Successful Total Management of Multi-Causative Sleep-Disordered Breathing Complicated with Patient with Adult Congenital Heart Disease.

Sleep-disordered breathing is one of the complications commonly seen in patients with adult congenital heart disease (ACHD) due to multiple causes including complex underlying cardiac defects, cardiomegaly, previous thoracotomies, obesity, scoliosis, and paralysis of the diaphragm. It is often hard to determine its main cause and predict the efficacy of each treatment in its management. We herein report a 30-year-old woman after biventricular repair of pulmonary atresia with intact ventricular septum diagnosed as sleep-related hypoventilation disorder. Simultaneous treatment targeting obesity, paralysis of the diaphragm, and cardiomegaly followed by respiratory muscle reinforcement through non-invasive ventilation resolved her sleep-related hypoventilation disorder. Such management for each factor responsible for the hypoventilation is expected to provide synergetic therapeutic efficacy and increase daily activity in a patient with ACHD.

Accumulated nocturnal hypoxemia predict arterial endothelial function in patients with sleep-disordered breathing with or without chronic heart failure.

ABTSRACT: Sleep-disordered breathing (SDB) is often accompanied with the chronic heart failure (CHF). Hypoxemia due to pulmonary congestion from CHF and concurrent SDB might synergistically impair endothelial function and worsen the prognosis. However, the main factors affecting deterioration of endothelial function are unknown and whether the influence of hypoxemia differs in SDB patients with and without CHF remains unclear. Fifty-three patients (CHF group, n = 23; non-CHF group, n = 30) underwent polysomnography to evaluate their SDB and flow-mediated vasodilation (FMD) measurements to assess arterial endothelial function. We examined the relationships between FMD and SDB-related parameters, including our original index of accumulated hypoxemia by SDB throughout one-night sleep: the time desaturation summation index (TDS), calculated as follows: (100% - averaged arterial oxygen saturation during sleep) × total sleep time. The mean age in the CHF and non-CHF groups was 59.0 ± 13.5 and 57.7 ± 11.4 years, respectively. Although the FMD in the 2 groups were not significantly different, well-known adverse factors for FMD such as serum lipid profiles, blood pressure levels, and conventional indices of SDB were worse in the non-CHF group. Only the TDS was not significantly different between 2 groups and associated with FMD as shown by the univariate analysis (CHF: p < 0.05, non-CHF: p < 0.01) and multivariate analysis (CHF: p < 0.05, non-CHF: p < 0.01). Accumulated hypoxemia (TDS) rather than the frequency of hypoxemia might more influence on the endothelial function irrespective of the cardiac state. Removal of accumulation of nocturnal hypoxemia might be a target for treatment equally in the patients with and without CHF.

Elaborate evaluation of serial changes in electrocardiograms of atrial septal defects after transcatheter closure for a better understanding of the recovery process.

Serial changes of electrocardiograms (ECG) could be used to assess their clinical features in atrial septal defects (ASD) after transcatheter closure together with other clinical parameters. We retrospectively studied 100 ASD patients who underwent transcatheter closure. Complications of persistent atrial fibrillation occurred in five ASD patients, and they were excluded. We divided the other 95 patients according to PQ intervals before closure (normal: < 200 ms, n = 51; prolonged: ≥ 200 ms, n = 44) to evaluate their clinical characteristics and parameters such as echocardiography, chest X-rays, and brain natriuretic protein (BNP) levels. Individuals in the prolonged PQ group were significantly older, had higher incidences of paroxysmal atrial fibrillation (PAF) and heart failure (HF) treated with more ß-blockers and diuretics, and with a higher tendency of NYHA functional classification and BNP levels than the normal PQ group. The prolonged PQ group also had a significantly higher incidence of complete right bundle branch block, wider QRS intervals, and larger cardiothoracic ratios in chest X-rays accompanied by larger right atrial-areas and larger left atrial dimensions in echocardiograms. Furthermore, the prolonged PQ intervals with less PQ interval shortening after transcatheter closure revealed that the patients were the oldest at the time of closures and showed less structural normalization of the right heart and left atrium after ASD closure. PAF and HF also occurred more frequently in this subgroup. These results suggested that the ASD patients with prolonged PQ intervals with less PQ shortening were accompanied by more advanced clinical conditions. Together with other clinical parameters, detailed analyses of ECG and their changes after closure could elucidate the clinical characteristics and status of ASD patients with transcatheter closure and were useful for predicting structural normalization after transcatheter closure.

