Ultrasound Carotid Intima-media Thickness Research Articles

Cardiovascular Aging and Risk Assessment: How Multimodality Imaging Can Help.

Aging affects the cardiovascular system, and this process may be accelerated in individuals with cardiovascular risk factors. The main vascular changes include arterial wall thickening, calcification, and stiffening, together with aortic dilatation and elongation. With aging, we can observe left ventricular hypertrophy with myocardial fibrosis and left atrial dilatation. These changes may lead to heart failure and atrial fibrillation. Using multimodality imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging, it is possible to detect these changes. Additionally, multimodality imaging, mainly via CT measurements of coronary artery calcium or ultrasound carotid intima-media thickness, enables advanced cardiovascular risk stratification and helps in decision-making about preventive strategies. The focus of this manuscript is to briefly review cardiovascular changes that occur with aging, as well as to describe how multimodality imaging may be used for the assessment of these changes and risk stratification of asymptomatic individuals.

ASSOCIATION OF AMBULATORY BLOOD PRESSURE PARAMETERS WITH CAROTID DAMAGE IN PATIENTS WITH TYPE-2 DIABETES/PRE-DIABETES AND HYPERTENSION

Objective: This study investigated the association between ambulatory blood pressure (ABP) parameters and carotid damage in patients with type-2 diabetes/pre-diabetes and hypertension. Design and method: Adults with hypertension and type-2 diabetes/prediabetes were subjected to (i) 24-hour ABP monitoring (20 min intervals, Microlife WatchBPO3) and (ii) estimation of preclinical carotid damage (ultrasound carotid intima-media thickness [cIMT] and carotid plaque score [CPS]). BP variability was quantified using the standard deviation (SD) and coefficient of variation (CV). Results: Seventy individuals were analyzed [age 65.2±9.7 years, 47 men, body mass index (BMI) 31.6±4.8 kg/m2, HbA1c 6.6±0.8%, 86% diabetics, average 24-hour ABP (systolic/diastolic) 123±12/69±7 mmHg, cIMT 0.8±0.2 mm, CPS 5.4±4.7 mm]. There was a significant correlation between 24-hour/daytime systolic ABP and cIMT (r = 0.34/0.34 respectively, p<0.01) and CPS (r = 0.26/0.25 respectively, p<0.05). 24-hour/daytime/nighttime pulse pressure was associated with cIMT (r = 0.39/0.41/0.28 respectively, p<0.05) and CPS (r = 0.26/0.28/0.23, p< = 0.05). No significant association was found between indices of carotid damage and SD or CV of systolic ABP. Stepwise multivariable regression analysis with age, sex, BMI, smoking and daytime pulse pressure as independent variables, revealed that cIMT was determined by the daytime pulse pressure and age (R2 = 0.27), whereas CPS was determined by daytime pulse pressure and smoking (R2 = 0.23). Conclusions: These preliminary data suggest that in patients with type-2 diabetes/pre-diabetes and hypertension ambulatory pulse pressure might have a critical role in the development of carotid damage.

An Italian observational study on subclinical cardiovascular risk factors and depressive symptomatology. A suggestion for the potential utility of a sinergic cardio-psychiatric perspective

