Triple-combination therapy in the treatment of hypertension: a review of the evidence.

Hypertension is a serious public health concern with inadequate control of blood pressure (BP) worldwide. Contributing factors include low efficacy of drugs, underuse of combination therapies, irrational combinations, physicians' therapeutic inertia and poor adherence to treatment. Current guidelines recommend the use of initial (dual) combination therapy in high-risk patients for immediate BP response, better short- and long-term BP control, and continued/improved patient adherence. This article aims to review the existing evidence of triple-combination therapies with respect to efficacy, safety and adherence to treatment. It is estimated that three drugs are required to achieve BP control in approximately one-fourth to one-third of patients. Randomised controlled trials (RCTs) have shown that triple combinations of amlodipine/valsartan/hydrochlorothiazide, amlodipine/olmesartan/hydrochlorothiazide and amlodipine/telmisartan/hydrochlorothiazide produce greater BP reductions, with greater proportions of patients achieving BP control compared with dual therapies. Further evidence also demonstrates that triple-combination therapy is efficacious for moderate to severe hypertension, with substantial additional BP reduction over dual regimens. Both RCTs and post-marketing observational studies have shown consistent and comparable efficacy in both the general population and high-risk hypertensive subgroups. Triple therapies are generally well tolerated with adverse event profiles similar to dual regimens. In addition, fixed-dose combinations used as single pill improve patient adherence leading to better long-term BP control. Depending on regional circumstances, they may also be cost effective. Thus, single-pill triple combinations of different classes of drugs with complementary mechanisms of action help to treat patients to goal with improved efficacy and better adherence to treatment.

Physiological response to whole-body vibration in athletes and sedentary subjects.

Whole-body vibration (WBV) is a new exercise method, with good acceptance among sedentary subjects. The metabolic response to WBV has not been well documented. Three groups of male subjects, inactive (SED), endurance (END) and strength trained (SPRINT) underwent a session of side-alternating WBV composed of three 3-min exercises (isometric half-squat, dynamic squat, dynamic squat with added load), and repeated at three frequencies (20, 26 and 32 Hz). VO(2), heart rate and Borg scale were monitored. Twenty-seven healthy young subjects (10 SED, 8 SPRINT and 9 END) were included. When expressed in % of their maximal value recorded in a treadmill test, both the peak oxygen consumption (VO(2)) and heart rate (HR) attained during WBV were greatest in the SED, compared to the other two groups (VO(2): 59.3 % in SED vs 50.8 % in SPRINT and 48.0 % in END, p<0.01; HR 82.7 % in SED vs 80.4 % in SPRINT and 72.4 % in END, p<0.05). In conclusions, the heart rate and metabolic response to WBV differs according to fitness level and type, exercise type and vibration frequency. In SED, WBV can elicit sufficient cardiovascular response to benefit overall fitness and thus be a potentially useful modality for the reduction of cardiovascular risk.

High mobility group box 1 protein (HMGB-1): a pathogenic role in preeclampsia?

We evaluated whether preeclampsia is associated with elevated circulating levels of High mobility group box 1 protein (HMGB-1), a nuclear protein with proinflammatory effects when released extracellularly. We enrolled 48 women, 32 in third trimester pregnancy (16 with, 16 without preeclampsia), and 16 healthy non pregnant. In the peripheral blood of pregnant women, HMGB-1 concentration was assessed serially, before and after delivery. With or without preeclampsia, third trimester pregnancy was associated with elevated levels of HMGB-1. This elevation is exaggerated in preeclampsia. The source of HMGB-1 observed in these conditions is likely to involve tissues other than the placenta itself.

[Hypertension. Effects of antihypertensive therapy on cognitive functions]. / Hypertension. Effets du traitement antihypertenseur sur les fonctions cognitives.

A cause and effect relationship between arterial hypertension and decline of cognitive function has long been suspected. In middle-age subjects indeed, an abnormally high blood pressure is a risk factor for the long-term development of dementia. Presently, it seems crucial to treat hypertensive patients in order to better protect them against cognitive decline. However, in the elderly patients the risk of mental deterioration may also be enhanced when diastolic pressure becomes too low, for example below 70 mmHg. Further studies are required to better define the antihypertensive drug regimen and target blood pressure which would be optimal for the prevention of cerebral small vessel disease.

Are all diuretics equal for the treatment of hypertensive patients?

