Completeness of carotid intima media thickness measurements depends on body composition: the RADIANCE 1 and 2 trials.

Contains fulltext : 89728.pdf (publisher's version ) (Open Access)AIM: Ultrasound protocols to measure carotid intima media thickness (CIMT) differ considerably with regard to the inclusion of the number of carotid segments and angles used. Detailed information on the completeness of CIMT information is often lacking in published reports, and at most, overall percentages are presented. We therefore decided to study the completeness of CIMT measurements and its relation with vascular risk factors using data from two CIMT intervention studies: one among familial hypercholesterolemia (FH) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 1), and one among mixed dyslipidemia (MD) patients, the Rating Atherosclerotic Disease change by Imaging With A New CETP Inhibitor (RADIANCE 2). METHODS: We used baseline ultrasound scans from the RADIANCE 1 (n=872) and RADIANCE 2 (n=752) studies. CIMT images were recorded for 12 artery-wall combinations (near and far walls of the left and right common carotid artery (CCA), bifurcation (BIF) and internal carotid artery (ICA) segments) at 4 set angles, resulting in 48 possible measurements per patient. The presence or absence of CIMT measurements was assessed per artery-wall combination and per angle. The relation between completeness and patient characteristics was evaluated with logistic regression analysis. RESULTS: In 89% of the FH patients, information on CIMT could be obtained on all twelve carotid segments, and in 7.6%, eleven segments had CIMT information (nearly complete 96.6%). For MD patients this was 74.6% and 17.9%, respectively (nearly complete: 92.5%). Increased body mass index and increased waist circumference were significantly (p=0.01) related to less complete data in FH patients. For MD patients, relations were seen with increased waist circumference (p98%). In MD patients, completeness was lower for the near wall of both the right and left carotid arteries: 86.0% and 90.8%, respectively, as compared to other segments (all >97%). CONCLUSIONS: With the current ultrasound protocols it is possible to obtain a very high level of completeness. Apart from the population studied, body mass index and waist circumference are important in achieving complete CIMT measurements

Ultrasound protocols to measure carotid intima-media thickness in trials; comparison of reproducibility, rate of progression, and effect of intervention in subjects with familial hypercholesterolemia and subjects with mixed dyslipidemia.

Item does not contain fulltextBACKGROUND: Current ultrasound protocols to measure carotid intima-media thickness (CIMT) in trials rather differ. The ideal protocol combines high reproducibility with a high precision in the measurement of the rate of change in CIMT over time and with a precise estimate of a treatment effect. To study these aspects, a post-hoc analysis was performed using data from two randomized double-blind, placebo-controlled trials: one among 872 subjects with familial hypercholesterolemia (FH) and the other among 752 subjects with mixed dyslipidemia (MD), respectively. Participants were randomized to torcetrapib or placebo on top of optimal atorvastatin therapy. METHODS: CIMT information was collected from the left and right carotid artery from two walls (the near and far wall) of three segments (common carotid, bifurcation, and internal carotid artery) at four different angles (right: 90, 120, 150, and 180 degrees on Meijer's carotid arc; left: 270, 240, 210, and 180 degrees, respectively). Based on combinations of these measurements, 60 different protocols were constructed to estimate a CIMT measure per participant (20 protocols for mean common CIMT, 40 protocols for mean maximum CIMT). For each protocol we assessed reproducibility (intra-class correlation coefficient (ICC), mean difference of duplicate base-line scans); 2-year progression rate in the atorvastatin group with its standard error (SE); and treatment effect (difference in rate of change in CIMT between torcetrapib and placebo) with its SE. RESULTS: Reproducibility: ICC ranged from 0.77 to 0.91 among FH patients and from 0.68 to 0.86 among MD patients. CIMT progression rates ranged from -0.0030 to 0.0020 mm/year in the FH trial and from 0.00084 to 0.01057 mm/year in the MD trial, with SE ranging from 0.00054 to 0.00162 and from 0.00083 to 0.00229, respectively. The difference in CIMT progression rate between treatment arms ranged from -0.00133 to 0.00400 mm/year in the FH trial and from -0.00231 to 0.00486 mm/year in the MD trial. The protocol with the highest reproducibility, highest CIMT progression/precision ratio, and the highest treatment effect/precision ratio were those measuring mean common CIMT with measurements of the near and far wall at multiple angles. When the interest is in the mean maximum CIMT, protocols using multiple segments and angles performed the best. CONCLUSION: Our findings support the position that the number and specific combination of segments, angles, and walls interrogated are associated with differences in reproducibility, magnitude, and precision of progression of CIMT over time, and treatment effect. The best protocols were mean common CIMT protocols in which both the near and far walls are measured at multiple angles.1 september 201

Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia

Background: Torcetrapib, an inhibitor of cholesteryl ester transfer protein, may reduce atherosclerotic vascular disease by increasing levels of high-density lipoprotein (HDL) cholesterol. Methods: A total of 850 patients with heterozygous familial hypercholesterolemia underwent B-mode ultrasonography at baseline and at follow-up to measure changes in carotid intima-media thickness. The patients completed an atorvastatin run-in period and were subsequently randomly assigned to receive either atorvastatin monotherapy or atorvastatin combined with 60 mg of torcetrapib for 2 years. Results: After 24 months, in the atorvastatin-only group, the mean (±SD) HDL cholesterol level was 52.4±13.5 mg per deciliter and the mean low-density lipoprotein (LDL) cholesterol level was 143.2±42.2 mg per deciliter, as compared with 81.5±22.6 mg per deciliter and 115.1±48.5 mg per deciliter, respectively, in the torcetrapib-atorvastatin group. During the study, average systolic blood pressure increased by 2.8 mm Hg in the torcetrapib-atorvastatin group, as compared with the atorvastatin-only group. The increase in maximum carotid intima-media thickness, the primary measure of efficacy, was 0.0053±0.0028 mm per year in the atorvastatin-only group and 0.0047±0.0028 mm per year in the torcetrapib-atorvastatin group (P=0.87). The secondary efficacy measure, annualized change in mean carotid intima-media thickness for the common carotid artery, indicated a decrease of 0.0014 mm per year in the atorvastatin-only group, as compared with an increase of 0.0038 mm per year in the torcetrapib-atorvastatin group (P=0.005). Conclusions: In patients with familial hypercholesterolemia, the use of torcetrapib with atorvastatin, as compared with atorvastatin alone, did not result in further reduction of progression of atherosclerosis, as assessed by a combined measure of carotid arterial-wall thickness, and was associated with progression of disease in the common carotid segment. These effects occurred despite a large increase in HDL cholesterol levels and a substantial decrease in levels of LDL cholesterol and triglycerides. Copyright © 2007 Massachusetts Medical Society.Articl

Lipid-Reduction Variability and Antidrug-Antibody Formation with Bococizumab

Cardiolog

Eukaryotic microbes, species recognition and the geographic limits of species: examples from the kingdom Fungi

The claim that eukaryotic micro-organisms have global geographic ranges, constituting a significant departure from the situation with macro-organisms, has been supported by studies of morphological species from protistan kingdoms. Here, we examine this claim by reviewing examples from another kingdom of eukaryotic microbes, the Fungi. We show that inferred geographic range of a fungal species depends upon the method of species recognition. While some fungal species defined by morphology show global geographic ranges, when fungal species are defined by phylogenetic species recognition they are typically shown to harbour several to many endemic species. We advance two non-exclusive reasons to explain the perceived difference between the size of geographic ranges of microscopic and macroscopic eukaryotic species when morphological methods of species recognition are used. These reasons are that microbial organisms generally have fewer morphological characters, and that the rate of morphological change will be slower for organisms with less elaborate development and fewer cells. Both of these reasons result in fewer discriminatory morphological differences between recently diverged lineages. The rate of genetic change, moreover, is similar for both large and small organisms, which helps to explain why phylogenetic species of large and small organisms show a more similar distribution of geographic ranges. As a consequence of the different rates in fungi of genetic and morphological changes, genetic isolation precedes a recognizable morphological change. The final step in speciation, reproductive isolation, also follows genetic isolation and may precede morphological change