Prevalence of dementia, heart disease and stroke in community-dwelling adults in Canada, 2016-2021: opportunities for joint prevention.

INTRODUCTION: This aim of this study is to provide updated estimates on the prevalence of dementia, heart disease, and stroke in Canadian communities. Targeting all three conditions together, at the community level, may be key to disease prevention and health aging in the Canadian population. METHODS: Using nationwide health survey data, we calculated the age-standardized prevalence of self-reported dementia, heart disease and stroke in adults aged 18 years and over residing in Canadian communities from 2016 to 2021. Poisson regression models were used to detect statistically significant changes in the prevalence of all three conditions from 2016 to 2021. RESULTS: Less than 1% (~ 175,000 individuals) of adults residing in Canadian communities reported dementia, 5% (~ 1.5 million individuals) reported heart disease, and more than 1% (~ 370,000 individuals) reported stroke annually from 2016 to 2021. Overall, the age-standardized prevalence for stroke decreased minimally from 2016 to 2021 (p = 0.0004). Although the age-standardized prevalence of heart disease and dementia decreased from 2016 to 2018, subsequent increases in prevalence from 2018 to 2021 led to a lack of overall statistically significant changes from 2016 to 2021 (p = 0.10 for heart disease and p = 0.37 for dementia). CONCLUSION: Recent increases in the prevalence of dementia, heart disease and stroke in Canadian communities threaten to reverse any gains in vascular disease prevention over the past six years. Findings reveal the urgent need for intensified prevention efforts that are community-based with a focus on joint reduction in the shared risk factors contributing to all three diseases.

Perspectives of online anatomy teachers: A neglected study population struggles with the invisible student.

Online teachers are an under-researched population, but their perspectives are crucial to the successful implementation of online education. A fully online section of an established face-to-face (F2F) two-semester undergraduate anatomy course with a prosection laboratory commenced in 2012 at The University of Western Ontario, Canada. Professors' lectures for F2F students were broadcast in live and archived format to online students using Blackboard Collaborate (BBC) video conferencing software. Teaching assistants (TAs) delivered online laboratories using BBC and three-dimensional (3D) anatomical computer models. This study explored the common experiences and issues faced by the course teachers from 2012 to 2014. Transcripts from open-ended, individual interviews with professors (n = 4) and TAs (n = 5) were coded and analyzed thematically. The teachers' concern for their inability to see the students during sessions to assess class engagement and their teaching effectiveness, and to develop social relationships, was the main finding. However, video conferencing software and email were sufficient communication methods for the students' questions and the teachers' answers. The TAs noted usability challenges and anatomical inaccuracies in the 3D models compared to cadavers. Due to limitations of BBC's screen sharing function, live manipulation for the 3D computer models was not possible; however, the TAs found pedagogical value in using screen captures of the models for drawing activities with the students. Overall, preparation time for teaching online was longer than for F2F. The study's findings provide science educators with issues to consider when preparing for online teaching and recommendations to optimize the teaching experience.

Correction to: Are Clerks Proficient in the Basic Sciences? Assessment of Third-Year Medical Students' Basic Science Knowledge Prior to and at the Completion of Core Clerkship Rotations.

[This corrects the article DOI: 10.1007/s40670-021-01249-3.].

Are Clerks Proficient in the Basic Sciences? Assessment of Third-Year Medical Students' Basic Science Knowledge Prior to and at the Completion of Core Clerkship Rotations.

