Continuous Positive Airway Pressure Reduces Night-Time Blood Pressure and Heart Rate in Patients With Obstructive Sleep Apnea and Resistant Hypertension: The RHOOSAS Randomized Controlled Trial.

OBJECTIVE: Most patients with resistant hypertension (RH) have obstructive sleep apnea (OSA). We aimed to determine the impact of OSA and continuous positive airway pressure (CPAP) treatment on the leptin profile and blood pressure (BP) in patients with RH. METHODS: After an initial case-control study (RH with and without OSA), we performed a randomized, single blind study in OSA + RH patients receiving either sham CPAP (3 months) followed by active CPAP (6 months) or 6 months of active CPAP. The primary outcome was the comparison of leptin levels between groups of RH patients with or without OSA. Secondary outcomes were the comparison of metabolic parameters, biomarkers of sympathetic activity, and BP indices between the two groups of RH patients with or without OSA. The same outcomes were then evaluated and compared before and after sham and effective CPAP intervention. RESULTS: Sixty-two patients (60 ± 10 years; 77% men) with RH (24-h daytime systolic BP (SBP)/diastolic BP: 145 ± 13/85 ± 10 mmHg, 3.7 antihypertensive drugs) were included. The 37 RH patients exhibiting OSA (60%) were predominantly men (87 vs 64% for non-OSA patients), with a greater prevalence of metabolic syndrome and higher creatininemia. Their leptin concentrations were significantly lower than in non-OSA patients [9 (6; 15) vs 17 (6; 29) ng/mL] but increased after 6 months of CPAP. Three months of effective CPAP significantly decreased night-time SBP by 6.4 mmHg and heart rate (HR) by 6.0 bpm, compared to sham CPAP. CONCLUSION: The association between OSA and RH corresponds to a specific, predominately male phenotype with a higher burden of metabolic syndrome and higher creatininemia but there was no significant difference between OSA and non-OSA patients regarding BP indices, and the number of antihypertensive drugs used. Active CPAP could be efficient at decreasing night-time BP and HR, but there was no difference between CPAP and sham CPAP groups for all metabolic and SNS markers (NCT00746902 RHOOSAS).

[Obstructive sleep apnea syndrome in woman: Knowing its specificities for a better management]. / Le syndrome d'apnées obstructives du sommeil de la femme : connaître ses spécificités pour une meilleure prise en charge.

Cardiovascular diseases are the first cause of death in women. Their frequency is underestimated because of their atypical feminine clinical presentation. The pathway "heart, arteries and women", initiated at Lille's hospital center in 2013, was designed to improve pluridisciplinar approaches for women. Thus, obstructive sleep apnea (OSA), known as a metabolic risk factor, was studied in several works. In post-menopausal women with cardiovascular risk, frequency of OSA seems underestimated. Clinical presentation of OSA in feminine patients can be misleading, and its screening seems essential, in light of its major cardiovascular impact.

Arterial stiffness evaluated by pulse wave velocity is not predictive of the improvement in hypertension after adrenal surgery for primary aldosteronism: A multicentre study from the French European Society of Hypertension Excellence Centres.

BACKGROUND: Predictive factors associated with normal blood pressure (BP) after unilateral adrenalectomy for primary aldosteronism (PA) are not clearly identified. AIMS: To evaluate the predictive value of arterial stiffness before surgery on BP after surgery. METHODS: During 2009-2013, 96 patients with PA due to unilateral adrenal adenoma who underwent surgery were enrolled in a multicentre open-label, prospective study. Aortic pulse wave velocity (PWV) was assessed before surgery. Patients underwent ambulatory blood pressure monitoring (ABPM) before surgery and 6 and 12months after surgery. Twenty-four h SBP/DBP values were compared in subjects with PWV

High Prevalence of Multiple Arterial Bed Lesions in Patients With Fibromuscular Dysplasia: The ARCADIA Registry (Assessment of Renal and Cervical Artery Dysplasia).

