. RESULTS: In 2014, 30% of the population aged 35 and over (11.6 million) was treated with antihypertensive drugs. The number of treated hypertensive was: 3.45 million in the 75 and older, 2.96 million in 65-74 years, 3.24 million in 55-64 years, 1.58 million in the 45-54 years and 0.441 million in 35-44. The mono/bi/tri/quad-therapy is used in 46%/35%/14%/5% of patients. This distribution varies with age with monotherapy used in 63% of subjects under 55 years but in 40% of subjects 75 years and over. A positive QPC was noted in 11% of 55-64 years, in 21% of 75 years and older (P<0.001), in 20% of uncontrolled hypertensive patients, and in 34% of subjects with a personal history of stroke. CONCLUSION: In France, hypertension is a disease that affects mainly the elderly. The modalities of treatment are different depending on age. Cognitive complaints are more common in uncontrolled hypertensive patients and in patients with a history of stroke.

[How to manage a patient with chronic arterial hypertension during pregnancy and the postpartum period]. / Conduite à tenir chez une hypertendue artérielle chronique pendant la grossesse et le postpartum.

The management of chronic arterial hypertension during pregnancy and postpartum requires first to estimate the risk of the pregnancy, linked with the severity of hypertension, with cardiac and renal involvement, with its cause as well as with the background (obesity, diabetes, possible history of placental vascular pathology). On a very practical approach, antihypertensive drug has to be started or increased if systolic pressure reaches or exceeds 160 mmHg or if diastolic pressure reaches or exceeds 105 mmHg. Below this level, there are no evidence-based medicine data, but it seems reasonable to treat if pressure increases over 150/100 mmHg (140/90 mmHg in case of ambulatory monitoring). Excessive pressure figures control must be avoided as much as insufficient ones: in practice, it is necessary to decrease the treatment dose if figures are below 130/80 mmHg. Three antihypertensive drugs are consensually recommended today: alphametyldopa, calcium-channel blockers and labetalol. Monotherapy is most often sufficient; if needed, two of these drugs can easily be associated, and even three if necessary. Converting enzyme inhibitors and angiotensin receptor II antagonists should not be prescribed to pregnant women. Betablockers and diuretics are not recommended. Whatever is the antihypertensive drug used, it is necessary to detect the signs of bad placenta blood circulation with uterine Doppler ultrasound and regular controls of fetal growth, and to check for appearance of proteinuria, defining then over-imposed pre-eclampsia needing immediate admission to the maternity. After delivery, lacatation suppresion with bromocriptin should not be prescribed.

[Current management of arterial hypertension]. / Prise en charge actuelle de l'hypertension artérielle.

Hypertension is a common health problem with serious consequences for individuals and a heavy attributable burden for populations. Reducing this burden requires preventive actions at the population level and early diagnosis at the individual level, followed by proactive interventions with proven benefits. Given the variability of blood pressure measurement, diagnosis is established only after repeated measurements under standardized conditions, if possible outside the clinic. Lifestyle changes can modestly reduce blood pressure; their impact is significant if they can be achieved on a large scale. Hypertension treatment requires a rational pharmacological approach, which can reach the target blood pressure within less than 6 months and three pharmacological classes at most in more than 80% of cases. Specialized consultation is required in the remaining 20% to detect secondary hypertensions, to optimize drug therapy and to discuss, in a minority of cases, non-pharmacological treatments. Recommendations are written by experts who select, interpret, and extrapolate the results of clinical research. As a consequence, they are sometimes unsuitable for primary care practice and frequently inconsistent across guidelines. Efforts are currently made to produce less disputable and more usable guidelines.

[Trends in the use of antihypertensive drugs in France from 2002 to 2012: FLAHS surveys]. / Évolution dans l'usage des traitements antihypertenseurs en France entre 2002 et 2012: enquêtes FLAHS.

OBJECTIVE: To evaluate from studies conducted between 2002 and 2012, trends in the use of antihypertensive drugs in France. METHOD: French League Against Hypertension Survey (FLAHS) were conducted in a representative sample of subjects aged 35 and over living in France. A list including the names for all antihypertensive drugs marketed at the time of each survey made it possible to detail drug therapies employed. Data analysis has taken the patient as a unity. The data obtained in 2002, 2007 and 2012 are subject to this analysis. RESULTS: In 2012, 30% of the French population aged 35 and older was treated with antihypertensive drugs (11.4 million), while 24% were treated in 2002 (8.2 million). On average, prescription of antihypertensive included 1.4 ± 0.7 pills in 2002, 1.5 ± 0.8 in 2007 and 1.8 ± 0.9 in 2012, which corresponds to a pharmacological monotherapy prescribed in 47% of subjects in 2012, a different percentage than in 2007 (46%) and 2002 (56%). Over the period, the percentage of prescriptions of diuretics (41% to 42%) and ACE inhibitors (24% to 23%) and beta-blockers (35% to 36%) is stable, but they are increasing with ARBs (23% to 47%) and calcium antagonists (24% to 34%). The prescriptions of fixed-dose combinations were also increased (19% to 30%). In 2012, fixed-dose combinations included a diuretic (79%), an ARB (65%), an ACEI (23%) and a calcium antagonist (20%). Blood pressure control estimated with home blood pressure monitoring increases from 38% in 2002 to 50% in 2007 and 2012. CONCLUSION: Changes in the use of antihypertensive drugs in France between 2002 and 2012 led to the prescription of antihypertensive treatment with associations in the majority. ARBs or ACEI are present on 70% of prescriptions with diuretics combined in 80%. Extensive use of fixed-dose combinations with diuretics and ARA2 characterizes this period in which it was observed an increase in blood pressure control in France.

[Not Available]. / Les médicaments génériques et l'évolution de la consommation des antihypertenseurs au Maroc.

BACKGROUND: To evaluate the evolution of consumption of antihypertensive drugs generic among 1991-2010, to assess the impacts after the institution of Mandatory Health Insurance and the marketing of generic drugs. METHODS: We used sales data from the Moroccan subsidiary of IMS Health Intercontinental Marketing Service. RESULTS: Consumption of generic antihypertensive drugs increased from 0.08 to 10.65 DDD/1 000 inhabitants/day between 1991 and 2010. In 2010, generic of the calcium channel blockers (CCBs) represented 4.08 DDD/1 000 inhabitants/day (82.09%), followed by angiotensin converting enzyme inhibitors (ACEI) by 2.40 DDD/1 000 inhabitants/day (48.29%). The generics market of CCBs is the most dominant and represented in 2010, 79.21% in volume and 62.58% in value. CONCLUSION: In developing countries like Morocco, the generic drug is a key element for access to treatment especially for the poor population.