Crossover comparison between CPAP and mandibular advancement device with adherence monitor about the effects on endothelial function, blood pressure and symptoms in patients with obstructive sleep apnea.

Mandibular advancement device (MAD) is an alternative therapeutic option for CPAP to treat obstructive sleep apnea (OSA). While MAD showed the better adherence, patients with over moderate OSA have been treated more frequently with CPAP despite increasing positive evidence on the cardiovascular outcome with MAD, even in severe patients. Thus, more information is needed regarding the cardiovascular and symptomatic outcome of MAD treatment objectively compared to CPAP. Forty-five supine-dependent OSA patients (apnea-hypopnea index 20-40/h) were randomized to either CPAP or MAD and treated for 8 weeks and switched to another for 8 weeks. The primary endpoint was improvement in the endothelial function, indexed by the flow-mediated dilatation (FMD), and the secondary endpoint was the sleep-time blood pressure (BP). The duration of MAD use was evaluated objectively by an implanted adherence monitor. Treatment efficacy was also evaluated by home sleep monitor and a questionnaire about the symptoms. The adherence was not significantly different (CPAP vs. MAD: 274.5 ± 108.9 min/night vs. 314.8 ± 127.0 min/night, p = 0.095). FMD and sleep-time mean BP were not markedly changed from the baseline with either approach (CPAP vs. MAD: FMD, + 0.47% ± 3.1% vs. + 0.85% ± 2.6%, p = 0.64; BP, - 1.5 ± 5.7 mmHg vs. - 1.2 ± 7.5 mmHg, p = 0.48), although sleepiness, nocturia, and sleep-related parameters were similarly improved and more patients preferred MAD. As MAD and CPAP showed similar effects on cardiovascular outcome and symptomatic relief even with a comparable length of usage, we might expect MAD as an alternative treatment option for CPAP in this range of OSA group.

Three nights leg thermal therapy could improve sleep quality in patients with chronic heart failure.

Sleep quality is often impaired in patients with chronic heart failure (HF), which may worsen their quality of life and even prognosis. Leg thermal therapy (LTT), topical leg warming, has been shown to improve endothelial function, oxidative stress, and cardiac function in patients with HF. However, its short-term influence to sleep quality has not been evaluated in HF patients. Eighteen of 23 patients with stable HF received LTT (15 min of warming at 45 °C and 30 min of insulation) at bedtime for 3 consecutive nights and 5 patients served as control. Subjective sleep quality was evaluated by St. Mary's Hospital Sleep Questionnaire, Oguri-Shirakawa-Azumi Sleep Inventory, and Epworth sleepiness scale, and also objectively evaluated by polysomnography. LTT significantly improved subjective sleep quality indicated by depth of sleep (p < 0.01), sleep duration (p < 0.05), number of awaking (p < 0.01), nap duration (p < 0.01), sleep quality (p < 0.05), and sleep satisfaction (p < 0.05). It was also objectively affirmed by a slight but significant decrease of sleep stage N1 (p < 0.01), and increase in sleep stage N2 (p < 0.05). No significant changes occurred in the controls. Hence, the short-term LTT could improve subjective and objective sleep quality in patients with HF. LTT can be a complimentary therapy to improve sleep quality in these patients.

Seasonal ambient changes influence inpatient falls.

