Ramon C Hermida

University of Vigo | UVIGO · Bioengineering and Chronobiology Laboratories

The conduct of molecular and laboratory animal circadian rhythm research has increased exponentially in the past few decades, such that today investigations are being performed by scientists of many diverse disciplines. Knowledge gained from past works is now being explored for translational applications to clinical medicine, often termed "circadia...

Objectives: Major objectives of this work were to: (i) substantiate the 24-hour pattern in the occurrence of childhood febrile seizures (CFSs) by a novel time series meta-analysis of past reported time-of-day data and (ii) discuss its potential circadian rhythm-dependencies. Methods: Comprehensive search of the published literature retrieved eig...

Blood pressure (BP) follows a circadian variation, increasing during active hours, showing a small postprandial valley and a deeper decrease during sleep. Nighttime reduction of 10–20% relative to daytime BP is defined as a dipper pattern, and a reduction of less than 10%, as a non-dipper pattern. Despite this BP variability, hypertension’s diagnos...

An appreciable number of medicines have a recommended unique single time-of-day or asymmetrical or unequal-interval multiple-daily administration schedule. Many prescription and over-the-counter (OTC) products, according to administration time, can exert positive or negative impact on nighttime sleep and daytime wakefulness. Intuitively, medicines...

We reviewed medication package inserts, US Food and Drug Administration (FDA) reports, and journal publications concerning the 10 nonbiosimilar patient-applied (PA) testosterone (T) replacement therapies (TRTs) for intraday serum T patterning and blood pressure (BP) effects. Blood T concentration is circadian rhythmic in young adult eugonadal males...

The sleep–wake cycle is regulated by circadian Process C and homeostatic Process S. Selective thermal stimulation (STS) of the cervical spine region enhances glabrous skin blood flow (GSBF) and augments body heat dissipation to increase distal‐to‐proximal skin gradient (DPG) causing decrease of core body temperature (CBT), which can shorten sleep o...

Atherosclerosis, a chronic inflammatory disease of the arteries that appears to have been as prevalent in ancient as in modern civilizations, is predisposing to life-threatening and life-ending cardiac and vascular complications, such as myocardial and cerebral infarctions. The pathogenesis of atherosclerosis involves intima plaque buildup caused b...

The pharmacodynamics of hypertension medications can be significantly affected by circadian rhythms in the biological mechanisms of the 24 h blood pressure (BP) pattern. Hypertension guidelines fail to recommend the time of day when patients, including those who require treatment with multiple medications, are to ingest BP-lowering therapy. We cond...

Borbély proposed an interacting two-component model of sleep regulation comprising a homeostatic Process S and a circadian Process C. The model has provided understanding of the association between core body temperature (CBT) as a key element of Process C that is deterministic of sleep onset and offset. However, it additionally provides a new persp...

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...

The pharmacokinetics (PK) – absorption, distribution, metabolism, and elimination – and pharmacodynamics (PD) of hypertension medications can be significantly affected by circadian rhythms. As a consequence, the time when blood pressure (BP) lowering medications are ingested, with reference to the staging of all involved circadian rhythms modulatin...

This article summarizes the current literature and documents new evidence concerning drug-drug interactions (DDI) stemming from pharmacogenomic and circadian rhythm determinants of therapies used to treat common cardiovascular diseases (CVD), such as atherosclerosis and hypertension. Patients with CVD often have more than one pathophysiologic condi...

Circadian rhythms impact cardiac and vascular pathophysiology, resulting in 24-hour patterning of symptoms and life-threatening/ending events (chronopathology), plus kinetics and dynamics of medications (chronopharmacology), resulting in administration-time differences in efficacy and safety. Scheduling medications according to circadian rhythm det...

Combined evidence of published prospective outcome trials and meta-analyses substantiate elevated asleep blood pressure (BP) and blunted sleep-time relative BP decline (non-dipping), regardless of wake-time office BP and awake or 24h BP means, are jointly the most highly significant independent prognostic markers of cardiovascular disease (CVD) ris...

Pharmacokinetics of hypertension medications is significantly affected by circadian rhythms that influence absorption, distribution, metabolism and elimination. Furthermore, their pharmacodynamics is affected by ingestion-time differences in kinetics and circadian rhythms comprising the biological mechanism of the 24 h blood pressure (BP) pattern....

