Does Obstructive Sleep Apnea Influence Blood Pressure and Arterial Stiffness in Response to Antihypertensive Treatment?

Untreated obstructive sleep apnea (OSA) is common in patients with hypertension and may impair blood pressure (BP) and target-organ damage responses to antihypertensive therapy. In this study, we recruited hypertensive patients who underwent treatment with a 30-day regimen of hydrochlorothiazide 25 mg plus enalapril (20 mg BID) or losartan (50 mg BID) and were assessed with a baseline clinical evaluation, polysomnography, 24-hour ambulatory BP monitoring, and carotid-femoral pulse wave velocity. All the examinations except for polysomnography were repeated at 6 and 18 months of follow-up. We studied 94 hypertensive patients (mean age, 55±9 years). The frequency of OSA was 55%. Compared with baseline, we did not observe significant differences between groups in 24-hour BP, daytime systolic and diastolic BPs, or night-time systolic BP at 6 and 18 months. The BP control rate at 24 hours (<130/80 mm Hg) was similar between the groups (baseline, 42.3% versus 45.2%; 6 months, 46.9% versus 57.5%; 18 months, 66.7% versus 61.5%). However, patients with OSA had higher night-time diastolic BP decrease than did the non-OSA group (6 months, -4.9±11.8 versus -0.3±10.3 mm Hg; 18 months, -6.7±11.1 versus -1.2±10.6 mm Hg; P=0.027). There were no differences in the number and class of antihypertensive medications prescribed during follow-up. In terms of arterial stiffness, patients with OSA had higher pulse wave velocity than did patients without OSA at baseline (10.3±1.9 versus 9.2±1.7 m/s; P=0.024), but both groups had similar decreases in pulse wave velocity during follow-up. In conclusion, with combined antihypertensive treatment aimed at controlling BP, hypertensive patients with OSA had similar 24-hour BP and arterial stiffness to those without OSA.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment)

ABSTRACT: The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy.

Spironolactone Versus Clonidine as a Fourth-Drug Therapy for Resistant Hypertension: The ReHOT Randomized Study (Resistant Hypertension Optimal Treatment).

The aim of this study is to compare spironolactone versus clonidine as the fourth drug in patients with resistant hypertension in a multicenter, randomized trial. Medical therapy adherence was checked by pill counting. Patients with resistant hypertension (no office and ambulatory blood pressure [BP] monitoring control, despite treatment with 3 drugs, including a diuretic, for 12 weeks) were randomized to an additional 12-week treatment with spironolactone (12.5-50 mg QD) or clonidine (0.1-0.3 mg BID). The primary end point was BP control during office (<140/90 mm Hg) and 24-h ambulatory (<130/80 mm Hg) BP monitoring. Secondary end points included BP control from each method and absolute BP reduction. From 1597 patients recruited, 11.7% (187 patients) fulfilled the resistant hypertension criteria. Compared with the spironolactone group (n=95), the clonidine group (n=92) presented similar rates of achieving the primary end point (20.5% versus 20.8%, respectively; relative risk, 1.01 [0.55-1.88]; P=1.00). Secondary end point analysis showed similar office BP (33.3% versus 29.3%) and ambulatory BP monitoring (44% versus 46.2%) control for spironolactone and clonidine, respectively. However, spironolactone promoted greater decrease in 24-h systolic and diastolic BP and diastolic daytime ambulatory BP than clonidine. Per-protocol analysis (limited to patients with ≥80% adherence to spironolactone/clonidine treatment) showed similar results regarding the primary end point. In conclusion, clonidine was not superior to spironolactone in true resistant hypertensive patients, but the overall BP control was low (≈21%). Considering easier posology and greater decrease in secondary end points, spironolactone is preferable for the fourth-drug therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01643434.

Association of obstructive sleep apnea with arterial stiffness and nondipping blood pressure in patients with hypertension.

