Paradoxical Association of C-Reactive Protein with Endothelial Function in Rheumatoid Arthritis

Background: Within the general population, levels of C-reactive protein (CRP) are positively associated with atherosclerotic cardiovascular disease (CVD). Whether CRP is causally implicated in atherogenesis or is the results of atherosclerosis is disputed. A role of CRP to protect endothelium-derived nitric oxide (EDNO) has been suggested. We examined the association of CRP with EDNO-dependent vasomotor function and subclinical measures of atherosclerosis and arteriosclerosis in patients with raised CRP resulting from rheumatoid arthritis (RA).Methodology/Principal Findings: Patients with RA (n = 59) and healthy control subjects (n = 123), underwent measures of high sensitivity CRP, flow-mediated dilation (FMD, dependent on EDNO), intima-media thickness (IMT, a measure of subclinical atherosclerosis) and aortic pulse wave velocity (PWV, a measure of arteriosclerosis). IMT and PWV were elevated in patients with RA compared to controls but FMD was similar in the two groups. In patients with RA, IMT and PWV were not correlated with CRP but FMD was positively independently correlated with CRP (P<0.01).Conclusions/Significance: These findings argue against a causal role of CRP in atherogenesis and are consistent with a protective effect of CRP on EDNO bioavailability

Microbubbles shunting via a patent foramen ovale impair endothelial function

Objectives Exposure to intravascular microbubbles after diving and during medical procedures alters endothelial function. The aim of this study was to investigate whether a patent foramen ovale altered forearm endothelial function by facilitating microbubbles transfer. Design Patients attended on two separate visits, at least seven days apart receiving agitated saline or no active intervention in random order. On both days, flow-mediated dilatation of the brachial artery was measured using vascular ultrasound. On the intervention visit, agitated saline was injected and the passage of microbubbles into the arterial circulation was confirmed by echocardiography. Serial flow-mediated dilatation measurements were made after agitated saline and at the same time points after no intervention. Setting St Thomas’ Hospital in London. Participants Patients with a patent foramen ovale (PFO+n = 14, 9 male, mean ± SD age 42.2 ± 10.5 years) and patients without a patent foramen ovale (PFO− n = 10, 7 male, mean ± SD age 49.4 ± 18.4 years) were recruited. Main outcome measures Change in brachial artery flow-mediated dilatation. Results In patent foramen ovale + patients, flow-mediated dilatation did not change significantly on the control day but after agitated saline reduced by 2.3 ± 0.3%, 20 minutes after bubble injection ( P  < 0.005 vs. corresponding change in flow-mediated dilatation during control study). There was no significant change in flow-mediated dilatation for patent foramen ovale− patients at either visit. Conclusion These results suggest that the presence of a patent foramen ovale facilitated impairment of endothelial function acutely by the transfer of microbubbles into the arterial circulation. As a patent foramen ovale is a common condition, this may be relevant to microbubbles exposure in medical procedures and in decompression illness

Progression of Central Pulse Pressure Over 1 Decade of Aging and its Reversal by Nitroglycerin:A Twin Study

ObjectivesThe goal of this study was to examine the progression of central arterial pulse pressure (cPP) in women and the degree to which this can be reversed by nitrovasodilation.BackgroundcPP can be partitioned into height of the first systolic shoulder (P1), generated by a forward pressure wave and related to arterial stiffness, and augmentation pressure (AP), thought to be influenced by pressure wave reflection from muscular arteries and/or aortic reservoir.MethodsUsing a longitudinal cohort design, cPP, P1, and AP were estimated (using the SphygmoCor System [AtCor Medical Pty Ltd., West Ryde, Australia]) in 411 female twins over a mean follow-up of 10.8 years. In a subsample (n = 42), cPP, arterial stiffness (using pulse wave velocity [PWV]) and arterial diameters (using ultrasonography) were measured before and after nitroglycerin administration (400 μg s/l).ResultscPP increased more than peripheral pulse pressure (10.3 and 9.2 mm Hg, respectively; p < 0.0001). In women <60 years of age at follow-up, AP contributed more to the increase in cPP than did P1 (increases of 6.5 ± 6.4 mm Hg and 4.2 ± 7.8 mm Hg, respectively). P1 was significantly positively correlated to PWV (p < 0.0001); AP was correlated to aorto-femoral tapering (p < 0.0001) but not PWV. Nitroglycerin reduced cPP by 10.0 ± 6.0 mm Hg (p < 0.0001), equivalent to a decade of aging. The reduction in cPP was entirely explained by a decrease in AP, with no significant change in P1 or PWV but an increase in large artery diameters of 4% to 18% (p < 0.0001).ConclusionsAge-related widening of cPP is driven in large part by an increase in AP, which can be reversed by selective dilation of muscular arteries, independent of PWV

Flow-Mediated Dilation of the Radial Artery Is Offset by Flow-Induced Reduction in Transmural Pressure

Flow-mediated dilation of the brachial or radial artery in response to transient hyperaemic flow, the most widely used test of endothelial function, is only manifest after flow decays back to baseline. We examined whether this dissociation of flow and diameter might be explained by a reduction in transmural pressure generated by high flow. Studies were performed in healthy subjects 20 to 55 years of age. Flow-mediated dilation was measured in the radial artery using a standard protocol and after flow interruption at peak hyperemia during brachial artery infusion of saline and the NO synthase inhibitor N G -monomethyl- l -arginine (8 μmol/min). Flow interruption 20 seconds after cuff release (during high flow but no dilatation) produced an immediate increase in radial artery diameter of 5.36±2.12%, inhibited by N G -monomethyl- l -arginine to 1.09±0.67% (n=8; P &lt;0.001). Mean intra-arterial radial blood pressure and, hence, transmural pressure fell after cuff release by a mean of 26±1.8 mm Hg (n=6; P &lt;0.0001) at the time of peak hyperemic flow. Modulation of transmural pressure within the brachial artery by cuff inflation around the artery demonstrated that this fall is sufficient to reduce arterial diameter by an amount similar to flow-mediated dilation. These results suggest that flow-dependent, NO-dependent dilation is offset by a flow-induced fall in local arterial pressure and, hence, in transmural pressure. Shear related NO release is likely to play a greater role in the short-term regulation of arterial tone than that suggested by flow-mediated dilation. </jats:p

