RESUMO
BACKGROUND: Millions of individuals with obstructive sleep apnoea (OSA) are treated by CPAP aimed at reducing blood pressure (BP) and thus cardiovascular risk. However, evidence is scarce concerning the impact of different CPAP modalities on BP evolution. METHODS: This double-blind, randomised clinical trial of parallel groups of patients with OSA indicated for CPAP treatment compared the efficacy of fixed-pressure CPAP (FP-CPAP) with auto-adjusting CPAP (AutoCPAP) in reducing BP. The primary endpoint was the change in office systolic BP after 4â months. Secondary endpoints included 24â h BP measurements. RESULTS: Patients (322) were randomised to FP-CPAP (n=161) or AutoCPAP (n=161). The mean apnoea+hypopnoea index (AHI) was 43/h (SD, 21); mean age was 57 (SD, 11), with 70% of males; mean body mass index was 31.3â kg/m(2) (SD, 6.6) and median device use was 5.1â h/night. In the intention-to-treat analysis, office systolic blood pressure decreased by 2.2â mmâ Hg (95% CI -5.8 to 1.4) and 0.4â mmâ Hg (-4.3 to 3.4) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.3â mmâ Hg (95% CI -4.1 to 1.5); p=0.37, adjusted for baseline BP values). 24â h diastolic BP (DBP) decreased by 1.7â mmâ Hg (95% CI -3.9 to 0.5) and 0.5â mmâ Hg (95% CI -2.3 to 1.3) in the FP-CPAP and AutoCPAP group, respectively (group difference: -1.4â mmâ Hg (95% CI -2.7 to -0.01); p=0.048, adjusted for baseline BP values). CONCLUSIONS: The result was negative regarding the primary outcome of office BP, while FP-CPAP was more effective in reducing 24â h DBP (a secondary outcome). TRIAL REGISTRATION NUMBER: NCT01090297.
Assuntos
Pressão Sanguínea , Pressão Positiva Contínua nas Vias Aéreas/métodos , Apneia Obstrutiva do Sono/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Monitorização Ambulatorial da Pressão Arterial , Índice de Massa Corporal , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Polissonografia , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/etiologiaRESUMO
BACKGROUND: Insulin resistance, glucose dyshomeostasis and oxidative stress are associated to the cardiovascular consequences of obstructive sleep apnea (OSA). The effects of a long-term continuous positive airway pressure (LT-CPAP) treatment on such mechanisms still remain conflicting. OBJECTIVE: To investigate the effect of LT-CPAP on glucose tolerance, insulin sensitivity, oxidative stress and cardiovascular biomarkers in non-obese non-diabetic OSA patients. PATIENTS & METHODS: Twenty-eight apneic, otherwise healthy, men suffering from OSA (mean age = 48.9 ± 9.4 years; apnea-hypopnea index = 41.1 ± 16.1 events/h; BMI = 26.6 ± 2.8 kg/m(2); fasting glucose = 4.98 ± 0.37 mmol/L) were evaluated before and after LT-CPAP by an oral glucose tolerance test (OGTT), measuring plasma glucose, insulin and proinsulin. Glycated hemoglobin, homeostasis model assessment resistance insulin, blood lipids, oxidative stress, homocysteine and NT-pro-brain natriuretic peptide (NT-proBNP) were also measured. RESULTS: LT-CPAP treatment lasted 13.9 ± 6.5 months. At baseline, the time spent at SaO2<90%, minimal and mean SaO2 were associated with insulin area under the curve during OGTT (r = 0.448, P = 0.011; r = -0.382; P = 0.047 and r = -0.424; P = 0.028, respectively) and most other glucose/insulin homeostasis biomarkers, as well as with homocysteine (r = 0.531, P = 0.006; r = -0.487; P = 0.011 and r = -0.409; P = 0.034, respectively). LT-CPAP had no effect on all the OGTT-related measurements, but increased plasma total antioxidant status (+7.74%; P = 0.035) in a duration-dependent manner (r = 0.607; P < 0.001), and decreased both homocysteine (-15.2%; P = 0.002) and NT-proBNP levels (-39.3%; P = 0.002). CONCLUSIONS: In non-obese non-diabetic OSA patients, nocturnal oxygen desaturation is strongly associated to insulin resistance. LT-CPAP does not improve glucose homeostasis nor insulin sensitivity but has a favorable effect on antioxidant capacity and cardiovascular risk biomarkers.