Whether sex influences the association of obstructive sleep apnea (OSA) with markers of cardiovascular risk in patients with hypertension is unknown. In this study, 95 hypertensive participants underwent carotid-femoral pulse wave velocity, 24-hour ambulatory blood pressure monitoring, echocardiogram, and polysomnography after a 30-day standardized treatment with hydrochlorothiazide plus enalapril or losartan. OSA was present in 52 patients. Compared with non-OSA patients, pulse wave velocity values were higher in the OSA group (men: 11.1±2.2 vs 12.7±2.4 m/s, P=.04; women: 11.8±2.4 vs 13.2±2.2 m/s, P=.03). The proportion of diastolic dysfunction was significant in men and women with OSA. Compared with non-OSA patients, nondipping systolic blood pressure in OSA was higher in men (14.3% vs 46.4%) and in women (41.4% vs 65.2%). OSA was independently associated with pulse wave velocity (ß=1.050; P=.025) and nondipping systolic blood pressure (odds ratio, 3.03; 95% confidence interval, 1.08-8.55; P=.035) in the regression analysis. In conclusion, OSA is independently associated with arterial stiffness and nondipping blood pressure in patients with hypertension regardless of sex.

The Role of Acute Intermittent Hypoxia in Neutrophil-Generated Superoxide, Sympathovagal Balance, and Vascular Function in Healthy Subjects.

Introduction: Recurrent hypoxia (HPX), a hallmark of the obstructive sleep apnea (OSA), impairs autonomic balance, and increases arterial blood pressure (BP). Oxidative stress is one of the mechanisms involved in these alterations. The cumulative effect of acute intermittent HPX and the chronicity may determine whether the response crosses the threshold from having protective value to pathology. However, the impact of acute intermittent HPX-reoxygenation on markers of oxidative stress in healthy individuals remains to be fully understood. Objective: To analyze the effects of the acute intermittent HPX on the generation of neutrophil-derived superoxide, sympathovagal balance, and vascular function in healthy subjects. Methods: We applied six cycles of intermittent HPX (10% O2 and 90% N2) for 5 min followed by 2 min of room-air in 15 healthy volunteers (34 ± 2 years; 22.3 ± 0.46 kg/m2), without OSA (polysomnography), during wakefulness. During the experimental protocol, we recorded O2 saturation, end-tidal CO2, heart rate (HR), systolic, and diastolic BP, cardiac output (CO) and peripheral resistance (PR). Cardiac sympathovagal balance was determined by HR variability analysis (low frequency and high frequency bands, LF/HF). Superoxide generation in polymorphonuclear neutrophil cells were established using relative luminescence units (PMNs RLU) at baseline (pre-HPX) and immediately after hypoxia induction (post-HPX6). Results: The studied subjects had normal levels of BP, plasma glucose, lipid profile, and inflammatory marker (C-reactive protein). Acute intermittent HPX increased HR, systolic BP, CO, and decreased PR. Additionally, acute intermittent HPX increased PMNs RLU, measured post-HPX6 (470 ± 50 vs. 741 ± 135, P < 0.05). We found a similar increase in LF/HF post-HPX6 (0.91 ± 0.11 vs. 2.85 ± 0.40, P < 0.05). PR was diminished from pre-HPX to post-HPX6 (1.0 ± 0.03 vs. 0.85 ± 0.06, P < 0.05). Further analysis showed significant association between O2 saturation and PMNs RLU (R = -0.62, P = 0.02), and with LF/HF (R = -0.79, P = 0.02) post-HPX6. In addition, an association was found between PMNs RLU and PR post-HPX6 (R = 0.58, P = 0.04). Conclusion: Acute exposure to intermittent HPX not only increased superoxide generation in neutrophils, but also impaired cardiac sympathovagal balance in healthy subjects. These data reinforce the role of intermittent HPX in superoxide generation on neutrophils, which may lead to an impairment in peripheral vascular resistance.

Resistant hypertension optimal treatment trial: a randomized controlled trial.

