H. Sillesen

Echo-Lucency of Computerized Ultrasound Images of Carotid Atherosclerotic Plaques Are Associated With Increased Levels of Triglyceride-Rich Lipoproteins as Well as Increased Plaque Lipid Content

BACKGROUNDnEcho-lucency of carotid atherosclerotic plaques on computerized ultrasound B-mode images has been associated with a high incidence of brain infarcts as evaluated on CT scans. We tested the hypotheses that triglyceride-rich lipoproteins in the fasting and postprandial state predict carotid plaque echo-lucency and that echo-lucency predicts a high plaque lipid content.nnnMETHODS AND RESULTSnThe study included 137 patients with neurological symptoms and > or = 50% stenosis of the relevant carotid artery. High-resolution B-mode ultrasound images of carotid plaques were computer processed to yield a measure of echogenicity (gray-scale level). Lipoproteins were measured before and hourly for 4 hours after a standardized fatty meal. A subgroup of 58 patients underwent endarterectomy. On linear regression analysis, echo-lucency (low gray-scale level) was associated with elevated levels of fasting and postprandial plasma triglycerides (P=.0002 and P=.002), IDL cholesterol (P=.0009 and P=.006), and VLDL/chylomicron remnant cholesterol (P=.0003 and P=.0004) and triglycerides (P=.0003 and P=.003), the area under the plasma triglyceride curve 0 to 4 hours after a fatty meal (P=.001), and body mass index (P=.0001). On ANCOVA, body mass index, fasting IDL cholesterol, and fasting plasma triglycerides were independent predictors of echo-lucency. Echo-lucency was associated with increased relative plaque lipid content (P=.02).nnnCONCLUSIONSnIncreased plasma levels of triglyceride-rich lipoproteins predict echo-lucency of carotid plaques, which is associated with increased plaque lipid content. Because echo-lucency has been associated with a high incidence of brain infarcts on CT scans, triglyceride-rich lipoproteins may predict a plaque type particularly vulnerable to rupture.

Quantitative analysis of ultrasound B-mode images of carotid atherosclerotic plaque: correlation with visual classification and histological examination

This paper presents a quantitative comparison of three types of information available for 52 patients scheduled for carotid endarterectomy: subjective classification of the ultrasound images obtained during scanning before operation, first- and second-order statistical features extracted from regions of the plaque in still ultrasound images from three orthogonal scan planes and finally a histological analysis of the surgically removed plaque. The quantitative comparison was made with the linear model and with separation of the available data into training and test sets. The comparison of subjective classification with features from still ultrasound images revealed an overall agreement of 60% for classification of echogenicity and 70% for classification of structure. Comparison of the histologically determined relative volume of soft materials with features from the still images revealed a correlation coefficient of r=-0.42 (p=0.002), for mean echogenicity of the plaque region. The best performing feature was of second order and denoted contrast (r=-0.5). Though significant, the latter correlation is probably not strong enough to be useful for clinical prediction of relative volume of soft materials for individual patients. Reasons for this is discussed in the paper, together with suggestions for improvements.

Lipid-rich carotid artery plaques appear echolucent on ultrasound B-mode images and may be associated with intraplaque haemorrhage

OBJECTIVEnTo relate the histological composition of carotid artery plaques with morphology as evaluated by B-mode ultrasound.nnnDESIGNnProspective study.nnnMATERIAL AND METHODSnSeventy-eight symptomatic patients underwent carotid endarterectomy after preoperative ultrasound Duplex scanning evaluating plaque morphology. Morphometric analysis of the removed specimen was performed in order to quantify content of lipid, haemorrhage, calcification and fibrous tissue.nnnRESULTSnEcholucent plaques contained more lipid (p = 0.01) and less calcification (p = 0.01) and fibrous tissue (p = 0.03) than echo-rich plaques. Intraplaque haemorrhage was directly related to lipid content (p = 0.004) and inversely related to amount of fibrous tissue in the plaque (p = 0.02).nnnCONCLUSIONnThe intensity of the reflected B-mode ultrasound signal appears related to the histological composition of the plaque. The association between intraplaque haemorrhage and a high lipid content may support the theory of the lipid-rich plaque being more prone to rupture.