Assuntos
Glicemia/metabolismo , Doenças Cardiovasculares/metabolismo , Pressão Positiva Contínua nas Vias Aéreas , Resistência à Insulina , Estresse Oxidativo , Apneia Obstrutiva do Sono/terapia , Adulto , Biomarcadores/metabolismo , Doenças Cardiovasculares/diagnóstico por imagem , Espessura Intima-Media Carotídea , Estudos de Casos e Controles , Colesterol/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/metabolismo , Homocisteína/metabolismo , Humanos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Polissonografia , Proinsulina/metabolismo , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/metabolismo , Resultado do Tratamento , Triglicerídeos/metabolismoRESUMO
UNLABELLED: Fibromuscular dysplasia (FMD) is an idiopathic, segmentary, non-inflammatory and non-atherosclerotic disease that can affect all layers of both small- and medium-calibre arteries. The prevalence of FMD is estimated between 4 and 6 % in the renal arteries and between 0.3 and 3 % in the cervico-encephalic arteries. FMD most frequently affects the renal, carotid and vertebral arteries, but it can theoretically affect any artery. Radiologists play an important role in the diagnosis of FMD, and good knowledge of FMD's signs will certainly help reduce the delay between the first symptoms and diagnosis. The common string-of-beads aspect is well known, but less common presentations also have to be considered. These less common imaging findings include vascular loops, fusiform vascular ectasia, arterial dissection, aneurysm and subarachnoid haemorrhage. These radiologic presentations should be known by radiologists in order to diagnose possible FMD, particularly when present in young females or when associated with personal or familial hypertension, to reduce the delay between the onset of the first symptom and the final diagnosis. The patients have to be referred to specialised FMD centres for dedicated management. TEACHING POINTS: ⢠Fibromuscular dysplasia is not a rare disease. ⢠Radiologists should recognise less common presentations to orient specific management. ⢠Vascular loops, fusiform vascular ectasia and a "string-of-beads" aspect are typical presentations. ⢠Arterial dissection, aneurysm and subarachnoid haemorrhage are less typical radiologic presentations.
RESUMO
Current antihypertensive strategies do not take into account that individual characteristics may influence the magnitude of blood pressure (BP) reduction. Guidelines promote trial-and-error approaches with many different drugs. We conducted the Identification of the Determinants of the Efficacy of Arterial blood pressure Lowering drugs (IDEAL) Trial to identify factors associated with BP responses to perindopril and indapamide. IDEAL was a cross-over, double-blind, placebo-controlled trial, involving four 4-week periods: indapamide, perindopril and two placebo. Eligible patients were untreated, hypertensive and aged 25-70 years. The main outcome was systolic BP (SBP) response to drugs. The 112 participants with good compliance had a mean age of 52. One in every three participants was a woman. In middle-aged women, the SBP reduction from drugs was -11.5 mm Hg (indapamide) and -8.3 mm Hg (perindopril). In men, the response was significantly smaller: -4.8 mm Hg (indapamide) and -4.3 (perindopril) (P for sex differences 0.001 and 0.015, respectively). SBP response to perindopril decreased by 2 mm Hg every 10 years of age in both sexes (P=0.01). The response to indapamide increased by 3 mm Hg every 10 years of age gradient in women (P=0.02). Age and sex were important determinants of BP response for antihypertensive drugs in the IDEAL population. This should be taken into account when choosing drugs a priori.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Pressão Arterial/efeitos dos fármacos , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Indapamida/uso terapêutico , Perindopril/uso terapêutico , Adulto , Fatores Etários , Idoso , Estudos Cross-Over , Método Duplo-Cego , Feminino , França , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Fatores Sexuais , Fatores de Tempo , Resultado do TratamentoAssuntos
Aldosterona/sangue , Antagonistas de Receptores de Angiotensina/uso terapêutico , Hipertensão/sangue , Hipertensão/tratamento farmacológico , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/tratamento farmacológico , Biomarcadores/sangue , Estudos Cross-Over , Feminino , Humanos , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/epidemiologia , Resultado do TratamentoRESUMO
INTRODUCTION: The obstructive sleep apnoea syndrome (OSAS) had become a major public health concern in modern society due to its high prevalence but, above all, to its associated morbidity, especially cardiovascular. BACKGROUND: Untreated OSAS is associated with an increased incidence of fatal (myocardial infarction and stroke) (odds ratio: 2.87) and non-fatal cardiovascular events (myocardial infarction, stroke, coronary artery bypass surgery and coronary angiography) (odds ratio: 3.17). Moreover, the prevalence of hypertension in patients with OSAS is high, between 35 and 80%. The pathophysiological mechanisms leading to these complications are mainly due to intermittent hypoxia secondary to repeated episodes of apnoea/hypopnoea during sleep. These mechanisms include sympathetic hyperactivation, impairment of vasomotor reactivity, vascular inflammation, oxidative stress and metabolic disorders. In patients with OSAS, the impact of continuous positive pressure is proven in terms of prevention of cardiovascular events although blood pressure reduction is limited. Obviously these effects are proportional to observance. CONCLUSION: OSAS does increase the cardiovascular risk, independently of other risk factors. Although the impact of treatment is relatively low in decreasing blood pressure, it seems essentially effective in preventing cardiovascular morbidity. Therefore, OSAS screening, and the association of specific treatments in cardio-metabolic patients and OSAS patients respectively, should be included in clinical strategies.
