Key result
Positive family history links to ~40% higher secondary event risk post-carotid endarterectomy independent of polygenic risk.
Why the study?
The influence of family history and polygenic risk scores on secondary cardiovascular events in patients undergoing carotid endarterectomy was not well understood.
Are family history and polygenic risk scores associated with secondary cardiovascular events in patients undergoing carotid endarterectomy?
Cohort (n=1,788)
Yes
Are family history and polygenic risk scores associated with secondary cardiovascular events in patients undergoing carotid endarterectomy?
Both family history and high polygenic risk scores are independent predictors of secondary cardiovascular events and vulnerable plaque characteristics in patients undergoing carotid endarterectomy.
Answers are grounded in this paper and cite their sources.
May refine post-endarterectomy risk stratification; hypothesis-generating and requires prospective validation before clinical use.
Background Family history (FHx) of cardiovascular disease (CVD) is a risk factor for CVD and a proxy for cardiovascular heritability. Polygenic risk scores (PRS) summarizing >1 million variants for coronary artery disease (CAD) are associated with incident and recurrent CAD events. However, little is known about the influence of FHx or PRS on secondary cardiovascular events (sCVE) in patients undergoing carotid endarterectomy (CEA). Methods We included 1,788 CEA patients from the Athero-Express Biobank. A weighted PRS for CAD including 1.7 million variants was calculated (MetaGRS). The composite endpoint of sCVE during three years follow-up included coronary, cerebrovascular and peripheral events and cardiovascular death. We assessed the impact of FHx and MetaGRS on sCVE and carotid plaque composition. Results Positive FHx was associated with a higher 3-year risk of sCVE independent of cardiovascular risk factors and MetaGRS (adjusted HR 1.40, 95%CI 1.07-1.82, p=0.013). Patients in the highest MetaGRS quintile had a higher 3-year risk of sCVE compared to the rest of the cohort independent of cardiovascular risk factors including FHx (adjusted HR 1.35, 95%CI 1.01-1.79, p=0.043), and their atherosclerotic plaques contained more fat (adjusted OR 1.59, 95%CI, 1.11-2.29, p=0.013) and more macrophages (OR 1.49, 95%CI 1.12-1.99, p=0.006). Conclusion In CEA patients, both positive FHx and higher MetaGRS were independently associated with increased risk of sCVE. Moreover, higher MetaGRS was associated with vulnerable plaque characteristics. Future studies should unravel underlying mechanisms and focus on the added value of PRS and FHx in individual risk prediction for sCVE.
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Timmerman et al. (2019) conducted a cohort in Severe carotid artery stenosis (n=1,788). Positive family history of cardiovascular disease (FHx) vs. Negative family history of cardiovascular disease was evaluated on Composite secondary cardiovascular event (sCVE) within three years (HR 1.40, 95% CI 1.07-1.82, p=0.013). Positive family history and high polygenic risk score independently increased the 3-year risk of secondary cardiovascular events in patients undergoing carotid endarterectomy.
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