No description available.

No description available.

Visit-to-visit variability in blood pressure (BP) increases stroke risk, independent of mean BP. However, its physiological validity, the ideal method of measurement and the mechanisms increasing cardiovascular risk are unclear. In meta-analyses of individual patient data, I pooled associations between BP variability and risk of stroke, all cardiovascular events and death. I then determined antihypertensive drug-class differences in cardiovascular risk, intra-individual (I-VR) and inter-individual BP variability (M-VR). In 500 Oxford Vascular Study (OXVASC) patients undergoing thrice-daily home (HBPM) and awake ambulatory monitoring (ABPM), associations between mean, maximum or variability in BP (CV-BP) were determined with premorbid BP, hypertensive arteriopathy (creatinine, aortic stiffness, cognitive impairment, stroke versus TIA and leukoaraiosis) and cardiovascular events. In 200 patients, I determined associations with pulsatility or stiffness (pulse wave velocity) in cerebral and aortic vessels. There was a 21% and 27% increased risk of stroke and myocardial infarction per standard deviation of CV-SBP in 318700 patients, independent of mean SBP. In 244,479 patients, SBP variability was reduced by CCBs and diuretics within (I-VR=0.89, 95% CI=0.82-0.96, p=0.0001) and between individuals (M-VR 0.83, 0.77-0.89, p<0.0001), especially in the first year of treatment, explaining drug class differences in stroke risk (OR=0.76, 0.68-0.87, p<0.0001). In OXVASC, drug class differences on day-to-day SBP variability were greatest immediately after waking. Residual hypertension after treatment on HBPM but not ABPM (BP>135/85) predicted recurrent cardiovascular events (HR 2.82, 1.44-5.51, p=0.002 vs. 1.48, 0.68-3.23, p=0.33), reflecting stronger associations with premorbid BP and hypertensive arteriopathy, due largely to inaccuracy of ABPM in patients aged >65 years. Furthermore, day-to-day maximum and CV-SBP were associated with premorbid BP, hypertensive arteriopathy and cardiovascular events, with no additional predictive value of mean SBP when analysed with maximum SBP. Maximum SBP was greater in men and CV-SBP in women, whilst age and creatinine determined both. Increased stroke risk may partly be due to the association between BP variability and cerebral pulsatility, which was correlated with leukoaraiosis (p=0.01) and determined by aortic stiffness (p=0.016) and pulsatility (p<0.001). BP variability is clinically significant and physiologically valid, and is treatable with CCBs and diuretics. After TIA or minor stroke, HBPM best identifies residual hypertension and demonstrates the predictive value of BP variability and maximum BP, but associated arterial changes might explain some of the increased stroke risk.

Slow and deep breathing (SDB) has long been regarded as a nonpharmacological method for dealing with several physiological and emotional imbalances, and widely used for relaxation purposes. There is, however, limited understanding of the putative mechanisms by which SDB acutely impacts the cardiovascular and autonomic systems to elicit chronic adaptations. The present thesis explored how the manipulation of breathing pattern and intrathoracic pressure during SDB could further the understanding of the regulatory mechanisms that underpin the acute cardiovascular response to SDB. This thesis makes an original contribution to the existing knowledge by reporting a previously undescribed inversion of normal within-breath (inspiration vs. expiration) left ventricular stroke volume (LVSV) pattern for breathing frequencies < 8 breaths∙min-1. This finding might reflect the influence of a lag between enhanced right atrial filling and right ventricular stroke volume during inspiration, and its expression in left ventricular stroke volume; this lag results from the time required for blood to transit the pulmonary circulation. Furthermore, blood pressure variability (BPV) was reduced significantly at the lowest breathing frequencies, likely due to the involvement of baroreflex mediated responses. The pattern of responses was consistent with the buffering of respiratory-driven fluctuations in left ventricular cardiac output (Q̇) and arterial blood pressure (ABP) by within breath fluctuations in heart rate (fc), i.e., respiratory sinus arrhythmia (RSA) (Chapter 4). Chapter 5 demonstrated that magnifying negative intrathoracic pressure with inspiratory loading during SDB increased inspiratory pressure-driven fluctuations in LVSV and fc, and enhanced Q̇, independently of changes in VT and fR. The data support an important contribution to the amplification of RSA, during SDB, of previously underappreciated reflex, and/or 'myogenic', cardiac response mechanisms. The findings in Chapter 6 confirmed that inspiratory loading during SDB amplified the effects observed with un-loaded SDB (reported in chapter 5). In contrast, expiratory loading increased ABP and attenuated RSA, LVSV and Q̇ during SDB. A lower RSA for higher ABP, supports the presence of a formerly underappreciated contribution of sinoatrial node stretch to RSA, and throws into question the clinical benefits of expiratory resisted SDB, particularly in hypertensive populations. In conclusion, the findings of the present thesis provide novel information regarding the mechanisms contributing to acute cardiovascular response to SDB. These new insights may contribute to the development of more effective SDB interventions, geared towards maximising the perturbation to the cardiovascular control systems.