Current hypertension guidelines fail to provide a recommendation on when-to-treat, thus disregarding relevant circadian rhythms that regulate blood pressure (BP) level and 24 h patterning and medication pharmacokinetics and pharmacodynamics. The ideal purpose of ingestion-time (chronopharmacology, i.e. biological rhythm-dependent effects on the kin...

Resumen Introducción y objetivos La presión arterial (PA) ambulatoria predice el riesgo de enfermedad cardiovascular (ECV) mejor que las mediciones clínicas (MCPA). Sin embargo, los modelos actuales de estratificación del riesgo de ECV se basan exclusivamente en las MCPA junto con otros factores tradicionales, como edad, sexo, tabaquismo, dislipem...

Introduction: Hypertension guidelines do not recommend the time to administer blood pressure (BP)-lowering medications, despite multiple prospective clinical trials reporting both improved normalization of BP 24h patterning and reduced cardiovascular disease (CVD) events when ingested at bedtime rather than upon awakening. Areas covered: We revi...

Introduction and objectives: Ambulatory blood pressure (BP) better predicts cardiovascular disease (CVD) outcomes than office BP measurements (OBPM). Nonetheless, current CVD risk stratification models continue to rely on exclusively daytime OBPM along with traditional factors, eg, age, sex, smoking, dyslipidemia, and/or diabetes. Methods: Data...

The purpose of this communication is to respond to the continuing invalid criticism by Lemmer and Middeke of the MAPEC and Hygia Chronotherapy Trial by emphasizing the: (i) already unambiguously reported ambulatory blood pressure monitoring (ABPM)-based definition of hypertension utilized as the inclusion criterion of both investigations and (ii)...

Purpose of review: Current hypertension guidelines do not provide recommendation on when-to-treat. Herein, we review the current evidence on ingestion-time differences of hypertension medications in blood pressure (BP)-lowering effects and prevention of cardiovascular disease (CVD) events. Recent findings: The vast (81.6%) majority of the 136 pu...

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. M...

The purpose of this communication is to describe the unique features of the investigative protocols of both MAPEC and Hygia Chronotherapy Trial and to discuss in detail the advantages, limitations, and potential implications of their findings, both for the diagnosis and management of true arterial hypertension that we propose must be defined accord...

The main purpose of this commentary is to update, based on our extensive review of the published literature of the past 45 yrs, the differential therapeutic effects of hypertension medications of various classes and their combinations when ingested in the evening/at-bedtime versus in the morning/upon-awakening. Interestingly, revision of the curren...

Reinhold Kreutz and colleagues in a recent editorial claim the Hygia Chronotherapy Trial lacks credibility because of deficient methods, thereby dismissing both the plausibility and clinical significance of its reported findings. They misstate and misrepresent crucial information, findings and conclusions unambiguously detailed in the published rep...

The specific purpose of this communication is to summarize the relevant details of the methods utilized to conduct, analyze, and interpret the ambulatory blood pressure (BP) monitoring (ABPM)-obtained patient data in both MAPEC and Hygia Chronotherapy Trial, including details of the sampling requirements in terms of duration and frequency, proper c...

Introduction Office blood pressure measurements (OBPM), still used today for diagnosis and management of hypertension, fail to reveal clinically important features of the mostly predictable blood pressure (BP) 24 h pattern, and lead to >45% of individuals being misclassified. Current hypertension guidelines do not provide recommendation on when-to-...

Numerous prospective studies establish that elevated asleep blood pressure (BP) constitutes a significant cardiovascular disease (CVD) risk factor, irrespective of daytime office BP measurements or awake and 24 h BP measurements. Moreover, except for a small number of studies with flawed methodology, multiple clinical trials of high consistency doc...

Resumen Diversos estudios prospectivos han demostrado de forma concordante que la elevación en la media de descanso de la presión arterial (PA) constituye un factor de riesgo cardiovascular (CV) significativo e independiente de la PA clínica, o de las medias de actividad o de 24 horas derivadas de la monitorización ambulatoria de la PA. Además, múl...

Aims: The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction. Methods and results: In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive p...

