Fixed-pressure CPAP versus auto-adjusting CPAP: comparison of efficacy on blood pressure in obstructive sleep apnoea, a randomised clinical trial.

BACKGROUND: Millions of individuals with obstructive sleep apnoea (OSA) are treated by CPAP aimed at reducing blood pressure (BP) and thus cardiovascular risk. However, evidence is scarce concerning the impact of different CPAP modalities on BP evolution. METHODS: This double-blind, randomised clinical trial of parallel groups of patients with OSA indicated for CPAP treatment compared the efficacy of fixed-pressure CPAP (FP-CPAP) with auto-adjusting CPAP (AutoCPAP) in reducing BP. The primary endpoint was the change in office systolic BP after 4 months. Secondary endpoints included 24 h BP measurements. RESULTS: Patients (322) were randomised to FP-CPAP (n=161) or AutoCPAP (n=161). The mean apnoea+hypopnoea index (AHI) was 43/h (SD, 21); mean age was 57 (SD, 11), with 70% of males; mean body mass index was 31.3 kg/m(2) (SD, 6.6) and median device use was 5.1 h/night. In the intention-to-treat analysis, office systolic blood pressure decreased by 2.2 mm Hg (95% CI -5.8 to 1.4) and 0.4 mm Hg (-4.3 to 3.4) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.3 mm Hg (95% CI -4.1 to 1.5); p=0.37, adjusted for baseline BP values). 24 h diastolic BP (DBP) decreased by 1.7 mm Hg (95% CI -3.9 to 0.5) and 0.5 mm Hg (95% CI -2.3 to 1.3) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.4 mm Hg (95% CI -2.7 to -0.01); p=0.048, adjusted for baseline BP values). CONCLUSIONS: The result was negative regarding the primary outcome of office BP, while FP-CPAP was more effective in reducing 24 h DBP (a secondary outcome). TRIAL REGISTRATION NUMBER: NCT01090297.

14 nights of intermittent hypoxia elevate daytime blood pressure and sympathetic activity in healthy humans.

Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⁻¹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⁻¹ ·mmHg⁻¹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.

Left ventricular diastolic dysfunction is linked to severity of obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) has been linked to increased cardiovascular risk. The present study examined the relationships between respiratory parameters and left ventricular abnormalities in OSA. 150 newly diagnosed OSA patients without any known cardiovascular disease were included in the study (mean ± sd age 49 ± 11 yrs, body mass index 27.1 ± 3.3 kg·m⁻², respiratory disturbance index 41 ± 18 h⁻¹). Haemodynamic, biological, respiratory, cardiac and arterial parameters were assessed at inclusion. 34 (22.7%) patients had a grade 1 left ventricular diastolic dysfunction. Patients with an abnormal diastole were older (p < 0.001) and 81% of them were hypertensive. The only respiratory parameter independently associated with the peak flow velocity in early diastole/peak flow velocity at atrial contraction ratio was mean nocturnal oxygen saturation. 17 (13%) patients had left ventricular hypertrophy. A multivariate analysis showed that clinic systolic blood pressure and mean nocturnal oxygen saturation were independently associated with left ventricular hypertrophy. In a logistic regression model, age ≥ 58 yrs (OR 3.29, 95% CI 1.78-5.64) and mean nocturnal oxygen saturation < 92% (OR 2.76, 95% CI 1.45-4.91) were associated with left ventricular diastolic dysfunction. Our findings demonstrate that left ventricular diastolic dysfunction frequently occurs in patients with OSA and that it is related to the severity of oxygen desaturation.

Clinical and microcirculatory effects of transcutaneous CO2 therapy in intermittent claudication. Randomized double-blind clinical trial with a parallel design.