IntroductionGrowing evidence has been collected over the complex, intertwined pathophysiological connection among subclinical cardiovascular (CV) disease, i.e. atherosclerosis, systemic low pro-inflammatory states and psychiatric disorders/symptomatology (anxiety, depression), with controversial results.AimAim of this study was to investigate the possible link between subclinical CV risk factors (atherosclerosis), depressive symptoms, and inflammation.MethodsCross-sectional study. Inclusion criteria: outpatients aged ≥40 years, attending colonoscopy after positive faecal occult blood test, negative medical history for cancer. Collected data: blood pressure, glycaemia, lipid profile, waist circumference, BMI, PCR (C reactive protein), LPS (bacterial lipopolysaccharide), ultrasound carotid intima-media thickness (c-IMT). Psychometric tests: HADS, TCI, IMSA, SF36. Statistical analysis performed with STATA13.ResultsThe 54 patients enrolled were equally distributed by gender. CV risk factors were common in the study population, with 33 patients (61.11%) with hypertension, 14 (25.93%) with hyperglycaemia, 20 (37.4%) with hypertriglyceridemia, 19 (35.19%) with low HDL and 64.81% with overweight. High levels of PCR were found in 24 subjects (44.44%). Right c-IMT was increased in 26.41% of the sample, and 11.32% had an atheromatous plaque. Left c-IMT was increased in 24.53% of patients, with a plaque in 7.55% of them. Clinically relevant depressive symptoms were found in the 18.87% of the sample and were statistically significantly associated with PCR (OR = 28.63; P = 0.01).ConclusionsEvidence contributing to the so-called “inflammation theory” of depression and supporting the association between mood and CV disorders was here collected, supporting the need for a multidisciplinary approach to the diagnosis and treatment of such conditions, assuming a clinically-translated PNEI (psycho-neuro-endocrino-immunological) perspective.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Atherosclerosis is Evident in Treated HIV-Infected Subjects With Low Cardiovascular Risk by Carotid Cardiovascular Magnetic Resonance

Premature atherosclerosis has been observed among HIV-infected individuals with high cardiovascular risk using one-dimensional ultrasound carotid intima-media thickness. We evaluated the assessment of HIV-infected individuals with low traditional cardiovascular disease risk using cardiovascular magnetic resonance, which allows three-dimensional assessment of the carotid artery wall. Carotid cardiovascular magnetic resonance was performed in 33 HIV-infected individuals (cases) (19 male, 14 female), and 35 HIV-negative controls (20 male, 15 female). Exclusion criteria included smoking, hypertension, hyperlipidemia (total cholesterol/HDL ratio > 5) or family history of premature atherosclerosis. Cases were stable on combination antiretroviral therapy with plasma HIV-1 RNA <50 copies per milliliter. Using computer modeling, the arterial wall, lumen, and total vessel volumes were calculated for a 4-cm length of each carotid artery centered on the bifurcation. The wall/outer-wall ratio (W/OW), an index of vascular thickening, was compared between the groups. Cases had a median CD4 cell count of 690 cells per microliter. Mean (±SD) age and 10-year Framingham coronary risk scores were similar for cases and controls (45.2 ± 9.7 years versus 46.9 ± 11.6 years and 3.97% ± 3.9% versus 3.72% ± 3.5%, respectively). W/OW was significantly increased in cases compared with controls (36.7% versus 32.5%, P < 0.0001); this was more marked in HIV-infected females. HIV status was significantly associated with increased W/OW after adjusting for age (P < 0.0001). No significant association between antiretroviral type and W/OW was found-W/OW lowered comparing abacavir to zidovudine (P = 0.038), but statistical model fits poorly. In a cohort of treated HIV-infected individuals with low measurable cardiovascular risk, we have observed evidence of premature subclinical atherosclerosis.

A new method for IVUS-based coronary artery disease risk stratification: A link between coronary & carotid ultrasound plaque burdens

