Carotid Plaque Regression Research Articles

A new approach of statin therapy in carotid atherosclerosis: Targeting indices of plaque vulnerability on the top of lipid-lowering. A narrative review.

Novel imaging techniques and biomarkers have emerged as surrogate markers of carotid plaque vulnerability. In parallel, statin administration in patients with established carotid atherosclerosis not requiring revascularization has reduced the number of consequent cerebrovascular events. This reduction is not only attributed to the lipid-lowering properties of statins but also to their pleiotropic actions. The present literature review aimed to summarize the stabilizing effects of statins on carotid plaques based on imaging modalities and biomarkers and propose an alternative approach to their implementation. Moreover, we assessed the perioperative use of statins in patients undergoing carotid revascularization and the impact of aggressive vs. conventional statin therapy. Recent studies using: (1) ultrasound indices of plaque echogenicity; (2) fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) scans for plaque inflammation assessment; or (3)magnetic resonance imaging (MRI) scans quantifying intraplaque hemorrhage, and lipid-rich necrotic core (LRNC) have shown quite promising results in evaluation of carotid plaque vulnerability. Based on those imaging modalities, a growing number of studies have demonstrated a very modest carotid plaque regression due to/induced by statins, while their stabilizing impact is disproportionally higher. Other studies assaying several biomarkers (e.g. inflammation, etc.) have confirmed a statin-induced carotid plaque stabilization. All the aforementioned benefits followed a dose-dependent pattern of statins, on top of the low-density lipoprotein cholesterol (LDL-C) target in current guidelines. In the case of symptomatic patients with carotid atherosclerosis suitable for revascularization, robust evidence implicates a significant statin-related reduction of perioperative cardiovascular risk only in patients undergoing endarterectomy.

CARotid plaqUe StabilizatiOn and regression with evolocumab: Rationale and design of the CARUSO study

While the experience with PCSK9i in patients with coronary artery disease has been wide, and coronary plaque regression has been documented, little is known regarding the role of these drugs on carotid plaque regression. The CARotid plaqUe StabilizatiOn and regression with evolocumab (CARUSO) study is a randomized, single-center, investigator-initiated trial aiming at evaluating carotid plaque morphological stabilization and regression following, respectively, 6 and 12 months of therapy with evolocumab. Asymptomatic patients with uni- or bilateral de novo carotid artery stenosis ≥50% and LDL-C values ≥100 mg/dl despite maximum tolerated lipid lowering therapy (LLT) will be randomized to evolocumab 140 mg s.c. every 2 weeks on top of ongoing LLT, or no additional treatment. 100 patients (50 in each arm) will be enrolled. Serial carotid duplex ultra-sonography will be performed to monitor the carotid plaque morphology and stenosis over time. The primary end point of the study is, (a) carotid plaque morphological stabilization at 6 months, defined as defined as the disappearance of ulcerations and fluffy components and the achievement of a regular plaque morphology with prevalence of fibrous atheroma and/or (b) carotid plaque regression at 12 months, defined as reduction of the entity of the stenosis and/or peak systolic velocity by at least 5%, as compared with baseline. The CARUSO trial will test the superiority of evolocumab on top of ongoing LLT versus ongoing LLT alone regarding carotid plaque morphological stabilization and regression. The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Morphological stabilization and regression of carotid plaque following therapy with evolocumab in a high‐risk patient

