Circadian Blood Pressure Regulation Research Articles

The association between blood pressure variability and renal damage in patients with primary aldosteronism.

This research examines the association between blood pressure variability (BPV) and renal damage in a cohort of 129 primary aldosteronism (PA) patients, employing ambulatory blood pressure monitoring (ABPM) for comparative analysis with individuals diagnosed with essential hypertension (EH). The study reveals that PA patients exhibited significantly elevated levels of cystatin C and urine microalbumin/creatinine ratio (UACR). Additionally, a higher prevalence of non-dipping blood pressure patterns in PA patients suggests an increased risk of circadian blood pressure regulation disturbances. Notably, while most BPV indices were comparable between the two groups, the standard deviation of 24-h weighted diastolic blood pressure was markedly lower in the PA cohort, distinguishing it as a unique variable. Through multiple linear regression analysis, the duration of hypertension, angiotensin II concentrations, and daytime systolic blood pressure standard deviation emerged as significant determinants of estimated glomerular filtration rate (eGFR) in PA patients. Furthermore, UACR was significantly influenced by variables including the 24-h weighted standard deviation (wSD) of systolic BP, glycosylated hemoglobin levels, nocturnal systolic BP peaks, aldosterone-renin ratio (ARR), and total cholesterol, with the most pronounced association observed with the 24-h wSD of systolic BP (β=0.383).The study also found significant correlations between the 24-h wSD of systolic BP, ARR, HbA1c, serum potassium levels, and 24-h urinary microalbumin, underscoring the critical role of the 24-h wSD of systolic BP (β=0.267). These findings underscore the imperative of an integrated management strategy for PA, addressing the intricate interconnections among metabolic abnormalities, blood pressure variability, and renal health outcomes.

Low pregnancy-specific beta-1-glycoprotein is associated with nondipper hypertension and increased risk of preeclampsia in pregnant women with newly diagnosed chronic hypertension

Chronic hypertension is one of the major risk factors for preeclampsia. Pregnancy-specific beta-1-glycoprotein (PSG-1) is a protein that plays a critical role in fetomaternal immune modulation and has been shown to be closely associated with pregnancy adverse events such as preeclampsia. It is also known that PSG-1 and its source placenta are associated with many molecular pathways associated with blood pressure regulation. In addition, the nondipping pattern (NDP) of chronic hypertension has been shown to be an independent risk factor for preeclampsia. Dipper individuals experience a notable nighttime drop in blood pressure, typically around 10% or more compared to daytime levels, while nondipper individuals show a smaller nighttime blood pressure decrease, indicating potential circadian blood pressure regulation disruption. In this context, we aimed to reveal the relationship between PSG-1, NDP and preeclampsia in this study. A total of 304 pregnant women who were newly diagnosed in the first trimester and started on antihypertensive medication were included in this study. All subjects performed 24-h ambulatory blood pressure monitoring twice throughout pregnancy, the first in the 1. trimester to confirm the diagnosis of hypertension and the second between 20+0 and 21+1 gestational weeks to determine the dipper–nondipper status of hypertension. Subjects were grouped as dipper and nondipper according to blood pressure, and groups were compared in terms of PSG-1 levels. In this study, low PSG-1 levels and NDP were independently associated with preeclampsia. Findings from this study suggest that PSG-1 may play an important role in the causal relationship between NDP and preeclampsia.

"Arterial stiffness is not associated with changes in the circadian pattern of blood pressure in patients with type 1 diabetes mellitus and cardiovascular autonomic dysfunction".