Thiazide (hydrochlorothiazide, etc.) and thiazide-like (chlortalidone, indapamide,etc.) diuretics are widely used to treat hypertensive patients. There is growing evidence that these diuretics are not interchangeable and that it might be preferable to choose a thiazide-likediuretic whenever the use of a diuretic is considered. This is in order to prevent optimally the development of cardiovascular complications and the occurrence of metabolic side effects, in particular diabetes (AU)

Las tiazidas (hidroclorotiazida, etc.) y los diuréticos de tipo tiazídico (clortalidona,indapamida, etc.) son fármacos ampliamente utilizados para tratar la hipertensión. Existe pruebas crecientes de que estos diuréticos no son intercambiables y sería preferible elegir un diurético de tipo tiazídico siempre que se considere el uso de los mismos. La razón para ello es evitar de manera óptima el desarrollo de complicaciones cardiovasculares y la aparición de efectos secundarios metabólicos, en particular la diabetes (AU)

[Are all diuretics equal for the treatment of hypertensive patients?]. / Tous les diurétiques sont-its égaux pour traiter les matolades hypertendus?

Thiazide (hydrochlorothiazide,...) and thiazide-like (chlortalidone, indapamide,...) diuretics are widely used to treat hypertensive patients. There is growing evidence that these diuretics are not interchangeable and that it might be preferable to choose a thiazide-like diuretic whenever the use of a diuretic is considered. This is in order to prevent optimally the development of cardiovascular complications and the occurrence of metabolic side effects, in particular diabetes.

[Obstructive sleep apnea and drugs as causes of treatment-resistant hypertension]. / Hypertension artérielle réfractaire au traitement due au syndrome d'apnées du sommeil et à la prise de médicaments.

Treatment-resistant hypertension is still common despite the availability of several types of antihypertensive agents acting by different mechanisms. The existence of refractory hypertension should lead to rule out "white-coat hypertension", poor adherence to prescribed drugs as well as classical causes of secondary hypertension such as renal artery stenosis, primary aldosteronism, pheochromocytoma and renal disease. It is also important to consider the possible existence of obstructive sleep apnea or the regular intake of vasopressive drugs or substances.

PP125. High mobility group box 1 protein (HMGB1): A pathogenic role in preeclampsia?

INTRODUCTION: A central pathogenic mechanism of preeclampsia is believed to be the production by the hypoxic placenta of various mediators which promote inflammation and oxidative stress when released into the maternal circulation. The high mobility group box 1 protein (HMGB1) is a ubiquitous nuclear protein. In conditions of hypoxic cellular stress or necrosis, HMGB1 is released into the extracellular milieu. Extracellular HMGB1 has proinflammatory effects, due to the engagement of various cell membrane receptors, notably the receptor for advanced glycation products (RAGE). OBJECTIVES: In preeclampsia, there is evidence for activation of RAGE, and enhanced amounts of HMGB1 have also been demonstrated in the placenta and amniotic fluid, but not, so far, in maternal blood. We hypothesize therefore that, in preeclampsia, the concentration of HMGB1 is abnormally high in maternal blood. METHODS: We enrolled 16 women in third trimester pregnancy and suffering from preeclampsia (blood pressure > 140/90mmHg with significant proteinuria), 16 women with normal pregnancies who were matched pairwise with the former for BMI and gestation week, and 16 non pregnant healthy women, matched for age with the other two groups. HMGB1 was assessed in peripheral blood with a commercial ELISA kit. The variance between the three groups was appreciated using an ANOVA analysis. Significance was considered for a probability value of < 0.5. RESULTS: The median [interquartile range] HMGB1 concentrations (in ng/mL) were 2.1 [1.1-3.2] in preeclamptic pregnancies, 1.1 [1.0-1.2] in normal pregnancies (p<0.05 vs preeclamptic group), and 0.6 [0.5-0.8] in non pregnant women (p<0.01 vs both other groups). CONCLUSION: In third trimester pregnancy, the presence of preeclampsia is associated with an approximately two-fold increase of HMGB1 concentration in maternal peripheral blood. Considering its known proinflammatory effects, HMGB1 could be one mediator responsible for the maternal manifestations of preeclampsia.

[Usefulness of BNP measurement for stratifying cardiovascular risk in hypertensive patients]. / Une place pour le BNP dans ta stratification du risque cardiovas- culaire chez le malade hypertendu?

The production of brain natriuretic peptide (BNP) by ventricular cardiomyocytes is increased in patients with left ventricular hypertrophy (LVH). Increased plasma levels of BNP or of the inactive fragment NP-proBNP are associated with an increased cardiovascular risk. The measurement of plasma concentrations of these peptides may be useful for stratifying the cardiovascular risk of hypertensive patients, particularly if there is no electrocardiographic evidence for LVH.

[Angiotensin II receptor blockers (ARBs) and cancer: a reassuring balance]. / Antagonistes de l'angiotensine II et cancer: un bilan rassurant.