Background: falls by inpatients often result in serious injuries and deterioration in a patient's physical abilities and quality of life, especially among older individuals. Although various factors have been found to be associated with falls, the combined effects of behavioural and ambient factors are not fully evaluated. Objective: we investigated the influence of both behavioural and ambient factors on inpatient falls, focusing on seasonal and diurnal variations. Design: retrospective study. Methods: we surveyed the incident reports related to falls from April 2010 to March 2014 and examined the relationship between the incidents and seasonal and diurnal variations in behavioural and ambient factors, including the sunrise time, the night-time length and temperature. Results: we identified 464 fallers from 3,037 incident reports. The average fall-rate of the study population was 1.4 ± 0.5/1,000 occupied bed-days. The seasonal and diurnal variations in falls were compared. The number of falls around dawn in October-February was higher than that in April-September. Toileting was the behaviour most frequently related to the falls (56.9%, n = 264), and 57.1% of the falls occurred at night. A multivariate analysis showed that the night-time length was significantly related to an increase in night-time falls (P = 0.047). Conclusion: these results suggested that the inpatient falls increased in the early morning from November to March and tended to be related to toileting activities. Considering these results, additional attention and support during the higher risk hours and seasons, especially in relation to toileting activities, might help to reduce the incidence of falls. Clinical trial name, URL and registration number: N/A (Because of retrospective nature).

Obstructive sleep apnea-related symptoms in Japanese people with Down syndrome.

This study evaluated the prevalence of obstructive sleep apnea-related symptoms and assessed the relationship with obesity or unusual sleep postures in Down syndrome patients in Japan. We obtained the demographic characteristics, sleep postures, and obstructive sleep apnea-related symptoms experienced by 90 people as reported by their caregivers. Although 71% reported snoring and 59% arousals, obstructive sleep apnea-related symptoms were not significantly different between obese and non-obese participants. The youngest age group had the fewest obstructive sleep apnea-related symptoms, especially symptoms of snoring. The odds for arousal, nocturia, and apnea tended to be higher in the unusual sleep-postures group. Unusual sleep postures were most frequent in the group 6-15 years of age. People with Down syndrome might sleep in unusual postures to avoid upper airway obstruction caused by other anatomical factors. For nurses and other health professionals working in mainstream service, it is important to screen all persons with Down syndrome for symptoms suggestive of obstructive sleep apnea, particularly those six years of age and older, and to refer them for further evaluation for sleep disorders.

Characteristics of sleep-disordered breathing in children with down syndrome - A comparison with typically developing children.

Background: Compared with typically developing control children (CC), children with Down syndrome (DS) frequently exhibit sleep-disordered breathing (SDB) and unusual sleep postures (USPs). No studies have directly compared SDB-related signs and symptoms, SDB-related parameters, and USPs between children with DS and CC. This study aimed to evaluate the prevalences of SDB and USPs in children with DS and CC. Methods: We analyzed SDB-related parameters measured via overnight pulse oximetry and questionnaires administered to parents on SDB-related signs and symptoms, including sleeping postures. Estimated SDB was defined as a 3% oxygen desaturation index (ODI) ≥5 dips/h. Results: Fifty-one children with DS (4-5 years: N = 12, 6-10 years: N = 23, 11-15 years: N = 16) and sixty-three CC (4-5 years: N = 18, 6-10 years: N = 27, 11-15 years: N = 18) were included. The prevalence of estimated SDB and observed USPs was higher in children with DS than in CC (p < 0.0001). Among children aged 11-15 years old, but not those aged 4-5 and 6-10 years old, frequency of arousal and apnea (p = 0.045 and p = 0.01, respectively) were higher in children with DS than in CC. Multivariate analyses showed that DS was associated with SDB-related signs and symptoms, estimated SDB, 3% ODI, average oxygen saturation (SpO2), and nadir SpO2, while USPs were associated only with higher values of SpO2 <90%. Conclusions: Estimated SDB tended to increase in children with DS but decreased in CC with growth. USPs were more frequent in children with DS than in CC, especially in older children. USPs might indicate severe hypoxemia due to SDB in DS.

A Cross-Sectional Comparison of the Prevalence of Obstructive Sleep Apnea Symptoms in Adults With Down Syndrome in Scotland and Japan.

Small studies in Western populations report a high prevalence of obstructive sleep apnea (OSA) in adults with Down syndrome. To date, ethnic differences have not been explored. A questionnaire sent to 2,752 adults with Down syndrome aged ≥16 years in Scotland and Japan (789 valid responses) estimated OSA prevalence based on reported symptoms. Symptoms were common in both countries, with snoring (p = 0.001) and arousals (p = 0.04) more prevalent in Japan. Estimated OSA prevalence in adults with Down syndrome was similar in the two countries, and raised in comparison with the general adult population (19.6% in Scotland and 14.3% in Japan; p = 0.08), though BMI was a confounder. Identification and treatment of OSA is recommended in adults with Down syndrome, regardless of ethnicity.