The prevalence of resistant hypertension (ReHy) is not well established. Furthermore, diuretics, angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and calcium channel blockers are largely used as the first 3-drug combinations for treating ReHy. However, the fourth drug to be added to the triple regimen is still controversial and guided by empirical choices. We sought (1) to determine the prevalence of ReHy in patients with stage II hypertension; (2) to compare the effects of spironolactone vs clonidine, when added to the triple regimen; and (3) to evaluate the role of measuring sympathetic and renin-angiotensin-aldosterone activities in predicting blood pressure response to spironolactone or clonidine. The Resistant Hypertension Optimal Treatment (ReHOT) study (ClinicalTrials.gov NCT01643434) is a prospective, multicenter, randomized trial comprising 26 sites in Brazil. In step 1, 2000 patients will be treated according to hypertension guidelines for 12 weeks, to detect the prevalence of ReHy. Medical therapy adherence will be checked by pill count monitoring. In step 2, patients with confirmed ReHy will be randomized to an open label 3-month treatment with spironolactone (titrating dose, 12.5-50 mg once daily) or clonidine (titrating dose, 0.1-0.3 mg twice daily). The primary endpoint is the effective control of blood pressure after a 12-week randomized period of treatment. The ReHOT study will disseminate results about the prevalence of ReHy in stage II hypertension and the comparison of spironolactone vs clonidine for blood pressure control in patients with ReHy under 3-drug standard regimen.

Arousals are frequent and associated with exacerbated blood pressure response in patients with primary hypertension.

BACKGROUND: Spontaneous arousals are relatively common during sleep, and induce hemodynamic responses. We sought to investigate the frequency and magnitude of blood pressure (BP) increases triggered by spontaneous arousals in patients with primary hypertension. METHODS: We conducted a study in which we divided 18 nonobese, sedentary adults without sleep-disordered breathing into two groups, consisting of: (i) hypertensive (HT, n = 8) patients; and (ii) normotensive (NT, n = 10) controls. The groups were matched for age and body mass index. All subjects underwent full polysomnography with simultaneous monitoring of heart rate (HR) and beat-by-beat BP. Each subject's BP and HR were analyzed immediately before BP peaks triggered by spontaneous arousals during stage 2 of nonrapid eye movement sleep. RESULTS: The total sleep time, sleep efficiency, and sleep structure in the two study groups were similar. In contrast, the number of arousals was significantly higher in the HT than in the NT group, at 25 ± 5 vs. 12 ± 3 events/h, respectively (P < 0.05). The HR of the HT and NT groups was similar before arousal (65 ± 3 bpm vs. 67 ± 3 bpm, respectively, P < 0.01) and increased significantly and similarly in the two groups upon arousal (to 79 ± 6 bpm vs. 74 ± 4 bpm, respectively, P < 0.01). Systolic and diastolic BPs were significantly higher throughout sleep in the HT than in the NT group. During spontaneous arousals, BP increased in both groups (P < 0.05). However, the magnitude of the increase in systolic BP was significantly greater in the HT than in the NT group (22 ± 3 mm Hg vs. 15 ± 3 mm Hg, P < 0.05). CONCLUSIONS: Patients with hypertension who do not have sleep-disordered breathing have an increased cardiovascular burden during sleep, which may be due to the greater number of arousals and exacerbated systolic BP response that they experience during sleep. These novel findings may have cardiovascular implications in patients with hypertension.

Cardiovascular effects of partial sleep deprivation in healthy volunteers.

Sleep deprivation is common in Western societies and is associated with increased cardiovascular morbidity and mortality in epidemiological studies. However, the effects of partial sleep deprivation on the cardiovascular system are poorly understood. In the present study, we evaluated 13 healthy male volunteers (age: 31 ± 2 yr) monitoring sleep diary and wrist actigraphy during their daily routine for 12 nights. The subjects were randomized and crossover to 5 nights of control sleep (>7 h) or 5 nights of partial sleep deprivation (<5 h), interposed by 2 nights of unrestricted sleep. At the end of control and partial sleep deprivation periods, heart rate variability (HRV), blood pressure variability (BPV), serum norepinephrine, and venous endothelial function (dorsal hand vein technique) were measured at rest in a supine position. The subjects slept 8.0 ± 0.5 and 4.5 ± 0.3 h during control and partial sleep deprivation periods, respectively (P < 0.01). Compared with control, sleep deprivation caused significant increase in sympathetic activity as evidenced by increase in percent low-frequency (50 ± 15 vs. 59 ± 8) and a decrease in percent high-frequency (50 ± 10 vs. 41 ± 8) components of HRV, increase in low-frequency band of BPV, and increase in serum norepinephrine (119 ± 46 vs. 162 ± 58 ng/ml), as well as a reduction in maximum endothelial dependent venodilatation (100 ± 22 vs. 41 ± 20%; P < 0.05 for all comparisons). In conclusion, 5 nights of partial sleep deprivation is sufficient to cause significant increase in sympathetic activity and venous endothelial dysfunction. These results may help to explain the association between short sleep and increased cardiovascular risk in epidemiological studies.

