The rs9349379-A risk allele was associated with a significantly higher risk of spontaneous coronary artery dissection (OR 1.67; 95% CI 1.50-1.86 per copy).
Meta-Analysis (n=8,245)
Yes
Odds Ratio: 1.67 (95% CI 1.5–1.86)
BACKGROUND Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. OBJECTIVES This study sought to test the association between the rs9349379 genotype and SCAD. METHODS Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. RESULTS The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval CI: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. CONCLUSIONS The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD.
“Why is this important? Because if we understand that it is not as rare as we initially thought, people maybe will start looking for it and making the diagnosis. It's just about the perception in the clinics. If the people now understand from our study, and from other studies also, that SCAD is not that rare, it may improve how cardiovascular disease is dealt with for middle-age women who are in theory considered protected from cardiovascular disease.”
Adlam et al. (Tue,) conducted a meta-analysis in Spontaneous coronary artery dissection (SCAD) (n=8,245). rs9349379-A risk allele (PHACTR1/EDN1 locus) vs. Controls (without the risk allele / per copy) was evaluated on Risk of spontaneous coronary artery dissection (OR 1.67, 95% CI 1.50 to 1.86). The rs9349379-A risk allele was associated with a significantly higher risk of spontaneous coronary artery dissection (OR 1.67; 95% CI 1.50-1.86 per copy).
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