Simulating impaired left ventricular-arterial coupling in aging and disease: a systematic review.

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular-vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart-vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers.

Coronary artery segmentation in CCTA images based on multi-scale feature learning.

BACKGROUND: Coronary artery segmentation is a prerequisite in computer-aided diagnosis of Coronary Artery Disease (CAD). However, segmentation of coronary arteries in Coronary Computed Tomography Angiography (CCTA) images faces several challenges. The current segmentation approaches are unable to effectively address these challenges and existing problems such as the need for manual interaction or low segmentation accuracy. OBJECTIVE: A Multi-scale Feature Learning and Rectification (MFLR) network is proposed to tackle the challenges and achieve automatic and accurate segmentation of coronary arteries. METHODS: The MFLR network introduces a multi-scale feature extraction module in the encoder to effectively capture contextual information under different receptive fields. In the decoder, a feature correction and fusion module is proposed, which employs high-level features containing multi-scale information to correct and guide low-level features, achieving fusion between the two-level features to further improve segmentation performance. RESULTS: The MFLR network achieved the best performance on the dice similarity coefficient, Jaccard index, Recall, F1-score, and 95% Hausdorff distance, for both in-house and public datasets. CONCLUSION: Experimental results demonstrate the superiority and good generalization ability of the MFLR approach. This study contributes to the accurate diagnosis and treatment of CAD, and it also informs other segmentation applications in medicine.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.

Cuffless Blood Pressure Measurement.

Cuffless blood pressure (BP) measurement has become a popular field due to clinical need and technological opportunity. However, no method has been broadly accepted hitherto. The objective of this review is to accelerate progress in the development and application of cuffless BP measurement methods. We begin by describing the principles of conventional BP measurement, outstanding hypertension/hypotension problems that could be addressed with cuffless methods, and recent technological advances, including smartphone proliferation and wearable sensing, that are driving the field. We then present all major cuffless methods under investigation, including their current evidence. Our presentation includes calibrated methods (i.e., pulse transit time, pulse wave analysis, and facial video processing) and uncalibrated methods (i.e., cuffless oscillometry, ultrasound, and volume control). The calibrated methods can offer convenience advantages, whereas the uncalibrated methods do not require periodic cuff device usage or demographic inputs. We conclude by summarizing the field and highlighting potentially useful future research directions.

The Severity of Obstructive Sleep Apnea Increases the Risk of Arteriosclerosis.

BACKGROUND: Obstructive sleep apnea (OSA) is a common disorder worldwide. It is associated with myocardial remodeling and arteriosclerosis in patients with hypertension. Our study investigated the relationship between OSA severity and arteriosclerosis and blood pressure in an Asian population. METHODS: We enrolled 365 subjects from July 2018 to December 2020 at Ruijin Hospital. We recorded data from the medical history and collected blood samples from all participants. We performed 24-hour ambulatory Blood Pressure (BP) monitoring and Carotid-femoral pulse wave velocity (cf-PWV) measurements. Overnight polysomnography (PSG) was performed using Respironics Alice PDxSleepware. RESULTS: PSG was performed in a total of 365 subjects; mean age of 49.1 ± 12.8 years and Body Mass Index (BMI) 28.1 ± 3.8 kg/m2. The majority (89.3%) were male. The office systolic BP was significantly higher in the moderate to severe group than mild OSA group (148 ± 21 mmHg vs 139 ± 19 mmHg, p < 0.01). The subjects with moderate to severe OSA presented higher cf-PWV values than those in the mild group (10.03 ± 3.67 m/s vs 7.62 ± 1.48 m/s, p < 0.01). BMI was significantly higher in the moderate to severe than the mild OSA groups (28.3 ± 4.0 kg/m2 vs 27.5 ± 3.2 kg/m2, p < 0.05). The Pearson correlation showed that the apnea-hypopnea index (AHI) was significantly and positively correlated with cf-PWV (r = 0.217, p < 0.01), Age (r = 0.148, p < 0.01), BMI (r = 0.228, p < 0.01) and HbA1c (r = 0.172, p < 0.01). After adjusting for age, BMI, low density lipoprotein cholesterin (LDL-c), FGB, AHI, estimated Glomerular Filtration Rate (eGFR), Night BP, office diastolic BP and Day BP in Logistic regression model, AHI (OR = 1.03, 95% CI: 1.01-1.05) and office diastolic pressure (OR = 1.04, 95% CI: 1.00-1.08) and age (OR = 1.12, 95% CI: 1.06-1.19) were independent risk factors for arteriosclerosis. CONCLUSIONS: The severity of OSA was positively correlated with pulse wave velocity. AHI, office BP and age were independent risk factors for arteriosclerosis.