Basic sciences are a cornerstone of undergraduate medical education (UME), yet research indicates that students' basic science knowledge is not well retained. Many UME curricula are increasing the integration between the basic and clinical sciences with the goal of enhancing students' knowledge levels; however, the impact of clerkship training on students' basic science knowledge remains inconclusive. Thus, using clerkship directors' expectations as framework, we aimed to assess third-year medical students' basic science knowledge during clerkship training and evaluate the influence of clerkship training on their basic science knowledge. Using concepts deemed necessary by clerkship directors, we created a basic science assessment for each clerkship rotation. Assessments were distributed to third-year medical students as a pre- and post-test to assess their basic science knowledge prior to and at the completion of each rotation. On average, students retained ≥ 60% of relevant basic science knowledge from pre-clerkship, and neither clerkship rotation order, nor the basic science discipline being assessed, impacted students' basic science knowledge levels. Post-test data revealed that students, on average, reinforced fundamental concepts during clerkship. Interestingly, even though lower-performing students demonstrated the greatest post-test improvement, they still left each rotation with knowledge deficits compared with their highest-performing peers, suggesting that the clinical experience of clerkship appears to be particularly beneficial for lower-performing students, in regard to enhancing their basic science knowledge. Overall, results indicate that earlier exposure to clinical learning in UME, along with integration of basic science education into clerkship, could promote students' basic science knowledge acquisition and retention.

Expectations and Perceptions of Students' Basic Science Knowledge: Through the Lens of Clerkship Directors.

Basic sciences are a cornerstone of undergraduate medical education (UME) as they provide a necessary foundation for the clinical sciences to be built upon and help foster trainees' competency. However, research indicates that students' basic science knowledge is not well retained, and as a result, students are ill-prepared, with respect to their basic science knowledge, when entering clerkship. One potential reason why students may not be prepared for clerkship is a lack of understanding as to which basic science concepts are critical for medical students to retain from pre-clerkship. We facilitated interviews with all core UME clerkship directors to establish which basic science concepts they expect students to know prior to each clerkship rotation, along with student's basic science strengths and areas of improvement. Interviews revealed that students are expected to have some knowledge of every basic science prior to clerkship, with pharmacology being a strong focus, as many specialties deal with common drugs and classes of drugs. Additionally, general anatomy and physiology knowledge were deemed student strengths in two rotations. Clerkship directors focused on perceived areas of improvement more than perceived strengths, with the most prevalent areas being pharmacology, microbiology, and detailed anatomy. These results represent views of clerkship directors from one Canadian institution; however, since clerks rotate through institutions across Canada, this data provides the impetus for creating a national discussion to help foster standardization of UME curricula, with the overarching goal of ensuring all graduates are proficient in the necessary fundamentals as they transition into residency.

Quantification of Morphological Modulation, F-Actin Remodeling, and PECAM-1 (CD-31) Redistribution in Endothelial Cells in Response to Fluid-Induced Shear Stress Under Various Flow Conditions.

Cardiovascular diseases (CVDs) are the number one cause of death globally. Arterial endothelial cell (EC) dysfunction plays a key role in many of these CVDs, such as atherosclerosis. Blood flow-induced wall shear stress (WSS), among many other pathophysiological factors, is known to significantly contribute to EC dysfunction. The present study reports an in vitro investigation of the effect of quantified WSS on ECs, analyzing the EC morphometric parameters and cytoskeletal remodeling. The effects of four different flow cases (low steady laminar (LSL), medium steady laminar (MSL), nonzero-mean sinusoidal laminar (NZMSL), and laminar carotid (LCRD) waveforms) on the EC area, perimeter, shape index (SI), angle of orientation, F-actin bundle remodeling, and platelet endothelial cell adhesion molecule-1 (PECAM-1) localization were studied. For the first time, a flow facility was fully quantified for the uniformity of flow over ECs and for WSS determination (as opposed to relying on analytical equations). The SI and angle of orientation were found to be the most flow-sensitive morphometric parameters. A two-dimensional fast Fourier transform (2D FFT) based image processing technique was applied to analyze the F-actin directionality, and an alignment index (AI) was defined accordingly. Also, a significant peripheral loss of PECAM-1 in ECs subjected to atheroprone cases (LSL and NZMSL) with a high cell surface/cytoplasm stain of this protein is reported, which may shed light on of the mechanosensory role of PECAM-1 in mechanotransduction.