Lipid-lowering therapy is a mainstay for the management of coronary and carotid disease. Actually, progression of atherosclerosis and adverse events are reduced in proportion to the achieved levels of LDL cholesterol (LDL-C). A 67-year-old patient underwent two hospitalizations 6 months apart due to acute coronary syndromes. In the first, PCI with drug-eluting stents (DES) was performed to treat ulcerated stenoses in the left anterior descending artery. In the second, lipid-rich critical disease was found on the right coronary artery and treated with PCI + DES. Later, carotid duplex ultra-sonography (DU) was done due to some episodes of dizziness. It showed an 80% critical stenosis (peak systolic velocity, PSV 239 cm/s) of the left internal carotid artery (LICA) with high-risk features (hypoechogenic and irregular plaque with "fluffy" components). In consideration of the plaque morphology and the unmet LDL-C targets, evolocumab was added to the ongoing statin therapy. In the following months, we observed a parallel trend between carotid plaque regression and LDL-C lowering. Initial plaque remodeling was seen after 5months: the atheroma appeared fibrotic, with no more fluffy components. At 10 months, in conjunction with the achievement of LDL-C goal (23 mg/dl), a fibrocalcific atheroma was observed; PSV, after an initial rise, fell to 229 cm/s. No further cardiovascular event occurred at 46 months. Last DUS showed a 60% fibrocalcific mid LICA stenosis with PSV of 180 cm/s. Our experience highlights the important role of proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors in promoting remodeling and hopefully regression of atherosclerotic plaques.

A Voxel-Based Fully Convolution Network and Continuous Max-Flow for Carotid Vessel-Wall-Volume Segmentation From 3D Ultrasound Images.

Vessel-wall-volume (VWV) is an important three-dimensional ultrasound (3DUS) metric used in the assessment of carotid plaque burden and monitoring changes in carotid atherosclerosis in response to medical treatment. To generate the VWV measurement, we proposed an approach that combined a voxel-based fully convolution network (Voxel-FCN) and a continuous max-flow module to automatically segment the carotid media-adventitia (MAB) and lumen-intima boundaries (LIB) from 3DUS images. Voxel-FCN includes an encoder consisting of a general 3D CNN and a 3D pyramid pooling module to extract spatial and contextual information, and a decoder using a concatenating module with an attention mechanism to fuse multi-level features extracted by the encoder. A continuous max-flow algorithm is used to improve the coarse segmentation provided by the Voxel-FCN. Using 1007 3DUS images, our approach yielded a Dice-similarity-coefficient (DSC) of 93.2±3.0% for the MAB in the common carotid artery (CCA), and 91.9±5.0% in the bifurcation by comparing algorithm and expert manual segmentations. We achieved a DSC of 89.5±6.7% and 89.3±6.8% for the LIB in the CCA and the bifurcation respectively. The mean errors between the algorithm-and manually-generated VWVs were 0.2±51.2 mm3 for the CCA and -4.0±98.2 mm3 for the bifurcation. The algorithm segmentation accuracy was comparable to intra-observer manual segmentation but our approach required less than 1s, which will not alter the clinical work-flow as 10s is required to image one side of the neck. Therefore, we believe that the proposed method could be used clinically for generating VWV to monitor progression and regression of carotid plaques.

Deep learning-based carotid media-adventitia and lumen-intima boundary segmentation from three-dimensional ultrasound images.

PurposeQuantification of carotid plaques has been shown to be important for assessing as well as monitoring the progression and regression of carotid atherosclerosis. Various metrics have been proposed and methods of measurements ranging from manual tracing to automated segmentations have also been investigated. Of those metrics, quantification of carotid plaques by measuring vessel‐wall‐volume (VWV) using the segmented media‐adventitia (MAB) and lumen‐intima (LIB) boundaries has been shown to be sensitive to temporal changes in carotid plaque burden. Thus, semi‐automatic MAB and LIB segmentation methods are required to help generate VWV measurements with high accuracy and less user interaction.MethodsIn this paper, we propose a semiautomatic segmentation method based on deep learning to segment the MAB and LIB from carotid three‐dimensional ultrasound (3DUS) images. For the MAB segmentation, we convert the segmentation problem to a pixel‐by‐pixel classification problem. A dynamic convolutional neural network (Dynamic CNN) is proposed to classify the patches generated by sliding a window along the norm line of the initial contour where the CNN model is fine‐tuned dynamically in each test task. The LIB is segmented by applying a region‐of‐interest of carotid images to a U‐Net model, which allows the network to be trained end‐to‐end for pixel‐wise classification.ResultsA total of 144 3DUS images were used in this development, and a threefold cross‐validation technique was used for evaluation of the proposed algorithm. The proposed algorithm‐generated accuracy was significantly higher than the previous methods but with less user interactions. Comparing the algorithm segmentation results with manual segmentations by an expert showed that the average Dice similarity coefficients (DSC) were 96.46 ± 2.22% and 92.84 ± 4.46% for the MAB and LIB, respectively, while only an average of 34 s (vs 1.13, 2.8 and 4.4 min in previous methods) was required to segment a 3DUS image. The interobserver experiment indicated that the DSC was 96.14 ± 1.87% between algorithm‐generated MAB contours of two observers' initialization.ConclusionsOur results showed that the proposed carotid plaque segmentation method obtains high accuracy and repeatability with less user interactions, suggesting that the method could be used in clinical practice to measure VWV and monitor the progression and regression of carotid plaques.