Cardiovascular autonomic neuropathy (CAN) associates an abnormal circadian pattern in blood pressure (BP) regulation that might be aggravated by the coexistence of arterial stiffness. We aimed to evaluate the effect of arterial stiffness in the circadian rhythm of BP in patients with type 1 diabetes and CAN. Cross-sectional study including 56 consecutive patients with type 1 diabetes and CAN, with (n = 28) or without (n = 24) arterial stiffness as defined by an ankle-brachial index above 1.2. CAN was diagnosed by BP and heart rate responses to active standing and cardiovascular autonomic reflex tests. Absence of nocturnal decrease in BP-"non-dipping" pattern- was defined by a daytime to nighttime decrease in mean BP smaller than 10%. The study's subjects mean age was 40 ± 11 years-old, their mean duration of diabetes was 22 ± 10 years, and their mean A1c was 7.9 ± 1.5%. A "non-dipping" pattern was observed in 28 patients (54%) regardless of the presence or absence of arterial stiffness. Age, waist circumference, body mass index, and A1c, were introduced as independent variables into a multiple regression analysis. The stepwise model (R2: 0.113, p = 0.016) retained only A1c levels (β: ‒ 0.333, 95% confidence interval [CI]: -3.10 to -0.33) as significant predictor of the percentage of nighttime decrease in mean BP. A non-dipping pattern in BP is very common in patients with type 1 diabetes presenting with subclinical CAN and is associated with a poorer metabolic control. On the contrary, coexistence of arterial stiffness is not associated with abnormalities in circadian BP regulation.

Circadian rhythm of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy

ObjectiveTo determine whether patients with drug-resistant mesial temporal lobe epilepsy present with an alteration in the autonomic circadian regulation of blood pressure. MethodsA prospective case‒control study was designed, with a case group comprising patients with drug-resistant mesial temporal lobe epilepsy and a control group comprising healthy volunteers. Twenty-four-hour outpatient blood pressure monitoring was performed to assess the existence of a normal (dipping) or altered (non-dipping) circadian pattern. In addition, analytical and ultrasound parameters (carotid intima-media thickness) of vascular risk and sleep quality were evaluated. ResultsTwenty-four subjects were recruited in each study group, amongst whom no demographic differences or history of vascular risk were observed. A higher percentage of participants with a non-dipping pattern was observed in the group of patients with epilepsy (62.5% vs. 12.5, p = 0.001). In the case group, significant differences were also observed in carotid intima-media thickness, with a greater probability of presenting with pathological values (p = 0.022). ConclusionThe results suggest a disorder of the central autonomic control of blood pressure in patients with drug-resistant mesial temporal lobe epilepsy, with a greater probability of developing an alteration of the circadian rhythm of blood pressure. This dysfunction may be a factor involved in the increased cardiovascular risk in this population.

Abnormal circadian blood pressure regulation and cognitive impairment in α-synucleinopathies.

Circadian blood pressure (BP) rhythm is important for the maintenance of healthy daily life, and its disruption is associated with poor outcomes. Cardiovascular autonomic failure is often observed in older populations but has a greater impact on neurodegenerative disorders such as α-synucleinopathies. These BP abnormalities include orthostatic hypotension (OH), supine hypertension (SH), and a loss of nocturnal BP fall. OH not only causes falls or syncope but is also related to cognitive impairment in α-synucleinopathies. For example, OH doubles or triples the risk for the development of cognitive impairment in Parkinson's disease (PD). The diffuse central and peripheral neuropathology of α-synuclein may contribute to both OH and cognitive impairment. Moreover, repeated cerebral hypoperfusion in OH is thought to be related to cerebrovascular and neuronal damage, which may cause cognitive impairment. SH, which often coexists with OH, is also associated with cognitive impairment through cerebrovascular damage, such as white matter lesions and cerebral microbleeds. The reverse-dipping (riser) pattern on ambulatory BP monitoring is commonly observed in PD (∼56%), regardless of disease duration and severity. It is also related to cognitive impairment and more pronounced when coexisting with OH. These abnormal circadian BP profiles may be synergistically associated with cognitive impairment and poor outcomes in α-synucleinopathies. Although evidence for aggressive control of BP dysregulation improving cognitive impairment and outcomes is limited, regular BP monitoring appears to be important for total management of α-synucleinopathies.

