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An obesity paradox wherein a lower incidence of cardiovascular (CV) morbidity and mortality is seen in overweight/ obese patients compared with patients with a ‘normal’ body mass index (BMI) has been reported in patients with type 2 diabetes mellitus (T2DM). We evaluated the relationship between BMI and coronary atherosclerosis in a cohort of subjects with T2DM who were asymptomatic for CV disease using computed tomography coronary angiography. Subjects were followed up for a composite endpoint of all-cause death, non-fatal myocardial infarction or late coronary artery revascularisation. Of the 258 patients enrolled, 226 were eligible for follow-up over a median of 22.8 months. In patients with a normal BMI (30 kg/m2 at baseline. Subjects with a BMI ≥35 kg/m2 were 82% less likely to present with significant coronary artery plaque at baseline compared with those with a BMI 25 kg/m2) was approximately 70% lower than in subjects with normal weight. In conclusion, higher BMI may be associated with a lower prevalence of coronary atherosclerosis in patients with T2DM.

Epicardial adipose tissue has a paracrine effect, enhancing coronary artery atherosclerotic plaque development. This study evaluated epicardial fat volume (EFV), adipokines, coronary atherosclerosis, and adverse cardiovascular events in a cohort of asymptomatic patients with type 2 diabetes mellitus (T2DM). Epicardial fat volume was calculated using data from computed tomography coronary angiograms. Adipokines and inflammatory cytokines were also assayed and correlated with EFV. Epicardial fat volume was also assessed as a predictor of coronary artery calcium (CAC) score, number of coronary artery plaques, and significant plaque (>50% luminal stenosis). Data from the EFV analysis were available for 221 (85.7%) participants. Median EFV was 97.4 cm3, mean body mass index was 28.1 kg/m2, and mean duration of T2DM was 13 years. Statistically significant, but weak, correlations were observed between several adipokines, inflammatory cytokines, and EFV. Epicardial fat volume was a significant univariate ( P = .01), but not multivariate, predictor of the number of coronary plaques, but not of CAC score or significant plaque. After a mean follow-up of 22.8 months, 12 adverse cardiovascular events were reported, exclusively in participants with EFV >97.4 cm3. Epicardial fat volume has limited utility as a marker of coronary artery plaque in patients with T2DM and is weakly correlated with adipokine expression.

Hepatocyte growth factor (HGF) is released by stressed human vascular cells and promotes vascular cell repair responses in both autocrine and paracrine ways. Subjects with a low capacity to express HGF in response to systemic stress have an increased cardiovascular risk. Human atherosclerotic plaques with a low content of HGF have a more unstable phenotype. The present study shows that subjects with a low ability to express HGF in response to metabolic stress have an increased risk to suffer myocardial infarction and stroke.

Background Evidence from imaging studies suggests a high prevalence of coronary artery disease (CAD) in patients with type 2 diabetes mellitus (T2DM). However, there are no criteria for initiating screening for CAD in this population. The current study investigated whether clinical and demographic characteristics can be used to predict significant CAD in patients with T2DM. Methods Computed tomography coronary angiography (CTCA) and laboratory assessments were performed in 259 patients diagnosed with T2DM attending clinics in Northwest London, UK. Coronary artery calcium (CAC) was calculated during CTCA. Significant plaque was defined as one causing more than 50% luminal stenosis. Associations between groups and variables were evaluated using Student’s t test, Chi-square tests and univariate and multivariate regression analysis. P Results Among patients with a median duration of T2DM of 13 years and a mean age of 62.0 years, median CAC score was 105.91 Agatston Units. In a multivariate analyses, duration of diabetes, CAC score and the presence and number of coronary artery plaques and presence of significant plaque were significant predictors of cardiovascular adverse events. Systolic blood pressure (SBP) had borderline significance as a predictor of cardiovascular events (p = 0.05). In a receiver operating characteristic curve (ROC) analysis, duration of diabetes of > 10.5 years predicted significant CAD (sensitivity, 75.3%; specificity 48.2%). Area under the ROC curve was 0.67 when combining duration of T2DM > 10.5 years and SBP of > 139 mm Hg. Adverse cardiovascular events after a median follow-up of 22.8 months were also significantly higher in those with duration of T2DM > 10.5 years and SBP > 140 mm Hg (log rank p = 0.02 and 0.009, respectively). Conclusions Routine screening for CAD using CTCA should be considered for patients with a diagnosis of T2DM for > 10.5 years and SBP > 140 mm Hg. Trial registration Clinicaltrials.gov identifier: NCT02109835, 10 April 2014 (retrospectively registered)

Endothelial dysfunction is common in patients with type 2 diabetes mellitus (T2DM) and is associated with atherosclerotic disease. This study aimed to determine prognostic factors for endothelial dysfunction and identify relationships between reactive hyperemia index (RHI) score, clinically relevant coronary artery disease (>50% stenosis), and major adverse cardiovascular events (MACEs) in patients with T2DM. Endothelial function was assessed using peripheral arterial tonometry and correlated with patient characteristics and cardiovascular outcomes during a median follow-up of 22.8 months. Among 235 patients with a median duration of T2DM of 13 years, mean (standard deviation) RHI score was 2.00 (0.76). Serum low- and high-density lipoprotein cholesterol levels positively ( P = .004) and negatively ( P = .02) predicted RHI score, respectively. Median coronary artery calcium (CAC) score was 109 Agatston units, but no correlation between CAC and RHI scores was observed. The RHI score did not predict the number or severity of coronary plaques identified using computed tomography coronary angiography. Additionally, there was no association between RHI score and the risk of an MACE during follow-up. Overall, endothelial function was not predictive of CAC score, extent, and severity of coronary plaque or MACEs and did not demonstrate utility in cardiovascular risk stratifying patients with T2DM.

