Aortic Plaque Burden Research Articles

Sex-Dependent Attenuation of Plaque Growth After Treatment With Bone Marrow Mononuclear Cells

There are clinically relevant differences in symptomatology, risk stratification, and efficacy of therapies between men and women with coronary artery disease. Sex-based differences in plaque attenuation after administration of bone marrow mononuclear cells (BMNCs) are unknown. Forty-five male and 57 female apolipoprotein-E knockout (apoE(-/-)) mice were fed a high-fat diet. At 14 weeks of age, animals received 4 biweekly intravenous sex-matched (males, n=11; females, n=13) or -mismatched (males, n=12; females, n=14) BMNCs obtained from C57BL6/J mice. The rest of the apoE(-/-) mice were vehicle treated (males, n=13; females, n=20) or were age-matched untreated controls (males, n=9; females, n=10). Aortic plaque burden, progenitor cell profiles in bone marrow (BM) and 22 circulating cytokines/chemokines were examined 1 week following the final injection. Only female BMNCs infused into male apoE(-/-) recipients significantly decreased plaque formation (P<0.001). This reparative response univariately correlated with increased CD34(+) (P=0.02), CD45(+) (P=0.0001), and AC133(+)/CD34(+) (P=0.001) cell percentages in the BM of recipients but not with total serum cholesterol or percentage of BM-CD31(+)/CD45(low) cells. In a multivariate analysis, BM-AC133(+)/CD34(+) and BM-CD45(+) percentage counts correlated with a lower plaque burden (P<0.05). Increased granulocyte colony-stimulating factor levels highly correlated with plaque attenuation (r=-0.86, P=0.0004). In untreated apoE(-/-) mice of either sex, BM-AC133(+)/CD34(+) cells rose initially and then fell as plaque accumulated; however, BM-AC133(+)/CD34(+) percentages were higher in females at all times (P<or=0.01). We have demonstrated an atheroprotective effect of female-derived BMNCs administered to male atherosclerotic apoE(-/-) mice; this reparative response correlated with the upregulation of BM-AC133(+)/CD34(+) and CD45(+) cells and of circulating granulocyte colony-stimulating factor. Atherosclerotic female apoE(-/-) mice did not exhibit atheroprotection after BMNCs of either sex. Our findings may have implications for clinical cell therapy trials for coronary artery disease. Further exploration of sex-based differences in atheroprotection and vascular repair is warranted.

Assessment by Cardiovascular Magnetic Resonance, Electron Beam Computed Tomography, and Carotid Ultrasonography of the Distribution of Subclinical Atherosclerosis Across Framingham Risk Strata

Screening for subclinical atherosclerosis has been advocated for individuals at intermediate global risk for coronary heart disease (CHD). However, the distribution of subclinical atherosclerosis test values across CHD risk strata is unknown. We studied a stratified random sample of 292 participants (mean age 59.5 years, 50% women) from the offspring cohort of the Framingham Heart Study who were free of clinically apparent cardiovascular disease. We assessed abdominal and thoracic aortic plaque burden by cardiovascular magnetic resonance (CMR), coronary artery calcification (CAC) and thoracic aortic calcification (TAC) by electron beam computed tomography, and common carotid intima-media thickness (C-IMT) by ultrasonography. We categorized the upper 20% of each measurement as a high level of atherosclerosis and evaluated these variables across clinically relevant Framingham CHD risk score strata (low, intermediate, and high risk). In age-adjusted analyses in men and women, correlations across CMR aortic plaque, CAC, TAC, and C-IMT were low (maximum r = 0.30 for CAC:TAC in women, p <0.005). In men and women, the proportion of subjects with high atherosclerosis test results for any of these measurements increased significantly across Framingham CHD risk score strata (Kruskal-Wallis test, p <0.0001). In the intermediate Framingham CHD risk score category, 14% of men and 25% of women had a high atherosclerosis result on >or=2 measurements. However, different participants were identified as having high atherosclerosis by each modality. For example, in a comparison of the overlap across CMR aortic plaque, CAC, and C-IMT, only 4% of men and 16% of women were classified as having high atherosclerosis on all 3 measurements. In conclusion, in a community-based sample, correlations among subclinical atherosclerosis test results are low, and a substantial proportion has high levels of subclinical atherosclerosis detected on >or=2 imaging tests.

