A novel multi-ancestry proteome-wide Mendelian randomization study implicates extracellular proteins, tubular cells, and fibroblasts in estimated glomerular filtration rate regulation.

Estimated glomerular filtration rate (eGFR) impacts the concentration of plasma biomarkers confounding biomarker association studies of eGFR with reverse causation. To identify biomarkers causally associated with eGFR, we performed a proteome-wide Mendelian randomization study. Genetic variants nearby biomarker coding genes were tested for association with plasma concentration of 1,161 biomarkers in a multi-ancestry sample of 12,066 participants from the Prospective Urban and Rural Epidemiological (PURE) study.

Surrogate Adiposity Markers and Mortality.

Importance: Body mass index (BMI) is an easily obtained adiposity surrogate. However, there is variability in body composition and adipose tissue distribution between individuals with the same BMI, and there is controversy regarding the BMI associated with the lowest mortality risk.

Objective: To evaluate which of BMI, fat mass index (FMI), and waist-to-hip (WHR) has the strongest and most consistent association with mortality.

Deep Learning for Echocardiography: Introduction for Clinicians and Future Vision: State-of-the-Art Review.

Exponential growth in data storage and computational power is rapidly narrowing the gap between translating findings from advanced clinical informatics into cardiovascular clinical practice. Specifically, cardiovascular imaging has the distinct advantage in providing a great quantity of data for potentially rich insights, but nuanced interpretation requires a high-level skillset that few individuals possess. A subset of machine learning, deep learning (DL), is a modality that has shown promise, particularly in the areas of image recognition, computer vision, and video classification.

Cost-Effectiveness of Polygenic Risk Scores to Guide Statin Therapy for Cardiovascular Disease Prevention.

Background: Atherosclerotic cardiovascular diseases (CVDs) are leading causes of death despite effective therapies and result in unnecessary morbidity and mortality throughout the world. We aimed to investigate the cost-effectiveness of polygenic risk scores (PRS) to guide statin therapy for Canadians with intermediate CVD risk and model its economic outlook.

Methods: This cost-utility analysis was conducted using UK Biobank prospective cohort study participants, with recruitment from 2006 to 2010, and at least 10 years of follow-up.

Elevated Lipoprotein(a) and Risk of Atrial Fibrillation: An Observational and Mendelian Randomization Study.

Background: Atrial fibrillation (AF) is a cardiac arrhythmia associated with an elevated risk of stroke, heart failure, and mortality. However, preventative therapies are needed with ancillary benefits on its cardiovascular comorbidities. Lipoprotein(a) (Lp[a]) is a recognized risk factor for atherosclerotic cardiovascular disease (ASCVD), which itself increases AF risk, but it remains unknown whether Lp(a) is a causal mediator of AF independent of ASCVD.

GWAS and ExWAS of blood mitochondrial DNA copy number identifies 71 loci and highlights a potential causal role in dementia.

Background: Mitochondrial DNA copy number (mtDNA-CN) is an accessible blood-based measurement believed to capture underlying mitochondrial (MT) function. The specific biological processes underpinning its regulation, and whether those processes are causative for disease, is an area of active investigation.

Methods: We developed a novel method for array-based mtDNA-CN estimation suitable for biobank-scale studies, called 'automatic mitochondrial copy (AutoMitoC).

Mitochondrial DNA Copy Number as a Marker and Mediator of Stroke Prognosis: Observational and Mendelian Randomization Analyses.

Background And Objectives: Low buffy coat mitochondrial DNA copy number (mtDNA-CN) is associated with incident risk of stroke and poststroke mortality; however, its prognostic utility has not been extensively explored. Our goal was to investigate whether low buffy coat mtDNA-CN is a marker and causal determinant of poststroke outcomes using epidemiologic and genetic studies.

Methods: First, we performed association testing between baseline buffy coat mtDNA-CN measurements and 1-month poststroke outcomes in 3,498 cases of acute, first stroke from 25 countries from the international, multicenter case-control study Importance of Conventional and Emerging Risk Factors of Stroke in Different Regions and Ethnic Groups of the World (INTERSTROKE).

Measuring sodium intake: research and clinical applications.

Although most current guidelines recommend a daily sodium intake of less than 2.3 g/day, most people do not have a reliable estimate of their usual sodium intake. In this review, we describe the different methods used to estimate sodium intake and discuss each method in the context of specific clinical or research questions.