Fibromuscular dysplasia (FMD) commonly affects the renal and cervical arteries but has been described to affect other vascular beds as well. The prevalence of and clinical characteristics associated with multisite FMD (string-of-beds or focal stenoses affecting at least 2 vascular beds) are not known. In the prospective ARCADIA registry (Assessment of Renal and Cervical Artery Dysplasia), symptomatic patients with renal artery (RA) FMD underwent tomographic- or magnetic resonance-angiography from the aortic arch to the intracranial arteries and those with cervical FMD from the diaphragm to the pelvis. Of 469 patients (84.0% women), 225 (48.0%) had multisite FMD. In addition, 86 of 244 patients with single-site disease had dissections or aneurisms affecting other vascular beds, totaling 311 patients (66.3%) with lesions in >1 vascular bed. Among patients with a cerebrovascular presentation, the prevalence of RA lesions was higher in patients with than in those without hypertension (odds ratio, 3.4; 95% confidence interval, 1.99-6.15). Among patients with a renal presentation, the prevalence of cervical lesions was higher in patients with bilateral than in those with unilateral RA lesions (odds ratio, 1.9; 95% confidence interval, 0.99-3.57). In conclusion, FMD is a systemic arterial disease. At least 2 vascular beds were affected by dysplastic stenoses in 48.0% of cases and by dysplastic stenoses, aneurysms, and dissections in 66.1% of cases. RA imaging should be proposed to hypertensive patients with a cerebrovascular presentation. Cervical artery imaging should be considered in patients with a renal presentation and bilateral RA lesions. CLINICAL TRIAL REGISTRATION: URL: www.Clinicaltrials.gov. Unique identifier: NCT02884141.

[Acute aortic syndromes and sleep apnea]. / Syndromes aortiques aigus et syndrome d'apnées du sommeil.

Obstructive sleep apnea (OSA) is a common disease, often present in "cardiovascular or metabolic patients". OSA favours the occurrence of arterial lesions, all the more if severe. There is a strong relationship between OSA and acute aortic syndromes (AAS). This relationship is in part explained by aortic dilatation linked to OSA. The presence of repeated episodes of sudden variation of transmural pressure applied on aortic wall seems to play a major role in this dilatation. All OSA patients should have a search of aortic dilatation by ultrasound (at a thoracic and abdominal level). Also, screening of OSA should be systematically performed in patients with aortic disease. The effect of continuous positive airway pressure in apneic patients with AAS has not been studied.

SFE/SFHTA/AFCE primary aldosteronism consensus: Introduction and handbook.

The French Endocrinology Society (SFE) French Hypertension Society (SFHTA) and Francophone Endocrine Surgery Association (AFCE) have drawn up recommendations for the management of primary aldosteronism (PA), based on an analysis of the literature by 27 experts in 7 work-groups. PA is suspected in case of hypertension associated with one of the following characteristics: severity, resistance, associated hypokalemia, disproportionate target organ lesions, or adrenal incidentaloma with hypertension or hypokalemia. Diagnosis is founded on aldosterone/renin ratio (ARR) measured under standardized conditions. Diagnostic thresholds are expressed according to the measurement units employed. Diagnosis is established for suprathreshold ARR associated with aldosterone concentrations >550pmol/L (200pg/mL) on 2 measurements, and rejected for aldosterone concentration<240pmol/L (90pg/mL) and/or subthreshold ARR. The diagnostic threshold applied is different if certain medication cannot be interrupted. In intermediate situations, dynamic testing is performed. Genetic forms of PA are screened for in young subjects and/or in case of familial history. The patient should be informed of the results expected from medical and surgical treatment of PA before exploration for lateralization is proposed. Lateralization is explored by adrenal vein sampling (AVS), except in patients under 35 years of age with unilateral adenoma on imaging. If PA proves to be lateralized, unilateral adrenalectomy may be performed, with adaptation of medical treatment pre- and postoperatively. If PA is non-lateralized or the patient refuses surgery, spironolactone is administered as first-line treatment, replaced by amiloride, eplerenone or calcium-channel blockers if insufficiently effective or poorly tolerated.

SFE/SFHTA/AFCE consensus on primary aldosteronism, part 1: Epidemiology of PA, who should be screened for sporadic PA?

