Objectives:In hemodialysis patients, central hemodynamics, stiffness, and wave reflections assessed through ambulatory blood pressure monitoring (ABPM) showed superior prognostic value for cardiovascular (CV) events than peripheral blood pressures (BPs). No such evidence is available for lower-risk hypertensive patients.Methods:In 591 hypertensive patients (mean age 58 +/- 14 years, 49% males), ambulatory brachial and central BP, pulse wave velocity (PWV), and augmentation index (AIx) were obtained with a validated upper arm cuff-based pulse wave analysis technology. Information on treatment for hypertension (73% of patients), dyslipidemia (27%), diabetes (8%), CV disease history (25%), was collected. Patients were censored for CV events or all-cause death over 4.2 years.Results:One hundred and four events (24 fatal) were recorded. Advanced age [hazard ratio and 95% confidence interval: 1.03 (1.01, 1.05), P = 0.0001], female sex [1.57 (1.05, 2.33), P = 0.027], CV disease [2.22 (1.50, 3.29), P = 0.0001], increased 24-h central pulse pressure (PP) [1.56 (1.05, 2.31), P = 0.027], PWV [1.59 (1.07, 2.36), P = 0.022], or AIx [1.59 (1.08, 2.36), P = 0.020] were significantly associated with a worse prognosis (univariate Cox regression analysis). The prognostic power of peripheral and central BPs was lower. However, PWV [1.02 (0.64, 1.63), P = 0.924], AIx [1.06 (0.66, 1.69), P = 0.823], and central PP [1.18 (0.76, 1.82), P = 0.471], were not significant predictors in multivariate analyses.Conclusions:In hypertensive patients, ambulatory central PP, PWV, and AIx are associated with an increased risk of CV morbidity and all-cause mortality. However, this association is not independent of other patient characteristics.

Isolated systolic hypertension in the young (ISHY) remains a challenging problem, partly due to the differences in central aortic pressure observed in studies investigating ISHY. The fundamental relationship between heart rate and central aortic pressure, and more precisely, the relationship between heart rate and amplification of central aortic pressure in the periphery, underpins the assessment and, as a consequence, the treatment of ISHY. Physiology warrants that an increase in heart rate would lead to increased amplification of the pressure pulse between the aorta and the brachial artery. Heart rate generally decreases with age, in particular over the first two decades of life. Thus, a higher heart rate in the young would result in higher pulse pressure amplification, and therefore an elevated brachial systolic pressure would not necessarily translate to elevated aortic systolic pressure. However, elevated heart rate is not a consistent feature in ISHY, and studies have shown that ISHY can present with either high or low central aortic systolic pressure. In this brief review, we summarize the physiological aspects underlying the relationship between heart rate and central aortic blood pressure and its amplification in the brachial artery, how this relationship changes with age, and examine the implications of these effects on the assessment and treatment of ISHY.

Alzheimer’s disease (AD) neuropathology begins 20 to 30 years before clinical diagnosis. Thus, there is an opportunity to implement strategies to prevent the progression of AD. Insulin resistance in the brain causes a disruption in glucose utilisation. Medium-chain fatty acids (MCFA) are readily available substrates for the synthesis of ketone bodies (KB), which are an alternative brain fuel not controlled by insulin. A constant supply of KB may close the energy gap in the AD-prone brain, and in doing so prevent or delay symptom onset, or protect the brain from further degeneration. There is increasing evidence that multidomain lifestyle interventions with dietary components significantly impact cognitive decline. Yet, these interventions have not considered the effects MCFA supplementation, to ensure sufficient energy for the brain. This is a phase II placebo-controlled, randomised double-blind 24-month intervention trial of MCFA supplementation within the AUstralian-multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention (AU-ARROW) study, to investigate the additive effect of MCFA supplementation in older adults at increased risk of AD. A total of 124 participants will be recruited aged 60-79 years, with subjective cognitive decline. Participants will be randomised 1:1 into either the intervention or placebo groups and will consume 3 daily doses at 15mL per dose of either MCFA or placebo supplement whilst continuing the AU-ARROW protocol, which includes dietary education, physical activity, brain training, and health education. The primary outcomes involve statistical assessment of cognition, blood ketone body levels, and brain glucose utilisation. At baseline, and every 6 months, participants will have fasting blood samples collected. At baseline, 12, and 24 months, participants will undergo cognitive assessments. At baseline and 24 months, participants will undergo fluorodeoxyglucose positron emission tomography scans to determine brain glucose utilisation. The final protocol is expected to maximise data collection and analyses. Combined with AU-ARROW, it will allow for a) the implementation of MCFA supplementation guidelines in a plan to reduce cognitive decline and risk of AD, b) the determination of effects of MCFA consumption on neuroimaging and blood-based biomarkers, and c) the comparison of between subject differences.