Close Association of Myeloperoxidase-Producing Activated Microglia with Amyloid Plaques in Hypercholesterolemic Rabbits.

Microglial activation and oxidative stress have been linked to the formation of amyloid plaques found in Alzheimer's disease (AD). Epidemiologic and experimental evidence also suggests that cholesterol (CH) contributes to the pathogenesis of AD, particularly the formation of amyloid plaques. We have previously described the development of amyloid-ß (Aß) plaques in New Zealand white rabbits maintained on a 0.125%-0.25% w/w CH diet for extended periods of time (28 months). Here we further characterize this model with combined immunofluorescence and immunohistochemical staining to evaluate markers of immune cell activation. Five out of eight CH-fed rabbits, but not control rabbits, developed extracellular Aß plaques in both the hippocampus and cortex. Significantly (p < 0.05) higher CD11b microglial staining was found in the hippocampus, temporal cortex, and frontal cortex of CH-fed versus control rabbits. In the temporal cortex and parietal cortex, active CD-11b- and ferritin-positive microglia were found in close proximity to Aß plaques. Classification and quantification of activated microglia in the temporal cortex showed that 68±12.9%, 25±7.3%, and 7±2.7% of all microglia had a primed, reactive, and amoeboid phenotype, respectively. Activated microglia also expressed myeloperoxidase which was co-localized to amyloid deposits. Our findings in this dietary-based model lend further support of a role of activated microglia and oxidative stress during the development of AD and strengthens the links between hypercholesterolemia, inflammatory status, and AD.

In Vivo MRI of Amyloid Plaques in a Cholesterol-Fed Rabbit Model of Alzheimer's Disease.

Hypercholesterolemia has been identified as a risk factor for Alzheimer's disease. In this study, rabbits were fed either a cholesterol diet or normal chow diet for 24 months. At endpoint, in vivo MRI was performed at the field strength of 3 Tesla using fast imaging employing steady state acquisition without (FIESTA) or with susceptibility-weighted post-processing (SWI-FIESTA) and susceptibility-weighted imaging with multi-echo acquisition (SWAN). This imaging revealed signal voids/hypointensities throughout the cortex, sub-cortex, and hippocampus of cholesterol-fed animals compared to control animals. Quantitative image analysis corroborated these qualitative findings and highlighted that SWI processing of FIESTA images significantly improved the detectability of plaques (p < 0.05). Aß immunostaining and Prussian blue staining for iron demonstrated that the voids in MR images corresponded to iron-laden Aß-positive plaques. This study demonstrates non-invasive in vivo visualization of Aß plaques in a diet-induced large animal model of Alzheimer's disease. This work lays the foundation for future work focusing on longitudinal monitoring of plaque formation in this model and the effects of diet or drug interventions.

Improving Online Interactions: Lessons from an Online Anatomy Course with a Laboratory for Undergraduate Students.

An online section of a face-to-face (F2F) undergraduate (bachelor's level) anatomy course with a prosection laboratory was offered in 2013-2014. Lectures for F2F students (353) were broadcast to online students (138) using Blackboard Collaborate (BBC) virtual classroom. Online laboratories were offered using BBC and three-dimensional (3D) anatomical computer models. This iteration of the course was modified from the previous year to improve online student-teacher and student-student interactions. Students were divided into laboratory groups that rotated through virtual breakout rooms, giving them the opportunity to interact with three instructors. The objectives were to assess student performance outcomes, perceptions of student-teacher and student-student interactions, methods of peer interaction, and helpfulness of the 3D computer models. Final grades were statistically identical between the online and F2F groups. There were strong, positive correlations between incoming grade average and final anatomy grade in both groups, suggesting prior academic performance, and not delivery format, predicts anatomy grades. Quantitative student perception surveys (273 F2F; 101 online) revealed that both groups agreed they were engaged by teachers, could interact socially with teachers and peers, and ask them questions in both the lecture and laboratory sessions, though agreement was significantly greater for the F2F students in most comparisons. The most common methods of peer communication were texting, Facebook, and meeting F2F. The perceived helpfulness of the 3D computer models improved from the previous year. While virtual breakout rooms can be used to adequately replace traditional prosection laboratories and improve interactions, they are not equivalent to F2F laboratories.

