Stitziel et al. report that a common gain-of-function genetic variant in LPL, which encodes lipoprotein lipase, is associated with a reduction in the risk of coronary artery disease. The authors speculate that therapeutic activation of this pathway might reduce the risk of coronary artery disease. test this hypothesis, we analyzed data from 4414 persons involved in the ACCORD Lipid randomized clinical trial to determine whether the cardioprotective effect of fenofibrate (a drug with widespread effects on lipid metabolism, including LPL activation) was influenced by the common gain-of-function LPL variant (p.S447*) described in the article by Stitziel et al. In the ACCORD Lipid trial, patients with type 2 diabetes who were receiving simvastatin and who were at high risk for cardiovascular events were assigned to receive either fenofibrate or placebo. In the overall ACCORD Lipid trial, fenofibrate did not have a significant effect on cardiovascular events. However, consistent with the working hypothesis, a negative interaction (P=0.01) was observed between the use of fenofibrate and p.S447*. Fenofibrate was beneficial in p.S447 homozygotes but not in carriers of the gain-of-function p.447* variant (Figure 1). By showing that there was no association between fenofibrate and protection against risk among persons in whom LPL activity was already elevated, our findings provide some support for the importance of this pathway as a target for cardioprotective interventions.

Variants in ANGPTL4 and the Risk of Coronary Artery Disease

Morieri Mario Luca
Primo
Writing – Original Draft Preparation
;
2016

Abstract

Stitziel et al. report that a common gain-of-function genetic variant in LPL, which encodes lipoprotein lipase, is associated with a reduction in the risk of coronary artery disease. The authors speculate that therapeutic activation of this pathway might reduce the risk of coronary artery disease. test this hypothesis, we analyzed data from 4414 persons involved in the ACCORD Lipid randomized clinical trial to determine whether the cardioprotective effect of fenofibrate (a drug with widespread effects on lipid metabolism, including LPL activation) was influenced by the common gain-of-function LPL variant (p.S447*) described in the article by Stitziel et al. In the ACCORD Lipid trial, patients with type 2 diabetes who were receiving simvastatin and who were at high risk for cardiovascular events were assigned to receive either fenofibrate or placebo. In the overall ACCORD Lipid trial, fenofibrate did not have a significant effect on cardiovascular events. However, consistent with the working hypothesis, a negative interaction (P=0.01) was observed between the use of fenofibrate and p.S447*. Fenofibrate was beneficial in p.S447 homozygotes but not in carriers of the gain-of-function p.447* variant (Figure 1). By showing that there was no association between fenofibrate and protection against risk among persons in whom LPL activity was already elevated, our findings provide some support for the importance of this pathway as a target for cardioprotective interventions.
Morieri, MARIO LUCA; Hetal, Shah; Doria, Alessandro
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2384246
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