The physiologic complexity of beat-to-beat blood pressure is associated with age-related alterations in blood pressure regulation.

The fluctuations in resting-state beat-to-beat blood pressure (BP) are physiologically complex, and the degree of such BP complexity is believed to reflect the multiscale regulation of this critical physiologic process. Hypertension (HTN), one common age-related condition, is associated with altered BP regulation and diminished system responsiveness to perturbations such as orthostatic change. We thus aimed to characterize the impact of HTN on resting-state BP complexity, as well as the relationship between BP complexity and both adaptive capacity and underlying vascular characteristics. We recruited 392 participants (age: 60-91 years), including 144 that were normotensive and 248 with HTN (140 controlled- and 108 uncontrolled-HTN). Participants completed a 10-min continuous finger BP recording during supine rest, then underwent measures of lying-to-standing BP change, arterial stiffness (i.e., brachial-ankle pulse wave velocity), and endothelial function (i.e., flow-mediated vasodilation). The complexity of supine beat-to-beat systolic (SBP) and diastolic (DBP) BP was quantified using multiscale entropy. Thirty participants with HTN (16 controlled-HTN and 14 uncontrolled-HTN) exhibited orthostatic hypotension. SBP and DBP complexity was greatest in normotensive participants, lower in those with controlled-HTN, and lowest in those in uncontrolled-HTN (p < 0.0005). Lower SBP and DBP complexity correlated with greater lying-to-standing decrease in SBP and DBP level (ß = -0.33 to -0.19, p < 0.01), greater arterial stiffness (ß = -0.35 to -0.18, p < 0.01), and worse endothelial function (ß = 0.17-0.22, p < 0.01), both across all participants and within the control- and uncontrolled-HTN groups. These results suggest that in older adults, BP complexity may capture the integrity of multiple interacting physiologic mechanisms that regulate BP and are important to cardiovascular health.

The alterations in multiple neurophysiological procedures are associated with frailty phenotype in older adults.

Background: Older adults oftentimes suffer from the conditions in multiple physiologic systems, interfering with their daily function and thus contributing to physical frailty. The contributions of such multisystem conditions to physical frailty have not been well characterized. Methods: In this study, 442 (mean age = 71.4 ± 8.1 years, 235 women) participants completed the assessment of frailty syndromes, including unintentional weight loss, exhaustion, slowness, low activity, and weakness, and were categorized into frail (≥3 conditions), pre-frail (1 or 2 conditions), and robust (no condition) status. Multisystem conditions including cardiovascular diseases, vascular function, hypertension, diabetes, sleep disorders, sarcopenia, cognitive impairment, and chronic pain were assessed. Structural equation modeling examined the interrelationships between these conditions and their associations with frailty syndromes. Results: Fifty (11.3%) participants were frail, 212 (48.0%) were pre-frail, and 180 (40.7%) were robust. We observed that worse vascular function was directly associated with higher risk of slowness [standardized coefficient (SC) = -0.419, p < 0.001], weakness (SC = -0.367, p < 0.001), and exhaustion (SC = -0.347, p < 0.001). Sarcopenia was associated with both slowness (SC = 0.132, p = 0.011) and weakness (SC = 0.217, p = 0.001). Chronic pain, poor sleep quality, and cognitive impairment were associated with exhaustion (SC = 0.263, p < 0.001; SC = 0.143, p = 0.016; SC = 0.178, p = 0.004, respectively). The multinomial logistic regression showed that greater number of these conditions were associated with increased probability of being frail (odds ratio>1.23, p < 0.032). Conclusion: These findings in this pilot study provide novel insights into how multisystem conditions are associated with each other and with frailty in older adults. Future longitudinal studies are warranted to explore how the changes in these health conditions alter frailty status.

The Next Frontier in Noninvasive Prenatal Diagnostics: Cell-Free Fetal DNA Analysis for Monogenic Disease Assessment.

