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Introduction: Atherosclerotic cardiovascular disease (ASCVD) prognostic models have well-documented poor generalizability in contemporary populations. Sustained, accurate performance of risk prediction models is challenging given demographic shifts, changes in practice patterns, and geographic variation. We propose an approach to tailor known risk prediction models for local settings while preserving known disease risk mechanisms. Here, as a case study, we recalibrate the Pooled Cohort Equations (PCE) in a contemporary (1997-2018), local electronic health records (EHR) cohort in New England. Methods: We conducted a retrospective cohort study using EHR from large Boston-area hospitals. 61,808 patients 45+ years old, without ASCVD in 1997-2006 and complete data to calculate PCE model were split into training (50%), validation (10%), and test sets (40%). We used XGBoost to recalibrate PCE model (XGB-PCE) using PCE risk score, age, race/ethnicity, and sex (Figure). We constrained the XGB-PCE model to preserve known physiologic trends i.e. increase in ASCVD risk with increase in total cholesterol and systolic blood pressure. Models’ discrimination and calibration were calculated in a set aside test set using the Harrell’s c-index and modified Nam D’Agostino χ2 test. Results: In the test set, XGB-PCE exhibited improved calibration across ASCVD risk categories (p=0.37) and race/ethnicity populations (p=0.73). In contrast, even after recalibration in the large, PCE was poorly calibrated across risk categories (p Conclusions: Our recalibration approach maintained comparable discriminative performance and demonstrated improved calibration relative to the PCE while preserving known disease risk mechanisms. Methods that are flexible and preserve disease mechanisms have the potential to locally tailor existing models to be better calibrated for contemporary populations.

BACKGROUND: Elevated postprandial triglycerides reflect a pro-atherogenic milieu, but underlying mechanisms are unclear. OBJECTIVE: We examined differences between fasting and nonfasting profiles of directly measured lipoprotein size and subfractions to assess if postprandial triglycerides reflected increases in very low density and intermediate density lipoproteins (VLDL and IDL) and remnants, or small dense lipid depleted LDL particles (sdLDL). METHODS: We conducted a cross-sectional analysis of 15,397 participants (10,135 fasting; 5262 nonfasting [0.05). CONCLUSIONS: Directly measured particle and cholesterol concentrations of VLDL, not sdLDL, were higher nonfasting and may partly contribute to the pro-atherogenicity of postprandial hypertriglyceridemia. These differences, although statistically significant, were small and may not fully explain the increased risk of postprandial hypertriglyceridemia. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov Unique identifier: NCT01169259.

PURPOSE OF REVIEW Nonfasting lipid testing has been introduced into several guidelines over the past decade or so however, the uptake into clinical practice has not been universal. This review highlights some of the prevalent reasons for provider reluctance to use nonfasting testing and the evidence to support nonfasting testing for routine screening in most patients. RECENT FINDINGS Several studies have found nonfasting lipids to be as, or more, strongly associated with cardiovascular disease (CVD) risk prediction. In particular, nonfasting tests improve system efficiency, are safe for patients with diabetes, the elderly, children, and in the vast majority of patients, do not need to be followed up with fasting studies due to severe hypertriglyceridemia. SUMMARY Nonfasting lipids are a convenient first test for screening that offers equivalent, if not improved CVD risk prediction. Common misconceptions about nonfasting tests are not supported by the evidence.

Background: It is unclear if lipoprotein(a) cholesterol (LpaC), the cholesterol carried by Lpa, is associated with CVD similar to Lpa mass, and if omega-3 fatty acids (n-3 FA) modify risk. Methods: 13,175 participants of the VITAL trial (NCT01169259) had baseline LpaC measured by density-gradient ultracentrifugation and were examined for incident CVD (n=416) by Cox models adjusted for risk factors. In a subset of participants (N=1639) with baseline and 1 year samples, we also analyzed randomized n-3 FA effects (1 g/d EPA+DHA) vs. placebo. Results: In unadjusted models, LpaC was associated with increased CVD risk (Table). After adjustment, risk was somewhat attenuated, with borderline significant association for LpaC >30 mg/dL (HR 1.37 [0.99, 1.90), p=0.056). N-3 FA increased median LpaC from 7 mg/dL (IQR, 5-10) at baseline to 8 mg/dL [IQR, 5-10] at 1 year (mean increase of 4.05% vs placebo, p=0.006 using natural logarithmic transformation for mean LpaC percent change). There was no effect modification (P interaction>0.05) by n-3 FA, race, sex or LDL-C. Conclusion: Very high LpaC had borderline significant increased risk for incident CVD, without diminution of levels or associated risk by n-3 FA treatment.

