Aims Carotid–femoral pulse wave velocity (PWV), a direct measure of aortic stiffness, has become increasingly important for total cardiovascular (CV) risk estimation. Its application as a routine tool for clinical patient evaluation has been hampered by the absence of reference values. The aim of the present study is to establish reference and normal values for PWV based on a large European population. Methods and results We gathered data from 16 867 subjects and patients from 13 different centres across eight European countries, in which PWV and basic clinical parameters were measured. Of these, 11 092 individuals were free from overt CV disease, non-diabetic and untreated by either anti-hypertensive or lipid-lowering drugs and constituted the reference value population, of which the subset with optimal/normal blood pressures (BPs) (n = 1455) is the normal value population. Prior to data pooling, PWV values were converted to a common standard using established conversion formulae. Subjects were categorized by age decade and further subdivided according to BP categories. Pulse wave velocity increased with age and BP category; the increase with age being more pronounced for higher BP categories and the increase with BP being more important for older subjects. The distribution of PWV with age and BP category is described and reference values for PWV are established. Normal values are proposed based on the PWV values observed in the non-hypertensive subpopulation who had no additional CV risk factors. Conclusion The present study is the first to establish reference and normal values for PWV, combining a sizeable European population after standardizing results for different methods of PWV measurement.

Determinants of pulse wave velocity in healthy people and in the presence of cardiovascular risk factors

Aims
Excessive arterial pulsatility may contribute to cognitive decline and risk of dementia via damage to the fragile cerebral microcirculation. We hypothesized that the intensity of downstream-travelling pulsatile waves measured by wave intensity analysis in the common carotid artery during mid- to late-life would be associated with subsequent cognitive decline.

Methods and results
Duplex Doppler ultrasound was used to calculate peak forward-travelling compression wave intensity (FCWI) within the common carotid artery in 3191 individuals [mean ± standard deviation (SD), age = 61 ± 6 years; 75% male] assessed as part of the Whitehall II study in 2003–05. Serial measures of cognitive function were taken between 2002–04 and 2015–16. The relationship between FCWI and cognitive decline was adjusted for sociodemographic variables, genetic and health-related risk factors, and health behaviours. Mean (SD) 10-year change in standardized global cognitive score was -0.39 (0.18). Higher FCWI at baseline was associated with accelerated cognitive decline during follow-up [difference in 10-year change of global cognitive score per 1 SD higher FCWI = −0.02 (95% confidence interval −0.04 to −0.00); P = 0.03]. This association was largely driven by cognitive changes in individuals with the highest FCWI [Q4 vs. Q1–Q3 = −0.05 (−0.09 to −0.01), P = 0.01], equivalent to an age effect of 1.9 years. Compared to other participants, this group was ∼50% more likely to exhibit cognitive decline (defined as the top 15% most rapid reductions in cognitive function during follow-up) even after adjustments for multiple potential confounding factors [odds ratio 1.49 (1.17–1.88)].

Conclusion
Elevated carotid artery wave intensity in mid- to late-life predicts faster cognitive decline in long-term follow-up independent of other cardiovascular risk factors.

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Carotid artery wave intensity in mid- to late-life predicts cognitive decline: The Whitehall II study

While there is a developing understanding of the influence of sleep on cardiovascular autonomic activity in humans, there remain unresolved issues. In particular, the effect of time within the sleep period, independent of sleep stage, has not been investigated. Further, the influence of sleep on central sympathetic nervous system (SNS) activity is uncertain because results using the major method applicable to humans, the low frequency (LF) component of heart rate variability (HRV), have been contradictory, and because the method itself is open to criticism. Sleep and cardiac activity were measured in 14 young healthy subjects on three nights. Data was analysed in 2-min epochs. All epochs meeting specified criteria were identified, beginning 2 h before, until 7 h after, sleep onset. Epoch values were allocated to 30-min bins and during sleep were also classified into stage 2, slow wave sleep (SWS) and rapid eye movement (REM) sleep. The measures of cardiac activity were heart rate (HR), blood pressure (BP), high frequency (HF) and LF components of HRV and pre-ejection period (PEP). During non-rapid eye movement (NREM) sleep autonomic balance shifted from sympathetic to parasympathetic dominance, although this appeared to be more because of a shift in parasympathetic nervous system (PNS) activity. Autonomic balance during REM was in general similar to wakefulness. For BP and the HF and LF components the change occurred abruptly at sleep onset and was then constant over time within each stage of sleep, indicating that any change in autonomic balance over the sleep period is a consequence of the changing distribution of sleep stages. Two variables, HR and PEP, did show time effects reflecting a circadian influence over HR and perhaps time asleep affecting PEP. While both the LF component and PEP showed changes consistent with reduced sympathetic tone during sleep, their pattern of change over time differed.

Autonomic activity during human sleep as a function of time and sleep stage

Components of the neurovascular unit (NVU) establish dynamic crosstalk that regulates cerebral blood flow and maintain brain homeostasis. Here, we describe accumulating evidence for cellular elements of the NVU contributing to critical physiological processes such as cerebral autoregulation, neurovascular coupling, and vasculo-neuronal coupling. We discuss how alterations in the cellular mechanisms governing NVU homeostasis can lead to pathological changes in which vascular endothelial and smooth muscle cell, pericyte and astrocyte function may play a key role. Because hypertension is a modifiable risk factor for stroke and accelerated cognitive decline in aging, we focus on hypertension-associated changes on cerebral arteriole function and structure, and the molecular mechanisms through which these may contribute to cognitive decline. We gather recent emerging evidence concerning cognitive loss in hypertension and the link with vascular dementia and Alzheimer’s disease. Collectively, we summarize how vascular dysfunction, chronic hypoperfusion, oxidative stress, and inflammatory processes can uncouple communication at the NVU impairing cerebral perfusion and contributing to neurodegeneration.

