Nighttime Blood Pressure Research Articles

Night-Time Non-dipping Blood Pressure and Heart Rate: An Association With the Risk of Silent Small Vessel Disease in Patients Presenting With Acute Ischemic Stroke.

Background and Purpose: Nocturnal non-dipping blood pressure and heart rate are associated with an increased risk of cardiovascular disease. The effects of such variance on cerebrovascular disease have not been well studied.Methods: The 24-h ambulatory blood pressure (ABPM) and heart rate were monitored with B-pro in patients with acute stroke within the initial week of hospital admission. The risk factor profiles, clinical presentation, imaging, and short-term prognosis were compared in nocturnal dippers and non-dippers (more than 10% nocturnal decrease) of blood pressure and heart rate.Results: We enrolled 234 patients in whom ABPM and MRI data were available. Heart rate data were available in 180 patients. Lacunar sub-cortical stroke was the most common acute lesion (58.9%), while hypertension (74%) and diabetes (41.5%) were the most common associated risk factors. ABPM revealed non-dipping in 69% of patients. On univariate analysis, Small Vessel Disease (SVD) was significantly more frequent in non-dippers vs. dippers (BP: 56.8 vs. 40.3% p = 0.02; heart rate: 57.9 vs. 40.7% p = 0.03). Silent strokes were also more frequent in non-dippers vs. dippers (BP: 40.7 vs. 26.4% p = 0.35; heart rate: 44.6 vs. 25.4% p = 0.01). Multivariate analysis revealed SVD to be significantly related to age, hypertension, blood pressure non-dipping, and severity of symptoms at index event.Conclusions: The presence of nocturnal non-dipping of blood pressure and heart rate are associated with an increased risk of silent stroke and SVD. Increased use of ABPM may allow for improved diagnosis of non-dippers.

Bloodletting has no effect on the blood pressure abnormalities of hyperandrogenic women taking oral contraceptives in a randomized clinical trial

Normoferritinemic women with functional hyperandrogenism show a mild iron overload. Iron excess, hyperandrogenism, and cardioautonomic dysfunction contribute to blood pressure (BP) abnormalities in these patients. Furthermore, combined oral contraceptives (COC) prescribed for hyperandrogenic symptoms may worse BP recordings. Iron depletion by phlebotomy appears to lower BP in other acquired iron overload conditions. We aimed to determine the effect of iron depletion on the office BP, ambulatory BP monitoring, and frequency of hypertension in patients with functional hyperandrogenism submitted to standard therapy with COC. We conducted a phase 2 randomized, controlled, parallel, open-label clinical trial (NCT02460445) in adult women with functional hyperandrogenism including hyperandrogenic polycystic ovary syndrome and idiopathic hyperandrogenism. After a 3-month run-in period of treatment with 35 µg ethinylestradiol plus 2 mg cyproterone acetate, participants were randomized (1:1) to three scheduled bloodlettings or observation for another 9 months. Main outcome measures were the changes in office BP, 24-h-ambulatory BP, and frequency of hypertension in both study arms. From June 2015 to June 2019, 33 women were included in the intention-to-treat analyses. We observed an increase in mean office systolic BP [mean of the differences (MD): 2.5 (0.3–4.8) mmHg] and night-time ambulatory systolic BP [MD 4.1 (1.4–6.8) mmHg] after 3 months on COC. The percentage of nocturnal BP non-dippers also increased, from 28.1 to 92.3% (P < 0.001). Office and ambulatory BP did not change throughout the experimental period of the trial, both when considering all women as a whole or as a function of the study arm. The frequency of the non-dipping pattern in BP decreased during the experimental period [OR 0.694 (0.577–0.835), P < 0.001], regardless of the study arm. Decreasing iron stores by scheduled bloodletting does not override the BP abnormalities caused by COC in women with functional hyperandrogenism.

