Regression Of Intima-media Thickness Research Articles

Long-term effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia: an observational case series

BackgroundWe assessed long-term real-world effectiveness and safety of lomitapide in patients with homozygous familial hypercholesterolemia (HoFH).MethodsRetrospective case series of six patients with HoFH treated with lomitapide in an Italian clinic. Changes in low-density lipoprotein cholesterol (LDL-C) during lomitapide treatment were assessed. The effect on LDL-C of PCSK9 inhibitors, apheresis and lomitapide was evaluated. Additionally, high-density lipoprotein cholesterol (HDL-C), gastrointestinal tolerability, hepatic steatosis/elasticity, transaminases, and cardiovascular events and symptoms were assessed.ResultsMedian age at HoFH clinical and molecular diagnoses was 25 (range 2–49) and 40 (29–71) years, respectively. Five (83.3%) had prior cardiovascular events. One patient received apheresis, which was subsequently discontinued. All patients received PCSK9 inhibitors but discontinued due to minimal effectiveness. Median (range) age at lomitapide initiation was 44 (28–73) years, with a median 47 (18–85) months’ treatment (mean dose 17.5 [5–40] mg/day). Mean (SD) baseline LDL-C was 263.2 (148.1) mg/dL, which decreased by 80% at nadir (52.8 [19.2] mg/dL) and 69% at last follow-up (81.3 [30.5] mg/dL). Four patients (66.7%) achieved LDL-C < 70 mg/dL sometime during follow-up, all of whom also achieved LDL-C < 55 mg/dL. Adverse events (AEs) were generally mild to moderate, hepatic steatosis was either absent or mild/moderate and hepatic elasticity remained normal in all but two patients (> 70 years old). All patients with reported cardiovascular symptoms had improvements in symptoms, and all patients reported stabilization or regression of intima-media thickness and atheromatous plaques.ConclusionsThese long-term, real-world data demonstrate that lomitapide substantially reduced LDL-C for up to seven years. Most patients achieved LDL-C goal at some point, consistent with published Phase III trial and real-world evidence data. No patient discontinued lomitapide treatment. Further long-term follow-up in a larger patient population will be important to determine cardiovascular and other outcomes.

Vasoprotective effect of effective lipid-lowering therapy in patients with ST-segment elevation myocardial infarction

To study the vasoprotective effects of atorvastatin depending on the achievement of the target level of low-density lipoprotein cholesterol (LDL-C) in patients with ST-segment elevation myocardial infarction (STEMI) within 48 weeks of follow-up. Included were 112 STEMI patients who received atorvastatin 20-40-80 mg. On days 7-9 from the onset of the disease, after 24 and 48 weeks, ultrasound examination of the carotid arteries with RF technology and applanation tonometry were performed, the lipid profile was determined. The patients were divided into groups: group 1 (n=41) of highly effective therapy (HET) - who achieved the target LDL-C after 24 and 48 weeks; group 2 (n=29) in relatively effective therapy (RET) - achieving target values at 24th or 48th week; group 3 (n=42) insufficiently effective therapy (IET) - did not reach the target LDL-C. When examining the carotid arteries in the HET group, the intima-media thickness (IMT) decreased by 10.7-13.1%, the b index - by 14.9-26.3% after 24-48 weeks. In the RET group, the IMT regression was 10.4-13.3%; b index - 23.9% by the 48th week. In the IET group, the b index decreased by the 48th week by 14.3%. According to applanation tonometry in the HET group, the central pressure did not change. In the RET group, systolic pressure in the aorta increased by 10-15.7% after 24-48 weeks, pulse pressure - by 33.9% by the end of observation. With IET, the increase was 8.6-6.8 and 19.8-25.9%, respectively. The odds ratio of developing endpoints in the RET group was 4.7 (95% CI 1.2-26.4; p=0.02), in the IET group - 3.9 (95% CI 1.1-24.8; p=0.03) compared with HET. The most pronounced vasoprotective effect and a decrease in cardiovascular risk are associated with the achievement of the target LDL-C throughout the entire treatment period.