Introdução: O desenvolvimento de hipertensão arterial e doença cardiovascular relacionado à síndrome das apnéia obstrutiva do sono (SAOS) parece estar relacionado a alterações sobre a regulação autonômica cardiovascular. Este estudo investigou se a SAOS influência a variabilidade da pressão arterial (PA). Métodos: Estudo transversal, com pacientes hipertensos que foram submetidos à polissonografia nível III, por meio de um monitor portátil de uso domiciliar para detectar SAOS (índice de apnéia-hipopnéia (IAH) ≥ 10). A variabilidade da PA foi avaliada pela taxa de variação da pressão arterial no tempo (índice “time rate” - a primeira derivada da pressão arterial ao longo do tempo) e desvio padrão (DP) da PA obtidos dos dados da monitorização ambulatorial da pressão arterial (MAPA). Análises univariadas e multivariadas foram utilizadas para testar a associação entre a SAOS, IAH e variabilidade da pressão arterial. Resultados: Os pacientes com SAOS (n = 57) eram mais velhos, apresentavam pressão arterial mais elevada e maior duração da hipertensão do que pacientes sem SAOS (n = 50). Não houve nenhuma associação consistente entre o diagnóstico de SAOS e variabilidade da PA aferida pelo DP e pela taxa de variação da PA no tempo, tanto na análise univariada como após o ajuste para idade, IMC e respectiva medida de PA na MAPA. Não houve correlação significativa entre o AIH e os índices de variabilidade da PA em um modelo de regressão linear múltipla, controlando para idade, IMC e PA correspondente. Conclusão: SAOS não influencou a variabilidade da pressão arterial, aferida por estes métodos, em pacientes com hipertensão. / Background The risk of obstructive sleep apnea syndrome (OSAS) for the development of hypertension and cardiovascular disease may be intermediate by influence over autonomic cardiovascular regulation. This study investigated if OSAS influences blood pressure (BP) variability. Methods In a cross-sectional study, patients with hypertension underwent level III polysomnography by means of a home portable monitor to detect OSAS, (apnea-hypopnea index (AHI) ≥10). BP variability was assessed by the time rate index (the first derivative of BP over time) and standard deviation (SD) of BP measured by 24-h ambulatory blood pressure measurement (ABPM). The association between OSAS, AHI and blood pressure variability was tested by univariate and multivariate methods. Results: Patients with OSAS (n = 57) were older, had higher blood pressure, and longer duration of hypertension than patients without OSAS (n = 50). There was no consistent association between the diagnosis of OSAS and BP variability assessed by the time-rate index and SD both in the univariate and after adjustment for age, BMI and the respective BP. There was no significant correlation between AIH and the indexes of BP variability in a multiple linear regression model controlling for age, BMI and the corresponding BP. Conclusion OSAS does not influence blood pressure variability in patients with hypertension.

Introdução: O desenvolvimento de hipertensão arterial e doença cardiovascular relacionado à síndrome das apnéia obstrutiva do sono (SAOS) parece estar relacionado a alterações sobre a regulação autonômica cardiovascular. Este estudo investigou se a SAOS influência a variabilidade da pressão arterial (PA). Métodos: Estudo transversal, com pacientes hipertensos que foram submetidos à polissonografia nível III, por meio de um monitor portátil de uso domiciliar para detectar SAOS (índice de apnéia-hipopnéia (IAH) ≥ 10). A variabilidade da PA foi avaliada pela taxa de variação da pressão arterial no tempo (índice “time rate” - a primeira derivada da pressão arterial ao longo do tempo) e desvio padrão (DP) da PA obtidos dos dados da monitorização ambulatorial da pressão arterial (MAPA). Análises univariadas e multivariadas foram utilizadas para testar a associação entre a SAOS, IAH e variabilidade da pressão arterial. Resultados: Os pacientes com SAOS (n = 57) eram mais velhos, apresentavam pressão arterial mais elevada e maior duração da hipertensão do que pacientes sem SAOS (n = 50). Não houve nenhuma associação consistente entre o diagnóstico de SAOS e variabilidade da PA aferida pelo DP e pela taxa de variação da PA no tempo, tanto na análise univariada como após o ajuste para idade, IMC e respectiva medida de PA na MAPA. Não houve correlação significativa entre o AIH e os índices de variabilidade da PA em um modelo de regressão linear múltipla, controlando para idade, IMC e PA correspondente. Conclusão: SAOS não influencou a variabilidade da pressão arterial, aferida por estes métodos, em pacientes com hipertensão. / Background The risk of obstructive sleep apnea syndrome (OSAS) for the development of hypertension and cardiovascular disease may be intermediate by influence over autonomic cardiovascular regulation. This study investigated if OSAS influences blood pressure (BP) variability. Methods In a cross-sectional study, patients with hypertension underwent level III polysomnography by means of a home portable monitor to detect OSAS, (apnea-hypopnea index (AHI) ≥10). BP variability was assessed by the time rate index (the first derivative of BP over time) and standard deviation (SD) of BP measured by 24-h ambulatory blood pressure measurement (ABPM). The association between OSAS, AHI and blood pressure variability was tested by univariate and multivariate methods. Results: Patients with OSAS (n = 57) were older, had higher blood pressure, and longer duration of hypertension than patients without OSAS (n = 50). There was no consistent association between the diagnosis of OSAS and BP variability assessed by the time-rate index and SD both in the univariate and after adjustment for age, BMI and the respective BP. There was no significant correlation between AIH and the indexes of BP variability in a multiple linear regression model controlling for age, BMI and the corresponding BP. Conclusion OSAS does not influence blood pressure variability in patients with hypertension.