Elevated matrix metalloproteinase-9 associated with stroke or cardiovascular death in patients with carotid stenosis.

Background— Matrix metalloproteinase-9 could exhibit an important role in the destabilization of atherosclerotic carotid plaques. We hypothesized that in patients with carotid stenosis, elevated levels of plasma matrix metalloproteinase-9 are associated with ipsilateral stroke or cardiovascular death. Methods and Results— We followed up 207 patients with ≥50% carotid stenosis initially for a mean of 4.4 years, during which time 53 patients developed ipsilateral stroke or died of cardiovascular causes. The cumulative incidence of ipsilateral stroke or cardiovascular death was higher in those with matrix metalloproteinase-9 above versus below the median of 41.9 ng/mL (log-rank P=0.002). Matrix metalloproteinase-9 above versus below the median had a hazard ratio for ipsilateral stroke or cardiovascular death of 1.9 (95% confidence interval [CI], 1.1 to 3.5); during extended follow-up, this remained significant until 10 years. The absolute risk of ipsilateral stroke or cardiovascular death at 4.4 years was 34% and 17% in those with matrix metalloproteinase-9 above and below the median, respectively. Elevated matrix metalloproteinase-9 and an echolucent plaque on B-mode ultrasound versus a low matrix metalloproteinase-9 and an echorich plaque had a hazard ratio for ipsilateral stroke or cardiovascular death of 4.4 (95% CI, 1.8 to 11.1) and for ipsilateral stroke of 3.3 (95% CI, 1.1 to 9.7). Conclusions— Elevated levels of matrix metalloproteinase-9 in patients with ≥50% carotid stenosis were associated with a 2-fold risk of ipsilateral stroke or cardiovascular death. Combining elevated matrix metalloproteinase-9 and plaque echolucency was associated with a 4-fold risk for ipsilateral stroke or cardiovascular death and a 3-fold risk for ipsilateral stroke.

Fibrinogen predicts ischaemic stroke and advanced atherosclerosis but not echolucent, rupture-prone carotid plaques The Copenhagen City Heart Study

AIMSnWhether the association between fibrinogen and cardiovascular events reflects an association with advanced atherosclerosis in general, or rupture-prone plaques in particular, is unclear. We examined whether fibrinogen predicts incidence of ischaemic stroke, advanced atherosclerosis (measured as carotid artery stenosis) and/or echolucent, rupture-prone plaques.nnnMETHODS AND RESULTSnStudy 1-8755 Copenhagen City Heart Study stroke-free participants; we observed 235 ischaemic strokes during 6 years of follow-up. Study 2-318 carotid stenosis patients and 1584 age- and gender-matched controls. Study 3-159 patients with echolucent vs 159 patients with echo-rich carotid artery plaques. Fibrinogen above vs below the median value of 3 g l(-1)predicted risk of ischaemic stroke (relative risk: 1.9; 95% CI: 1.4-2.5; 235 events). Significant risk was found in men (2.7; 1.7-4.2; 113 events) and with a similar trend in women (1.4; 0.9-2.0; 122 events), in young (5.2; 1.1-26; eight events) and middle aged (2.9; 1.6-5.4; 64 events) with a similar trend in the elderly (1.4; 1.0-2.0; 163 events). Fibrinogen levels in those with and without ischaemic stroke were 3.6 and 3.1 g l(-1)(ANCOVA: P<0.0001). Likewise, in those with and without carotid artery stenosis fibrinogen levels were 4.7 and 3.1 g l(-1)(P<0.0001); equivalent values for high-sensitive C-reactive protein were 3.6 and 1.4 mg l(-1)(P<0.0001). Finally, neither fibrinogen nor high-sensitive C-reactive protein levels differed between those with echolucent and echo-rich carotid artery plaques (P=0.61 and P=0.28); the power to exclude a 15% increase in fibrinogen or a 50% increase in high-sensitive C-reactive protein was 98 and 54%, respectively.nnnCONCLUSIONSnElevated fibrinogen predicts future ischaemic strokes, particularly in men and in the young and middle aged. This is most likely a reflection of advanced atherosclerosis, rather than an association with rupture-prone plaques.