Nonclassical Monocytes (CD14dimCD16+) Are Associated With Carotid Intima-Media Thickness Progression for Men but Not Women

Objective: Few studies of population-based cohorts have investigated prospective associations of lymphoid and myeloid cell subsets in cardiovascular disease onset and progression. The purpose of this analysis was to determine associations of prespecified myeloid and lymphoid lineage cell subsets with common carotid artery intima-media thickness (IMT) progression. Approach and Results: We performed a prospective case-cohort study of 1195 participants from the Multi-Ethnic Study of Atherosclerosis who had peripheral blood mononuclear cells stored from the baseline examination. Key exposure variables were prespecified subsets of lymphoid and myeloid lineage immune cells, phenotyped by multicolor flow cytometry. The primary outcome was progression from baseline (Exam 1) to year 10 (Exam 5) in common carotid IMT. Higher proportions of nonclassical monocytes (CD14dimCD16++) were significantly associated with IMT progression over 10 years, but classical monocytes (CD14++CD16−), CD4+CD28− T cells, and T helper cells producing IL-17 (interleukin 17; T helper 17 cells) were not associated with significant changes in IMT over 10 years. There were significant interactions between monocyte subsets and sex with respect to IMT progression: in sex-stratified analyses, nonclassical monocytes were associated with significant IMT progression and classical monocytes were associated with significant IMT regression for men, whereas there were no significant associations of monocyte subsets with IMT change for women. Conclusions: Nonclassical monocytes were associated with progression of carotid IMT. There were significant sex differences in associations of monocyte subsets with IMT progression: for men, nonclassical monocytes were associated with IMT progression and classical monocytes were associated with regression, whereas these associations were null for women.

Apolipoprotein E gene polymorphisms: a relationship with the risk of coronary artery disease and the effectiveness of lipid-lowering therapy with rosuvastatin

Aim . To analyze the associations of apolipoprotein E (APOE) gene polymorphisms (rs7412 and rs4420638) with the risk of coronary artery disease (CAD) and the effectiveness of lipid-lowering therapy with rosuvastatin. Material and methods . The study involved the analysis of deoxyribonucleic acid samples and phenotypic data of 1700 unrelated individuals of Slavic origin, natives of Central Russia. A pharmacogenetic testing included 205 patients with CAD. Patients were prescribed rosuvastatin with determination of lipid levels and intima-media thickness (IMT) after 6 and 12 months of follow-up. Results. Carriers of the minor T allele for rs7412 polymorphism of the APOE gene were characterized by a lower CAD risk and a higher baseline level of low-density lipoprotein cholesterol (LDL-C). Associations of this polymorphism depended on body mass index. An association with an increased CAD risk was typical for male carriers of the variant G allele for rs4420638 polymorphism of the APOE gene. When treating CAD patients with rosuvas-tatin, a more pronounced lipid-lowering effect on total cholesterol and LDL-C was characteristic of individuals homozygous for the minor T allele for rs7412 of the APOE gene after 1 month of therapy; decrease of the lipidlowering effect with respect to total cholesterol took place in carriers of the heterozygous A/G genotype of rs4420638 polymorphism of the APOE gene after 12 months of therapy. An association was found between the rs7412 polymorphism of the APOE gene and the changes of maximum IMT in CAD patients treated with rosuvastatin. It consisted of the absence of IMT regression in T allele carriers after 6 months of lipid-lowering therapy. Conclusion. Polymorphisms of the APOE gene are associated with parameters of cholesterol metabolism, the risk of CAD and the effectiveness of lipid-lowering therapy with rosuvastatin.

EFFECT OF ROSUVASTATIN ON CAROTID INTIMAMEDIA THICKNESS IN PATIENTS WITH CORONARY ARTERY DISEASE OF DIFFERENT GENDER AND CARDIOVASCULAR RISK PROFILE

