Circadian Rhythm Of Blood Pressure Research Articles

Circadian blood pressure dysregulation in children with obstructive sleep apnea.

Obstructive sleep apnea (OSA) adversely affects normal blood pressure (BP) and may disrupt circadian BP patterns. We sought to examine 24-hour circadian BP rhythms in children with OSA and healthy controls. Children 5-14 years with OSA and healthy controls underwent 24-hour BP monitoring and actigraphy to quantify sleep. Shape invariant statistical models compared circadian BP patterns (e.g. times of BP peaks, time arrived at peak BP velocity [TAPV]) in the OSA and control groups. The analytic sample included 219 children (mild OSA: n = 52; moderate-to-severe OSA (MS-OSA): n = 50; controls: n = 117). In the morning, the MS-OSA group had earlier TAPV for DBP than controls (51 minutes, p < 0.001). TAPV in the evening was earlier for the MS-OSA group than controls (SBP: 95 minutes, p < 0.001; DBP: 28 minutes, p = 0.028). At mid-day, SBP and DBP velocity nadirs were earlier for the MS-OSA group than controls (SBP: 57 minutes, p < 0.001; DBP: 38 minutes, p < 0.01). The MS-OSA group reached most BP values significantly earlier than controls; the largest differences were 118 minutes (SBP) and 43 minutes (DBP) (p < 0.001). SBP and DBP were elevated in the MS-OSA group (hours 18-21 and 7--12, respectively, p < 0.01) compared to controls. The MS-OSA group was prone to "non-dipping" compared to controls (SBP: odds ratio [OR] = 2.16, 95% CI: 1.09, 4.29; DBP: OR = 3.45, 95% CI: 1.21, 10.23). Children with MS-OSA had changes in circadian BP patterns, namely earlier TAPV and BP peaks and nadirs than controls. Circadian disturbances in BP rhythms may be key to mapping the natural history of BP dysregulation in children with OSA.

Cardiovascular rhythmicity in overweight and obese children.

Obesity is thought to play a role in the disruption of cardiac rhythmicity in obese children, but this is mostly an unexplored field of investigation. We aimed to evaluate the impact of overweight and obesity on circadian and ultradian cardiovascular rhythmicity of prepubertal children, in comparison with normal weight counterparts. We performed a cross sectional study of 316 children, followed in the birth cohort Generation XXI (Portugal). Anthropometrics and 24-hour ambulatory blood pressure were measured and profiles were examined with Fourier analysis for circadian and ultradian blood pressure (BP) and heart rate (HR) rhythms. Overweight/obese children presented more frequently a non-dipping BP pattern than normal weight counterparts (31.5% vs. 21.6%, p = 0.047). The prevalence of 24-hour mean arterial pressure (MAP) and 8-hour HR rhythmicity was significantly lower in obese children (79.3% vs. 88.0%, p = 0.038 and 33.3% vs. 45.2%, p = 0.031, respectively). The prevalence of the remaining MAP and HR rhythmicity was similar in both groups. No differences were found in the median values of amplitudes and acrophases of MAP and HR rhythms. The alterations found in rhythmicity suggest that circadian and ultradian rhythmicity analysis might be sensitive in detecting early cardiovascular dysregulations, but future studies are needed to reinforce our findings and to better understand their long-term implications.

The effects of Olmesartan/amlodipine administered in the Morning or At Night on nocturnal blood pressure reduction in Chinese patients with mild-moderate essential hypertension (OMAN Trial): study protocol for a prospective, multicenter, randomized, open-label clinical trial {1}

IntroductionHypertension increases the risk of cardiovascular disease. Uncontrolled nocturnal blood pressure is prevalent in patients taking antihypertensive medication, with an incidence rate of 30–60%. Although chronotherapy with antihypertensive agents may provide a new direction for effective control of nocturnal blood pressure, the clinical evidence base remains controversial. This research is presently underway to compare the effects of morning and bedtime administration of antihypertensive medication on nocturnal reduction and circadian rhythm of blood pressure in patients with hypertension.Methods and analysisThis study is being performed as a randomized, multicenter, open-label, parallel-group, clinical trial in which 720 participants are to undergo 24-h ambulatory blood pressure measurement (ABPM) and office blood pressure measurement (OBPM) at baseline before being randomly assigned to a morning (6–10 am) or a bedtime (6–10 pm) administration group. Each participant receives one 20/5-mg tablet of olmesartan/amlodipine (OA) daily for 4 weeks and is then followed up at 4-week intervals for a total of 12 weeks. During follow-up, the OA dosage is adjusted according to the ABPM and OBPM results. Patients with uncontrolled hypertension at the first follow-up visit will receive an increase in OA dosage to 1.5 tablets/day. For patients with blood pressure that is still uncontrolled after a further 4 weeks, the dosage of OA can be increased to 2 tablets/day. The primary objective is the reduction in mean nocturnal systolic blood pressure between baseline and week 12. The secondary objectives are the reduction in ambulatory blood pressure at weeks 4 and 12 and the blood pressure control rate at weeks 4, 8, and 12.DiscussionAntihypertensive chronotherapy remains controversial. A superiority test hypothesis design has been adopted for this trial, in which all participants will be taking the same antihypertensive medication. We anticipate that our findings will determine if nocturnal blood pressure control in Chinese patients with essential hypertension varies according to whether antihypertensive medication is taken in the morning or at bedtime. This study may provide scientific evidence for the application of chronotherapy in clinical practice.Trial registrationChiCTR2200059719. Registered on 10 May 2022(http://www.chictr.org.cn/edit.aspx?pid=169782&htm=4) {2a,2b}