Medium-chain triglycerides (MCT), unlike other type of fats, are quickly digested into medium-chain fatty acids (MCFA), which are metabolized by the liver into energy in the form of ketones. Ketones are then transported to the brain for energy supply. In Alzheimer’s disease (AD), the brain becomes less efficient in glucose uptake and metabolism, resulting in an energy deficiency. The only backup source of energy for the brain is ketones. In this study we examined the potential for MCT to serve as a fuel source during energy deprivation, such as what is observed in AD. Healthy males and females aged 50 to 77 years old (n=19) consumed MCT oil (40% caprylic acid, 28% capric acid, 32% lauric acid) for 7 weeks. The National Institutes of Health (NIH) Executive Abilities: Measures and Instruments for Neurobehavioral Evaluation and Research (EXAMINER) neuropsychological battery was administered at baseline, midway and last appointment. Participants could discontinue at any time during the intervention period. Descriptive statistics determined the data were not normally distributed, therefor a non-parametric Wilcoxon Rank Test was performed to compare cognitive performance at baseline to mid-way, and baseline to last appointment. Baseline to mid-way analyses showed significant (α=.05) improvement in performance for the Continual Performance Task (CPT) (p=0.012), N-Back-2 (p=0.049), and anti-saccade (p=0.036). Baseline to last analyses showed significant improvement (α=.05) in performance for the CPT task (p=0.034), N-Back-1 (p=0.027), N-Back-2 (p=0.038), and saccades (p=0.036). Both the N-back-1 and Saccades measures for baseline to mid-way analyses approached significance. No significant changes were observed in the remaining tasks of the NIH EXAMINER. MCT oil may improve working memory, inhibitory processing, problem solving, and motor control in older adults with no currently diagnosed memory problems. However, a further longitudinal study with a larger sample size is required to validate these preliminary results.

Objective: Single point calibration is common in cuffless blood pressure (BP) measurement devices. Consequently, they may be apt at re-assessing BP at that same calibration BP but have potential for increased error as BP changes from that calibration point. This study investigates one pulse waveform-based (BPro, HealthStats) and one pulse arrival time-based (Maisense Freescanâ) cuffless device in their tracking of BP changes as compared to that of conventional cuff-based oscillometric devices. Design and method: 14 participants had 24-hour assessment of BP using BPro and a validated cuff-based oscillometric device (BPLab, Petr Telegin). Nocturnal BP dipping as measured by both devices was compared. In a separate study, six participants had BP measured with a validated cuff-based oscillometric device (OMRONâ HEM-7121) and either the BPro (n = 3) or Freescanâ device (n = 3) before and during a 2-minute cold-pressor challenge. BP change from baseline as reported by the devices were compared. Results: Average nocturnal fall in BP (mean ± SD) as reported by the cuff-based device and BPro were -15 ± 8% and -10 ± 6% (p = 0.061), respectively, for systolic BP; -19 ± 8% and -10 ± 7% (p = 0.008), respectively, for diastolic BP. Nocturnal dipping (defined as nocturnal fall > 10% in either systolic or diastolic BP) was detected in 6 participants with the BPro device as opposed to 14 as detected with the cuff-based device. During cold-pressor challenge, Freescanâ reported a systolic BP change of -4 ± 8 mmHg compared to the cuff measured change of 12 ± 8 mmHg (p = 0.017). BPro followed a similar trend to the Freescanâ device and reported a systolic BP change of -2 ± 2 mmHg compared to the cuff measured change of 14 ± 4 mmHg (p = 0.002). Conclusions: The BPro device was able to track nocturnal dipping in some but not all participants, with significant underestimation of nocturnal dipping in diastolic BP. Cold-pressor challenge induced BP changes that were unable to be detected by the cuffless devices. Whilst single point calibration may permit a cuffless device to assess when BP returns to that calibration point, tracking of BP changes appears to be inconsistent. Further investigation is required to understand the underlying factors that contribute to this inconsistency.