With the widespread clinical adoption of noninvasive screening for fetal chromosomal aneuploidies based on cell-free DNA analysis from maternal plasma, more researchers are turning their attention to noninvasive prenatal assessment for single-gene disorders. The development of a spectrum of approaches to analyze cell-free DNA in maternal circulation, including relative mutation dosage, relative haplotype dosage, and size-based methods, has expanded the scope of noninvasive prenatal testing to sex-linked and autosomal recessive disorders. Cell-free fetal DNA analysis for several of the more prevalent single-gene disorders has recently been introduced into clinical service. This article reviews the analytical approaches currently available and discusses the extent of the clinical implementation of noninvasive prenatal testing for single-gene disorders.

The Multiscale Dynamics of Beat-to-Beat Blood Pressure Fluctuation Links to Functions in Older Adults.

Background: The blood pressure (BP) is regulated by multiple neurophysiologic elements over multiple temporal scales. The multiscale dynamics of continuous beat-to-beat BP series, which can be characterized by "BP complexity", may, thus, capture the subtle changes of those elements, and be associated with the level of functional status in older adults. We aimed to characterize the relationships between BP complexity and several important functions in older adults and to understand the underlying factors contributing to BP complexity. Method: A total of 400 older adults completed a series of clinical and functional assessments, a finger BP assessment of at least 10 min, and blood sample and vessel function tests. Their hypertensive characteristics, cognitive function, mobility, functional independence, blood composition, arterial stiffness, and endothelial function were assessed. The complexity of systolic (SBP) and diastolic (DBP) BP series was measured using multiscale entropy. Results: We observed that lower SBP and DBP complexity was significantly associated with poorer functional independence (ß > 0.17, p < 0.005), cognitive function (ß > 0.45, p = 0.01), and diminished mobility (ß < -0.57, p < 0.003). Greater arterial stiffness (ß < -0.48, p = 0.02), decreased endothelial function (ß > 0.42, p < 0.03), and excessed level of blood lipids (p < 0.03) were the main contributors to BP complexity. Conclusion: Blood pressure complexity is closely associated with the level of multiple functional statuses and cardiovascular health in older adults with and without hypertension, providing novel insights into the physiology underlying BP regulation. The findings suggest that this BP complexity metric would serve as a novel marker to help characterize and manage the functionalities in older adults.

The Multiscale Dynamics of Beat-to-Beat Blood Pressure Fluctuation Mediated the Relationship Between Frailty and Arterial Stiffness in Older Adults.

BACKGROUND: Beat-to-beat blood pressure (BP) is an important cardiovascular output and regulated by neurophysiological elements over multiple temporal scales. The multiscale dynamics of beat-to-beat BP fluctuation can be characterized by "BP complexity" and has been linked to age-related adverse health outcomes. We here aimed to examine whether BP complexity mediates the association between arterial stiffness and frailty. METHOD: This cross-sectional study was completed between January and October 2021. A total of 350 older adults completed assessments for frailty, arterial stiffness (ie, average brachial-ankle pulse wave velocity), and beat-to-beat finger BP. The complexity of beat-to-beat systolic blood pressure (SBP) and diastolic blood pressure (DBP) BP series was measured using multiscale entropy. The relationships between frailty, BP complexity, and arterial stiffness were examined using analysis of variance and linear regression models. The effects of BP complexity on the association between arterial stiffness and frailty were examined using mediation analyses. RESULTS: Compared with non-frail, prefrail, and frail groups had significantly elevated lower SBP and DBP complexity (F > 11, p < .001) and greater arterial stiffness (F = 16, p < .001). Greater arterial stiffness was associated with lower BP complexity (ß < -0.42, p < .001). Beat-to-beat SBP and DBP complexity mediated the association between arterial stiffness and frailty (indirect effects >0.28), accounting for at least 47% of its total effects on frailty (mediated proportion: SBP: 50%, DBP: 47%). CONCLUSION: This study demonstrates the association between BP complexity and frailty in older adults, and BP complexity mediates the association between arterial stiffness and frailty, suggesting that this metric would serve as a marker to help characterize important functions in the older adults.