The prevalence and impact of orthostatic intolerance in young women across the hypermobility spectrum.

Orthostatic intolerance (OI) is frequently reported in young women with generalized hypermobility spectrum disorder (G-HSD) and hypermobile EDS (hEDS). However, it remains currently unclear whether OI is a comorbidity or fundamental part of the pathophysiology of G-HSD or hEDS. This study investigated the prevalence and impact of OI in young women across the hypermobility spectrum. Forty-five women (14-30 years, 15 controls, 15 G-HSD, and 15 hEDS) undertook a head-up tilt (HUT) and active stand test. Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH) were assessed using age-related criteria. Autonomic dysfunction and quality-of-life questionnaires were also completed. The prevalence of POTS was higher in women with G-HSD than hEDS and control groups during HUT (43% vs. 7% and 7%, respectively, p < 0.05), but similar between groups during the active stand (47%, 27%, and 13% for G-HSD, hEDS, and control, respectively). No participants had OH. hEDS and G-HSD participants reported more severe orthostatic symptoms and poorer quality of life than controls. Although POTS was observed in hypermobile participants, there is no conclusive evidence that its prevalence differed between groups due to differences between the HUT and active stand assessments. Nevertheless, OI and broader autonomic dysfunction impacted on their quality of life.

Measuring Arterial Stiffness in Animal Experimental Studies.

The arterial wall is a composite material of elastin, collagen, and extracellular matrix with acutely modifiable material properties through the action of smooth muscle cells. Therefore, arterial stiffness is a complex parameter that changes not only with long-term remodeling of the wall constituents but also with acute contraction or relaxation of smooth muscle or with changes in the acute distending pressure to which the artery is exposed. It is not possible to test all these aspects using noninvasive or even invasive techniques in humans. Full characterization of the mechanical properties of the artery and the specific arterial factors causing changes to stiffness with disease or modified lifestyle currently require animal studies. This article summarizes the major in vivo and ex vivo techniques to measure the different aspects of arterial stiffness in animal studies.

Vascular Ageing in Youth: A Call to Action.

Extensive evidence shows that risk factors for cardiovascular disease (CVD) begin to develop early in life. Childhood obesity and elevated blood pressure (BP) have become overwhelmingly challenging, with 57% of today's children predicted to be obese by the age of 35 years, and global rates of hypertension in children and adolescents increasing by 75% from 2000 to 2015. Thus, there is an urgent need for tools that can assess early CVD risk in youth, which may lead to better risk stratification, preventative intervention, and personalised medicine. Vascular ageing (the deterioration in vascular structure and function) is a pivotal progenitor of health degeneration associated with elevated BP. Exposure to adverse environmental and genetic factors from fetal life promotes the development and accumulation of subclinical vascular changes that direct an individual towards a trajectory of early vascular ageing (EVA)-an independent predictor of target organ damage in the heart, brain, and kidneys. Therefore, characterising vascular ageing from youth may provide a window into cardiovascular risk later in life. However, vascular ageing measurements only have value when techniques are accurate/validated and when reliable thresholds are available for defining normal ranges and ranges that signal increased risk of disease. The aim of this paper is to summarise current evidence on the importance of vascular ageing assessment in youth and the impact of interventions to prevent or delay EVA, to highlight the need for standardisation and validation of measurement techniques in children and adolescents, and the importance of establishing reference values for vascular ageing measures in this population.

Of Machines and Men: Intelligent Diagnosis and the Shape of Things to Come.

Artificial Intelligence (AI), although well established in many areas of everyday life, has only recently been trialed in the diagnosis and management of common clinical conditions. This editorial review highlights progress to date and suggests further improvements in and trials of AI in the management of conditions such as hypertension.

The effect of interval sprinting exercise on vascular function and aerobic fitness of post-menopausal women.