The skeletons in our closet: E-learning tools and what happens when one side does not fit all.

In the anatomical sciences, e-learning tools have become a critical component of teaching anatomy when physical space and cadaveric resources are limited. However, studies that use empirical evidence to compare their efficacy to visual-kinesthetic learning modalities are scarce. The study examined how a visual-kinesthetic experience, involving a physical skeleton, impacts learning when compared with virtual manipulation of a simple two-dimensional (2D) e-learning tool, A.D.A.M. Interactive Anatomy. Students from The University of Western Ontario, Canada (n = 77) participated in a dual-task study to: (1) investigate if a dual-task paradigm is an effective tool for measuring cognitive load across these different learning modalities; and (2) to assess the impact of knowledge recall and spatial ability when using them. Students were assessed using knowledge scores, Stroop task reaction times, and mental rotation test scores. Results demonstrated that the dual-task paradigm was not an effective tool for measuring cognitive load across different learning modalities with respect to kinesthetic learning. However, our study highlighted that handing physical specimens yielded major, positive impacts on performance that a simple commercial e-learning tool failed to deliver (P < 0.001). Furthermore, students with low spatial ability were significantly disadvantaged when they studied the bony joint and were tested on contralateral images (P = 0.046, R = 0.326). This suggests that, despite limbs being mirror images, students should be taught the anatomy of, as well as procedures on, both sides of the human body, enhancing the ability of all students, regardless of spatial ability, to take anatomical knowledge into the clinic and perform successfully. Anat Sci Educ 10: 570-588. © 2017 American Association of Anatomists.

Educational software usability: Artifact or Design?

Online educational technologies and e-learning tools are providing new opportunities for students to learn worldwide, and they continue to play an important role in anatomical sciences education. Yet, as we shift to teaching online, particularly within the anatomical sciences, it has become apparent that e-learning tool success is based on more than just user satisfaction and preliminary learning outcomes-rather it is a multidimensional construct that should be addressed from an integrated perspective. The efficiency, effectiveness and satisfaction with which a user can navigate an e-learning tool is known as usability, and represents a construct which we propose can be used to quantitatively evaluate e-learning tool success. To assess the usability of an e-learning tool, usability testing should be employed during the design and development phases (i.e., prior to its release to users) as well as during its delivery (i.e., following its release to users). However, both the commercial educational software industry and individual academic developers in the anatomical sciences have overlooked the added value of additional usability testing. Reducing learner frustration and anxiety during e-learning tool use is essential in ensuring e-learning tool success, and will require a commitment on the part of the developers to engage in usability testing during all stages of an e-learning tool's life cycle. Anat Sci Educ 10: 190-199. © 2016 American Association of Anatomists.

Academic nightmares: Predatory publishing.

Academic researchers who seek to publish their work are confronted daily with a barrage of e-mails from aggressive marketing campaigns that solicit them to publish their research with a specialized, often newly launched, journal. Known as predatory journals, they often promise high editorial and publishing standards, yet their exploitive business models, poor quality control, and minimal overall transparency victimize those researchers with limited academic experience and pave the way for low-quality articles that threaten the foundation of evidence-based research. Understanding how to identify these predatory journals requires thorough due diligence on the part of the submitting authors, and a commitment by reputable publishers, institutions, and researchers to publicly identify these predators and eliminate them as a threat to the careers of young scientists seeking to disseminate their work in scholarly journals. Anat Sci Educ 10: 392-394. © 2016 American Association of Anatomists.