The effects of drugs on new cancer and cancer-related death are a major concern. Recently, a meta-analysis raised the possibility that ARBs might have an adverse impact in this respect. This point of view was highly debated until the publication of two other meta-analyses which did not demonstrate any increased risk of new cancer occurrence as well as of cancer related-death with the use of ARBs in patients with hypertension, heart failure and/or nephropathy. This illustrates that the results of meta-analyses should be interpreted cautiously and critically in order to avoid biased conclusions. Overall the bulk of evidence today indicates that ARBs are not associated with an increased cancer risk.

Enhanced diastolic reflections on arterial pressure pulse during exercise recovery.

During recovery from a maximal or submaximal aerobic exercise, augmentation of central (aortic) systolic pressure by reflected pressure waves is blunted in healthy humans. However, the extent to which reflected pressure waves modify the central pulse in diastole in these conditions remains unknown. We evaluated systolic and diastolic central reflected waves in 11 endurance-trained athletes on recovery from a maximal running test on a treadmill (treadmill-max) and a 4000 m run in field conditions. On both occasions in each subject, the radial pulse was recorded with applanation tonometry in the resting preexercise state and then 5, 15, 25, 35, and 45 min after exercise termination. From the central waveform, as reconstructed by application of a generalized transfer function, we computed a systolic (AIx) and a diastolic index (AId) of pressure augmentation by reflections. At 5 min, both indices were below preexercise. At further time-points, AIx remained low, while AId progressively increased, to overshoot above preexercise at 45 min. The same behavior was observed with both exercise types. Beyond the first few minutes of recovery following either maximal or submaximal aerobic exercise, reflected waves selectively augment the central pressure pulse in diastole, at least in endurance-trained athletes.

European Society of Hypertension practice guidelines for home blood pressure monitoring.

Self-monitoring of blood pressure by patients at home (home blood pressure monitoring (HBPM)) is being increasingly used in many countries and is well accepted by hypertensive patients. Current hypertension guidelines have endorsed the use of HBPM in clinical practice as a useful adjunct to conventional office measurements. Recently, a detailed consensus document on HBPM was published by the European Society of Hypertension Working Group on Blood Pressure Monitoring. However, in daily practice, briefer documents summarizing the essential recommendations are needed. It is also accepted that the successful implementation of clinical guidelines in routine patient care is dependent on their acceptance by involvement of practising physicians. The present document, which provides concise and updated guidelines on the use of HBPM for practising physicians, was therefore prepared by including the comments and feedback of general practitioners.

[Evaluation using a logbook of mastering of clinical skills by medical students]. / Evaluation à l'aide d'un livre de bord compétences clinques acquises par des stagiaires en médecine.

The mastering of the clinical skills is of utmost importance for the physician. The teaching of the skills is nowadays made easier with the <> which lists all the skills and their respective level of expected mastering at graduation. In order to do a survey on how good the students are at those skills, a logbook based on this document has been setup at the Faculty of biology and medicine of the University of Lausanne. This has shown that students went through a clear progression of the mastering of the skills during their elective year in internal medicine, surgery/orthopaedics, paediatric, obstetric and gynaecology as well as psychiatry. Such an instrument should in the future help to better guide the learning process of the clinical skills and to do a better follow-up of their progress.

[Practice guidelines of the European Society of Hypertension for home blood pressure measurement]. / Directives pratiques de la Société européenne d'hypertension sur la mesure de la pression artérielle à domicile.

Self-measurement of blood pressure at home is increasingly used in the diagnostic and therapeutic approach of hypertension. This technique allows multiple measurements of blood pressure away from the clinical setting, making it possible to improve the evaluation of cardiovascular risk. Recently new guidelines on the use of self-measured blood pressure have been made available by the European Society of Hypertension, as summarized in the present paper.

Cost-effectiveness of antihypertensive treatment in patients 80 years of age or older in Switzerland: an analysis of the HYVET study from a Swiss perspective.

This analysis shows the economic benefit of antihypertensive treatment in patients 80 years of age or older from the perspective of the Swiss healthcare system. The cost-effectiveness analysis of antihypertensive treatment in the elderly was carried out applying the results of the Hypertension in the Very Elderly Trial study to the Swiss healthcare system. The analysis shows that hypertension treatment provides, compared with placebo, an additional life expectancy of 0.0457 years per patient, over a follow-up period of 2 years. The medication cost was covered by the reduction of costs related to the treatment of strokes, myocardial infarctions and heart failure: the total cost per patient in the active group resulted in a dominant strategy of savings compared with the placebo group. Sensitivity analysis yielded a stable estimate after varying the costs of medication, stroke, myocardial infarction, heart failure and life expectancy, confirming the robustness of these results. Moreover, considering that antihypertensive treatment also positively affects the incidence of dementia, those net benefits might even be underestimated.