Secondary prevention in patients with coronary artery disease (CAD) is provided by the use of statins, as well as by the impact on modiable risk factors. Rosuvastatin causes the regression of intima-media thickness (IMT) of common carotid artery (CCA), which is signicantly associated with CAD. The aim of the study was to evaluate the change in carotid intima-media thickness (CIMT) in patients with CAD of different gender, and having different number of cardiovascular risk factors, provided that patients attain target levels of total cholesterol (TC <4.0 mmol/l) and low density lipoprotein-cholesterol (LDL-C<1.8 mmol/l). Materials and methods. 72 patients with CAD: Stable angina of functional Classes II–III were recruited. They were treated with rosuvastatin, with gradual increase of its dose from 5 to 40 mg daily to attain target levels of TC and LDL-C. Maximum CIMT was assessed at the time of inclusion into the study and after 12 months of therapy. Results and discussion. In conditions of attaining target TC and LDL-C levels, maximum CIMT signicantly decreased both in men (p=0,006) and in women (p=0,002), the latter had lower CIMT (p=0,03) than men after 1 year of therapy, taking into account no difference in baseline values. The patients who had 2 or fewer risk factors (RF) (hypertension, a family history of cardiovascular disease, smoking, obesity, diabetes mellitus were taken into consideration) showed decrease in CIMT (p=0.0001), and those who were characterized by 3 or more RF, showed only lack of its growth (p=0.07). Attained lipid levels in the compared groups of different gender and number of RF did not differ. Conclusion. The study revealed the differences in the change of CIMT in patients with CAD of different sex, and of different number of cardiovascular risk factors.

Dietary quality and carotid intima media thickness in type 1 and type 2 diabetes: Follow-up of a randomised controlled trial

Background and aimsThe relationship between dietary intake and carotid intima media thickness (IMT) and pulse wave velocity (PWV) in individuals with type 1 and type 2 diabetes has not been well studied. We investigated the association between dietary intake and common carotid artery intima media thickness (CCA IMT) and PWV in a cohort with type 1 and type 2 diabetes. Methods and resultsA one-year randomised controlled trial was conducted to investigate the effect of improving dietary quality on CCA IMT. These subjects were followed up again approximately 12 months after the completion of the trial (i.e. approximately 24 month since baseline). The study cohort included 87 subjects that had dietary intake and CCA IMT measured at baseline and after a mean of 2.3 years' follow-up. PWV was measured in a subsample of this cohort.Age and baseline mean CCA IMT were strongly associated with mean CCA IMT at 24 months. After adjustment for age and baseline mean CCA IMT, baseline consumption of carbohydrate (r = −0.28; p = 0.01), sugars (r = −0.27; p = 0.01), fibre (r = −0.26; p = 0.02), magnesium (r = −0.25; p = 0.02) and the Alternate Health Eating Index (AHEI) score (r = −0.23; p = 0.03) were inversely associated with mean CCA IMT at 24 months. Mixed linear modelling showed an interaction between mean CCA IMT and AHEI at baseline (p = 0.024). Those who were in the highest AHEI tertile at baseline had greater CCA IMT regression at 24 months compared to those in the lowest tertile, after adjustment for baseline age, BMI, smoking pack years, time since diabetes diagnosis, and mean arterial pressure at baseline (mean −0.043 mm; 95% CI -0.084, −0.003; p = 0.029). ConclusionsIn this prospective analysis greater diet quality at baseline, as measured by the AHEI, was associated with greater CCA IMT regression after approximately two years. This suggests that greater diet quality is associated with better longer term vascular health in individuals with type 1 and type 2 diabetes.

Carotid and femoral intima-media thickness as an early atherosclerotic marker. Advantages and limits

The intima-media thickness (IMT) is defined as the distance between the hyperechogenic inner (blood-intima interface) and outer line (media-adventitia interface) of the arterial wall. It is a surrogate marker of atherosclerotic damage. No consensus guidelines are available on which site and how carotid IMT sampling should be performed, and comparison among data from different studies is difficult. IMT is the "phenotype" of the early phases of atherosclerotic disease and is related to the main traditional risk factors. Moreover, IMT is a marker of organ damage either in the heart or in other vascular districts. Although threshold IMT values for the prediction of cardiovascular events have not been identified, high IMT values are associated with an increased occurrence of cardiovascular events. Indeed, an IMT > or = 0.9 mm was demonstrated to be associated with an increased cardiovascular risk even after age adjustment. The value of IMT as an independent risk factor is still under debate, especially in young patients at intermediate risk. Moreover, the IMT regression reported in therapeutic trials with statins and antihypertensive drugs was only weakly or not at all associated with a decrease in cardiovascular events. In comparison to carotid IMT, femoral IMT is more strictly correlated with the severity of coronary artery disease and the need for revascularization in effort angina. The simultaneous measurement of carotid and femoral IMT may improve risk stratification in patients with coronary heart disease. The challenge for the future is to establish an IMT cut-off value for a better definition of the individual cardiovascular risk. Such cut-off value may be derived from the combined measurement of carotid and femoral IMT.

