Background: End-stage renal disease is a major health problem worldwide nowadays. Although conven... more Background: End-stage renal disease is a major health problem worldwide nowadays. Although conventional hemodialysis is the most widely used modality, short daily hemodialysis has been proposed as a more physiologic treatment. The objective of this article is to compare the quality of life of patients on each hemodialysis modality. Methods: A multicentric cross-sectional study was performed in 9 Spanish hospitals. Patients treated for at least 3 months with conventional or short daily hemodialysis were included and quality of life measured using the Euroqol-5D quality of life questionnaire. Bayesian models were used for analyzing quality of life results. Results: Ninety-three patients were included, 27 were on daily hemodialysis and 66 on conventional hemodialysis. All models demonstrated a better quality of life for daily hemodialysis versus conventional hemodialysis. Only 14% of the patients on conventional hemodialysis were willing to change to a daily schedule. Conclusions: Shor...
Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted s... more Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning. Despite the established clinical relevance of the asleep BP, past as do present hypertension guidelines recommend the diagnosis of hypertension rely on OBPM and, when around-the-clock ambulatory BP monitoring (ABPM) is conducted to confirm the elevated OBPM, either on the derived 24 h or "daytime" BP means. Additionally, hypertension guidelines do not advise the time-of-day when BP-lowering medications should be ingested, in spite of known ingestion-time differences in their pharmacokinetics and pharmacodynamics. Between 1976 and 2020, 155 unique trials of ingestion-time differences in the effects of 37 different single and 14 dual-combination hypertension medications, collectively involving 23,972 patients, were published. The vast majority (83.9%) of them found the at-bedtime/evening in comparison to upon-waking/morning treatment schedule resulted in more greatly enhanced: (i) reduction of asleep BP mean without induced sleep-time hypotension; (ii) reduction of the prevalence of the higher CVD risk non-dipper/riser 24 h BP phenotypes; (iii) improvement of kidney function, reduction of cardiac pathology, and with lower incidence of adverse effects. Most notably, no single published randomized trial found significantly better BP-lowering, particularly during sleep, or medical benefits of the most popular upon-waking/morning hypertension treatment-time scheme. Additionally, prospective outcome trials have substantiated that the bedtime relative to the upon-waking, ingestion of BP-lowering medications not only significantly reduces risk of HF but also improves overall CVD event-free survival time.
The extent of blood pressure (BP) surge upon waking has been associated with increased cardiovasc... more The extent of blood pressure (BP) surge upon waking has been associated with increased cardiovascular (CVD) risk in some, but not all, studies. Numerous studies, however, have consistently shown the association between elevated sleep-time BP mean and the rising BP pattern with increased CVD risk, leading to a paradox, as patients with sleep-time hypertension or non-dipper/riser BP pattern have attenuated morning BP surge. We evaluated the comparative prognostic value for CVD events of the morning BP surge and sleep-time BP among the participants in the ongoing Hygia Project. This study involved 11255 subjects, 6028 men/5227 women, 58.9 ± 14.5 years of age, prospectively evaluated throughout a 4.0-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed and awakening. We documented 1539 total events, including 400 deaths, 176 strokes, 144 myocardial infarctions, 147 coronary revascularizations, and 193 heart failures. A greater prewaking systolic BP surge was associated with significantly lower, not higher, CVD risk in a Cox proportional-hazard model adjusted for the significant influential characteristics of age, sex, diabetes, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event (hazard ratio [HR] 0.83 [95%CI 0.78-0.88] per each 1-SD increment; P < 0.001). The HR was progressively and significantly higher in the first three than in the last two quintiles of increasing prewaking BP surge. The prognostic value of morning surge markedly decreased after correcting by the asleep BP mean, the single most significant prognostic marked of total CVD events (HR = 1.37 [1.29-1.44], P < 0.001). Our findings document that, when properly analyzed as a continuous variable, a larger morning BP surge is associated with a significantly lower CVD risk, in line with the markedly greater risk associated with decreasing dipping of the BP pattern, and the most highly significant prognostic value of progressively elevated asleep BP, an independent prognostic marker of CVD risk that has also been prospectively validated as a relevant therapeutic target for CVD risk reduction.
Nefrología : publicación oficial de la Sociedad Española Nefrologia, 2011
During recent years, increasing recognition has been given to the endocrine action that vitamin D... more During recent years, increasing recognition has been given to the endocrine action that vitamin D has on the extraskeletal system, and its deep involvement in CKD. This has meant that many vitamin D compounds (both nutritional and active) have been made available, with an important cost reduction. This review looks at the evidence available regarding the usefulness of different types of vitamin D (nutritional and active) for patients with stage 3-5 CKD and those undergoing dialysis. Emphasis is given to its usefulness to control hyperparathyroidism and its impact on morbidity and mortality. We also analysed pharmacoeconomic studies that have been published which compare active vitamin D metabolites. From this review, we are able to conclude that there is still not enough scientific evidence to be able to prefer one active vitamin D over another. In the meantime, doctors should follow the recommendations given in clinical practice guidelines, always taking into account their personal...