Background: Acute cardiovascular events arise when the arterial wall fails to repair the damage caused by cardiovascular risk factors. Hepatocyte growth factor (HGF) stimulates growth of vascular cells but has been associated with increased risk of cardiovascular disease (CVD) in epidemiological studies. Here we tested the hypothesis that this association reflects activation of a protective vascular repair response. Methods: Small interfering RNA (siRNA) and recombinant human HGF were used to assess the role of HGF in regulation of human umbilical cord endothelial and coronary artery smooth muscle cell proliferation, migration and viability. Proximity extension assay was used to determine HGF and other biomarkers in 4742 subjects participating in the Malmo Diet and Cancer study and in extracts of 200 human carotid plaques. Findings: HGF promoted migration, proliferation and survival of human endothelial and smooth muscle cells. Human atherosclerotic plaques with a high content of HGF had a more stable phenotype. Cultured vascular cells expressed HGF in response to stress. Plasma HGF correlated with circulating levels of cellular stress biomarkers such as soluble TRAIL receptor-2 and caspase-8. Decreased ability to respond with elevated HGF levels to cellular stress, as assessed by the ratios of HGF to soluble TRAIL receptor-2 and caspase-8, associated with increased risk of cardiovascular events during a follow-up period of 19.4±5.0 years. Interpretations: These findings provide support for a protective role of HGF in CVD and show that subjects with a low ability to express HGF in response to stress have an increased risk of cardiovascular events. Funding Information: The work was supported by the Swedish Society for Medical Research, Emil and Wera Cornell foundation, Hjelt foundation, the Swedish Research Council, the Swedish Foundation for International Cooperation in Research and Higher Education, Crafoord foundation, the Swedish Medical Society, Diabetes foundation, Swedish Heart and Lung Foundation, Diabetes Research and Wellness foundation, Albert Pahlssons foundation, SUS foundations and funds, Lund University Infrastructure grant ”Malmo population-based cohorts” (STYR 2019/2046) and Lund University Diabetes Center (Swedish Research Council - Strategic Research Area Exodiab Dnr 2009-1039 and the Swedish Foundation for Strategic Research Dnr IRC15-006). Declaration of Interests: None. Ethics Approval Statement: All studies were approved by the respective Regional Ethical Review Boards and conducted in accordance with the Helsinki Declaration. All subjects gave written consent.

Placental growth factor (PlGF) is a mitogen for endothelial cells, but it can also act as a proinflammatory cytokine. Because it promotes early stages of plaque formation in experimental models of atherosclerosis and was implicated in epidemiological associations with risk of cardiovascular disease (CVD), PlGF has been attributed a pro-atherogenic role. Here, we investigated whether PlGF has a protective role in CVD and whether elevated PlGF reflects activation of repair processes in response to vascular stress. In a population cohort of 4742 individuals with 20 years of follow-up, high baseline plasma PlGF was associated with increased risk of cardiovascular death, myocardial infarction, and stroke, but these associations were lost or weakened when adjusting for cardiovascular risk factors known to cause vascular stress. Exposure of cultured endothelial cells to high glucose, oxidized low-density lipoprotein (LDL) or an inducer of apoptosis enhanced the release of PlGF. Smooth muscle cells and endothelial cells treated with PlGF small interference RNA demonstrated that autocrine PlGF stimulation plays an important role in vascular repair responses. High expression of PlGF in human carotid plaques removed at surgery was associated with a more stable plaque phenotype and a lower risk of future cardiovascular events. When adjusting associations of PlGF with cardiovascular risk in the population cohort for plasma soluble tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor-2, a biomarker of cellular stress, a high PlGF/TRAIL receptor-2 ratio was associated with a lower risk. Our findings provide evidence for a protective role of PlGF in CVD.

Carotid intima-media thickness (CIMT) measurement and carotid plaque detection by B-mode ultrasound are frequently used as surrogates to predict coronary artery disease (CAD). However, their systematic use in routine clinical management of asymptomatic patients with diabetes mellitus (DM) has not been studied. The aim of the study was to identify carotid parameters that predict cardiovascular events in patients with asymptomatic type 2 DM by evaluating the relation between carotid disease and CAD. This multicenter, observational, prospective study included 259 asymptomatic patients with type 2 DM followed-up for 34 months after measurement of CIMT and carotid plaque with carotid ultrasound, and CAD assessment with computed tomography coronary angiography. Statistically significant differences between patients with and without carotid plaque were found for coronary plaque >50% stenosis (59 vs 36, p = 0.02). Greater maximal CIMT was associated with an increased risk of coronary plaque >50% (odds ratio 1.21 [1.02, 1.44], p = 0.03) and >70% stenosis (odds ratio 1.23 [1.01, 1.50], p = 0.04) after adjusting for traditional risk factors. At 34-month follow-up, the occurrence of total major adverse cardiovascular event was estimated to be 7.1% (mean age 68 years, 6% male and 1.1% female) in the whole study population. The subgroup of patients with carotid plaque showed increased incidence of major adverse cardiovascular event compared with patients with no carotid plaque (p = 0.005). In conclusion, carotid plaque was a strong predictor of future cardiovascular events and may be a prognostic marker in asymptomatic patients with type 2 DM. Carotid plaque and maximal intima-media thickness were independently associated with obstructive CAD.

Management of significant coronary artery disease is comprised of medical management, whereby risk factors are addressed, and coronary revascularization. The data regarding the survival benefits afforded by emergent coronary revascularization of the culprit vessel in ST elevation myocardial infarction (STEMI) are robust and irrefutable. Revascularization in stable patients with chest pain and the factors guiding it is certainly more contentious. Boden et al, in their landmark, COURAGE trial, showed that despite objective evidence of ischaemia, revascularization with bare metal stents in the patients of the per-cutaneous coronary intervention (PCI) plus optimal medical therapy arm did not provide any survival benefit when compared to optimal medical therapy alone. It is also important to note that target revascularization was always attempted and complete revascularizationwas undertaken where clinically appropriate in the PCI arm. They concluded that revascularization could be delayed without adverse outcomes in this group of patients with stable heart disease evenwith evidence of ischaemia in the medium term. Does this imply that revascularization should be the last resort in patients with refractory angina or the sole preserve of acute coronary syndromes? Even when the decision has been made to proceed with revascularization, there are a multitude of questions that need answered. Do we target just the culprit lesion or is there a role for complete revascularization, whereby all plaques deemed obstructive on invasive coronary angiography are stented? Some may argue that it would be most prudent to let ischaemia guide the revascularization. Physiologically, this argument is unimpeachable but its application would hinge on a functional test that provided evidence of not just degree of stenosis in a single vessel but also multi-vessel disease with a high degree of sensitivity and specificity. The largest body of evidence belongs to myocardial perfusion imaging (MPI) and its value, not just in the diagnosis of ischaemic heart disease but also in predicting shortand medium-term prognosis is well established. In the paper by Li et al in this issue of the Journal of Nuclear Cardiology, the authors have conducted a retrospective study of 170 patients where in they have explored complete vs incomplete coronary revascularization (CCR vs ICR) guided either by coronary angiography (CA) parameters or by myocardial ischaemic burden using MPI. Patients were followed up for 47 ? 21 months and evaluated for a primary end point of all-cause mortality and secondary end points of all major adverse cardiac events and repeat revascularization. For the sake of analysis, four sub-groups were created, CCR-CA ? CCR-MPI (Group 1), CCR-CA ? ICR-MPI (Group 2), ICR-CA ? CCR-MPI (Group 3), and ICR-CA and ICR-MPI (Group 4). All-cause mortality and MACE were significantly different in patients who underwent CCR as compared to those with ICR based on MPI parameters. When CCR and ICR were compared using the CA criteria, there was a difference noted but it was not statistically significant. Cumulative incidence of mortality and MACE was also significantly different in patients undergoing CCR by both CA and MPI parameters when compared to those who had incomplete revascularization based on both CA and MPI Reprint requests: Shreenidhi Venuraju, Clinical Imaging and Research Centre, Wellington Hospital, St. Johns Wood, London, NW89LE, UK; shreenidhimv@gmail.com. J Nucl Cardiol 2016;23:556–9. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.

