BackgroundIn an era of expanded treatment options for severe aortic stenosis, it is important to understand risk factors for the condition. It has been suggested that severe aortic stenosis is less common in African Americans, but there are limited data from large studies.Methods and ResultsThe Synthetic Derivative at Vanderbilt University Medical Center, a database of over 2.1 million de‐identified patient records, was used to identify individuals who had undergone echocardiography. The association of race with severe aortic stenosis was examined using multivariable logistic regression analyses adjusting for conventional risk factors. Of the 272 429 eligible patients (mean age 45 years, 44% male) with echocardiography, 14% were African American and 82% were Caucasian. Severe aortic stenosis was identified in 106 (0.29%) African‐American patients and 2030 (0.91%) Caucasian patients (crude OR 0.32, 95% CI [0.26, 0.38]). This difference persisted in multivariable‐adjusted analyses (OR 0.41 [0.33, 0.50], P<0.0001). African‐American individuals were also less likely to have severe aortic stenosis due to degenerative calcific disease (adjusted OR 0.47 [0.36, 0.61]) or congenitally bicuspid valve (crude OR 0.13 [0.02, 0.80], adjusted OR dependent on age). Referral bias against those with severe valvular disease was assessed by comparing the prevalence of severe mitral regurgitation in Caucasians and African Americans and no difference was found.ConclusionsThese findings suggest that African Americans are at significantly lower risk of developing severe aortic stenosis than Caucasians.

IMPORTANCE National guidelines recommend cardiac rehabilitation (CR) after cardiac valve surgery, and CR is covered by Medicare for this indication. However, few data exist regarding current CR enrollment after valve surgery.OBJECTIVE To characterize CR enrollment after cardiac valve surgery and its association with outcomes, including hospitalizations and mortality. DESIGN, SETTING, AND PARTICIPANTS This cohort study of patients undergoing valve surgery was conducted in calendar year 2014, with follow-up through 2015. The study included all fee-for-service Medicare beneficiaries undergoing open cardiac valve surgery in 2014. Patients identified by inpatient diagnosis codes for open aortic, mitral, tricuspid, and pulmonary valve surgery were included. Data analysis occurred from January 2018 to March 2019. EXPOSURES Logistic regression was used to evaluate sociodemographic and clinical factors associated with CR enrollment. MAIN OUTCOMES AND MEASURES We used Andersen-Gill models to evaluate the association of CR enrollment with 1-year hospitalization risk and Cox regression models to evaluate the association of CR enrollment with 1-year mortality risk. RESULTS A total of 41 369 Medicare beneficiaries (median [interquartile range] age, 73 [68-79] years; 16 935 [40.9%] female) underwent open valve surgery in the United States in 2014. Fewer than half of patients (17 855 [43.2%]) who had valve surgery enrolled in CR programs. Several racial/ethnic groups had lower odds of enrolling in CR programs after valve surgery compared with white patients, including Asian patients (odds ratio [OR], 0.36 [95% CI, 0.28-0.47]), black patients (OR, 0.60 [95% CI, 0.54-0.67]), and Hispanic patients (OR, 0.36 [95% CI, 0.28-0.46]). Patients undergoing concomitant coronary artery bypass grafting had higher odds of CR enrollment (OR, 1.26 [95% CI,) than those without the concomitant coronary artery bypass graft procedure, as did patients in the Midwest census region (OR, 2.40 [95% CI, 2.28-2.54]) compared with those in the South (reference). Cardiac rehabilitation enrollment was associated with fewer hospitalizations within 1 year of discharge (hazard ratio, 0.66 [95% CI, 0.63-0.69] after multivariable adjustment). Enrollment was also associated with a 4.2% absolute decrease in 1-year mortality risk (hazard ratio, 0.39 [95% CI, 0.35-0.44] after multivariable adjustment).CONCLUSIONS AND RELEVANCE Fewer than half of Medicare beneficiaries undergoing cardiac valve surgery enroll in CR programs, and there are marked racial/ethnic disparities among those that do. Cardiac rehabilitation is associated with decreased 1-year cumulative hospitalization and mortality risk after valve surgery. These results invite further study on barriers to CR enrollment in this population.

The current guidelines recommend the new risk score, Atherosclerotic Cardiovascular Disease score (ASCVD), to assess an individual׳s risk of future cardiovascular disease (CVD) events. No data exist on the predictive utility of ASCVD score with the incremental value of coronary artery calcium scoring (CACS) across ethnicities and gender. Multi-Ethnic Study of Atherosclerosis (MESA) is a population based study (n=6814) of White (38%), Black (28%), Chinese (22%) and Hispanic (12%) subjects, aged 45–84 years, free from clinical cardiovascular disease. We performed a post-hoc analysis of 6742 participants (mean age 62, 53% female) from the MESA cohort. We evaluated the predictive accuracy for the ASCVD score for each participant in accord with the American College of Cardiology/American Heart Association guidelines using pooled cohort equations. Similar to the publication by Fudim et al. “The Metabolic Syndrome, Coronary Artery Calcium Score and Cardiovascular Risk Reclassification” [1] the analytic properties of models incorporating the ASCVD score with and without CACS were compared for cardiovascular disease CVD prediction. Here the analysis focused on ASCVD score (with and without CACS) performance across gender and ethnicities.

The advent of high throughput screening (HTS) technology permits identification of compounds that influence various cellular phenotypes. However, screening for small molecule chemical modifiers of neurotoxicants has been limited by the scalability of existing phenotyping assays. Furthermore, the adaptation of existing cellular assays to HTS format requires substantial modification of experimental parameters and analysis methodology to meet the necessary statistical requirements. Here we describe the successful optimization of the Cellular Fura-2 Manganese Extraction Assay (CFMEA) for HTS. By optimizing cellular density, manganese (Mn) exposure conditions, and extraction parameters, the sensitivity and dynamic range of the fura-2 Mn response was enhanced to permit detection of positive and negative modulators of cellular manganese status. Finally, we quantify and report strategies to control sources of intra-and inter-plate variability by batch level and plate-geometric level analysis. Our goal is to enable HTS with the CFMEA to identify novel modulators of Mn transport.

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