Clinical and therapeutic value of carotid intima-media thickness

Carotid Intima Media Thickness (IMT) has been widely used to predict cardiovascular events in primary and secondary prevention studies. Yet, the power of IMT to reclassify risk level on top of conventional risk assessment based on classical risk factors remains unsettled. In fact, recent data indicate that the prognostic power of IMT is lower than that provided by the identification of carotid plaques. The role of IMT as surrogate endpoint to assess the efficacy of cardiovascular protective therapies is also still debated. In fact, no studies have ever been designed and powered to show a relationship between changes in carotid IMT during follow-up and cardiovascular events. Recently, two meta-analysis of trials using IMT as surrogate endpoint failed to demonstrate an association between IMT regression and cardiovascular events. The reasons for the lack of predictive role for changes in IMT are uncertain. It has been shown that IMT is not a pure atherosclerotic index, being substantially affected by age and hemodynamic factors including blood pressure and vessel wall shear stress. In addition, the status of carotid vessels does not strictly reflect that of coronary arteries. Finally, intra and inter-observer variability of measurements may further limit the association between IMT changes in individual patients and cardiovascular risk. Thus, IMT represents a valuable risk marker in population studies but its role for tailoring cardiovascular therapy in clinical practice remains currently uncertain.

High HDL cholesterol level after treatment with pitavastatin is an important factor for regression in carotid intima–media thickness

This study is a prospective multicenter study designed to investigate the effects of lipid-lowering therapy with pitavastatin on atherosclerotic plaque in patients with coronary heart disease, and to determine which factor is more closely associated with plaque regression. Participants (n = 63) were treated with pitavastatin for 12 months, and the carotid intima-media thickness (IMT) was measured by ultrasound before and after treatment. Mean IMT slightly but significantly decreased (from 0.99 ± 0.33 to 0.94 ± 0.28 mm for overall, P = 0.01) regardless of the presence of pretreatment with other statins. There were no significant relations with hs-CRP, malondialdehyde-LDL, LDL cholesterol, and smaller LDL cholesterol levels despite their decrease by pitavastatin. Decreases in mean IMT were observed significantly more frequently in subjects with high on-treatment HDL cholesterol levels than with low HDL cholesterol levels (P = 0.017). The change in mean IMT tended to be inversely correlated with increments in HDL cholesterol and apolipoprotein A-I. The IMT regression was more often observed in the absence of diabetes and metabolic syndrome. In conclusion, we demonstrated that treatment with pitavastatin attenuated atherosclerotic plaque. This effect was associated with the level of HDL cholesterol, and was stronger in the absence of diabetes and metabolic syndrome in our ischemic heart disease patients.

Progression of Carotid Plaque Volume Predicts Cardiovascular Events

Carotid ultrasound evaluation of intima-media thickness (IMT) and plaque burden has been used for risk stratification and for evaluation of antiatherosclerotic therapies. Increasing evidence indicates that measuring plaque burden is superior to measuring IMT for both purposes. We compared progression/regression of IMT, total plaque area (TPA), and total plaque volume (TPV) as predictors of cardiovascular outcomes. IMT, TPA, and TPV were measured at baseline in 349 patients attending vascular prevention clinics; they had TPA of 40 to 600 mm(2) at baseline to qualify for enrollment. Participants were followed up for ≤5 years (median, 3.17 years) to ascertain vascular death, myocardial infarction, stroke, and transient ischemic attacks. Follow-up measurements 1 year later were available in 323 cases for IMT and TPA, and in 306 for TPV. Progression of TPV predicted stroke, death or TIA (Kaplan-Meier logrank P=0.001), stroke/death/MI (P=0.008) and Stroke/Death/TIA/Myocardial infarction (any Cardiovascular event) (P=0.001). Progression of TPA weakly predicted Stroke/Death/TIA (P=0.097) but not stroke/death/MI (P=0.59) or any CV event (P=0.143); likewise change in IMT did not predict Stroke/Death/MI (P=0.13) or any CV event (P=0.455 ). In Cox regression, TPV progression remained a significant predictor of events after adjustment for coronary risk factors (P=0.001) but change in TPA did not. IMT change predicted events in an inverse manner; regression of IMT predicted events (P=0.004). For assessment of response to antiatherosclerotic therapy, measurement of TPV is superior to both IMT and TPA.

