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.

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.

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.

[Cardiovascular morbidity associated with obstructive sleep apnea syndrome]. / Morbidité cardiovasculaire associée au syndrome d'apnée obstructive du sommeil.

INTRODUCTION: The obstructive sleep apnoea syndrome (OSAS) had become a major public health concern in modern society due to its high prevalence but, above all, to its associated morbidity, especially cardiovascular. BACKGROUND: Untreated OSAS is associated with an increased incidence of fatal (myocardial infarction and stroke) (odds ratio: 2.87) and non-fatal cardiovascular events (myocardial infarction, stroke, coronary artery bypass surgery and coronary angiography) (odds ratio: 3.17). Moreover, the prevalence of hypertension in patients with OSAS is high, between 35 and 80%. The pathophysiological mechanisms leading to these complications are mainly due to intermittent hypoxia secondary to repeated episodes of apnoea/hypopnoea during sleep. These mechanisms include sympathetic hyperactivation, impairment of vasomotor reactivity, vascular inflammation, oxidative stress and metabolic disorders. In patients with OSAS, the impact of continuous positive pressure is proven in terms of prevention of cardiovascular events although blood pressure reduction is limited. Obviously these effects are proportional to observance. CONCLUSION: OSAS does increase the cardiovascular risk, independently of other risk factors. Although the impact of treatment is relatively low in decreasing blood pressure, it seems essentially effective in preventing cardiovascular morbidity. Therefore, OSAS screening, and the association of specific treatments in cardio-metabolic patients and OSAS patients respectively, should be included in clinical strategies.

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

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

[Aortic dissection spread to the renal arteries: role of renal volumetry after angioplasty]. / Dissection aortique étendue aux artères rénales : intérêt de la volumétrie rénale après angioplastie.

OBJECTIVE: Type A or B aortic dissection can extend to renal arteries, causing a renal ischemia which treatment is usually endovascular. The aim of our study is to show the interest of the renal volumetry in the follow-up of these patients. PATIENTS AND METHODS: Twenty-two patients (16 men, mean age 63.4±11.8years, BMI 25.2±3.4kg/m(2)) with a type A or B aortic dissection spread to one or to both renal arteries and followed at Grenoble university hospital were consecutively included. All patients underwent renal angiography with aorto-renal pressure gradients measurements and follow-up by renal volumetry (scanner Siemens(®)). A renal ischemia was defined by a decrease of 20% or more of the volumetry. RESULTS: Sixteen patients (73%) were hypertensive before the aortic dissection among which ten (62%) were treated. Eight patients (36%) have a significant renal pressure gradient among which five (62%) underwent renal endovascular therapy. The renal volumetry of these five patients remained unchanged while six of 17 patients (36%) without angioplasty have a decreasing volumetry. CONCLUSION: Renal volumetry appeared an effective and attractive option for the follow-up of the patients with aortic dissection spread to the renal arteries. These results should be taken into account to put the indication of an endovascular treatment.

The impact of obstructive sleep apnea on homocysteine and carotid remodeling in metabolic syndrome.

Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA+MetS; n=26) or the absence of OSA (MetS; n=9). In OSA+MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 ± 3.8 vs. 9.5 ± 2.5 µmol/L; P=0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r=0.522; P=0.001) and CIMT (r=0.376; P=0.026). Homocysteine was negatively correlated with plasma thiols (r=-0.406; P=0.017) and positively with urinary 15-F2t-isoprostanes (r=0.347; P=0.044). Multivariate regression analysis revealed that AHI (ß=0.559; P<0.001) and urinary 15-F2t-isoprostane (ß=0.310; P=0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress.

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.

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

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

Hypertension and obstructive sleep apnoea syndrome: current perspectives.

Obstructive sleep apnoea syndrome (OSAS), due to the collapse of the upper airways, is a common but still underestimated condition. The 'dose-response' type relationship between OSAS and hypertension (HT) has now been clearly proven. There are multiple mechanisms explaining this relationship, the main one being an increase in sympathetic activity during the apnoeas. HT associated with OSAS has several characteristics: high prevalence, diastolic and nocturnal predominance, and frequent non-dipper status. Furthermore, as OSAS is found in the majority of subjects with refractory HT, it should be systematically investigated in this situation. HT associated with OSAS should be tested for by means of a clinical blood pressure (BP) measurement, to which 24-h ambulatory BP monitoring (ABPM) is often added due to the fact that BP anomalies are frequently present at night. HT during OSAS is frequently associated with metabolic anomalies (for example, obesity, dyslipidaemia and insulin resistance), therefore explaining the high prevalence of metabolic syndrome in this population. The reference treatment for OSAS-nasal continuous positive airway pressure (nCPAP)-seems to be able to lower the BP of hypertensive patients, especially if the HT is severe, untreated or refractory. Moreover, the BP response to nCPAP depends on the severity of the OSAS, in particular the scale of the nocturnal desaturations, and on patient tolerance of the treatment. Optimal treatment for HT associated with OSAS has not been evidenced. Antihypertensive drugs do not change the respiratory parameters during OSAS.

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.

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.

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.

[Diagnosis and post-operative evolution of patients operated for adrenal adenoma (Conn syndrome). A 12-years retrospective study]. / Diagnostic et évolution postopératoire des patients opérés d'un adénome de Conn. Etude rétrospective sur 12 ans.

The prevalence and characteristics of patients operated for adrenal adenoma (Conn syndrome) as well as their post-operative arterial pressure evolution are varying through literature. Our aim was to report the Grenoble University Hospital experience. From 1993 to 2005, 24 patients (mean age = 46 +/-11 years) presented the biological criteria of primary hyperaldosteronism and benefited from adrenalectomy with confirmation of adrenal adenoma. All had an uncontrolled hypertension, refractory in 42% of cases, with a hypokaliemia (mean = 2.65 +/- 0.47 mmol/l). All adenomas measured more than 10 mm in scanner imaging. After a mean post-operative follow-up of 46 +/- 43 months, 70% of them were normotensive, with (45%) or without (25%) anti-hypertensive therapy. the post-operative kaliemia was normal in all cases. Only 25% had post-operative hormonal dosages for control. Post-operative spontaneous normotensive patients had, at the diagnosis of adrenal adenoma, a more recent and non-refractory hypertension, with a lower number of antihypertensive drugs, a better response to spirinolactone and higher aldosterone plasmatic levels. Two lessons can be taken from this study: 1) Whether 70% of patients operated for adrenal adenoma are normotensive (with or without treatement) post-operatively, only 25% are definitely cured after 4 years. Factors associated to a post-operative cure highlight the interest of an ealy diagnosis. 2) There is probably an underdiagnosis of adrenal adenoma (Conn syndrome) because neither adenomas with normokaliemia, nor adenomas <10 mm in scanner imaging have ever been diagnosed or at least, sent to surgery.

Association of eNOS Glu298Asp gene polymorphism with circadian blood pressure rhythm.

Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).