Daytime office blood pressure (BP) measurements (OBPM), still recommended and utilized today for ... more Daytime office blood pressure (BP) measurements (OBPM), still recommended and utilized today for diagnosis and management of hypertension and categorization of cardiovascular disease (CVD) risk, fail to reveal clinically important features of the mostly predictable BP 24h pattern and leads to a large proportion of individuals being misclassified. Most clinical guidelines now recommend ambulatory BP monitoring (ABPM) be applied to adult patients to confirm the OBPM-based diagnosis of hypertension, based on the high prevalence of masked hypertension and masked normotension plus demonstrated significantly better CVD prognostic value of around-the-clock ABPM than daytime OBPM. Nonetheless, there is as yet no consensus of which parameter(s) and ABPM thresholds to utilize to diagnose hypertension. Findings of large prospective ABPM-based CVD outcome trials permit prospective evaluation of treatment and other induced changes in OBPM and ABPM during follow-up on CVD risk by incorporating multiple periodic (at least annual) patient ABPM assessments. They indicate the: (i) asleep systolic BP (SBP) mean and sleeptime relative SBP decline (dipping) together are the most significant and only BP-derived prognostic markers of CVD risk; accordingly, around-the-clock ABPM should be the recommended method to diagnose true arterial hypertension and accurately assess CVD risk; (ii) treatmentinduced lowering of the asleep SBP mean and rise of the sleep-time relative SBP decline towards the normal dipper BP pattern are both significantly protective against CVD events, thus constituting novel therapeutic targets to substantially better reduce CVD risk compared to the traditional approach that targets control of daytime OBPM or awake BP mean.
ABSTRACT The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the critic... more ABSTRACT The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the criticisms of its published findings, which have been unjustifiably misrepresented in letters to the editors and commentaries, perhaps because of lack of understanding of the foundations of the Hygia Project, in which the HCT is nested. Thus, our purpose through this communication is to highlight the unique features of the Hygia Project and HCT in terms of: (i) organization, management, and quality control, (ii) physician training/continuing medical education, and (iii) impact on every-day primary-care clinical practice specifically improved patient care through 48 h ambulatory blood pressure monitoring to diagnose and optimally manage by bedtime hypertension chronotherapy true arterial hypertension to markedly improve the cardiovascular health of our patients.
Background: End-stage renal disease is a major health problem worldwide nowadays. Although conven... more Background: End-stage renal disease is a major health problem worldwide nowadays. Although conventional hemodialysis is the most widely used modality, short daily hemodialysis has been proposed as a more physiologic treatment. The objective of this article is to compare the quality of life of patients on each hemodialysis modality. Methods: A multicentric cross-sectional study was performed in 9 Spanish hospitals. Patients treated for at least 3 months with conventional or short daily hemodialysis were included and quality of life measured using the Euroqol-5D quality of life questionnaire. Bayesian models were used for analyzing quality of life results. Results: Ninety-three patients were included, 27 were on daily hemodialysis and 66 on conventional hemodialysis. All models demonstrated a better quality of life for daily hemodialysis versus conventional hemodialysis. Only 14% of the patients on conventional hemodialysis were willing to change to a daily schedule. Conclusions: Shor...
Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted s... more Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning. Despite the established clinical relevance of the asleep BP, past as do present hypertension guidelines recommend the diagnosis of hypertension rely on OBPM and, when around-the-clock ambulatory BP monitoring (ABPM) is conducted to confirm the elevated OBPM, either on the derived 24 h or "daytime" BP means. Additionally, hypertension guidelines do not advise the time-of-day when BP-lowering medications should be ingested, in spite of known ingestion-time differences in their pharmacokinetics and pharmacodynamics. Between 1976 and 2020, 155 unique trials of ingestion-time differences in the effects of 37 different single and 14 dual-combination hypertension medications, collectively involving 23,972 patients, were published. The vast majority (83.9%) of them found the at-bedtime/evening in comparison to upon-waking/morning treatment schedule resulted in more greatly enhanced: (i) reduction of asleep BP mean without induced sleep-time hypotension; (ii) reduction of the prevalence of the higher CVD risk non-dipper/riser 24 h BP phenotypes; (iii) improvement of kidney function, reduction of cardiac pathology, and with lower incidence of adverse effects. Most notably, no single published randomized trial found significantly better BP-lowering, particularly during sleep, or medical benefits of the most popular upon-waking/morning hypertension treatment-time scheme. Additionally, prospective outcome trials have substantiated that the bedtime relative to the upon-waking, ingestion of BP-lowering medications not only significantly reduces risk of HF but also improves overall CVD event-free survival time.