BACKGROUND: The value of screening sub‐clinical atherosclerosis in asymptomatic patients with type 2 diabetes mellitus (T2DM) remains controversial. HYPOTHESIS: An integrated model incorporating carotid intima‐media thickness (CIMT) and carotid plaque with traditional risk factors can be used to predict prevalence and severity of coronary artery calcification in asymptomatic T2DM patients. METHODS: A cohort of 262 asymptomatic T2DM patients were prospectively studied with carotid ultrasound to evaluate CIMT and carotid plaque and also a computed tomography coronary artery calcium (CT‐CAC) scan. RESULTS: Carotid plaque was detected in 124 (47%) patients and mean CIMT was 0.75±0.14 mm. Two hundred (76%) patients had a CAC score >0, of whom 57 (22%) had severe coronary atherosclerosis (>400 Au). In this group, carotid plaque was present in 40 (70%) patients (p400 Au; 3.26 [2.05 ‐5.19]). Upper CIMT quartiles showed a similar association (2.55 [1.33 ‐4.87]). CONCLUSION: Carotid plaque is more predictive of underlying silent coronary atherosclerosis prevalence, severity and extent in asymptomatic T2DM patients.

We determined whether increased carotid intima–media thickness (cIMT) and prevalence of carotid plaque (CP) are predictive of prevalence and severity of coronary atherosclerosis. Consecutive patients (n = 150) with no history of coronary artery disease (CAD), who underwent both carotid ultrasound and computed tomographic coronary angiography, were included in the analysis. The mean cIMT was higher in patients with CAD than in those without CAD (0.76 vs 0.66 mm, P < .003). In a logistic regression analysis, diabetes ( P = .03) and CP ( P = .02) were associated with significant coronary plaque. Backward selection analysis (after removing nonsignificant variables) showed higher mean cIMT measurement correlated well with prevalence of any coronary plaque ( P = .03) and obstructive coronary plaque disease ( P = .05), whereas presence of CP was a good predictor of both obstructive (>50% stenosis P = .003) and any coronary plaque ( P = .003). In conclusion, CP and cIMT can be useful predictors of prevalence of CAD and its severity.

Background Coronary artery calcium (CAC) imaging by unenhanced computed X-ray tomography (CT) is recommended as an initial diagnostic test for patients with stable chest pain symptoms but a low likelihood (10–29%) of underlying obstructive coronary artery disease (CAD) after clinical assessment. The recommendation has not previously been tested prospectively in a rapid access chest pain clinic (RACPC). Methods We recruited 300 consecutive patients presenting with stable chest pain to the RACPC of three hospitals. All patients underwent CAC imaging, followed by invasive coronary angiography (ICA) in patients with CAC ≥1000Agatston units (Au) and CT coronary angiography (CTCA) in those with CAC 400 Au have a high prevalence of obstructive CAD and further investigation with ICA or functional imaging may be warranted rather than CTCA. These findings support NICE guidance for the investigation of stable chest pain. ClinicalTrials. gov Identifier NCT01464203

Unlike idealized solutions to Maxwell’s equations such as a monochromatic plane wave, a spherical wave, or a cylindrical wave, real-life optical fields are universally characterized by fluctuations, and are to be described in statistical terms. The sources of an electromagnetic field are microscopic in nature, while only certain macroscopic features of the sources can be controlled by us. This corresponds to the contrast between microscopic and macroscopic descriptions of the fields produced by the sources. While the microscopic features relate to spatial and temporal field fluctuations on all scales, requiring an infinite number of details for a complete description, a macroscopic description requires only a few parameters relating to averages of products of the field functions. This chapter aims at a statistical description of optical fields, of the latter category. We first introduce the concepts of stochastic processes, joint probability distributions, autocorrelations, and cross correlations, and briefly explain the notions of stationary, wide-sense stationary, and ergodic processes. The frequency domain description of the statistical features in terms of the power spectrum of a process is explained, along with the idea of the cross-spectral density for two processes, and the Wiener-Kinchin theorem is stated in brief.

An electromagnetic wave propagating through a material medium produces an electrical response in it in the form of an oscillating dipole moment in every small volume element, while the magnetic response is usually small in the visible part of the spectrum. For a wave of a sufficiently large amplitude, the polarization density depends nonlinearly on the electric field amplitude and can be expressed by means of a series of terms of successively higher degrees in the field strength, involving the frequency-dependent susceptibilities of various orders as coefficients, where the susceptibility tensors satisfy a number of symmetry requirements. The polarization density, in turn, acts as the source of the electric field, and the two are then determined by a set of nonlinear wave equations in the medium under consideration. Under appropriate conditions, including those relating to phase matching, the nonlinear wave equation possesses a solution in the form of a superposition of plane waves with a number of different frequencies and with slowly varying amplitudes. A set of ‘input’ waves of specified frequencies results in a set of ‘output’ waves, where the latter include a set of newly generated waves in the medium, depending on the dominant degree of nonlinearity. The medium is commonly a crystalline one whose symmetry class and geometrical orientation determine the amplitude distribution of the waves propagating in the medium, and also the amplitudes of the output waves. The nonlinear susceptibilities can be determined in a theoretical scheme where the quantum mechanical master equation of the atom-field system is set up and its dissipative interaction with a background reservoir is taken into account. The susceptibilities of successively higher orders are then determined in a step-by-step process, where the susceptibility of a given order is determined in terms of the susceptibility of a lower order. These results can then be compared with the susceptibilities calculated in the classical theory, where one finds that the latter theory enjoys a measure of relevance in sofar as the frequency dependence of the susceptibilities is concerned. Explaining all these basic ideas in the present chapter, we consider a number of nonlinear optical processes, setting up the relevant nonlinear wave equations and making a number of simplifying assumptions and approximations. A number of salient features of the second-order nonlinear processes of sum-frequency generation, difference-frequency generation, optical parametric amplification, second-harmonic generation, and parametric down conversion are explained. The working principle of the optical parametric oscillator, a device of great practical importance, is outlined. Several aspects of the third-order process of the optical Kerr effect are explained with reference to the nonlinear wave equation. A number of quantum mechanical aspects of second-harmonic generation and parametric down conversion that are not explained in the classical theory are illustrated by reference to phenomenological Hamiltonians and by working out approximate solutions to the Heisenberg equations for a set of slowly varying annihilation and creation operators. A feature of crucial relevance in the quantum theory of nonlinear processes relates to the role of field fluctuations, including the vacuum fluctuations.

