Circadian Rhythm of Blood Pressure of Dipper and Non-dipper Patients With Essential Hypertension: A Mathematical Modeling Approach.

Blood pressure in humans presents a circadian variation profile with a morning increase, a small postprandial valley, and a deeper descent during night-time rest. Under certain conditions, the nocturnal decline in blood pressure can be reduced or even reversed (non-dipper), which is related to a significantly worse prognosis than a normal fall pattern (dipper). Despite several advances in recent years, our understanding of blood pressure's temporal structure, its sources and mechanisms is far from complete. In this work, we developed an ordinary differential equation-based mathematical model capable of capturing the circadian rhythm of blood pressure in dipper and non-dipper patients with arterial hypertension. The model was calibrated by means of global optimization, using 24-h data of systolic and diastolic blood pressure, physical activity, heart rate, blood glucose and norepinephrine, obtained from the literature. After fitting the model, the mean of the normalized error for each data point was <0.2%, and confidence intervals indicate that all parameters were identifiable. Sensitivity analysis allowed identifying the most relevant parameters and therefore inferring the most important blood pressure regulatory mechanisms involved in the non-dipper status, namely, increase in sympathetic over parasympathetic nervous tone, lower influence of physical activity on heart rate and greater influence of physical activity and glucose on the systemic vascular resistance. In summary, this model allows explaining the circadian rhythm of blood pressure and deepening the understanding of the underlying mechanisms and interactions integrating the results of previous works.

Hipertensión matinal y comportamiento non-dipper en embarazadas con hipertensión de guardapolvo blanco / Morning Hypertension and Non-dipper Behavior in Pregnant Women with White Coat Syndrome

Introducción: La hipertensión de guardapolvo blanco (HGB) es común en el embarazo, aunque su evolución clínica durante la gestación se conoce poco. La hipertensión matinal y el comportamiento non-dipper, medidos por monitoreo ambulatorio de la presión arterial (MAPA), se asocian con mayor riesgo de eventos cardiovasculares; no obstante ello, son escasos los estudios en la gestación. Objetivos: El objetivo primario del estudio fue evaluar la hipertensión matinal y el comportamiento non-dipper en embarazadas con HGB versus un grupo control de normotensas. Se planteó como objetivo secundario evaluar si la HGB, la hipertensión matinal y el comportamiento non-dipper en el segundo trimestre del embarazo se relacionan con mayor hipertensión sostenida en el tercer trimestre. Material y métodos: Estudio prospectivo en el que se incluyeron 95 primigestas en la semana 20 de gestación, 50 con HGB y 45 normotensas como grupo control. Se registraron laboratorio de rutina, presión de consultorio y MAPA en la inclusión y a las 32 semanas de gestación. La hipertensión matinal y el comportamiento non-dipper se evaluaron por MAPA. Resultados: La edad, la glucemia y la presión diurna y nocturna por MAPA fueron similares en el examen basal en ambos grupos. Por el contrario, las pacientes con HGB presentaron valores significativamente superiores de hipertensión matinal y comportamiento non-dipper, lo cual se asoció en forma independiente con hipertensión sostenida en el tercer trimestre del embarazo. Conclusiones: Las gestantes con HGB en la semana 20 de embarazo presentaron mayor hipertensión matinal y comportamiento non-dipper y evolucionaron con más frecuencia a hipertensión sostenida que el grupo control de normotensas.

Background: White coat syndrome (WCS) is common during pregnancy, although little is known about its clinical outcome during gestation. Morning hypertension and the non-dipper behavior, measured by ambulatory blood pressure monitoring (ABPM), are associated with greater risk of cardiovascular events. However, there are few studies during pregnancy. Objectives: The primary aim of the study was to evaluate morning hypertension and the non-dipper behavior in pregnant women with WCS versus a control normotensive group. A secondary objective was to evaluate whether WCS, morning hypertension and the non-dipper behavior in the second trimester of pregnancy were associated with greater hypertension in the third trimester. Methods: This prospective study included 95 primiparae in the 20th week of gestation, 50 with WCS and 45 as normotensive control group. Routine lab tests, office blood pressure and ABPM at inclusion and in the 32th week of gestation were recorded. Morning hypertension and the non-dipper behavior were evaluated by ABPM. Results: Age, and baseline blood glucose level and daytime and nighttime blood pressure by ABPM were similar in both groups. Conversely, patients presenting WCS had significantly higher values of morning hypertension and non-dipper behavior, which were independently associated with sustained hypertension in the third trimester of pregnancy. Conclusions: Pregnant women with WCS in the 20th week of gestation presented greater morning hypertension and non-dipper behavior and progressed more frequently to sustained hypertension than the control normotensive group.

Tratamiento antihipertensivo diurno y nocturno: efecto en la función endotelial de pacientes con patrón non-dipper / Day and night antihypertensive treatment: effect on endothelial function in patients with non-dipper pattern

Analizar el efecto del tratamiento antihipertensivo diurno y nocturno sobre la función endotelial en pacientes con patrón non-dipper identificados en la consulta de la Unidad Cardiometabólica del Departamento de Medicina Interna del Hospital Militar Dr. Carlos Arvelo durante el segundo cuatrimestre (Mayo – Agosto) del año 2012. Se realizó un estudio abierto, prospectivo, descriptivo y analítico durante un período de 8 semanas comparando la respuesta de la hiperemia reactiva y microalbuminuria con el horario de administración del tratamiento antihipertensivo, independientemente del tipo y número de drogas utilizadas. La muestra fue constituida por pacientes hipertensos con patrón non-dippersin otras comorbilidades que fueron diagnosticados en la Unidad Cardiometabólica del Hospital Militar Dr. Carlos Arvelo durante el segundo cuatrimestre del año 2012. La media de edades fue 57,84 ± 5,01DE para el grupo diurno y 55,07 ± 3,77DE para el grupo nocturno. Predominó el sexo femenino 69,23% y 92,3% respectivamente. Se observó mayor caída sistólica y mayor cambio de patrón non-dipper a dipper en el grupo con tratamiento nocturno que en aquel con tratamiento diurno (p=0,016 y p=0,011 respectivamente). No se observaron diferencias significativas con el resto de las variables. Se demostró una relación estadísticamente significativa entre la administración nocturna del tratamiento antihipertensivo y la caída nocturna de presión sistólica, condicionando el cambio del patrón non-dipper a dipper.