Renal artery denervation in patients with resistant arterial hypertension: clinical and organ-protective effect

Aim. To assess the clinical efficacy of renal artery denervation (RAD) in treatment of patients with resistant arterial hypertension (RAH) compared to patients taking drug therapy (DT) at long-term follow-up and the possibility of RAD impact on target organs (heart, kidneys).&#x0D; Materials and methods. 80 RAH patients were examined (mean age 54.3010.19 years). Patients were divided in two groups: the basic group was comprised of 40 RAH patients taking antihypertensive DT, who underwent RAD (gr. 1) and comparison group was composed of 40 RAH patients taking only antihypertensive DT (gr. 2). Gender and age differences between groups were statistically insignificant (p0.05). Mean duration of AH was 18.638.96 years. The follow-up was carried out during one year.&#x0D; Results. In RAD group there was confirmed decrease not only in the office, but also in the average day-time and night-time blood pressure (BP), changes were more significant in systolic BP (SBP) indicators: the overall daytime SBP was 17.369.31 mmHg (p0.001), the average day-time SBP was 17.1810.53 mmHg (p0.001), the average night-time SBP was 19.2210.76 mmHg (p0.001). At the same time, in DT group changes in values of overall, maximum, minimum, average day-time and average night-time SBP and diastolic BP were not statistically significant in 12 months. RAD in RAH was accompanied by decrease in left ventricular hypertrophy with initial hypertrophy (p0.05), decrease in microalbuminuria (p0.05), decrease in velocity in segmental (p0.05) and interlobar renal arteries (p0.01).&#x0D; Conclusion. RAD in patients with RAH had not only antihypertensive effect but also positive effect on target organs of AH (heart, kidneys).

Diurnal Cortisol Slope and Nighttime Blood Pressure: A Study in European Americans and African Americans.

African Americans (AAs) have higher nighttime blood pressure (BP) than European Americans (EAs). Stress has been suggested to play a role in this difference, but the mechanism is not well-understood. Flatter diurnal cortisol slope (DCS) is a well-known biological marker of stress. The objectives of this study were to: 1) examine ethnic differences in DCS; 2) evaluate the association between DCS and nighttime BP; and 3) determine the extent to which ethnic differences in nighttime BP can be explained by ethnic differences in DCS. A total of 510 participants (age range: 14-35 years; 49.6% AAs, 54.5% females) provided four salivary cortisol samples at bedtime, wakeup, 30-minutes post-wakeup, and 60-minutes post-wakeup. Additionally, participants wore an ambulatory BP monitor for 24 hours. DCS was calculated as the average of the three morning samples minus the bedtime measurement. After adjustment for age, sex, BMI, and smoking, AAs had blunted DCS (P=.018) and higher nighttime systolic BP (SBP) and diastolic BP (DBP) (Ps<.001) compared with EAs. The DCS was inversely related to nighttime SBP and this relationship did not depend on ethnicity. The ethnic difference of nighttime SBP was significantly attenuated upon addition of DCS to the model. Mediation test showed that 9.5% of ethnic difference in nighttime SBP could be explained by DCS (P=.039). This study confirms ethnic differences in DCS and nighttime BP and further demonstrates that the ethnic differences in DCS can, at least partially, explain the ethnic differences found in nighttime BP.

Blood Pressure and Arterial Stiffness in Association With Aircraft Noise Exposure:Long-Term Observation and Potential Effect of COVID-19 Lockdown.

In a cross-sectional analysis of a case-control study in 2015, we revealed the association between increased arterial stiffness (pulse wave velocity) and aircraft noise exposure. In June 2020, we evaluated the long-term effects, and the impact of a sudden decline in noise exposure during the coronavirus disease 2019 (COVID-19) lockdown, on blood pressure and pulse wave velocity, comparing 74 participants exposed to long-term day-evening-night aircraft noise level >60 dB and 75 unexposed individuals. During the 5-year follow-up, the prevalence of hypertension increased in the exposed (42% versus 59%, P=0.048) but not in the unexposed group. The decline in noise exposure since April 2020 was accompanied with a significant decrease of noise annoyance, 24-hour systolic (121.2 versus 117.9 mm Hg; P=0.034) and diastolic (75.1 versus 72.0 mm Hg; P=0.003) blood pressure, and pulse wave velocity (10.2 versus 8.8 m/s; P=0.001) in the exposed group. Less profound decreases of these parameters were noticed in the unexposed group. Significant between group differences were observed for declines in office and night-time diastolic blood pressure and pulse wave velocity. Importantly, the difference in the reduction of pulse wave velocity between exposed and unexposed participants remained significant after adjustment for covariates (-1.49 versus -0.35 m/s; P=0.017). The observed difference in insomnia prevalence between exposed and unexposed individuals at baseline was no more significant at follow-up. Thus, long-term aircraft noise exposure may increase the prevalence of hypertension and accelerate arterial stiffening. However, even short-term noise reduction, as experienced during the COVID-19 lockdown, may reverse those unfavorable effects.

