OBSERVED EFFECTS OF BODY MASS INDEX ON BLOOD PRESSURE DIPPING PATTERN, IN A PRIVATE HOSPITAL IN ABUJA, NIGERIA

During a normal 24-hour ambulatory blood pressure monitoring (ABPM), there should be a more than 10% drop in average nighttime blood pressure (BP), compared to the average daytime BP. This is called the normal ABPM dipping pattern. Abnormal dipping patterns occur when the average night-time blood pressure drop is lower than 10%. A high body mass index has been described as a contributing factor for unusual ABPM dipping patterns, which predisposes an individual to a higher likelihood of developing cardiovascular disease. The goal of this research was to assess the link between the body mass index (BMI) and the dipping pattern during ABPM in the adult population who underwent ABPM at Cardiocare Abuja. Anthropometric data from 100 patients who had done ABPM were used, together with data obtained from the CONTEC ABPM50 device. The BMI was calculated with the weight and height, and they were grouped into weight classes using their BMI. The proportions of the various dipping patterns were then determined within each class. Majority of the participants involved in the study had BMI between 30-39 kg/m2. Those who presented with higher BMI classes were also discovered to have unusual dipping patterns, indicating a link with relation to the BMI and the ABPM dipping pattern. In the morbidly obese class, with BMI >40 kg/m2 there was a trend of the reverse dipping. It concluded that ABPM should be done routinely for persons with a high BMI for early detection of unusual dipping patterns and prompt intervention.

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

Objectives: 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.Methods: 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.Results: 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).Conclusion: 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. Ethn Dis. 2021;31(4):481-488; doi:10.18865/ed.31.4.481

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

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. FUNDunding Acknowledgement Type of funding sources: None. Figure 1

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<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<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<0.05) and cerebral resistance basilar artery (41% vs 77%, n=4-6, p<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.

Nocturnal Hypertension and Heart Failure: Mechanisms, Evidence, and New Treatments

Heart failure (HF) is a common condition with an increasing prevalence. Despite a variety of evidence-based treatments for patients with HF with reduced ejection fraction, morbidity and mortality rates remain high. Furthermore, there are currently no treatments that have yet been shown to reduce complication and death rates in patients who have HF with preserved ejection fraction. Hypertension is a common comorbidity in patients with HF, contributing to disease development and prognosis. For example, hypertension is closely associated with the development of left ventricular hypertrophy, which an important precursor of HF. In particular, nighttime blood pressure (BP) appears to be an important, modifiable risk factor. Both nighttime BP and an abnormal circadian pattern of nighttime BP dipping have been shown to predict development of HF and the occurrence of cardiovascular events, independent of office BP. Key mechanisms for this association include sodium handling/salt sensitivity and increased sympathetic activation. These pathogenic mechanisms are targeted by several new treatment options, including sodium-glucose cotransporter 2 inhibitors, angiotensin receptor neprilysin inhibitors, mineralocorticoid receptor antagonists, and renal denervation. All of these could form part of antihypertensive strategies designed to control nighttime BP and contribute to the goal of achieving perfect 24-hour BP management. Nevertheless, additional research is needed to determine the effects of reducing nighttime BP and improving the circadian BP profile on the rate of HF, other cardiovascular events, and mortality.