Medium-chain fatty acids (MCFA) are quickly absorbed and transported to the liver. Where they are preferentially metabolised into energy and ketone bodies, as compared to long-chain fatty acids. Ketone bodies are then transported to the brain and other tissues for energy supply. This makes MCFA the ideal energy source for patients with conditions in which energy deprivation is observed, such as Alzheimer’s disease (AD). In AD, insulin resistance in the brain causes partial glucose deprivation. However, the brain is still able use ketone bodies for energy. Despite the MCFA potential, to our knowledge, a dose effect study has not been previously done in older adults, This sequential feeding study involved 20 healthy adults aged 50 to 77 years. Participants consumed 3 daily doses of MCFA oil (40% caprylic acid, 28% capric acid, 32% lauric acid) for 7 weeks, doses were increased in 15 mL/day every week (0mL/day in week 1 increasing to 90mL/day in week 7). At baseline and at the end of each week, participants had their anthropometric measurements taken, donated fasting blood and underwent a 2-hour postprandial analysis. Participation could be discontinued at any time. Change in postprandial area under the curve for ketone body levels increased compared to baseline in 45% with 5mL (n=20), 42% with 10mL (n=19), 74% with 15mL (n=19), 73% with 20mL (n=15), 79% with 25mL (n=14), 100% with 30mL (n=11), and 75% with 35mL (n=8). However, there were no significant changes in body mass index (BMI), fasting triglycerides and total, low-density lipoprotein and high-density lipoprotein cholesterol, Supplementation with MCFA oil increased postprandial ketone levels in a dose dependent manner, without a significant impact to blood lipids or BMI. However, further investigation is warranted to correlate this increase in postprandial ketone with its brain uptake and utilisation.

The importance of the arterial blood pressure pulse has been recognized since ancient times, and from then to the present, the interaction of the observer and the patient has progressed in gradual steps. It evolved from the presence of a palpable arterial pulse, being accepted as a sign of life and health condition, to the registration of the features of the arterial pulse as the first ever graphical representation of any physiological parameter in medicine, culminating in the quantification of the tension in the arterial wall as a measurement of arterial “blood pressure.”[1] The current acceptance of high blood pressure (hypertension) as a major cardiovascular risk can claim to have part of its origins in the actuarial and data gathering endeavors of life insurance companies.[2] The ubiquitous use of the brachial cuff sphygmomanometer in the early 20th century enabled collection of numerical data on blood pressure over long periods. The accumulation of blood pressure measurements also enabled data to be collected across the whole human life span. This demonstrated that in the otherwise healthy population, that is, in the normal population with no symptoms of overt ill health, there was a wide range of blood pressure values. Systolic blood pressure varied much more than diastolic blood pressure but increased with age. Since blood pressure was thought to be related to (and drive) tissue and organ perfusion, the marked increase in blood pressure was thought to be essential for adequate blood flow, as is required for efficient organ function. Hence, the concept of “essential hypertension”[3] was used to describe this condition of elevated blood pressure as being due to the essential readjustment of the cardiovascular system to accommodate age-related changes that occur in the vasculature (such as reduced capillary density with sequelae of increased peripheral resistance, hence requiring a higher pressure for adequate tissue perfusion). However, calculations of risk of morbidity and mortality (perhaps related to the forecasting of life insurance premiums) showed that those with elevated diastolic pressure were at higher risk of clinical and multiorgan complications affecting their health. Hence, the accepted notion of how to qualitatively understand elevated blood pressure was that it was essential that mean blood pressure would increase with age (leading to essential hypertension, with no overt symptoms or identifiable cause), that systolic pressure was mainly related to the strength of cardiac contraction (and so related to stroke volume), and that hypertension-related health complications were mainly associated with high diastolic pressure,[4] presumably as diastolic pressure was thought to be more closely associated with total peripheral vascular resistance. However, with accumulation of information from many large epidemiological studies in the latter part of the 20th century, and in particular with longitudinal and generational data from the Framingham Heart Study,[5] it is now accepted that systolic pressure is the major blood pressure component that is related to cardiovascular risk of morbidity and mortality.[6] Systolic pressure shows a much more pronounced increase with age compared to diastolic pressure, and that, in fact, diastolic pressure actually tends to decrease in the latter two decades of life, with the majority of hypertension in the elderly being categorized as “isolated systolic hypertension.” This implies that it is the pulse pressure that shows the most pronounced increase with age, in particular after the sixth decade of life.[7] This marked increase in pulse pressure is not related to changes in stroke volume, which can also show a slight reduction with age, but rather to the known increase of arterial stiffness with age; and arterial stiffness itself has been shown to be an independent factor of cardiovascular risk.[8] While arterial blood pressure is perhaps the most widely measured physiological parameter in clinical medicine, with methods that have essentially not changed since the inception of the brachial sphygmomanometer in late 19th and early 20th century, it still presents formidable challenges in how to improve the understanding of the effects of high blood pressure on endorgan damage leading to health complications. It is some of these important challenges that are addressed in the series of comprehensive review articles and commentaries in this Special Issue of Hypertension Journal presented by investigators and G u e s t E d i t o r i a l