Effect of esaxerenone on nocturnal blood pressure and natriuretic peptide in different dipping phenotypes.

There are limited data on the nighttime blood pressure (BP)-lowering effect of esaxerenone and its effect on N-terminal pro b-type natriuretic peptide (NT-proBNP), a predictor of cardiovascular risk, according to different dipping patterns of nocturnal BP. This was a post hoc analysis of a multicenter, open-label, long-term phase 3 study of esaxerenone, a new highly selective mineralocorticoid receptor blocker, in patients with essential hypertension. Patients were classified by dipping pattern (extreme dippers, dippers, non-dippers, risers). Mean changes in BP, changes in dipping pattern, mean NT-proBNP levels, and percentage of patients with normal NT-proBNP levels (<55 pg/mL) at baseline and Weeks 12 and 28 were evaluated. Nighttime systolic BP decreased in all dipping pattern groups at Week 28, with the riser group showing the greatest change (−25.5 mmHg). A significant shift in dipping pattern and riser/non-dipper pattern changes to dipper/extreme dipper pattern were found from baseline to Week 28 (p < 0.0001). The prevalence of the riser pattern decreased from 14.4% to 9.8%, and that of the non-dipper pattern from 44.7% to 39.2%. The decrease in NT-proBNP from baseline to Week 28 was statistically significant in risers, non-dippers, dippers, and extreme dippers (p < 0.001, respectively). At baseline, the proportion of patients with NT-proBNP <55 pg/mL was lowest in risers versus the other dipping pattern types, but after reductions in NT-proBNP in all groups to Week 28, these differences disappeared. Long-term administration of esaxerenone may be a useful treatment option for nocturnal hypertension, especially in patients with a riser pattern.

Evaluation of a cuffless watch-like sensor for 24-hour ambulatory blood pressure monitoring

Abstract Introduction Ambulatory blood pressure monitoring (ABPM) is increasingly used in clinical practice for the formal diagnosis of hypertension, and particularly indicated in cases of suspected white-coat effect, masked, or nocturnal hypertension. However, the use of cuffs for ABPM may be painful and cause discomfort, particularly at night, where it may even provoke arousal from sleep and lead to non-representative nighttime blood pressure (BP) values. Purpose To investigate the feasibility of using a cuffless watch-like photoplethysmographic (PPG) sensor for 24-hour ABPM by comparing the PPG-based BP estimates with conventional cuff-derived ABPM values. Methods Our study was approved by the local ethical committee and conducted in 70 participants (43±18 y, 35 with hypertension, 41 male) undergoing cuff-based ABPM. At the contralateral side of the cuff, a cuffless watch-like PPG sensor was worn at the wrist or upper arm. Systolic (SBP) and diastolic (DBP) BP values were estimated by pulse wave analysis on the measured PPG signals. Following a calibration procedure, the PPG-based daytime and nighttime BP estimates were compared to their cuff-based counterparts. The agreement between both methods was evaluated via the mean (bias) and standard deviation (SD) of their differences by Bland-Altman analysis. The agreement on the nocturnal dipping estimates of both devices was also assessed. Finally, the concordance rate (CR) was assessed as the percentage of dipping values showing a concordant direction (dipping vs. non-dipping) between both methods. Results The data of 4 participants were incomplete due to technical issues and had to be rejected prior to analysis. In 4 additional participants, the PPG data quality was insufficient to provide enough BP estimates, probably due to poor sensor tightening. In the remaining 62 participants, we found (see Figure 1) differences between the daytime PPG-based and cuff-based BP estimates of −0.9±3.6 mmHg and −1.4±2.9 mmHg for SBP and DBP, respectively. The differences between the nighttime estimates were −0.8±6.8 mmHg and 0.5±5.3 mmHg, resulting in dipping differences of 0.1±6.8% and −2.0±8.6% for SBP and DBP, respectively. CR on dipping was 97% for both SBP and DBP. Conclusions Good agreement was found between the PPG-based and the cuff-based daytime and nighttime BP averages, with generally negligible (∼1 mmHg) biases. The direction of dipping was highly concordant between both methods. The estimation of its amplitude showed a low bias (∼1%) but a non-negligible spread (SD), which can be in part attributed to the uncertainty on the cuff-based dipping estimates (95% confidence interval range of 12.5% and 16.5% on average for SBP and DBP, respectively), more than twice as large than their PPG-based counterparts (5.7% and 7.8%). Although our study was designed as a method-comparison feasibility study, these results encouragingly suggest that cuffless ABPM may soon become a clinical possibility. Funding Acknowledgement Type of funding sources: None. Figure 1