0214 Effects of Simulated Night-Shiftwork Induced Circadian Misalignment on the Human Plasma Metabolome

Abstract Introduction Circadian misalignment occurs when behaviors such as food intake and sleep happen at inappropriate endogenous circadian times, is common among shift-workers, and is a risk factor for cardiometabolic disease. Identifying mechanisms underlying adverse cardiometabolic risk linked to circadian misalignment could help develop new countermeasure strategies to mitigate health consequences of shiftwork. Thus, we analyzed 24-hour profiles of plasma metabolites during circadian alignment and misalignment in a night-shiftwork protocol. Methods 14 healthy adults (6M/8F), aged 26.4±1.2y (mean±SD), completed a 6 day in-laboratory simulated night-shiftwork study. The protocol comprised 2 baseline days (circadian alignment) followed by a transition day to shiftwork, and then 2 simulated night-shiftwork days (circadian misalignment). Participants consumed energy-balanced diets throughout the protocol, starting 3 days prior to laboratory admission. Plasma was collected every 4h during circadian alignment and misalignment conditions and was analyzed via untargeted metabolomics (liquid chromatography/mass-spectrometry). A model selection approach (best fit) with circadian and behavioral cosine models identified metabolites influenced by circadian (central circadian clock measured via dim-light melatonin onset) versus behavioral cycles (food intake/sleep). Results 5,171 metabolites were detected with average abundance of 424 (~8%) changing between conditions (false discovery rate (FDR)<0.05). 380 metabolites had significant (FDR<0.05) 24-h time-of-day patterns. Of these 380 metabolites, 248 had 24-h time-of-day patterns during circadian alignment, 283 had 24-h time-of-day patterns during misalignment, and 141 had 24-h time-of-day patterns during both conditions. Of the metabolites with 24-h time-of-day patterns in both conditions, 50 were circadian-influenced (e.g., arachidinoyl-serine) and 91 were behaviorally-influenced (e.g., propionylcarnitine). Conclusion Almost twice as many metabolites were influenced by the behavioral versus circadian cycle suggesting altered timing of behaviors like food intake and sleep have a significant impact on 24-h time-of-patterns in the human plasma metabolome. For example, propionylcarnitine is involved in energy metabolism and likely reflects 24h time-of-day patterns altered by food intake. Alternatively, arachidinoyl-serine was circadian influenced, is involved in vasodilation, and thus may contribute to circadian regulation of blood pressure. Further understanding circadian and behavioral regulation of the metabolome could have application in identifying mechanisms of physiological dysregulation and targets for intervention to mitigate health consequences of circadian misalignment. Support (If Any) NIH-DK092624, NIH-TR001082, NIH-DK048520, NIH-HL132150, NIH-HL145099, NIH-DK111161

Glutamatergic Activity in the Nucleus of the Solitary Tract contributes to the Circadian Regulation of Blood Pressure

Cardiorespiratory parameters including blood pressure are governed by a 24‐hour circadian rhythm. Blood pressure follows a circadian cycle and dips during the resting/sleeping period while peaking during the active/awake period. During sleep blood pressure is 10%‐20% lower than average daytime blood pressure, a phenomenon described as “dipping”. The brain regions and mechanisms by which the circadian rhythm of blood pressure is controlled are not fully understood. To address this knowledge gap, we examined the nucleus of the solitary tract (nTS). The nTS is the first central site for integration and modulation of reflexes including the baroreflex. The nTS receives sensory information through glutamate release from baroreceptors that sense changes in blood pressure, eliciting reflex responses in the nTS to maintain BP homeostasis. Previous studies have shown that injections of glutamate or increases of extracellular glutamate decrease blood pressure. Due to its integral role in the autonomic system, we hypothesized that the nTS is involved in circadian blood pressure regulation through alterations in glutamate. Specifically, the present study sought to identify if decreased glutamate raised blood pressure during the active period and if increased glutamate reduced blood pressure in the inactive period. To address this, we used 7‐week‐old male Sprague Dawley rats and a combination of electrophysiology, molecular methods, immunohistochemistry, and 24/7 telemetry. Rats acclimated for 2 weeks prior to telemetry recordings. Measurements were compared at four different time points in one day (6 hours apart) except for electrophysiological recordings which were taken 12 hours apart. During the active period, blood pressure significantly increased in comparison to the inactive period. We next examined the relationship between changes in blood pressure and changes in glutamatergic activity. We first determined if activation of glutamatergic neurons differed across the 4 time periods. We took 30 µm of coronal slices containing the nTS (at the level of area postrema) from perfused animals. Active glutamatergic neurons (denoted by cFos expression) significantly decreased during the active period in comparison to the inactive period. To examine if this increase in glutamatergic neuronal cFos expression correlated with channel expression, we used western blot and found that the expression of AMPA receptors (GluA1 subunit) also decreased during the active period. During the active period, the resting membrane potential of nTS neurons were hyperpolarized in comparison to the inactive period. This lead to a significant decrease in spontaneous excitatory post‐synaptic currents in nTS neurons during the active period. The data indicate that glutamatergic activity decreased during the active period when blood pressure was higher in comparison to the inactive period. Taken together, these results suggest that nTS glutamatergic activity may have a circadian pattern and may contribute to the circadian blood pressure rhythm.