Interventional cardiologists have a deep interest in risk stratification prior to stenting and percutaneous coronary intervention (PCI) procedures. Intravascular ultrasound (IVUS) is most commonly adapted for screening, but current tools lack the ability for risk stratification based on grayscale plaque morphology. Our hypothesis is based on the genetic makeup of the atherosclerosis disease, that there is evidence of a link between coronary atherosclerosis disease and carotid plaque built up. This novel idea is explored in this study for coronary risk assessment and its classification of patients between high risk and low risk.This paper presents a strategy for coronary risk assessment by combining the IVUS grayscale plaque morphology and carotid B-mode ultrasound carotid intima-media thickness (cIMT) – a marker of subclinical atherosclerosis. Support vector machine (SVM) learning paradigm is adapted for risk stratification, where both the learning and testing phases use tissue characteristics derived from six feature combinational spaces, which are then used by the SVM classifier with five different kernels sets. These six feature combinational spaces are designed using 56 novel feature sets. K-fold cross validation protocol with 10 trials per fold is used for optimization of best SVM-kernel and best feature combination set.IRB approved coronary IVUS and carotid B-mode ultrasound were jointly collected on 15 patients (2 days apart) via: (a) 40MHz catheter utilizing iMap (Boston Scientific, Marlborough, MA, USA) with 2865 frames per patient (42,975 frames) and (b) linear probe B-mode carotid ultrasound (Toshiba scanner, Japan). Using the above protocol, the system shows the classification accuracy of 94.95% and AUC of 0.95 using optimized feature combination. This is the first system of its kind for risk stratification as a screening tool to prevent excessive cost burden and better patients’ cardiovascular disease management, while validating our two hypotheses.

No evidence of association between subclinical thyroid disorders and common carotid intima medial thickness or atherosclerotic plaque

Background and aimsIncreased carotid artery intima-media thickness (IMT) and the presence of plaques have been shown to be predictors of cardiovascular disease. The cardiovascular risk in patients with overt thyroid diseases is related to increased risk of atherosclerosis, but there has been no clear evidence about subclinical disorders. We have assessed whether subclinical thyroid dysfunction is associated with arterial thickening and plaque. Methods and resultsThe SardiNIA study is a population-based survey on the Italian island of Sardinia. We reviewed data from 5815 subjects (aged 14–102 years), none of whom had overt hyperthyroidism or hypothyroidism or was taking thyroid medication. Serum thyrotropin (TSH), free thyroxine, together with carotid ultrasound IMT and the presence of common carotid plaques were analysed in all subjects. Possible association of IMT and carotid plaques with thyroid parameters was evaluated by univariate and multivariate analyses. IMT was significantly associated with age, sex, smoking, low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol, pulse pressure (PP), history of arterial hypertension, diabetes, and previous cardiovascular events (p = 0.001 or lower, R2 = 0.47). Carotid plaques were predicted by age, sex, LDL, PP, history of diabetes, previous cardiovascular events, and the use of statins (p = 0.029 or lower). Thyroid hormone was not predictive of carotid atherosclerosis when adjusted for confounders. ConclusionThyroid hormone is not associated with increased IMT or with the presence of carotid artery plaque. Our data do not support the idea that treating subclinical disorders might help to prevent arterial remodelling or carotid atherosclerosis.

Epicatechin induced vasorelaxation of human internal mammary artery

Epicatechin induced vasorelaxation of human internal mammary artery

Abstract 267: CD93: A Novel Myocardial Infarction- Associated Protein with Glucose Regulatory Properties in Humans and Mice