Clinical Significance of Nocturnal Hypertension and Nighttime Blood Pressure Dipping in Hypertension.

This narrative review article aims to discuss more recent evidence, current challenges, and future perspectives regarding the clinical importance of nocturnal hypertension and nighttime blood pressure dipping, with particular reference to diagnosis, prognostic value, and therapeutic approach. The importance of nighttime blood pressure and nighttime blood pressure dipping has been demonstrated in decades. Increased nighttime blood pressure has been acknowledged as an unfavorable clinical trait. However, more recent evidence suggests that the abolishment of normal circadian blood pressure rhythm is not always a solid predictor of adverse cardiovascular events and needs to be interpreted in the light of each patients' individual characteristics. Physicians treating hypertensive patients with adverse nighttime blood pressure profiles often face the dilemma of chronotherapy. This has been a blurred field for years, yet very recent evidence from appropriately designed studies attempts to shed light on this puzzling question. As 24-h ambulatory blood pressure monitoring is being increasingly recommended and applied in real-world practice for the diagnosis and monitoring of hypertension, information on nighttime blood pressure and nocturnal dipping profile is collected but is not always easy to interpret.

Effect of renal denervation on diastolic function in patients with resistant hypertension and type 2 diabetes mellitus

Aim: To assess the change in the left ventricular (LV) diastolic function (DF) in patients with resistant hypertension (RHTN) and type 2 diabetes mellitus (T2DM) during 6-month follow-up after renal denervation (RDN) according to echocardiography in conjunction with changes in hemodynamic parameters.Material and Methods. A single center prospective interventional study with renal denervation included 30 patients with RHTN and T2DM. All patients underwent measurement of office and 24-hour blood pressure (BP), echocardiography according to the standard method with an assessment of LV DF.Results. At 6 months after RDN, a significant antihypertensive effect was noted (p &lt; 0.05), as well as an improvement in LV DF in the form of a decrease in E/e` by 1 c.u. was observed in 50% (15) patients. A significant decrease in the average E/e` was documented (–1.3 [95% CI –2.55; –0.08], р = 0.038). There were no changes in the indexed volumes of the left atrium (р = 0.940). The baseline values of E/e` had correlation with the level of mean pulse BP 24h (r = 0.51, р = 0.001) in the absence of significant relationships with other ABPM parameters. A decrease in systolic BP 24h by 3 mm Hg and an increase in nocturnal systolic BP fall by 1.6% were accompanied by a decrease in the average E/e` by 1 unit. According to the ROC-analysis, baseline level of nocturnal systolic BP fall 5.5% or less associated with a decrease in the E/e` ratio by more than 1 unit.Conclusion. Renal denervation in patients with RHTN and T2DM is accompanied by a favorable effect on LV diastolic function during 6-month follow-up, closely related to the hemodynamic effects of the procedure such as a decrease in systolic and pulse BP 24h, as well as improvement in the circadian rhythm of BP.

Cognitive impairment in heart failure patients: association with abnormal circadian blood pressure rhythm: a review from the HOPE Asia Network.

Cognitive impairment (CI) is frequently a comorbid condition in heart failure (HF) patients, and is associated with increased cardiovascular events and death. Numerous factors contribute to CI in HF patients. Decreased cerebral blood flow, inflammation, and activation of neurohumoral factors are all thought to be factors that exacerbate CI. Hypoperfusion of the brain due to decreased systemic blood flow, cerebral venous congestion, and atherosclerosis are the main mechanism of CI in HF patients. Abnormal circadian BP rhythm is one of the other conditions associated with CI. The conditions in which BP does not decrease sufficiently or increases during the night are called non-dipper or riser BP patterns. Abnormal circadian BP rhythm worsens CI in HF patients through cerebral congestion during sleep and atherosclerosis due to pressure overload. Interventions for CI in HF patients include treatment for HF itself using cardiovascular drugs, and treatment for fluid retention, one of the causes of abnormal circadian rhythms. Proposed pathways of cognitive impairment in heart failure through abnormal circadian blood pressure rhythm.