Assuntos
Doenças Cardiovasculares/etiologia , Apneia Obstrutiva do Sono/complicações , Fármacos Cardiovasculares/uso terapêutico , Doenças Cardiovasculares/fisiopatologia , Doenças Cardiovasculares/prevenção & controle , Transtornos Cerebrovasculares/etiologia , Transtornos Cerebrovasculares/prevenção & controle , Comorbidade , Pressão Positiva Contínua nas Vias Aéreas , Endotélio Vascular/fisiopatologia , Intolerância à Glucose/etiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/etiologia , Hipóxia/etiologia , Hipóxia/prevenção & controle , Síndrome Metabólica/etiologia , Óxido Nítrico/biossíntese , Obesidade/epidemiologia , Estresse Oxidativo , Prevalência , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Sistema Nervoso Simpático/fisiopatologia , Vasculite/etiologiaRESUMO
OBJECTIVE: This pilot study aimed to compare metabolic disturbances, particularly insulin resistance (IR) and cardiovascular risk factors (CRFs), following two types of acute vascular atherothrombotic disease events: ischaemic atherothrombotic stroke (AS); and acute coronary syndrome (ACS). DESIGN AND METHODS: A total of 110 non-diabetic patients presenting with either AS (n=55) or ACS (n=55) were included in our prospective comparative study, and matched for age and gender. IR was determined using the homoeostasis model assessment of insulin resistance (HOMA-IR) method, and each patient's personal and family history were also recorded. RESULTS: IR was significantly higher in the ACS vs AS group (HOMA-IR index 2.17±1.90 vs 1.50±0.81, respectively; P=0.03). The AS group had a significantly higher prevalence of personal history of hypertension (51% vs 31%; P=0.03), while current smoking was more prevalent in the ACS group (30% vs 18%; P=0.04). There were no significant differences between the two groups as regards any other CRFs. CONCLUSION: The distribution of CRFs varied depending on the vascular event, and metabolic disturbances differed according to the atherothrombotic disease. IR was greater after ACS than AS.
Assuntos
Síndrome Coronariana Aguda/metabolismo , Resistência à Insulina , Placa Aterosclerótica/metabolismo , Acidente Vascular Cerebral/metabolismo , Síndrome Coronariana Aguda/patologia , Idoso , Feminino , Humanos , Masculino , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Placa Aterosclerótica/patologia , Prevalência , Estudos Prospectivos , Acidente Vascular Cerebral/patologia , Trombose/metabolismo , Trombose/patologiaRESUMO
OBJECTIVE: Type A or B aortic dissection can extend to renal arteries, causing a renal ischemia which treatment is usually endovascular. The aim of our study is to show the interest of the renal volumetry in the follow-up of these patients. PATIENTS AND METHODS: Twenty-two patients (16 men, mean age 63.4±11.8years, BMI 25.2±3.4kg/m(2)) with a type A or B aortic dissection spread to one or to both renal arteries and followed at Grenoble university hospital were consecutively included. All patients underwent renal angiography with aorto-renal pressure gradients measurements and follow-up by renal volumetry (scanner Siemens(®)). A renal ischemia was defined by a decrease of 20% or more of the volumetry. RESULTS: Sixteen patients (73%) were hypertensive before the aortic dissection among which ten (62%) were treated. Eight patients (36%) have a significant renal pressure gradient among which five (62%) underwent renal endovascular therapy. The renal volumetry of these five patients remained unchanged while six of 17 patients (36%) without angioplasty have a decreasing volumetry. CONCLUSION: Renal volumetry appeared an effective and attractive option for the follow-up of the patients with aortic dissection spread to the renal arteries. These results should be taken into account to put the indication of an endovascular treatment.