Alzheimer's disease (AD) is the most common form of dementia. Currently, there is no effective medication for the prevention or treatment of AD. This has led to the search for alternative therapeutic strategies. Coconut oil (CO) has a unique fatty acid composition that is rich in medium chain fatty acids(MCFA), a major portion of which directly reaches the liver via the portal vein, thereby bypassing the lymphatic system. Given that brain glucose hypometabolism is a major early hallmark of AD, detectable well before the onset of symptoms, ketone bodies from MCFA metabolism can potentially serve as an alternative energy source to compensate for lack of glucose utilisation in the brain. Additionally, neuroprotective antioxidant properties of CO have been attributed to its polyphenolic content. This review discusses how the metabolism of CO and MCFA may aid in compensating the glucose hypometabolism observed in the AD brain. Furthermore, we present the current evidence of the neuroprotective properties of CO on cognition, amyloid-beta pathogenicity, inflammation and oxidative stress. The current review addresses the influence of CO/MCFA on other chronic disorders that are risk factors for AD, and addresses existing gaps in the literature regarding the use of CO/MCFA as a potential treatment for AD.

Elevated blood pressure (BP) relates to long-term prognosis including the development of heart failure (HF),[1] and its control will effectively prevent HF.[2] In addition to absolute systolic and diastolic pressures, recording widened pulse pressure, patterns of variability, ambulatory BP phenotypes, and even non-linear patterns of pressure values provide mechanistic insights into the pathophysiology of complicated hypertension. Nonetheless, the brachial cuff BP can have limited value in informing the development of the left ventricular hypertrophy (LVH) and complex evolution of HF later in hypertension. HF is not always heralded by the presence of LVH despite the presence of impaired diastolic function.[3] Structural remodeling, which follows treatment of hypertension or HF, may occur within the myocardium as well as in large conduit arteries,[4] with limited structural and functional information provided by brachial cuff measurements. Central aortic BP also relates to prognosis, ventricular remodeling, and complications of hypertension.[5] Its effects in hypertension can be seen through the differential influence of medications or heart rate.[6] Due to the heart rate dependence of pulse amplification between the aorta and brachial artery,[7] betablockers have been shown to have a reduced effect on regression of LVH compared to other antihypertensive agents for a similar decrease in brachial systolic pressure.[8,9] Being a more proximate measure of the ventricular-arterial (V-A) coupling interface, it may more closely reflect LV loading conditions; however, large cohort studies are awaited to establish the clinical value of central aortic pressure in treatment and management of hypertension and associated cardiac complications.[10] The definition and onset detection of HF, which is a clinical syndrome, remains multifaceted[11] and cannot be evaluated by simply recording arterial pressures. Even though hypertension is a risk factor for the development of HF, a rise in BP accompanies clinical improvement and predicts a better prognosis in HF.[12] Despite the increased understanding of various phenotypes of hypertension,[13,14] it remains unclear which are the best parameters obtained from a 24 h ambulatory BP recording,[15] for example, which influence or promote LVH and predict the development of HF. Abstract