Renal tubular SGK1 is required to achieve blood pressure surge and circadian rhythm.

Blood pressure (BP) follows a circadian pattern that rises during the active phase of the day (morning surge) and decreases during the inactive (night dipping) phase of the day. The morning surge coincides with increased circulating glucocorticoids and aldosterone, ligands for glucocorticoid receptors and mineralocorticoid receptors, respectively. Serum- and glucocorticoid-induced kinase 1 (SGK1), a clock-controlled and glucocorticoid receptor- and mineralocorticoid receptor-induced gene, plays a role in BP regulation in human and animal models. However, the role of SGK1 in BP circadian regulation has not yet been demonstrated. Using telemetry, we analyzed BP in the inducible renal tubule-specific Sgk1Pax8/LC1 model under basal K+ diet (1% K+) and high-K+ diet (HKD; 5% K+). Our data revealed that, under basal conditions, renal SGK1 plays a minor role in BP regulation; however, after 1 wk of HKD, Sgk1Pax8/LC1 mice exhibited significant defects in diastolic BP (DBP), including a blunted surge, a decreased amplitude, and reduced day/night differences. After prolonged HKD (7 wk), Sgk1Pax8/LC1 mice had lower BP than control mice and exhibited reduced DBP amplitude, together with decreased DBP day/night differences and midline estimating statistic of rhythm (MESOR). Interestingly, renal SGK1 deletion increased pulse pressure, likely secondary to an increase in circulating aldosterone. Taken together, our data suggest that 1) the kidney plays a significant role in setting the BP circadian rhythm; 2) renal tubule SGK1 mediates the BP surge and, thus, the day/night BP difference; 3) long-term renal SGK1 deletion results in lower BP in mutant compared with control mice; and 4) renal SGK1 indirectly regulates pulse pressure due to compensatory alterations in aldosterone levels.NEW & NOTEWORTHY Dysregulation of blood pressure (BP) circadian rhythm is associated with metabolic, cardiovascular, and kidney diseases. Our study provides experimental evidence demonstrating, for the first time, that renal tubule serum- and glucocorticoid-induced kinase 1 (SGK1) plays an essential role in inducing the BP surge. Inhibitors and activators of SGK1 signaling are parts of several therapeutic strategies. Our findings highlight the importance of the drug intake timing to be in phase with SGK1 function to avoid dysregulation of BP circadian rhythm.

Possibilities and Prospects of Hypoxytherapy Application in Cardiology

Despite the achievements of modern cardiology, the cardiovascular morbidity and mortality in most countries of the world remains high, which motivates the wider use of additional (alternative) preventive and therapeutic approaches, one of which is hypoxytherapy. Over several decades of using this method, a large amount of data has been accumulated that allows us to state the beneficial effect of various hypoxytherapy regimens on the clinical course of cardiovascular diseases and can potentially improve prognosis of them. The use of hypoxytherapy is associated with an improvement in blood pressure circadian rhythm, flow-dependent vasodilation, an insulin resistance decrease, a vascular wall stiffness redaction, an improvement in blood rheology, endothelial function and nitric oxide system, a decrease of proinflammatory and prothrombotic cytokines levels. A number of modern experts consider hypoxytherapy as an affordable and perspective method of prevention and treatment of cardiovascular disease, effectively supporting traditional non-drug and drug-based approaches. Contemporary data indicate serious future perspectives for an expanded study of the hypoxytherapy possibilities in cardiac patients, including through the State research programmes. This review is devoted to the discussion of the physiological effects of hypoxytherapy, the possibilities of its application in cardiological practice, including with the analysis of own data, as well as precautions during its implementation.