Introduction: Coronary artery disease (CAD) is a complex disorder involving metabolic, and inflammatory mechanisms. Previously, we have shown that plasma levels of soluble CD93 (sCD93) are inversely associated with CAD events in women. Yet, little is known about the role of sCD93 in disease progression or its association with metabolic pathways. Hypothesis: In this study we asked whether plasma levels of sCD93 could be associated with type 2 diabetes (T2D), a major risk factor for CAD. In parallel, we investigated CD93-mediated effects in metabolism and inflammation using a newly established mouse model. Methods: Soluble CD93 was measured by Mesoscale® in plasma of subjects from the IMPROVE cohort, (3371 subjects). IMPROVE is a prospective, multicentre, longitudinal, observational study with subjects presenting at least 3 established CVD risk factors but no clinical coronary artery disease at baseline. T2D was defined clinically or by blood fasting glucose ≥7mmol/L. Detailed ultrasound carotid intima-media thickness (cIMT) phenotypes at baseline, 15 and 30 months were assessed. In parallel, cd93 heterozygous deficient mice were established by KOMP repository using C57Bl/6N ES cells (CD93low). These mice were then used in a T2D model by giving a high fat diet (21% fat 0.2% cholesterol) or crossed into C57Bl6/N.ApoE deficient mice in order to establish a murine atherosclerosis model. Results: Soluble CD93 levels presented significantly lower in subjects with T2D compared to those without (n= 901 vs 2470; mean ± sd = 156.6±40.0ng/ml vs 164.1±44.8ng/ml, respectively; p&lt;0.0001). However, no association between sCD93 cIMT was observed. In line with this, analysis of ApoE-/-CD93low revealed no changes in atherosclerotic lesion development compared to ApoE-/-CD93 sufficient littermates. Nevertheless, in consensus with the clinical findings, CD93low mice showed impaired glucose clearance and reduced insulin sensitivity compared to littermate controls in the T2D model. Conclusion: Levels of sCD93 were inversely correlated with T2D in a CAD high-risk cohort, furthermore the mouse T2D models indicates CD93 as a glucose-regulating molecule. However, it remains to be determined how CD93 is involved in glucose regulation.

Ultrasound carotid intima–media thickness, carotid plaque and cardiac calcium incrementally add to the Framingham Risk Score for the prediction of angiographic coronary artery disease: A multicenter prospective study

Ultrasound carotid intima–media thickness, carotid plaque and cardiac calcium incrementally add to the Framingham Risk Score for the prediction of angiographic coronary artery disease: A multicenter prospective study☆☆☆ Nicola Gaibazzi ⁎, Fausto Rigo , Rita Facchetti , Scipione Carerj , Cristina Giannattasio , Antonella Moreo , Gianfrancesco Mureddu , Anna Paini , Elisabetta Grolla , Giacomo Faden , Francesca Cesana , Pompilio Faggiano g

What Do Carotid Intima-Media Thickness and Plaque Add to the Prediction of Stroke and Cardiovascular Disease Risk in Older Adults? The Cardiovascular Health Study

The aim of this study was to evaluate whether the addition of ultrasound carotid intima-media thickness (CIMT) measurements and risk categories of plaque help predict incident stroke and cardiovascular disease (CVD) in older adults. Carotid ultrasound studies were recorded in the multicenter Cardiovascular Health Study. CVD was defined as coronary heart disease plus heart failure plus stroke. Ten-year risk prediction Cox proportional-hazards models for stroke and CVD were calculated using Cardiovascular Health Study-specific coefficients for Framingham risk score factors. Categories of CIMT and CIMT plus plaque were added to Framingham risk score prediction models, and categorical net reclassification improvement (NRI) and Harrell's c-statistic were calculated. In 4,384 Cardiovascular Health Study participants (61% women, 14% black; mean baseline age, 72±5 years) without CVD at baseline, higher CIMT category and the presence of plaque were both associated with higher incidence rates for stroke and CVD. The addition of CIMT improved the ability of Framingham risk score-type risk models to discriminate cases from noncases of incident stroke and CVD (NRI= 0.062, P=.015, and NRI= 0.027, P < .001, respectively), with no further improvement by adding plaque. For both outcomes, NRI was driven by down-classifying those without incident disease. Although the addition of plaque to CIMTdid not result in a significant NRI for either outcome, it was significant among those without incident disease. In older adults, the addition of CIMT modestly improves 10-year risk prediction for stroke and CVD beyond a traditional risk factor model, mainly by down-classifying risk in those without stroke or CVD; the addition of plaque to CIMT adds no statistical benefit in the overall cohort, although there is evidence of down-classification in those without events.