Importance of the renal ion channel TRPM6 in the circadian secretion of renin to raise blood pressure

Blood pressure has a daily pattern, with higher values in the active period. Its elevation at the onset of the active period substantially increases the risk of fatal cardiovascular events. Renin secretion stimulated by renal sympathetic neurons is considered essential to this process; however, its regulatory mechanism remains largely unknown. Here, we show the importance of transient receptor potential melastatin-related 6 (TRPM6), a Mg2+-permeable cation channel, in augmenting renin secretion in the active period. TRPM6 expression is significantly reduced in the distal convoluted tubule of hypotensive Cnnm2-deficient mice. We generate kidney-specific Trpm6-deficient mice and observe a decrease in blood pressure and a disappearance of its circadian variation. Consistently, renin secretion is not augmented in the active period. Furthermore, renin secretion after pharmacological activation of β-adrenoreceptor, the target of neuronal stimulation, is abrogated, and the receptor expression is decreased in renin-secreting cells. These results indicate crucial roles of TRPM6 in the circadian regulation of blood pressure.

Human Stool Metabolome Differs upon 24 h Blood Pressure Levels and Blood Pressure Dipping Status: A Prospective Longitudinal Study.

Dysbiosis of gut microbiota (GM) has been involved in the pathophysiology of arterial hypertension (HT), via a putative role of short chain fatty acids (SCFAs). Its role in the circadian regulation of blood pressure (BP), also called “the dipping profile”, has been poorly investigated. Sixteen male volunteers and 10 female partners were subjected to 24 h ambulatory BP monitoring and were categorized in normotensive (NT) versus HT, as well as in dippers versus non-dippers. Nuclear magnetic resonance (NMR)-based metabolomics was performed on stool samples. A 5-year comparative follow-up of BP profiles and stool metabolomes was done in men. Significant correlations between stool metabolome and 24 h mean BP levels were found in both male and female cohorts and in the entire cohort (R2 = 0.72, R2 = 0.79, and R2 = 0.45, respectively). Multivariate analysis discriminated dippers versus non-dippers in both male and female cohorts and in the entire cohort (Q2 = 0.87, Q2 = 0.98, and Q2 = 0.68, respectively). Fecal amounts of acetate, propionate, and butyrate were higher in HT versus NT patients (p = 0.027; p = 0.015 and p = 0.015, respectively), as well as in non-dippers versus dippers (p = 0.027, p = 0.038, and p = 0.036, respectively) in the entire cohort. SCFA levels were significantly different in patients changing of dipping status over the 5-year follow-up. In conclusion, stool metabolome changes upon global and circadian BP profiles in both genders.

Circadian Regulation of Blood Pressure: of Mice and Men.