Menopausal transition accelerates an age-associated decrease in vascular function and a decline in aerobic fitness. The purpose of this study was to examine the effect of 8 weeks of interval sprinting cycle ergometer exercise on arterial stiffness, basal forearm blood flow, and aerobic fitness of post-menopausal women. Sixty overweight post-menopausal women were randomized into either exercise (Ex, n = 30) or control (C, n = 30) groups. Ex participants completed 24 interval sprinting exercise (ISE) sessions over 8 weeks. Each 20-minute ISE session comprised of alternating 8 seconds sprints and 12 seconds of light pedaling. Arterial stiffness assessed through ankle-brachial pulse wave velocity (baPWV) and augmentation index (AIx), basal forearm blood flow (FBF) assessed using venous occlusion, and aerobic fitness were assessed before and after the intervention. baPWV was significantly decreased in the Ex group by 7.2%, P = .03, whereas AIx demonstrated a 10% decrease, P = .002. No changes were found in basal FBF. Aerobic fitness was significantly increased, P = .002, in the Ex group (14%) with no change occurring in the control group.ISE training, despite minimal exercise commitment time (8 hours over 8 weeks), significantly lowered the arterial stiffness and increased the aerobic fitness of post-menopausal women. These results suggest that ISE positively influences the negative change in arterial stiffness and aerobic fitness that typically accompanies menopause.

Central aortic pressure improves prediction of cardiovascular events compared to peripheral blood pressure in short-term follow-up of a hypertensive cohort.

Objective: The aim of this study was to assess indices of a comprehensive panel of central aortic pressure and arterial stiffness for prediction of cardiovascular events in a hypertensive cohort.Methods: Noninvasive measurements of central aortic blood pressure, brachial pressure, wave reflection augmentation index, pressure amplification, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) were obtained in 675 hypertensive patients (age 61 ± 9 years, 425 males) for a mean follow-up period 25 ± 4 months. The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD.Results: After adjusting for confounding factors, central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events (CV) compared to peripheral pressure indices (pSBP, pPP) at age >60 years (cSBP: HR = 1.18, pSBP: HR = 1.17, p = 0.034; cPP: HR = 1.28, pPP: HR = 1.2, p = 0.019). Each SD increase in IMT and in central augmented pressure (cAP) entailed a 1.4 times higher risk of increased total events in elderly patients (age >60 years). For males, each SD increase in cAP was associated with 1.36 times higher risk of increased total events. For females, each SD increase in cAIx and cAP was associated with 0.4 and 0.5 times lower risk of increased total and major CV, respectively. This sex difference is most likely due to lack of age-related increase of cAIx in females after age >60 years compared to males.Conclusions: Central pressure improved prediction of CVD compared to peripheral pressure during a relatively short-term follow up of approximately 2 years at age >60 years.

Reply to Comments: Using the Cardio-Ankle Vascular Index (CAVI) or the Mathematical Correction Form (CAVI0) in Clinical Practice.

We read with great interest Alizargar et al [...].

Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γnorm) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γnorm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γnorm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γnorm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and reflection index as wave reflection indexes.

Influence of dietary nitrate supplementation on lung function and exercise gas exchange in COPD patients.

BACKGROUND: During exercise as pulmonary blood flow rises, pulmonary capillary blood volume increases and gas exchange surface area expands through distention and recruitment. We have previously demonstrated that pulmonary capillary recruitment is limited in COPD patients with poorer exercise tolerance. Hypoxia and endothelial dysfunction lead to pulmonary vascular dysregulation possibly in part related to nitric oxide related pathways. PURPOSE: To determine if increasing dietary nitrate might influence lung surface area for gas exchange and subsequently impact exercise performance. METHODS: Subjects had stable, medically treated COPD (n = 25), gave informed consent, filled out the St George Respiratory Questionnaire (SGRQ), had a baseline blood draw for Hgb, performed spirometry, and had exhaled nitric oxide (exNO) measured. Then they performed the intra-breath (IB) technique for lung diffusing capacity for carbon monoxide (DLCO) as well as pulmonary blood flow (Qc). Subsequently they completed a progressive semi-recumbent cycle ergometry test to exhaustion with measures of oxygen saturation (SpO2) and expired gases along with DLCO and Qc measured during the 1st work load only. Subjects were randomized to nitrate supplement group (beetroot juice) or placebo group (black currant juice) for 8 days and returned for repeat of the above protocol. RESULTS: Exhaled nitric oxide levels rose >200% in the nitrate group (p < 0.05) with minimal change in placebo group. The SGRQ suggested a small fall in perceived symptom limitation in the nitrate group, but no measure of resting pulmonary function differed post nitrate supplementation. With exercise, there was no influence of nitrate supplementation on peak VO2 or other measures of respiratory gas exchange. There was a tendency for the exercise DLCO to increase slightly in the nitrate group with a trend towards a rise in the DLCO/Qc relationship (p = 0.08) but not in the placebo group. The only other significant finding was a fall in the exercise blood pressure in the nitrate group, but not placebo group (p < 0.05). CONCLUSION: Despite evidence of a rise in exhaled nitric oxide levels with nitrate supplementation, there was minimal evidence for improvement in exercise performance or pulmonary gas exchange surface area in a stable medically treated COPD population.

