Cardiovascular

Pressor Reactions to Psychological Stress and Prediction of Future Blood Pressure: Data From the Whitehall II Study

by David Sheffield

Cardiovascular Reactivity and Development of Preclinical and Clinical Disease States

by David Sheffield

CO-AUTHORED WITH FRANK A. TREIBER, PHD, THOMAS KAMARCK, PHD, NEIL SCHNEIDERMAN, PHD, GASTON KAPUKU, MD, PHD, AND TELETIA TAYLOR, PHD. Published in Psychosomatic Medicine

Objective: The objective of this review is to evaluate the evidence for the hypothesis that cardiovascular reactivity... more Objective: The objective of this review is to evaluate the evidence for the hypothesis that cardiovascular reactivity can predict the development of preclinical (elevated blood pressure, ventricular remodeling, carotid atherosclerosis) and/or clinical cardiovascular disease states. Methods: A review of the literature was conducted examining prospective studies. Results: Three large epidemiological studies with long-term follow-up periods (20 years or more) have found blood pressure responses to the cold pressor task to be predictive of subsequent essential hypertension in initially normoten- sive samples. Studies showing less consistent results have tended to use shorter-term follow-up periods. A larger body of literature demonstrates consistent associations between stress-related cardiovascular reactivity and blood pressure elevations in youth over the course of 1 to 6 years; such relationships have not been consistently shown among adult samples. Moderately consistent evidence points to a positive relationship between reactivity and other measures of subclinical disease (increased left ventricular mass and carotid atherosclerosis) among the few prospective studies that have examined these issues to date. A number of additional factors, however, such as baseline levels of disease risk and exposure to psychosocial stress, seem to moderate these relationships. Health status at baseline also seems to moderate the association between reactivity and clinical coronary heart disease in recent reports: two of three existing studies in initially healthy samples show no evidence of a relationship between reactivity and clinical outcomes, whereas three of four studies in samples with preexisting coronary heart disease or essential hypertension show a positive relationship between reactivity and subsequent disease states. Conclusions: There is reasonable evidence to suggest that cardiovas- cular reactivity can predict the development of some preclinical states (eg, increased left ventricular mass and blood pressure) states and perhaps even new clinical events in some patients with essential hypertension or coronary heart disease. However, much more information is needed concerning moderating and potentially confounding variables before the robustness of the positive relationships can become clinically useful.

Filingeri, D., Mancuso, E. P., Paoli, A., Bianco, A., Palma, A. (2011) Is hypoxia a training stimulus for endurance athletes’ performance? a brief review. Italian Journal of Sport Sciences and Law. 4 (4): 153-162.

by Davide Filingeri

Exercise intervention and inflammatory markers in coronary artery disease: a meta-analysis

by Walter Swardfager

Swardfager W, Herrmann N, Cornish S, Mazereeuw G, Marzolini S, Sham L, Lanctôt KL. Am Heart J 2012;163:666-676.e3

Background: Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD),... more Background: Inflammatory activity plays a role in the development and progression of coronary artery disease (CAD), and exercise confers survival benefit. We performed a meta-analysis of changes in inflammatory biomarkers over the course of exercise interventions in patients with CAD.

Methods: We searched MEDLINE, Embase, the Cochrane Collaboration, AMED, and CINAHL for studies reporting peripheral inflammatory biomarker concentrations before and after exercise interventions of ≥2 weeks in patients with CAD. Data were summarized using standard mean differences (SMD) and 95% CIs.

Results: Twenty-three studies were included. Concentrations of C-reactive protein (CRP; SMD −0.345, 95% CI −0.444 to −0.246, n = 1,466, P < .001), interleukin 6 (SMD −0.546, 95% CI −0.739 to −0.353, n = 280, P < .001), fibrinogen (SMD −0.638, 95% CI −0.953 to −0.323, n = 247, P < .001), and vascular cell adhesion molecule 1 (SMD −0.413, 95% CI −0.778 to −0.048, n = 187, P = .027) were lower postintervention. Higher total cholesterol (B = −0.328, 95% CI −0.612 to −0.043, P = .026) and higher total/high-density lipoprotein cholesterol ratios (B = −0.250, 95% CI −0.425 to −0.076, P = .008) at baseline were associated with greater reductions in CRP. In controlled studies, follow-up concentrations of CRP (SMD −0.500, 95% CI −0.844 to −0.157, nexercise/control = 485/284, P = .004), and fibrinogen (SMD −0.544, 95% CI −1.058 to −0.030, nexercise/control = 148/100, P = .038) were lower in subjects who exercised compared with controls.