Attenuated NOx responses and myocardial ischemia, a possible risk for structural vascular disease in African men: the SABPA study

Chronically elevated blood pressure has been associated with impaired NO-mediated vasodilation and structural vascular disease risk. This study aimed to determine whether significant associations exist regarding NO metabolite (NOx) responses, cardiovascular function and structural vascular disease in a cohort of African and Caucasian men. The study included 81 African and 94 Caucasian male teachers stratified via median splits into low and high NOx ethnic groups. Ambulatory blood pressure, electrocardiogram monitoring and ultrasound carotid intima-media thickness (CIMT) images were obtained. Cardiovascular measurements and fasting blood for NOx responses were measured during rest and on challenging the cardiovascular system with the Stroop colour-word conflict test. African men displayed significantly higher resting NOx as well as higher number of 24 h silent ischemic events than their Caucasian counterparts. Low NOx African men displayed enhanced α-adrenergic and ECG ST segment depression acute mental stress responses as well as 24 h silent ischemic events associated with CIMT (adjusted R(2) = 0.47; β = 0.25; confidence interval (CI) = 0.13, 0.41). African men demonstrated a vulnerable cardiovascular profile. Novel findings revealed α-adrenergic-driven blood pressure responses and less NO bioavailability during acute stress. The association between myocardial ischemia and CIMT in this group emphasized their risk for future coronary artery disease and cerebrovascular events.

Structural Vascular Disease in Africans: Performance of Ethnic-specific Waist Circumference Cut Points using Logistic Regression and Neural Network Analyses: The SABPA Study

A recently proposed model for waist circumference cut points (RPWC), driven by increased blood pressure, was demonstrated in an African population. We therefore aimed to validate the RPWC by comparing the RPWC and the Joint Statement Consensus (JSC) models via Logistic Regression (LR) and Neural Networks (NN) analyses. Urban African gender groups (N=171) were stratified according to the JSC and RPWC cut point models. Ultrasound carotid intima media thickness (CIMT), blood pressure (BP) and fasting bloods (glucose, high density lipoprotein (HDL) and triglycerides) were obtained in a well-controlled setting. The RPWC male model (LR ROC AUC: 0.71, NN ROC AUC: 0.71) was practically equal to the JSC model (LR ROC AUC: 0.71, NN ROC AUC: 0.69) to predict structural vascular -disease. Similarly, the female RPWC model (LR ROC AUC: 0.84, NN ROC AUC: 0.82) and JSC model (LR ROC AUC: 0.82, NN ROC AUC: 0.81) equally predicted CIMT as surrogate marker for structural vascular disease. Odds ratios supported validity where prediction of CIMT revealed -clinical -significance, well over 1, for both the JSC and RPWC models in African males and females (OR 3.75-13.98). In conclusion, the proposed RPWC model was substantially validated utilizing linear and non-linear analyses. We therefore propose ethnic-specific WC cut points (African males, ≥90 cm; -females, ≥98 cm) to predict a surrogate marker for structural vascular disease.

Silent Ischemia Is Associated With Subclinical Atherosclerosis in African Males: The Sympathetic Activity and Ambulatory Blood Pressure in Africans Study

Silent myocardial ischemia is a predictor of subclinical atherosclerosis driven by increased cardiovascular risk markers, although still unknown in Africans. The aim of this study was to assess if cardiovascular risk markers will be associated with subclinical atherosclerosis. African men were stratified into (i) 24-hour silent ischemia (SI, n = 38) and (ii) without (nSI, n = 40) groups. Ambulatory blood pressure (BP), SI, 12-lead resting electrocardiogram, ultrasound carotid intima-media thickness (CIMT) measurements, and fasting blood samples were obtained. Above-normal cardiovascular risk markers, that is, glucose level, heart rate, BP, and CIMT, were evident in men with SI. Hypertension prevalence was 89% in the African SI men as opposed to 64% in the nSI men. Regression analyses revealed that only SI events in SI men explained 35% (95% confidence interval [CI]: 0.22;0.52) of the variance in CIMT, while in all African men it explained 29% (95% CI: 0.19;0.39). In conclusion, SI was associated with structural vascular disease in African men. This could imply that SI is not necessarily driven by hypertension in African men but through other possible mechanisms such as increased sympathetic nervous system activity.

