Kohei Takata

CETP Inhibition in CVD Prevention: an Actual Appraisal

By virtue of their effects on low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and cellular cholesterol efflux, there is considerable interest in the potential use of pharmacological inhibitors of cholesteryl ester transfer protein (CETP) as a novel approach for cardiovascular disease prevention. This is supported by observations from genetic and animal studies suggesting that less CETP activity has favorable cardiovascular effects. Despite the adverse effects of the first CETP inhibitor to move forward in clinical development, torcetrapib, there remains considerable interest in developing alternative CETP inhibitors without the off-target effects of torcetrapib. The clinical development programs leading to a number of promising CETP inhibitors will be reviewed.

Investigating the long-term legacy of statin therapy

For more than a quarter century, statins have been the predominant pharmacological approach to lowering levels of low-density lipoprotein cholesterol (LDL-C). On the basis of successive clinical trials, their use has expanded, spanning a wide range of cardiovascular risk. Despite their widespread use, there continue to be many unanswered questions with regard to understanding how these agents impact the natural history of atherosclerosis. As the seminal trials of statin therapy were performed more than 20 years ago, there is a unique opportunity to determine the long-term impact of these agents on cardiovascular outcomes in order to investigate potential legacy effects. In particular, such analyses permit evaluation of the long-term effects of relatively finite statin treatment on both cardiovascular outcomes and safety.

Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio and Vulnerable Plaque Features With Statin Therapy in Diabetic Patients With Coronary Artery Disease: Frequency-Domain Optical Coherence Tomography Analysis

Ongoing cardiovascular risks in patients with type 2 diabetes mellitus (T2DM), despite the use of statins, need additional therapeutic targets. We investigated whether diabetic dyslipidemia, characterized by hypertriglyceridemia and low high-density lipoprotein cholesterol (HDL-C), was associated

High-Density Lipoprotein Infusions

High-density lipoproteins (HDLs) have presented an attractive target for development of new therapies for cardiovascular prevention on the basis of epidemiology and preclinical studies demonstrating their protective properties. Development of HDL mimetics provides an opportunity to administer functional HDL. However, clinical trials have produced variable results, with no evidence to date that they reduce cardiovascular events. This article reviews development programs of HDL mimetics.

The relationship between segmental wall shear stress and lipid core plaque derived from near-infrared spectroscopy

BACKGROUND AND AIMS Wall shear stress (WSS) has an important role in the natural history of coronary atherosclerosis. The aim of this study is to investigate the relationship between WSS and the lipid content of atherosclerotic plaques as assessed by near-infrared spectroscopy (NIRS). METHODS We performed serial NIRS and intravascular ultrasound (IVUS) upon Doppler coronary flow guidewire of coronary plaques at baseline and after 12-18 months in 28 patients with <30% angiographic stenosis, who presented with coronary artery disease. Segmental WSS, plaque burden and NIRS-derived lipid rich plaque (LRP) were evaluated at both time-points in 482 consecutive 2-mm coronary segments. RESULTS Segments with LRP at baseline (n = 106) had a higher average WSS (1.4 ± 0.6 N/m2), compared to those without LRP (n = 376) (1.2 ± 0.6 N/m2, p<0.001). In segments without baseline LRP, WSS was higher in those who subsequently developed new LRP (n = 35) than those who did not (n = 341) (1.4 ± 0.8 vs. 1.1 ± 0.6 N/m2, p=0.002). Conversely, in segments with baseline LRP, WSS was lower in those who had regression of lipid content (n = 41) than those who did not (n = 65) (1.2 ± 0.4 vs. 1.6 ± 0.7 N/m2, p=0.007). Segments with the highest tertile of WSS displayed greater progression of LCBI irrespective of baseline lipid content (p<0.001). Multivariate analysis revealed that baseline WSS (p=0.017), PAV (p<0.001) and LCBI (p<0.001) were all independent predictors of change in LCBI over time. CONCLUSIONS Coronary segments with high WSS associate with progression of lipid content over time, which may indicate transformation to a more vulnerable phenotype.