Physical activity is favourably associated with certain markers of lipid metabolism. The relationship of physical activity with lipoprotein particle profiles in children is not known. Here we examine cross-sectional associations between objectively measured physical activity and sedentary time with serum markers of lipoprotein metabolism.Our cohort included 880 children (49.0% girls, mean age 10.2 years). Physical activity intensity and time spent sedentary were measured objectively using accelerometers. 30 measures of lipoprotein metabolism were quantified using nuclear magnetic resonance spectroscopy. Multiple linear regression models adjusted for age, sex, sexual maturity and socioeconomic status were used to determine associations of physical activity and sedentary time with lipoprotein measures. Additional models were adjusted for adiposity. Isotemporal substitution models quantified theoretical associations of replacing 30 min of sedentary time with 30 min of moderate- to vigorous-intensity physical activity (MVPA).Time spent in MVPA was associated with a favourable lipoprotein profile independent of sedentary time. There were inverse associations with a number of lipoprotein measures, including most apolipoprotein B-containing lipoprotein subclasses and triglyceride measures, the ratio of total to high-density lipoprotein (HDL) cholesterol, and non-HDL cholesterol concentration. There were positive associations with larger HDL subclasses, HDL cholesterol concentration and particle size. Reallocating 30 min of sedentary time to MVPA had broadly similar associations. Sedentary time was only partly and weakly associated with an unfavourable lipoprotein profile.Physical activity of at least moderate-intensity is associated with a favourable lipoprotein profile in schoolchildren, independent of time spent sedentary, adiposity and other confounders.

The Middle East and North Africa (MENA) region has a high burden of morbidity and mortality due to premature (≤55 years in men; ≤65 years in women) myocardial infarction (MI) and acute coronary syndrome (ACS). Despite this, the prevalence of risk factors in patients presenting with premature MI or ACS is incompletely described. We compared lifestyle, clinical risk factors, and biomarkers associated with premature MI/ACS in the MENA region with selected non-MENA high-income countries. We identified English-language, peer-reviewed publications through PubMed (up to March 2018). We used the World Bank classification system to categorize countries. Patients with premature MI/ACS in the MENA region had a higher prevalence of smoking than older patients with MI/ACS but a lower prevalence of diabetes, hypertension, and dyslipidemia. Men with premature MI/ACS had a higher prevalence of smoking than women but a lower prevalence of diabetes and hypertension. The MENA region had sparse data on lifestyle, diet, psychological stress, and physical activity. To address these knowledge gaps, we initiated the ongoing Gulf Population Risks and Epidemiology of Vascular Events and Treatment (Gulf PREVENT) case–control study to improve primary and secondary prevention of premature MI in the United Arab Emirates, a high-income country in the MENA region.

Yes. The time has come to change the way we think about fasting before routine lipid testing. We now have robust evidence supporting the routine use of nonfasting lipid testing. Fasting lipid testing is rarely needed, but may be considered for patients with very high triglycerides or before starting

Supplemental Material, Angiology_Supplemental_Material_April_13_2019_Clean for Premature Myocardial Infarction in the Middle East and North Africa: Rationale for the Gulf PREVENT Study by Sagar B. Dugani, Waheed Murad, Karisamae Damilig, Jean Atos, Eshraga Mohamed, Edward Callachan, Zareen Farukhi, Arshia Shaikh, Abubaker Elfatih, Salwa Yusef, Yousif M. Hydoub, M. Vinayaga Moorthy, Bassem Mora, Ahlam Alawadhi, Robin Issac, Abdulkarim Saleh, Arif Al-Mulla, Samia Mora and Alawi A. Alsheikh-Ali in Angiology

