Rationale
Abdominal aortic aneurysm (AAA) is a complex disease with both genetic and environmental risk factors. Together, 6 previously identified risk loci only explain a small proportion of the heritability of AAA.
Objective
To identify additional AAA risk loci using data from all available genome-wide association studies (GWAS).
Methods and Results
Through a meta-analysis of 6 GWAS datasets and a validation study totalling 10,204 cases and 107,766 controls we identified 4 new AAA risk loci: 1q32.3 (SMYD2), 13q12.11 (LINC00540), 20q13.12 (near PCIF1/MMP9/ZNF335), and 21q22.2 (ERG). In various database searches we observed no new associations between the lead AAA SNPs and coronary artery disease, blood pressure, lipids or diabetes. Network analyses identified ERG, IL6R and LDLR as modifiers of MMP9, with a direct interaction between ERG and MMP9.
Conclusions
The 4 new risk loci for AAA appear to be specific for AAA compared with other cardiovascular diseases and related traits suggesting that traditional cardiovascular risk factor management may only have limited value in preventing the progression of aneurysmal disease.
Preliminary evidence suggests that in-home telephone or video-based interventions do improve health-related outcomes for newly injured SCI patients. Telehealth interventions may be cost-saving if program costs are more than offset by a reduction in rehospitalization costs, but differential advantages of video-based interventions versus telephone alone warrant further examination.
This study provides further evidence to support the role of MMP-9 in the pathogenesis of AAA, and indicates that the MMP9 C-1562T functional polymorphism may represent a genetic component contributing to susceptibility to this vascular disease.
Aim
To determine if frailty is associated with poor outcome following in-hospital cardiac arrest; to find if there is a “frailty threshold” beyond which cardiopulmonary resuscitation (CPR) becomes futile.
Methods
Retrospective review of patients aged over 60 years who received CPR between May 2017 and December 2018, in a tertiary referral hospital, which does not provide primary coronary revascularisation. Clinical Frailty Scale (CFS) and Charlson Comorbidity Index were retrospectively assigned.
Results
Data for 90 patients were analysed, the median age was 77 (IQR 70-83); 71% were male; 44% were frail (CFS > 4). Frailty was predictive of in-hospital mortality independent of age, comorbidity and cardiac arrest rhythm (OR 2.789 95% CI 1.145–6.795). No frail patients (CFS > 4) survived to hospital discharge, regardless of cardiac arrest rhythm, whilst 13 (26%) of the non-frail (CFS ≤ 4) patients survived to hospital discharge. Of the 13 survivors (Age 72; range 61–86), 12 were alive at 1 year and had a good neurological outcome, the outcome for the remaining patient was unknown.
Conclusion
Frail patients are unlikely to survive to hospital discharge following in-hospital cardiac arrest, these results may facilitate clinical decision making regarding whether CPR may be considered futile. The Clinical Frailty Scale is a simple bedside assessment that can provide invaluable information when considering treatment escalation plans, as it becomes more widespread, larger scale observations using prospective assessments of frailty may become feasible.
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