A family history of cardiovascular disease (CVD) and higher polygenic risk scores for coronary artery disease (CAD) were found to be associated with an increased risk for secondary cardiovascular events in patients with severe carotid artery stenosis who undergo carotid endarterectomy, according to a study published in Atherosclerosis.

In this study, the data of 1788 patients from the Athero-Express Biobank were examined. Patients had severe carotid artery stenosis and underwent carotid endarterectomy at 2 large tertiary hospitals in the Netherlands between 2006 and 2016. All patients had family history and 3-year follow-up data.

Weighted polygenic risk scores for CAD (MetaGRS), which included 1.7 million variants, were calculated and matched to 1,742,593 variants in the study data. The MetaGRS was established from a meta-analysis of 3 genomic risk scores and includes 1,745,179 genetic variants with a minor allele frequency >0.1% associated with CAD.

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During the 3-year follow-up period, the composite endpoint of secondary cardiovascular events, comprising coronary, cerebrovascular and peripheral events, and cardiovascular death, was assessed. The impacts of family history and MetaGRS on carotid plaque composition and the risk for secondary cardiovascular events were evaluated.

A total of 744 patients (41.6%) of patients had a positive family history of CAD. A positive vs negative family history was found to be associated with an increased risk for secondary cardiovascular events (26.5% vs 21.2%, respectively; hazard ratio [HR], 1.292; 95% CI, 1.066-1.566; P =.009). Additionally, patients in the top 20% vs bottom 80% of the MetaGRS had a 1.4-fold higher risk for secondary cardiovascular events within 3 years (29.5% vs 23.5%, respectively; HR, 1.353; 95% CI, 1.047-1.749; P =.021), an association which persisted  after adjusting for family history and other potential confounders (adjusted HR, 1.35; 95% CI, 1.01-1.79; P =.043).

Patients at high genetic risk (ie, in the top 20% of MetaGRS) had atherosclerotic plaques with a lipid core comprising more than 10% of the total plaque (adjusted odds ratio [aOR], 1.591; 95% CI, 1.105-2.291; P =.013) and greater infiltration of macrophages (aOR, 1.490; 95% CI, 1.118-1.986; P =.006).

Limitations of this study include the lack of data on medication use and adherence during the follow-up period and the inability to test for the predictive value of MetaGRS.

”[B]oth higher MetaGRS and positive [family history] were independently associated with increased risk for [secondary cardiovascular events in patients undergoing carotid endarterectomy]. Higher MetaGRS was also associated with more vulnerable atherosclerotic plaque characteristics indicating possible underlying mechanisms of how genetic variants influence CVD. [Polygenic risk scores] could identify high-risk individuals and may help select future study populations when investigating new therapeutic CVD prevention strategies,” concluded the study authors.


Timmerman N, de Kleijn DPV, de Borst GJ, et al. Family history and polygenic risk of cardiovascular disease: Independent factors associated with secondary cardiovascular events in patients undergoing carotid endarterectomy [published online May 03, 2020]. Atherosclerosis.  doi:10.1016/j.atherosclerosis.2020.04.013