Immediate Compared With Delayed Percutaneous Coronary Intervention for Patients With ST-Segment–Elevation Myocardial Infarction Presenting ≥12 Hours After Symptom Onset Is Not Associated With Improved Clinical Outcome

Background: The role of immediate percutaneous coronary intervention (PCI; door-to-balloon time ≤90 minutes) in patients with ST-segment–elevation myocardial infarction who present ≥12 hours after symptom onset is still obscure. We sought to explore the clinical outcomes of immediate PCI in patients with ST-segment–elevation myocardial infarction depending on presentation time. Methods: Using the Korea Acute Myocardial Infarction Registry, a nationwide prospective multicenter registry in the Republic of Korea, we analyzed data from 5968 patients with ST-segment–elevation myocardial infarction. These patients were classified into the following groups: early presenters (n=5104 with symptom onset-to-door time &lt;12 hours), late presenters (n=599 with symptom onset-to-door time 12–48 hours), and very late presenters (n=265 with symptom onset-to-door time ≥48 hours). The primary outcome was major adverse cardiac events, a composite of cardiac death, any myocardial infarction, and clinically driven target lesion revascularization. Results: In early presenters, immediate PCI was significantly associated with a lower rate of major adverse cardiac events compared with delayed PCI (door-to-balloon time &gt;90 minutes; immediate versus delayed PCI, 8.6% versus 17.9%; inverse probability weighting adjusted hazard ratio, 0.63 [95% CI, 0.56–0.71]). In late presenters, immediate PCI was not associated with better major adverse cardiac events outcomes (13.0% versus 14.8%; inverse probability weighting adjusted hazard ratio, 1.05 [95% CI, 0.77–1.44]). The same trend was found for cardiac death (early presenters: immediate versus delayed PCI, 5.6% versus 14.3%; inverse probability weighting adjusted hazard ratio, 0.55 [95% CI, 0.48–0.64]; late presenters: 9.9% versus 9.8%; inverse probability weighting adjusted hazard ratio, 1.25 [95% CI, 0.86–1.82]). Very late presenters also showed the same trends as late presenters. Immediate PCI was an independent predictor of major adverse cardiac events in early presenters but not in late presenters. Conclusions: Immediate PCI, defined by time door-to-balloon time ≤90 minutes, for patients with ST-segment–elevation myocardial infarction who present ≥12 hours after symptom onset is not associated with improved long-term clinical outcomes as compared with delayed PCI (door-to-balloon time &gt;90 minutes). </jats:sec

Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus

ObjectiveSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci. Nevertheless, these loci only partially explain SLE heritability and their putative causal variants are rarely prioritised, which make challenging to elucidate disease biology. To detect new SLE loci and causal variants, we performed the largest genome-wide meta-analysis for SLE in East Asian populations.MethodsWe newly genotyped 10 029 SLE cases and 180 167 controls and subsequently meta-analysed them jointly with 3348 SLE cases and 14 826 controls from published studies in East Asians. We further applied a Bayesian statistical approach to localise the putative causal variants for SLE associations.ResultsWe identified 113 genetic regions including 46 novel loci at genome-wide significance (p&lt;5×10−8). Conditional analysis detected 233 association signals within these loci, which suggest widespread allelic heterogeneity. We detected genome-wide associations at six new missense variants. Bayesian statistical fine-mapping analysis prioritised the putative causal variants to a small set of variants (95% credible set size ≤10) for 28 association signals. We identified 110 putative causal variants with posterior probabilities ≥0.1 for 57 SLE loci, among which we prioritised 10 most likely putative causal variants (posterior probability ≥0.8). Linkage disequilibrium score regression detected genetic correlations for SLE with albumin/globulin ratio (rg=−0.242) and non-albumin protein (rg=0.238).ConclusionThis study reiterates the power of large-scale genome-wide meta-analysis for novel genetic discovery. These findings shed light on genetic and biological understandings of SLE.</jats:sec

Meta-analysis of 208,370 East Asians identifies 113 genomic loci and yields new non-immune cell relevant biological insights for systemic lupus erythematosus

AbstractSystemic lupus erythematosus (SLE), an autoimmune disorder, has been associated with nearly 100 susceptibility loci1-8. Nevertheless, these loci only partially explain SLE heritability and provide limited biological insight. We report the largest study of SLE in East Asians (13,377 cases and 194,993 controls), identifying 233 association signals within 113 (46 novel) genetic loci. We detect six new lead missense variants and prioritize ten most likely putative causal variants, one of which we demonstrate exhibits allele-specific regulatory effect on ACAP1 in vitro. We suggest 677 effector genes with potential for drug repurposing, and provide evidence that two distinct association signals at a single locus act on different genes (NCF2 and SMG7). We demonstrate that SLE-risk variants overlap with cell-specific active regulatory elements, notably EBNA2-mediated super-enhancers in Epstein-Barr Virus-transformed B cells, and implicate the role for non-immune cells in SLE biology. These findings shed light on genetic and biological understandings of SLE.</jats:p