Depending on the study, the prevalence of primary aldosteronism (PA) in patients with hypertension varies from 6 to 18%. Prevalence is higher in each of the following conditions, any one of which requires screening for PA: severe hypertension (systolic blood pressure [BP]≥180mmHg and/or diastolic BP≥110mmHg); resistant hypertension (systolic BP≥140mmHg and/or diastolic BP≥90mmHg despite adherence to a tritherapy including a thiazide diuretic); hypertension associated with hypokalemia (either spontaneous or associated with a diuretic); Hypertension or hypokalemia associated with adrenal incidentaloma. It should be borne in mind that PA can induce hypertension without hypokalemia or, less frequently, hypokalemia without hypertension. Finally, as cardiovascular and renal morbidity in PA is greater than in essential hypertension of equivalent level, screening for PA is indicated when cardiovascular or renal morbidity is more severe than predicted from BP level.

Comparison of continuous positive airway pressure and bosentan effect in mildly hypertensive patients with obstructive sleep apnoea: A randomized controlled pilot study.

BACKGROUND AND OBJECTIVE: Randomized controlled trials (RCT) have shown that continuous positive airway pressure (CPAP) has only limited impact on blood pressure (BP). Alternative strategies for obstructive sleep apnoea (OSA)-associated hypertension are therefore needed. Endothelin-1 has been demonstrated a key player in the deleterious cardiovascular consequences of OSA. In OSA, CPAP treatment has never been compared with endothelin receptor antagonist medications. Thus, we assessed the respective efficacy of CPAP and bosentan in reducing 24-h diastolic BP (DBP) in patients with OSA never treated by either therapy. METHODS: In a crossover pilot study, 16 mildly hypertensive patients (office systolic BP (SBP)/DBP: 142 ± 7/85 ± 8 mm Hg) with severe OSA (55 ± 8 years; body mass index, 29.6 ± 4.2 kg/m(2) ; apnoea-hypopnoea index, 40.8 ± 20.2/h) were randomized to either CPAP (n = 7) or bosentan (125 mg/day, n = 9) first for 4 weeks. After 2-weeks of washout, the second 4-week period consisted of the alternative treatment (in crossover). The primary outcome was the 24-h mean DBP change after treatment. RESULTS: In intention-to-treat analysis, the mean difference in 24-h DBP measurements between treatments was -3.1 (-6.9/0.7) mm Hg (median, 25th/75th percentiles) (P = 0.101) with bosentan having a greater effect. CONCLUSION: In this RCT, in mildly hypertensive patients with OSA, bosentan did not modify 24-h DBP but only reduced office BP suggesting that Endothelin-1 blockade does not play a major role in treatment of OSA-related hypertension.

[Hypertension during obstructive sleep apnea syndrome]. / Hypertension artérielle au cours du syndrome d'apnées obstructives du sommeil.

Hypertension (HT) related to obstructive sleep apnea syndrome (OSAS) is one of the secondary forms of HT. It must be systematically evoked in hypertensive patient because the association "obesity, major snoring and excessive diurnal sleepiness" is fickle during OSAS. HT in apneic patient is more often diastolic, nocturnal, with a non-dipper profile. Moreover, OSAS is very frequently present during resistant hypertension. There are many mechanisms linking OSAS to HT. The main stimulus is intermittent hypoxia and the most important pathophysiological consequence is high sympathetic activity. After doing the diagnosis of OSAS, its treatment principally associated lifestyle changes with continuous positive airway pressure (CPAP). CPAP can significantly decrease blood pressure, especially if compliance to treatment is good and hypertension is resistant.

Development and validation of a method using supported liquid extraction for aldosterone determination in human plasma by LC-MS/MS.