AbstractBackgroundThe highly encouraging findings from the Finnish Geriatric Intervention Study (known as FINGER) led to the global initiative for dementia risk reduction known as world‐wide FINGERS (WW FINGERS). As part of the collaboration, our Australian AU‐ARROW trial will follow the general protocol of the FINGER trial, and will also be aligned with the U.S. arm of the study, US‐POINTER, though will have minor cultural and dietary modifications to determine the validity of the intervention in an Australian setting.MethodAU‐ARROW is a randomised, single‐blind 2‐year clinical trial that will recruit 600 participants aged 60‐79 satisfying specific inclusion/exclusion criteria, including normal cognition and one or more cardiovascular risk factors that place them at greater risk of cognitive decline. Participants will be distributed across two sites (a) Macquarie University Health Clinics, Sydney, NSW and (b) Sarich Neuroscience Research Institute, Edith Cowan University, Perth, WA, and will be randomised equally into either the innovative multi‐modal intervention group or the study control group, who will receive general lifestyle advice and annual health check‐ups, without treatment. Multi‐modal intervention consists of aerobic exercise, resistance training and stretching; dietary advice with monitoring to encourage adherence to the MIND diet; cognitive training sessions via the Brain HQ computerised online training system; and medical monitoring and regular health education sessions. Heart rate trackers, diet and exercise log books, and the monitoring of Brain HQ sessions will all help with adherence. Primary outcome measure is improvement in global cognitive score, measured using neurocognitive tests identical to those in the US‐POINTER protocol. Additional neurocognitive tests, physical function improvements, detailed diet monitoring and sleep monitoring will provide added data. The unique extra value of AU‐ARROW trial consists of the testing for Alzheimer’s disease (AD) blood biomarkers in all participants; as well as the AD Aβ amyloid‐specific ligand‐PET imaging, brain MRI and retinal biomarker tests that half of the participants will undergo. These tests will provide comprehensive data which have the ultimate purpose of increasing knowledge of the preclinical stages of AD, and help not only to develop preclinical AD diagnostic tests but also efficacy of AU‐ARROW’s intervention.

Congestive Heart Failure accounted for 16,757 hospital admissions between 2016-2017 in NSW.[1]Multiple contributors“ACI - CHF Clinical Documentation Audit Statewide Report”. Audit and Improvement Team, Clinical Information and Decision Support, System Transformation Evaluation and Patient Experience. Agency for Clinical Innovation, 2019Google Scholar Length of stay varied between 1-69 days, with median length of stay being 5.3 days in metropolitan areas.[1]Multiple contributors“ACI - CHF Clinical Documentation Audit Statewide Report”. Audit and Improvement Team, Clinical Information and Decision Support, System Transformation Evaluation and Patient Experience. Agency for Clinical Innovation, 2019Google Scholar 18.3% of patients were readmitted in 28 days with a principal diagnosis of heart failure [[1]Multiple contributors“ACI - CHF Clinical Documentation Audit Statewide Report”. Audit and Improvement Team, Clinical Information and Decision Support, System Transformation Evaluation and Patient Experience. Agency for Clinical Innovation, 2019Google Scholar]. After piloting a model for early review post discharge successfully, we present 2 years of data to demonstrate sustained reductions in readmission rates and patient outcomes. Inpatients were recruited from Ryde Hospital, who had been admitted with a principal/secondary diagnosis of heart failure, and had been treated by/or consulted by the cardiology team for heart failure optimisation. Patients were seen within an average of 9.54 days of discharge, and had blood tests prior to review. In its second year, the clinic was run as a registrar-led clinic. Every patient received one appointment and were followed up with their regular cardiologist, or advised to present to ED for review. Unplanned readmission rates in 28 days have been 5.95% over one year (2019), and 6.7% over 2 years (2019-20). 92.5% of patients underwent a medication change at the review. Patient reported feedback was also very positive. Following the initial success of the clinic, improvements in readmission and patient outcomes have been sustained and remain higher than that of larger peer hospitals. The findings suggest that this model would be a valuable addition to any hospital which manages heart failure.