Invited commentary

Using diffusion-weighted magnetic resonance imaging (DWI), Hammer et al have demonstrated an alarming rate (40%) of new microinfarcts after filter-protected carotid artery stenting (CAS). These data support previous studies that have demonstrated new microinfarcts in 20% to 43% of patients after CAS.1Schluter M. Tubler T. Steffens J.C. Mathey D.G. Schofer J. Focal ischemia of the brain after neuroprotected carotid artery stenting.J Am Coll Cardiol. 2003; 42: 1007-1013Abstract Full Text Full Text PDF PubMed Scopus (130) Google Scholar, 2Flach H.Z. Ouhlous M. Hendriks J.M. et al.Cerebral ischemia after carotid intervention.J Endovasc Ther. 2004; 11: 251-257Crossref PubMed Scopus (112) Google Scholar They are to be commended on their overall results: there were only two (4%) minor strokes that resolved completely, no myocardial infarctions, and no deaths. The pattern of these cerebral infarcts suggests that they are not due to failure of the embolic protection device. Ipsilateral DWI infarcts occurred with equal frequency in cases with and without visible debris captured in the filter. More importantly, the DWI lesions frequently involved the contralateral cerebral hemisphere, thus suggesting that many occurred before cannulation of the target carotid artery. The occurrence of these DWI lesions seems, on the basis of Hammer and associates’ analysis, to correlate with difficult arch anatomy, supra-aortic carotid torutuosity, and the performance of contralateral brachiocephalic selective catheterization. Thankfully, most of these lesions seem clinically silent, but this would be better evaluated with formal neuropsychiatric testing. These results argue against routine contraleral diagnostic arteriography as part of a CAS procedure, especially because one of the two strokes did occur in the contralateral occipital lobe. In our center, like many, we are careful to minimize manipulations in the aortic arch and attempt to cannulate only the target carotid artery during CAS. Proper patient selection and technical skill will be critical in decreasing CAS neurologic event rates to those seen with carotid endarterectomy, especially in older patient populations, in which CAS stroke and death rates have exceeded 12%.3Hobson II, R.W. Howard V.J. Roubin G.S. et al.Carotid artery stenting is associated with increased complications in octogenarians 30-day stroke and death rates in the CREST lead-in phase.J Vasc Surg. 2004; 40: 1106-1111Abstract Full Text Full Text PDF PubMed Scopus (503) Google Scholar We use computed tomographic angiography to screen patients for difficult arch anatomy, evaluate aortic arch plaque burden, and evaluate the carotid lesion length and calcification. We have used this information to exclude some patients from further consideration for CAS on the basis of anatomic concerns. This study by Hammer et al supports the concepts that minimal, focused catheter manipulation within the aortic arch and careful patient selection based on evaluation of aortic arch/carotid anatomy will limit the incidence of neurologic events during CAS. CorrectionJournal of Vascular SurgeryVol. 42Issue 6PreviewFor the article “Interval Gangrene Complicating Superficial Femoral Artery Stent Placement” published in J Vasc Surg 2005:42;564-66, one author was inadvertently left off, Dr. Neal Cayne. The correct order of authors should read: Full-Text PDF Open Archive

