78 research outputs found

    Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial

    Get PDF
    Background: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor efect of salt is viewed as a chronic efect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this efect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. Methods: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2g of sodium chloride; their BP was monitored for 120minutes in intervals of 10minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. Results: Median age was 30 years (interquartile range, 22–46 years) and 52% were female patients. An increase of ≄10mmHg in mean arterial pressure (MAP), considered a clinically signifcant IPROS, was present in 62% of participants. Systolic BP 30minutes after the salt load was a signifcant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. Conclusions: We confrm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral saltloads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our fndings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP

    Physics-Based Model-Guided Machine Learning Analysis of Wrist Ballistocardiography for Cuff-Less Blood Pressure Monitoring

    Get PDF
    Cuff-less blood pressure (BP) monitoring technology is being widely pursued today. In this research we investigated the wrist ballistocardiogram (BCG) as a limb BCG, to develop a scientific basis to use the limb BCG to for cuff-less BP monitoring. In our study, we pursue two alternative approaches to the use of wrist BCG signal for BP monitoring: (1) use of the wrist BCG as proximal timing in pulse transit time (PTT) based methods; (2) use of wrist BCG wave features for BP monitoring. In this regard, the physics-based model is developed to elucidate the mechanism responsible for the generation of the BCG signal at the body’s extremity limb locations. The developed and experimentally validated mathematical model can predict the limb BCG in responses to the arterial BP waves in the aorta. The model suggests that the limb BCG waveform reveals the timings and amplitudes associated with the aortic BP waves and it exhibits meaningful morphological changes in response to the alterations in the CV risk predictors. Such understanding combined with machine learning techniques has helped us to extract viable features, and construct predictive models that can estimate BP. The findings of this study show that limb BCG has the potential to realize convenient cuff-less BP monitoring. First, it is a strong candidate to extract the proximal timing for PTT based methods. Second, BCG wave features are associated with BP and it could be used for BP monitoring. Third, we can combine the PTT with BCG wave features to achieve more comprehensive prediction models with superior performance

    Simple Tests for Assessing Kidney and Cardiovascular Function in Chromic Kidney Disease Patients (Stages 2, 3 and 4)

    Full text link
    Reliable measurement of glomerular filtration rate (GFR) is an important aspect of clinical decision making and forms the basis of classification for kidney function. Moreover the interpretation of risk factors for progression of CKD linked to cardiovascular disease (CVD) remains difficult, particularly in older subjects. To address this GFR and the cardiovascular parameters arterial stiffness, heart rate variability (HRV) and natriuretic peptides (NT- proBNP and NT-proCNP) were measured in a cohort of CKD patients of stages 2,3 and 4. The primary aim however of the thesis was to measure the Kidney Functional Reserve (KFR) of CKD3 and CKD4 patients as it has been thought of as analogous to cardiac functional reserve. CysC, creatinine clearance (CrCl) and with simultaneous radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m) measured GFR (mGFR) of KFR in 19 CKD Stage 3 and 21 CKD Stage 4 patients yielded good agreement. KFR was not correlated with baseline kidney function. Eight CKD Stage 3 (42%) and 11 CKD Stage 4 (52%) subjects reached their lowest serum CysC concentration 4 hours after OPL. CysC KFR and baseline serum creatinine (sCr) predicted Major Adverse Kidney Event, death or dialysis (MAKE-T) and MAKE-F (fast progression with GFR decrease > 5ml/min/year) with a respective area under the curve (AUC) of 0.73 (95% confidence interval [CI] 0.48 – 0.890) and 0.71 (95% CI: 0.51–0.84). Including CysC KFR, age, baseline sCr and nadir CysC predicted a decrease in sCr-estimated GFR >1.2 ml/min/year (MAKE-S) with an AUC of 0.89. In the latter case the inclusion of cardiovascular variables; “Recovery” (1-4 minutes post exercise) RMSSD, urinary and serum NT-proCNP concentration and whether CysC GFR reserve was early or late in nadir improved the AUC to 1.00 (AICc =15.41). In conclusion serial CysC may facilitate monitoring of KFR in clinical practice along with the use of a portable exercise stress test to increase c-f-PWV (carotid-femoral Pulse Wave Velocity) and identify CKD patients with serious/subliminal vascular stiffening. Future research may confirm this studies other preliminary finding that urinary NT-proCNP concentration may relate to renal haemodynamic function in CKD stages, as this correlated with stimulated mGFR (R2 = 0.41). In short this thesis has furthered the premise that the heart and kidney are interlinked via cardiovascular physiology which likely can be used to predict CKD progression

    Examining endothelial function in humans in vivo: improving guidelines and exploring novel measures