Article, see p 10 Lipid testing plays a major role in cardiovascular risk stratification and management in clinical practice. Fasting samples have long been the standard for assessing low-density lipoprotein cholesterol (LDL-C) and triglycerides because fasting is believed to reduce variability and to allow more accurate derivation of the commonly used Friedewald-calculated LDL-C. In 2009, the Danish guidelines recommended nonfasting lipid testing across Denmark. In 2014, the US Department of Veterans Affairs, the Joint British Societies, and the National Clinical Guideline Center practice guidelines recommended nonfasting lipids for cardiovascular risk assessment. In 2016 to 2017, several additional clinical guidelines and expert consensus statements1–3 from Europe, Canada, and the United States have also recommended nonfasting lipid testing for most routine clinical evaluations (Figure). As more of the worldwide medical community moves toward obtaining nonfasting lipids for routine testing,3 the time is opportune for reassessing whether Friedewald LDL-C or other methods for determining LDL-C could result in improved accuracy of LDL-C, whether assessed nonfasting or fasting. Figure. Timeline of countries and the respective guidelines advocating nonfasting lipid tests as preferred or acceptable alternative to fasting lipids. AACE/ACE indicates American Association of Clinical Endocrinologists and American College of Endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease; CCSG, Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovascular disease in the adult; CHEP, Canadian Hypertension Education Program; EAS/EFLM, European Atherosclerotic Society/European Federation of Clinical Chemistry and Laboratory Medicine joint consensus statement; JBS, Joint British Societies guidelines on prevention of cardiovascular disease in clinical practice; NICE, National Institute for Health and Care Excellence cardiovascular disease: risk assessment and reduction, including lipid modification clinical guideline; and VA DOD, Veterans Affairs/Department of Defense clinical practice guideline for the management of dyslipidemia for cardiovascular risk reduction. In their …

Lipid testing plays a major role in cardiovascular risk stratification and management in clinical practice. Despite the fact that we spend the vast majority of our time in a non-fasting state, fasting samples have long been the standard for measurement of triglycerides and cholesterol, as fasting is believed to reduce variability and allow for a more accurate derivation of the commonly used Friedewald-calculated low-density lipoprotein (LDL) cholesterol. Another reason for preferring fasting lipid profiles has been the concern for an increase in triglyceride concentration seen after consuming a fatty meal (i.e., a fat tolerance test). However, the increase in plasma triglycerides observed after habitual food intake is much less than that observed during a fat tolerance test, making this concern less of a concern. In addition, recent studies suggest that postprandial effects do not weaken, and may even strengthen, the risk associations of lipids with cardiovascular disease (CVD). If postprandial effects do not substantially alter lipid levels or their association with cardiovascular risk, then a non-fasting blood draw has many practical and possibly economic advantages (1).

Background: Five NAPDH oxidase (NOX) isoforms have been implicated in reactive oxygen species (ROS) generation in a cell type- and agonist-specific manner. We previously showed that α 1 -adrenoreceptor (α 1 -AR) stimulation in cultured adult rat ventricular myocytes (ARVM) leads to NADPH-dependent ROS-production, suggesting that a NOX may be responsible. The goal of this project was to determine whether NOX mediates α 1 -AR-stimulated ROS production in ARVM, and if so, which isoform(s) is responsible. Methods and Results: ROS production, assessed by dichlorofluoresceine (DCF) fluorescence, was increased by 51±7 % in ARVM subjected to α 1 -AR stimulation (norepinephrine 1μM + propranolol 2 μM; 30 min; p=0.002, n=3/group). Apocynin (Apo, 50 μM), a broad-spectrum NOX inhibitor, prevented α1-AR-mediated ROS generation (+19±8% vs Apo-treated/α 1 -AR-unstimulated cells, n=4, NS), suggesting a role for NOX. Expression of NOX1, 2 and 4, as well as regulatory proteins p22 phox , p47 phox , Rac1 and Rac2, but not NOX3, was detected by RT-PCR in ARVM. Neither the inhibitory Nox4-tat peptide (+56±7% vs NOX4-tat-treated/α 1 -AR-unstimulated cells) nor adenovirus-mediated overexpression of NOX4 dominant-negative protein (+84±17% vs NOX4DN-infected/α 1 -AR-unstimulated cells) reduced α 1 -AR-induced DCF fluorescence increase (n=4/ group, both p1 -AR-unstimulated cells). In contrast, adenovirus-mediated overexpression of dominant negative p47 phox , p67 phox and Rac1 proteins prevented α 1 -AR-mediated ROS production, suggesting that the responsible NOX requires each of these proteins. NOX2-tat inhibitory peptide (+18.4±7.3% vs NOX2-tat-treated/α 1 -AR-unstimulated cells, n=6, NS), but not NOX1-tat inhibitory peptide (+51±8% vs NOX1-tat-treated/α 1 -AR-unstimulated cells, n=3, p1 -AR-mediated ROS production. Conclusion: The NOX2 complex, including the catalytic subunit gp91 phox , and the regulatory proteins p47 phox , p67 phox and Rac1, is directly responsible for α 1 -adrenergic-receptor induced ROS production in adult rat ventricular myocytes.