The severity of obstructive sleep apnea syndrome cannot predict the accumulation of brain amyloid by imaging with [11C]-Pittsburgh compound B PET computed tomography in patients with a normal cognitive function.

OBJECTIVE: Disturbed sleep due to obstructive sleep apnea syndrome (OSAS) might accelerate amyloidß (Aß) deposition, which can be a crucial factor in Alzheimer's disease. We studied Aß deposition in untreated OSAS patients with normal cognition. METHOD: We performed polysomnography (PSG) and Aß imaging with [11C]-Pittsburgh compound B PET computed tomography (11C-PiB PET CT) in 14 untreated OSAS patients (apnea-hypopnea index: 43.8 ± 26.3/h). RESULTS: The abnormal accumulation of enhanced 11C-PiB PET was observed only one patient with severe, but not the most severe. CONCLUSIONS: The OSAS severity alone may not predict Aß deposition in OSAS patients with normal cognition.

Assessment by airway ellipticity on cine-MRI to differentiate severe obstructive sleep apnea.

INTRODUCTION: The severity of obstructive sleep apnea (OSA) is assessed by the apnea-hypopnea index (AHI) determined from polysomnography (PSG). However, PSG requires a specialized facility with well-trained specialists and takes overnight. Therefore, simple tools, which could distinguish severe OSA, have been needed before performing PSG. OBJECTIVES: We propose the new index using cine-MRI as a screening test to differentiate severe OSA patients, who would need PSG and proper treatment. METHODS: Thirty-six patients with suspected OSA (mean age 54.6 y, mean AHI 52.6 events/h, 33 males) underwent airway cine-MRI at the fourth cervical vertebra level during 30 s of free breathing and PSG. The minimum airway ellipticity (AE) in 30 s duration was measured, and was defined as the severity of OSA. Patients were divided into severe OSA, not-severe OSA, and normal groups, according to PSG results. The comparison of AE between any two of the three groups was performed by Wilcoxon rank-sum test. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cut-off of AE for identifying severe OSA patients. RESULTS: The minimum AE for severe OSA was significantly lower than that for not-severe OSA and normal (severe, 0.17 ± 0.16; not severe, 0.31 ± 0.17; normal, 0.38 ± 0.19, P < .05). ROC analysis revealed that the optimal cutoff of the minimum AE 0.21 identified severe OSA patients, with an area under the curve of 0.75, 68% sensitivity, and 83% specificity. CONCLUSION: AE is a feasible quantitative index, and a promising screening test for detecting severe OSA patients.

Aldosterone excess and resistance to 24-h blood pressure control.

BACKGROUND: Aldosterone excess has been reported to be a common cause of resistant hypertension. To what degree this represents true treatment resistance is unknown. OBJECTIVE: The present study aimed to compare the 24-h ambulatory blood pressure monitoring (ABPM) levels in resistant hypertensive patients with or without hyperaldosteronism. METHODS: Two hundred and fifty-one patients with resistant hypertension were prospectively evaluated with an early-morning plasma renin activity (PRA), 24-h urinary aldosterone and sodium, and 24-h ABPM. Daytime, night-time, and 24-h blood pressure (BP) and nocturnal BP decline were determined. Hyperaldosteronism (H-Aldo) was defined as suppressed PRA (<1.0 ng/ml per h or <1.0 mug/l per h) and elevated 24-h urinary aldosterone excretion (>/= 12 mug/24-h or >/= 33.2 nmol/day) during ingestion of the patient's routine diet. RESULTS: In all patients, the mean office BP was 160.0 +/- 25.2/89.4 +/- 15.3 mmHg on an average of 4.2 medications. There was no difference in mean office BP between H-Aldo and normal aldosterone status (N-Aldo) patients. Daytime, night-time, and 24-h systolic and diastolic BP were significantly higher in H-Aldo compared to N-Aldo males. Daytime, night-time, and 24-h systolic BP were significantly higher in H-Aldo compared to N-Aldo females. Multivariate analysis indicated a significant interaction between age and aldosterone status such that the effects of aldosterone on ambulatory BP levels were more pronounced with increasing age. CONCLUSIONS: In spite of similar office BP, ABPM levels were higher in resistant hypertensive patients with H-Aldo. These results suggest that high aldosterone levels impart increased cardiovascular risk not reflected by office BP measurements.