    Get PDF
    Chapter 1 introduced the old and new measurement of endothelial function, and vascular health. The first part of this thesis focussed on the “old” flow-mediated dilation measurement, introduced in 1992, which relies on brachial artery vasodilation after a hyperaemic stimulus (e.g. after occlusion of a pneumatic cuff), and the susceptibility of the FMD measurement to variability. In Chapter 2 we sought for factors that might help to improve the reproducibility of the FMD measurement. We performed an analysis including 672 participants with repeated FMD. Overall we found an acceptable reproducibility, with 33% of the FMD measurements showing an excellent-to-moderate reproducibility. We identified several factors that independently increased the variation of the FMD, including the presence of hypertension, a lower resting FMD%, a larger baseline artery diameter, a longer time between subsequent measurements, and less laboratory experience with the measurement. Future studies should take these factors into consideration, as certain measures may lower variability of the FMD or more subjects should be included in individual studies when variation relates to non-modifiable factors. Unfortunately, we also found that a large proportion of our study population demonstrated a moderate-to-poor reproducibility, despite all included studies adhered to expert-consensus guidelines. In Chapter 3, we described the relation between adherence to the expertconsensus guidelines and reproducibility of the FMD. In this meta-analysis, we combined data from twenty-seven studies, comprising 48 study groups, with a total of 1537 subjects. Adherence to expert guidelines was inversely related to the measurement error and adopting the guidelines (with specific notification of the use of a stereotactic probe-holder, continuous diameter recording and the use of automated wall-detection and analysis software) was crucial for improving the reproducibility of the FMD. The second part of this thesis introduced the “new” carotid artery reactivity (CAR) measurement, which depends on carotid artery vasomotor responses following sympathetic stimulation (e.g. after a cold pressor test, CPT). The carotid artery appears to mirror coronary responses to CPT, as it shows dilation in healthy participants, whilst those at risk demonstrate a constriction. In this thesis, we sought to understand the relation of CAR with risk factors, and the similarity with the coronary responses. An attempt was made to unravel the underlying physiological mechanism of CAR. Finally, the prognostic value of CAR was examined in peripheral arterial disease patients, to further investigate to clinical potential of the CAR test. In Chapter 4 we explored the relation of CAR with cardiovascular risk, followed by assessing the similarity in response to sympathetic stimulation between the carotid artery and coronary arteries. We first compared CAR between 50 young and 44 older participants to assess relationships between CAR and traditional cardiovascular risk factors. We found that CAR was lower in participants with ≄2 risk factors, compared to those with lesser risk factors. Secondly, we compared left anterior descending (LAD) artery velocity with carotid artery diameter in a subgroup of 33 participants, to assess similarity between coronary and carotid artery responses. We found that CAR correlated well with coronary artery velocity. This implies that CAR is related to increased CV risk and may represent a surrogate measure for coronary vascular health. In Chapter 5, the physiological mechanism underlying the CAR was further explored, by examining carotid artery responses to different sympathetic stimuli (e.g. the cold pressor test [CPT] and the lower body negative pressure test [LBNP]), exploring the role of α1-receptors, (nor) epinephrine receptors contributing to vasoconstriction, and assessing similarity between carotid and coronary arteries. First, 10 participants underwent both sympathetic tests in randomized order, whilst concurrently measuring CAR and coronary artery velocity. We found distinct carotid artery responses to different tests of sympathetic stimulation (e.g. dilation in response to CPT, and constriction following LBNP). Second, when measurements were repeated following α1-receptor blockade by Prazosin, we found α1-receptors partly contributed to CPT-induced responses. Finally, we found agreement between carotid and coronary artery responses, during both types of sympathetic nerve stimulation as well as during α1-receptor blockade. These data indicate strong similarity between carotid and coronary responses to sympathetic tests and the role of α1-receptors. Since the CAR test was newly introduced, the prognostic value of the test remained unknown and this question is highly relevant to understand its clinical utility. Therefore, in Chapter 6, we examined whether CAR predicts (cardiovascular) events in patients with peripheral arterial disease. A total of 172 PAD patients were included, and we recorded cardiac and cerebrovascular events, mortality and clinical progression to percutaneous transluminal angioplasty or loss of patency during a 12-months follow-up. We found that patients with carotid constriction showed a four-fold higher risk for cardiovascular events and two-fold increased risk for clinical deterioration, even after adjustment for other risk factors. This indicates that CAR provides a simple, novel strategy to predict CV events and progression in PAD patients, which has stronger prognostic value than current techniques. Chapter 7 summarizes, discusses, and explains the findings of these studies, and aims to provide recommendations and implications. We discuss future prospects, and provide perspective for future vascular health assessment