Assuntos
Angiografia , Angioplastia com Balão , Aneurisma da Aorta Torácica/diagnóstico por imagem , Dissecção Aórtica/diagnóstico por imagem , Volume Sanguíneo , Isquemia/diagnóstico por imagem , Rim/irrigação sanguínea , Artéria Renal/diagnóstico por imagem , Circulação Renal , Idoso , Dissecção Aórtica/complicações , Dissecção Aórtica/terapia , Angioplastia com Balão/métodos , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/terapia , Índice de Massa Corporal , Estudos de Coortes , Feminino , Seguimentos , Hospitais Universitários , Humanos , Isquemia/etiologia , Isquemia/terapia , Rim/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Grau de Desobstrução VascularRESUMO
Obstructive sleep apnea (OSA) and metabolic syndrome (MetS) are associated with increased cardiovascular morbidity and mortality. Increased homocysteine is suggested as an independent risk factor for atherosclerosis and cardiovascular disease but remains disputed in OSA. We assessed polysomnography, carotid intima-media thickness (CIMT) and biology in 35 MetS patients, according to the presence (OSA+MetS; n=26) or the absence of OSA (MetS; n=9). In OSA+MetS patients, homocysteine levels were increased compared to MetS subjects (12.8 ± 3.8 vs. 9.5 ± 2.5 µmol/L; P=0.026). In the whole population, homocysteine correlated with apnea-hypopnea index (AHI) (r=0.522; P=0.001) and CIMT (r=0.376; P=0.026). Homocysteine was negatively correlated with plasma thiols (r=-0.406; P=0.017) and positively with urinary 15-F2t-isoprostanes (r=0.347; P=0.044). Multivariate regression analysis revealed that AHI (ß=0.559; P<0.001) and urinary 15-F2t-isoprostane (ß=0.310; P=0.018) were independently associated with homocysteine level. We conclude that homocysteine level was higher in MetS when associated with OSA and proportional to OSA severity. In this context, vascular remodeling appeared more severe and mediated by oxidative stress.
Assuntos
Artérias Carótidas/patologia , Homocisteína/metabolismo , Síndrome Metabólica/patologia , Apneia Obstrutiva do Sono/patologia , Antioxidantes/metabolismo , Nível de Alerta/fisiologia , Aterosclerose/complicações , Aterosclerose/metabolismo , Pressão Sanguínea/fisiologia , Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Cromatografia Líquida de Alta Pressão , Dinoprosta/análogos & derivados , Endotélio Vascular/fisiologia , Feminino , Humanos , Isoprostanos/urina , Lipídeos/sangue , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo/fisiologia , Polissonografia , Apneia Obstrutiva do Sono/etiologia , Apneia Obstrutiva do Sono/metabolismo , Compostos de Sulfidrila/sangue , Espectrometria de Massas em TandemRESUMO
Obstructive sleep apnoea syndrome (OSAS) causes nocturnal chronic intermittent hypoxia (IH) that contributes to excess cardiovascular morbidity. To explore the consequences of IH, we used our recently developed model of nocturnal IH in healthy humans to characterise the profile of this blood pressure increase, to determine if it is sustained and to explore potential physiological mechanisms. We performed 24-h ambulatory monitoring of blood pressure in 12 healthy subjects before and after 2 weeks of IH exposure. We also assessed systemic haemodynamics, muscle sympathetic nerve activity (MSNA), ischaemic calf blood flow responses and baroreflex gain. We obtained blood samples for inflammatory markers before, during and after exposure. IH significantly increased daytime ambulatory blood pressure after a single night of exposure (3 mmHg for mean and diastolic) and further increased daytime pressures after 2 weeks of exposure (8 mmHg systolic and 5 mmHg diastolic). Mean ± sd MSNA increased across the exposure (17.2 ± 5.1 versus 21.7 ± 7.3 bursts·min⻹; p < 0.01) and baroreflex control of sympathetic outflow declined from -965.3 ± 375.1 to -598.4 ± 162.6 AIU·min⻹ ·mmHg⻹ (p < 0.01). There were no evident changes in either vascular reactivity or systemic inflammatory markers. These data are the first to show that the arterial pressure rise is sustained throughout the waking hours beyond the acute phase immediately after exposure. Moreover, they may suggest that sympathoactivation induced by IH likely contributes to blood pressure elevation and may derive from reduced baroreflex inhibition. These mechanisms may reflect those underlying the blood pressure elevation associated with OSAS.