Cerebral Haemodynamics: Effects of Systemic Arterial Pulsatile Function and Hypertension.

PURPOSE OF REVIEW: Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion. RECENT FINDINGS: Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

Arterial Flow, Pulse Pressure and Pulse Wave Velocity in Men and Women at Various Ages.

The increase in pulse pressure (PP) that occurs with advancing age is predominantly due to reduced arterial distensibility leading to decreased aortic compliance, particularly in the elderly, in whom high blood pressure mainly manifests as isolated systolic hypertension. Since age-related changes in stroke volume are minimal compared with changes in PP, PP is often considered a surrogate measure of arterial stiffness. However, since PP is determined by both cardiac and arterial function, a more precise and reliable means of assessment of arterial stiffness is arterial pulse wave velocity (PWV), a parameter that is only dependent on arterial properties. Arterial stiffness as measured by PWV has been found to be a powerful pressure-related indicator for cardiovascular morbidity and mortality. We analyzed PP and PWV in men and women of various age groups in healthy volunteers as well as cardiac patients with different types of diseases. The findings identified several striking sex-specific differences which demand consideration in guidelines for diagnostic procedures, for epidemiological analysis, and in evaluation of therapeutic interventions.

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries.

Experimental investigations have established that the stiffness of large arteries has a dependency on acute heart rate (HR) changes. However, the possible underlying mechanisms inherent in this HR dependency have not been well established. This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWVTan) and by phase velocity from the transfer function (afPWVTF) in the time and frequency domain, respectively. PWV was significantly and positively associated with HR for α ≥ 0.6; for α = 0.6, 0.8, and 1, HR-dependent changes in afPWVTan were 0.01 ± 0.02, 0.07 ± 0.04, and 0.22 ± 0.09 m/s per 5 beats/min; HR-dependent changes in afPWVTF were 0.02 ± 0.01, 0.12 ± 0.00, and 0.34 ± 0.01 m/s per 5 beats/min, respectively. This crosses the range of previous physiological studies where the dependence of PWV on HR was found to be between 0.08 and 0.10 m/s per 5 beats/min. Therefore, viscoelasticity of the arterial wall could contribute to mechanisms through which large artery stiffness changes with changing HR. Physiological studies are required to confirm this mechanism.NEW & NOTEWORTHY This study used a transmission line model to elucidate the role of arterial viscoelasticity in the dependency of pulse wave velocity on heart rate. The model uses fractional viscoelasticity concepts, which provided novel insights into arterial hemodynamics. This study also provides a means of assessing the clinical manifestation of the association of pulse wave velocity and heart rate.

One protein, multiple pathologies: multifaceted involvement of amyloid ß in neurodegenerative disorders of the brain and retina.

Accumulation of amyloid ß (Aß) and its aggregates in the ageing central nervous system is regarded synonymous to Alzheimer's disease (AD) pathology. Despite unquestionable advances in mechanistic and diagnostic aspects of the disease understanding, the primary cause of Aß accumulation as well as its in vivo roles remains elusive; nonetheless, the majority of the efforts to address pathological mechanisms for therapeutic development are focused towards moderating Aß accumulation in the brain. More recently, Aß deposition has been identified in the eye and is linked with distinct age-related diseases including age-related macular degeneration, glaucoma as well as AD. Awareness of the Aß accumulation in these markedly different degenerative disorders has led to an increasing body of work exploring overlapping mechanisms, a prospective biomarker role for Aß and the potential to use retina as a model for brain related neurodegenerative disorders. Here, we present an integrated view of current understanding of the retinal Aß deposition discussing the accumulation mechanisms, anticipated impacts and outlining ameliorative approaches that can be extrapolated to the retina for potential therapeutic benefits. Further longitudinal investigations in humans and animal models will determine retinal Aß association as a potential pathognomonic, diagnostic or prognostic biomarker.