    The impact of blood flow restricted exercise on the peripheral vasculature

    Get PDF
    Distortion to hemodynamic, ischemic and metabolic stimuli during low load resistance exercise with blood flow restriction (BFR) may influence regional vascular adaptation. This thesis investigated the acute response and chronic adaptations of the peripheral vasculature to low load resistance exercise with BFR. The methodology utilised Doppler ultrasound, strain gauge plethysmography and muscle biopsy for insightful measures of the vasculature at different regions of the arterial tree. Short term (4-6 weeks) localised low load (30-40% 1RM) resistance exercise with BFR increased brachial (3.1%) and popliteal (3.3%) artery maximal diameter (in response to ischemic exercise), forearm (29%) and calf (24%) post-occlusive blood flow, and calf filtration capacity (14%). These findings indicate potential vascular remodelling at the conduit (chapters 3, 4) resistance (chapter 4) and capillary (chapter 4) level of the vascular tree. Regional, rather than systemic, factors are responsible for these adaptations as evidenced by an absent response in the contralateral control limb. Transient improvements in popliteal artery FMD% occurred at week 2 before increased maximal diameter at week 6, suggesting functional changes precede structural remodelling (chapter 4). Maximal brachial artery diameter and forearm post-occlusive blood flow returned to baseline values after a 2 week detraining period, signifying rapid structural normalisation after stimulus removal (chapter 3). Enhanced capillarity, despite low training loads, could be explained by augmentation of VEGF (~7 fold), PGC-1α (~6 fold) and eNOS (~5 fold) mRNA, and upregulation VEGFR-2 (~5 fold) and HIF-1α (~2.5 fold) mRNA with BFR (chapter 5). This indicates a targeted angiogenic response potentially mediated through enhanced metabolic, ischemic and shear stress stimuli. Large between subject variability in the level of BFR was observed during upper and lower limb cuff inflation protocols. Adipose tissue thickness and mean arterial pressure were the largest independent determinants of upper and lower limb BFR, respectively (Chapter 6). In conclusion, this thesis demonstrates that low load resistance exercise with BFR induces adaptation in the conduit, resistance and capillary vessels. The mediators of this response are likely to be the hemodynamic and chemical signals elicited by repeated bouts of BFR resistance exercise, although confirmation of these mechanisms is required. The functional significance of these adaptations is unknown and warrants further investigation

    Clinical Effectiveness of Tailored E2coaching in Reducing Cardiovascular Risk Assessed Using Cardiovascular Imaging and Functional Assessment 2 A Primary Prevention Trial in Moderate to High Risk Individuals

    Get PDF
    PhDCardiovascular disease remains one of the leading causes of mortality globally. Innovative techniques are required to tackle its anticipated rise due to rising obesity, diabetes and an ageing population. Personalised electronic coaching (eb coaching) using the Internet and emails may help motivate healthier living and be of clinical benefit in complementing current programmes for cardiovascular risk reduction. I investigated whether personalised ebcoaching on top of SOC was more clinically effective than SOC alone, in reducing cardiovascular risk in asymptomatic individuals with high cardiovascular risk. I lead a randomised controlled trial of 402 participants using robust surrogate markers to identify change over 6 months. I assessed the feasibility of using cardiovascular magnetic resonance surrogate markers to guide their use in future studies of lifestyle interventions. I performed systematic reviews to identify 1) similarities and differences among leading primary prevention guidelines that address cardiovascular screening and risk assessment and 2) guideline recommendations on lifestyle advice and interventions to identify how ebcoaching could be used and what advice to incorporate in ebcoaching platforms. I found modest but statistically significant improvements in both ebcoaching and SOC groups to a similar level. Personalised ebcoaching did not show additional benefit in a highbrisk primary prevention cohort. It is feasible to use cardiovascular surrogate markers derived from cardiovascular magnetic resonance in lifestyle interventions studies. However, further studies correlating change in these markers with longbterm outcomes are required. Considerable discrepancies exist in the guidelines on risk on cardiovascular screening and risk assessment, with no consensus on optimum screening strategies or classification of high risk thus affecting treatment threshold. Guidelines did highlight the importance of lifestyle interventions in primary prevention and generally provided similar advice. Ebcoaching should not be incorporated into current prevention programmes for high risk populations unless the tools are improved and effectiveness is proven

    Automated deep phenotyping of the cardiovascular system using magnetic resonance imaging