Carotid Artery Intima-Media Thickness and the Renin-Angiotensin System

Carotid artery intima-media thickness (IMT) is a biomarker for cardiovascular disease that also predicts the risk of cardiovascular mortality. Angiotensin-Converting enzyme (ACE) inhibition is a unique therapeutic modality because it both treats hypertension and improves arterial health and cardiovascular disease outcomes. Controversy exists regarding the role of ACE inhibitors and angiotensin receptor blockers (ARBs) in IMT regression. Our article provides an update on how ACE inhibitors and ARBs could play a role in decreasing IMT.

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events? A Meta-Analysis of 41 Randomized Trials

Conclusion: Slowed progression or regression of carotid intima-media thickness (IMT) induced by drug therapy does not translate into reduction in clinical cardiovascular events. Summary: Carotid intima-media thickness (IMT) predicts cardiovascular events. IMT is therefore a potentially attractive biomarker as a therapeutic target in subjects at increased cardiovascular risk. IMT is considered a manifestation of subclinical atherosclerosis. It has been included in the list of organ damaged conditions in European Hypertensive Guidelines and in the European Prevention Guidelines. (Mancia G, et al. Eur Heart J 2007;28:1462-536, and Graham I, et al. Eur J Cardiovasc Prev Rehabil 2007;14 Suppl 2:e1-40). IMT changes have been employed as surrogate clinical end-points in randomized clinical studies of lipid lowering agents, antihypertensive agents, oral antidiabetic agents, and antioxidant drugs in subjects at intermediate to high cardiovascular risk. Information verifying whether changes in IMT were associated with consistent changes in cardiovascular risk profile would be relevant for interpretation of IMT variations and surrogate clinical-end points and for identifying therapeutic targets for cardiovascular therapies. The author's designed this meta-analysis to verify whether IMT regression is associated with reduced incidence of cardiovascular events. Cochrane and the Medline databases were searched for articles published until August 2009. Included articles were randomized trials that assessed carotid IMT at baseline and at follow-up and that also reported clinical end-points. A weighted random-affects analysis was used to determine a relationship between mean and maximum IMT changes and outcome. Baseline patient characters, cardiovascular risk profile, IMT at baseline and follow up and quality of the trials were also explored. Estimates and effects were calculated with a fixed-effects model, random-effects model or Peto method. There were 18,307 participants and 41 trials included in the analysis. There were significant reductions in coronary heart disease, cerebral vascular disease events and all cause death induced by active treatments in the trial. However, there was no significant relationship between IMT regression and coronary heart disease events (tau, 0.91; P = .37), cerebral vascular events (tau, −0.32; P = .75) and all cause death (tau, −0.41; P = .69). The association between IMT changes and clinical outcomes was not influenced by subject's baseline characters, cardiovascular risk profile, IMT at baseline, follow up or quality of the trials. Comment: The principle finding of the study is carotid IMT changes do not correlate with changes in major cardiovascular events that are induced by drug treatments in subjects at intermediate to high cardio vascular risk. The US Preventative Task Force considers correlation of IMT changes with clinical events to be unproven (Helfand M, et al. Ann Intern Med 2009;151:496-507). There may be many unknown determinates of IMT that reduce the clinical strength and statistical significance of IMT changes associated with cardiovascular outcomes when compared to more direct atherosclerotic risk factors. It may also be, that atherosclerosis in the carotid artery, is not generally representative of atherosclerosis throughout the body. Atherosclerotic plaques in the carotid artery grow longitudinally at twice the rate that they grow in thickness. Therefore, IMT may be a less sensitive measure of plaque evolution than total plaque burden (Mackinnon AD, et al. Stroke 2004;35:2150-4). The bottom line, however, is that while IMT increase indicates increased cardiovascular risk, changes in IMT induced by drug therapy do not appear to reflect clinical outcome.