High prevalence of non-dipping patterns among black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial

Abstract Background Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of anti-hypertensive therapy, and intensifying salt restriction. Objectives To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of three 6-months anti-hypertensive regimens on the dipping pattern among Black African hypertensive patients. Methods This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-hour ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. Results The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium &amp;gt;140mmol/l (OR=1.72, 95% CI: 1.17–2.51, p-value 0.005), a higher office systolic BP (OR=1.03, 95% CI: 1.01–1.05, p-value 0.003) and a lower office diastolic BP (OR=0.97, 95% CI: 0.95–0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar's χ2 0.71, p-value 0.40). Conclusion There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Fogarty International Center and the National Institutes of Health of the United States of America Figure 1

Efficacy &amp; tolerability of bisoprolol in comparison to metoprolol in Indian patients with stage-1 hypertension: multicentre, parallel group, open labelled, randomised noninferiority clinical study

Abstract Introduction Bisoprolol &amp; Metoprolol are selective β1 adrenergic blockers used in treatment of several diseases, including hypertension (HTN). Unlike Metoprolol, the β1-receptor selectivity of Bisoprolol does not change with increasing dose and Bisoprolol also has a longer half-life. The objective was to compare the efficacy &amp; tolerability of Bisoprolol with Metoprolol in Indian patients with Stage-1 HTN. Method Multicentre, parallel group, open labelled, randomised noninferiority trial was conducted at 6 cardiology centres in India (2010 – 2011). The study was approved by the institutional ethics committee at each centre and was performed in accordance with the good clinical practice guidelines and ICH-GCP. Out 218 adult patients screened, 200 patients between the age group of 18 to 65 years, with systolic blood pressure (SBP) 140–159 mm Hg or diastolic blood pressure (DBP) 90–99 mm Hg were randomly assigned to receive either Bisoprolol 5 mg once daily or Metoprolol-SR 50 mg once daily. Primary outcome measure was the responder rate (% of patients achieving BP &amp;lt;140/90 mm Hg throughout 24 hours) at 12 weeks. The secondary outcome measures were the percentage of patients requiring dose titration at 6 weeks, change in the SBP &amp; DBP from baseline at 6 and 12 weeks, change in the mean night-time blood pressure from baseline at 12 weeks &amp; global efficacy and tolerability assessment on a four-point scale. Results 200 patients (100 each in the 2 arms, 74.5% Males, mean age of 49.55 and 53.39 in the bisoprolol and metoprolol arms respectively) were enrolled in the study. Efficacy analysis was done on 165 patients who completed the study. There was a trend towards a better 24 hr BP control rate with Bisoprolol, responder rates were 68.33% for Bisoprolol and 62.9% for Metoprolol as measured by continuous ambulatory blood pressure measurement. Also Bisoprolol was non-inferior to Metoprolol with respect to percentage of patients requiring dose titration (12.3% vs 11.6%), change in SBP (7.7% vs 7.2%) &amp; DBP (9.6% vs 9.1%), change in mean night-time blood pressure (29.1% vs 25.3%) and reduction in heart rate (9.2% vs 6.7%). The two treatments were also similar with respect to efficacy &amp; tolerability on Global Assessment by doctors &amp; patients respectively. Conclusion Bisoprolol is non-inferior to Metoprolol-SR with respect to efficacy &amp; safety in patients of stage-1 HTN, with a trend towards better control of 24 hr BP in this non-inferiority trial. This study was conducted at a time when β-blockers were considered as first-line therapies for the management of hypertension. Our study supports the use of bisoprolol in Indian patients, based on the non-inferiority (as compared to metoprolol) and with the advantageous profile of the molecule. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): The study was supported by a research grant from Merck.