Although general principles guiding the transition of individuals with chronic illness from pediatric to adult care have been established, guidelines specific for the transition of individuals with cystic fibrosis (CF) have not. To aid in the development of CF-specific transition guidelines, an anonymous pretransition questionnaire and posttransition interview were used to assess the concerns and expectations of 60 CF patients and their parents as they went through the transition from pediatric to adult care. Along with demographic and clinical information, respondents were asked to rate on a scale of 1–5 their general attitude toward, or level of concern on 22 questions involving transition concerns, adult program expectations, and general view of transition. The two most important concerns identified by patients prior to transition to adult care were potential exposure to infection (3.4 ± 1.3) and having to leave their previous caregivers (3.4 ± 1.0). Introduction to the adult CF team prior to transition was associated with significantly lower levels of concern in all areas, particularly about having to leave previous caregivers (3.9 ± 0.7 vs. 2.5 ± 0.6, P

Determine variables in the acute care period associated with survival and pediatric intensive care unit (PICU) length of stay (LOS) for children with severe traumatic brain injury.Retrospective cohort.Level 1 pediatric trauma center.Children (0-17 yrs) admitted 1991 to 1995 with nonpenetrating traumatic brain injury and admission Glasgow Coma Scale score ofor=8.None.The first 72 hrs of hospitalization were analyzed in detail for 136 patients. The primary end point was survival; secondary end points were PICU LOS, cost, and day at which Glasgow Coma Scale score wasor=14. Predictors of outcome were abstracted, including Pediatric Trauma Score, Glasgow Coma Scale score, Pediatric Risk of Mortality, physiologic variables, computed tomography evidence of brain injury, and neuroresuscitative medications. The fatality rate was 24%. Age and gender were similar between groups (por= .1). Survival was independently predicted by 6-hr Glasgow Coma Scale score (odds ratio [OR] 4.6; 95% confidence interval [CI] 2.06-11.9; p.001) and maximum systolic blood pressure (OR 1.05; 95% CI 1.01-1.09; p.02). Odds of survival increased 19-fold when maximum systolic blood pressure wasor=135 mm Hg (OR 18.8; 95% CI 2.0-178.0; p.01). By discharge, 67% of patients had an age-appropriate Glasgow Coma Scale score. Median hospital costs were 8,798 dollars for survivors: only mannitol use independently predicted high cost (odds ratio 4.9; 95% CI 1.2-19.1; p.01). For survivors, median PICU LOS was 2 days, although 25% had LOS6 days. Six-hour Glasgow Coma Scale score (OR 0.62; 95% CI 0.48-0.80; p.001) and mannitol (OR 7.9; 95% CI 2.3-27.3; p.001) were each independently associated with a prolonged LOS among survivors.Patients with higher 6-hr Glasgow Coma Scale scores were more likely to survive. Adjusting for severity of injury, survival was associated with maximum systolic blood pressureor=135 mm Hg, suggesting that supranormal blood pressures are associated with improved outcome. Mannitol administration was associated with prolonged LOS, yet conferred no survival advantage. We suggest reevaluation of blood pressure targets and mannitol use in children with severe traumatic brain injury.