A dverse drug reactions (ADRs) are a major public health problem given such events are the most common type of injuries experienced by hospitalized patients. 1 ADRs may lead to hospitalization or occur during hospitalization and contribute to an increased length of stay. The recent focus on patient safety and the concern about the number of negative outcomes resulting from drug use, rather than the underlying diseases, has prompted health care professionals to take a critical look at these drug responses. A series of studies examined ADRs among hospitalized patients in the US and Australia 2-6 ; however, less research is available about these events in hospitalized patients in Canada. A US-based metaanalysis revealed that the incidence of serious ADRs in hospitalized patients was 2.1%, with the incidence in those newly admitted to a hospital 4.7%. The same study reported ADRs to be between the fourth and sixth leading cause of death. 6 Other studies have found that ADRs occurred in 2-20% of hospitalized patients. 4-6 Baker et al. provided a national estimate of the incidence of adverse events among adult patients in Canada (7.5 per 100 hospital admissions); after extrapolation, the number of hospital admissions attributed

P roprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized for its pivotal role in low-density lipoprotein-cholesterol (LDL-C) metabolism.1-3 PCSK9 plays a key role in the post-translational regulation 4 of hepatic LDLreceptor (LDL-R) activity, with the binding of PCSK9 to LDL-R promoting receptor degradation and impeding the ability of the liver to remove circulating LDL particles. 5,6 Because an elevated plasma concentration of LDL-C has been well established as an atherosclerotic risk factor, 7 PCSK9 presents itself as a potential novel predictor of cardiovascular risk and as a target for lipid-lowering therapy.Flow-mediated dilation (FMD) and carotid intima-media thickness (cIMT) are measures of vascular function and subclinical atherosclerosis 8,9 ; along with reactive hyperemic velocity time integral (VTI), 10 a more recently described marker of microvascular function, these 3 measures have been established as surrogate markers of atherosclerotic risk. The relationship between traditional cardiovascular risk factors and these vascular measures has been well studied, but the impact of PCSK9 concentration on vascular measures has yet to be evaluated. Consequently, this study sought to examine the impact of PCSK9 concentration on measures of vascular function in a population of healthy, middle-aged men. Predictors of PCSK9 concentration and the relationship between the proprotein and the cardiovascular events were also investigated as secondary objectives. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement.© 2015 American Heart Association, Inc. Objective-Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of low-density lipoprotein metabolism. This study was conducted to evaluate the relationship between serum PCSK9 concentrations and measures of vascular health, subclinical atherosclerosis, and adverse cardiovascular events. The relationship between traditional risk factors and PCSK9 concentrations was also examined. Approach and Results-The cohort consisted of 1527 middle-aged men enrolled in the Firefighters and Their Endothelium (FATE) study, who were free of vascular disease and followed up over a mean period of 7.2±1.7 years. Baseline evaluation included assessment of traditional cardiovascular risk factors and measurements of flow-mediated dilation, reactive hyperemic velocity time integral, and carotid intima-media thickness. Biochemical parameters, including serum PCSK9 concentrations, were analyzed to determine predictors of vascular measures and to evaluate the role of PCSK9 in the occurrence of adverse cardiovascular events. Multivariate linear regression analyses indicated that body mass index, insulin, low-density lipoprotein-cholesterol, and triglycerides were independent predictors of PCSK9. Further modeling revealed no correlation between PCSK9 concentration and carotid intima media thickness, flow-mediated dilation, or reactive hyperemic velocity time integral. Analyses indicated no signific...