“Time rate” of 24‐hour blood pressure variability

“Time rate” of 24‐hour blood pressure variability

Abstract 228: The Establishment of a Novel Atherosclerosis Regression Model in Mice

Background: Inhibition of plaque progression by various anti-atherosclerotic drugs is a canonical aspect underlying their therapeutic efficacy. Although existed animal models of plaque regression are available for drug evaluation, they are either highly invasive or time-consuming. We therefore aimed to establish a practical method to study the mechanism of atherosclerosis regression based on hemodynamic regulation of atherosclerosis. Methods: A carotid plaque regression model in mice was developed based on the previously described model. Briefly, a single slipknot was applied to all three branches of the left carotid artery (LCA) in ApoE -/- mice. After 2 weeks on HFD, the blood flow in LCA was reconstructed by slipknot release. Mice were housed for additional 4 weeks. Carotid ultrasonography was used to verify successful induction of disturbed flow and the reconstruction of the blood flow. Atherosclerotic plaques were stained with Sudan IV. The infiltration of smooth muscle cells and macrophages were determined by immunofluorescence staining. Results: Histology studies demonstrated similar cellular components and lipid deposition between the d-flow induced plaques in the LCA in WT mice and atherosclerotic plaques in aorta of ApoE -/- mice on HFD. However, a significantly higher proportion of SMC (n=5, p<0.0001) and lower macrophage infiltration (n=6, p=0.0056) were observed in the induced carotid plaques compared to the aortic plaques. After the release of the knots, an abrupt increase in flow velocity indicated a successful restoration of blood flow from the LCA to its branches. At this point, the restored flow in ligated LCA was still lower compared to the untied right carotid artery (RCA). After the procedure, mice were given chew diet for additional 4 weeks and blood flow was re-accessed using carotid ultrasonography. Results showed no significant difference of blood flow between LCA and RCA, indicating nearly complete regression of carotid atherosclerosis. Conclusion: We have established a highly reproducible atherosclerosis regression model with less invasiveness and genetic independence that supplies a practical tool for evaluation of anti-atherosclerotic drugs and for the pathophysiology of atherosclerosis regression.

Efficacy of Zofenopril vs. Irbesartan in Combination with a Thiazide Diuretic in Hypertensive Patients with Multiple Risk Factors not Controlled by a Previous Monotherapy: A Review of the Double-Blind, Randomized "Z" Studies.

Combinations between an angiotensin converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) are among the recommended treatments for hypertensive patients uncontrolled by monotherapy. Four randomized, double-blind, parallel group studies with a similar design, including 1469 hypertensive patients uncontrolled by a previous monotherapy and with ≥1 cardiovascular risk factor, compared the efficacy of a combination of a sulfhydryl ACE inhibitor (zofenopril at 30 or 60 mg) or an ARB (irbesartan at 150 or 300 mg) plus HCTZ 12.5 mg. The extent of blood pressure (BP)-lowering was assessed in the office and over 24 h. Pleiotropic features of the treatments were evaluated by studying their effect on systemic inflammation, organ damage, arterial stiffness, and metabolic biochemical parameters. Both treatments similarly reduced office and ambulatory BPs after 18–24 weeks. In the ZODIAC study a larger reduction in high sensitivity C reactive protein (hs-CRP) was observed under zofenopril (−0.52 vs. +0.97 mg/dL under irbesartan, p = 0.001), suggesting a potential protective effect against the development of atherosclerosis. In the ZENITH study the rate of carotid plaque regression was significantly larger under zofenopril (32% vs. 16%; p = 0.047). In the diabetic patients of the ZAMES study, no adverse effects of treatments on blood glucose and lipids as well as an improvement of renal function were observed. In patients with isolated systolic hypertension of the ZEUS study, a slight and similar improvement in renal function and small reductions in pulse wave velocity (PWV), augmentation index (AI), and central systolic BP were documented with both treatments. Thus, the fixed combination of zofenopril and HCTZ may have a relevant place in the treatment of high-risk or monotherapy-treated uncontrolled hypertensive patients requiring a more prompt, intensive, and sustained BP reduction, in line with the recommendations of current guidelines.