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events? A Meta-Analysis of 41 Randomized Trials

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events? A Meta-Analysis of 41 Randomized Trials

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events?: A Meta-Analysis of 41 Randomized Trials

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events?: A Meta-Analysis of 41 Randomized Trials

Does Carotid Intima-Media Thickness Regression Predict Reduction of Cardiovascular Events?: A Meta-Analysis of 41 Randomized Trials

the purpose of this study was to verify whether intima-media thickness (IMT) regression is associated with reduced incidence of cardiovascular events. Carotid IMT increase is associated with a raised risk of coronary heart disease (CHD) and cerebrovascular (CBV) events. However, it is undetermined whether favorable changes of IMT reflect prognostic benefits. the MEDLINE database and the Cochrane Database were searched for articles published until August 2009. All randomized trials assessing carotid IMT at baseline, at end of follow-up, and reporting clinical end points were included. A weighted random-effects meta-regression analysis was performed to test the relationship between mean and maximum IMT changes and outcomes. The influence of baseline patients' characteristics, cardiovascular risk profile, IMT at baseline, follow-up, and quality of the trials was also explored. Overall estimates of effect were calculated with a fixed-effects model, random-effects model, or Peto method. forty-one trials enrolling 18,307 participants were included. Despite significant reduction in CHD, CBV events, and all-cause death induced by active treatments (for CHD events, odds ratio [OR]: 0.82, 95% confidence interval [CI]: 0.69 to 0.96, p = 0.02; for CBV events, OR: 0.71, 95% CI: 0.51 to 1.00, p = 0.05; and for all-cause death, OR: 0.71, 95% CI: 0.53 to 0.96, p = 0.03), there was no significant relationship between IMT regression and CHD events (tau(2)0.91, p = 0.37), CBV events (tau(2)-0.32, p = 0.75), and all-cause death (tau(2)-0.41, p = 0.69). In addition, subjects' baseline characteristics, cardiovascular risk profile, IMT at baseline, follow-up, and quality of the trials did not significantly influence the association between IMT changes and clinical outcomes. regression or slowed progression of carotid IMT, induced by cardiovascular drug therapies, do not reflect reduction in cardiovascular events.

Long-Term Effects of Pioglitazone on Carotid Atherosclerosis in Japanese Patients with Type 2 Diabetes without a Recent History of Macrovascular Morbidity

No previous studies have evaluated the long-term anti-atherosclerotic effects of pioglitazone in Asian patients with type 2 diabetes. Therefore, the present study investigated the protective effects of pioglitazone on the progression of carotid intima-media thickness (IMT), an established surrogate marker of cardiovascular events in Japanese type 2 diabetic patients without a recent history of cardiovascular morbidity. This 2.5-4-year, randomized, open-label, blinded endpoint study was conducted in 6 centers across Japan. Patients received pioglitazone with or without other oral glucose-lowering drugs (excluding another thiazolidinedione) (n=89) or oral glucose-lowering drugs, excluding thiazolidinediones (n=97). Treatment was adjusted to achieve HbA(1c) <6.5%. The primary endpoints of the study were the absolute changes from the baseline to final visit in max- and mean-IMT in the average of bilateral common carotid arteries. Pioglitazone induced carotid IMT regression compared to baseline measurements (from 1.060 ± 0.2368 to 0.992 ± 0.1921 mm; p=0.0042 in max-IMT and from 0.839 ± 0.1873 to 0.780 ± 0.1571 mm; p=0.0019 in mean-IMT). Although the between-group difference did not reach statistical significance, the regression of carotid IMT values was greater in the pioglitazone-treatment group than in the non-pioglitazone group, (max-IMT: -0.069 ± 0.2199 mm vs -0.031 ± 0.2327 mm, respectively; p=NS, mean-IMT: -0.058 ± 0.1718 mm vs -0.043 ± 0.1644 mm, respectively; p=NS). Pioglitazone induced and maintained the long-term regression of carotid IMT in Japanese type 2 diabetic patients. This suggests that pioglitazone may inhibit the progression of atherosclerosis in this patient group. Further studies are required to verify these findings.