99 Bedside Carotid Ultrasonography to Risk Stratify Patients With Chest Pain in the Emergency Department

The purpose of this study was to determine the role of bedside ultrasound carotid intima-media thickness measurements as an additional diagnostic test to risk stratify patients presenting with chest pain in the emergency department (ED).

Completely Automated Multiresolution Edge Snapper—A New Technique for an Accurate Carotid Ultrasound IMT Measurement: Clinical Validation and Benchmarking on a Multi-Institutional Database

The aim of this paper is to describe a novel and completely automated technique for carotid artery (CA) recognition, far (distal) wall segmentation, and intima-media thickness (IMT) measurement, which is a strong clinical tool for risk assessment for cardiovascular diseases. The architecture of completely automated multiresolution edge snapper (CAMES) consists of the following two stages: 1) automated CA recognition based on a combination of scale-space and statistical classification in a multiresolution framework and 2) automated segmentation of lumen-intima (LI) and media-adventitia (MA) interfaces for the far (distal) wall and IMT measurement. Our database of 365 B-mode longitudinal carotid images is taken from four different institutions covering different ethnic backgrounds. The ground-truth (GT) database was the average manual segmentation from three clinical experts. The mean distance ± standard deviation of CAMES with respect to GT profiles for LI and MA interfaces were 0.081 ± 0.099 and 0.082 ± 0.197 mm, respectively. The IMT measurement error between CAMES and GT was 0.078 ± 0.112 mm. CAMES was benchmarked against a previously developed automated technique based on an integrated approach using feature-based extraction and classifier (CALEX). Although CAMES underestimated the IMT value, it had shown a strong improvement in segmentation errors against CALEX for LI and MA interfaces by 8% and 42%, respectively. The overall IMT measurement bias for CAMES improved by 36% against CALEX. Finally, this paper demonstrated that the figure-of-merit of CAMES was 95.8% compared with 87.4% for CALEX. The combination of multiresolution CA recognition and far-wall segmentation led to an automated, low-complexity, real-time, and accurate technique for carotid IMT measurement. Validation on a multiethnic/multi-institutional data set demonstrated the robustness of the technique, which can constitute a clinically valid IMT measurement for assistance in atherosclerosis disease management.

Completely automated robust edge snapper for carotid ultrasound IMT measurement on a multi-institutional database of 300 images

The carotid intima-media thickness (IMT) is the most used marker for the progression of atherosclerosis and onset of cardiovascular diseases. Computer-aided measurements improve accuracy and precision, but usually require user interaction. In this paper we characterized a new and completely automated technique for carotid segmentation and IMT measurement based on the merits of two previously developed techniques. We used an integrated approach of intelligent image feature extraction and line fitting for automatically locating the carotid artery in the image frame, followed by wall interfaces extraction based on a Gaussian edge operator. We called our system-CARES. We validated CARES on a multi-institutional database of 300 carotid ultrasound images. The IMT measurement bias was 0.032 ± 0.141 mm. Our novel approach of CARES processed 96% of the images in the database taken from two different institutions. In order to evaluate its performance, the figure-of-merit (FoM) was defined as the percent ratio between the average IMT computed by CARES and the one obtained from manual tracings by expert sonographers. The estimated FoM by CARES was 95.7%. Comparing the IMT bias of CARES with our previously published method CALEX that showed an IMT bias equal to 0.099 ± 0.137 mm, CARES improved the IMT accuracy by 67%, while increasing the standard deviation by 3%. CARES could be a useful research tool for processing large datasets in multi-center studies involving atherosclerosis.