Assuntos
Pressão Sanguínea , Hipóxia/fisiopatologia , Adiponectina/sangue , Adulto , Índice de Massa Corporal , Proteína C-Reativa/biossíntese , Quimiocina CCL5/sangue , Feminino , Humanos , Hipertensão/etiologia , Molécula 1 de Adesão Intercelular/sangue , Interleucina-8/sangue , Leptina/sangue , Masculino , Receptores de Interleucina-1/biossíntese , Síndromes da Apneia do Sono/complicações , Síndromes da Apneia do Sono/fisiopatologia , Sistema Nervoso Simpático/fisiopatologia , Fator de Necrose Tumoral alfa/sangueRESUMO
Obstructive sleep apnoea (OSA) has been linked to increased cardiovascular risk. The present study examined the relationships between respiratory parameters and left ventricular abnormalities in OSA. 150 newly diagnosed OSA patients without any known cardiovascular disease were included in the study (mean ± sd age 49 ± 11 yrs, body mass index 27.1 ± 3.3 kg·m⻲, respiratory disturbance index 41 ± 18 h⻹). Haemodynamic, biological, respiratory, cardiac and arterial parameters were assessed at inclusion. 34 (22.7%) patients had a grade 1 left ventricular diastolic dysfunction. Patients with an abnormal diastole were older (p < 0.001) and 81% of them were hypertensive. The only respiratory parameter independently associated with the peak flow velocity in early diastole/peak flow velocity at atrial contraction ratio was mean nocturnal oxygen saturation. 17 (13%) patients had left ventricular hypertrophy. A multivariate analysis showed that clinic systolic blood pressure and mean nocturnal oxygen saturation were independently associated with left ventricular hypertrophy. In a logistic regression model, age ≥ 58 yrs (OR 3.29, 95% CI 1.78-5.64) and mean nocturnal oxygen saturation < 92% (OR 2.76, 95% CI 1.45-4.91) were associated with left ventricular diastolic dysfunction. Our findings demonstrate that left ventricular diastolic dysfunction frequently occurs in patients with OSA and that it is related to the severity of oxygen desaturation.
Assuntos
Apneia Obstrutiva do Sono/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Adulto , Feminino , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Respiração , Índice de Gravidade de DoençaRESUMO
In hypertension and diabetes, early structural changes of the arterial wall precede or support atherosclerosis. There is evidence that some antihypertensive drugs exert an antiathero-sclerotic effect. Over 36 months, we investigated the effect of candesartan cilexetil (CC) on the common carotid intima-media thickness (IMT) vs amlodipine besylate (AML) in patients with type 2 diabetes and mild to moderate essential hypertension. After a 4-week wash-out period, 209 patients were randomized to either CC 8 mg or AML 5 mg once daily for a minimum of 1 month, after which, if BP was not normalized, the dosage was doubled, followed by the addition of hydrochlorothiazide 12.5 mg if necessary. No significant differences were observed between the two groups for change in IMT at M12 (-0.001 vs -0.027 mm/year for CC and AML respectively, p = 0.425), at M24 (-0.033 vs -0.019 mm per year respectively, p = 0.442), and at the last visit (-0.016 vs -0.039 mm per year respectively, p = 0.549). Within the group, comparisons did not show a significant difference in changes in IMT from baseline to the three visits. At the last visit, IMT regression was observed in 52.2% of patients receiving CC and in 51.3% of those receiving AML (p = 0.908). The augmentation in carotid lumen diameter from baseline was statistically greater in the AML group at the last visit (p = 0.034). BP variations during the study were similar in the two groups. The results of this study show that CC and AML treatments may alter identically the natural progression of carotid IMT in hypertensive type 2 diabetic patients.