BACKGROUND: This randomized, double blind trial determined the short and long-term clinical and hemodynamic vasodilator effects induced by percutaneous applications of natural CO2 gas in patients with moderate Fontaine stage II. PATIENTS AND METHODS: 62 patients with intermittent claudication (100-500 meters) were randomized to 18 consecutive days of CO2 treatment or placebo (air). The gas fluids were applied at a constant temperature of 30 degrees C on pre-humidified skin. The effects of the treatment were evaluated by total distance walked (primary criterion) and hemodynamic and microcirculatory findings. Patients also answered a quality of life questionnaire. RESULTS: The Strandness test showed a significant increase in total distance walked (+ 131 meters, 66%; p = 0.001) and pain-free distance (+ 81 meters, 73%; p = 0.02) after 18 days of CO2 treatment. The improvement was maintained 3 and 12 months later. The systolic pressure index (ABI) increased by 37% (p = 0.001) 1 minute after treadmill walking and ABI recovery time decreased significantly by 38% (p = 0.002). Microcirculatory findings showed an increase in systolic pressure of the great toe (13%; p < 0.0001), in baseline pO2 (20%; p = 0.01) and in vasomotion (78%; p = 0.001) in the treatment group. The improvement in total walking distance was correlated with the increase in ABI and peripheral cutaneous oxygenation. Patients' subjective assessments corroborated the benefits. No significant change was observed in the placebo group. CONCLUSIONS: This study demonstrates that 18 consecutive days of percutaneous CO2 treatment significantly increases walking distance in patients with moderate intermittent claudication. This effect, which was associated with an increase in peripheral systolic pressure and pO2, is evidence of a better ability to withstand effort.

Impairment of serum albumin antioxidant properties in obstructive sleep apnoea syndrome.

Antioxidant counteraction of oxidative stress has been poorly explored in obstructive sleep apnoea (OSA). Serum albumin is a major antioxidant agent and structural modifications induced by glucose or free radicals impair its antioxidant properties. The aim of the present study was to compare antioxidant capacities and structural changes of albumin in nonobese OSA patients and healthy volunteers. Albumin structural changes were studied by quenching of fluorescence in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidation- and glycation-induced changes in serum albumin, respectively, were assessed. Albumin structural changes were demonstrated by a significant decrease in quenching of fluorescence in OSA patients. Oxidation, resulting in a significant decrease in thiol groups (3.7+/-0.7 versus 2.3+/-0.4 micromol x g(-1) protein), and glycation, associated with a significant increase in fructosamines (226.6+/-27 versus 286+/-44.4 micromol x L(-1)), were found when comparing healthy volunteers with OSA patients. There was a significant relationship between both parameters and sleep apnoea severity. After continuous positive airway pressure intervention, albumin thiol groups were reassessed in seven of the 16 OSA patients and increased significantly from 2.25+/-0.39 to 2.79+/-0.31 micromol x g(-1) protein. Obstructive sleep apnoea patients demonstrated a reduction in serum albumin antioxidant properties that may aggravate oxidative stress and, thus, contribute to cardiovascular and metabolic morbidities.

Leukotriene B4: early mediator of atherosclerosis in obstructive sleep apnoea?

Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B(4) is a lipid mediator involved in atherogenesis. In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB(4) production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB(4) production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB(4) production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB(4) production, which was measured by liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls. LTB(4) production was increased in OSA patients compared with controls. LTB(4) levels correlated with the mean and minimal arterial oxygen saturation (S(a,O(2))). LTB(4) production correlated with luminal diameter data in patients with a mean S(a,O(2)) of < or = 94% but not with IMT. Lastly, CPAP significantly reduced LTB(4) production by 50%. Leukotriene B(4) production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B(4) could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.

Overexpression of Sp1 transcription factor induces apoptosis.

Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.

Transcription factor ATF2 cooperates with v-Jun to promote growth factor-independent proliferation in vitro and tumor formation in vivo.