Introdução: O desenvolvimento de hipertensão arterial e doença cardiovascular relacionado à síndrome das apnéia obstrutiva do sono (SAOS) parece estar relacionado a alterações sobre a regulação autonômica cardiovascular. Este estudo investigou se a SAOS influência a variabilidade da pressão arterial (PA). Métodos: Estudo transversal, com pacientes hipertensos que foram submetidos à polissonografia nível III, por meio de um monitor portátil de uso domiciliar para detectar SAOS (índice de apnéia-hipopnéia (IAH) ≥ 10). A variabilidade da PA foi avaliada pela taxa de variação da pressão arterial no tempo (índice “time rate” - a primeira derivada da pressão arterial ao longo do tempo) e desvio padrão (DP) da PA obtidos dos dados da monitorização ambulatorial da pressão arterial (MAPA). Análises univariadas e multivariadas foram utilizadas para testar a associação entre a SAOS, IAH e variabilidade da pressão arterial. Resultados: Os pacientes com SAOS (n = 57) eram mais velhos, apresentavam pressão arterial mais elevada e maior duração da hipertensão do que pacientes sem SAOS (n = 50). Não houve nenhuma associação consistente entre o diagnóstico de SAOS e variabilidade da PA aferida pelo DP e pela taxa de variação da PA no tempo, tanto na análise univariada como após o ajuste para idade, IMC e respectiva medida de PA na MAPA. Não houve correlação significativa entre o AIH e os índices de variabilidade da PA em um modelo de regressão linear múltipla, controlando para idade, IMC e PA correspondente. Conclusão: SAOS não influencou a variabilidade da pressão arterial, aferida por estes métodos, em pacientes com hipertensão. / Background The risk of obstructive sleep apnea syndrome (OSAS) for the development of hypertension and cardiovascular disease may be intermediate by influence over autonomic cardiovascular regulation. This study investigated if OSAS influences blood pressure (BP) variability. Methods In a cross-sectional study, patients with hypertension underwent level III polysomnography by means of a home portable monitor to detect OSAS, (apnea-hypopnea index (AHI) ≥10). BP variability was assessed by the time rate index (the first derivative of BP over time) and standard deviation (SD) of BP measured by 24-h ambulatory blood pressure measurement (ABPM). The association between OSAS, AHI and blood pressure variability was tested by univariate and multivariate methods. Results: Patients with OSAS (n = 57) were older, had higher blood pressure, and longer duration of hypertension than patients without OSAS (n = 50). There was no consistent association between the diagnosis of OSAS and BP variability assessed by the time-rate index and SD both in the univariate and after adjustment for age, BMI and the respective BP. There was no significant correlation between AIH and the indexes of BP variability in a multiple linear regression model controlling for age, BMI and the corresponding BP. Conclusion OSAS does not influence blood pressure variability in patients with hypertension.

京都大学 / 0048 / 新制・論文博士 / 博士(医学) / 乙第13233号 / 論医博第2173号 / 新制||医||1036(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 川村 孝, 教授 横出 正之, 教授 福原 俊一 / 学位規則第4条第2項該当 / Doctor of Medical Science / Kyoto University / DFAM

No description available.

This study examined the effects of isometric handgrip (IHG) training on resting blood pressure (RBP), heart rate variability (HRV) and blood pressure variability (BPV) in older adults with hypertension. Nine subjects performed four 2-minute IHG contractions at 30% maximal voluntary contraction (MVC) 3 days/week for 10 weeks and 8 subjects served as controls. Power spectral analysis (PSA) of HRV and BPV was used to assess changes in modulation of the autonomic nervous system. After training, there was a marked attenuation in arterial pressure and evidence for a shift in HR.V and BPV sympathovagal balance. There was a reduction in systolic blood pressure (156 ± 9.4 to 137 ± 7.8 mm Hg; p<0.05), diastolic blood pressure (82 ± 9.3 to 75 ± 10.9 mm Hg; N.S), mean arterial pressure (107 ± 8.53 to 96 ± 8.7 mm Hg; p<0.05) and resting heart rate (RHR) (70 ± 14.2 to 68 ± 12.1 beats/min). In addition, PSA of HRV showed a decrease in sympathetic modulation represented by low frequency (LF) area, an increase in parasympathetic modulation represented by high frequency (HF) area (p<0.05) and a decrease in LF:HF area ratio. After training, BPV PSA showed a decrease in systolic blood pressure LF area (p<0.05), an increase in HF area (p<0.05) and decrease in LF:HF area (p<0.05). Similar, but non-significant changes occurred in diastolic BPV. It is concluded that isometric training at a moderate intensity can elicit a hypotensive response and can potentially alter sympathovagal balance of HRV and BPV in older adults with hypertension. / Thesis / Master of Science (MS)