Blood Pressure Response to Zofenopril or Irbesartan Each Combined with Hydrochlorothiazide in High-Risk Hypertensives Uncontrolled by Monotherapy: A Randomized, Double-Blind, Controlled, Parallel Group, Noninferiority Trial

In this randomized, double-blind, controlled, parallel group study (ZENITH), 434 essential hypertensives with additional cardiovascular risk factors, uncontrolled by a previous monotherapy, were treated for 18 weeks with zofenopril 30 or 60 mg plus hydrochlorothiazide (HCTZ) 12.5 mg or irbesartan 150 or 300 mg plus HCTZ. Rate of office blood pressure (BP) response (zofenopril: 68% versus irbesartan: 70%; p = 0.778) and 24-hour BP response (zofenopril: 85% versus irbesartan: 84%; p = 0.781) was similar between the two treatment groups. Cardiac and renal damage was equally reduced by both treatments, whereas the rate of carotid plaque regression was significantly larger with zofenopril. In conclusion, uncontrolled monotherapy treated hypertensives effectively respond to a combination of zofenopril or irbesartan plus a thiazide diuretic, in terms of either BP response or target organ damage progression.

Rosuvastatin induced carotid plaque regression in patients with inflammatory joint diseases

Objective. Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of £1.8 mmoles/liter (£70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height. Methods. Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography. Results. The mean6SD age of the patients was 60.86 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0–99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1–8) and 1.80 mm (IQR 1.60–2.10), respectively. The mean6SD change in carotid plaque height after 18 months of treatment with rosuvastatin was 20.196 0.35 mm (P < 0.0001). The mean6SD baseline LDL cholesterol level was 4.06 0.9 mmoles/liter (154.76 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was 22.3 mmoles/liter (95% confidence interval [95% CI] 22.48, 22.15) (288.9 mg/dl [95% CI 295.9, 283.1]). The mean 6 SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.76 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of £1.8 mmoles/liter (£70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction. Conclusion. Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression ClinicalTrials.gov identifier: NCT01389388. EudraCT database no. 2008-005551-20. Supported by the South-Eastern Regional Health Authority of Norway. AstraZeneca provided the study drug. S. Rollefstad, MD, PhD, E. Ikdahl, MD, I. C. Olsen, PhD, H. B. Hammer, MD, PhD, T. K. Kvien, MD, A. G. Semb, MD, PhD: Diakonhjemmet Hospital, Oslo, Norway; J. Hisdal, PhD: Oslo University Hospital, Aker, Oslo, Norway; I. Holme, PhD: Oslo University Hospital, Ulleval, Oslo, Norway; K. T. Smerud, MSc: Smerud Medical Research International AS, Oslo, Norway; G. D. Kitas, MD, PhD, FRCP: The Dudley Group NHS Foundation Trust, West Midlands, UK; T. R. Pedersen, MD, PhD: Centre of Preventive Medicine, Oslo University Hospital, Ulleval, and University of Oslo, Oslo, Norway. Dr. Hammer has received consulting fees, speaking fees, and/ or honoraria from Pfizer, Roche, AbbVie, UCB, and Merck Sharp & Dohme (less than $10,000 each). Dr. Pedersen has received speaking fees from Amgen (less than $10,000) and consulting/speaking fees from Merck Sharp & Dohme (more than $10,000). Dr. Semb has received speaking fees, consulting fees, and/or honoraria from Merck Sharp & Dohme, Schering Plough, AbbVie, Bristol-Myers Squibb, UCB, Wyeth/ Pfizer, and Hoffmann-La Roche/Genentech (less than $10,000 each). Address correspondence to S. Rollefstad, MD, PhD, Preventive Cardio-Rheuma Clinic, Department of Rheumatology, Diakonhjemmet Hospital, PO Box 23 Vinderen, NO-0319 Oslo, Norway. E-mail: s-rollef@diakonsyk.no or s.c.h.rollefstad@medisin.uio.no. Submitted for publication October 20, 2014; accepted in revised form March 10, 2015.