ATF2 belongs to the bZIP family of transcription factors and controls gene expression via 8-bp ATF/CREB motifs either as a homodimer or as a heterodimer-for instance, with Jun-but has never been shown to be directly involved in oncogenesis. Experiments were designed to evaluate a possible role of ATF2 in oncogenesis in chick embryo fibroblasts (CEFs) in the presence or absence of v-Jun. We found that (i) forced expression of ATF2 cannot alone cause transformation, (ii) overexpression of ATF2 plus v-Jun specifically stimulates v-Jun-induced growth in medium with a reduced amount of serum, and (iii) the efficiency of low-serum growth correlates with the activity of a Jun-ATF2-dependent model promoter in stably transformed CEFs. Analysis of ATF2 and Jun dimerization mutants showed that the growth-stimulatory effect of ATF2 is likely to be mediated by v-Jun-ATF2 heterodimers since (i) v-Jun-m1, a mutant with enhanced affinity for ATF2, induces growth in low-serum medium much more efficiently than v-Jun, when expressed alone or in combination with ATF2; and (ii) ATF2/fos, a mutant that efficiently binds to v-Jun but is unable to form stable homodimers, shows enhanced oncogenic cooperation with v-Jun. In addition, we examined the role of ATF2 in tumor formation by subcutaneous injection of CEFs into chickens. In contrast to v-Jun, v-Jun-m1 gave rise to numerous fibrosarcomas while coexpression of ATF2 and v-Jun-m1 led to a dramatic development of fibrosarcomas visible within 1 week. Together these data demonstrate that overexpressed ATF2 potentiates the ability of v-Jun-transformed CEFs to grow in low-serum medium in vitro and contributes to the formation of tumors in vivo.

Attitudes to and application of the concept of overall cardiovascular risk: comparison of male and female primary care providers.

The aim of this observational study was to assess whether there were differences in perception of overall cardiovascular risk (OCVR) in hypertensive patients depending on the gender of the primary care provider (PCP). We performed this study in 2003: 2979 male PCPs (MPCPs) and 562 female PCPs (FPCPs) participated throughout France. The patients included were hypertensive either treated or untreated, uncontrolled (blood pressure (BP) >or=140/90 mm Hg) with at least one other cardiovascular risk factor (CVRF) associated. OCVR of patients was both calculated according to French Agence Nationale d'Accréditation et d'Evaluation en Santé guidelines for uncontrolled hypertensive patients and subjectively estimated by the PCP as 'low', 'moderate', 'high' or 'very high'. About 11 770 patients were included, mean age was 63.7+/-11.2 years and 54.1% were men. Mean BP was 157+/-13/90+/-9 mm Hg. According to French guidelines, the calculated OCVR was 'moderate' in 23.7% of patients, 'high' in 47.5% and 'very high' in 28.8%. The PCP perceived OCVR was that 9.1% of patients were considered to be at 'low risk', 40.7% at 'moderate risk', 38.1% at 'high risk', and only 11.2% at 'very high risk' (OCVR was not estimated for 0.9% of patients). The overall agreement rate between the PCPs' estimation of OCVR and its calculation was 43.5%. Thus, in spite of extensive diffusion of ANAES guidelines, we found that PCPs in France generally underestimated OCVR though there were no significant differences between male and female physicians (45% for FPCPs and 43.2% for MPCPs).

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.

Updated meta-analytical approach to the efficacy of antihypertensive drugs in reducing blood pressure.

BACKGROUND AND OBJECTIVE: Despite advances in the treatment of hypertension, control rates continue to be suboptimal in both Europe and the US. Strategies that improve hypertension control are therefore urgently needed. This study aimed to assess the relative efficacies of various antihypertensive drugs commonly used in France in reducing systolic and diastolic blood pressure (SBP and DBP) by using a meta-analytical approach. This update of a previously published meta-analytical approach extends the number of drugs evaluated from 13 to 19. METHODS: A total of 80 randomised, controlled trials published between 1973 and 2007 involving 10 818 patients were selected for inclusion in the meta-analytical approach. Data were examined for 19 drugs, and 16 drugs were included in the analysis: hydrochlorothiazide, indapamide sustained-release (SR), atenolol, amlodipine, lercanidipine, manidipine, enalapril, ramipril, trandolapril, candesartan cilexetil, irbesartan, losartan, olmesartan medoxomil, telmisartan, valsartan and aliskiren. Weighted average reductions in SBP and DBP over a period of 8-12 weeks were calculated for each drug from information on both the mean and the variability in BP reduction. No trials evaluating furosemide, spironolactone or cicletanine satisfied the inclusion criteria for this analysis. RESULTS: The average weighted reductions in SBP over 8-12 weeks were most marked with diuretics, and in particular indapamide SR 1.5 mg/day (mean change from baseline -22.2mm Hg), which reduced SBP to a greater extent than any of the other drugs evaluated (at any dosage considered). Average weighted reductions in DBP were generally similar with all classes of antihypertensives and ranged from -11.4mm Hg with the beta-adrenoceptor blocker atenolol and calcium channel antagonists to -10.3mm Hg with the angiotensin II type 1 receptor antagonists. CONCLUSION: This new analysis supports the results of the earlier investigation, in that indapamide SR 1.5 mg/day appeared to be the most effective drug for producing significant reductions in SBP within 8-12 weeks, which is an essential element in optimising cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.