Obstructive sleep apnea: the most common secondary cause of hypertension associated with resistant hypertension.

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension may help to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluating secondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients with resistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, including aortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renal parenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52±1 years, 43% males, systolic and diastolic blood pressure: 176±31 and 107±19 mm Hg, respectively), obstructive sleep apnea (apnea-hypopnea index: >15 events per hour) was the most common condition associated with resistant hypertension (64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%), oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified (primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age >50 years (odds ratio: 5.2 [95% CI: 1.9-14.2]; P<0.01), neck circumference ≥41 cm for women and ≥43 cm for men (odds ratio: 4.7 [95% CI: 1.3-16.9]; P=0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3-11]; P=0.02) were predictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common condition associated with resistant hypertension. Age >50 years, large neck circumference measurement, and snoring are good predictors of obstructive sleep apnea in this population.

Avanços recentes do impacto da apneia obstrutiva do sono na hipertensão arterial sistêmica / Recent advances of the impact of obstructive sleep apnea on systemic hypertension / Avances recientes del impacto de la Apnea Obstructiva del Sueño en la Hipertensión Arterial Sistémica

A apneia obstrutiva do sono (AOS) é uma condição clínica comum na população em geral, principalmente entre os pacientes portadores de doenças cardiovasculares. Mais do que um fenômeno local de obstrução das vias aéreas superiores, a AOS traz repercussões sistêmicas que podem incluir a hipóxia intermitente, a redução abrupta da pressão intratorácica e a ocorrência de microdespertares com fragmentação do sono. Nas últimas décadas, inúmeras evidências apontam de forma consistente a AOS como um importante fator envolvido na ocorrência de doenças cardiovasculares. Particularmente, a relação entre a AOS e a hipertensão arterial sistêmica (HAS) é a que encontra um maior conjunto de evidências. Atualmente, encontram-se dados que consideram a AOS uma importante causa secundária de HAS. Mais do que isso, a AOS está independentemente associada a um pior controle pressórico, alteração do descenso noturno da pressão arterial e à presença de lesões de órgãos-alvo, tais como a hipertrofia do ventrículo esquerdo e a microalbuminúria. Estudos randomizados sugerem que o tratamento da AOS, especialmente com a pressão positiva contínua de vias aéreas superiores (CPAP), considerado o tratamento padrão para a AOS, promove redução significante da pressão arterial nas 24 horas, efeito esse mais significante no subgrupo de pacientes com HAS não controlada e nos pacientes com HAS resistente. A despeito de todas essas evidências, a AOS ainda continua sendo subdiagnosticada. O objetivo desta revisão é discutir os recentes avanços nos mecanismos fisiopatológicos, na apresentação clínica e no tratamento da AOS, e o benefício sobre a pressão arterial.

Obstructive sleep apnea (OSA) is a common clinical condition in the general population, especially among patients with cardiovascular diseases. More than just a local phenomenon of upper respiratory tract obstruction, OSA leads to systemic consequences that may include intermittent hypoxia, sudden reduction of the intrathoracic pressure, and the occurrence of micro-awakenings with sleep fragmentation. In the past decades, innumerous evidences have consistently pointed to OSA as an important factor related to the presence of cardiovascular diseases. In particular, the relationship between OSA and systemic hypertension (SH) is the one supported by the largest body of evidence. Currently, there are data suggesting that OSA is an important secondary cause of SH. More importantly, OSA is independently associated with poorer blood pressure control, changes in sleep dip, and presence of target-organ damage such as left ventricular hypertrophy and microalbuminuria. Randomized studies suggest that the management of OSA, especially with continuous positive airway pressure (CPAP) - which is considered the standard treatment for OSA - promotes a significant 24-hour blood pressure reduction, and this effect is more significant in the subgroup of patients with uncontrolled SH and drug-resistant SH. Despite all those evidences, OSA has still been underdiagnosed. The objective of this review is to discuss the recent advances in the pathophysiological mechanisms, clinical presentation, and treatment of OSA, as well as the benefits this treatment can bring on blood pressure.