Modern methods of researching autonomic functions in children with syncope: A literature review

The research of autonomic functions in children with non-cardiogenic syncope allows improving differential diagnosis and treatment tactics in children depending on the pathogenetic mechanisms of syncope development. The purpose of the research was to analyse modern scientific achievements in the field of autonomic functions in children with different types of syncope. The review used the full texts of English-language studies published between January 2018 and December 2022 and published in the PubMed Medline and Scopus databases. It has been established that the active orthostasis test, tilt test, circadian blood pressure rhythms and heart rate variability are the most commonly used functional autonomic tests in paediatric practice. They allow evaluating the spectrum of pathological cardiovascular reactions in a standing position; identifying types of orthostatic hypotension and causes of orthostatic intolerance; diagnosing orthostatic hypertension, postural orthostatic tachycardia syndrome, presyncope or syncope; to differentiating between sympathetic and parasympathetic autonomic dysfunctions and psychogenic transient syncope and epilepsy; to recommend orthostatic training as a method of treatment of syncope with an orthostatic mechanism of development. Despite this, there is no consensus on the definition of autonomic disorders and the methodology for conducting functional autonomic tests in children of different ages, considering their gender, body mass index and time of assessment during the day. Thus, functional autonomic tests are additional methods of physical and instrumental examination of the patient that allow effective assessment of the autonomic nervous system and possible mechanisms of syncope development, differentiation of transient loss of consciousness, stratification of future risks and optimisation of treatment and preventive tactics of the child's management based on an individual patient-centred approach

ARTERIAL HYPERTENSION AMONG MEDICAL WORKERS. ANALYSIS. EVALUATION

The aim. To examine the impact of individual medical and social factors, including work experience, lifestyle and living conditions, excess body weight, metabolic syndrome, types of circadian rhythms of blood pressure, and heredity, on the frequency of arterial hypertension (hypertensive disease - HD) formation.&#x0D; Materials and methods. The study involved the collection of anamnestic data, conducting interviews, performing objective examinations, and monitoring blood pressure in 391 medical workers, predominantly from therapeutic, surgical, and intensive care backgrounds. The obtained data were statistically processed using probability assessment criteria, risks assessed through odds ratio (OR), and ROC analysis.&#x0D; The results. The study revealed that only 33% of medical workers have a normal body weight. The risk of developing hypertensive disease (HD) is 3.24 times higher in the group with excess body weight and 8.72 times higher in the group with obesity compared to the examined subjects with normal body weight (p&lt;0.0001). Daily blood pressure monitoring results showed a statistically significant difference in 12 out of the 21 studied parameters (p&lt;0.05) between patients with HD, with and without metabolic syndrome. This indicates that the presence of metabolic syndrome affects the severity of hypertensive disease. Additionally, a statistically significant difference (p&lt;0.05) was observed in the distribution of circadian rhythm types of blood pressure between groups with and without hypertension. It was established that there is a predominance of unfavorable types of circadian blood pressure rhythm in medical worker groups experiencing high professional psycho-emotional stress (78.1-85.5%). Recognizing the risk factors for HD occurrence in medical workers can significantly enhance the effectiveness of a comprehensive hypertensive disease prevention program, leading to reduced blood pressure levels and a lower frequency of complications.&#x0D; Conclusions. It has been established that excess body weight is a risk factor for the development of hypertensive disease (HD) in medical personnel. The presence of metabolic syndrome has been proven to affect the severity of the hypertensive disease course. There is a certain association between disruptions in circadian blood pressure rhythms, professional psycho-emotional stress, and the development of arterial hypertension in medical workers of certain specialties. The prognostically significant threshold level of work experience for the formation of a group at an increased risk of developing HD is 11 years.

The relationship between morning blood pressure surge and serum IGF-1 level in acromegaly patients with hypertension.

High levels of insulin-like growth factor 1 (IGF-1) in patients with acromegaly cause structural and functional changes specific to the disease. These changes lead to mortality if the disease is not treated. Circadian blood pressure (BP) rhythm as measured by 24-h ambulatory blood pressure monitoring (ABPM) can change with a decrease in BP during sleep and a sudden increase in wakefulness. We aim to evaluate the relationship between changes in BP and IGF-1 levels in patients with acromegaly. Patients who were diagnosed with acromegaly and the patient group with hypertension were included. Serum biochemistry parameters, serum IGF-1 level and ABPM follow-ups were compared in these patients. In our study, 30 patients with acromegaly and 30 patients with hypertension without acromegaly were included. Thirty of the patients were male and 30 were female. There was a statistically significant difference between the groups in terms of IGF-1(p = < 0.001) and GH(p = 0.004). There was no significant difference between patients' office systolic/diastolic BP measurements, day/night, systolic/diastolic BP measurements and all systolic/diastolic BP measurements in ambulatory blood pressure follow-ups. There was a significant difference in morning blood pressure surge(p = < 0.001). A statistically significant difference was found between the acromegaly patient groups with MBPS below and above 25mmHg in terms of IGF-1 (p = 0.025) and platelet levels (p = 0.004). As a result, cardiovascular disease risks can be predicted in patients with high serum IGF-1 levels by planning ambulatory blood pressure in the early period.