Sex differences in ambulatory blood pressure levels, control, and phenotypes of hypertension in kidney transplant recipients.

Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Twenty-four-hour blood pressure profile in idiopathic REM sleep behavior disorder.

To determine whether autonomic dysfunction in idiopathic REM sleep behavior disorder (iRBD) affects circadian blood pressure (BP) profile. Twenty-one iRBD (mean age 68.8 ± 6.4, mean age at onset 62.2 ± 9.3), 21 drug-free de novo Parkinson's disease (PD) and 21 control participants (HCs), comparable for age and sex, underwent 24-h ambulatory BP monitoring. A prospective follow-up study was performed to evaluate the occurrence of neurodegenerative disorders in the iRBD cohort. In the iRBD group, nighttime systolic BP (SBP) was higher (124.0 ± 20.0, p = .026), nocturnal BP decrease lower (4.0 ± 8.7% for SBP and 8.7 ± 8.0% for diastolic BP [DBP], p = .001), and nondipping status more frequent (71.4% for SBP and 52.4% for DBP; p = .001 and p = .01, respectively) than in the HCs. Reverse dipping of SBP was found in 23.8% (p = .048) of the iRBD participants. Nondipping status was not associated with differences in gender, age, disease duration, age at disease onset, UPDRS score, presence of antihypertensive therapy, or polysomnographic measures. Patients with PD showed daytime and nighttime BP profiles comparable to those observed in iRBD. A subgroup analysis considering only the participants without antihypertensive therapy (12 iRBD, 12 PD) showed results superimposable on those of the whole iRBD and PD groups. Longitudinal follow-up (mean 5.1 ± 1.9 years) showed no differences in BP profile at baseline between converters (n = 6) and nonconverters. Twenty-four-hour BP control was impaired in iRBD. This impairment, similar to patterns observed in de novo PD, consisted of reduced amplitude of nocturnal dipping and increased frequency of nondipping status. These findings could have implications for cardiovascular morbidity and mortality in iRBD.

Суточный профиль артериального давления у детей с хроническим пиелонефритом и хронической болезнью почек I–III стадии

Актуальность. В ведении пациентов с хронической болезнью почек (ХБП) важное значение как для снижения традиционного сердечно-сосудистого риска, так и для сохранения остаточной функции почек в течение длительного времени имеет контроль артериального давления (АД). Цель работы: изучить особенности суточного профиля АД у детей с хроническим пиелонефритом (ХПН) с І–ІІІ стадией ХБП. Материалы и методы. Обследованы 94 ребенка в возрасте от 6 до 17 лет с хроническим пиелонефритом вне обострения и ХБП I–III стадии. Проводилось суточное мониторирование артериального давления (СМАД) с последующей математической обработкой результатов. Результаты. При сравнительном анализе показателей АД, полученных при разовом измерении и при проведении СМАД, выявлено их расхождение в 25,5 % случаев. По данным СМАД, у детей с ХПН в целом повышенное АД регистрировалось у 22,3 % больных, АГ — у 34,0 %. Установлено, что со снижением функции почек (легкая или умеренная степень ХБП) постепенно увеличивалось относительное количество больных со стабильной и лабильной артериальной гипертензией (АГ). Анализ степени ночного снижения АД у пациентов с ХПН показал постепенное уменьшение относительного количества пациентов с оптимальным уровнем снижения как систолического АД (от 61,7 % при ХБП I стадии до 47,1 % при ХБП III стадии), так и диастолического АД (53,2 и 11,8 % соответственно; р = 0,0049). Среди больных с ХБП III стадии регистрировались пациенты night peakers, которые имели устойчивое повышение систолического (11,8 %) и диастолического АД (29,4 %) ночью. Выводы. Во время прогрессирования ХБП среди детей с ХПН увеличивается количество пациентов с повышенным АД и АГ. Характерными признаками АГ у этой категории пациентов являются существенный вклад диастолической составляющей и устойчивое повышение ночного АД.

Seasonal variation in blood pressure: current evidence and recommendations for hypertension management.

