While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation. We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro. A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.

Individuals with features of metabolic syndrome are particularly susceptible to SARS-CoV-2, a novel coronavirus associated with the severe respiratory disease COVID-19. Despite considerable attention dedicated to COVID-19, the link between metabolic syndrome and SARS-CoV-2 infection remains unclear. Using data from the UK Biobank, we investigated the relationship between severity of COVID-19 and metabolic syndrome-related serum biomarkers measured prior to SARS-CoV-2 infection. Logistic regression analyses were used to test biomarker levels and biomarker-associated genetic variants with SARS-CoV-2-related outcomes. Among SARS-CoV-2-positive cases and negative controls, a 10mg/dL increase in serum high-density lipoprotein (HDL) cholesterol or apolipoprotein A1 (ApoA1) levels was associated with ∼10% reduced risk of SARS-CoV-2 infection, after adjustment for age, sex, obesity, hypertension, type 2 diabetes, and coronary artery disease. Evaluation of known genetic variants for HDL cholesterol revealed that individuals homozygous for ApoE4 alleles had ∼2-3-fold higher risk of SARS-CoV-2 infection or mortality from COVID-19 compared to ApoE3 homozygotes, even after adjustment for HDL cholesterol levels. However, cumulative effects of all evaluated HDL cholesterol-raising alleles and Mendelian randomization analyses did not reveal association of genetically higher HDL cholesterol levels with decreased risk of SARS-CoV-2 infection. These results implicate serum HDL cholesterol and ApoA1 levels measured prior to SAR-CoV-2 exposure as clinical risk factors for severe COVID-19 infection but do not provide evidence that genetically elevated HDL cholesterol levels are associated with SAR-CoV-2 infection.

Purpose of review: Pediatric trauma centers (PTCs) have been championed as multidisciplinary facilities specializing in the care of pediatric trauma, the leading cause of childhood mortality in the United States.¹ However, the vast majority of pediatric trauma is still seen in trauma centers focused on treating adults. This article reviews the latest evidence comparing the relative strengths of PTCs and adult trauma centers (ATCs) in treating childhood injury. Recent findings: Recent multicenter studies comparing outcomes of pediatric injury in PTCs and ATCs have found no differences in mortality or hospital length of stay, contradicting earlier findings. However, fewer invasive procedures and CT scans were performed at PTCs, and more children were discharged back to their homes. Summary: It is difficult to demonstrate a difference in outcomes for children treated at PTCs vs. ATCs. However, PTCs do offer a multidisciplinary, nuanced approach to pediatric trauma care, which may result in long term benefits and offer opportunities for regional collaboration.