The basic task in Fourier optics is to describe the wave function in an optical field in terms of spatial frequencies, where such a description is achieved by means of the operation of Fourier transformation. This makes possible a neat and useful description of the transformation of the optical field from an input plane to an output plane in an optical system. We begin by recalling the fundamentals of Fourier transformation, with a number of examples. The important concepts of convolution and correlation are introduced, on the basis of which the convolution theorem and the correlation theorem are explained. The propagation of an optical field from a given plane to another in a source-free region is described in the Fresnel (or paraxial) approximation, with the example of a Gaussian beam. In a diffraction situation the propagation in the paraxial approximation through a large distance (or between conjugate planes of an optical system) leads to the Fraunhofer diffraction formula, which can be interpreted in terms of the Fourier transform of the field in the plane of the exit pupil. The action of a thin lens in transforming the phase of an incident field is outlined, and the operation of Fourier transformation of an object field, achieved at the back focal plane of the lens, is explained with reference to various different locations of the object. The operator formalism in the description of field transformation by an optical system is briefly outlined. The concept of a point spread function is explained, and the point spread function for an imaging system between a pair of conjugate planes is related to the Fraunhofer diffraction pattern of the exit pupil. The important concepts of the amplitude transfer function and the optical transfer function, which assume relevance in the contexts of imaging by coherent and incoherent radiation respectively, are elaborated. The effects of aberrations in coherent and incoherent imaging are briefly described. A few applications of Fourier optics are pointed out, proceeding from the central idea of (spatial) frequency filtering, and citing the example of the phase contrast microscope. The principle underlying the action of a ‘4f correlator’ is outlined, referring to its use in optical character recognition. The basic principle underlying the technique of holography is explained in brief.

The term interference refers to phenomena that can be explained in terms of the superposition of two or more wave solutions of Maxwell’s equations, where such an explanation is in the nature of an approximation. We address the problem of interference in a double-slit setup and also in a variant of the Michelson interferometer setup, taking into account the vector nature of electromagnetic waves, and then explain how and to what extent one can obtain an equivalent description of the interference patterns in terms of scalar waves. A fact of central importance is that an interference pattern can be explained primarily in terms of the phase difference of the interfering waves (whether of scalar or vector nature) at various points in space. The vector nature of the waves relates to their states of polarization, which, however, can be accounted for in terms of two sets of scalar waves. The concepts of temporal and spatial coherence are elaborated, and their relevance in explaining interference patterns is underlined. The interference pattern in a double-slit setup with a linearly extended source is considered as an instance of interference by division of the wave front, where an extended fringe system is formed. This is followed by an examination of interference by division of amplitude in a thin film, where, once again, temporal and spatial coherence are of crucial relevance. The use of an extended source leads to loss of spatial coherence, whereby one gets a localized fringe system. For a film of uniform thickness the fringes are localized at infinity, while for a wedge-shaped film, the localization is on the surface of the film. Examples of the two types are found in the Michelson interferometer (fringes of equal inclination) and in Newton’s rings (fringes of equal thickness). The working principle of the Mach-Zehnder interferometer is explained, along with its different modes of operational use. The principle of the stellar interferometer is explained with reference to the aspects of temporal and spatial coherence. The working principles of the Fabry-Perot and Lummer-Gehrcke interferometers are outlined as instances of multiple beam interferometry. A few applications of interferometers are described. Finally, we briefly look at interference as a quantum phenomenon.

In this chapter the basic principles of ray optics are used in the determination of ray paths in optical systems and in the outlining of the fundamentals of optical imaging. Considering the course of a ray through an optical system, one can, in general, define a set of four ‘ray coordinates’ at any given plane that the ray passes through. Considerations are limited, in the main, to linear optics, where one can determine the ray path by successive applications of transfer matrices whereby the ray coordinates are sequentially transformed from one plane to another in the linear approximation. We consider, in particular, Gaussian optics where the optical system is an axially symmetric one. Here it suffices to consider 2 × 2 unimodular transfer matrices instead of the more general 4 × 4 symplectic matrices of linear optics. Starting from the basic translation and refraction matrices, we build up the system matrix for an axially symmetric system, which then gives the condition for image formation and the matrix relating the object plane to the image plane. In considering image formation by such an axially symmetric system, one needs to take into account only the meridional rays, since skew rays lead to the same image as do the meridional ones. The cardinal points of an axially symmetric system are introduced, and a number of specific examples are cited, with examples of the system matrix and the conjugation matrix. The Lagrange-Helmholtz invariant is defined and explained. Basic ideas in Hamiltonian optics are outlined. The Abbe and Herschel conditions for stigmatic imaging are derived. Looking beyond the limits set by Gaussian optics, we outline the theory of Seidel aberrations in axially symmetric systems and explain the various Seidel aberrations, while elaborating the concepts of ray aberration and wave aberration. The idea underlying the calculation of Seidel sums is outlined. The definition and quantitative measure of chromatic aberration is explained. The role of diffraction in imaging is briefly discussed. The working principles of the three classical optical instruments—namely, the telescope, the microscope, and the camera—are briefly outlined.

Maxwell’s equations constitute the basis of optics and electromagnetic theory, where these equations may be considered from the classical or the quantum point of view. Basic ideas and relations in the classical electromagnetic theory are briefly reviewed in this chapter. Important features of the monochromatic plane wave are indicated, including reflection, refraction, and total internal reflection at a planar interface. Features of plane wave propagation in dispersive dielectrics and conducting media are outlined. The relation between group velocity, velocity of energy propagation, and signal velocity is elucidated, referring to Sommerfeld’s and Brillouin’s work. It is briefly explained why a superluminal group velocity does not imply a violation of causality. Spherical and cylindrical wave solutions of Maxwell’s equations are introduced. Features of plane wave propagation in anisotropic media are discussed. Wave propagation in artificially engineered metamaterials is explained in outline. Basic concepts relating to coherence and states of polarization of electromagnetic waves are introduced.