To analyze the effect of diurnal and nocturnal anti-hypertensive treatment on endothelial function in patients with a non-dipper pattern identified at the Cardio-metabolic Unit of the Internal Medicine Department, Military Hospital Dr. Carlos Arvelo, Caracas, Venezuela during the second quarter (May – August) of 2012. An open-label, prospective, descriptive and analytical study, was conducted over a period of 8 weeks comparing the reactive hyperemia and microalbuminuria to the schedule of administration of the anti-hypertensive treatment, regardless of the type and number of drugs used. The sample was composed of hypertensive patients with a non-dipper pattern without other comorbidities who consulted at the Cardiometabolic Unit of the Internal Medicine Department at the Military Hospital Dr. Carlos Arvelo during the second quarter of 2012. The average age was 57.84 ± 5.01SD for the day-time group and 55.07 ± 3.77SD for the nocturnal group. Females were predominant over males with 69.23% and 92.3% respectively. There was a greater systolic drop and a greater change from non-dipperto a dipper pattern in the group receiving nocturnal treatment than in the diurnal group (p=0.016 and p=0.011 respectively). No significant differences were observed in the rest of the variables. There was a statistically significant relationship between the nocturnal administration of anti-hypertensive treatment and the night systolic pressure drop, conditioning a change from non-dipper to a dipper pattern.

Relationship between homocysteine and non-dipper pattern in patients with type 2 diabetes mellitus / Relação entre a homocisteína e a condição não dipper em pacientes com diabetes melito tipo 2

OBJECTIVE: The rate of reduction of nocturnal blood pressure (NBP) is lesser than normal in patients with type 2 diabetes mellitus (type 2 DM). Hyperhomocysteinemia (HHC) disrupts vascular structure and function, no matter the underlying causes. The risk of development of vascular disease is greater in diabetic patients with hyperhomocysteinemia than in patients with normal homocystein levels. The aim of the study was to investigate whether there are differences of homocystein levels in dipper and non-dippers patients with type 2 DM. SUBJECTS AND METHODS: We compared 50 patien­ts (33 females, 17 males) with type 2 DM and 35 healthy individuals (18 females, 17 males ) in a control group. Ambulatory blood pressure monitoring (ABPM) was performed and homocysteine levels were measured in all patients. RESULTS: We found that the percentage of non-dipper pattern was 72% in patients with type 2 DM and 57% in control group. In diabetic and control individuals, homocystein levels were higher in non-dipper (respectively 13.4 ± 8.1 µmol/L and 11.8 ± 5 µmol/L) than in dipper subjects (respectively, 11.8 ± 5.8 µmol/L and 10.1 ± 4.2 µmol/L), but there was no significant difference between the two groups (respectively, p = 0.545, p = 0.294). CONCLUSION: In both groups, homocystein levels were higher in non-dipper than in dipper participants, but there was no significant difference between the groups. High homocystein levels and the non-dipper pattern increases cardiovascular risk. Therefore, the relationship between nocturnal blood pressure changes and homocystein levels should be investigated in a larger study.

OBJETIVO: A taxa de redução da pressão arterial noturna (PAN) é menor em pacientes com diabetes melito tipo 2 (DM tipo 2). A hiper-homocisteinemia (HHC) perturba a estrutura e a função vascular, independentemente das causas subjacentes. O risco de desenvolvimento de doenças vasculares é maior em pacientes diabéticos com hiper-homocisteinemia do que em pacientes com níveis normais de homocisteína. O objetivo deste estudo foi investigar se há diferenças entre os níveis de homocisteína em pacientes com DM2 em condição dipper ou não dipper. SUJEITOS E MÉTODOS: Comparamos 50 pacientes (33 mulheres, 17 homens) com DM tipo 2 e 35 indivíduos saudáveis (18 mulheres, 17 homens), usados como grupo controle. A monitorização ambulatorial da pressão arterial (MAPA) e os níveis de hemocisteína foram medidos em todos os pacientes. RESULTADOS: Observamos que a porcentagem de não dipper foi de 72% em pacientes com DM tipo 2 e 57% no grupo controle. Em indivíduos diabéticos e controle, os níveis de homocisteína foram mais altos em indivíduos não dipper (respectivamente 13,4 ± 8,1 µmol/L e 11,8 ± 5 µmol/L) do que em indivíduos dipper (respectivamente, 11,8 ± 5,8 µmol/L e 10,1 ± 4,2 µmol/L), mas não houve diferença significativa entre os dois grupos (respectivamente, p = 0,545, p = 0,294). CONCLUSÃO: Em ambos os grupos, os níveis de homocisteína foram mais altos nos indivíduos não dipper do que nos indivíduos dipper, mas não houve diferença significativa entre os grupos. Altos níveis de homocisteína e a condição não dipper aumentam o risco cardiovascular. Portanto, a relação entre as alterações da pressão arterial noturna e os níveis de homocisteína deve ser investigada em um estudo mais amplo.