Physicians' Academy for Cardiovascular Education

Genetically determined dyslipidemia associated with abdominal aortic aneurysm

Genetic Association of Lipids and Lipid Drug Targets With Abdominal Aortic Aneurysm - A Meta-analysis

Harrison SC, Holmes MV, Burgess S, et al. - JAMA Cardiol 2017; published online ahead of print


Guidelines recommend the screening of patients at high risk for abdominal aortic aneurysm (AAA), particularly men aged 65 to 75 years with a history of smoking [1]. Studies suggest that AAA and CHD have some, but not all, risk factors in common [2]. For example, there is a consistent inverse association between HDL-c and AAA risk, but the association with LDL-c is rather unclear, whereas there are no data on the association between TGs and AAA risk [3].

In this study, the role of lipids in the etiology of AAA was investigated. For this purpose, the association of genetic risk scores (GRS) for lipid traits with AAA were reported in up to 4914 cases and 48002 controls in 5 international AAA genome-wide association studies (GWASs) from January 2015 to December 2016 [4]. In all studies, AAA was defined as an infra-renal aortic diameter of ≥3 cm by ultrasound or CT imaging, unless there was a history of previous AAA rupture or repair.

Single-nucleotide polymorphisms (SNPs) associated with lipids were identified in the Global Lipid Genetics Consortium [5], using the SNP selection criteria by Do et al. [6]. SNPs were selected in association with at least 1 of the 3 lipid traits (LDL-c, HDL-c, or TG concentrations) at a genome-wide significance level (P < 5 × 10−8). A conventional Mendelian Randomization (MR) analysis was conducted, as well as a multivariable MR, a MR-Egger, and a weighted median MR as sensitivity analyses.

Main results


In a meta-analysis of 5 GWASs, the genetic elevation of LDL-c and TG levels was associated with an increased risk of AAA, whereas increased HDL-c level was associated with a lower risk of AAA. These results suggest that patients with an AAA have a high burden of genetically determined dyslipidemia; appropriate treatment of this may lower their AAA risk.


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Find this article online at JAMA Cardiol