Conclusion: Exercise training is associated with reduced inflammatory activity in patients with CAD. C-reactive protein and fibrinogen have provided the strongest evidence. Higher baseline CRP and adverse baseline lipid profiles predicted greater reductions in CRP.

Human cord blood CD34+ progenitor cells acquire functional cardiac properties through a cell fusion process

by Gabriele Toietta

Daniele Avitabile, Alessia Crespi, Chiara Brioschi, Valeria Parente, Gabriele Toietta, Paolo Devanna, Mirko Baruscotti, Silvia Truffa, Angela Scavone, Francesca Rusconi, Andrea Biondi, Yuri D'Alessandra, Elisa Vigna, Dario Difrancesco, Maurizio Pesce, Maurizio C Capogrossi, Andrea Barbuti
Am J Physiol Heart Circ Physiol. (2011) 300(5):H1875-84.

Cocoa Intake, Blood Pressure, and Cardiovascular Mortality: The Zutphen Elderly Study

by Brian Buijsse

Chocolate consumption in relation to blood pressure and risk of cardiovascular disease in German adults

by Brian Buijsse

High-frequency subharmonic emission with chirp-coded excitation: implications for imaging

by Himanshu Shekhar

There is growing interest in developing techniques to assess the structure and function of microvasculature, to enable... more There is growing interest in developing techniques to assess the structure and function of microvasculature, to enable clinical diagnosis and to gain insights into disease pathology. High-frequency subharmonic imaging is an emerging technique that can visualize the microvasculature with high specificity. However, the sensitivity of high-frequency subharmonic imaging is compromised because of the pressure threshold for subharmonic behavior, which may limit its potential for preclinical and clinical imaging. The goal of this work was to demonstrate that the sensitivity of subharmonic imaging could be improved by rectangular apodization and chirp-coding of the excitation pulse. We report an experimental study carried out at 20-MHz transmit frequency to compare the efficacy of narrowband sine bursts and coded-chirps towards generating subharmonics. It was demonstrated that chirp-coding of the excitation pulse could generate stable subharmonic signals for excitation bandwidths of 10-20%. The threshold for onset of subharmonic behavior was lowest when rectangularwindowed excitation pulses were employed. The subharmonic to fundamental ratio of RF spectra using coded chirps was up to 5.7 dB higher for sine bursts, and the axial resolution obtained with chirp-coded excitation was up to twofold better compared to that obtained using sine bursts. At 20-MHz transmit frequency, 20% bandwidth rectangular chirp-coded pulse appears to be a good tradeoff between sensitivity and axial resolution.

Zebrafish VEGF receptors: a guideline to nomenclature

by Jeroen Bussmann

To reflect that flk1/kdra is a prominent receptor in VEGF-A signaling in zebrafish, while at the same time indicating... more To reflect that flk1/kdra is a prominent receptor in VEGF-A signaling in zebrafish, while at the same time indicating that it represents a fourth class of vertebrate VEGF receptors (and is not the result of a teleost gene duplication), we propose to rename this gene kdr-like. As the zebrafish kdrb gene is clearly orthologous to mammalian KDR, we propose to rename this gene kdr.

von Hippel-Lindau tumor suppressor mutants faithfully model pathological hypoxia-driven angiogenesis and vascular retinopathies in zebrafish.