Ray optics, or geometrical optics, is based on the short-wavelength approximation of electromagnetic theory. It is defined in terms of a package of rules (the rules of geometrical optics) that can be arrived at from the Maxwell equations in a consistent approximation scheme, referred to as the eikonal approximation , which is briefly outlined in this chapter. The basic concepts of geometrical wave front, the ray path, and the optical path length are elaborated, and the rules relating to the transport of the field vectors along ray paths are explained. The laws of reflection and refraction are derived, and the approximation scheme leading to the Fresnel formulae is briefly outlined. Basic ideas in variational calculus are explained. The characterization of ray paths in terms of Fermat’s principle is elaborated, and the nature of stationarity of the optical path length is explained with examples. The Lagrangian and Hamiltonian formulations of geometrical optics are outlined, where the determination of the ray path is seen to be analogous to a constrained problem in mechanics. The concepts of caustics and conjugate points are explained, with examples. The path integral formulation is outlined as a useful heuristic principle in geometrical optics. The Luneburg-Kline approach, which gives geometrical optics a secure foundation, is briefly mentioned.

The chapter begins with an explanation of the diffraction problem in optics and electromagnetic theory, with examples. The theory of diffraction involves an approximation scheme that may be considered an improvement over the ray approximation while being distinct from scattering theory. The determination of the diffracted field requires us to take into consideration a set of relevant boundary conditions and the vector nature of the electromagnetic field. For a large class of diffraction problems, however, a scalar approach is effective, while the boundary conditions are also not of crucial relevance. The Kirchhoff scalar theory serves as an important starting point, though it suffers from a number of theoretical limitations, notably those relating to the screen boundary conditions and to the assumption that the aperture field can be replaced with the incident field. The use of Dirichlet- and Neumann-type Green’s functions in Rayleigh-Sommerfeld scalar theory circumvents the first of these but the theory continues to suffer from the second.

Quantum optics deals with processes and phenomena where the quantum states of the electromagnetic field are of central relevance. This chapter begins with a brief summary of the way states and observables are described in the classical theory, explaining the concepts of pure and mixed states and those relating to states of composite systems. The equations describing the time evolutions of pure and mixed states in the phase spaces of systems are stated. The corresponding features of a quantum system are outlined, indicating the contrast between classical and quantum systems. The concept of entanglement as a nonclassical correlation in a composite quantum system is briefly explained. The quantum mechanics of the harmonic oscillator, which is of fundamental relevance in quantum optics, is outlined, highlighting the concepts of number states, coherent states, and squeezed states, comparing the number distributions (mean and variance of the number operator) in these three types of states. The concept of classical and nonclassical states of the quantum harmonic oscillator is explained with reference to the P-representation. The mode decomposition of the electromagnetic field in free space (under periodic boundary conditions) and in a cavity is explained, first in the classical context and then in the quantum mechanical description, where the concept of photons is of central relevance. The modes appear as independent harmonic oscillators, each with its own creation and annihilation operators and with its own photon number distribution. Single-mode number states, coherent states, and squeezed states of the electromagnetic field are described, along with the statistics of field fluctuations in these states. Multimode states are briefly described, and the wave packet number states (including photon-pair states), coherent states, chaotic states, and squeezed states in the continuous-mode description are also explained. The distinction between classical and nonclassical states of the electromagnetic field is explained, and the optical equivalence theorem is outlined. The quantum mechanical description of field transformations by beam splitters and Mach-Zehnder interferometers is explained in brief. With all this background, the chapter contains an outline of the theory of the atom-field interaction, starting from the semiclassical theory of the interaction where the classical electromagnetic field is assumed to interact with the atom possessing quantized energy levels. An expression for the atomic transition rate is derived in the weak interaction limit, followed by an explanation of Rabi oscillations in the nonperturbative regime. The expression for Einstein’s B coefficient is derived. The Jaynes-Cummings model is analyzed, explaining the collapse and revival of the atomic oscillations, and the relation between the bare and dressed states. The idea underlying the master equation as describing the dissipative interaction with a reservoir is explained, and the quantum mechanical derivation of the A and B coefficients is outlined. The principles underlying the working of a laser are briefly explained in terms of the rate equations for a three-level lasing scheme that is effectively a four-level one. A simplified treatment of laser fluctuations is presented. The quantum theory of photon counting is outlined and is compared with the semiclassical theory, and the photon count distribution formula is stated. The quantum correlation functions are introduced, and the quantum mechanical first- and second-order coherence characteristics are compared with the corresponding classical ones with reference to the first- and second-order degrees of coherences for the various types of single- and continuous-mode states of the field. The basic ideas underlying photon antibunching and two-photon interference—two nonclassical phenomena—are briefly explained. The principle of homodyne detection is outlined. The fundamental concepts relating to cavity quantum electrodynamics are developed, and phenomena in the weak and strong coupling regimes are briefly explained. The master equations describing the dissipative interactions of the single atom, the single cavity mode, and the atom-field system with the background field acting as a reservoir are stated, explaining the damped oscillations of the atom-field system. The relevance of quantum optics setups in quantum information processing is briefly outlined, indicating the ways of realizing qubits and quantum gates.

Pericardial fat is emerging as a unique risk factor for coronary disease. We examined the relationship between objectively measured physical activity during free-living and pericardial fat. Participants were 446 healthy men and women (mean age = 66 ± 6 years), without history or objective signs of cardiovascular disease (CVD), drawn from the Whitehall II epidemiological cohort. Physical activity was objectively measured using accelerometers (Actigraph GT3X) worn around the hip during waking hours for 7 consecutive days (average daily wear time = 889 ± 68 min/day), and was classified as sedentary (

Background CT coronary angiography (CTCA) is an evolving modality for the diagnosis of coronary artery disease. Radiation burden associated with CTCA has been a major concern in the wider application of this technique. It is important to reduce the radiation dose without compromising the image quality. Objectives To estimate the radiation dose of CTCA in clinical practice and evaluate the effect of dose-saving algorithms on radiation dose and image quality. Methods Effective radiation dose was measured from the dose-length product in 616 consecutive patients (mean age 58 ± 12 years; 70% males) who underwent clinically indicated CTCA at our institution over 1 year. Image quality was assessed subjectively using a 4-point scale and objectively by measuring the signal- and contrast-to-noise ratios in the coronary arteries. Multivariate linear regression analysis was used to identify factors independently associated with radiation dose. Results Mean effective radiation dose of CTCA was 6.6 ± 3.3 mSv. Radiation dose was significantly reduced by dose saving algorithms such as 100 kV imaging (−47%; 95% CI, −44% to −50%), prospective gating (−35%; 95% CI, −29% to −40%) and ECG controlled tube current modulation (−23%; 95% CI, −9% to −34%). None of the dose saving algorithms were associated with a significant reduction in mean image quality or the frequency of diagnostic scans ( P = non-significant for all comparisons). Conclusion Careful application of radiation-dose saving algorithms in appropriately selected patients can reduce the radiation burden of CTCA significantly, without compromising the image quality.

