Background: Administration of the CETP inhibitor torcetrapib does not slow the rate of progression of coronary atherosclerosis. The reason for the lack of therapeutic efficacy remains unknown. This analysis investigated the relationship between changes in HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) and atheroma volume in patients treated with torcetrapib. Methods: 910 patients with angiographic coronary artery disease underwent IVUS imaging within a single coronary artery before and during 24 months of treatment with torcetrapib (n = 464) or placebo (n = 446) on a background of atorvastatin therapy. The relationship between changes in levels of HDL-C and LDL-C and both percent atheroma volume (PAV) and total atheroma volume (TAV) was evaluated in patients treated with torcetrapib. Results: Administration of torcetrapib raised HDL-C by 61% and lowered LDL-C by 20% when compared to atorvastatin alone. An inverse relationship was observed between changes in HDL-C and both PAV (r = −0.17, p < 0.001) and TAV (r = −0.17, p < 0.001). Patients with the highest level of HDL-C (> 87 mg/dL) had the lowest rate of progression of PAV (−0.7 v +0.7%, p = 0.0003) and TAV (−9.2 v −4.6 mm 3 , p = 0.09). The greatest elevation in level of HDL-C (> 80%) was associated with the lowest progression of PAV (−0.3 v +0.9%, p = 0.002) and TAV (−12.6 v −3.4 mm 3 , p = 0.0006). Patients undergoing regression (any reduction in PAV) had greater absolute levels (73 v 66 mg/dL, p = 0.02) and changes (59.5 v 48.3%, p = 0.02) of HDL-C. No difference in the impact of torcetrapib on changes in PAV (+0.3 v +0.1%, p = 0.34) and TAV (−9.1 v −9.3 mm 3 , p = 0.95) was observed in patients with baseline levels below or above 40 mg/dL. No relationship was observed between changes in LDL-C and either PAV (r = 0.06, p = 0.20) or TAV (r = 0.07, p = 0.12) in torcetrapib treated patients. On multivariate analysis, changes in levels of HDL-C independently predicted the impact of torcetrapib on progression of PAV (p = 0.007) and TAV (p = 0.004). Conclusion: Increasing levels of HDL-C from torcetrapib treatment were associated with a beneficial impact of torcetrapib on plaque progression. This is consistent with the generation of functional HDL particles and suggests other effects to be responsible for the lack of benefit of torcetrapib.
Background: While the importance of coronary artery disease in females has become increasingly recognized, little is known regarding the impact of gender with regard to changes in arterial wall dimensions with progression and regression of atherosclerosis. This study investigated the remodeling response of the artery wall accompanying changes in atheroma burden in response to use of medical therapies, stratified according to gender. Methods: 1533 patients (27.5% female) underwent serial intravascular ultrasound evaluation of a single coronary artery in the context of clinical trials that assess the impact of medical therapies on plaque progression. The relationship between gender and remodeling of the arterial wall at baseline and its serial change in association with plaque progression and regression were studied. Results: Females were older (59 v 57 years, p<0.01), had a higher body mass index (31.5 v 29.5 kg/m 2 , p<0.01), were more likely to have hypertension (86 v 71.5%, p<0.01) and metabolic syndrome (57 v 49%, p<0.01) and less likely to have a history of smoking (57.5 v 73.5%, p=0.01) and myocardial infarction (27.5 v 35.5%, p<0.01). After adjusting for body surface area, females demonstrated a trend towards smaller external elastic membrane (EEM) (226.3 v 234.3 mm 3 , p=0.09) and larger lumen (143.7 v 137.7 mm 3 , p=0.01) volumes. The remodeling index at the most diseased site did not differ between genders (0.95 v 0.95, p=0.95). No differences were observed between genders with regard to changes in EEM (−5.6 v −6.2 mm 3 , p=0.29) and lumen (−4.9 v −4.5 mm 3 , p=0.82) volumes and remodeling index (−0.02 v −0.03, p=0.43) in response to use of medical therapies. Similarly, there were no differences between genders with regard to the percentage of patients undergoing expansion (34.7 v 35.5%, p=0.86) or contraction (20.4 v 21.8%, p=0.69) of lumen volume in association with regression of atherosclerotic plaque. Conclusion: A similar pattern of remodeling of the arterial wall was observed between genders in association with serial changes in atheroscle-rotic plaque. This further highlights our understanding of the pathological interactions between atherosclerosis and the arterial wall in females.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.