The cost-effectiveness of ambulatory blood pressure (BP) monitoring (ABPM) versus traditional office BP measurement (OBPM) for the diagnosis and management of hypertension has been evaluated only by few studies and based solely on the reduction of medical care expenses through avoiding treatment of isolated-office hypertension. Data from the 21963...

Aims: Sleep-time blood pressure (BP) is a stronger risk factor for cardiovascular disease (CVD) events than awake and 24 h BP means, but the potential role of asleep BP as therapeutic target for diminishing CVD risk is uncertain. We investigated whether CVD risk reduction is most associated with progressive decrease of either office or ambulatory...

This trial investigated whether therapy with the entire daily dose of ≥1 hypertension medications at bedtime exerts a greater reduction in the risk of incident chronic kidney disease (CKD) than therapy with all medications upon awakening. We conducted a prospective, open-label, blinded endpoint trial of 2078 hypertensive patients without CKD (1017...

Diagnosis of hypertension – elevated blood pressure (BP) associated with increased cardiovascular disease (CVD) risk – and its management for decades have been based primarily on single time-of-day office BP measurements (OBPM) assumed representative of systolic (SBP) and diastolic BP (DBP) during the entire 24h span. Around-the-clock ambulatory bl...

The bases for bedtime hypertension chronotherapy (BHCT) as superior chronoprevention against cardiovascular disease (CVD) are: (1) correlation between blood pressure (BP) and various risks is greater for ambulatory BP monitoring (ABPM) than office BP measurements (OBPM); (2) asleep BP mean is a better predictor of CVD risk than ABPM awake and 24-ho...

Consistent evidence of numerous studies substantiates the asleep blood pressure (BP) mean derived from ambulatory BP monitoring (ABPM) is both an independent and a stronger predictor of cardiovascular disease (CVD) risk than are daytime clinic BP measurements or the ABPM-determined awake or 24-hour BP means. Hence, cost-effective adequate control o...

The prognostic value of clinic and ambulatory BP in predicting incident CKD and whether CKD risk reduction associates with progressive treatment-induced decrease of clinic, awake, or asleep BP are unknown. We prospectively evaluated 2763 individuals without CKD, 1343 men and 1420 women (mean±SD age: 51.5±14.3 years old), with baseline ambulatory BP...

We are pleased to read the recently featured Cardiology News article published in Circulation .1 The article highlights research findings demonstrating the important role that circadian clock genes play in regulating cardiac and vascular physiology and, based on animal experiments, the negative consequences of circadian disruption on recovery after...

Biological processes are organized in time as innate rhythms defined by the period (τ), phase (peak [Φ] and trough time), amplitude (A, peak-trough difference) and mean level. The human time structure in its entirety is comprised of ultradian (τ < 20 h), circadian (20 h > τ < 28 h) and infradian (τ > 28 h) bioperiodicities. The circadian time struc...

This article describes the rationale, objectives, design and conduct of the ambulatory blood pressure monitoring (ABPM)-based Hygia Project. Given the substantial evidence of the significantly better prognostic value of ABPM compared to clinic BP measurements, several international guidelines now propose ABPM as a requirement to confirm the office...

Correlation between blood pressure (BP) and target organ damage, vascular risk, and long-term patient prognosis is greater for measurements derived from around-the-clock ambulatory BP monitoring than in-clinic daytime ones. Numerous studies consistently substantiate the asleep BP mean is both an independent and much better predictor of cardiovascul...

In most persons, blood pressure (BP) rises slowly during late sleep; increases rapidly upon morning awakening and commencement of diurnal activity; exhibits two -- morning and afternoon/early evening -- daytime peaks; minor midday nadir, and decline during nighttime sleep by 10 to 20% in systolic BP and somewhat lesser amount in diastolic BP relati...

Correlation between blood pressure (BP) and target organ damage, cardiovascular disease (CVD) risk, and long-term prognosis is greater for ambulatory BP monitoring (ABPM) than daytime in-clinic measurements. Additionally, consistent evidence from numerous studies substantiates that ABPM-determined asleep BP mean is an independent and stronger predi...

The prognostic importance of the nocturnal systolic blood pressure (SBP) fall, adjusted for average 24-hour SBP levels, is unclear. The Ambulatory Blood Pressure Collaboration in Patients With Hypertension (ABC-H) examined this issue in a meta-analysis of 17 312 hypertensives from 3 continents. Risks were computed for the systolic night-to-day rati...