FRI0050 Rosuvastatin Induced Carotid Plaque Regression in Patients with Inflammatory Joint Diseases

BackgroundPatients with rheumatoid arthritis (RA) and carotid artery plaques (CP) have increased risk of acute coronary syndrome. Statin treatment with low density lipoprotein cholesterol (LDL-c) goal ≤1.8 mmol/L is recommended...

Regression of Carotid Plaques in Individuals at Low-to-intermediate Cardiovascular Risk Treated with Citozym and Propulzym

A prospective trial was performed to assess coronary plaque regression following about 5 months of treatments with two dietary supplements, Citozym and Propulzym. Coronary segments that included the most diseased plaque of 20 selected patients were analyzed using carotid ultrasound (CDUS). Inclusion criteria were as follows: 20 subjects (10 of control group and 10 of test group) aged between 54 and 74 years with a clear diagnosis of carotid plaque and stenosis percentage of not less than 40% and not more than 70%. The data obtained showed a wide inter-individual variability, with a range of reduction from 4% to 27%. It is interesting to note that the plaque reduction in one patient reached a value of about 27% observable with the ultrasonic examination. Since it is clear that carotid plaque morphology/stability is one of the most important factor regarding the definition of cardiovascular risk, our preliminary results suggest the possibility of a non-invasive treatment of carotid plaque.

Impact of Cilostazol on the Progression of Carotid Atherosclerosis in Patients with Retinal Vascular Occlusion

Cilostazol, a selective phosphodiesterase three inhibitor, has been proposed to have beneficial effects in the prevention of atherosclerosis. We aimed to investigate the effects of cilostazol on carotid intima-media thickening (IMT) and total plaque area (TPA) in patients with retinal vascular occlusion. A total of 63 consecutive vascular occlusive retinopathy patients with carotid atherosclerosis were enrolled. We examined changes in the carotid IMT/TPA and visual acuity/macular thickness before and after 1-year treatment with cilostazol (200mg/day). The mean IMT of both common carotid arteries (CCAs) and internal carotid arteries (ICAs) were significantly reduced after cilostazol treatment. There was no significant difference in the TPA of both CCAs before and after the treatment (before; 0.61±0.94 vs. after; 0.45±0.79cm(2) , P=0.291); however, significant plaque regression (before; 0.14±0.15 vs. after; 0.25±0.14 cm(2) , P=0.004) was observed in selected patients (n=30) with a TPA <0.5cm(2) . The improvement in macular thickness was significantly associated with an improvement in carotid IMT (r=0.42, P=0.001) and TPA (r=0.23, P=0.04). Cilostazol potently inhibited the progression of carotid IMT and may play a role in the early carotid plaque regression in patients with retinal vascular occlusion.