Background and Aim: Heart failure is one of the leading causes for hospitalisation and imposes a significant economic burden on the health system. Atrial fibrillation affects one in three patients with heart failure (REF), and is a common cause of heart failure admission. The aim of our study is to evaluate the impact of AF-related heart failure (HF) admissions relative to admissions for HF without AF. Method: Patients admitted to Ryde Hospital with a primary diagnosis of decompensated HF in the time period of Jan-2018 to Dec-2018 were evaluated. We grouped patients based on the primary cause of decompensation (AF vs Non AF). We compared admission indices including length of stay and complications during admission. Results: 164 patients were included (Group 1: AF-related decompensation, n = 56; Group 2: Non-AF-related decompensation n = 108). The mean age was (84.59 ± 8.2SD, 45.7% females). 48% of patients had history of ischaemic heart disease, 14.9% had COPD, and 28.4% had diabetes mellitus. On between-group analysis, patients with AF mediated decompensations had a significantly longer length of stay (7.04 ± 5.20 SD vs 5.16 ± 3.94 SD, p = 0.01), compared to non-AF mediated decompensations. Troponin and haemoglobin levels were not significantly different between groups. However, a higher proportion of patients in the AF group had history of anaemia (58% vs 66%, p = 0.40), and raised troponin levels (31% vs 41%, p = 0.40). Conclusion: Our finding suggest AF mediated decompensated HF is associated with longer lengths of stay and trend towards higher complications.

Objective: Despite being established as the gold standard for quantifying large artery stiffness and its additive value beyond traditional risk factors in the prognosis of hypertension, carotid-femoral pulse wave velocity (cfPWV) is not recommended for routine clinical practice in the current guidelines due, in part, to practical limitations with its measurement. A formula was recently developed (Weir-McCall et al. Hypertension. 2018;71 (5):937–945) for calculation of both left- and right-side arterial path length for cfPWV determination using routinely collected clinical parameters (gender, age, weight, height, heart rate, diastolic blood pressure). However, only the right-side formula was validated. This study aimed to determine the validity of the left-side formula and whether accounting for side of cfPWV measurement would improve the agreement between formula-calculated and measured cfPWV. Design and method: Arterial path length was re-calculated in 127 subjects (aged 65 ± 12 years, 51 females) using the left- (n = 71) and right-side (n = 56) formula according to the side on which their cfPWV was previously measured. The formula-calculated distances were then used to re-calculate cfPWV. Arterial path length and cfPWV were also re-calculated in all 127 subjects using only either the left- or right-side formula. Results: Mean differences between formula-calculated and measured arterial path length and cfPWV were 29.5 ± 42.5 mm (mean ± SD, P < 0.001), 0.03 ± 1.0 m/s (P = 0.775) and 5.1 ± 35.4 mm (P = 0.286), 0.8 ± 0.7 m/s (P < 0.001) for left- and right-side, respectively, giving an average difference of 18.7 ± 41.2 mm (P < 0.001), 0.4 ± 0.9 m/s (P < 0.001). When only the left-side arterial length formula was used, the mean differences were 34.2 ± 40.9 mm (P < 0.001), 0.7 ± 0.9 m/s (P < 0.001). When only the right arterial path length formula was used, the mean differences were −0.21 ± 39.6 mm (P = 0.953), 0.1 ± 0.9 m/s (P = 0.378). Conclusions: Whilst the left-side formula resulted in a larger bias in arterial path length compared with the right-side formula, the resulting cfPWV had a better agreement with measured values. On a sample population level, the best agreement was achieved when only the right-side formula was used. These findings demonstrate that if a formula for path length is used, the left-side and right-side formulae result in different ranges of cfPWV differences in individual measurements and in population studies.