We consider a finite number of coupled oscillators on a ring as an adaptation of the Kuramoto model of populations of oscillators. The synchronized solutions are characterized by an integer m, the winding number, and a second integer l, with solutions of type (m, l = 0) being all stable. Following a number of recent works (see below) we indicate how the various solutions emerge as the coupling strength K is varied, presenting a perturbative expression for these for large K. The low K scenario is also briefly outlined, where the onset of synchronization by a tangent bifurcation is explained. The simplest situation involving three oscillators is described, where more than one tangent bifurcations are involved. Immediately before the tangent bifurcation leading to synchronization, the system exhibits the phenomenon of frequency- (or phase) splitting where more than one (usually two) phase clusters are involved. All the synchronized solutions are seen to be entrained by an external periodic driving, provided that the driving frequency is sufficiently close to the frequency of the synchronized population. A perturbative approach is outlined for the construction of the entrained solutions. Under a periodic driving with an appropriately limited detuning, there occurs entrainment of the phase-split solutions as well.

Objective— Physical activity is related to lower risk of cardiovascular disease, but data relating to coronary lesions have been conflicting. These inconsistencies may in part be due to unreliable assessment of physical activity and limitations imposed by self-reported data. The purpose of this study was to determine the relationship between objectively measured physical activity and coronary artery calcium (CAC). Methods and Results— Participants were 443 healthy men and women (mean age=66±6 years), without history or objective signs of coronary heart disease, drawn from the Whitehall II epidemiological cohort. Physical activity was objectively measured using accelerometers worn during waking hours for 7 consecutive days (average daily wear time=889±68 minutes/day). CAC was measured in each participant using electron beam computed tomography and was quantified according to the Agatston scoring system. On average, 54.4% of the sample recorded at least 30 minutes/day of moderate to vigorous physical activity (MVPA). There was no association between MVPA and presence of detectable CAC. For the participants with detectable CAC (n=283) a weak inverse relationship between MVPA (minutes/day) and log Agatston score was observed (B=−0.008, 95% CI: −0.16 to 0.00, P =0.05), although the association was no longer present after adjustments for age, sex, and conventional risk factors. No associations were seen for light activity or sedentary time. Conclusion— Our results confirm no association between objectively assessed physical activity and CAC. Because CAC measures cannot identify more vulnerable lesions, additional studies are required to examine whether physical activity can promote plaque stability.

Coronary heart disease (CHD) mortality is 70% higher among Indian Asians (IA) than European whites (EW), the reasons for this excess remain unexplained. Coronary artery calcification (CAC) is highly correlated with coronary plaque burden and silent myocardial ischaemia in EW; but fails to identify excess risk in IA. We hypothesised that IA have a higher prevalence of silent myocardial ischaemia compared to EW, despite similar CAC, and this may explain their excess CHD mortality. CAC was measured for 2,369 asymptomatic men and women, aged 35 to 75 years, as part of the London Life Sciences Population (LOLIPOP) study. 518 subjects had CAC scores >100 Agatston units and of these 256 (49%) patients underwent myocardial perfusion scintigraphy (MPS). CAC scores were similar among IA and EW, after adjustment for conventional risk factors. MPS abnormalities were seen in 56 (22%) subjects. Presence of diabetes (P = .03) and increasing CAC (P

We have described a myocardial infarct scar identified by a standard dual source CT coronary angiography (CTCA). We were able to detect the scar during the routine coronary assessment without contrast late enhancement and without additional radiation exposure. It is therefore feasible to assess chronic scar using a standard CTCA technique.

Objective Extended walking speed is a predictor of incident cardiovascular disease (CVD) in older individuals, but the ability of an objective short-distance walking speed test to stratify the severity of preclinical conditions remains unclear. This study examined whether performance in an 8-ft walking speed test is associated with metabolic risk factors and subclinical atherosclerosis. Design Cross-sectional. Setting Epidemiological cohort. Participants 530 adults (aged 6366 years, 50.3% male) from the Whitehall II cohort study with no known history or objective signs of CVD. Main outcome Electron beam computed tomography and ultrasound was used to assess the presence and extent of coronary artery calcification (CAC) and carotid intima-media thickness (IMT), respectively. Results High levels of CAC (Agatston score >100) were detected in 24% of the sample; the mean IMT was 0.75 mm (SD 0.15). Participants with no detectable CAC completed the walking course 0.16 s (95% CI 0.04 to 0.28) faster than those with CAC $400. Objectively assessed, but not self-reported, faster walking speed was associated with a lower risk of high CAC (odds ratio 0.62, 95% CI 0.40 to 0.96) and lower IMT (b¼� 0.04, 95% CI � 0.01 to � 0.07 mm) in comparison with the slowest walkers (bottom third), after adjusting for conventional risk factors. Faster walking speed was also associated with lower adiposity, C-reactive protein and low-density lipoprotein cholesterol. Conclusions Short-distance walking speed is associated with metabolic risk and subclinical atherosclerosis in older adults without overt CVD. These data suggest that a non-aerobically challenging walking test reflects the presence of underlying vascular disease.

We consider a class of entangled states of a quantum system (S) and a second system (A) where pure states of the former are correlated with mixed states of the latter, and work out the entanglement measure with reference to the nearest separable state. Such `pure-mixed' entanglement is expected when the system S interacts with a macroscopic measuring apparatus in a quantum measurement, where the quantum correlation is destroyed in the process of environment-induced decoherence whereafter only the classical correlation between S and A remains, the latter being large compared to the former. We present numerical evidence that the entangled S-A state drifts towards the nearest separable state through decoherence, with an additional tendency of equimixing among relevant groups of apparatus states., RevTeX4 document, 20 pages, 7 eps figure files

AIMS/HYPOTHESIS: Oxidation of LDL in the arterial extracellular matrix is a key event in the development of atherosclerosis and autoantibodies against oxidised LDL antigens reflect disease severity and the risk of developing acute cardiovascular events. Since type 2 diabetes is associated with increased oxidative stress, we tested the hypothesis that autoantibodies against oxidised LDL antigens are biomarkers for vascular complications in diabetes. METHODS: We studied 497 patients with type 2 diabetes without clinical signs of coronary heart disease. Oxidised LDL autoantibodies were determined by ELISA detecting IgG and IgM specific for native and malondialdehyde (MDA)-modified apolipoprotein B-100 peptides p45 and p210. The severity of coronary disease was assessed as the coronary artery calcium score. RESULTS: Patients affected by retinopathy had significantly higher levels of IgG against MDA-p45 and MDA-p210. In contrast, high levels of autoantibodies against the corresponding native peptides were associated with less coronary calcification and a lower risk of progression of coronary disease. CONCLUSIONS/INTERPRETATION: Our observations suggest that LDL oxidation is involved in the pathogenesis of diabetic retinopathy and that autoantibodies against apolipoprotein B peptides may act as biomarkers for both micro- and macrovascular complications in diabetes.