Effects of Atorvastatin on Carotid Atherosclerotic Plaques: A Randomized Trial for Quantitative Tissue Characterization of Carotid Atherosclerotic Plaques with Integrated Backscatter Ultrasound

Background: Instability of carotid plaques has been reported to be associated with stroke and other cerebrovascular events. The purpose of this study was to examine whether cholesterol-lowering therapy with atorvastatin in nonhypercholesterolemic patients reduces carotid plaque instability as assessed by ultrasound integrated backscatter (IBS) analysis. Methods: Consecutive non- or slightly hypercholesterolemic patients with moderate carotid artery stenosis were randomly assigned to a diet group (n = 20) or a statin group (atorvastatin; n = 20). Carotid plaques were monitored by measuring intima media thickness (IMT) and IBS values at baseline and after 6 months. Results: Three-dimensional IBS imaging showed that relative lipid volume of carotid plaques significantly decreased from 58.4 ± 25.6 to 47.8 ± 23.5% in the statin group (p < 0.01), whereas there was no significant decrease in the diet group. Significant regression of IMT was not observed in either group. The changes of IBS values and relative lipid volume between baseline and 6 months were correlated with the change in low-density lipoprotein cholesterol (r = 0.31, p < 0.05, and r = 0.34, p < 0.05, respectively). Conclusions: Lipid-lowering therapy by atorvastatin decreased relative lipid volume without significant regression of plaque volume during short-term follow-up in patients with moderate carotid artery stenosis. Quantitative assessment of carotid plaques by IBS analysis was clinically useful for monitoring atherosclerotic lesions.

Statins and their use in preventing carotid disease

Carotid disease may be evaluated by surrogate outcomes, such as intima-media thickness and carotid plaque features, and by clinical end points. Statins stop progression or may induce regression of intima-media thickness, and statins may also stop plaque growth or even induce reduction of plaque volume. Areas rich in lipids within plaques may be reduced in size and/or in number of inflammatory cells. Ultrasound reflectivity may be reduced by statin treatment, indicating less lipid/inflammatory content. Finally, statins appear to reduce the risk of all cardiovascular events (eg, stroke, myocardial infarction, need for revascularization) in patients with carotid stenosis. This review summarizes and discusses the existing data.

Statins and Carotid Intima-Media Thickness Reduction: An Up-to-Date Review

Carotid artery intima-media thickness measured by ultrasound has been shown to be correlated with the presence of cardiovascular disease and is now accepted and used as a surrogate marker for atherosclerotic disease, an important organ damage of hypercholesterolemia. In particular, statins reduce ischemic heart disease, improve endothelial function, reduce pro-inflammatory cytokines, reduce left ventricular hypertrophy and adverse remodeling, and slow/arrest atherosclerotic process. This last effect represents one of the most important targets of lipid-lowering drugs, in particular, carotid intima-media thickness, and an early-onset of atherosclerotic process. The acute anti-inflammatory effects of statins should further be explored as a potential mediator of change in intima-media thickness. Larger randomized controlled trials with selected patients and more detailed measurements of carotid intima-media thickness are needed to determine the clinical practice implications of these findings in participants who have asymptomatic evidence of atherosclerosis. The aim of this review is to explore the effectiveness of several used statins on carotid intima-media thickness regression.

Effects of candesartan cilexetil on carotid remodeling in hypertensive diabetic patients: the MITEC study

In hypertension and diabetes, early structural changes of the arterial wall precede or support atherosclerosis. There is evidence that some antihypertensive drugs exert an antiathero-sclerotic effect. Over 36 months, we investigated the effect of candesartan cilexetil (CC) on the common carotid intima-media thickness (IMT) vs amlodipine besylate (AML) in patients with type 2 diabetes and mild to moderate essential hypertension. After a 4-week wash-out period, 209 patients were randomized to either CC 8 mg or AML 5 mg once daily for a minimum of 1 month, after which, if BP was not normalized, the dosage was doubled, followed by the addition of hydrochlorothiazide 12.5 mg if necessary. No significant differences were observed between the two groups for change in IMT at M12 (-0.001 vs -0.027 mm/year for CC and AML respectively, p = 0.425), at M24 (-0.033 vs -0.019 mm per year respectively, p = 0.442), and at the last visit (-0.016 vs -0.039 mm per year respectively, p = 0.549). Within the group, comparisons did not show a significant difference in changes in IMT from baseline to the three visits. At the last visit, IMT regression was observed in 52.2% of patients receiving CC and in 51.3% of those receiving AML (p = 0.908). The augmentation in carotid lumen diameter from baseline was statistically greater in the AML group at the last visit (p = 0.034). BP variations during the study were similar in the two groups. The results of this study show that CC and AML treatments may alter identically the natural progression of carotid IMT in hypertensive type 2 diabetic patients.