La apnea obstructiva del sueño (AOS) es una condición clínica común en la población en general, principalmente entre los pacientes portadores de enfermedades cardiovasculares. Más que un fenómeno local de obstrucción de las vías aéreas superiores, la AOS trae repercusiones sistémicas que pueden incluir la hipoxia intermitente, la reducción abrupta de la presión intratorácica y la ocurrencia de microdespertares con fragmentación del sueño. En las últimas décadas, innúmeras evidencias señalan de forma consistente la AOS como un importante factor envuelto en la ocurrencia de enfermedades cardiovasculares. Particularmente, la relación entre la AOS y la Hipertensión Arterial Sistémica (HAS) es la que encuentra un mayor conjunto de evidencias. Actualmente, se encuentran datos que consideran la AOS una importante causa secundaria de HAS. Más que eso, la AOS está independientemente asociada a un peor control presórico, alteración del descenso nocturno de la presión arterial y a la presencia de lesiones de órganos-blanco, tales como la hipertrofia del ventrículo izquierdo y la microalbuminuria. Estudios randomizados sugieren que el tratamiento de la AOS, especialmente con la presión positiva continua de vías aéreas superiores (CPAP), considerado el tratamiento estándar para la AOS, promueve reducción significativa de la presión arterial en las 24 horas, efecto ese más significativo en el subgrupo de pacientes con HAS no controlada y en los pacientes con HAS resistente. A despecho de todas esas evidencias, la AOS aun continúa siendo subdiagnosticada. El objetivo de esta revisión es discutir los recientes avances en los mecanismos fisiopatológicos, en la presentación clínica y en el tratamiento de la AOS, y el beneficio sobre la presión arterial.

Recent advances of the impact of obstructive sleep apnea on systemic hypertension.

Obstructive sleep apnea (OSA) is a common clinical condition in the general population, especially among patients with cardiovascular diseases. More than just a local phenomenon of upper respiratory tract obstruction, OSA leads to systemic consequences that may include intermittent hypoxia, sudden reduction of the intrathoracic pressure, and the occurrence of micro-awakenings with sleep fragmentation. In the past decades, innumerous evidences have consistently pointed to OSA as an important factor related to the presence of cardiovascular diseases. In particular, the relationship between OSA and systemic hypertension (SH) is the one supported by the largest body of evidence. Currently, there are data suggesting that OSA is an important secondary cause of SH. More importantly, OSA is independently associated with poorer blood pressure control, changes in sleep dip, and presence of target-organ damage such as left ventricular hypertrophy and microalbuminuria. Randomized studies suggest that the management of OSA, especially with continuous positive airway pressure (CPAP) - which is considered the standard treatment for OSA - promotes a significant 24-hour blood pressure reduction, and this effect is more significant in the subgroup of patients with uncontrolled SH and drug-resistant SH. Despite all those evidences, OSA has still been underdiagnosed. The objective of this review is to discuss the recent advances in the pathophysiological mechanisms, clinical presentation, and treatment of OSA, as well as the benefits this treatment can bring on blood pressure.

The effects of continuous positive airway pressure on prehypertension and masked hypertension in men with severe obstructive sleep apnea.

Obstructive sleep apnea and hypertension are common conditions that frequently coexist. Continuous positive airway pressure (CPAP) reduces blood pressure in patients with obstructive sleep apnea and sustained hypertension. However, the impact of CPAP on patients with obstructive sleep apnea and prehypertension and masked hypertension, conditions associated with increased cardiovascular risk, is unknown. Thirty-six male patients (age, 43 ± 7 years; body mass index, 28.8 ± 3.0 kg/m(2)) with untreated severe obstructive sleep apnea (apnea-hypopnea index, 56 ± 22 events/hr on polysomnography) with diagnostic criteria for prehypertension and/or masked hypertension, based on office and 24-hour ambulatory blood pressure monitoring, respectively, were studied. The patients randomized to no treatment (control; n=18) or CPAP (n=18) for 3 months had similar frequency of prehypertension and masked hypertension at study entry. There were no significant changes in blood pressure in patients randomized to the control group. In contrast, patients randomized to CPAP presented significant reduction in office systolic (from 126 ± 5 to 121 ± 7 mm Hg; P=0.001) and a trend for diastolic blood pressure (from 75 ±7 to 73 ± 8 mm Hg; P=0.08) as well as a significant decrease in daytime and nighttime systolic and diastolic blood pressure (P<0.05 for each comparison). There was a significant reduction in the frequency of prehypertension (from 94% to 55%; P=0.02) and masked hypertension (from 39% to 5%; P=0.04) only in the CPAP group. In conclusion, effective CPAP therapy promotes significant reduction in the frequency of prehypertension and masked hypertension by promoting significant blood pressure reductions in patients with severe obstructive sleep apnea.