by Jeroen Bussmann

Biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes human patients to the... more Biallelic inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene predisposes human patients to the development of highly vascularized neoplasms in multiple organ systems. We show that zebrafish vhl mutants display a marked increase in blood vessel formation throughout the embryo, starting at 2 days post-fertilization. The most severe neovascularization is observed in distinct areas that overlap with high vegfa mRNA expression, including the vhl mutant brain and eye. Real-time quantitative PCR revealed increased expression of the duplicated VEGFA orthologs vegfaa and vegfab, and of vegfb and its receptors flt1, kdr and kdr-like, indicating increased vascular endothelial growth factor (Vegf) signaling in vhl mutants. Similar to VHL-associated retinal neoplasms, diabetic retinopathy and age-related macular degeneration, we show, by tetramethyl rhodamine-dextran angiography, that vascular abnormalities in the vhl(-/-) retina lead to vascular leakage, severe macular edema and retinal detachment. Significantly, vessels in the brain and eye express cxcr4a, a marker gene expressed by tumor and vascular cells in VHL-associated hemangioblastomas and renal cell carcinomas. VEGF receptor (VEGFR) tyrosine kinase inhibition (through exposure to sunitinib and 676475) blocked vhl(-/-)-induced angiogenesis in all affected tissues, demonstrating that Vegfaa, Vegfab and Vegfb are key effectors of the vhl(-/-) angiogenic phenotype through Flt1, Kdr and Kdr-like signaling. Since we show that the vhl(-/-) angiogenic phenotype shares distinct characteristics with VHL-associated vascular neoplasms, zebrafish vhl mutants provide a valuable in vivo vertebrate model to elucidate underlying mechanisms contributing to the development of these lesions. Furthermore, vhl mutant zebrafish embryos carrying blood vessel-specific transgenes represent a unique and clinically relevant model for tissue-specific, hypoxia-induced pathological angiogenesis and vascular retinopathies. Importantly, they will allow for a cost-effective, non-invasive and efficient way to screen for novel pharmacological agents and combinatorial treatments.

Ccbe1 is required for embryonic lymphangiogenesis and venous sprouting

by Jeroen Bussmann

Lymphatic vessels have important roles in fluid homeostasis, fat absorption, inflammation and cancer metastasis and... more Lymphatic vessels have important roles in fluid homeostasis, fat absorption, inflammation and cancer metastasis and develop in a dynamic process (called lymphangiogenesis) involving budding, migration and proliferation of lymphangioblasts. Using a genetic screen in zebrafish we identify ccbe1 (collagen and calcium-binding EGF domain-1) as indispensible for embryonic lymphangiogenesis. Ccbe1 acts at the same stage of development as Vegfc and is required for lymphangioblast budding and angiogenic sprouting from venous endothelium.

Role of Dll4/Notch in the formation and wiring of the lymphatic network in zebra fish

by Jeroen Bussmann

Objective— To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls... more Objective— To study whether Notch signaling, which regulates cell fate decisions and vessel morphogenesis, controls lymphatic development.

Methods and Results— In zebrafish embryos, sprouts from the axial vein have lymphangiogenic potential because they give rise to the first lymphatics. Knockdown of delta-like-4 (Dll4) or its receptors Notch-1b or Notch-6 in zebrafish impaired lymphangiogenesis. Dll4/Notch silencing reduced the number of sprouts producing the string of parchordal lymphangioblasts; instead, sprouts connecting to the intersomitic vessels were formed. At a later phase, Notch silencing impaired navigation of lymphatic intersomitic vessels along their arterial templates.

Conclusion— These studies imply critical roles for Notch signaling in the formation and wiring of the lymphatic network.

Arteries provide essential guidance cues for lymphatic endothelial cells in the zebrafish trunk

by Jeroen Bussmann

The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the... more The endothelial cells of the vertebrate lymphatic system assemble into complex networks, but local cues that guide the migration of this distinct set of cells are currently unknown. As a model for lymphatic patterning, we have studied the simple vascular network of the zebrafish trunk consisting of three types of lymphatic vessels that develop in close connection with the blood vasculature. We have generated transgenic lines that allow us to distinguish between arterial, venous and lymphatic endothelial cells (LECs) within a single zebrafish embryo. We found that LECs migrate exclusively along arteries in a manner that suggests that arterial endothelial cells serve as the LEC migratory substrate. In the absence of intersegmental arteries, LEC migration in the trunk is blocked. Our data therefore demonstrate a crucial role for arteries in LEC guidance.

