Leg Ischaemia Management collaboration (LIMb): study protocol for a prospective cohort study at a single UK centre

Introduction Severe limb ischaemia (SLI) is the end-stage of peripheral arterial occlusive disease where the viability of the limb is threatened. Around 25% of patients with SLI will ultimately require a major lower limb amputation which has a substantial adverse impact on quality of life. A newly established rapid-access vascular limb salvage clinic and modern revascularisation techniques may reduce amputation rate. The aim of this study is to investigate the 12-month amputation rate in a contemporary cohort of patients and compare this to a historical cohort. Secondary aims are to investigate the use of frailty and cognitive assessments, and cardiac MRI in risk-stratifying patients with SLI undergoing intervention and establish a biobank for future biomarker analyses. Methods & analysis This single-centre prospective cohort study will recruit patients aged 18-110 years presenting with SLI. Those undergoing intervention will be eligible to undergo additional venepuncture (for biomarker analysis) and/or cardiac MRI. Those aged ≥65 years and undergoing intervention will also be eligible to undergo additional frailty and cognitive assessments. Follow-up will be at 12 and 24 months and subsequently via data-linkage with NHS digital to 10 years post-recruitment. Those undergoing cardiac MRI and/or frailty assessments will receive additional follow-up during the first 12 months to investigate for peri-operative myocardial infarction and frailty related outcomes, respectively. A sample size of 420 patients will be required to detect a 10% reduction in amputation rate in comparison to a similar sized historical cohort, with 90% power and 5% type-I error rate. Statistical analysis of this comparison will be by adjusted and unadjusted logistic regression analyses. Ethics & dissemination Ethical approval for this study has been granted by the UK National Research Ethics Service (19/LO/0132). Results will be disseminated to participants, via scientific meetings, peerreviewed medical journals and social media. Study registration ClinicalTrials.gov [NCT04027244

Genetic analysis for a shared biological basis between migraine and coronary artery disease.

OBJECTIVE: To apply genetic analysis of genome-wide association data to study the extent and nature of a shared biological basis between migraine and coronary artery disease (CAD). METHODS: Four separate methods for cross-phenotype genetic analysis were applied on data from 2 large-scale genome-wide association studies of migraine (19,981 cases, 56,667 controls) and CAD (21,076 cases, 63,014 controls). The first 2 methods quantified the extent of overlapping risk variants and assessed the load of CAD risk loci in migraineurs. Genomic regions of shared risk were then identified by analysis of covariance patterns between the 2 phenotypes and by querying known genome-wide significant loci. RESULTS: We found a significant overlap of genetic risk loci for migraine and CAD. When stratified by migraine subtype, this was limited to migraine without aura, and the overlap was protective in that patients with migraine had a lower load of CAD risk alleles than controls. Genes indicated by 16 shared risk loci point to mechanisms with potential roles in migraine pathogenesis and CAD, including endothelial dysfunction (PHACTR1) and insulin homeostasis (GIP). CONCLUSIONS: The results suggest that shared biological processes contribute to risk of migraine and CAD, but surprisingly this commonality is restricted to migraine without aura and the impact is in opposite directions. Understanding the mechanisms underlying these processes and their opposite relationship to migraine and CAD may improve our understanding of both disorders