Lack of circadian variation of pulse wave velocity measurements in healthy volunteers.

Arterial stiffness is an independent marker of cardiovascular events. Pulse wave velocity (PWV) is a validated method to detect arterial stiffness that can be influenced by several factors including age and blood pressure. However, it is not clear whether PWV could be influenced by circadian variations. In the present study, the authors measured blood pressure and carotid-femoral PWV measurements in 15 young healthy volunteers in 4 distinct periods: 8 am, noon, 4 pm, and 8 pm. No significant variations of systolic (P=.92), mean (P=.77), and diastolic (P=.66) blood pressure among 8 am (113±15, 84±8, 69±6 mm Hg), noon (114±13, 83±8, 68±6 mm Hg), 4 pm (114±13, 85±8, 70±7 mm Hg), and 8 pm (113±7, 83±10, 68±7 mm Hg), respectively, were observed. Similarly, carotid-femoral PWV did not change among the periods (8 am: 7.6 ± 1.4 m/s, noon: 7.4±1.1 m/s, 4 pm: 7.6±1.0 m/s, 8 pm, 7.6±1.3 m/s; P=.85). Considering all measurements, mean blood pressure significantly correlated with PWV (r=.31; P=.016). In young healthy volunteers, there is no significant circadian variation of carotid-femoral PWV. These findings support the concept that it does not appear mandatory to perform PWV measurements at exactly the same period of the day.

Unexplained sudden death in patients on the waiting list for renal transplantation.

BACKGROUND: The incidence of unexplained sudden death (SD) and the factors involved in its occurrence in patients with chronic kidney disease are not well known. METHODS: We investigated the incidence and the role of co-morbidities in unexplained SD in 1139 haemodialysis patients on the renal transplant waiting list. RESULTS: Forty-four patients died from SD of undetermined causes (20% of all deaths; 3.9 deaths/1000 patients per year), while 178 died from other causes and 917 survived. SD patients were older and likely to have diabetes, hypertension, past/present cardiovascular disease, higher left ventricular mass index, and lower ejection fraction. Multivariate analysis showed that cardiovascular disease of any type was the only independent predictor of SD (P = 0.0001, HR = 2.13, 95% CI 1.46-3.22). Alterations closely associated with ischaemic heart disease like angina, previous myocardial infarction and altered myocardial scan were not independent predictors of SD. The incidence of unexplained SD in these haemodialysis patients is high and probably a consequence of pre-existing cardiovascular disease. CONCLUSIONS: Factors influencing SD in dialysis patients are not substantially different from factors in the general population. The role played by ischaemic heart disease in this context needs further evaluation.

Day-night pattern of autonomic nervous system modulation in patients with heart failure with and without sleep apnea.

INTRODUCTION: Among patients with congestive heart failure (CHF) both obstructive and central sleep apnea (SA) are associated with increased sympathetic activity. However, the day-night pattern of cardiac autonomic nervous system modulation in CHF patients with and without sleep apnea is unknown. MATERIAL AND METHODS: Twenty-five CHF patients underwent polysomnography with simultaneous beat-to-beat blood pressure (Portapres), respiration and electrocardiogram monitoring. Patients were divided according to the presence (SA, n=17) and absence of SA (NoSA, n=8). Power spectral analyses of heart rate variability (HRV) and spontaneous baroreflex sensitivity (BRS) were determined in periods with stable breathing while awake at 6 am, 10 am, 10 pm, as well as during stage 2 sleep. In addition, muscle sympathetic nerve activity (MSNA) was evaluated at 10 am. RESULTS: RR variance, low-frequency (LF), high-frequency (HF) powers of HRV, and BRS were significantly lower in patients with SA compared with NoSA in all periods. HF power, a marker of vagal activity, increased during sleep in patients with NoSA but in contrast did not change across the 24-hour period in patients with SA. MSNA was significantly higher in patients with SA compared with NoSA. RR variance, LF and HF powers correlated inversely with simultaneous MSNA (r=-0.64, -0.61, and -0.61 respectively; P<0.01). CONCLUSIONS: Patients with CHF and SA present a reduced and blunted cardiac autonomic modulation across the 24-hour period. These findings may help to explain the increased cardiovascular risk in patients with CHF and SA.