Assuntos
Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Compostos de Bifenilo/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doenças das Artérias Carótidas/prevenção & controle , Artéria Carótida Primitiva/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Angiopatias Diabéticas/prevenção & controle , Hipertensão/tratamento farmacológico , Tetrazóis/uso terapêutico , Idoso , Anlodipino/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Benzimidazóis/efeitos adversos , Compostos de Bifenilo/efeitos adversos , Pressão Sanguínea/efeitos dos fármacos , Bloqueadores dos Canais de Cálcio/efeitos adversos , Doenças das Artérias Carótidas/diagnóstico por imagem , Doenças das Artérias Carótidas/etiologia , Artéria Carótida Primitiva/diagnóstico por imagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Angiopatias Diabéticas/diagnóstico por imagem , Angiopatias Diabéticas/etiologia , Progressão da Doença , Diuréticos/uso terapêutico , Método Duplo-Cego , Feminino , França , Humanos , Hidroclorotiazida/uso terapêutico , Hipertensão/complicações , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Tetrazóis/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Túnica Íntima/diagnóstico por imagem , Túnica Íntima/efeitos dos fármacos , Túnica Média/diagnóstico por imagem , Túnica Média/efeitos dos fármacos , UltrassonografiaRESUMO
Obstructive sleep apnoea syndrome (OSAS), due to the collapse of the upper airways, is a common but still underestimated condition. The 'dose-response' type relationship between OSAS and hypertension (HT) has now been clearly proven. There are multiple mechanisms explaining this relationship, the main one being an increase in sympathetic activity during the apnoeas. HT associated with OSAS has several characteristics: high prevalence, diastolic and nocturnal predominance, and frequent non-dipper status. Furthermore, as OSAS is found in the majority of subjects with refractory HT, it should be systematically investigated in this situation. HT associated with OSAS should be tested for by means of a clinical blood pressure (BP) measurement, to which 24-h ambulatory BP monitoring (ABPM) is often added due to the fact that BP anomalies are frequently present at night. HT during OSAS is frequently associated with metabolic anomalies (for example, obesity, dyslipidaemia and insulin resistance), therefore explaining the high prevalence of metabolic syndrome in this population. The reference treatment for OSAS-nasal continuous positive airway pressure (nCPAP)-seems to be able to lower the BP of hypertensive patients, especially if the HT is severe, untreated or refractory. Moreover, the BP response to nCPAP depends on the severity of the OSAS, in particular the scale of the nocturnal desaturations, and on patient tolerance of the treatment. Optimal treatment for HT associated with OSAS has not been evidenced. Antihypertensive drugs do not change the respiratory parameters during OSAS.
Assuntos
Hipertensão/etiologia , Apneia Obstrutiva do Sono/complicações , Pressão Sanguínea , Determinação da Pressão Arterial , Pressão Positiva Contínua nas Vias Aéreas , Endotélio Vascular/fisiologia , Humanos , Hipercapnia/complicações , Hipertensão/tratamento farmacológico , Inflamação/complicações , Estresse Oxidativo , Oxigênio/sangue , Sistema Renina-Angiotensina/fisiologia , Apneia Obstrutiva do Sono/fisiopatologia , Apneia Obstrutiva do Sono/terapia , Sistema Nervoso Simpático/fisiopatologia , Trombofilia/complicaçõesRESUMO
Severity of oxygen desaturation is predictive of early atherosclerosis in obstructive sleep apnoea (OSA). Leukotriene (LT)B(4) is a lipid mediator involved in atherogenesis. In 40 non-obese OSA patients, free of a cardiovascular history, and 20 healthy volunteers, the following were evaluated: 1) LTB(4) production by polymorphonuclear leukocytes (PMNs) stimulated with A23187; and 2) the relationships between LTB(4) production and both OSA severity and infraclinical atherosclerosis markers. The effect of continuous positive airway pressure (CPAP) on LTB(4) production was also studied. An overnight sleep study was followed by first-morning blood sampling. Isolated PMNs were stimulated with A23187 in order to induce LTB(4) production, which was measured by liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (IMT) and luminal diameter were measured in subset groups of 28 OSA patients and 11 controls. LTB(4) production was increased in OSA patients compared with controls. LTB(4) levels correlated with the mean and minimal arterial oxygen saturation (S(a,O(2))). LTB(4) production correlated with luminal diameter data in patients with a mean S(a,O(2)) of < or = 94% but not with IMT. Lastly, CPAP significantly reduced LTB(4) production by 50%. Leukotriene B(4) production is increased in obstructive sleep apnoea in relation to oxygen desaturation. Leukotriene B(4) could promote early vascular remodelling in moderate-to-severe hypoxic obstructive sleep apnoea patients.
