Abstract 17635: Angiopoietin-like 3 and Cardiovascular Events in Patients With Peripheral Arterial Disease
Introduction: Angiopoietin-like protein 3 (ANGPTL3), which is primarily expressed in the liver, is associated with an altered serum lipoprotein profile due to its inhibitory effects on lipoprotein lipase as well as endothelial cell lipase activity.
Hypothesis: We investigated whether increased serum ANGPTL3 contributes to the progression of atherosclerosis by examining its association with adverse events in patients with peripheral arterial disease (PAD), a population at very high risk for cardiovascular events.
Methods: We measured serum ANGPTL3 levels in 326 PAD patients in an observational study, at baseline and at a follow-up visit five years later. Adverse outcome was defined as the composite of death, myocardial infarction or stroke (MACE) during the same period. The changes between the ANGPTL3 values of the two visits (Δ) were calculated and correlated with the changes in other risk factors.
Results: At baseline, ANGPTL3 (46.7 [34.1 - 59.3] ng/ml) correlated with total cholesterol (R=0.304, p<0.001) and non-HDL-c (R=0.329, p<0.001). Patients on statin treatment (81.3%) exhibited lower ANGPTL3 (43.7 [32.6 - 55.6] ng/ml) than patients without (61.6 [43.9 - 74] ng/ml, p<0.001]. In survival analysis, the crude HR per IQR of ANGPTL3 was 1.34 (95%CI: 1.04 - 1.73) which increased to 1.44 (1.13 - 1.96) after adusting for classical risk factors including all lipid parameters and statin treatment. The association between ANGPTL3 and MACE was significantly weaker (p=0.031) in patients with diabetes (HR: 1.21 [0.83 - 1.77]) than in patients without (2.24 [1.43 - 3.5]). Concerning longitudinal changes, ΔANGPTL3 correlated significantly with Δtriglycerides (R=0.131, p=0.018), Δcholesterol (R=0.283, p<0.001), and Δnon-HDL-c (R=0.267, p<0.001). Additionally, patients who initiated statin treatment during follow-up showed a steeper decrease in ANGPTL3 than those with unchanged statin status (-24.1 [-33.3 - -0.7] vs. -2.2 [-14.6 - 7.8] ng/ml, p<0.001).
Conclusions: We demonstrated that ANGPTL3 predicts cardiovascular survival unconfounded by classical risk factors but dependent on diabetes. Further research beyond its role in lipid metabolism is warranted to unveil possible direct pro-atherogenic properties of this fascinating protein.
Author Disclosures: C.T. Herz: None. C. Hoebaus: None. R. Koppensteiner: None. G.H. Schernthaner: None.
- © 2016 by American Heart Association, Inc.