The IMAGING in Heart Failure study was a prospective, multi-national trial designed to explore the role of single-photon emission computed tomographic (SPECT) myocardial perfusion imaging (MPI) as an initial investigative strategy in patients hospitalized with new-onset heart failure. We recruited 201 patients (age 65.3 ± 14.5 years, 43% women) hospitalized with their first episode of heart failure. Rest/stress gated SPECT Tc-99m sestamibi MPI was performed during or within 2 weeks of the index hospitalization, in addition to standard care. SPECT MPI revealed a broad range of ejection fractions with preserved systolic function in 36% of patients. Forty-one percent of patients had normal perfusion. In the remaining patients, perfusion abnormalities were predominantly due to prior myocardial infarction, with extensive ischemia seen only in 6%. Among patients who underwent coronary angiography, SPECT performance characteristics revealed excellent negative predictive value (96%) for extensive coronary artery disease (CAD). In multivariable analyses, the extent of perfusion abnormality and advancing age predicted the presence of extensive CAD. These preliminary data derived from a non-randomized observational cohort suggest potential diagnostic utility of MPI for ischemic LV dysfunction in new-onset HF, and sets the stage for a prospective randomized study to confirm these findings.

Accelerated atherosclerosis occurs in aortocoronary saphenous vein grafts, contributing to increased morbidity and mortality rates. We estimated the prevalence of asymptomatic graft failure in patients 5 years or more after coronary artery bypass grafting (CABG) using electron-beam computed tomographic angiography (EBA).EBA was performed in 45 symptom-free patients (mean age, 66 +/- 9 years; 87% male; mean time interval after CABG, 8 +/- 5 years). A total of 102 vein grafts and 37 internal mammary artery grafts were evaluated. Patients with graft stenosis or occlusion on EBA underwent myocardial perfusion scintigraphy and invasive angiography. Six grafts were unevaluable by EBA. Twenty patients had evidence of graft stenosis or occlusion on EBA. Of 20 asymptomatic patients with graft disease, 17 (85%) had abnormal myocardial perfusion, with moderate to severe reversible ischemia occurring in one third of subjects. Fourteen occluded and eleven stenosed vein grafts were correctly diagnosed by EBA. There were 2 false-positive EBA diagnoses of graft stenosis, resulting in a 100% positive predictive accuracy for detecting graft occlusion and 85% positive predictive accuracy for detecting graft stenosis. All occluded internal mammary artery grafts (n = 3) were accurately diagnosed.Computed tomographic coronary angiography permits reliable identification of bypass graft stenoses and occlusions in symptom-free patients more than 5 years after CABG. Future studies are needed to assess the prognostic benefit of early detection of graft disease and intervention in asymptomatic patients.

Diabetes is a major cause of mortality and morbidity worldwide, and its prevalence is increasing at alarming proportions. Coronary artery disease (CAD) accounts for 70% of the deaths among diabetic patients. Patients with diabetes have a 2-to-4-fold higher risk of cardiac events than their nondiabetic counterparts. In fact, the risk of myocardial infarction in diabetic patients without previous CAD is comparable to the risk of reinfarction in nondiabetic subjects with previous CAD. Furthermore, patients with diabetes are less likely to survive a first myocardial infarction (MI) than those without diabetes, and those who survive the first MI face a higher risk of reinfarction. Hence it is crucial to diagnose CAD at an early subclinical stage in patients with diabetes, so that high-risk patients can be targeted for aggressive management. The search for a robust, noninvasive technique to screen asymptomatic diabetic patients has been a focus of research, and the potential role of noninvasive techniques such as coronary artery calcium (CAC) imaging and myocardial perfusion imaging (MPI) has triggered controversy and several interesting debates. On the one hand, any strategy involving the use of screening may spiral healthcare budgets out of control, and there is no strong evidence from prospective, randomized trials that a particular strategy can improve clinical outcomes. Diamond et al, in their recent essay on this controversial subject, highlighted the great difficulty in conducting a prospective, randomized trial to evaluate the cost-effectiveness of screening asymptomatic diabetic subjects. They estimated that such a trial would require the randomization of 80,000 subjects followed for 5 years, i.e., a huge investment of resources in view of the small differences in projected outcomes. On the other hand, in diabetic patients, CAD is often asymptomatic and can be well-advanced by the time of presentation. Therefore, it may be negligent to ignore these patients when diabetes is considered a “surrogate” for CAD. It is worth noting here that lack of evidence of effect does not necessarily imply evidence of lack of effect. In the absence of prospective trials exploring the clinical effectiveness and cost-effectiveness of screening strategies for asymptomatic diabetic subjects, we examined the available evidence from several studies that may provide a basis for future trials.

Objectives This study prospectively evaluated the relationship between cardiovascular risk factors, selected biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin [IL]-6, and osteoprotegerin [OPG]), and the progression of coronary artery calcification (CAC) in type 2 diabetic subjects. Background Coronary artery calcification is pathognomonic of coronary atherosclerosis. Osteoprotegerin is a signaling molecule involved in bone remodeling that has been implicated in the regulation of vascular calcification and atherogenesis. Methods Three hundred ninety-eight type 2 diabetic subjects without prior coronary disease or symptoms (age 52 ± 8 years, 61% male, glycated hemoglobin [HbA1c] 8 ± 1.5) were evaluated serially by CAC imaging (mean follow-up 2.5 ± 0.4 years). Progression/regression of CAC was defined as a change ≥2.5 between the square root transformed values of baseline and follow-up volumetric CAC scores. Demographic data, risk factors, glycemic control, medication use, serum hs-CRP, IL-6, and plasma OPG levels were measured at baseline and follow-up. Results Two hundred eleven patients (53%) had CAC at baseline. One hundred eighteen patients (29.6%) had CAC progression, whereas 3 patients (0.8%) had regression. Age, male gender, hypertension, baseline CAC, HbA1c >7, waist-hip ratio, IL-6, OPG, use of beta-blockers, calcium channel antagonists, angiotensin-converting enzyme (ACE) inhibitors, statins, and Framingham/UKPDS (United Kingdom Prospective Diabetes Study) risk scores were univariable predictors of CAC progression. In the multivariate model, baseline CAC (odds ratio [OR] for CAC >400 = 6.38, 95% confidence interval [CI] 2.63 to 15.5, p 7 (OR 1.95, CI 1.08 to 3.52, p = 0.03), and statin use (OR 2.27, CI 1.38 to 3.73, p = 0.001) were independent predictors of CAC progression. Conclusions Baseline CAC severity and suboptimal glycemic control are strong risk factors for CAC progression in type 2 diabetic subjects.