/pdf/vasculo-neuronal-coupling-and-neurovascular-coupling-at-the-2hb7cagoz1.pdf

Vasculo-Neuronal Coupling and Neurovascular Coupling at the Neurovascular Unit: Impact of Hypertension.

Background and Purpose— Aortic stiffening increases the transfers of high pressure and flow pulsatility to small cerebral vessels potentially causing the accumulation of vascular brain injury. Our aim was to investigate the prospective association of aortic stiffness with the risks of incident mild cognitive impairment and dementia.

Methods— We studied 1101 dementia-free Framingham Offspring study participants (mean age, 69±6 years; 54% women). Aortic stiffness was measured as carotid–femoral pulse wave velocity using applanation tonometry and modeled as a linear variable and the top 2 quintiles (>11.4 m/s). Outcomes were the 10-year risk of incident mild cognitive impairment and dementia, including clinically characterized Alzheimer disease. We observed 106, 77, and 59 events of mild cognitive impairment, all-cause dementia, and clinical Alzheimer disease, respectively.

Results— After adjustment for age and sex, higher continuous aortic stiffness predicted an increased risk of mild cognitive impairment (hazard ratio, 1.40 [95% confidence interval, 1.13–1.73]), all-cause dementia (hazard ratio, 1.45 [95% confidence interval, 1.13–1.87]), and Alzheimer disease (hazard ratio, 1.41 [95% confidence interval, 1.06–1.87]). In risk factor–adjusted statistical models, aortic stiffness remained a significant predictor of mild cognitive impairment but not incident dementia. In nondiabetic patients, the top 2 quintiles of aortic stiffness were associated with a higher risk of incident all-cause dementia across all statistical models.

Conclusions— Aortic stiffness was an independent predictor of incident mild cognitive impairment in the whole sample and with incident dementia in nondiabetic patients. Our findings suggest aortic stiffness as a potentially modifiable risk factor for clinical cognitive impairment and dementia.

Aortic stiffness and the risk of incident mild cognitive impairment and dementia

Structural and functional dysfunction in both the macro- and microvasculature are a feature of essential hypertension. In a healthy cardiovascular system, the elastic properties of the large arteries ensure that pulsations in pressure and flow generated by cyclic left ventricular contraction are dampened, so that less pulsatile pressure and flow are delivered at the microvascular level. However, in response to aging, hypertension, and other disease states, arterial stiffening limits the buffering capacity of the elastic arteries, thus exposing the microvasculature to increased pulsatile stress. This is thought to be particularly pertinent to high flow/low resistance organs such as the brain and kidney, which may be sensitive to excess pressure and flow pulsatility, damaging capillary networks, and resulting in target organ damage. In this review, we describe the clinical relevance of the pulsatile interaction between the macro- and microvasculature and summarize current methods for measuring the transmission of pulsatility between the two sites.

/pdf/measuring-the-interaction-between-the-macro-and-micro-2njre3ti2r.pdf

Measuring the Interaction Between the Macro- and Micro-Vasculature

Multi-omics applied to fibromuscular dysplasia: first steps on a new research avenue.

This study reports on a multivariate complexity assessment for cardiovascular dynamics during REM sleep leading to a dream recall. Heart rate variability, as well as systolic and diastolic time interval variability series were gathered from eight volunteers during night sleep, and were considered input of a trivariate Multichannel Complexity Index (MCI) analysis. MCI is a recently proposed index based on a multivariate phase space reconstruction accounting for the intrinsic nonlinearity of the autonomic nervous system dynamics. Results show a significant MCI decrease during REM sleep epochs followed by a dream recall as compared to those associated with no dream recall (p < 10−18). This implies a lower interplay between complex cardiovascular subcomponents during dreaming, complementing current psychophysiological correlates of sleep.

Multichannel Complexity Index Analysis for Cardiovascular Dynamics associated with a Dream Recall

Dreams may be recalled after awakening from sleep following a defined electroencephalographic pattern that involves local decreases in low-frequency activity in the posterior cortical regions. While a dreaming experience implies bodily changes at many organ-, system-, and timescale-levels, the entity and causal role of such peripheral changes in a conscious dream experience are unknown. We performed a comprehensive, causal, multivariate analysis of physiological signals acquired during REM sleep at night, including high-density EEG and peripheral dynamics including electrocardiography and blood pressure. In this preliminary study, we investigated multiple recalls and non-recalls of dream experiences using data from nine healthy volunteers. The aim was not only to investigate the changes in central and autonomic dynamics associated with dream recalls and non-recalls, but also to characterize the central-peripheral dynamical and (causal) directional interactions, and the temporal relations of the related arousals upon awakening. We uncovered a brain-body network that drives a conscious dreaming experience that acts with specific interaction and time delays. Such a network is sustained by the blood pressure dynamics and the increasing functional information transfer from the neural heartbeat regulation to the brain. We conclude that bodily changes play a crucial and causative role in a conscious dream experience during REM sleep.

Rosa Maria Bruno

Papers

Measuring the Interaction Between the Macro- and Micro-Vasculature

Multi-omics applied to fibromuscular dysplasia: first steps on a new research avenue.

Multichannel Complexity Index Analysis for Cardiovascular Dynamics associated with a Dream Recall

Activation of brain-heart axis during REM sleep: a trigger for dreaming