Changes in Blood Pressure Variability in Children with Postural Tachycardia Syndrome.

(1) Objective: In this research, we explored the difference in blood pressure variability (BPV) between children with postural tachycardia syndrome (POTS) and healthy children. Furthermore, we tried to investigate the effect of BPV on POTS and its relationship with prognosis of POTS. (2) Methods: 47 children with POTS (11.2 ± 1.8 years, 23 males) were enrolled in the POTS group and 30 healthy children (10.9 ± 1.9 years, 15 males) were matched for the control group. All participants completed 24 h ambulatory blood pressure monitoring (24hABPM). Thirty-three children with POTS were followed up for 52.0 (30.5, 90.5) days and were divided into a response group and a non-response group after evaluation. (3) Results: The 24 h diastolic blood pressure standard deviation (24hDSD), daytime diastolic blood pressure standard deviation (DDSD), nighttime systolic blood pressure standard deviation (NSSD), daytime diastolic blood pressure variation coefficient (DDCV) and nighttime systolic blood pressure variation coefficient (NSCV) in the control group were lower than those in the POTS group (p < 0.05). Percentage of females, age and height were lower in the response group than in the non-response group in children with POTS (p < 0.05). Univariate analysis showed that 24hDSD, DDSD, NSSD, DDCV and NSCV were potential risk factors for POTS, and sex and height were potential risk factors for poor prognosis of POTS. After adjusting for covariates, the risk of POTS increased by 48%, 53% and 49% when DDSD, NSSD and NSCV increased by 1 mmHg, 1 mmHg and 1%, respectively. The risk of poor prognosis in females was 12.99 times higher than that in males. (4) Conclusions: The results suggest that children with POTS may have an abnormal circadian rhythm in blood pressure and increased BPV. DDSD, NSSD and NSCV are independent risk factors for POTS, and being female is an independent risk factor for poor prognosis of POTS.

The relationship between circadian rhythm of blood pressure and vascular dysfunction in essential hypertension

ABSTRACT Objective This study aimed to explore whether circadian rhythm of blood pressure is associated with brachial-ankle pulse wave velocity (baPWV) and brachial artery flow-mediated dilation (FMD) in patients with essential hypertension. Method This cross-sectional study included 4,217 patients with essential hypertension who completed 24-hour ambulatory blood pressure monitoring, baPWV, and FMD. BaPWV and FMD were measured to evaluate arterial stiffness and endothelial dysfunction. Participants were divided into dipper, non-dipper, and reverse dipping groups according to the nocturnal systolic blood pressure dipping percentage. Results In this study, baPWV was highest in the reverse dipping groups, followed by non-dipper and dipper groups (1667.11 ± 327.90 vs. 1613.88 ± 325.11 vs. 1577.45 ± 306.15 cm/s, P < .001) and FMD gradually increased (4.41 ± 2.87 vs. 4.70 ± 2.84 vs. 4.92 ± 2.79%, P = .001). baPWV and FMD were significantly associated with declining nocturnal systolic blood pressure (SBP). Interestingly, FMD (β = 0.042, P = .014) was only positively associated with a drop in nocturnal SBP decline in patients <65 years of age. Whereas baPWV was consistently negatively associated with nocturnal SBP decline regardless of age (β = -0.065, P < .001, age <65 years; β = -0.149, P = .002, age ≥ 65). Receiver operating characteristics (ROC) curves analysis showed areas under the curve (AUC) of baPWV/FMD for predicting circadian rhythm of blood pressure are 0.562/0.554 with a sensitivity of 51.7%/53.9% and specificity of 56.4%/53.4. Conclusion Impairment of baPWV and FMD were correlated with abnormal circadian rhythm of blood pressure in essential hypertension, suggesting a decrease in nighttime SBP may associate with endothelial function and arterial stiffness.

Exposure to unmethylated CpG oligonucleotides disrupts blood pressure circadian rhythms and placental clock gene network in pregnant rats.