MRI and histopathologic study of a novel cholesterol-fed rabbit model of xanthogranuloma.

PURPOSE: To develop a rabbit model of xanthogranuloma based on supplementation of dietary cholesterol. The aim of this study was to analyze the xanthogranulomatous lesions using magnetic resonance imaging (MRI) and histological examination. MATERIALS AND METHODS: Rabbits were fed a low-level cholesterol (CH) diet (n = 10) or normal chow (n = 5) for 24 months. In vivo brain imaging was performed on a 3T MR system using fast imaging employing steady state acquisition, susceptibility-weighted imaging, spoiled gradient recalled, T1 -weighted inversion recovery imaging and T1 relaxometry, PD-weighted and T2 -weighted spin-echo imaging and T2 relaxometry, iterative decomposition of water and fat with echo asymmetry and least-squares estimation, ultrashort TE MRI (UTE-MRI), and T2* relaxometry. MR images were evaluated using a Likert scale for lesion presence and quantitative analysis of lesion size, ventricular volume, and T1 , T2 , and T2* values of lesions was performed. After imaging, brain specimens were examined using histological methods. RESULTS: In vivo MRI revealed that 6 of 10 CH-fed rabbits developed lesions in the choroid plexus. Region-of-interest analysis showed that for CH-fed rabbits the mean lesion volume was 8.5 ± 2.6 mm(3) and the volume of the lateral ventricle was significantly increased compared to controls (P < 0.01). The lesions showed significantly shorter mean T2 values (35 ± 12 msec, P < 0.001), longer mean T1 values (1581 ± 146 msec, P < 0.05), and shorter T2* values (22 ± 13 msec, P < 0.001) compared to adjacent brain structures. The ultrashort T2* components were visible using UTE-MRI. Histopathologic evaluation of lesions demonstrated features of human xanthogranuloma. CONCLUSION: Rabbits fed a low-level CH diet develop sizable intraventricular masses that have similar histopathological features as human xanthogranuloma. Multiparametric MRI techniques were able to provide information about the complex composition of these lesions. J. Magn. Reson. Imaging 2016;44:673-682.

The anatomy of E-Learning tools: Does software usability influence learning outcomes?

Reductions in laboratory hours have increased the popularity of commercial anatomy e-learning tools. It is critical to understand how the functionality of such tools can influence the mental effort required during the learning process, also known as cognitive load. Using dual-task methodology, two anatomical e-learning tools were examined to determine the effect of their design on cognitive load during two joint learning exercises. A.D.A.M. Interactive Anatomy is a simplistic, two-dimensional tool that presents like a textbook, whereas Netter's 3D Interactive Anatomy has a more complex three-dimensional usability that allows structures to be rotated. It was hypothesized that longer reaction times on an observation task would be associated with the more complex anatomical software (Netter's 3D Interactive Anatomy), indicating a higher cognitive load imposed by the anatomy software, which would result in lower post-test scores. Undergraduate anatomy students from Western University, Canada (n = 70) were assessed using a baseline knowledge test, Stroop observation task response times (a measure of cognitive load), mental rotation test scores, and an anatomy post-test. Results showed that reaction times and post-test outcomes were similar for both tools, whereas mental rotation test scores were positively correlated with post-test values when students used Netter's 3D Interactive Anatomy (P = 0.007), but not when they used A.D.A.M. Interactive Anatomy. This suggests that a simple e-learning tool, such as A.D.A.M. Interactive Anatomy, is as effective as more complicated tools, such as Netter's 3D Interactive Anatomy, and does not academically disadvantage those with poor spatial ability. Anat Sci Educ 9: 378-390. © 2015 American Association of Anatomists.

An In Vitro Hemodynamic Flow System to Study the Effects of Quantified Shear Stresses on Endothelial Cells.

