Advancing Beyond Failed High-density Lipoprotein Clinical Trials to Pharmacogenetic Studies of ADCY9 and Cholesterol Ester Transfer Protein Inhibition.

Atherosclerosis has been effectively avoided with many therapies that lower low-density lipoprotein cholesterol. However, significant cardiovascular burden remains. The effect of raising high-density lipoprotein (HDL) has been confounded by other factors (such as lowering triglycerides or LDL) and unsuccessful when attempting to solely increase HDL.

Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial.

Objectives: The study aimed to evaluate inclacumab for the reduction of myocardial damage during a percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation myocardial infarction.

Background: P-selectin is an adhesion molecule involved in interactions between endothelial cells, platelets, and leukocytes. Inclacumab is a recombinant monoclonal antibody against P-selectin, with potential anti-inflammatory, antithrombotic, and antiatherogenic properties.

Atherosclerosis imaging and the Canadian Atherosclerosis Imaging Network.

Atherosclerosis exacts a large toll on society in the form of cardiovascular morbidity, mortality, and resource use and is exacerbated by the epidemics of obesity and diabetes. Consequently, there is a critical need for more-effective methods of diagnosis, treatment, and prevention of the complications of atherosclerosis. Careful and well-conducted large population studies are needed in order to truly understand the natural history of the disease, its imaging biomarkers, and their links to patient outcomes.

Cardiovascular biomarkers and surrogate end points: key initiatives and clinical trial challenges.

Biomarkers have proven to be critical tools in both cardiovascular clinical practice and clinical research. In clinical practice, biomarkers are used to identify patients at risk for disease, stratify disease severity, guide intervention decisions and monitor patient response to therapy. Biomarkers are also used extensively to improve the design of cardiovascular clinical trials, identify 'at-risk' populations, allow for preliminary screening for response, identify appropriate dose ranges, study subgroup differences and identify early safety concerns.

Surrogate endpoints and emerging surrogate endpoints for risk reduction of cardiovascular disease.

This article reviews surrogate endpoints and emerging biomarkers that were discussed at the annual "Cardiovascular Biomarkers and Surrogate Endpoints" symposium cosponsored by the US Food and Drug Administration (FDA) and the Montreal Heart Institute. The FDA's Center for Food Safety and Applied Nutrition (CFSAN) uses surrogate endpoints in its scientific review of a substance/disease relationship for a health claim. CFSAN currently recognizes three validated surrogate endpoints: blood pressure, blood total cholesterol, and blood low-density lipoprotein (LDL) concentration in its review of a health claim for cardiovascular disease (CVD).

Anti-inflammatory drugs and atherosclerosis.

Purpose Of Review: Inflammation contributes to the formation and progression of atherosclerosis and the therapeutic potential of some anti-inflammatory drugs has been evaluated for possible antiatherosclerotic effects. This review will briefly describe the mechanisms underlying the inflammation-atherosclerosis connection, the effect of various anti-inflammatory therapies on atherosclerotic disease and a sampling of the potential targets and agents under evaluation.

Recent Findings: Some agents with anti-inflammatory properties appear to have beneficial effects on atherosclerosis or subsequent risk for cardiovascular events, while others have been disappointing.

Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial.

Context: High-density lipoprotein (HDL) cholesterol is an inverse predictor of coronary atherosclerotic disease. Preliminary data have suggested that HDL infusions can induce atherosclerosis regression.

Objective: To investigate the effects of reconstituted HDL on plaque burden as assessed by intravascular ultrasound (IVUS).

Acyl coenzyme A:cholesterol acyltransferase inhibition: potential atherosclerosis therapy or springboard for other discoveries?

Cholesterol is an essential building block without which humans and other animals could not exist. As with most necessities, under certain conditions, excess can sharply tip the scale and lead to an unfavourable outcome. Excess cholesterol is stored as cholesteryl ester through an esterification process regulated in part by acyl coenzyme A:cholesterol acyltransferase (ACAT).

Inhibition of acyl coenzyme A-cholesterol acyltransferase: a possible treatment of atherosclerosis?

Our full understanding of atherosclerosis and our ability to prevent its sequellae are incomplete. As a result, further investigation of novel antiatherosclerotic mechanisms and agents continues. Acyl coenzyme A-cholesterol acyltransferase (ACAT) inhibition has been evaluated as a potential mechanism by which the current treatment arsenal may be expanded.