Arterial-venous network formation during brain vascularization involves hemodynamic regulation of chemokine signaling

by Jeroen Bussmann

During angiogenic sprouting, newly forming blood vessels need to connect to the existing vasculature in order to... more During angiogenic sprouting, newly forming blood vessels need to connect to the existing vasculature in order to establish a functional circulatory loop. Previous studies have implicated genetic pathways, such as VEGF and Notch signaling, in controlling angiogenesis. We show here that both pathways similarly act during vascularization of the zebrafish central nervous system. In addition, we find that chemokine signaling specifically controls arterial-venous network formation in the brain. Zebrafish mutants for the chemokine receptor cxcr4a or its ligand cxcl12b establish a decreased number of arterial-venous connections, leading to the formation of an unperfused and interconnected blood vessel network. We further find that expression of cxcr4a in newly forming brain capillaries is negatively regulated by blood flow. Accordingly, unperfused vessels continue to express cxcr4a, whereas connection of these vessels to the arterial circulation leads to rapid downregulation of cxcr4a expression and loss of angiogenic characteristics in endothelial cells, such as filopodia formation. Together, our findings indicate that hemodynamics, in addition to genetic pathways, influence vascular morphogenesis by regulating the expression of a proangiogenic factor that is necessary for the correct pathfinding of sprouting brain capillaries.

Rotation and asymmetric development of the zebrafish heart requires directed migration of cardiac progenitor cells

by Jeroen Bussmann

We have used high-resolution 4D imaging of cardiac progenitor cells (CPCs) in zebrafish to investigate the earliest... more We have used high-resolution 4D imaging of cardiac progenitor cells (CPCs) in zebrafish to investigate the earliest left-right asymmetric movements during cardiac morphogenesis. Differential migratory behavior within the heart field was observed, resulting in a rotation of the heart tube. The leftward displacement and rotation of the tube requires hyaluronan synthase 2 expression within the CPCs. Furthermore, by reducing or ectopically activating BMP signaling or by implantation of BMP beads we could demonstrate that BMP signaling, which is asymmetrically activated in the lateral plate mesoderm and regulated by early left-right signals, is required to direct CPC migration and cardiac rotation. Together, these results support a model in which CPCs migrate toward a BMP source during development of the linear heart tube, providing a mechanism by which the left-right axis drives asymmetric development of the vertebrate heart.

Early endocardial morphogenesis requires Scl/Tal1

by Jeroen Bussmann

The primitive heart tube is composed of an outer myocardial and an inner endocardial layer that will give rise to the... more The primitive heart tube is composed of an outer myocardial and an inner endocardial layer that will give rise to the cardiac valves and septa. Specification and differentiation of these two cell layers are among the earliest events in heart development, but the embryonic origins and genetic regulation of early endocardial development remain largely undefined. We have analyzed early endocardial development in the zebrafish using time-lapse confocal microscopy and show that the endocardium seems to originate from a region in the lateral plate mesoderm that will give rise to hematopoietic cells of the primitive myeloid lineage. Endocardial precursors appear to rapidly migrate to the site of heart tube formation, where they arrive prior to the bilateral myocardial primordia. Analysis of a newly discovered zebrafish Scl/Tal1 mutant showed an additional and previously undescribed role of this transcription factor during the development of the endocardium. In Scl/Tal1 mutant embryos, endocardial precursors are specified, but migration is severely defective and endocardial cells aggregate at the ventricular pole of the heart. We further show that the initial fusion of the bilateral myocardial precursor populations occurs independently of the endocardium and tal1 function. Our results suggest early separation of the two components of the primitive heart tube and imply Scl/Tal1 as an indispensable component of the molecular hierarchy that controls endocardium morphogenesis.

Punjabi Sikh Patients’ Perceived Barriers to Engaging in Physical Exercise Following Myocardial Infarction

by Paul Galdas

Galdas, P.M. Oliffe, J.L. Kang, H.B.K., Kelly, M.T.

Objective
The aim of this research was to describe Punjabi Sikh patients’ perceived barriers to engaging in... more Objective
The aim of this research was to describe Punjabi Sikh patients’ perceived barriers to engaging in physical exercise following myocardial infarction (MI).

Design and Sample
A qualitative, interpretive descriptive methodology was used. The sample included 15 Punjabi Sikh patients who were attending a cardiac rehabilitation education program in an urban center of British Columbia, Canada, following MI.

Measurements
Data were collected via semi-structured interviews and were audio recorded, translated from Punjabi to English, and transcribed verbatim. Data were analyzed using an interpretive thematic approach that involved a process of coding and constant comparison.