Numerous in vitro systems have previously been developed and employed for studying the effects of hemodynamics on endothelial cell (EC) dysfunction. In the majority of that work, accurate flow quantification (e.g., uniformity of the flow over the ECs) remains elusive and wall shear stress (WSS) quantifications are determined using theoretical relationships (without considering the flow channel aspect ratio effects). In addition, those relationships are not applicable to flows other than steady laminar cases. The present work discusses the development of a novel hemodynamic flow system for studying the effects of various well-quantified flow regimes over ECs. The current work presents a novel hemodynamic flow system applying the concept of a parallel plate flow chamber (PPFC) with live microscopy access for studying the effects of quantified WSS on ECs. A range of steady laminar, pulsatile (carotid wave form) and low-Reynolds number turbulent WSSs were quantified through velocity field measurements by a laser Doppler velocimetry (LDV) system, to validate the functionality of the current hemodynamic flow system. Uniformity of the flow across the channel width can be analyzed with the current system (e.g., the flow was uniform across about 65-75% of the channel width for the steady cases). The WSS obtained from the experiments had higher values in almost all of the cases when compared to the most commonly-used theoretical solution (9% < error < 16%), whereas another relationship, which considers the channel dimensions, had better agreement with the experimental results (1% < error < 8%). Additionally, the latter relationship predicted the uniform flow region in the PPFC with an average difference of <5% when compared to the experimental results. The experimental data also showed that the WSS at various locations (D, E and F) at the test section differed by less than 4% for the laminar cases representing a fully developed flow. WSS was also determined for a low-Re (Re = 2750) turbulent flow using (1) the Reynolds shears stress and (2) the time-averaged velocity profile gradient at the wall, with a good agreement (differences <16%) between the two where the first method returned a higher value than the second. Porcine aortic endothelial cell (PAEC) viability in the system and morphological cell response to laminar WSS of about 11 dyne/cm(2), were observed. These results provide performance validation of this novel in vitro system with many improved features compared to previous similar prototypes for investigation of flow effects on ECs. The integration of the LDV technique in the current study and the comparison of the results with those from theory revealed that great care must be taken when using PPFCs since the commonly used theoretical relation for laminar steady flows is unable to predict the flow uniformity (which may introduce significant statistical bias in biological studies) and the predicted WSS was subjected to greater error when compared to a more comprehensive equation presented in the current work. Moreover, application of the LDV technique in the current system is essential for studies of more complex cases, such as disturbed flows, where the WSS cannot be predicted using theoretical or numerical modelling methods.

E-learning, dual-task, and cognitive load: The anatomy of a failed experiment.

The rising popularity of commercial anatomy e-learning tools has been sustained, in part, due to increased annual enrollment and a reduction in laboratory hours across educational institutions. While e-learning tools continue to gain popularity, the research methodologies used to investigate their impact on learning remain imprecise. As new user interfaces are introduced, it is critical to understand how functionality can influence the load placed on a student's memory resources, also known as cognitive load. To study cognitive load, a dual-task paradigm wherein a learner performs two tasks simultaneously is often used, however, its application within educational research remains uncommon. Using previous paradigms as a guide, a dual-task methodology was developed to assess the cognitive load imposed by two commercial anatomical e-learning tools. Results indicate that the standard dual-task paradigm, as described in the literature, is insensitive to the cognitive load disparities across e-learning tool interfaces. Confounding variables included automation of responses, task performance tradeoff, and poor understanding of primary task cognitive load requirements, leading to unreliable quantitative results. By modifying the secondary task from a basic visual response to a more cognitively demanding task, such as a modified Stroop test, the automation of secondary task responses can be reduced. Furthermore, by recording baseline measures for the primary task as well as the secondary task, it is possible for task performance tradeoff to be detected. Lastly, it is imperative that the cognitive load of the primary task be designed such that it does not overwhelm the individual's ability to learn new material.

Mixed methods student evaluation of an online systemic human anatomy course with laboratory.