Bacterial infections and impaired circulating mitochondrial DNA dynamics are associated with adverse pregnancy outcomes. Unmethylated cytosine-guanine dinucleotide (CpG) motifs are common in bacterial and mitochondrial DNA and act as potent immunostimulators. We tested the hypothesis that exposure to CpG oligonucleotides (ODN) during pregnancy would disrupt blood pressure circadian rhythms and placental molecular clock network, mediating aberrant fetoplacental growth dynamics. Rats were repeatedly treated with CpG ODN in the third trimester [gestational days (GD) 14, 16, and 18] and euthanized on GD20 (near term) or treated with a single dose of CpG ODN on GD14 and euthanized 4 h after treatment. Hemodynamic circadian rhythms were analyzed via Lomb-Scargle periodogram analysis on 24-h raw data collected continuously via radiotelemetry. A P value ≥ 0.05 indicates the absence of a circadian rhythm. Following the first treatment with CpG ODN, maternal systolic and diastolic blood pressure circadian rhythms were lost (P ≥ 0.05). Blood pressure circadian rhythm was restored by GD16 and remained unaffected after the second treatment with CpG ODN (P < 0.0001). Diastolic blood pressure circadian rhythm was again lost after the last treatment on GD18 (P ≥ 0.05). CpG ODN increased placental expression of Per2, Per3, and Tnfα (P ≤ 0.05) and affected fetoplacental growth dynamics. Reduced fetal and placental weights were disproportionately associated with increases in the number of resorptions in ODN-treated dams compared with controls. In conclusion, gestational exposure to unmethylated CpG ODN dysregulates the placental molecular clock network and fetoplacental growth dynamics and disrupts blood pressure circadian rhythms.NEW & NOTEWORTHY Gestational exposure to unmethylated CpG ODN dysregulates placental molecular clock network and fetoplacental growth dynamics and disrupts blood pressure circadian rhythms. These findings provide novel insights into the relationship between circadian rhythms and immune responses in pregnancy and propose new mechanisms by which maternal responses to immune triggers could dictate circadian rhythms of cardiovascular processes and placental clock machinery function to determine fetal growth trajectories.

Blunted circadian variation of blood pressure in individuals with neurofibromatosis type 1

BackgroundCardiovascular events such as myocardial infarction and stroke are life-threatening complications associated with Neurofibromatosis type 1 (NF1). As previous studies observed an association between cardiovascular events and the loss of circadian variations of blood pressure, we investigated the 24 h circadian rhythm of blood pressure (BP) in 24 NF1 patients (10 males and 14 females, with a mean age of 39.5 years ± 14 years) by using ambulatory blood pressure monitoring (ABPM).ResultsOnly one-third of the patient were dippers, 50% were non-dippers, and 17% were risers. Reduced variability of systolic and diastolic nocturnal blood pressure was observed in NF1 patients compared with several studies of normotensive individuals (p = 0.024). In NF1 patients, the blunted systolic nocturnal decline was significantly associated with the number of neurofibromas (p = 0.049) and the presence of a plexiform neurofibroma (p = 0.020).ConclusionsMost NF1 patients in this study showed a “non-dipper” pattern with a blunted nocturnal BP decline, which is considered an independent risk factor for cardiovascular events in normotensive and hypertensive individuals. Periodic monitoring of BP should be included in NF1 follow-up guidelines to diagnose masked hypertension or a non-dipper/riser pattern which would significantly increase the morbidity and mortality of NF1 patients to implement therapeutic strategies.

Pers reverse angiotensin II -induced vascular smooth muscle cell proliferation by targeting cyclin E expression via inhibition of the MAPK signaling pathway

ABSTRACT The circadian rhythm of blood pressure (BP) is believed to be regulated by the clock system, which is closely linked to levels of angiotensin II (Ang II). This study aimed to investigate whether Ang II mediates the proliferation of vascular smooth muscle cells (VSMCs) through the interaction between the clock system and the mitogen-activated protein kinase (MAPK) signaling pathway. Primary rat aortic VSMCs were treated with Ang II, with or without MAPK inhibitors. VSMC proliferation, expression of clock genes, CYCLIN E, and MAPK pathways were assessed. Ang II treatment resulted in increased VSMC proliferation and rapid upregulation of clock gene Periods (Pers) expression. Compared to the non-diseased control (NC) group, VSMCs incubated with Ang II displayed a noticeable delay in the G1/S phase transition and downregulation of CYCLIN E upon silencing of Per1 and Per2 genes. Importantly, silencing Per1 or Per2 in VSMCs led to decreased expression of key MAPK pathway proteins, including RAS, phosphorylated mitogen-activated protein kinase (P-MEK), and phosphorylated extracellular signal-regulated protein kinase (P-ERK). Moreover, the MEK and ERK inhibitors, U0126 and SCH772986, significantly attenuated the Ang II-induced proliferation of VSMCs, as evidenced by an increased G1/S phase transition and decreased CYCLIN E expression. The MAPK pathway plays a critical role in regulating VSMC proliferation in response to Ang II stimulation. This regulation is controlled by the expression of circadian clock genes involved in the cell cycle. These findings provide novel insights for further research on diseases associated with abnormal VSMC proliferation.