Frontiers in Cardiovascular Magnetic Resonance

Cardiovascular magnetic resonance (MR) is emerging as a multipurpose imaging modality for the assessment of cardiovascular disease in general and ischemic heart disease in particular. Currently, the pace of innovation is rapid, and the modality is changing from one that is used primarily as a research tool to one that is increasingly used in routine clinical practice. The process of innovation includes not only improvements in scanner hardware, such as coil and gradient technology, and the development of new contrast agents but also the development of novel pulse sequences. The concept of the pulse sequence, in which programming changes at the scanner can lead to fundamental changes in activating tissue, is unique to MR and gives this modality the potential to assess a vast number of biological parameters. Cardiovascular MR promises to play an important clinical and investigational role in both vascular and cardiac systems. Current and potential future applications of cardiovascular MR will be discussed with a particular focus on ischemic heart disease. Multidetector-row computed tomography, another promising and complementary noninvasive imaging technology, will be discussed briefly in relation to cardiovascular MR for the assessment of atherothrombotic disease. ### Nomenclature and Evolving Imaging Assessment Atherothrombosis is a systemic or multiterritory arterial disease that primarily affects the large- and medium systemic arteries, including the aorta and the carotid, coronary, and peripheral arteries. Although the epicardial coronary arteries appear to be the most susceptible to atherothrombosis,1,2 intramyocardial arteries are relatively resistant. The concept of multiterritory atherothrombosis has been addressed in 2 large studies of symptomatic patients that showed that at entry into the studies, 3% to 8% had symptomatic atherothrombotic disease in all 3 main arterial districts and 23% to 32% had disease in 2 districts.3,4 From a structural point of view, the 4 main components of the atherothrombotic plaques are as follows: (1) fibrocellular, …

Atherosclerotic plaque characterization by MR imaging.

The MR imaging of carotid artery and aortic plaque has undergone significant improvement in the last decade. Early studies utilizing ex vivo specimens and spin echo or fast spin echo imaging, led to the conclusion that T2-weighting was the best single contrast to characterize carotid plaque morphology. On these images, the fibrous plaque appears bright and the lipid core is dark; thrombus can have variable intensity. There can be an overlap in T2w signal intensities among the various plaque components, which can be partially offset by the use of qualitative or multi-spectral analysis of multiple contrast images. With improvements in coil design, sequence design, main field and gradient capabilities, accurate in vivo differentiation and measurement of these various plaque components should be possible in a few years. Carotid and aortic plaque burden can be accurately measured in vivo today; ongoing longitudinal studies should lead to a better understanding of the relationship between plaque burden and the risk of thromboembolic complications, as well as the effect of diet and drug therapy in hyperlipidemic patients. With these developments in place or soon to be available, MR imaging of the diseased carotid artery and aortic wall may prove to be even more important than MR angiography or other current clinical tests.

E-selectin and P-selectin are markers of aortic plaque burden as measured by transesophageal magnetic resource imaging

E-selectin and P-selectin are markers of aortic plaque burden as measured by transesophageal magnetic resource imaging

Bedside quantification of atherosclerosis severity for cardiovascular risk stratification: a prospective cohort study

ObjectivesWe sought to assess the ability of a new noninvasive method to quantify atherosclerosis severity and to examine its power to predict cardiovascular events. BackgroundDrug prevention of cardiovascular events is effective but costly, leading to a debate about who should receive this treatment. Patient selection is often based on surrogate markers, but quantification of atherosclerosis severity is desirable. MethodsAtherosclerosis severity was quantified by determination of specific aortic wall elastance in transthoracic echocardiography, applying the biomechanics of pulse wave propagation. After validating the method in 52 patients by measuring aortic plaque burden in transesophageal echo directly, another 336 patients were prospectively studied by monitoring atherosclerotic events at one year and comparing the results with conventional risk stratification. ResultsSpecific aortic elastance was well correlated with plaque burden (p < 0.0001) and largely independent of confounding variables. Specific aortic elastance predicted the primary end point of “atherosclerotic death, myocardial infarction or stroke” at one year (p < 0.0002). Event rate at one year in the lowest specific elastance tertile was 1.8% (CI 0.0% to 4.3%), in the middle tertile 5.4% (CI 1.1% to 9.7%) and in the highest tertile 12.7% (CI 6.3% to 19%). Secondary end points supported these findings. Stepwise multivariate analysis identified specific aortic elastance, prior atherosclerotic events and left ventricular ejection fraction as independent risk predictors. Specific elastance was of incremental value to clinically identified variables. ConclusionsBedside measurement of specific aortic elastance allows assessment of atherosclerosis severity. It predicts the risk for future atherosclerotic events beyond conventional risk factors, promising better targeting of pharmacologic prevention and improved cost effectiveness.

