Dhakshinamurthy Vijay Anand

Increased volume of epicardial fat is an independent risk factor for accelerated progression of sub-clinical coronary atherosclerosis

BACKGROUND Epicardial adipose tissue (EAT), a metabolically active visceral fat depot surrounding the heart, has been implicated in the pathogenesis of coronary artery disease (CAD) through possible paracrine interaction with the coronary arteries. We examined the association of EAT with metabolic syndrome and the prevalence and progression of coronary artery calcium (CAC) burden. METHODS CAC scan was performed in 333 asymptomatic diabetic patients without prior history of CAD (median age 54 years, 62% males), followed by a repeat scan after 2.7±0.3 years. CAC progression was defined as >2.5mm(3) increase in square root transformed volumetric CAC scores. EAT and intra-thoracic fat volumes were quantified using a dedicated software (QFAT), and were examined in relation to the metabolic syndrome, baseline CAC scores and CAC progression. RESULTS Both epicardial and intra-thoracic fat were associated with metabolic syndrome after adjustment for conventional cardiovascular risk factors, but the association was attenuated after additional adjustment for body mass index. EAT, but not intra-thoracic fat, showed significant association with baseline CAC scores (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.04-1.22, p=0.04) and CAC progression (OR 1.12, 95% CI 1.05-1.19, p<0.001) after adjustment for conventional measures of obesity and risk factors. CONCLUSION EAT volume measured on non-contrast CT is an independent marker for the presence and severity of coronary calcium burden and also identifies individuals at increased risk of CAC progression. EAT quantification may thus add to the prognostic value of CAC imaging.

Associations between autoantibodies against apolipoprotein B-100 peptides and vascular complications in patients with type 2 diabetes

Aims/hypothesisOxidation 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.MethodsWe 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.ResultsPatients 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/interpretationOur 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.

High levels of IgM against methylglyoxal-modified apolipoprotein B100 are associated with less coronary artery calcification in patients with type 2 diabetes

Abstract.  Engelbertsen D, Anand DV, Fredrikson GN, Hopkins D, Corder R, Shah PK, Lahiri A, Nilsson J, Bengtsson E (Skåne University Hospital, Lund University, Malmö, Sweden; Cardiac Imaging and Research Centre, Wellington Hospital, London, UK; Malmö University, Malmö, Sweden; King’s College Hospital, London, UK; William Harvey Research Institute, London, UK; Cedars‐Sinai Medical Center, Los Angeles, CA, USA; David Geffen School of Medicine, UCLA School of Medicine, Los Angeles, CA, USA). High levels of IgM against methylglyoxal‐modified apolipoprotein B100 is associated with less coronary artery calcification in patients with type 2 diabetes. J Intern Med 2012; 271: 82–89.

Cardiac computed tomography and myocardial perfusion imaging for risk stratification in asymptomatic diabetic patients: A critical review

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.

Evaluation of graft patency by computed tomographic angiography in symptom-free post–coronary artery bypass surgery patients

BackgroundAccelerated 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).Methods and ResultsEBA was performed in 45 symptom-free patients (mean age, 66±9 year; 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.ConclusionComputed tomographic coronary angiography permits reliable identification of by pass graft stenoses and occlusion 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