Blood pressure (BP) exhibits strong diurnal variations that have been shown to be important for normal physiology and health. In this review, we highlight recent advances in both basic and clinic research on how the circadian clock affects these BP rhythms. Tissue-specific and inducible knockout rodent models have provided novel ways to dissect how circadian clocks regulate BP rhythms and demonstrated that loss of these rhythms is associated with the development of disease. The use of circadian-specific research protocols has translated findings from rodent models to humans, providing insight into circadian control of BP, as well as how sleep, activity, and other factors influence diurnal BP rhythms. Circadian mechanisms play an important role in the regulation of diurnal BP rhythms. Future research needs to extend these findings to clinical populations and determine the extent to which circadian factors may play a role in the development of novel treatment approaches to the management of hypertension.

Circulating plasma exosomes in obstructive sleep apnoea and reverse dipping blood pressure.

Obstructive sleep apnoea (OSA) increases the risk of an abnormal nondipping 24 h blood pressure profile, an independent risk factor for cardiovascular disease (CVD). We examined differential exosomal microRNA (miRNA) expression in untreated OSA patients with normal dipping blood pressure (NDBP) and reverse dipping blood pressure (RDBP), an extreme form of nondipping, to understand the mechanisms underlying nondipping blood pressure in OSA. 46 patients (15 RDBP versus 31 NDBP) matched for OSA severity (respiratory event index 32.6±22.5 versus 32.2±18.1 events·h-1; p=0.9), age (54.8±12.9 versus 49±9.9 years; p=0.09) and body mass index (36.2±6.6 versus 34.4±6.8 kg·m-2; p=0.4) were included. Plasma exosomes were characterised by flow cytometry and functional in vitro reporter assays were conducted on cultured endothelial cells. Exosome miRNA cargo was profiled with microarrays followed by bioinformatics analyses. Exosomes from RDBP patients increased the permeability of endothelial cell tight junctions and adhesion molecule expression. Principal component analyses of miRNA array data showed strict separation and identification of the two groups. A restricted and validated signature of exosomal miRNAs was identified in the RDBP versus NDBP group. Their predicted target genes involved phosphatidylinositol 3-kinase-Akt (p=0.004), Ras (p=3.42E-05), Wnt (p=0.003) and hypoxia inducible factor-1 signalling (p=0.04), inflammatory mediator regulation of transient receptor potential channels (p=0.01), and several cancer-related pathways. Patients with RDBP have altered miRNA cargoes in circulating exosomes that invoke in vitro endothelial dysfunction. A selected number of circulating exosomal miRNAs play an important role in abnormal circadian regulation of blood pressure and may provide prognostic biomarkers of CVD risk in OSA.

Kidney volume, kidney function, and ambulatory blood pressure in children born extremely preterm with and without nephrocalcinosis

BackgroundReduced kidney volume (KV) following prematurity is a proxy for reduced nephron number and is associated with the development of hypertension and end-stage renal disease in adults. We investigated whether extreme prematurity affects KV, function, and blood pressure in school-aged children and if nephrocalcinosis (NC) developed during the neonatal period had additional effects.MethodsWe investigated 60 children at a mean age of 7.7 years: 20 born extremely preterm (EPT < 28 weeks gestational age with NC (NC+)), 20 born EPT without NC (NC−), and 19 born as full-term infants (control). We measured KV by ultrasound, collected blood and urine samples to evaluate renal function, and measured office and 24-h ambulatory blood pressure (ABPM).ResultsChildren born EPT had significantly smaller kidneys (EPT (NC+ NC−) vs control (estimated difference, 11.8 (CI − 21.51 to − 2.09 ml), p = 0.018) and lower but normal cystatin C–based glomerular filtration rate compared with control (estimated difference, − 10.11 (CI − 0.69 to − 19.5), p = 0.035). KV and function were not different between NC+ and NC− groups. Change in KV in relation to BSA (KV/BSA) from the neonatal period to school age showed significantly more EPT children with neonatal NC having a negative evolution of KV (p = 0.01). Blood pressure was normal and not different between the 3 groups. Fifty percent of EPT had a less than 10% day-to-night decline in ABPM.ConclusionsKidney growth and volume is affected by EPT birth with NC being a potential aggravating factor. Circadian blood pressure regulation seems abnormal in EPT-born children.

