Dr Carolyn Lam:                Welcome to Circulation on the Run, your weekly podcast summary and backstage pass to the journal and its editors. I'm Dr. Carolyn Lam, Associate Editor from the National Heart Centre and Duke National University of Singapore. How common is perioperative myocardial injury after non-cardiac surgery, and what is its significance? A very important question and a very important feature discussion coming right up after these summaries.                                                 Our first original paper this week tells us that risk assessment using only non-laboratory based risk factors may be a useful alternative in the absence of informational lipids, in predicting adolescents at risk of developing pre-clinical atherosclerosis.                                                 First and corresponding author, Dr. Koskinen from University of Turku Finland and colleagues, studied almost 2,900 participants, age 12-18 years, from four longitudinal cohort studies from the United States, Australia, and Finland, and followed these adolescents into adulthood. When carotid intima media thickness was measured, a mean followup of 23 years later. Non-laboratory based risk factors such as age, blood pressure, body mass index, and lipids measured in adolescence, independently predicted high carotid intima media thickness in young adulthood. The addition of lipid measurements to these traditional clinic based risk factor assessments provided a statistically significant but clinically modest improvement on adolescent prediction of high carotid intima media thickness in adulthood.                                                 The next study demonstrates the feasibility of large scale aptamer multiplexing at a level that has not previously been reported and with sample proof that greatly exceeds other existing proteomic methods.                                                 Now, like antibodies, DNA aptamers can be generated as affinity reagents for proteins. Emerging data suggests that they can be used to measure blood protein levels in clinical cohorts. However, the technology has, to date, remained in its infancy. In today's study, co-first authors, Dr. Jacob and Dr. Ngo, co-corresponding authors, Dr. Jennings and Gerszten, from Beth Israel Deaconess Medical Center in Boston, tested the scalability of a highly multiplexed expended proteomic technique that uses single stranded DNA aptamers to assay human proteins with a markedly expended platform containing approximately 5,000 aptamers targeting a far broader range of analytes than previously examined using this technology. They applied the platform to a cohort of individuals undergoing septal alcohol ablation for hypertrophic cardiomyopathy, using this as a human model of planned myocardial injury.                                                 Now, in addition to confirming findings from prior studies, they identified nearly 150 additional putative markers of myocardial injury. Thus, these findings suggest that the expanded aptamer based proteomic platform may provide a unique opportunity for biomarker and pathway discovery following myocardial injury.                                                 The next study addresses the potential long-term effects of low LDL cholesterol on neurocognitive impairment and decline. This has been a concern with pharmacologic PCSK9 inhibition. The first author, Dr. Mefford, corresponding author, Dr. Levitan from University of Alabama at Birmingham, investigated the association between PCSK9 loss of function variants and neurocognitive impairment and decline in the regards study.                                                 In this general population sample of African American adults, they found no association between PCSK9 loss of function variants and neurocognitive impairment or longitudinal neurocognitive decline. There was also no association between lower LDL cholesterol levels and neurocognitive impairment