Assuntos
Leucotrieno B4/sangue , Neutrófilos/metabolismo , Apneia Obstrutiva do Sono/sangue , Adulto , Gasometria , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Feminino , Humanos , Hipóxia/sangue , Masculino , PolissonografiaRESUMO
Antioxidant counteraction of oxidative stress has been poorly explored in obstructive sleep apnoea (OSA). Serum albumin is a major antioxidant agent and structural modifications induced by glucose or free radicals impair its antioxidant properties. The aim of the present study was to compare antioxidant capacities and structural changes of albumin in nonobese OSA patients and healthy volunteers. Albumin structural changes were studied by quenching of fluorescence in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidation- and glycation-induced changes in serum albumin, respectively, were assessed. Albumin structural changes were demonstrated by a significant decrease in quenching of fluorescence in OSA patients. Oxidation, resulting in a significant decrease in thiol groups (3.7+/-0.7 versus 2.3+/-0.4 micromol x g(-1) protein), and glycation, associated with a significant increase in fructosamines (226.6+/-27 versus 286+/-44.4 micromol x L(-1)), were found when comparing healthy volunteers with OSA patients. There was a significant relationship between both parameters and sleep apnoea severity. After continuous positive airway pressure intervention, albumin thiol groups were reassessed in seven of the 16 OSA patients and increased significantly from 2.25+/-0.39 to 2.79+/-0.31 micromol x g(-1) protein. Obstructive sleep apnoea patients demonstrated a reduction in serum albumin antioxidant properties that may aggravate oxidative stress and, thus, contribute to cardiovascular and metabolic morbidities.
Assuntos
Antioxidantes/farmacologia , Albumina Sérica/farmacologia , Apneia Obstrutiva do Sono/fisiopatologia , Adulto , Antioxidantes/química , Antioxidantes/metabolismo , Estudos de Casos e Controles , Pressão Positiva Contínua nas Vias Aéreas , Frutosamina/sangue , Glicosilação , Humanos , Isoprostanos/urina , Pessoa de Meia-Idade , Oxirredução , Albumina Sérica/química , Albumina Sérica/metabolismo , Apneia Obstrutiva do Sono/sangue , Compostos de Sulfidrila/sangueRESUMO
BACKGROUND AND OBJECTIVE: Despite advances in the treatment of hypertension, control rates continue to be suboptimal in both Europe and the US. Strategies that improve hypertension control are therefore urgently needed. This study aimed to assess the relative efficacies of various antihypertensive drugs commonly used in France in reducing systolic and diastolic blood pressure (SBP and DBP) by using a meta-analytical approach. This update of a previously published meta-analytical approach extends the number of drugs evaluated from 13 to 19. METHODS: A total of 80 randomised, controlled trials published between 1973 and 2007 involving 10 818 patients were selected for inclusion in the meta-analytical approach. Data were examined for 19 drugs, and 16 drugs were included in the analysis: hydrochlorothiazide, indapamide sustained-release (SR), atenolol, amlodipine, lercanidipine, manidipine, enalapril, ramipril, trandolapril, candesartan cilexetil, irbesartan, losartan, olmesartan medoxomil, telmisartan, valsartan and aliskiren. Weighted average reductions in SBP and DBP over a period of 8-12 weeks were calculated for each drug from information on both the mean and the variability in BP reduction. No trials evaluating furosemide, spironolactone or cicletanine satisfied the inclusion criteria for this analysis. RESULTS: The average weighted reductions in SBP over 8-12 weeks were most marked with diuretics, and in particular indapamide SR 1.5 mg/day (mean change from baseline -22.2mm Hg), which reduced SBP to a greater extent than any of the other drugs evaluated (at any dosage considered). Average weighted reductions in DBP were generally similar with all classes of antihypertensives and ranged from -11.4mm Hg with the beta-adrenoceptor blocker atenolol and calcium channel antagonists to -10.3mm Hg with the angiotensin II type 1 receptor antagonists. CONCLUSION: This new analysis supports the results of the earlier investigation, in that indapamide SR 1.5 mg/day appeared to be the most effective drug for producing significant reductions in SBP within 8-12 weeks, which is an essential element in optimising cardiovascular prevention among hypertensive patients. The clinical application of these results should take into consideration all the limitations discussed in this analysis.