Cardiovascular disease is an escalating worldwide health problem. Effective tools to predict and prevent its development and progression are needed. Correctly diagnosing the metabolic syndrome, which identifies people at higher risk for developing diabetes mellitus and cardiovascular disease, may be valuable in guiding treatment and prevention of these major disorders. Several important definitions of the metabolic syndrome have been proposed. The authors discuss these definitions and how they vary in terms of their relationship to incident cardiovascular disease, type 2 diabetes mellitus, and surrogate markers of atherosclerosis. Establishing clarity on what is meant by the metabolic syndrome and agreement as to its underlying basis is needed to reach consensus between the many different definitions that have been proposed. This is particularly the case if it is to become a useful adjunct in clinical practice to identify those who may benefit from more intensive lifestyle interventions and more detailed short-term risk assessments.

Exercise electrocardiography (ETT) is frequently used in patients with suspected coronary artery disease (CAD). Single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) improves diagnostic stratification. There are no randomized trials comparing ETT and MPI. We hypothesized that first-line MPI would be effective and cost-saving versus ETT.We randomized 457 outpatients with stable chest pain and suspected CAD to either treadmill electrocardiography or MPI. The post-test likelihood incorporated the pretest likelihood and the test result, with clinically driven testing. The primary endpoint was cost to diagnosis based on institutional and National Institute for Clinical Excellence costs. MPI significantly reduced the intermediate post-test likelihood of CAD (30% for ETT vs 3% for MPI, P.0001) and further investigations (71% for ETT vs 16% for MPI, P.0001). Despite the reduction in downstream resource utilization after MPI, mean costs were not different between the 2 initial strategies: 490.44 pounds sterling (95% confidence interval, 453.80-527.08) for ETT versus 512.41 pounds sterling (95% confidence interval, 481.41-543.41) for MPI. MPI cost was no different from ETT cost in patients with an intermediate or high pretest likelihood (P = not significant). ETT was less expensive in low-risk patients.In this study there was no difference in cost to diagnosis between initial ETT and MPI. In low-likelihood patients ETT was less costly, whereas there was no cost difference in intermediate- or high-likelihood patients.

Following an earlier work (briefly reviewed below) we investigate the temporal stability of an exact travelling front solution, constructed in the form of an integral expression, for a one-dimensional discrete Nagumo-like model without recovery. Since the model is a piecewise linear one with an on-site reaction function involving a Heaviside step function, a straightforward linearisation around the front solution presents problems, and we follow an alternative approach in estimating a ‘stability multiplier’ by looking at the variational problem as a succession of linear evolution of the perturbations, punctuated with ‘kicks’ of small but finite duration. Stability depends crucially on perturbations located at specific sites relative to the moving front (the ‘significant perturbations’, see below). Comparison is made with results of numerical integration of the reaction–diffusion system, whereby it appears likely that the travelling front is temporally stable for all relevant parameter values characterising the model. We modify the system by introducing a slow variation of a relevant recovery parameter and perform a leading order singular perturbation analysis to construct a pulse solution in the resulting model. In addition, we obtain a 1-parameter family of periodic pulse trains for the system, modelling re-entrant pulses in a one-dimensional ring of excitable cells.

ObjectivesThis study sought to prospectively evaluate the relationship between plasma osteoprotegerin (OPG), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], coronary artery calcification (CAC), and cardiovascular events in patients with type 2 diabetes.BackgroundArterial calcification is a prominent feature of atherosclerosis and is associated with an increased risk of cardiovascular events. Osteoprotegerin is a cytokine that has recently been implicated in the regulation of vascular calcification.MethodsA total of 510 type 2 diabetic patients (53 ± 8 years; 61% male) free of symptoms of cardiovascular disease were evaluated by CAC imaging. Risk factors, hs-CRP, IL-6, and OPG levels were measured. Patients were followed up for cardiovascular events (cardiac death, myocardial infarction, acute coronary syndrome, late revascularization, and nonhemorrhagic stroke).ResultsSignificant CAC (>10 Agatston units) was seen in 236 patients (46.3%); OPG was significantly elevated in patients with increased CAC. In multivariable analyses, OPG retained a strong association with elevated CAC scores after adjustment for age, gender, and other risk factors (odds ratio = 2.84, 95% confidence interval 2.2 to 3.67; p < 0.01). Sixteen cardiovascular events occurred during a mean follow-up of 18 ± 5 months. The waist-to-hip ratio, United Kingdom Prospective Diabetes Study (UKPDS) risk score, OPG level, and CAC score were significant predictors of time to cardiovascular events in a univariate Cox proportional hazards model. In the multivariate model, the CAC score was the only independent predictor of adverse events. Levels of hs-CRP and IL-6 were related to neither the extent of CAC nor short-term events.ConclusionsA high proportion of asymptomatic diabetic patients have significant subclinical atherosclerosis. Of the biomarkers studied, only OPG predicted both subclinical disease and near-term cardiovascular events. Therefore, measurement of OPG merits further investigation as a simple test for identifying high-risk type 2 diabetic patients.

Aims To assess the screening characteristics and cost-effectiveness of screening for left ventricular systolic dysfunction (LVSD) in community subjects. Methods and results A total of 1392 members of the general public and 928 higher risk subjects were randomly selected from seven community practices. Attending subjects underwent an ECG, N-terminal pro-brain natriuretic peptide (NTproBNP) serum levels, and traditional echocardiography (TE). A total of 533 consecutive subjects underwent hand-held echocardiography (HE). The screening characteristics and cost-effectiveness (cost per case of LVSD diagnosed) of eight strategies to predict LVSD (LVSD