Abstract 5029: Carotid Plaque Regression Following 6-Month Statin Therapy Assessed by 3T MRI: Comparison With Ultrasound Intima-Media Thickness

Statin’s role in short-term plaque regression is unknown. 3T MRI has superior plaque volume (PV) measurement capacity compared to ultrasound intima-media thickness (IMT). We tested the hypothesis that carotid plaque progression is attenuated by 6 month statin therapy and this can be detected by MRI PV but not IMT. Methods : 15 subjects (68±3 years, 4F) with carotid atherosclerosis had carotid MRI (4 channel coil, resolution 0.3– 0.6×0.3– 0.6×2mm) and IMT assessed at baseline and 6 months post-statin treatment. T1, T2, proton density and time of flight images were obtained±12 mm from flow divider. PV and components were measured with Plaqueview software. Same day mean posterior IMT were measured by standard method. Observers were blinded to subject/scan order. Results : LDL changed from 90±7 to 78±7 mg/dL (p=NS). MRI PV decreased (1166±83 to 1084±102 mm 3 , p=0.007). Mean IMT was unchanged (1.14±0.07 vs. 1.14±0.07 mm, p=NS). Change in necrotic and hemorrhage volume correlated with MRI PV change (R=0.8, 0.7, all p&lt;0.001), but not IMT change. In 8 subjects, plaque spatial distribution (6 quadrants) was analyzed (see figure ). Greatest thickness was seen opposite the flow divider (241–300°, p&lt;0.01), a region not accessed by US IMT. Conclusions : In carotid disease, there was a measurable reduction in plaque burden following short-term statin treatment using 3T MRI that was not seen with US IMT. The heterogenous spatial distribution of plaque supports use of volumetric measurement for serial studies. 3T MRI may be useful to assess treatment efficacy, reduce number of subjects needed and be a better imaging tool to assess effects of novel therapies for carotid atherosclerosis in clinical trials.

Association of Cholesterol Subfractions and Carotid Lipid Core Measured by MRI

To the Editor: A strong relationship exists between cholesterol and atherosclerosis,1 with low density lipoprotein (LDL) being a major risk factor.2 However, 50% of patients with acute coronary events have “normal” cholesterol, and 75% patients with premature coronary heart disease (CHD) have normal LDL.3 Thus, contribution of other lipoproteins has been explored. High density lipoprotein (HDL), comprised primarily of 2 subfractions, HDL2 (large buoyant) and HDL3 (small dense), has a protective role in CHD.4,5 LDL can be dense or buoyant, and dense LDL is highly atherogenic, associated with 4-fold increased CHD risk.6 Lipoproteina [Lp(a)], is a strong risk factor for CHD and stroke.7 MRI can noninvasively visualize arterial wall remodelling and atherosclerotic plaque components (lipid core, fibrous cap, and calcium).8,9 However, in vivo relationships between plaque components and cholesterol subfractions have not been demonstrated in humans. We examined in vivo relationship between cholesterol subfractions and atherosclerotic plaque, measured by MRI, in internal carotid arteries (ICA) of atherosclerotic patients. This was an exploratory cross-sectional study of consecutively enrolled initial 28 patients who were part of an ongoing randomized trial testing the effects of extended release Niacin versus placebo station top of baseline therapy on carotid plaque regression, analyzed at baseline. All patients signed written informed consent and had documented atherosclerosis in …

Carotid plaque regression on oestrogen replacement: A pilot study

To investigate the effect of unopposed oestrogen on atheromatous carotid plaques. Seventeen postmenopausal women with known carotid disease. Carotid intimal thickness and plaque length and thickness were measured prior to and following 3 and 6 months of treatment, using Duplex ultrasound. A total of 22 plaques were followed up. There was a reduction in plaque length after 3 (-8.14%, p = 0.001) and 6 months (-28%, p = 0.001) of treatment. The reduction in plaque thickness (-18%, p = 0.004) was significant after 6 months of treatment. Reductions in intimal thickness were not statistically significant. Our results suggest that oestrogen replacement is associated with significant plaque regression.

Regression of carotid plaques during low density lipoprotein cholesterol elimination.

We performed serial prospective ultrasound examinations of four flat and 17 soft carotid plaques during an average of 17 months in seven patients with heterozygous hypercholesterolemia during heparin-induced extracorporeal low density lipoprotein elimination on precipitation from plasma. By means of a specially designed quantitative three-dimensional ultrasound analysis, significant plaque volume reduction could be evaluated in all subjects, along with a marked reduction of total and low density lipoprotein cholesterol and fibrinogen serum levels.