Assuntos
Anti-Hipertensivos/uso terapêutico , Hipertensão/tratamento farmacológico , Pressão Sanguínea/efeitos dos fármacos , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The prevalence and characteristics of patients operated for adrenal adenoma (Conn syndrome) as well as their post-operative arterial pressure evolution are varying through literature. Our aim was to report the Grenoble University Hospital experience. From 1993 to 2005, 24 patients (mean age = 46 +/-11 years) presented the biological criteria of primary hyperaldosteronism and benefited from adrenalectomy with confirmation of adrenal adenoma. All had an uncontrolled hypertension, refractory in 42% of cases, with a hypokaliemia (mean = 2.65 +/- 0.47 mmol/l). All adenomas measured more than 10 mm in scanner imaging. After a mean post-operative follow-up of 46 +/- 43 months, 70% of them were normotensive, with (45%) or without (25%) anti-hypertensive therapy. the post-operative kaliemia was normal in all cases. Only 25% had post-operative hormonal dosages for control. Post-operative spontaneous normotensive patients had, at the diagnosis of adrenal adenoma, a more recent and non-refractory hypertension, with a lower number of antihypertensive drugs, a better response to spirinolactone and higher aldosterone plasmatic levels. Two lessons can be taken from this study: 1) Whether 70% of patients operated for adrenal adenoma are normotensive (with or without treatement) post-operatively, only 25% are definitely cured after 4 years. Factors associated to a post-operative cure highlight the interest of an ealy diagnosis. 2) There is probably an underdiagnosis of adrenal adenoma (Conn syndrome) because neither adenomas with normokaliemia, nor adenomas <10 mm in scanner imaging have ever been diagnosed or at least, sent to surgery.
Assuntos
Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/cirurgia , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/cirurgia , Neoplasias do Córtex Suprarrenal/complicações , Adrenalectomia , Adenoma Adrenocortical/complicações , Adulto , Pressão Sanguínea , Feminino , Seguimentos , Humanos , Hiperaldosteronismo/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos RetrospectivosRESUMO
Hypertensive patients with altered circadian blood pressure (BP) profile experience greater repercussion of hypertension on target organs and a higher risk of cardiovascular events, compared with those with physiological variations in BP. It has been demonstrated in animal models, that circadian variations in BP depend on several regulatory systems, in particular the nitric oxide-cGMP pathway. eNOS298 Glu/Asp polymorphism is a functional variant and may alter the amount of NO generated or eNOS activity. The objective of the present study was to find out whether eNOS298 gene polymorphism affects circadian BP regulation in 110 healthy subjects and 155 never-treated hypertensive patients recruited at Hypertension Units in Grenoble, Toulouse and Lille (France).
Assuntos
Pressão Sanguínea/genética , Ritmo Circadiano/genética , Hipertensão/genética , Óxido Nítrico Sintase Tipo III/genética , Polimorfismo Genético , Adulto , Idoso , Ácido Aspártico/genética , Ácido Glutâmico/genética , Humanos , Pessoa de Meia-IdadeRESUMO
The aim of this observational study was to assess whether there were differences in perception of overall cardiovascular risk (OCVR) in hypertensive patients depending on the gender of the primary care provider (PCP). We performed this study in 2003: 2979 male PCPs (MPCPs) and 562 female PCPs (FPCPs) participated throughout France. The patients included were hypertensive either treated or untreated, uncontrolled (blood pressure (BP) >or=140/90 mm Hg) with at least one other cardiovascular risk factor (CVRF) associated. OCVR of patients was both calculated according to French Agence Nationale d'Accréditation et d'Evaluation en Santé guidelines for uncontrolled hypertensive patients and subjectively estimated by the PCP as 'low', 'moderate', 'high' or 'very high'. About 11 770 patients were included, mean age was 63.7+/-11.2 years and 54.1% were men. Mean BP was 157+/-13/90+/-9 mm Hg. According to French guidelines, the calculated OCVR was 'moderate' in 23.7% of patients, 'high' in 47.5% and 'very high' in 28.8%. The PCP perceived OCVR was that 9.1% of patients were considered to be at 'low risk', 40.7% at 'moderate risk', 38.1% at 'high risk', and only 11.2% at 'very high risk' (OCVR was not estimated for 0.9% of patients). The overall agreement rate between the PCPs' estimation of OCVR and its calculation was 43.5%. Thus, in spite of extensive diffusion of ANAES guidelines, we found that PCPs in France generally underestimated OCVR though there were no significant differences between male and female physicians (45% for FPCPs and 43.2% for MPCPs).