BACKGROUND: Accurate quantitation of aldosterone is essential for screening, diagnosis and subtype classification in primary aldosteronism. A simple, sensitive method for aldosterone in human plasma using supported liquid extraction (SLE) in combination with liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed and validated. METHODS: Plasma samples were diluted with water containing d7-aldosterone as internal standard. The samples were extracted with methyl-tert-butyl-ether (MTBE) on SLE cartridges. Separation was carried out on a Luna C18 (2) column using a methanol-water gradient. Detection was performed in the negative electrospray multiple reaction monitoring (MRM) quantitation. The use of water-based calibrators was evaluated against calibrators prepared in steroid-free serum. RESULTS: The assay was linear up to 3265pmol/L with an LOQ of approximately 40pmol/L. Within-run and between-run precision for plasma aldosterone were less than 10% except at low level near LOQ but were still less than 14.7% (Westgard's desirable specification). The mean recovery of the analyte added to plasma was greater than 97.7% and matrix effects were less than 4%. Comparison with another LC-MS/MS method was performed on a more sensitive instrument (ABSciex TQ 5500) and gave the equation API 3000=0.957×TQ 5500+12.6, linear regression r(2)=0.974 (n=43). An estimation of the reference interval for adults was established on a group of healthy volunteers (n=53). Calibration with water-based calibrators was validated and can be used for measurement of aldosterone by LC-MS/MS. CONCLUSIONS: This method is reliable, easy to perform on plasma specimens in a clinical environment and is attractive because of its simplicity.

Aortic dissection with acute malperfusion syndrome: Endovascular fenestration via the funnel technique.

OBJECTIVE: To analyze the short- and long-term results of an original aortic fenestration method using the funnel technique during aortic dissection complicated by malperfusion syndrome. METHODS: The funnel technique consists of deployment of an uncovered aortic stent graft placed from the false to the right lumen through an intimal flap aortic fenestration made by balloon angioplasty. Twenty-eight patients presenting with an aortic dissection (type A, n = 19; type B, n = 9) were treated for malperfusion syndrome owing to dynamic compression (16 renal, 17 bowel, and 13 lower limb ischemia) using the aforementioned technique, and had follow-up evaluation at short term (30 days) and long term (mean: 55 ± 40 months). Eight patients had severe ischemia on arrival (6 bowel, 7 renal, 3 lower limb). RESULTS: Technical success was achieved in 27 of 28 patients (96%), and ischemic symptoms had disappeared in 25 of 28 patients (89%) at short-term follow up. Five patients presented postprocedure complications: 4 minor and 1 major with arterial thrombosis which caused technical failure (3.6%). The 30-day mortality rate was 7% (n = 2), related to bowel ischemia complications. At long-term follow up, 21 patients had a stable thoracic aortic diameter (91%). CONCLUSIONS: The funnel technique, in cases of malperfusion syndrome after aortic dissection, safely improves short- and long-term clinical outcome, and could represent an interesting alternative in the management of patients. The hemodynamic efficiency of this technique may account for a lower mortality in our series.

Nocturia is an independent predictive factor of prevalent hypertension in obstructive sleep apnea patients.

OBJECTIVE: The aim of this study was to determine whether nocturia is an independent predictor for prevalent hypertension in obstructive sleep apnea (OSA). METHODS: We analyzed data from a national prospective clinical cohort of OSA patients participating in the French national prospective registry. Anthropometric data, comorbidities, OSA severity, and number of voids/night were included in multivariate analyses to determine the independent variables associated with prevalent hypertension. RESULTS: A total of 22,674 OSA patients were included, of which 11,332 were hypertensive. The prevalence of hypertension among OSA patients was about 1.3 times higher in patients suffering from nocturia at 61.45% versus 46.52% in hypertensive and non-hypertensive OSA patients (p <0.001). There was a significant positive relationship between hypertension and the severity of nocturia beyond two voids/night: two voids/night versus none: odds ratio (OR) = 1.270 (95% confidence interval (CI) = 1.175; 1.372), three voids/night versus none: OR = 1.422 (95% CI = 1.293; 1.565), and four voids/night versus none: OR = 1.575 (95% CI = 1.394; 1.781). The strength of the association was enhanced in patients over 64 years of age. CONCLUSIONS: Nocturia is a strong independent predictor of prevalent hypertension in OSA. This association exhibited a "dose-response" relationship beyond two voids/night. The resolution of nocturia after continuous positive airway pressure (CPAP) treatment might be an important outcome to consider for the response of hypertension to CPAP.

Reliability of a Bayesian network to predict an elevated aldosterone-to-renin ratio.