Aims/hypothesis We investigated whether therapy with the entire daily dose of ≥1 hypertension medications at bedtime exerts greater reduction in the risk of new-onset diabetes than therapy with all medications upon awakening. Methods We conducted a prospective, randomised, open-label, blinded endpoint trial of 2,012 hypertensive patients without di...

Aims/hypothesis: We investigated the prognostic value of clinic and ambulatory BP (ABP) to predict new-onset diabetes and whether risk reduction is related to the progressive decrease of clinic BP or awake or asleep ABP. Methods: We prospectively evaluated 2,656 individuals without diabetes, 1,292 men and 1,364 women, 50.6 ± 14.3 years of age, w...

Blood pressure (BP) exhibits significant 24 h variation; in most normotensive and uncomplicated hypertensive persons, BP declines during the first half of nighttime sleep by 10–20 % from its daytime mean level, starts rising in the second half of sleep, further increases with commencement of diurnal activity, and peaks in the afternoon or early eve...

Gestational hypertension (GH) and preeclampsia (PE) are major causes of perinatal morbidity and mortality. The diagnosis of these conditions still relies on unreliable conventional clinic blood pressure (BP) measurements and inappropriate thresholds of ≥140/90 mmHg for systolic/diastolic BP. Noninvasive around-the-clock ambulatory BP monitoring (AB...

Correlation between blood pressure (BP) and target organ damage, vascular risk and long-term patient prognosis is greater for measurements derived from around-the-clock ambulatory BP monitoring than in-clinic daytime ones. Numerous studies consistently substantiate the asleep BP mean is both an independent and a much better predictor of cardiovascu...

New information has become available since the ISC, AAMCC, and SECAC released their first extensive guidedelines to improve the diagnosis and treatment of adult arterial hypertension. A critical assessment of evidence and a comparison of what international guidelines now propose are the basis for the following statements, which update the recommend...

The diagnosis of hypertension and the clinical decisions regarding its treatment are usually based on daytime clinic blood pressure (BP) measurements. However, the correlation between BP levels and target organ damage, cardiovascular (CV) risk, and long-term prognosis, is higher for ambulatory (ABPM) than clinic measurements, both in the general po...

Objective: Many prospective trials have documented the safety and effects on the 24 h blood pressure (BP) pattern of several classes of hypertension medications are greatly improved when ingested at bedtime rather than upon awakening. Recent findings further indicate reduction of asleep BP by bedtime hypertension treatment significantly reduces the...

Objective: Several features of ambulatory (ABPM) blood pressure (BP) have been explored as potential predictors of stroke. Some studies, limited among other factors by relying on a single, low reproducible 24 h ABPM per participant, use of arbitrarily fixed clock hours to defined awake and asleep spans, and/or analysis of the prognostic value of a...

Objective: In hypertension, ingesting blood pressure (BP)-lowering medications at bedtime, compared to ingesting them upon awakening, is associated with significant improved reduction of sleep-time BP mean, a sensitive prognostic marker of cardiovascular disease (CVD) risk, also identified as a predictor of the risk of developing chronic kidney dis...

Objective: Recent guidelines suggest relying on the ambulatory blood pressure (BP) monitoring (ABPM) derived awake mean to corroborate the diagnosis of hypertension suspected by elevated clinic BP measurement. However, several prospective ABPM studies have found elevated sleep-time BP is a better predictor of cardiovascular disease (CVD) risk than...

Objective: 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 sl...

Objective: Independent studies have found that elevated sleep-time blood pressure (BP) is a better predictor of cardiovascular disease (CVD) risk than the awake or 24 h BP means in patients without as well as with chronic kidney disease (CKD). However, whether elevated asleep BP provides prognostic value for predicting the development of CKD has sc...

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 hy...

Whether ambulatory blood pressure (BP) among hypertensive patients better predicts cardiovascular events (CVEs) in women relative to men is unclear. We searched PUBMED and OVID databases. Cohorts were required to have hypertension, 1+ years of follow-up, with stroke and coronary artery disease as outcomes. Lead investigators for these cohorts provi...