Abnormal circadian blood pressure regulation in children with nocturnal enuresis

Introduction: To investigate autonomic nervous system function in enuretic children by performing ambulatory blood pressure monitor (ABPM) for 24 h. Methods: Twenty-eight children ranging in age from 6 to 15 years with primary nocturnal enuresis and 27 age-matched healthy controls were enrolled and they get 24 h ABPM. Hypertension was defined as standard deviation score (SDS) > 1.64 (i.e., >95th percentile) adjusted for gender and height. Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were carried out in all children. They have also requested to have a diary about daily fluid intake and urine volume. Results: Although the mean 24-h and daytime diastolic blood pressure (BP) did not differ between the groups, systolic BP (SBP) was significantly higher in enuretic children (p < 0.05). The mean night-time SBP, DBP values, SDS and BP loads were found to be significantly higher than those in the controls (p < 0.01). A lack of nocturnal decrease was more prevalent in the enuretic children compared with the control subjects, the difference was statistically significant for DBP but not for SBP. Patients with elevated night-time BP load was found to have higher frequency of urinary incontinence per week as well as per night when compared with enuretic children with normal night-time BP load (r = 0.72, r = 0.69, p < 0.01, respectively). Conclusion: Subtle abnormalities of circadian BP regulation in enuretic children indicated by a selective elevation of nocturnal SBP, DBP, and MAP, and attenuated nocturnal dipping may reflect sympathetic hyper activation and its possible role in pathogenesis of enuresis.

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children. Materials and Methods : In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine. Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value>0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value 0.05). Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE. Keywords : Child; Enuresis; Blood pressure; Autonomic dysfunction

Assessment of Blood Pressure in Primary Monosymptomatic Nocturnal Enuresis

Introduction: Enuresis is defined as the repeated voiding of urine into bed at least twice a week for at least 3 consecutive months in a child who is at least 5 years of age. Primary enuresis occurs in children who have never been consistently dry through the night. Monosymptomatic enuresis has no associated daytime symptoms. Increased nocturnal urine production in primary nocturnal enuretic patients could possibly be associated with autonomic nervous system dysfunction. The aim of this study was to investigate autonomic nervous system function in enuretic children.Materials and Methods: In this study, children with monosymptomatic primary nocturnal enuresis (MPNE) and healthy children without MPNE were enrolled and their blood pressure was measured twice a day (in the morning and afternoon). Urinalysis, urine electrolyte levels, urinary culture, and urinary system ultrasound were performed in all the children. They were also requested to have a diary about daily fluid intake and the volume of daily urine.Results: The MPNE group comprised 100 children (M/F: 58/42) and the control group included 100 healthy children (M/F: 51/49). The mean age of the children was 8.1±2.3 and (8.9±2.53 years in MPNE and control groups, respectively. The mean diastolic blood pressure (DBP) during the nighttime and daytime did not differ between the groups (p-value&gt;0.05); however, the mean systolic blood pressure (SBP) was significantly higher in the nighttime in the MPNE group (p-value&lt;0.05) but did not differ between the groups during the daytime (p-value&gt;0.05).Conclusions: Nighttime SBP was significantly higher in children with MPNE. These subtle abnormalities of the circadian blood pressure regulation may reflect autonomic nervous system dysfunction and contribute to the pathogenesis of MPNE.Keywords: Child; Enuresis; Blood pressure; Autonomic dysfunction

Autonomic dysfunction and circadian blood pressure variations in people with impaired glucose tolerance