BACKGROUND: Resistant hypertension is common, mainly idiopathic, but sometimes related to primary aldosteronism. Thus, most hypertension specialists recommend screening for primary aldosteronism. AIMS: To optimize the selection of patients whose aldosterone-to-renin ratio (ARR) is elevated from simple clinical and biological characteristics. METHODS: Data from consecutive patients referred between 1 June 2008 and 30 May 2009 were collected retrospectively from five French 'European excellence hypertension centres' institutional registers. Patients were included if they had at least one of: onset of hypertension before age 40 years, resistant hypertension, history of hypokalaemia, efficient treatment by spironolactone, and potassium supplementation. An ARR>32 ng/L and aldosterone>160 ng/L in patients treated without agents altering the renin-angiotensin system was considered as elevated. Bayesian network and stepwise logistic regression were used to predict an elevated ARR. RESULTS: Of 334 patients, 89 were excluded (31 for incomplete data, 32 for taking agents that alter the renin-angiotensin system and 26 for other reasons). Among 245 included patients, 110 had an elevated ARR. Sensitivity reached 100% or 63.3% using Bayesian network or logistic regression, respectively, and specificity reached 89.6% or 67.2%, respectively. The area under the receiver-operating-characteristic curve obtained with the Bayesian network was significantly higher than that obtained by stepwise regression (0.93±0.02 vs. 0.70±0.03; P<0.001). CONCLUSION: In hypertension centres, Bayesian network efficiently detected patients with an elevated ARR. An external validation study is required before use in primary clinical settings.

Stress thallium-201/rest technetium-99m sequential dual-isotope high-speed myocardial perfusion imaging validation versus invasive coronary angiography.

BACKGROUND: Recent advances in nuclear myocardial perfusion imaging (MPI) have made it possible to develop a dual-isotope protocol for high-speed acquisition with image quality and radiation delivery comparable to that obtained with conventional single isotope protocols. So far, no study has compared dual-isotope high-speed MPI to invasive coronary angiography (ICA) in a large cohort using a Cadmium-zinc-telluride SPECT system. METHODS: Over a 1-year period (May 2011 to April 2012), 1366 patients underwent dual-isotope high-speed MPI. Patients with ICA within 3 months after dual-isotope high-speed MPI were included together with patients with a low likelihood of coronary artery disease (CAD) in order to assess normalcy rate. Global summed stress score (SSS) and summed rest score (SRS) were calculated, and ICA results were analyzed independently. The main end point was a patient-based assessment of the diagnostic performance of dual-isotope high-speed MPI in detecting or ruling out significant CAD (>70% reduction in lumen diameter). RESULTS: Inclusion criteria were fulfilled for 214 patients (143 men; age 60 ± 14 years; ICA, n = 104; low likelihood for CAD, n = 110). An exercise stress test was performed in 62% of patients and a pharmacological stress test was performed with either dipyridamole (32%) or dobutamine (6%). Average examination duration was 22.4 ± 4.5 minutes. Mean SSS, SRS, and SDS were 8.0 ± 4.9, 3.1 ± 4.3, and 5.0 ± 3.2, respectively. Prevalence of angiographic CAD was 75%. ICA detected stenosis in the left main trunk, left anterior descending artery, left circumflex artery, and right coronary artery in 4, 33, 31, and 42 patients, respectively. Sensitivity of dual-isotope high-speed MPI was 94%, normalcy rate was 92%, and accuracy was 83% for detecting CAD. CONCLUSION: Dual-isotope high-speed MPI is reliable at detecting or ruling out CAD. NCT01785589.

CPAP treatment supported by telemedicine does not improve blood pressure in high cardiovascular risk OSA patients: a randomized, controlled trial.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) has been associated with hypertension, which is one of the intermediary mechanisms leading to increased cardiovascular morbidity. This study aimed at evaluating the effects of a combination of continuous positive airway pressure (CPAP) and telemedicine support on blood pressure (BP) reduction in high cardiovascular risk OSA patients. DESIGN: A multi-center randomized controlled trial that compared standard CPAP care and CPAP care and a telemedicine intervention. SETTING: Sleep clinics in France. PATIENTS OR PARTICIPANTS: 107 adult (18-65 years old) OSA patients (AHI > 15 events/h) with a high cardiovascular risk (cardiovascular SCORE > 5% or secondary prevention). INTERVENTIONS: Patients were randomized to either standard care CPAP (n = 53) or CPAP and telemedicine (n = 54). Patients assigned to telemedicine were equipped with a smartphone for uploading BP measurements, CPAP adherence, sleepiness, and quality of life data; in return, they received pictograms containing health-related messages. MEASUREMENTS: The main outcome was home self-measured BP and secondary outcomes were cardiovascular risk evolution, objective physical activity, CPAP adherence, sleepiness and quality of life. RESULTS: Self-measured BP did not improve in either group (telemedicine or standard care). Patients in primary prevention showed greater BP reduction with CPAP treatment than those in secondary prevention. CONCLUSIONS: CPAP treatment supported by telemedicine alone did not improve blood pressure and cardiovascular risk in high cardiovascular risk OSA patients. This study emphasizes the need for diet and physical activity training programs in addition to CPAP when aiming at decreasing cardiometabolic risk factors in these patients. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT01226641.

