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Role of lipids important in etiology of AAA
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A Mendelian randomization study has identified that abnormal lipid levels, including LDL and HDL, appear to play an important role in the etiology of abdominal aortic aneurysms, and that lowering LDL may prevent development of or help manage AAA.
Researchers investigated the associations between single nucleotide polymorphisms associated with certain lipids and risk for AAA.
Seamus C. Harrison, PhD, FCRS, from the cardiovascular epidemiology unit at University of Cambridge, and colleagues constructed genetic risk scores and tested their association with AAA using inverse-variance weighted Mendelian randomization and data from AAA genome-wide association studies. The analysis included 4,914 people with AAA and 48,002 without it.
The researchers also assessed the association between AAA and single nucleotide polymorphisms in loci that can act as proxies for drug targets.
The outcomes of interest were the association between genetic risk scores of lipid-related single nucleotide polymorphisms and AAA risk, and the association between AAA risk and single nucleotide polymorphisms acting as proxies for drug targets, including HMGCR for LDL reduction, CETP for HDL raising and PCSK9 for LDL reduction.
Harrison and colleagues found that a 1-standard deviation genetic elevation of LDL was associated with higher risk for AAA (OR = 1.66; 95% CI, 1.41-1.96), whereas a 1-standard deviation increase in HDL was associated with lower risk for AAA (OR = 0.67; 95% CI, 0.55-0.82), and a 1-standard deviation rise in triglycerides conferred increased AAA risk (OR = 1.69; 95% CI, 1.38-2.07).
Multivariable Mendelian randomization analyses and use of other Mendelian randomization methods did not change the results.
Harrison and colleagues also found that the rs12916 allele of HMGCR, known to be associated with LDL reduction, was also associated with reduced AAA risk (OR = 0.93; 95% CI, 0.89-0.98).
In addition, the rs3764261 allele of CETP, known to be associated with HDL elevation, was also associated with reduced AAA risk (OR = 0.89; 95% CI, 0.84-0.94).
An allele of PCSK9 known to be associated with reduced LDL, rs11206510, had a slight association with reduced AAA risk (OR = 0.94; 95% CI, 0.88-1), but another such allele, rs2479409, had no association with reduced AAA risk (OR = 0.97; 95% CI, 0.84-1.02), Harrison and colleagues wrote.
“Using contemporary [Mendelian randomization] approaches, we found data that lend support to the hypothesis that major lipid fractions are involved in the etiology of AAA,” the researchers wrote. “Consideration should be given to measures aimed at targeting lipids to reduce risk of AAA, using established and emerging therapies.” – by Erik Swain
Disclosures: Harrison reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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