The effects of rosiglitazone on atherosclerotic progression in patients with Type 2 diabetes at high cardiovascular risk

Cardiovascular mortality remains high despite intensive treatment of people with Type 2 diabetes mellitus. Meta-analyses on rosiglitazone have raised concerns regarding its cardiovascular safety. We studied the effects of rosiglitazone on ultrasonic indices of carotid arterial disease and inflammatory markers in a group of Type 2 diabetic patients at high cardiovascular risk. A trial of rosiglitazone in Type 2 diabetic patients with high cardiovascular risk and internal carotid artery plaque compared changes in carotid ultrasound intima-media thickness (IMT), plaque thickness, arterial stiffness and compliance, and inflammatory markers at baseline, 26 and 52 weeks. In the rosiglitazone group (n=28), carotid artery plaque thickness was reduced by 0.08 mm, compared with an increase of 0.19 mm (P=0.075) in the placebo group (n=29). There were no significant differences in changes of IMT, carotid wall compliance and stiffness between the two groups. Glycated haemoglobin reduced by -0.9 vs. 0.1% (-7 vs. 2 mmol/mol), (P<0.001); insulin resistance (HOMA-IR) reduced by -37.6 vs. -1.1% (P=0.016); and B cell function (HOMA-B) increased by 36.8 vs. 0.7% (P=0.009). Non-esterified fatty acids reduced by -23.5 vs. 7.9% (P=0.005); tissue plasminogen activator reduced by -25.0 vs. 0.6% (P=0.001); and plasminogen activator inhibitor activity reduced by -57.4 vs. -34.6% (P=0.052). Rosiglitazone reduced carotid artery plaque thickness, though not significantly, and there was no significant change in intima media thickness or other ultrasonic indices of carotid arterial disease. There were significant improvements in glycaemic control, insulin sensitivity and fibrinolytic, but not inflammatory, markers. There was no evidence in this study of any adverse effects on progression of carotid arterial disease.

HDL and LDL as therapeutic targets for cardiovascular disease prevention: The possible role of niacin

Recently two studies on the effect of addition of extended-release niacin to statin treatment on measures of carotid atherosclerosis were estimated in the ARBITER 6-HALTS study (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies) study and the Oxford Niacin Study were published. Adding niacin to statin treatment significantly diminished carotid atherosclerosis as measured by ultrasound carotid intima-media thickness or magnetic resonance imaging. An inhibitor of niacin induced flushing, laropiprant has been developed and demonstrated to considerably improve the tolerability of niacin therapy without impeding on its effect on lipoproteins. Still however clear evidence for the clinical benefit of long-term niacin treatment on cardiovascular morbidity and mortality is lacking. The development situation for ezetimibe is similar to that of niacin. Long-term interventional studies with hard endpoints of both therapies are ongoing. Also both drugs, when proven efficient and safe, are eagerly needed in the prevention of cardiovascular disease.

Relations between cardiovascular risk estimates and subclinical atherosclerosis in naïve HIV patients: results from the HERMES study