Obstructive sleep apnea the most common secondary cause of hypertension associated with resistant hypertension

Recognition and treatment of secondary causes of hypertension among patients with resistant hypertension mayhelp to control blood pressure and reduce cardiovascular risk. However, there are no studies systematically evaluatingsecondary causes of hypertension according to the Seventh Joint National Committee. Consecutive patients withresistant hypertension were investigated for known causes of hypertension irrespective of symptoms and signs, includingaortic coarctation, Cushing syndrome, obstructive sleep apnea, drugs, pheochromocytoma, primary aldosteronism, renalparenchymal disease, renovascular hypertension, and thyroid disorders. Among 125 patients (age: 52 1 years, 43%males, systolic and diastolic blood pressure: 176 31 and 107 19 mm Hg, respectively), obstructive sleep apnea(apnea-hypopnea index: 15 events per hour) was the most common condition associated with resistant hypertension(64.0%), followed by primary aldosteronism (5.6%), renal artery stenosis (2.4%), renal parenchymal disease (1.6%),oral contraceptives (1.6%), and thyroid disorders (0.8%). In 34.4%, no secondary cause of hypertension was identified(primary hypertension). Two concomitant secondary causes of hypertension were found in 6.4% of patients. Age 50years (odds ratio: 5.2 [95% CI: 1.9 –14.2]; P 0.01), neck circumference 41 cm for women and 43 cm for men (oddsratio: 4.7 [95% CI: 1.3–16.9]; P 0.02), and presence of snoring (odds ratio: 3.7 [95% CI: 1.3–11]; P 0.02) werepredictors of obstructive sleep apnea. In conclusion, obstructive sleep apnea appears to be the most common conditionassociated with resistant hypertension. Age 50 years, large neck circumference measurement, and snoring are goodpredictors of obstructive sleep apnea in this population.

The impact of obstructive sleep apnea on metabolic and inflammatory markers in consecutive patients with metabolic syndrome.

BACKGROUND: Obstructive Sleep Apnea (OSA) is tightly linked to some components of Metabolic Syndrome (MetS). However, most of the evidence evaluated individual components of the MetS or patients with a diagnosis of OSA that were referred for sleep studies due to sleep complaints. Therefore, it is not clear whether OSA exacerbates the metabolic abnormalities in a representative sample of patients with MetS. METHODOLOGY/PRINCIPAL FINDINGS: We studied 152 consecutive patients (age 48+/-9 years, body mass index 32.3+/-3.4 Kg/m2) newly diagnosed with MetS (Adult Treatment Panel III). All participants underwent standard polysomnography irrespective of sleep complaints, and laboratory measurements (glucose, lipid profile, uric acid and C-reactive protein). The prevalence of OSA (apnea-hypopnea index>or=15 events per hour of sleep) was 60.5%. Patients with OSA exhibited significantly higher levels of blood pressure, glucose, triglycerides, cholesterol, LDL, cholesterol/HDL ratio, triglycerides/HDL ratio, uric acid and C-reactive protein than patients without OSA. OSA was independently associated with 2 MetS criteria: triglycerides: OR: 3.26 (1.47-7.21) and glucose: OR: 2.31 (1.12-4.80). OSA was also independently associated with increased cholesterol/HDL ratio: OR: 2.38 (1.08-5.24), uric acid: OR: 4.19 (1.70-10.35) and C-reactive protein: OR: 6.10 (2.64-14.11). Indices of sleep apnea severity, apnea-hypopnea index and minimum oxygen saturation, were independently associated with increased levels of triglycerides, glucose as well as cholesterol/HDL ratio, uric acid and C-reactive protein. Excessive daytime sleepiness had no effect on the metabolic and inflammatory parameters. CONCLUSIONS/SIGNIFICANCE: Unrecognized OSA is common in consecutive patients with MetS. OSA may contribute to metabolic dysregulation and systemic inflammation in patients with MetS, regardless of symptoms of daytime sleepiness.