BLOOD PRESSURE VARIABILITY AND CIRCADIAN PATTERN AFTER RENAL DENERVATION - CROATIAN REAL-LIFE STUDY

Objective: Recent trials confirmed the lowering effect of renal denervation (RDN) on blood pressure (BP). We aimed to analyze the impact of RDN on BP variability and circadian rhythm. Design and method: Out of 31 truly resistant patients whose secondary forms of hypertension were ruled out and were enrolled into the Croatian Spyral RDN registry, 18 (10 m, 8 w, average age 49.3) were eligible for analyses. Office BP, ABPM, central BP, and PWV were measured with Omron M6, Mobilograph, and Sphygmocor devices. Sympathetic/parasympathetic activity was measured with ANX-3.0 ANSAR device. All RDN procedures (Spyral Medtronic) were done by one physician (average number of ablation spots was 41/procedure). Patients were examined the day before and that day, 1,3,6, and 12 months after the RDN. The response was a drop of office systolic BP by 10 mmHg or more 6 months after RDN. There were no differences in the RDN procedure between responders and non-responders. Results: Office and ABPM values dropped the day after RDN and remained significantly lower at the end of the follow-up (6.5/-5.5 and -16.2/9 mmHg, respectively). We failed to find changes in BP variability (SD) after RDN. However, a significant decrease in morning BP surge was observed immediately the day after RDN (-12.4) and was even lower at the end of the follow-up (-18.8 mmHg). Substantial number of patients who had an abnormal nocturnal BP pattern became dippers. Central systolic BP and PWV decreased (-6.3 mmHg and -0.72 m/s, respectively). LFa/RFa decreased the day after RDN and reminded lower during the follow-up period. After RDN morning BP surge remained stable and normal in responders; however, in non-responders, it decreased immediately after RDN (-21.2) and remained lower during the follow-up till the last visit (-33.3). Conclusions: Significant improvements in circadian rhythm and several parameters of central hemodynamics were observed after RDN indicating that RDN might be considered as a pathway to the complete, so-called perfect 24-hour BP control. Observed beneficial effects run in parallel with the observed decrease in sympathetic activity. Importantly, even in non-responders, RDN had a beneficial effect on morning BP surge.

ASSOCIATION BETWEEN BMI AND AMBULATORY BLOOD PRESSURE CHARACTERISTICS: EVIDENCE FROM POPULATION-BASED AMBULATORY BLOOD PRESSURE MONITORING COHORT

Objective: The aim of our study was to investigate the association between BMI and Chinese hypertensive patients’ ambulatory blood pressure characteristics. Design and method: According to the inclusion criteria and exclusion criteria, recruiting participants for analysis. Overweight was defined as BMI = &gt; 18.5 kg/m2, and obesity as BMI = &gt; 25 kg/m2. ABPM characteristics were defined according to European guidelines. Hypertension was defined as elevated mean ambulatory BP (&gt;135/85 mmHg in day-time, &gt;120/70 mmHg in the night-time, &gt;130/80 mmHg over 24-h). There are four kinds of blood pressure circadian rhythm, dippers, non-dippers, reverse dippers, and extreme dippers. The effects of BMI on ambulatory blood pressure characteristics were analyzed using between-group analysis of variance and logistic regression analysis. Results: In our cohort, 35367 hypertensive patients who were eligible for this study were analyzed finally, including 19380 men (54.8%) and 15987 women (45.2%) aged from 19 to 99 (mean age 58.86 years). The mean 24hBP of the study subjects was 126.41±16.00/78.79±11.62 mmHg. The different BMI groups showed that ambulatory BP increased with BMI, and the obese group had the highest increase in BP, HR, and systolic BP (P &lt; 0.05). Blood pressure variability and systolic load tended to increase with BMI, while the nocturnal blood pressure drop rate tended to decrease. When analyzing the type of hypertension among the participants, the prevalence of MBPS and morning hypertension increased significantly with the elevated BMI (P &lt; 0.05), and the highest prevalence of MBPS was found in the obese group. Logistic regression analysis revealed that the increased risks of MBPS and morning hypertension were the highest in the obese group, corresponding to a 2.1-fold (P &lt; 0.05) and 1.6-fold (P &lt; 0.05) increase in risk, respectively, with no change in trend after adjustment. Conclusions: BMI may affect the characteristics of hypertensive patients’ ambulatory blood pressure. The blood pressure variability and 24h SBP tended to increase with BMI, and the incidence of MBPS was highest in the obese group.