Response to statin therapy in obstructive sleep apnea syndrome: a multicenter randomized controlled trial.

RATIONALE: Accumulated evidence implicates sympathetic activation as inducing oxidative stress and systemic inflammation, which in turn lead to hypertension, endothelial dysfunction, and atherosclerosis in obstructive sleep apnea (OSA). Statins through their pleiotropic properties may modify inflammation, lipid profile, and cardiovascular outcomes in OSA. METHODS: This multicenter, randomized, double-blind study compared the effects of atorvastatin 40 mg/day versus placebo over 12 weeks on endothelial function (the primary endpoint) measured by peripheral arterial tone (PAT). Secondary endpoints included office blood pressure (BP), early carotid atherosclerosis, arterial stiffness measured by pulse wave velocity (PWV), and metabolic parameters. RESULTS: 51 severe OSA patients were randomized. Key demographics for the study population were age 54 ± 11 years, 21.6% female, and BMI 28.5 ± 4.5 kg/m(2). In intention to treat analysis, mean PAT difference between atorvastatin and placebo groups was 0.008 (-0.29; 0.28), P = 0.979. Total and LDL cholesterol significantly improved with atorvastatin. Systolic BP significantly decreased with atorvastatin (mean difference: -6.34 mmHg (-12.68; -0.01), P = 0.050) whereas carotid atherosclerosis and PWV were unchanged compared to the placebo group. CONCLUSION: In OSA patients, 3 months of atorvastatin neither improved endothelial function nor reduced early signs of atherosclerosis although it lowered blood pressure and improved lipid profile. This trial is registered with NCT00669695.

Imaging of functional and structural alterations of large arteries after acute ischaemic atherothrombotic stroke or acute coronary syndromes.

BACKGROUND: Non-invasive methods allow the evaluation of structural and functional arterial abnormalities. So far, no study has focused on the comparison of vascular parameters by type of cardiovascular event. METHODS: In this pilot study, cardiovascular risk factors, carotid parameters, carotid-to-femoral pulse wave velocity (PWV), brachial flow-mediated dilation and ambulatory blood pressure were assessed in patients who presented with acute coronary syndromes (ACS) or ischaemic atherothrombotic stroke (IAS). Groups were matched for age and gender. RESULTS: Prevalences of hypertension, diabetes and dyslipidaemia and heredity, smoking and body mass index were similar in the ACS (n=50) and IAS (n=50) groups. Carotid intima-media thickness (IMT) and PWV were significantly higher in the IAS vs. ACS group (769±180 vs. 701±136 µm; P=0.039 and 12.5±3.5 vs. 10.7±2.4 m/s; P=0.006). Carotid distensibility was significantly lower in the IAS vs. ACS group (16.2±3.2 vs. 18.9±7.6 10(-3)/kPa; P=0.02). These differences persisted after adjustment for blood pressure for carotid distensibility but not for PWV. The prevalences of endothelial dysfunction and carotid plaques were not significantly different in the ACS and IAS groups (86% and 74%; 80% and 78%). In a multivariable model, carotid distensibility remained associated with ACS (odds ratio 1.19; 95% confidence interval 1.03-1.38; P=0.016). CONCLUSIONS: Stiffness and carotid wall thickness were higher in IAS than in ACS patients. These differences may support the interest in new therapeutic targets for cardiovascular secondary prevention. NCT NO: NCT00926874.