Characteristics and predictors of obstructive sleep apnea in patients with systemic hypertension.

Obstructive sleep apnea (OSA) is a secondary cause of hypertension and independently associated with target-organ damage in hypertensive patients. However, OSA remains largely underdiagnosed and undertreated. The aim of the present study was to evaluate the characteristics and clinical predictors of OSA in a consecutive series of patients followed up in a hypertension unit. A total of 99 patients (age 46 + or - 11 years, body mass index 28.8 kg/m(2), range 25.1 to 32.9) underwent polysomnography. The clinical parameters included age, gender, obesity, daytime sleepiness, snoring, Berlin Questionnaire, resistant hypertension, and metabolic syndrome. Of the 99 patients, 55 (56%) had OSA (apnea-hypopnea index >5 events/hour). Patients with OSA were older and more obese, had greater levels of blood pressure, and presented with more diabetes, dyslipidemia, resistant hypertension, and metabolic syndrome than the patients without OSA. Of the patients with OSA, 51% had no excessive daytime sleepiness. The Berlin Questionnaire and patient age revealed a high sensitivity (0.93 and 0.91, respectively) but low specificity (0.59 and 0.48, respectively), and obesity and resistant hypertension revealed a low sensitivity (0.58 and 0.44, respectively) but high specificity (0.75 and 0.91, respectively) for OSA. Metabolic syndrome was associated with high sensitivity and specificity for OSA (0.86 and 0.85, respectively). Multiple regression analysis showed that age of 40 to 70 years (odds ratio 1.09, 95% confidence interval 1.03 to 1.16), a high risk of OSA on the Berlin Questionnaire (odds ratio 8.36, 95% confidence interval 1.67 to 41.85), and metabolic syndrome (odds ratio 19.04, 95% confidence interval 5.25 to 69.03) were independent variables associated with OSA. In conclusion, more important than the typical clinical features that characterize OSA, including snoring and excessive daytime sleepiness, the presence of the metabolic syndrome is as an important marker of OSA among patients with hypertension.

Myocardial scintigraphy and clinical stratification as predictors of events in renal transplant candidates.

BACKGROUND: We tested the hypothesis that the universal application of myocardial scanning with single-photon emission computed tomography (SPECT) would result in better risk stratification in renal transplant candidates (RTC) compared with SPECT being restricted to patients who, in addition to renal disease, had other clinical risk factors. METHODS: RTCs (n=363) underwent SPECT and clinical risk stratification according to the American Society of Transplantation (AST) algorithm and were followed up until a major adverse cardiovascular event (MACE) or death. RESULTS: Of the 363 patients, 79 patients (22%) had an abnormal SPECT scan and 270 (74%) were classified as high risk. Both methods correctly identified patients with increased probability of MACE. However, clinical stratification performed better (sensitivity and negative predictive value 99% and 99% vs. 25% and 87%, respectively). High-risk patients with an abnormal SPECT scan had a modest increased risk of events (log-rank = 0.03; hazard ratio [HR] = 1.37; 95% confidence interval [95% CI], 1.02-1.82). Eighty-six patients underwent coronary angiography, and coronary artery disease (CAD) was found in 60%. High-risk patients with CAD had an increased incidence of events (log-rank = 0.008; HR=3.85; 95% CI, 1.46-13.22), but in those with an abnormal SPECT scan, the incidence of events was not influenced by CAD (log-rank = 0.23). Forty-six patients died. Clinical stratification, but not SPECT, correlated with the probability of death (log-rank = 0.02; HR=3.25; 95% CI, 1.31-10.82). CONCLUSION: SPECT should be restricted to high-risk patients. Moreover, in contrast to SPECT, the AST algorithm was also useful for predicting death by any cause in RTCs and for selecting patients for invasive coronary testing.