    Get PDF
    Across a lifetime, the cardiovascular system must adapt to a great range of demands from the body. The individual changes in the cardiovascular system that occur in response to loading conditions are influenced by genetic susceptibility, and the pattern and extent of these changes have prognostic value. Brachial blood pressure (BP) and left ventricular ejection fraction (LVEF) are important biomarkers that capture this response, and their measurements are made at high resolution. Relatively, clinical analysis is crude, and may result in lost information and the introduction of noise. Digital information storage enables efficient extraction of information from a dataset, and this strategy may provide more precise and deeper measures to breakdown current phenotypes into their component parts. The aim of this thesis was to develop automated analysis of cardiovascular magnetic resonance (CMR) imaging for more detailed phenotyping, and apply these techniques for new biological insights into the cardiovascular response to different loading conditions. I therefore tested the feasibility and clinical utility of computational approaches for image and waveform analysis, recruiting and acquiring additional patient cohorts where necessary, and then applied these approaches prospectively to participants before and after six-months of exercise training for a first-time marathon. First, a multi-centre, multi-vendor, multi-field strength, multi-disease CMR resource of 110 patients undergoing repeat imaging in a short time-frame was assembled. The resource was used to assess whether automated analysis of LV structure and function is feasible on real-world data, and if it can improve upon human precision. This showed that clinicians can be confident in detecting a 9% change in EF or a 20g change in LV mass. This will be difficult to improve by clinicians because the greatest source of human error was attributable to the observer rather than modifiable factors. Having understood these errors, a convolutional neural network was trained on separate multi-centre data for automated analysis and was successfully generalizable to the real-world CMR data. Precision was similar to human analysis, and performance was 186 times faster. This real-world benchmarking resource has been made freely available (thevolumesresource.com). Precise automated segmentations were then used as a platform to delve further into the LV phenotype. Global LVEFs measured from CMR imaging in 116 patients with severe aortic stenosis were broken down into ~10 million regional measurements of structure and function, represented by computational three-dimensional LV models for each individual. A cardiac atlas approach was used to compile, label, segment and represent these data. Models were compared with healthy matched controls, and co-registered with follow-up one year after aortic valve replacement (AVR). This showed that there is a tendency to asymmetric septal hypertrophy in all patients with severe aortic stenosis (AS), rather than a characteristic specific to predisposed patients. This response to AS was more unfavourable in males than females (associated with higher NT-proBNP, and lower blood pressure), but was more modifiable with AVR. This was not detected using conventional analysis. Because cardiac function is coupled with the vasculature, a novel integrated assessment of the cardiovascular system was developed. Wave intensity theory was used to combine central blood pressure and CMR aortic blood flow-velocity waveforms to represent the interaction of the heart with the vessels in terms of traveling energy waves. This was performed and then validated in 206 individuals (the largest cohort to date), demonstrating inefficient ventriculo-arterial coupling in female sex and healthy ageing. CMR imaging was performed in 236 individuals before training for a first-time marathon and 138 individuals were followed-up after marathon completion. After training, systolic/diastolic blood pressure reduced by 4/3mmHg, descending aortic stiffness decreased by 16%, and ventriculo-arterial coupling improved by 14%. LV mass increased slightly, with a tendency to more symmetrical hypertrophy. The reduction in aortic stiffness was equivalent to a 4-year reduction in estimated biological aortic age, and the benefit was greater in older, male, and slower individuals. In conclusion, this thesis demonstrates that automating analysis of clinical cardiovascular phenotypes is precise with significant time-saving. Complex data that is usually discarded can be used efficiently to identify new biology. Deeper phenotypes developed in this work inform risk reduction behaviour in healthy individuals, and demonstrably deliver a more sensitive marker of LV remodelling, potentially enhancing risk prediction in severe aortic stenosis

    Vascular smooth muscle cells and arterial stiffening : relevance in development, aging, and disease

    Get PDF
    The cushioning function of large arteries encompasses distension during systole and recoil during diastole which transforms pulsatile flow into a steady flow in the microcirculation. Arterial stiffness, the inverse of distensibility, has been implicated in various etiologies of chronic common and monogenic cardiovascular diseases and is a major cause of morbidity and mortality globally. The first components that contribute to arterial stiffening are extracellular matrix (ECM) proteins that support the mechanical load, while the second important components are vascular smooth muscle cells (VSMCs), which not only regulate actomyosin interactions for contraction but mediate also mechanotransduction in cell-ECM homeostasis. Eventually, VSMC plasticity and signaling in both conductance and resistance arteries are highly relevant to the physiology of normal and early vascular aging. This review summarizes current concepts of central pressure and tensile pulsatile circumferential stress as key mechanical determinants of arterial wall remodeling, cell-ECM interactions depending mainly on the architecture of cytoskeletal proteins and focal adhesion, the large/small arteries cross-talk that gives rise to target organ damage, and inflammatory pathways leading to calcification or atherosclerosis. We further speculate on the contribution of cellular stiffness along the arterial tree to vascular wall stiffness. In addition, this review provides the latest advances in the identification of gene variants affecting arterial stiffening. Now that important hemodynamic and molecular mechanisms of arterial stiffness have been elucidated, and the complex interplay between ECM, cells, and sensors identified, further research should study their potential to halt or to reverse the development of arterial stiffness
    • 

    corecore