The aim of the study was to evaluate the cardiovascular risk factors associated with subclinical carotid atherosclerosis in antiretroviral therapy-naïve HIV-infected patients. The HERMES (HIV Exposure and Risk of Metabolic Syndrome) study enrolled therapy-naïve patients attending hospitals in the Italian coordination group for the study of allergies and HIV infection (CISAI [Coordinamento Italiano per lo Studio Allergia e Infezione da HIV]) in 2007. It was designed to identify metabolic syndrome (MS) and cardiovascular risk factors. The present analysis is a nested cross-sectional study with a subset of patients examined by carotid ultrasonography. Consecutive antiretroviral therapy-naïve HIV patients attending the facilities involved in the CISAI were included. Their 10-year probability of cardiovascular events was calculated using the Framingham Risk Score (FRS) and three other cardiovascular algorithms (the Global Framingham Risk Score - GFRS, 'Progetto Cuore' and 'SCORE'). Vascular age was estimated using a new model derived from GFRS and was compared with chronological age. The diagnosis of MS was based on the National Cholesterol Education Programme and International Diabetes Federation (IDF) definitions. Subclinical atherosclerosis was determined as ultrasound carotid intima-media thickness >0.9 mm. Out of 140 patients enrolled in the HERMES study by the four centres participating in the nested study, a total of 72 (51.4%) subjects, with no overt cardiovascular disease, were examined using carotid ultrasonography. The median age was 40 years, 79.2% men. The vascular age was 7.6 years higher than the chronological age. The factors associated with subclinical atherosclerosis were age (P < 0.0001), vascular age (P = 0.0002), body mass index (P = 0.003), waist circumference (P = 0.0002), MS (IDF definition, P = 0.004) and all the cardiovascular (CV) models (FRS, P = 0.01, GFRS, P = 0.002, Progetto Cuore, P = 0.018, SCORE, P = 0.03). Independent of other significant factors, waist circumference was significantly associated with pathological results (P = 0.007). The GFRS (area under the receiver-operating characteristic curves, 0.78; P < 0.001) had slightly better predictive accuracy than the other three CV models (FRS, areas under the curve [AUC] = 0.71, P = 0.003; Progetto Cuore, AUC = 0.74, P = 0.0005; SCORE, AUC = 0.77, P < 0.0001); 55% of patients at intermediate risk (6-20%) had subclinical carotid lesions. Subclinical carotid lesions had a highly significant direct association with all the CV risk predictors. The GFRS and vascular age were highly predictive. We recommend a carotid ultrasonographic examination at least among HIV patients with GFRS > or =6% or with an elevated waist circumference.

ACAT Inhibition and Progression of Carotid Atherosclerosis in Patients With Familial Hypercholesterolemia

Inhibition of acyl coenzyme A:cholesterol acyltransferase (ACAT), an intracellular enzyme involved in cholesterol accumulation, with pactimibe was developed to assist in the prevention of cardiovascular disease. To evaluate the efficacy and safety of pactimibe in inhibition of atherosclerosis. A prospective, randomized, stratified, double-blind, placebo-controlled study (Carotid Atherosclerosis Progression Trial Investigating Vascular ACAT Inhibition Treatment Effects [CAPTIVATE]) of 892 patients heterozygous for familial hypercholesterolemia conducted at 40 lipid clinics in the United States, Canada, Europe, South Africa, and Israel between February 1, 2004, and December 31, 2005. Study was terminated on October 26, 2005. Participants received either 100 mg/d of pactimibe (n = 443) or matching placebo (n = 438), in addition to standard lipid-lowering therapy. Carotid atherosclerosis, assessed by ultrasound carotid intima-media thickness (CIMT), at baseline, 12, 18, and 24 months. Maximum CIMT was the primary end point and mean CIMT the secondary end point. Because pactimibe failed to show efficacy in the intravascular coronary ultrasound ACTIVATE study, the CAPTIVATE study was terminated prematurely after a follow-up of 15 months. After 6 months of treatment with pactimibe, low-density lipoprotein cholesterol increased by 7.3% (SD, 23%) compared with 1.4% (SD, 28%) in the placebo group (P = .001). The carotid ultrasonographic scans of the 716 patients with at least 2 scans and obtained at least 40 weeks apart were analyzed. Maximum CIMT measurements did not show a pactimibe treatment effect (difference, 0.004 mm; 95% confidence interval [CI], -0.023 to 0.015 mm; P = .64); however, the less variable mean CIMT measurement revealed an increase of 0.014 mm (95% CI, -0.027 to 0.000 mm; P = .04) in patients administered pactimibe vs placebo. Major cardiovascular events (cardiovascular death, myocardial infarction, and stroke) occurred more often in patients administered pactimibe vs placebo (10/443 [2.3%] vs 1/438 [0.2%]; P = .01). In patients with familial hypercholesterolemia, pactimibe had no effect on atherosclerosis as assessed by changes in maximum CIMT compared with placebo but was associated with an increase in mean CIMT as well as increased incidence of major cardiovascular events. clinicaltrials.gov Identifier: NCT00151788.