Blood pressure (BP) exhibits seasonal variation, with an elevation of daytime BP in winter and an elevation of nighttime BP in summer. The wintertime elevation of daytime BP is largely attributable to cold temperatures. The summertime elevation of nighttime BP is not due mainly to temperature; rather, it is considered to be related to physical discomfort and poor sleep quality due to the summer weather. The winter elevation of daytime BP is likely to be associated with the increased incidence of cardiovascular disease (CVD) events in winter compared to other seasons. The suppression of excess seasonal BP changes, especially the wintertime elevation of daytime BP and the summertime elevation of nighttime BP, would contribute to the prevention of CVD events. Herein, we review the literature on seasonal variations in BP, and we recommend the following measures for suppressing excess seasonal BP changes as part of a regimen to manage hypertension: (1) out-of-office BP monitoring, especially home BP measurements, throughout the year to evaluate seasonal variations in BP; (2) the early titration and tapering of antihypertensive medications before winter and summer; (3) the optimization of environmental factors such as room temperature and housing conditions; and (4) the use of information and communication technology-based medicine to evaluate seasonal variations in BP and provide early therapeutic intervention. Seasonal BP variations are an important treatment target for the prevention of CVD through the management of hypertension, and further research is necessary to clarify these variations.

Abstract P190: Antihypertensive Treatment Improves Left Ventricular Geometry After 10 Years Even In Elderly Hypertensive Patients

Introduction: Both ageing and high blood pressure (BP) is associated with a risk of left ventricular hypertrophy; therefore, it is unclear whether antihypertensive treatment for 10 years period reduce cardiac hypertrophy and concentricity beyond the impact of ageing. We assessed the hypothesis that even in elderly patients, BP reduction is effective for left ventricular remodeling. Methods: Among 558 hypertensive patients without concurrent heart disease referred to a cardiology clinic who underwent echocardiography and ambulatory blood pressure monitoring, 151 patients’ data of echocardiography was available after 10 years of follow up period. We evaluated the relation among BP at baseline, antihypertensive medications, and change in echocardiographic parameters of left ventricular geometry. Results: Mean age was 70.8±8.2 years at baseline. 24-hour BP was 127.4±16.4/71.4±9.6mmHg, awake BP was 129.9±17.1/72.4±10.2mmHg, and asleep BP was 122.5±16.9/67.1±9.1 mmHg. After 10 years (mean age 81.0±9.0 years), number of antihypertensive increased from 1.3±1.2 to 2.0±1.1. Left ventricular mass index (LVMI) insignificantly decreased from 115.7 to 98.7mg/m 2 (p=0.167)and relative wall thickness (RWT) significantly decreased from 0.51 to 0.47(p&lt;0.001). There were 12% of patients with normal left ventricular geometry (N), 52% with concentric remodeling (CR), 9% with eccentric hypertrophy (EH), and 27% with concentric hypertrophy (CH) at baseline. Among patients with N or CR at baseline, those who developed to CH or EH had higher night time systolic BP (126.5±17.0 vs 118.9 ±15.4, p=0.037) than those who did not. Neither number nor type of antihypertensive was related to this geometry change. In logistic regression analysis, night time systolic BP was significantly related to the progression of hypertrophy adjusting for age, sex, BMI, LVMI, RWT, and clinic systolic BP at baseline (p=0.04). Conclusions: Even in elderly hypertensive patients, antihypertensive treatment for 10 years improved LV geometry in spite of ageing. Nighttime BP at baseline predicted worsening of LV geometry after 10 years beyond clinic BP.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension - Con Side of the Argument.

Abstract T1: Prognostic Value Of 24-hour Ambulatory Blood Pressure And Heart Rate Patterns In Diabetes: A 20-year Longitudinal Analysis Of The Chronic Diabetes Complications And All-cause Mortality In Pisa From 1999 Onwards (CHAMP1ON) Study Cohort