Results
Four key factors emerged that related to participants’ perceived barriers to sustained engagement in physical activity: (1) difficulty in determining safe exertion levels independently; (2) fatigue and weakness; (3) preference for ‘informal’ exercise; and (4) migration-related challenges.

Conclusions
The findings have implications for the design and delivery of health promotion strategies aimed at Punjabi Sikh patients’ post-MI that is contingent on the use of ‘formal’ exercise settings to promote regular physical activity. The willingness among Punjabi Sikh patients to practise brisk walking offers a positive direction that public health nurses and other healthcare professionals may want to capitalize on in the delivery of exercise-related health promotion.

Effects of Verbal Suggestion on Coronary Arteries: Results of a randomized controlled experimental investigation during coronary angiography

by Karin Meissner

Ronel J, Mehilli J, Ladwig K-H, Blättler H, Oversohl N, Byrne RA, Bauer A, Schneider S, Linde K, Henningsen P, Lahmann C, Noll-Hussong M, Meissner, K
American Heart Journal 2011;162(3):507-511

Background Decrease of chest pain perception under placebo conditions has been frequently observed. The aim of this... more Background Decrease of chest pain perception under placebo conditions has been frequently observed. The aim of this study was to examine whether placebo-induced chest pain improvement could be the result of changes in coronary blood flow. We, therefore, performed an experiment to investigate whether a verbal suggestion (VS) integrated in a cardiologic procedure has an impact on diameters of coronary arteries.Methods A total of 30 chest pain patients with normal diagnostic angiograms were assigned to a VS or a control group (CG). Saline solution was administered intracoronarily to both groups. The VS group received a standardized VS, implying coronary vasodilation. The CG remained without VS. Coronary end points were the changes in percentage diameter stenosis, Minimal lumen diameter and reference diameter of the index coronary segment before and 60 seconds after the administration of saline. Furthermore, changes in hemodynamics, psychological distress, and chest pain perception were recorded.Results The VS led to coronary vasoconstriction in comparison with CG (change in mean percentage diameter stenosis ± SD 3.2% ± 6.3% vs -1.7% ± 6.8%, P = .062; change in mean minimal lumen diameter ± SD -0.18 ± 0.32 mm vs 0.06 ± 0.23 mm, P = .029, no relevant change in the reference diameter). At the same time, the degree of chest pain perception was significantly reduced in the VS group (-0.7 ± 1.3) compared with the CG (0.3 ± 1.3), P = .024.Conclusion The findings of this study suggest that a VS results in a biological alteration within coronary arteries. Contrary to expectation, the VS led to vasoconstriction, whereas chest pain perception decreased. .

Therapeutic strategies targeting endothelial function in humans: clinical implications

by Regent Lee

Persistent oxidative stress in the vascular wall may lead to endothelial dysfunction, a pathological process widely... more Persistent oxidative stress in the vascular wall may lead to endothelial dysfunction, a pathological process widely implicated in the morbidities observed in a spectrum of cardiovascular disease. The production of reactive oxygen species (ROS) is regulated by various oxidase enzymes and mitochondrial electron transport mechanisms. Nitric oxide (NO) is a key mediator of endothelial function via its effect on endothelium dependent vascular relaxation. Therapeutic interventions that aimed to increase NO bioavailability in the vasculature may improve the long term cardiovascular outcome for healthy individuals, high-risk subjects, and patients with advanced atherosclerosis. Current therapeutic strategies focus on enhancing synthesis or lowering oxidative inactivation of NO in human vasculature. Of the available therapeutic agents, angiotensin converting enzyme inhibitors and statins have shown to be most promising at improving endothelial function and cardiovascular outcome after long term administration. Other therapeutic approaches may also be useful towards improving endothelial dysfunction. These strategies include targeting NO synthesis by modulation of endothelial nitric oxide synthase (eNOS) coupling, such as folates and tetrahydrobiopterin. Evidence for the benefits of gene therapy to improve endothelial function is also emerging. However, the long term direct clinical benefit of these strategies that aimed to improve endothelial function still remains unclear.

Participation in sports and leisure activities of young people with known cardiovascular abnormalities

by Leonidas Poulimenos

Hellenic J Cardiol. 2008 May-Jun;49(3):176-85.