Transesophageal magnetic resonance imaging of the aortic arch and descending thoracic aorta in patients with aortic atherosclerosis

OBJECTIVESWe sought to determine the feasibility and potential of transesophageal magnetic resonance imaging (TEMRI) for quantifying atherosclerotic plaque burden in the aortic arch and descending thoracic aorta in comparison with transesophageal echocardiography (TEE).BACKGROUNDImproved morphologic assessment of atherosclerotic plaque features in vivo is of interest because of the potential for improved understanding of the pathophysiology of plaque vulnerability to rupture and progression to clinical events. Magnetic resonance imaging (MRI) is well suited for atherosclerotic plaque imaging. Performing MRI using a radio frequency (RF) receiver probe placed near the region of interest improves the signal-to-noise ratio (SNR).METHODSHigh-resolution images of the thoracic aortic wall were obtained by TEMRI in 22 subjects (8 normals, 14 with aortic atherosclerosis). In nine subjects, we compared aortic wall thickness and circumferential extent of atherosclerotic plaque measured by TEMRI versus TEE using a Bland-Altman analysis. Additional studies were performed in a human cadaver with pathology as an independent gold standard for assessment of atherosclerosis.RESULTSIn clinical and experimental studies, we found similar measurements for aortic plaque thickness but a relative underestimation of circumferential extent of atherosclerosis by TEE (p = 0.001), due in large part to the lower SNR in the near field.CONCLUSIONSUsing TEMRI allows for quantitative assessment of thoracic aortic atherosclerotic plaque burden. This technique provides good SNR in the near field, which makes it a promising approach for detailed characterization of aortic plaque burden.

Reduction in aortic plaque burden in patients with familial hyperlipidemia as assessed by transesophageal echocardiography Susan D. Tiukinhoy, Neil J. Stone, Peter C. Dau, Bonnie J. Kane, Mark G. Rabbat, Noam Belkind, David D. McPherson. Northwestern University Medical School, Chicago &amp; Evanston, IL

Reduction in aortic plaque burden in patients with familial hyperlipidemia as assessed by transesophageal echocardiography Susan D. Tiukinhoy, Neil J. Stone, Peter C. Dau, Bonnie J. Kane, Mark G. Rabbat, Noam Belkind, David D. McPherson. Northwestern University Medical School, Chicago &amp; Evanston, IL

Plasma homocyst(e)ine levels correlate with thoracic aortic atherosclerotic plaque burden: Neal Konecky, MD, M. René Malinow, MD, Paul A. Tunick, MD, Robin S. Freedberg, MD, Barry P. Rosenzweig, MD, Edward S. Katz, MD, Blanche Leung, BS, Barbara Upson, RN, John L. Perez, Itzhak Kronzon, MD. NYU Medical Center, NYC, NY and Oregon Regional Primate Research Center, Beaverton, OR

Plasma homocyst(e)ine levels correlate with thoracic aortic atherosclerotic plaque burden: Neal Konecky, MD, M. René Malinow, MD, Paul A. Tunick, MD, Robin S. Freedberg, MD, Barry P. Rosenzweig, MD, Edward S. Katz, MD, Blanche Leung, BS, Barbara Upson, RN, John L. Perez, Itzhak Kronzon, MD. NYU Medical Center, NYC, NY and Oregon Regional Primate Research Center, Beaverton, OR