Plasma aldosterone is related to severity of obstructive sleep apnea in subjects with resistant hypertension.

OBJECTIVE: Obstructive sleep apnea (OSA) and primary aldosteronism are common in subjects with resistant hypertension; it is unknown, however, if the two disorders are causally related. This study relates plasma aldosterone and renin levels to OSA severity in subjects with resistant hypertension, and in those with equally severe OSA but without resistant hypertension serving as control subjects. METHODS: Seventy-one consecutive subjects referred to the University of Alabama at Birmingham (UAB) for resistant hypertension (BP uncontrolled on three medications) and 29 control subjects referred to UAB Sleep Disorders Center for suspected OSA were prospectively evaluated by an early morning plasma aldosterone concentration (PAC) and renin level, and by overnight, attended polysomnography. RESULTS: OSA (apnea-hypopnea index [AHI] > or = 5/h) was present in 85% of subjects with resistant hypertension. In these subjects, PAC correlated with AHI (rho = 0.44, p = 0.0002) but not renin concentration. Median PAC was significantly lower in control subjects compared to subjects with resistant hypertension (5.5 ng/dL vs 11.0 ng/dL, p < 0.05) and not related to AHI. In male subjects compared to female subjects with resistant hypertension, OSA was more common (90% vs 77%) and more severe (median AHI, 20.8/h vs 10.8/h; p = 0.01), and median PAC was significantly higher (12.0 ng/dL vs 8.8 ng/dL, p = 0.006). CONCLUSION: OSA is extremely common in subjects with resistant hypertension. A significant correlation between PAC and OSA severity is observed in subjects with resistant hypertension but not in control subjects. While cause and effect cannot be inferred, the data suggest that aldosterone excess may contribute to OSA severity.

An autopsy case report of annuloaortic ectasia with cardiac tamponade ruptured from an aneurysm of the right Valsalva sinus.

Annuloaortic ectasia (AAE) is a clinicopathologic condition with primary or secondary dilatation of the aortic annulus and aneurysm of the proximal thoracic aorta, leading to aortic regurgitation. We herein report an autopsy case of a Japanese 57-year-old male with AAE who died of a cardiac tamponade rupture from the sinus of the right coronary. The wall of the aortic root, particularly that of the sinus of the right coronary Valsalva, underwent extensive fibrosis with loss or fragmentation of the elastic lamina in the medial layer and perforation directly into the pericardial space. The adventitia of the proximal aorta to the aortic arch was diffusely fibrotic with both acute and chronic hemorrhage and chronic inflammatory infiltrate. However, the ascending aortic media was largely intact, except for focal laminar necrosis at the center of the medial layer; no medial cystic necrosis, laminar necrosis, or mesoaortitis/panaortitis was present in the thoracic or abdominal aorta, nor in the main aortic branches, which was suggestive of Takayasu disease and giant cell arteritis. Thus, this patient was diagnosed to have idiopathic AAE with sustained peri-aortic hemorrhage, and he finally died of a cardiac tamponade resulting from an aneurysmal rupture.

Evaluation of water content around airway in obstructive sleep apnea patients using peripharyngeal mucosal T2 magnetic resonance imaging.

INTRODUCTION: Obstructive sleep apnea (OSA) is common sleep disorder characterized by repetitive episodes of airway closure which usually occurs in the retropalatal region of the oropharynx. It has been known that upper airway mucosa in OSA patients is described as edematous, but not fully clarified. OBJECTIVES: This study aimed to investigate and establish magnetic resonance imaging (MRI) parameter to estimate tissue water content at retropalatal level and its relationship with sleep parameters in OSA patients. METHODS: Forty-eight subjects with OSA underwent overnight polysomnography and cervical MRI with 1.5-tesla [mean (SD) age 55 (14) years and apnea-hypopnea index (AHI) 45.2 (26.1) events/hour, 79.2% male]. On the axial T2-weighted images from epipharynx to oropharynx, the signal intensities of masseter muscle and peripharyngeal mucosa [T2 mucous-to-masseter intensity ratio (T2MMIR)], was used as water content estimation in the retropalatal region. Partial correlation analysis was performed to examine the correlation between T2MMIR and polysomnography parameters. RESULTS: We found that there were strong and positive correlations between the T2MMIR and AHI (r = 0.545, P < 0.05), supine AHI (r = 0.553, P < 0.05) and REM AHI (r = 0.640, P < 0.01) by partial correlation analysis. Besides, in patients with less efficient sleep who had more stage 1 sleep, significantly higher T2MMIR was noted (r = 0.357, P < 0.05). CONCLUSIONS: This study confirmed that peripharyngeal T2MMIR can be a simple parameter representing peripharyngeal tissue water contents related to severe OSA.