Multislice computed tomography evaluation of cardiac syndrome X patients

Cardiac syndrome X is characterized by presentation with typical anginal chest pain, findings compatible with myocardial ischemia on noninvasive testing, and angiographically unobstructed coronary arteries. Coronary endothelial dysfunction resulting in microvascular ischemia is thought to be the predominant underlying pathophysiologic basis for patients with syndrome X, although some patients have altered cardiac pain perception. Given the lack of uniform diagnostic criteria, clinical studies of syndrome X have often involved a heterogeneous group of patients, some of whom have associated cardiovascular risk factors such as hypertension and diabetes, evidence of myocardial ischemia, and abnormal myocardial flow reserve and mild coronary artery disease (CAD) on angiography. Although studies examining the prognosis of patients with syndrome X have reported excellent outcomes on long-term follow-up, certain patient subgroups—that is, those with demonstrable endothelial dysfunction—appear to have an increased occurrence of adverse cardiovascular events. On the other hand, quality of life is significantly impaired in syndrome X patients with recurring symptoms and hospital admissions leading to repeated diagnostic procedures. In this issue of the Journal, Mizia-Stec et al have evaluated the prevalence of coronary artery calcification (CAC) and other structural and functional indices of vascular remodeling (carotid intima-media thickness [IMT], brachial artery endothelium-dependent and endothelium-independent vasodilatation, and arterial stiffness) and their interrelationship in 46 patients with cardiac syndrome X and 21 healthy control subjects. Patients with cardiac syndrome X had increased carotid IMT and decreased brachial artery endothelium-dependent flow-mediated dilatation (FMD). CAC was detectable in a significant proportion (41%) of patients with syndrome X but only in 1 control subject. Indices of vascular remodeling such as IMT, FMD, and arterial stiffness were not associated with CAC. Age was the only independent predictor of CAC in patients with cardiac syndrome X in a multivariate logistic and linear regression analysis. The authors suggest that CAC evaluation by 64-slice multislice computed tomography (MSCT) and structural and functional indices of vascular remodeling may be complementary in assessing the risk of cardiac syndrome X patients. In a similar analysis that included 124 patients with suspected CAD, Huang et al reported an association between the degree of CAC and brachial artery FMD. In a previous study Chen et al evaluated the prevalence of coronary calcium in patients with CAD, patients with syndrome X, and healthy control subjects by electron beam computed tomography. The median CAC score in patients with syndrome X was significantly lower than that in patients with CAD (1 vs 202). In addition to standard cardiovascular risk factors, the authors found that a CAC threshold greater than 117 could discriminate patients with CAD from those with syndrome X. However, there was considerable overlap in the distribution of CAC in the different patient subgroups, with 45% of CAD patients having a CAC score lower than 117. In another study Shemesh et al similarly showed that the CAC score partially distinguishes patients with syndrome X from those with angiographic CAD and normal subjects. The independent and incremental long-term prognostic value of coronary artery calcium has been extensively validated in asymptomatic subjects. Clinical and histopathologic studies confirm the close correlation between the extent of CAC and the burden of atherosclerotic coronary disease. Although there is positive correlation between the amount of coronary calcium at a site and the severity of luminal stenosis at that site, this relationship is nonlinear, with large confidence limits. Consequently, the specificity of CAC for predicting obstructive CAD is low, and the absence of coronary calcium does not exclude obstructive coronary disease in symptomatic patients. Rubinshtein et al evaluated the extent of CAD by 64-slice contrast-enhanced MSCT in 231 patients with a CAC score of 0 or a low CAC score From the Department of Cardiology, Newham University Hospital, London, England. Reprint requests: Dhakshinamurthy Vijay Anand, MBBS, MRCP, Department of Cardiology, Newham University Hospital NHS Trust, Glen Road, Plaistow, London E13 8SL, England; vdanand@hotmail.com. J Nucl Cardiol 2008;15:615-6. 1071-3581/

Noninvasive Assessment of Asymptomatic Individuals at Risk of Coronary Heart Disease. Part a

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Risk stratification in uncomplicated type 2 diabetes: prospective evaluation of the combined use of coronary artery calcium imaging and selective myocardial perfusion scintigraphy

Cardiovascular risk estimates can be improved by several noninvasive imaging techniques, collectively called atherosclerosis imaging. Clinically useful techniques currently include coronary calcium imaging and carotid ultra sound. Both these tests are most valuable in intermediate-risk patients, in whom a significant proportion will be reassigned into either a higher- or lower-risk category. However, before widespread adoption of any of these techniques takes place, studies to establish treatment protocols based on atherosclerosis imaging tests and to determine the cost-effectiveness of atherosclerosis imaging tests are needed.