Continued versus interrupted direct oral anticoagulation for cardiac electronic device implantation: A systematic review.

Background: Many patients undergoing cardiac device implantation are taking direct oral anticoagulation (DOAC). Continuing DOAC during device implantation may increase periprocedural bleeding risk; however, interrupting DOACs may increase thromboembolic risk.

Objective: To compare the incidence of clinically significant pocket hematoma and thromboembolism in patients who have their DOAC continued or interrupted for cardiac device implantation.

Plasma ACE2 and risk of death or cardiometabolic diseases: a case-cohort analysis.

Background: Angiotensin-converting enzyme 2 (ACE2) is an endogenous counter-regulator of the renin-angiotensin hormonal cascade. We assessed whether plasma ACE2 concentrations were associated with greater risk of death or cardiovascular disease events.

Methods: We used data from the Prospective Urban Rural Epidemiology (PURE) prospective study to conduct a case-cohort analysis within a subset of PURE participants (from 14 countries across five continents: Africa, Asia, Europe, North America, and South America).

Including Insonation in Undergraduate Medical School Curriculum.

Insonation, or the use of ultrasound, has been proposed to be included in the medical school curriculum, both for education and bedside physical examination. It is important to consider what impact insonation should have on medical student education. Increasingly students are exposed to ultrasound use on clinical rotations, but to what extent should ultrasound be an integrated part of the preclinical curriculum in the United States? Ultrasound can serve to augment an existing curriculum in anatomy, physiology, physical examination, and disease assessment and treatment.

Rivaroxaban and Aspirin in Peripheral Vascular Disease: a Review of Implementation Strategies and Management of Common Clinical Scenarios.

Purpose Of Review: Peripheral artery disease (PAD) affects an estimated 200 million people worldwide and is associated with significant cardiovascular morbidity and mortality. Cardiovascular risk is further increased among individuals with polyvascular disease, where either cerebrovascular or coronary artery disease is present in addition to PAD. In this review, we present common clinical scenarios encountered when managing patients with PAD and provide an evidence-based approach to prescribing optimal antithrombotics in this population.

A Student-Led, Multifaceted Intervention to Decrease Unnecessary Folate Ordering in the Inpatient Setting.

To reduce unnecessary laboratory testing, a three-phase intervention was designed by students to decrease serum folate laboratory testing in the inpatient setting. These included an educational phase, a personalized feedback phase, and the uncoupling of orders in the electronic medical record. Average monthly serum folate ordering decreased by 87% over the course of the intervention, from 98.

Phenotypic Clustering of Left Ventricular Diastolic Function Parameters: Patterns and Prognostic Relevance.

Objectives: This study sought to explore the natural clustering of echocardiographic variables used for assessing left ventricular (LV) diastolic dysfunction (DD) in order to isolate high-risk phenotypic patterns and assess their prognostic significance.

Background: Assessment of LV DD is important in the management and prognosis of cardiovascular diseases. Data-driven approaches such as cluster analysis may be useful in segregating similar cases without the constraint of an a priori algorithm for risk stratification.

Precision Phenotyping in Heart Failure and Pattern Clustering of Ultrasound Data for the Assessment of Diastolic Dysfunction.

Objectives: The aim of this study was to investigate whether cluster analysis of left atrial and left ventricular (LV) mechanical deformation parameters provide sufficient information for Doppler-independent assessment of LV diastolic function.

Background: Medical imaging produces substantial phenotyping data, and superior computational analyses could allow automated classification of repetitive patterns into patient groups with similar behavior.

Methods: The authors performed a cluster analysis and developed a model of LV diastolic function from an initial exploratory cohort of 130 patients that was subsequently tested in a prospective cohort of 44 patients undergoing cardiac catheterization.

Machine-Learning Algorithms to Automate Morphological and Functional Assessments in 2D Echocardiography.

Background: Machine-learning models may aid cardiac phenotypic recognition by using features of cardiac tissue deformation.

Objectives: This study investigated the diagnostic value of a machine-learning framework that incorporates speckle-tracking echocardiographic data for automated discrimination of hypertrophic cardiomyopathy (HCM) from physiological hypertrophy seen in athletes (ATH).

Methods: Expert-annotated speckle-tracking echocardiographic datasets obtained from 77 ATH and 62 HCM patients were used for developing an automated system.