Background: Abnormal circadian blood pressure (BP) patterns and reduced heart rate variability (HRV) are established risk factors for cardiovascular events in diabetic patients. However, studies assessing all-cause mortality associated with altered BP patterns and HRV in diabetes are limited by follow-up periods of less than 10 years. Methods: We examined a cohort of 349 patients with type 2 diabetes ( n =284) or type 1 diabetes ( n =65) recruited in Pisa (Italy) from 1999 and followed-up for 21 years, all with available 24-hour ambulatory BP and HRV monitoring. Dipping, non-dipping and reverse dipping status were defined as a ≥10% decline, &lt;10% decline, and ≥0.1% increase in average night-time systolic BP (SBP) compared with average daytime SBP, respectively. Results: After 6,251 person-years of follow-up (median follow-up 21.0 [14.0-21.0] years, 183 [52%] women, age 57.1±11.9 y, BMI 29.4±5.9 kg/m 2 , HbA1c 8.6±2.1%), a total of 136 (39%) deaths occurred. Compared with dippers (n=166), non-dippers (n=144) and reverse dippers (n=39) showed progressively higher prevalence of cardiac autonomic neuropathy (11%, 16% and 31%, respectively), low HRV (45% vs 53% vs 62%), 24-hour hypertension (40%, 60% and 67%), isolated nocturnal hypertension (5%, 27% and 49%), postural hypotension (14%, 26% and 43%), and lower prevalence of white-coat hypertension (31%, 17% and 13%). Reverse dippers and non-dippers had progressively lower mean overall survival (OS) compared with dippers (16.1±5.3 years, 17.5±5.3 years and 18.6±4.6 years, respectively). Reverse dippers also showed an increased risk of all-cause mortality after adjustment for age, sex, BMI, office SBP, plasma glucose, and diabetes duration and type (HR 2.3 [1.4-3.8]). Patients with low HRV had reduced mean OS than those with high HRV (16.9±5.5 and 18.8±4.4, respectively) but similar adjusted risk (HR 1.3 [0.9-1.9]). No significant interactions emerged between BP patterns, HRV and diabetes type on OS. Conclusions: Non-dipping and reverse dipping BP patterns are associated with an increased prevalence of cardiac autonomic neuropathy and reduced survival probability in diabetic patients over a 21-year follow-up, with reverse dipping more than doubling the adjusted risk of all-cause mortality.

Abstract 21: Sex Differences In Circadian Blood Pressure

Hypertensive patients frequently show a lack of 10% decline in nighttime (or nondipping) blood pressure (BP), which is a strong predictor of a cardiovascular event. Clock genes are essential regulators in diurnal BP in the vasculature during hypertension. However, little is known if vascular circadian clock factors influence BP rhythms in a sex-dependent manner. To test the hypothesis that AngII-induced hypertension disrupts the expression pattern of peripheral clock genes, male and female C57Bl/6J mice were subjected to AngII (700 ng/kg/min) infusion for two weeks. BP was measured by radiotelemetry (N=7/group). After two weeks, the animals were sacrificed during daytime or nighttime, and aortas were assessed for expression of clock genes (Per1, Per2, Bmal1) and estrogen receptors (ERα and GPER). Two-way ANOVA was used to compare light-dark cycle and AngII treatment effects. Hypertensive females (MAP: day 121 ± 9 vs. night 126 ± 10 mmHg, P=0.39; 7.3% dipping) but not males (MAP: day 128 ± 3 vs. night 140 ± 2 mmHg, P=0.01; &gt;10% dipping) developed a non-dipping phenotype. AngII-hypertension amplified the circadian pattern of Per1 in the male aorta but removed the Per1 circadian variation in the female aorta. AngII did not alter Per2 oscillation in the aorta of either sex. Bmal1 patterns were also amplified in males and reversed in females. In response to AngII, aortic ERα expression was augmented during the day in females (control 287 ± 14 vs. AngII 413 ± 42 copies/ng RNA; P=0.01) but not in males (P=0.34). Furthermore, GPER expression exhibited a circadian oscillation in control (day 9 ± 1 vs. night 20 ± 7.6 copies/RNA ng) and hypertensive males (day 12 ± 17 vs. night 20 ± 5 copies/RNA ng, P=0.04), but not in females. In conclusion, sex differences exist in non-dipping BP patterns and circadian disruption of estrogen receptors and clock genes Per1 and Bmal1 in the vasculature after AngII treatment. This data suggest that females may be more vulnerable to circadian disruption during hypertension.