The extent of blood pressure (BP) surge upon waking has been associated with increased cardiovasc... more The extent of blood pressure (BP) surge upon waking has been associated with increased cardiovascular (CVD) risk in some, but not all, studies. Numerous studies, however, have consistently shown the association between elevated sleep-time BP mean and the rising BP pattern with increased CVD risk, leading to a paradox, as patients with sleep-time hypertension or non-dipper/riser BP pattern have attenuated morning BP surge. We evaluated the comparative prognostic value for CVD events of the morning BP surge and sleep-time BP among the participants in the ongoing Hygia Project. This study involved 11255 subjects, 6028 men/5227 women, 58.9 ± 14.5 years of age, prospectively evaluated throughout a 4.0-year median follow-up. BP was measured at 20-min intervals from 07:00 to 23:00 h and at 30-min intervals at night for 48 h. During monitoring, subjects maintained a diary listing the times of going to bed and awakening. We documented 1539 total events, including 400 deaths, 176 strokes, 144 myocardial infarctions, 147 coronary revascularizations, and 193 heart failures. A greater prewaking systolic BP surge was associated with significantly lower, not higher, CVD risk in a Cox proportional-hazard model adjusted for the significant influential characteristics of age, sex, diabetes, chronic kidney disease, cigarette smoking, waist perimeter, and history of previous CVD event (hazard ratio [HR] 0.83 [95%CI 0.78-0.88] per each 1-SD increment; P < 0.001). The HR was progressively and significantly higher in the first three than in the last two quintiles of increasing prewaking BP surge. The prognostic value of morning surge markedly decreased after correcting by the asleep BP mean, the single most significant prognostic marked of total CVD events (HR = 1.37 [1.29-1.44], P < 0.001). Our findings document that, when properly analyzed as a continuous variable, a larger morning BP surge is associated with a significantly lower CVD risk, in line with the markedly greater risk associated with decreasing dipping of the BP pattern, and the most highly significant prognostic value of progressively elevated asleep BP, an independent prognostic marker of CVD risk that has also been prospectively validated as a relevant therapeutic target for CVD risk reduction.
Nefrología : publicación oficial de la Sociedad Española Nefrologia, 2011
During recent years, increasing recognition has been given to the endocrine action that vitamin D... more During recent years, increasing recognition has been given to the endocrine action that vitamin D has on the extraskeletal system, and its deep involvement in CKD. This has meant that many vitamin D compounds (both nutritional and active) have been made available, with an important cost reduction. This review looks at the evidence available regarding the usefulness of different types of vitamin D (nutritional and active) for patients with stage 3-5 CKD and those undergoing dialysis. Emphasis is given to its usefulness to control hyperparathyroidism and its impact on morbidity and mortality. We also analysed pharmacoeconomic studies that have been published which compare active vitamin D metabolites. From this review, we are able to conclude that there is still not enough scientific evidence to be able to prefer one active vitamin D over another. In the meantime, doctors should follow the recommendations given in clinical practice guidelines, always taking into account their personal...
Daytime office blood pressure (BP) measurements (OBPM), still recommended and utilized today for ... more Daytime office blood pressure (BP) measurements (OBPM), still recommended and utilized today for diagnosis and management of hypertension and categorization of cardiovascular disease (CVD) risk, fail to reveal clinically important features of the mostly predictable BP 24h pattern and leads to a large proportion of individuals being misclassified. Most clinical guidelines now recommend ambulatory BP monitoring (ABPM) be applied to adult patients to confirm the OBPM-based diagnosis of hypertension, based on the high prevalence of masked hypertension and masked normotension plus demonstrated significantly better CVD prognostic value of around-the-clock ABPM than daytime OBPM. Nonetheless, there is as yet no consensus of which parameter(s) and ABPM thresholds to utilize to diagnose hypertension. Findings of large prospective ABPM-based CVD outcome trials permit prospective evaluation of treatment and other induced changes in OBPM and ABPM during follow-up on CVD risk by incorporating multiple periodic (at least annual) patient ABPM assessments. They indicate the: (i) asleep systolic BP (SBP) mean and sleeptime relative SBP decline (dipping) together are the most significant and only BP-derived prognostic markers of CVD risk; accordingly, around-the-clock ABPM should be the recommended method to diagnose true arterial hypertension and accurately assess CVD risk; (ii) treatmentinduced lowering of the asleep SBP mean and rise of the sleep-time relative SBP decline towards the normal dipper BP pattern are both significantly protective against CVD events, thus constituting novel therapeutic targets to substantially better reduce CVD risk compared to the traditional approach that targets control of daytime OBPM or awake BP mean.
ABSTRACT The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the critic... more ABSTRACT The participating doctors of the Hygia Chronotherapy Trial (HCT) are aware of the criticisms of its published findings, which have been unjustifiably misrepresented in letters to the editors and commentaries, perhaps because of lack of understanding of the foundations of the Hygia Project, in which the HCT is nested. Thus, our purpose through this communication is to highlight the unique features of the Hygia Project and HCT in terms of: (i) organization, management, and quality control, (ii) physician training/continuing medical education, and (iii) impact on every-day primary-care clinical practice specifically improved patient care through 48 h ambulatory blood pressure monitoring to diagnose and optimally manage by bedtime hypertension chronotherapy true arterial hypertension to markedly improve the cardiovascular health of our patients.
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