0017 Obstructive sleep apnea is associated with altered circadian rhythms in systolic blood pressure at rest and during exercise

Abstract Introduction Obstructive sleep apnea (OSA) is associated with an increased risk for major adverse cardiovascular events (MACE), such as sudden cardiac death. MACE is more frequent in the morning in the general population but more frequent in the middle of the night in people with OSA. Whether these differences are associated with changes in circadian rhythms of blood pressure regulation is unknown. We tested if circadian rhythms in systolic blood pressure (SBP) during rested wakefulness and in response to a standardized mild exercise are disturbed in people with OSA compared to healthy controls (HC). Methods We studied 39 participants (HC [n=25, age 52.8±7.8 {mean±SD} years], (OSA [n=14, 50.6±6.6 years]) during ten identical recurring 5-h 20-min behavioral cycles in dim light and in an environment free of time cues. SBP was measured in the supine position during rested wakefulness followed by while seated at rest and during mild-intensity (heart rate at 50% heart rate reserve using the Karvonen formula) exercise on a static cycle ergometer. Circadian phases were determined relative to the dim-light melatonin onset. We performed mixed-model cosinor analyses to test whether the groups differed in their SBP rhythms during rested wakefulness and in their BP responses to exercise. Results Melatonin levels or phases relative to clock time were not different between groups (p=0.17), suggesting similar timing of central circadian clock outputs. There was an overall rhythm (p&amp;lt; 0.001) and a trend to group x circadian phase interaction for resting SBP (p=0.10). A separate group analysis showed a significant circadian rhythm in SBP in HC (p&amp;lt; 0.001) with a peak in the evening but no evident circadian rhythm in people with OSA (p=0.17). There was no circadian phase x exercise reactivity interaction between groups, but overall, exercise reactivity of SBP was significantly higher in people with OSA (+4mmHg, p=0.001). Conclusion OSA is characterized by a blunted circadian rhythm in resting blood pressure and an exaggerated blood pressure reactivity to exercise. Mechanisms for these rhythm changes should be investigated further. Support (if any) Support: NIH F32HL163232, R01HL125893, R01HL163232, R35HL155681, R01HL156948, ULTR00128, Oregon Institute of Occupational Health Sciences.

Relationship between cognitive dysfunction and the promoter methylation of PER1 and CRY1 in patients with cerebral small vessel disease.

The prevalence of cerebral small vessel disease (CSVD) is increasing due to the accelerating global aging process, resulting in a substantial burden on all countries, as cognitive dysfunction associated with CSVD is also on the rise. Clock genes have a significant impact on cognitive decline and dementia. Furthermore, the pattern of DNA methylation in clock genes is strongly associated with cognitive impairment. Thus, the aim of this study was to explore the connection between DNA promoter methylation of PER1 and CRY1 and cognitive dysfunction in patients with CSVD. We recruited patients with CSVD admitted to the Geriatrics Department of the Lianyungang Second People's Hospital between March 2021 and June 2022. Based on their Mini-Mental State Examination score, patients were categorized into two groups: 65 cases with cognitive dysfunction and 36 cases with normal cognitive function. Clinical data, 24-h ambulatory blood pressure monitoring parameters, and CSVD total load scores were collected. Moreover, we employed methylation-specific PCR to analyze the peripheral blood promoter methylation levels of clock genes PER1 and CRY1 in all CSVD patients who were enrolled. Finally, we used binary logistic regression models to assess the association between the promoter methylation of clock genes (PER1 and CRY1) and cognitive dysfunction in patients with CSVD. (1) A total of 101 individuals with CSVD were included in this study. There were no statistical differences between the two groups in baseline clinical data except MMSE and AD8 scores. (2) After B/H correction, the promoter methylation rate of PER1 was higher in the cognitive dysfunction group than that in the normal group, and the difference was statistically significant (adjusted p < 0.001). (3) There was no significant correlation between the promoter methylation rates of PER1 and CRY1 in peripheral blood and circadian rhythm of blood pressure (p > 0.05). (4) Binary logistic regression models showed that the influence of promoter methylation of PER1 and CRY1 on cognitive dysfunction were statistically significant in Model 1 (p < 0.001; p = 0.025), and it still existed after adjusting for confounding factors in Model 2. Patients with the promoter methylation of PER1 gene (OR = 16.565, 95%CI, 4.057-67.628; p < 0.001) and the promoter methylation of CRY1 gene (OR = 6.017, 95%CI, 1.290-28.069; p = 0.022) were at greater risk of cognitive dysfunction compared with those with unmethylated promoters of corresponding genes in Model 2. The promoter methylation rate of PER1 gene was higher in the cognitive dysfunction group among CSVD patients. And the hypermethylation of the promoters of clock genes PER1 and CRY1 may be involved in affecting cognitive dysfunction in patients with CSVD.