Abstract P199: Circadian Contributions To Blood Pressure Variation Under Constant Conditions

The circadian clock is an endogenous biological timekeeper that responds to environmental changes and governs various physiological processes over a 24-hour cycle. Blood pressure (BP) variation is thought to be controlled by the circadian clock, but few studies have examined circadian control of BP in humans. Moreover, it is unknown whether nighttime BP dipping is driven by the circadian system or by external factors. We investigated whether the circadian system drives 24-hour rhythms in BP, including nighttime BP dipping, using a 30-hour constant routine (CR) protocol. The CR protocol controls for external factors, allowing circadian rhythms to be isolated and measured, by having participants lie in a semi-recumbent posture in dim light (&lt;10 lux) at a constant temperature, consume isocaloric snacks every 2 hours, and maintain wakefulness. To measure the BP rhythm, ambulatory BP was measured every 30 minutes (SpaceLabs 90227), and to measure the central circadian rhythm, core body temperature was measured every 10 seconds using an ingestible, wireless sensor (HQInc Core Body Temperature Wireless Data Record and Sensor). To date, 17 normotensive African American participants (13 females and 4 males), with a mean age of 37 (± 11.3) years and body mass index (BMI) of 32.5 kg/m 2 , have completed the study. Approximately 59% of participants (10 of 17) had non-dipping systolic BP at screening, defined as a &lt;10% decrease in mean systolic BP from daytime to nighttime. Under constant conditions, 94% of participants (16 of 17) had a non-dipping BP phenotype. Median systolic BP dipping was 0.8% for females and 2.2% for males. There was a robust rhythm in participants’ core body temperature but not BP, suggesting that the circadian clock may not contribute substantially to a nighttime decrease in BP in normotensive African Americans. Instead, the non-dipping BP phenotype is likely more so a result of behavioral and/or physiological sleep-related processes. Future research and interventions for non-dipping BP may need to target these underlying behavioral and physiological processes.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension-Pro Side of the Argument.

Lowering Nighttime Blood Pressure With Bedtime Dosing of Antihypertensive Medications: Controversies in Hypertension-Pro Side of the Argument.

Abstract MP14: Endothelial Cullin3 Mutation Causes Decreased Nitric Oxide (NO) Bioavailability And Vascular Dysfunction Through Protein Phosphatase 2A

Mutations in CULLIN3 gene (in-frame deletion of exon 9, termed Cul3Δ9) cause human hypertension (HT) driven by a combination of renal tubular and vascular mechanisms. To test the importance of endothelial Cul3 in vivo , we bred the conditionally activatable Cul3Δ9 mice with tamoxifen-inducible Tie2-CRE ERT2 mice. The resultant mice (E-Cul3Δ9) developed arterial stiffening (pulse wave velocity, 3.7±0.3 vs 2.7±0.1 m/s, n=5-7, p&lt;0.05) and a trend towards elevated nighttime blood pressure (peak systolic BP, E-Cul3Δ9 136±3 vs control 128±3 mmHg, n=9-11) that were not associated with any alterations in locomotion, food/water intake or sleep/wake behaviors. No difference was seen in daytime BP. To determine whether vascular remodeling impairs baroreflex function, we performed power spectral analysis. Heart rate (HR), low frequency/high frequency ratio of HR variability, and baroreflex gain were comparable between control and E-Cul3Δ9 mice, suggesting no change in cardiac sympathetic nerve activity. However, low frequency amplitude of arterial pressure variability (16±4 vs 7±2 mmHg 2 , n=5-9, p&lt;0.05) at night was markedly augmented in E-Cul3Δ9 mice, suggesting increased sympathetic activity in vascular tone regulation. Consistently, E-Cul3Δ9 mice exhibited impaired endothelial-dependent relaxation in carotid artery (max ACh relaxation: 69% vs 84%, n=5-7, p&lt;0.05) and cerebral resistance basilar artery (41% vs 77%, n=4-6, p&lt;0.05). However, no dilatory impairment in mesenteric resistance artery and no difference in smooth muscle function were observed, suggesting that the effects of Cul3Δ9 are arterial bed specific. Expression of Cul3Δ9 in primary mouse aortic endothelial cells markedly decreased wild type Cul3 protein, phosphorylated eNOS and NO production. Protein phosphatase (PP) 2A, a known Cul3 substrate, dephosphorylates eNOS. Therefore, we determined whether impaired eNOS activity was attributable to PP2A. Cul3Δ9-induced impairment of eNOS activity was rescued by a selective PP2A inhibitor okadaic acid (4nM), but not by a PP1 inhibitor tautomycetin (4nM). Thus, CUL3 mutations in the endothelium may contribute to human HT in part through decreased endothelial NO bioavailability, arterial stiffening and secondary sympathoexcitation.