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Are triglycerides causal in cardiovascular disease?

Insights from genetic studies have proved critical in investigating the causality of triglycerides in cardiovascular disease risk. This new review discusses the evidence from recent Mendelian randomization studies.
Meta-analyses of cohorts and population-based sequencing studies have investigated whether genes for lipoprotein lipase and proteins that interact with it, such as apolipoprotein (apo) A-V, apo C-III and the angiopoietin-like proteins 3 and 4, are associated with cardiovascular disease risk. The evidence to date shows that triglyceride-raising variants of these genes showed generally strong associations with clinical cardiovascular endpoints. However, these findings are confounded by the association of elevated triglycerides with low high-density lipoprotein cholesterol (HDL-C). Thus, while the evidence from these genetic studies points to a potential causal association with cardiovascular risk, further study is needed to tease out this confounding with low HDL-C. Ultimately, what is needed to resolve this uncertainty is outcomes studies with novel agents specifically aimed at targeting elevated triglycerides via inhibition of apoCIII or angiopoietin-like protein 3. This week’s Landmark study offers new hope.
Genetics of triglycerides and the risk of atherosclerosis.

Dron JS, Hegele RA.