Improved assessment of arterial stiffness using corrected cardio-ankle vascular index (CAVI0) in overweight adolescents with white-coat and essential hypertension.

Arterial stiffness is a marker of vascular damage. Although adiposity increases cardiovascular risk, the relationship between paediatric overweight and arterial stiffness is unclear. The study aimed to evaluate the simultaneous effect of hypertension and overweight on arterial stiffness using cardio-ankle vascular index (CAVI) and related novel, theoretically blood pressure (BP)-independent, index CAVI0. CAVI and CAVI0 were measured in 140 adolescent boys (16.0 ± 1.9 years) divided into age-matched groups: normal-weight normotensives, overweight normotensives, overweight white-coat hypertensives, and overweight essential hypertensives. Overweight normotensives had significantly lower CAVI and CAVI0 compared to normal-weight normotensives (4.81 ± 0.64 vs. 5.33 ± 0.66, p < .01; 7.10 ± 0.99 vs. 7.81 ± 1.00, p < .01, respectively). CAVI and CAVI0 in overweight essential hypertensives showed no significant difference compared to normal-weight normotensives and were significantly higher compared to overweight normotensives (5.32 ± 0.77 vs. 4.81 ± 0.64, p < .01; 7.77 ± 1.19 vs. 7.10 ± 0.99, p < .01, respectively). CAVI, but not CAVI0, was associated positively with diastolic pressure (0.022 mmHg-1, p = .002) and negatively with pulse pressure (-0.022 mmHg-1, p = .001), and it was significantly higher in overweight white-coat hypertensives compared to overweight normotensives (5.20 ± 0.63 vs. 4.81 ± 0.64, p < .05). The lowering effect of overweight on arterial stiffness indexed by CAVI and CAVI0 in hypertensive adolescents seems to counterbalance the early arteriosclerotic effect of essential hypertension. The increase in CAVI, but not CAVI0, in overweight white-coat hypertensives could be attributable to residual BP dependence of CAVI, which is not present in CAVI0. Under certain conditions, CAVI0 may offer a clinically relevant improved assessment of arterial stiffness superior to CAVI.

Influence of resting lung diffusion on exercise capacity in patients with COPD.

BACKGROUND: Lung diffusing capacity for carbon monoxide (DLCO) gives an overall assessment of functional lung surface area for gas exchange and can be assessed using various methods. DLCO is an important factor in exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). We investigated if the intra-breath (IBDLCO) method may give a more sensitive measure of available gas exchange surface area than the more typical single breath (SBDLCO) method and if COPD subjects with the largest resting DLCO relative to pulmonary blood flow (Qc) would have a more preserved exercise capacity. METHODS: Informed consent, hemoglobin, spirometry, SBDLCO, IBDLCO, and Qc during IBDLCO were performed in moderate to severe COPD patients, followed by progressive cycle ergometry to exhaustion with measures of oxygen saturation (SaO2) and expired gases. RESULTS: Thirty two subjects (47% female, age 66 ± 9 yrs., BMI 30.4 ± 6.3 kg/m2, smoking hx 35 ± 29 pkyrs, 2.3 ± 0.8 on the 0-4 GOLD classification scale) participated. The majority used multiple inhaled medications and 20% were on oral steroids. Averages were: FEV1/FVC 58 ± 10%Pred, peak VO2 11.4 ± 3.1 ml/kg/min, and IBDLCO 72% of the SBDLCO (r = 0.88, SB vs IB methods). Using univariate regression, both the SB and IBDLCO (% predicted but not absolute) were predictive of VO2peak in ml/kg/min; SBDLCO/Qc (r = 0.63, p < 0.001) was the best predictor of VO2peak; maximal expiratory flows over the mid to lower lung volumes were the most significantly predictive spirometric measure (r = 0.49, p < 0.01). However, in multivariate models only BMI added additional predictive value to the SBDLCO/Qc for predicting aerobic capacity (r = 0.73). Adjusting for current smoking status and gender did not significantly change the primary results. CONCLUSION: In patients with moderate to severe COPD, preservation of lung gas exchange surface area as assessed using the resting SBDLCO/Qc appears to be a better predictor of exercise capacity than more classic measures of lung mechanics.