Cumulative Hypoxemia During Sleep Predicts Vascular Endothelial Dysfunction in Patients With Sleep-Disordered Breathing.

BACKGROUND: Sleep-disordered breathing (SDB) is associated with repeated intermittent hypoxemia, and it is known as one of the risk factors for cardiovascular diseases. Previous studies assessing the effects of frequency and depth of hypoxemia on cardiovascular diseases have shown conflicting results. The aim of the current study was to clarify what SDB-related parameters most predict endothelial dysfunction to better understand the pathogenesis of endothelial dysfunction in patients with SDB. METHODS: We conducted polysomnography (PSG) and measured flow-mediated vasodilation response (%FMD) in 50 outpatients suspected of SDB. Evaluated indices included: apnea-hypopnea index (AHI), 3% oxygen desaturation index (3%ODI), averaged arterial oxygen saturation (averaged SpO2), lowest arterial oxygen saturation (lowest SpO2), ratio of arterial oxygen saturation <90% (

Prevalence of Sleep Disordered Breathing among Patients with Nocturia at a Urology Clinic.

OBJECTIVE: We assessed the prevalence of sleep disordered breathing (SDB) and characteristics among patients who visited a urology clinic complaining of nocturia (URO group) and those who visited a sleep apnea (SA) clinic complaining of excessive daytime sleepiness (EDS) (SA group). Additionally, we evaluated the effects of continuous positive airway pressure (CPAP) therapy in the URO group patients with nocturia and SDB resistant to conventional therapy for nocturia. METHODS: Questionnaires were used to assess EDS, nocturia and lower urinary tract symptoms in 34 URO group patients and 49 age-matched SA group patients. We also compared these factors in the male patients in both groups and the male and female patients in the SA group. Significant SDB was diagnosed as a 3% oxygen desaturation index (3%ODI) on pulse oximeter of >5/h. The treatment response was analyzed in six URO group patients treated with CPAP after not responding to the conventional medical treatment. RESULTS: SDB was found in 91.8% of the SA group patients and 70.6% of the URO group patients. The level of EDS and lower urinary tract symptoms were similar in both groups. The SA group showed higher 3%ODI values, while the frequency of urination during bedtime was higher in the URO group. The frequency of nocturnal urination was reduced after CPAP in the subjects resistant to conventional therapy. CONCLUSION: SDB is as prevalent in patients who visit a urology clinic complaining of nocturia as in those who visit a sleep apnea clinic. Patients who complains of nocturia must be assessed for SDB before starting therapy for nocturia.

Impaired endothelium-dependent flow-mediated vasodilation in hypertensive subjects with hyperaldosteronism.