To assess circadian blood pressure variability in people with impaired glucose tolerance and a healthy control population. Seventy-five people with impaired glucose tolerance and 40 healthy volunteers (frequency matched on 10-year age bands and sex) underwent a detailed neurological assessment. Autonomic neuropathy was detected by the five standard cardiovascular autonomic tests and heart rate variability was characterized by the triangle index. Diurnal indices were assessed by 24-h ambulatory blood pressure monitoring. Systolic and diastolic diurnal indices were defined as: (mean daytime blood pressure - mean night-time blood pressure) × 100/mean daytime blood pressure. Mean 24-h systolic and diastolic blood pressure was significantly higher in the group with impaired glucose tolerance compared with the control group [126 ± 12 (mean ± SD) vs. 117 ± 10, 75 ± 7 vs. 71 ± 6 mmHg, both P < 0.05). Systolic and diastolic diurnal indices and heart rate variability triangular index were significantly lower in people with impaired glucose tolerance compared with control subjects (9.1 ± 7.8 vs. 13.2 ± 5.4, 14.5 ± 9.7 vs. 18.4 ± 7.1 mmHg, 28.0 ± 8.4 vs. 39.5 ± 9.3, all P < 0.05). Differences in mean diastolic blood pressure, heart rate variability triangular index and the frequency of non-dippers between those with impaired glucose tolerance and control subjects seemed to be independent of BMI and the presence of cardiovascular autonomic neuropathy, as simultaneous adjustment for BMI and cardiovascular autonomic neuropathy had no major effect on the results. Our data suggest that people with impaired glucose tolerance have increased diastolic blood pressure and abnormal circadian blood pressure regulation, independent of obesity and the presence of cardiovascular autonomic neuropathy.

Abnormal circadian blood pressure regulation in liver transplanted children

HT is a frequent cardiovascular risk factor in liver transplant recipients. However, there are only few studies in the literature regarding the risk of HT in liver transplanted children. The aim of this study was to assess the 24 h BP profiles of liver transplanted patients and to compare the results with healthy children. ABPM was performed on 20 liver transplanted patients and 27 healthy children aged 7.1 ± 4.8 and 8.5 ± 2.9 yr, respectively. HT was defined as SDS > 1.64 (i.e., >95th percentile) adjusted for gender and height. The mean duration of post-transplant follow-up was 32 ± 19 months. Six (30%) patients were found to be hypertensive. The physiological nocturnal BP fall was attenuated significantly in the study group for diastolic BP (11.5 ± 6.1 mmHg vs. 17.7 ± 7.1 mmHg, p = 0.006). Specifically, the number of patients with high nighttime systolic and diastolic BP SDS (p = 0.02 and p = 0.004, respectively) as well as elevated nighttime systolic (p = 0.03) and diastolic (p = 0.003) BPLs was found to be significantly higher than those in the controls. Alteration of the "normal" circadian rhythm is very frequent in liver transplant recipients. Thus, it is recommended to perform ABPM on all liver transplanted children not to underdiagnose HT.

Abnormal Circadian Blood Pressure Regulation in Children Born Preterm

To assess a possible relationship between prematurity and casual blood pressure (BP) by means of 24-hour ambulatory BP monitoring (ABPM). ABPM was performed in 41 children aged 5 to 17 years who were born prematurely with (n = 11) or without intrauterine growth restriction, and in 27 matched children who were born at term with a birth weight appropriate for gestational age. Although BP did not differ between the preterm group and control subjects during the daytime, nocturnal standardized systolic BP was elevated (P < .05) and a lack of nocturnal decrease was more prevalent in the preterm children compared with the control subjects (73% versus 41%, P = .01). The difference was caused by a marked increase of nighttime systolic BP in the light-for-date children (1.17 +/- 0.61 standard deviation scores; P < .01), although preterm children with appropriate weight (0.33 +/- 1.00) were not different from control subjects (0.09 +/- 0.73). Nighttime BP standard deviation scores were closely correlated with standardized heart rate, compatible with a role of sympathetic hyperactivation. Subtle abnormalities of BP regulation, indicated by a selective increase of nocturnal systolic BP, are present during childhood in subjects born prematurely, and are prominent in those with intrauterine growth restriction.

High Prevalence of Abnormal Circadian Blood Pressure Regulation and Impaired Glucose Tolerance in Adults with Hypopituitarism

Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.

Circadian blood pressure regulation in hospitalized depressed patients and non-depressed comparison subjects

Circadian blood pressure regulation in hospitalized depressed patients and non-depressed comparison subjects