Blood Pressure in Healthy Humans is Regulated by Neuronal NO Synthase

NO is physiologically generated by endothelial and neuronal NO synthase (nNOS) isoforms. Although nNOS was first identified in brain, it is expressed in other tissues, including perivascular nerves, cardiac and skeletal muscle. Increasing experimental evidence suggests that nNOS has important effects on cardiovascular function, but its composite effects on systemic hemodynamics in humans are unknown. We undertook the first human study to assess the physiological effects of systemic nNOS inhibition on basal hemodynamics. Seventeen healthy normotensive men aged 24±4 years received acute intravenous infusions of an nNOS-selective inhibitor, S-methyl-l-thiocitrulline, and placebo on separate occasions. An initial dose-escalation study showed that S-methyl-l-thiocitrulline (0.1–3.0 µmol/kg) induced dose-dependent changes in systemic hemodynamics. The highest dose of S-methyl-l-thiocitrulline (3.0 µmol/kg over 10 minutes) significantly increased systemic vascular resistance (+42±6%) and diastolic blood pressure (67±1 to 77±3 mm Hg) when compared with placebo (both P<0.01). There were significant decreases in heart rate (60±4 to 51±3 bpm; P<0.01) and left ventricular stroke volume (59±6 to 51±6 mL; P<0.01) but ejection fraction was unaltered. S-methyl-l-thiocitrulline had no effect on radial artery flow-mediated dilatation, an index of endothelial NOS activity. These results suggest that nNOS-derived NO has an important role in the physiological regulation of basal systemic vascular resistance and blood pressure in healthy humans

Graph Embedding: A General Framework for Dimensionality Reduction

In the last decades, a large family of algorithms ─ supervised or unsupervised; stemming from statistic or geometry theory─have been proposed to provide different solutions to the problem of dimensionality reduction. In this paper, beyond the different motivations of these algorithms, we propose a general framework, graph embedding along with its linearization and kernelization, which in theory reveals the underlying objective shared by most previous algorithms. It presents a unified perspective to understand these algorithms; that is, each algorithm can be considered as the direct graph embedding or its linear/kernel extension of some specific graph characterizing certain statistic or geometry property of a data set. Furthermore, this framework is a general platform to develop new algorithm for dimensionality reduction. To this end, we propose a new supervised algorithm, Marginal Fisher Analysis (MFA), for dimensionality reduction by designing two graphs that characterize the intra-class compactness and interclass separability, respectively. MFA measures the intra-class compactness with the distance between each data point and its neighboring points of the same class, and measures the inter-class separability with the class margins; thus it overcomes the limitations of traditional Linear Discriminant Analysis algorithm in terms of data distribution assumptions and available projection directions. The toy problem on artificial data and the real face recognition experiments both show the superiority of our proposed MFA in comparison to LDA. 1

Relation of arterial stiffness to left ventricular structure and function in healthy women

Abstract Background Interactions between the left ventricular (LV) and the arterial system, (ventricular-arterial coupling) are key determinants of cardiovascular function. However, most of studies covered multiple cardiovascular risk factors, which also contributed to the morphological and functional changes of LV. The aim of this study was to examine the relationship between arterial stiffness and LV structure and function in healthy women with a low burden of risk factors. Methods Healthy women from the Twins UK cohort (n = 147, mean age was 54.07 ± 11.90 years) were studied. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV). LV structure and function were assessed by two-dimensional speckle tracking echocardiography. Results cf-PWV was significantly associated with most measures of LV geometry and function, including relative wall thickness (RWT), E/e’ ratio, global circumferential and radial strain, apical rotation and LV twist (each p <  0.05), but bore no relation to global longitudinal strain. After adjustment for age, body mass index, blood pressure and heart rate, cf-PWV was significantly correlated with RWT, global circumferential strain, apical rotation and LV twist (β = 0.011, − 0.484, 1.167 and 1.089, respectively, each p ≤  0.05). Conclusions In healthy women with a low burden of risk factors, elevated arterial stiffness was intimately interwoven with increased LV twisting even before LV dysfunction becomes clinically evident

Birth weight and cardiac structure in children

OBJECTIVE: Epidemiologic studies have shown associations between impaired fetal growth and risk for coronary heart disease in adults. The underlying mechanisms are unknown. We investigated whether restricted intrauterine growth affects cardiac structure. METHODS: We performed echocardiography on 216 9-year-old children who were measured previously at birth. The diameter of the coronary left and right main branches was derived from the widest dimension; total coronary artery diameter was calculated by adding the diameters of the left and right coronary arteries. Aortic root diameter, left atrial diameter, left ventricular diameter, left ventricular outflow tract diameter, and left ventricular mass were measured. RESULTS: On average, children who had weighed less at birth had a smaller total coronary artery diameter, aortic root diameter, and left ventricular outflow tract diameter after adjustment for gender, gestational age, current height and weight, and maternal height and prepregnant weight. For each SD increase in birth weight, total coronary diameter rose by 0.10 mm, log aortic root diameter rose by 1.5%, and log left ventricular outflow tract diameter rose by 1.6%. CONCLUSION: Impaired fetal growth may have long-term effects on cardiac structure. This may help to explain why adults whose birth weight was low are at greater risk for coronary heart disease