In vitro spatial compound scanning for improved visualization of atherosclerosis.

A new off-line multiangle ultrasound (US) compound scanner has been built with the purpose of investigating possible improvements in visualization of vascular structure. Images of two formalin-fixed human atherosclerotic plaques removed by carotid endarterectomy were recorded from seven insonification angles over a range of 42 degrees and the individual images were combined (averaged) into a single image (spatial compounding). Compared to conventional B-mode imaging, this multiangle compound imaging (MACI) method features images with reduced angle-dependence, reduced random variation (speckle) and improved delineation of the plaque outline. With the MACI approach, it is, thus, easier to assess e.g., a possible residual lumen of an atherosclerotic artery as well as the level of echogenicity for the different plaque constituents.

Blood Pressure, Risk of Ischemic Cerebrovascular and Ischemic Heart Disease, and Longevity in α1-Antitrypsin Deficiency The Copenhagen City Heart Study

Background—Because elastase in &agr;1-antitrypsin deficiency may attack elastin in the arterial wall, we tested whether &agr;1-antitrypsin deficiency is associated with reduced blood pressure, risk of ischemic cerebrovascular (ICVD) and ischemic heart disease (IHD), and longevity. Methods and Results—We genotyped 7963 control subjects from the adult general population of Denmark, 1131 Danish patients with ICVD, and 2221 Danish patients with IHD. Compared with MM/MS individuals, systolic blood pressure was lower by 15 mm Hg in ZZ homozygotes (n=6, P =0.03) and 9 mm Hg in MZ heterozygotes with IHD (n=39, P =0.02). Odds ratios for ICVD and IHD in MZ versus MM/MS individuals were 0.70 (0.51 to 0.96) and 0.77 (0.61 to 0.98). Finally, mean ages of MZ and MM/MS control subjects were 58 and 56 years (Mann-Whitney:P =0.008), and relative &agr;1-antitrypsin MZ genotype frequencies increased from 20 to 93 years among control subjects (&khgr;2, P =0.002). Conclusions—ZZ &agr;1-antitrypsin deficiency and MZ intermediate deficiency in the context of IHD are associated with reduced blood pressure, and MZ is associated with reduced risk of ICVD and IHD. Because MZ heterozygosity was associated with increased age, MZ heterozygosity could be a beneficial condition.

Statins for secondary stroke prevention in patients without known coronary heart disease: the jury is still out.

aDuke University Medical Center, Durham, N.C., USA; bHopital Lariboisiere, Paris, France; cCentre Hospitalier Universitaire, Lausanne, Switzerland; dNeurologic Consultants P.C., Nashville, Tenn., USA; eKlinikum Mannheim, Mannheim, Germany; fFinch Chicago Medical School, Chicago, Ill., and gUniversity of California San Diego, San Diego, Calif., USA; hGentofte Hospital, Hellerup, Denmark Published online: May 19, 2004

Ultrasound spatial compound scanner for improved visualization in vascular imaging

A new off-line multi-angle ultrasound compound scanner has been built with the aim of improving visualization of vascular tissue. Images are recorded from 3 to 11 insonification angles over a range of 40 to 50 degrees and the individual images are combined (averaged) into a single image (spatial compounding). Compared to conventional B-mode imaging, this multi-angle compound imaging (MACI) method features less angle-dependent images, since more scan lines are nearly perpendicular to the tissue interfaces. Further, the spatial compounding strongly diminishes the speckle pattern. These improvements are illustrated with in vitro images of porcine aorta and human atherosclerotic plaque.

Why the US Center for Medicare and Medicaid Services should not extend reimbursement indications for carotid artery angioplasty/stenting.

Why the US Center for Medicare and Medicaid Services Should Not Extend Reimbursement Indications for Carotid Artery Angioplasty/Stenting