A fully online section of an existing face-to-face (F2F) systemic human anatomy course with a prosection laboratory was offered for the first time in 2012-2013. Lectures for F2F students (N = 365) were broadcast in both live and archived format to online students (N = 40) using virtual classroom software. Laboratories were delivered online by a teaching assistant who manipulated 3D computer models in the virtual classroom environment. An exploratory sequential mixed methods approach was undertaken to determine the most important deciding factors that drive students' preferences for a given format and then to generate theory on the strengths and weaknesses of the online format. Students (20 online; 310 F2F) volunteered to participate in a crossover period of one week to expose them to the course section in which they were not originally registered. Open ended interviews (20 online; 20 F2F) and quantitative surveys (270 F2F) were conducted following a crossover. Students valued pace control, schedule, and location flexibility of learning from archived materials and being assessed online. In the online laboratory they had difficulty using the 3D models and preferred the unique and hands-on experiences of cadaveric specimens. The F2F environment was conducive to learning in both lecture and laboratory because students felt more engaged by instructors in person and were less distracted by their surroundings. These results suggest the need to improve the online experience by increasing the quality of student-instructor communication and in turn student-content interaction with the 3D models. Anat Sci Educ 9: 272-285. © 2015 American Association of Anatomists.

Design and implementation of an online systemic human anatomy course with laboratory.

Systemic Human Anatomy is a full credit, upper year undergraduate course with a (prosection) laboratory component at Western University Canada. To meet enrollment demands beyond the physical space of the laboratory facility, a fully online section was developed to run concurrently with the traditional face to face (F2F) course. Lectures given to F2F students are simultaneously broadcasted to online students using collaborative software (Blackboard Collaborate). The same collaborative software is used by a teaching assistant to deliver laboratory demonstrations in which three-dimensional (3D) virtual anatomical models are manipulated. Ten commercial software programs were reviewed to determine their suitability for demonstrating the virtual models, resulting in the selection of Netter's 3D Interactive Anatomy. Supplementary online materials for the central nervous system were developed by creating 360° images of plastinated prosected brain specimens and a website through which they could be accessed. This is the first description of a fully online undergraduate anatomy course with a live, interactive laboratory component. Preliminary data comparing the online and F2F student grades suggest that previous student academic performance, and not course delivery format, predicts performance in anatomy. Future qualitative studies will reveal student perceptions about their learning experiences in both of the course delivery formats.

Effects of an angiotensin II type 1 receptor blocker on aortic valve sclerosis in a preclinical model.

BACKGROUND: Aortic valve sclerosis (AVS) is a chronic progressive disease involving lipid infiltration, inflammation, and tissue calcification. Despite its high prevalence, there are currently no clinically approved pharmaceuticals for the management of AVS. The objective of the current study was to elucidate the effects of an angiotensin II type 1 receptor blocker, alone or in combination with statin therapy, on the progression of AVS. METHODS: Male New Zealand white rabbits were fed an atherogenic diet for a period of 12 months to induce AVS. Once disease was established, rabbits were randomly assigned to receive no treatment, olmesartan medoxomil, atorvastatin calcium, or a combination of both drugs for a period of 6 months. Disease progression was monitored in vivo using clinically relevant magnetic resonance imaging, and aortic valve cusps were examined ex vivo using histologic and immunohistochemical methods. RESULTS: Cusp thickness significantly increased (0.58 ± 0.03 vs 0.39 ± 0.03 mm for cholesterol and control animals, respectively; P < 0.0001) and all classic hallmarks of disease progression-including lipid infiltration, inflammation, and tissue calcification-were observed after 12 months. Unfortunately, neither olmesartan medoxomil nor atorvastatin calcium were able to reverse or delay disease progression during the 6-month treatment period. However, several histologic changes were observed in the valvular microenvironment. CONCLUSIONS: The current study suggests that angiotensin receptor blockers, alone or in combination with statin therapy, may not be suitable for management of clinical AVS.