BACKGROUND: Recent studies suggest that aldosterone may impair endothelium-dependent vascular function through suppression of nitric oxide formation. Assessments of forearm blood flow or arterial compliance suggest a similar effect in humans. The present study was designed to determine whether chronic aldosterone excess in subjects with resistant hypertension impairs endothelium-dependent vascular reactivity as indexed by direct assessment of brachial artery flow-mediated dilation (FMD). METHODS AND RESULTS: Consecutive subjects (n=80) with resistant hypertension were prospectively evaluated with an early-morning ratio of plasma aldosterone to plasma renin activity and 24-hour urinary aldosterone and sodium. Changes in brachial artery diameter during reactive hyperemia were measured by high-resolution ultrasound. Hyperaldosteronism was diagnosed on the basis of a renin activity <1.0 ng x mL(-1) x h(-1), urinary aldosterone >12 microg/24 h, and urinary sodium >200 mEq/24 h. FMD was significantly lower in 36 subjects with hyperaldosteronism (1.8+/-1.3% versus 3.9+/-1.9% from baseline; P<0.0001) compared with the 44 subjects without hyperaldosteronism. FMD was negatively and significantly correlated with plasma aldosterone (r=-0.38, P=0.0006), 24-hour urinary aldosterone (r=-0.49, P<0.0001), and ratio of plasma aldosterone to plasma renin activity (r=-0.43, P<0.0001) but was independent of blood pressure, age, and body mass index. In 30 subjects, 3 months of treatment with spironolactone significantly increased FMD (2.5+/-1.7 versus 6.0+/-2.0%; P<0.0001) independently of blood pressure change. CONCLUSIONS: These data demonstrate a strong association between aldosterone excess and impaired endothelial function in human subjects as indexed by flow-mediated arterial vasodilation. These results suggest that chronic aldosteronism may have a blood pressure-independent effect on cardiovascular disease progression in subjects with resistant hypertension.

Validity of plasma aldosterone-to-renin activity ratio in African American and white subjects with resistant hypertension.

BACKGROUND: Recent reports suggesting that primary aldosteronism (PA) is more common than historically thought have often relied on use of the plasma aldosterone concentration (PAC) to plasma renin activity (PRA) ratio (ARR) to identify patients with PA. Prior determinations of the validity of the ARR had been generally limited to subjects that could be withdrawn from antihypertensive therapy and to non-African American subjects. METHODS AND RESULTS: The current study was designed to evaluate prospectively the diagnostic value of the ARR in treated African American and white subjects with resistant hypertension. Consecutive subjects referred to a university hypertension clinic for resistant hypertension were evaluated with an early morning ARR and a 24-h urinary aldosterone and sodium. The presence of PA was defined as a suppressed PRA (<1.0 ng/mL/h) and elevated urinary aldosterone excretion (>12 microg/24 h) during high dietary sodium ingestion (>200 mEq/24 h). In 58 subjects, PA was confirmed. The ARR was elevated (>20) in 45 of 58 subjects with PA and in 35 of the 207 patients without PA, resulting in a sensitivity of 78% and specificity of 83% with a corresponding positive predictive value of 56% and a negative predictive value of 93%. Among African American subjects, the ARR was less sensitive than in white subjects (75% v 80%), but it still had a high negative predictive value (92% v 94%). CONCLUSIONS: These data indicate that the ARR is valid as a screening test for PA in African American and white patients on stable antihypertensive treatments, but a high percentage of false-positive results precludes using it for accurate diagnosis of PA.

A nationwide cross-sectional study on congenital heart diseases and symptoms of sleep-disordered breathing among Japanese Down's syndrome people.

OBJECTIVE: It is well known that people with Down's syndrome (DS) frequently complicate with congenital heart diseases (CHDs). Patients with heart diseases often have sleep-disordered breathing as a co-morbidity (SDB) which worsens the heart diseases. However, the relationship between SDB and CHDs in DS people has not yet been fully elucidated. The aim of this study was to establish the association between SDB and CHDs in DS people using data from a large nationwide questionnaire survey in Japan. METHODS: We conducted a cross-sectional questionnaire survey of a randomly selected sample of 2,000 DS people and their caregivers throughout Japan to examine the associations between observed signs of SDB and CHDs in DS people. The questionnaire included the presence of SDB symptoms (snoring, apnea, arousal, nocturia, and napping) and CHDs (the presence and types of CHDs). RESULTS: Of the 1,222 replies received from the caregivers, 650 reported complications of some type of CHDs. The observed apnea tended to be higher among DS people with CHDs than those without CHDs (OR=1.28, 95% CI=0.97-1.70, p=0.09). DS people with tetralogy of Fallot reported significantly more frequent apnea than those without CHDs (OR=3.10, 95% CI=1.36-7.05, p<0.01). CONCLUSION: SDB prevailed among DS people with severe CHDs, such as tetralogy of Fallot. Careful attention to the signs of SDB in such patients may lead to earlier clinical intervention removing the vicious cycle between SDB and CHDs.