Glucose tolerance and cardiovascular risk biomarkers in non-diabetic non-obese obstructive sleep apnea patients: Effects of long-term continuous positive airway pressure.

BACKGROUND: Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting. OBJECTIVE: To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients. PATIENTS & METHODS: Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 ± 9.4 years; apnea-hypopnea index = 41.1 ± 16.1 events/h; BMI = 26.6 ± 2.8 kg/m(2); fasting glucose = 4.98 ± 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured. RESULTS: LT-CPAP treatment lasted 13.9 ± 6.5 months. At baseline, the time spent at SaO2<90%, minimal and mean SaO2 were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002). CONCLUSIONS: In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers.

[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.

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.

Fibromuscular dysplasia: what the radiologist should know: a pictorial review.

UNLABELLED: Fibromuscular dysplasia (FMD) is an idiopathic, segmentary, non-inflammatory and non-atherosclerotic disease that can affect all layers of both small- and medium-calibre arteries. The prevalence of FMD is estimated between 4 and 6 % in the renal arteries and between 0.3 and 3 % in the cervico-encephalic arteries. FMD most frequently affects the renal, carotid and vertebral arteries, but it can theoretically affect any artery. Radiologists play an important role in the diagnosis of FMD, and good knowledge of FMD's signs will certainly help reduce the delay between the first symptoms and diagnosis. The common string-of-beads aspect is well known, but less common presentations also have to be considered. These less common imaging findings include vascular loops, fusiform vascular ectasia, arterial dissection, aneurysm and subarachnoid haemorrhage. These radiologic presentations should be known by radiologists in order to diagnose possible FMD, particularly when present in young females or when associated with personal or familial hypertension, to reduce the delay between the onset of the first symptom and the final diagnosis. The patients have to be referred to specialised FMD centres for dedicated management. TEACHING POINTS: • Fibromuscular dysplasia is not a rare disease. • Radiologists should recognise less common presentations to orient specific management. • Vascular loops, fusiform vascular ectasia and a "string-of-beads" aspect are typical presentations. • Arterial dissection, aneurysm and subarachnoid haemorrhage are less typical radiologic presentations.

Can we identify response markers to antihypertensive drugs? First results from the IDEAL Trial.

Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.

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.

Pharmacokinetics of quinupristin/ dalfopristin in patients with severe chronic renal insufficiency.

OBJECTIVE: To compare the pharmacokinetic profile of a single intravenous injection of quinupristin/dalfopristin, a new injectable streptogramin, in healthy young individuals and patients with severe chronic renal insufficiency. A secondary objective was to assess the relative tolerability of this dose in these patients compared with healthy individuals. PATIENTS AND PARTICIPANTS: 13 patients with severe chronic renal insufficiency (creatinine clearance 6 to 28 ml/min/1.73m2) were individually matched for gender, bodyweight and age to a healthy volunteer. METHODS: Participants received a single dose of quinupristin/dalfopristin 7.5 mg/kg bodyweight as a continuous 1-hour intravenous infusion, followed by serial blood sampling. RESULTS: The disposition profile of unchanged quinupristin was similar in the 2 groups. However, the elimination of quinupristin derivatives in patients with renal impairment tended to be decreased: mean peak plasma drug concentration (Cmax) and area under the concentration-time curve from zero to infinity (AUCinfinity) of quinupristin plus its active derivatives were about 1.4 times higher in the patients with renal impairment compared with healthy volunteers. The mean Cmax and AUCinfinity of both unchanged dalfopristin and dalfopristin plus its active derivatives were about 1.3 times higher in renally impaired patients than in healthy volunteers. Adverse events were generally mild and transient. No severe or serious adverse events were reported and no participants prematurely discontinued the study. Venous tolerability tended to be better in healthy volunteers than in the patients with renal impairment. CONCLUSION: These results suggest that no formal reduction in the dosage of quinupristin/dalfopristin is necessary in patients with severe chronic renal impairment.